determination of epistatic relationships in heterokaryons, to indicate the sequence of gene expression (Moore & Novak Frazer, 2002).
This, of course, now looks like a rather old-fashioned approach, though it's lost none of its power to dissect an individual pathway. The modern molecular approach is to use genomic analysis tools to analyse and compare the transcriptome (transcribed RNA population) and/or proteome (translated polypeptide population) to give expression profiles of different stages as the organism progresses through its developmental sequence. The classic approach ('first, find a variant') immediately focuses attention on a decisive event, though it can then be difficult to identify the network of interactions to which this belongs (the network only begins to become evident as more and more individual decisive events are dissected out, which can take a long time and a lot of work).
Finding out what all those genes do can take a long time and a lot of work. We will describe some of this work in this Section, as it applies to the organisms we have already mentioned and give more information about the methods used in Chapter 18. If you are impatient to find out about the methods employed, we recommend you refer to the following volumes in the Methods in Enzymology book series: Weissman et al., 2010 (volume 470); Jameson et al., 2011 (volume 500); DeLong, 2013 (volume 531); Doudna & Sontheimer, 2014 (volume 546).
It is easier for us to begin our summary of genetic aspects of fungal developmental biology with a trip down Memory Lane to the pre-genomics era, while we continue our story about Coprinopsis cinerea. The classic genetic approach, when applied to Coprinopsis cinerea, resulted in the isolation of, among others: stipe elongationless mutants, which were unable to elongate the stem but with normal cap expansion, or cap expansionless mutants unable to expand the cap but with normal stipe elongation, and sporeless mutants in which the fruit bodies were morphologically completely normal except for the total absence of spores (Takemaru & Kamada, 1971, 1972) (Fig. 26).
Fig. 26. Developmental mutants of the Ink-cap mushroom, Coprinopsis cinerea. Shown from left to right are A and B the wild type (A mid-development, B fully mature and autolysing), and then C sporeless, D cap expansionless, and E stipe elongationless (immature at top, fully mature and autolysing below). The three mutants are all dominant and segregate in crosses as single genes. All cultures are contained in 9 cm diameter crystallising dishes. Photographs by Dr Junxia Ji.
The three mutants were all dominant and segregated in crosses as single genes. Evidently, the pathways of cap and stem differentiation can be totally separated, and the sporulation pathway is separate from normal cap development. This leads to the conclusion that assembly of different parts of the same fruit body uses genetically distinct pathways. That conclusion can be generalised to: differentiation of fungal multicellular structures is genetically compartmentalised and normal morphogenesis is made up of several-to-many developmental subroutines.
For example, there may be subroutines for stem, cap, hymenium, hymenophore, etc. The subroutines can be put into operation independently of one another and are under separate genetic control and under separate physiological control. Normal morphogenesis of a specific fungus involves integration of these subroutines to produce the fruit body morphology that characterises that species. In their analysis of complex multicellularity in fungi, Nagy et al. (2018) use a slightly different description, suggesting that gene regulatory circuits that orchestrate fruit body development in fungi evolved in a stepwise manner, building on ancient regulatory modules, but also on co-option of conserved genes coupled with the evolution of new ones.
Another important point is that fungi are very tolerant of developmental imprecision. Providing only that the sporulation pathway is intact, even a grossly abnormal fruit body can produce and distribute spores. Variation in the morphology of fruit bodies of higher fungi has been reported in many species, often appearing to be a strategy for adaptation to environmental stress. Detailed analysis of such developmental plasticity in spontaneous abnormal fruit bodies of Volvariella bombycina has given more evidence for normal morphogenesis being an assemblage of distinct developmental segments (Chiu et al., 1989). Although the fruiting structures observed in this study varied from the normal agaric form to completely abnormal enclosed, puff-ball like structures, they were all able to act as production/dispersal structures for basidiospores (Fig. 27).
Thus, a fruit body may, quite abnormally, bear a functional hymenium on the upper surface of the cap, rather than (or even in addition to) its normal hymenium on the lower surface (Fig. 27). The important point is that although the development is abnormal because a morphogenetic subroutine has been invoked in the wrong place, the result is a functional and recognisable tissue, not a disorganised tumorous growth.
Fig. 27. Polymorphic fruit bodies of Volvariella bombycina. A is the normal morphology, of a typical agaric mushroom, which is characterised by a well-developed enclosing volva through which the mushroom cap emerges during development (bulbangiocarpic development, see Fig. 12.7); (scale bar = 20 mm) B to G illustrate a few of the polymorphisms which have arisen on otherwise normal cultures, though often seeming to be associated with some environmental stress, such as abnormal temperature and/or desiccation. B is apparently normal, but completely lacks the volva despite this being characteristic of the genus (scale bar = 5 mm). C, a gymnocarpous fruit body (see Fig. 12.3) with a grossly enlarged basal volva (scale bar = 2 mm). D, a fruit body with a sinuous extra hymenium formed by the proliferating margin of the cap curling onto the upper surface of the cap (scale bar = 10 mm); E is a scanning electron microscope (SEM) view of specimen D and shows the well developed gills on the upper surface of the cap (scale bar = 1 mm). F, a fruit body in which hymenium has formed all over the outer surface of the club-shaped fruit body (scale bar = 5 mm); G is an SEM view of the bisected fruit body and shows that the labyrinthine hymenophore covers the entire surface of the club-shaped 'pileus' (scale bar = 0.5 mm). This polymorph is called 'morchelloid' because of its resemblance to the normal fruit body of the morel (Morchella), which, of course, is a member of the Ascomycota! Photomicrographs by Prof. S.-W. Chiu, Chinese University of Hong Kong. Illustration modified from Chiu et al., 1988.
This tolerance of imprecision is an important biological attribute of fungal morphogenesis, as it provides the flexibility in expression of developmental subroutines that allows the fruit body to react to adverse conditions and still produce a crop of spores. Even when conditions are adverse to normal development, there is still sufficient flexibility in the developmental programme for the fruit body to fulfil its function (Moore, 2013).
The possibility has been discussed that fungal differentiation pathways exhibit what would be described as 'fuzzy logic' in cybernetic programming terms (Moore, 1998b). Instead of viewing fungal cell differentiation as involving individual major (yes/no) 'decisions' which switch progress between alternative developmental pathways that lead inevitably to specific combinations of features, this idea suggests that the end point in fungal differentiation depends on the balance of a network of minor 'approximations'. Fuzzy logic is an extension of conventional (Boolean) logic that can handle the concept of partial truth, that is truth-values between 'completely true' and 'completely false'. It is the logic underlying modes of decision-making that are approximate rather than exact, being able to handle uncertainty and vagueness and has been applied to a wide variety of problems.
The importance of fuzzy logic derives from the fact that the theory provides a mathematical basis for understanding how decision-making seems to operate generally in biological systems, which are not always 'all-or-none' decisions. In the case of fruit body structure, the outcome is that fungal cells are allowed the flexibility to assume a differentiation state even when all conditions of that state have not yet been met. In other words, developmental decisions between pathways of differentiation are able to cope with a degree of uncertainty. So the conclusion is that fungal differentiation pathways must be based on application of rules that allow considerable latitude in expression (fuzzy constraints), which in the ultimate can lead to highly polymorphic, yet functional, fruit bodies.
One consequence of this line of argument is that patterning genes may not be necessary to develop the patterns of a mushroom fruit body. Rather, as we have described, the patterns may arise from the regular application of simple, and fuzzy, developmental rules and basic metabolic regulation combined with physical forces (stretching, inflation, expansion). A specific gill pattern in an agaric, say, may not require a panel of regulatory genes that specify 'x number of gills per unit volume of cap' because that pattern 'invariably' results from the application of general rules about the local circumstances within the tissue that allow gills to be made and the subsequent set of circumstances that drive fruit body maturation.
The first complete genome sequence of any eukaryote to be released, in 1996, was that of the budding yeast Saccharomyces cerevisiae. It was the work of a worldwide team of hundreds of researchers (Goffeau et al., 1996). In the time since then, the yeast genome has been intensively studied (Cuomo & Birren, 2010) exemplifying numerous approaches that have been followed with other organisms. An updated reference genome sequence prepared with more recent (so-called second-generation) sequencing technologies using a single yeast colony of Saccharomyces cerevisiae strain S288C has been published by Engel et al. (2013). The genome sequence of Saccharomyces cerevisiae enabled systematic genome-wide experimental approaches. The approach has been called a genome-scale systems analysis (Weissman et al., 2010). Systems analysis is a problem-solving technique that involves study of the entire set of parts or components that are connected to form the more complex whole process (the 'system').
Molecular analysis provides an overview of the complex network of gene regulatory events that are involved in a developmental (or any other) process, but it can be difficult to focus on the unique decisive events that characterise (and/or initiate) the process. New sequencing methods have hastened genome scale comparative studies of fungi by reducing the cost and difficulty of sequencing. This has enabled wider use of sequencing applications, such as to study genome-wide variation in populations (for example, Wyss et al., 2016) or to profile RNA transcripts totally (Conesa et al., 2016). The rapid impact of this level of analysis on research with yeast prompted efforts to expand genomic resources for other fungi, and the Fungal Genome Initiative was launched as an organised genome sequencing effort to assemble genomes of over 100 fungi in public databases to promote comparative and evolutionary studies across the fungal kingdom (Cuomo & Birren, 2010; Stajich, 2017). If you've not already done so, check out volumes 470, 500, 531 and 546 in the Methods in Enzymology book series; the citations are given above.
Following on from the development of new sequencing technologies, the pace of progress accelerated considerably, and in 2011 [http://mycor.nancy.inra.fr/blogGenomes/?p=2659], the 1000 Fungal Genomes Project [http://1000.fungalgenomes.org/home/] aimed to '…sequence 1000+ fungal genomes…' and at the time of writing (2018), there are over 1000 fungal genomes listed as complete in at least draft form in the Mycocosm portal of the JGI (the U.S. Department of Energy (DOE) Joint Genome Institute; https://jgi.doe.gov/) [https://genome.jgi.doe.gov/fungi/] (Markowitz et al., 2012, 2015; Grigoriev et al., 2014; Nordberg et al., 2014) [and see JGI annual Progress Reports at https://jgi.doe.gov/about-us/progress-report/]. We will delve further into these general topic areas in Chapter 18, here, as an illustration of some of the extensive genomic systems analysis work that has been done, we will return to the Ink cap mushroom Coprinopsis cinerea, and particularly its fruit body development.
Coprinopsis cinerea was included in the list of fungi chosen for the Fungal Genome Initiative in 2002 (Cuomo & Birren, 2010), and the genome of Coprinopsis cinerea, which comprises 36 megabase pairs (a megabase pair (Mbp) is a unit of length of nucleic acids, equal to one million base pairs) was sequenced and assembled into 13 chromosomes by an international team of 47 researchers (Stajich et al., 2010). This was used to investigate how rates of meiotic recombination varied along the chromosomes, and the distribution, expression, and conservation of single-copy genes and gene families.
It was evident that regions of the genome of Coprinopsis cinerea that have been conserved over evolutionary time show low rates of meiotic recombination and lack sequences such as tandemly repeated members of large gene families, and transposable elements that could promote recombination between non-homologous chromosomes (called ectopic recombination), which can cause chromosomal rearrangements. Single-copy genes with identifiable orthologous genes in other basidiomycetes (orthologous means the same function in different species and descended from a common ancestor) were also mostly located in low-recombination regions of their chromosome. On the other hand, paralogous genes (meaning genes related by duplication that may evolve new functions) were found in the highly recombining regions and near chromosome ends. These latter included families of hydrophobin genes (Section 6.8) and cytochrome P450 gene families that code for the terminal oxidases of the electron transfer chains.
The genome project also revealed two genes of the DNA (cytosine-5)-methyltransferase-1 family that catalyses transfer of methyl groups to specific CpG structures in DNA to form 5-methylcytosine, a process called DNA methylation. This confirms prior studies which showed methylation of repeated genes in Coprinopsis cinerea. DNA methylation is used to control gene expression by changing the activity of DNA without changing the sequence; methylation of a gene's promoter typically represses transcription. The Coprinopsis cinerea genome contained 38 copies of a gene predicted to catalyse the formation of the additional modified base, 5-hydroxymethylcytosine, which has been detected in C. cinerea DNA. This is especially relevant to our current discussion of fungal development because 5-hydroxymethylcytosine has a role in the 'poised (or bivalent) chromatin' domains found in mammalian embryonic stem cells that play an important role in cell differentiation.
Poised (bivalent) chromatin is defined by the simultaneous presence of histone modifications associated with both gene activation and gene repression and is usually found near promoters of transcriptionally silent developmental regulatory genes. In general, pluripotent cells (capable of giving rise to several different cell types) have high numbers of poised domains compared with more differentiated cells, and these domains tend to resolve toward a purely active or purely repressed state during differentiation (Voigt et al., 2013; Lesch & Page, 2014).
5-Methylcytosine in DNA of eukaryotes is an important mark for epigenetic gene regulation; epigenetic marks silence certain gene sequences and activate others so that cells can differentiate. The 'ten eleven translocation' enzymes (TET; the enzymes are named for a common translocation in human cancers) oxidise 5-methylcytosines and promote locus-specific reversal of DNA methylation. 'J binding proteins' (JBP; originally named for their effect on glycosylated thymine in trypanosome DNA, which is known as base J) catalyse hydroxylation of bases in nucleic acids. TET/JBP enzymes are a family of nucleic acid base-modifying 2-oxoglutarate and iron-dependent dioxygenases that demethylate by converting 5-methylcytosine to oxidised methylcytosines, such as hydroxy-, formyl-, and carboxymethylcytosine, which serve as further epigenetic marks or intermediates for demethylation. Iyer et al. (2014) showed that fungi, especially all major clades of basidiomycetes, have numerous TET/JBP genes, which are often associated with a unique class of transposable elements. This pattern differs starkly from the situation in most other organisms that possess just a single or a few copies of the TET/JBP family. This unique transposon-TET/JBP association in fungi is likely to play important roles in speciation during evolution and epigenetic regulation. 5-methylcytosine (5mC) and oxidised methylcytosines (oxi-mCs) have been mapped in Coprinopsis cinerea at close to base-pair resolution (Chavez et al., 2014). Centromeres and transposable elements had distinctive patterns of 5mC and oxi-mC, and 5mC and oxi-mC within genes silenced duplicated genes.
The Coprinopsis cinerea genome includes several highly-expanded unusual protein kinase families including some orthologous to kinases of Saccharomyces cerevisiae, several kinase classes found in animals and/or Dictyostelium, but lost from yeast, and a hugely expanded, to 133 members, family of FunK1 kinases. Protein kinases are enzymes that regulate the activity of other enzymes by phosphorylation, which may turn an inactive enzyme into an active form (or vice versa), or otherwise change enzyme activity, cellular location, or its interaction with other proteins. FunK1 kinases are only found in multicellular ascomycete and basidiomycete fungi. The unusually large gene family in Coprinopsis cinerea shows considerable coding diversity; also 59 of the 133 FunK1 family genes are found within a short region near the end of chromosome 9, overlapping a recombination hot spot in a region where meiotic synapsis initiates. The FunK1 kinases are differentially expressed during dikaryon formation (mating), so they appear to have different functions during sexual morphogenesis and important roles development of Coprinopsis cinerea.
Finally, when the genomes of Coprinopsis cinerea and Laccaria bicolor, an ectomycorrhizal basidiomycete that grows in mixed birch and pine woods, were compared they were found to share extensive regions of synteny (meaning blocks of genes in a similar order within two sets of chromosomes that are being compared with each other). The largest syntenic blocks were found to occur in regions with low meiotic recombination rates, no transposable elements, and tight gene spacing (Stajich et al., 2010).
More evidence of tissue and development-specific gene control was found by studies that focussed on the transcriptional programme of Coprinopsis cinerea. Burns et al. (2010) examined the transcripts produced during meiosis, including time points extending over the 15 hours from before haploid nuclear fusion through to formation of basidiospore tetrads (see Section 8.4, Fig. 8.5 and Section 12.9). They found that about 20% of the genes in the genome are differentially regulated during this developmental process, with successive waves of transcription apparent in nine transcriptional clusters, one of which was enriched for meiotic functions. Transcriptional waves of this sort in other organisms have been found to represent differential expression of genes essential for recombination, chromosome cohesion, chromosome segregation, etc. Comparison with meiotic expression data from Saccharomyces cerevisiae and Schizosaccharomyces pombe showed that meiotic regulatory machinery was not conserved (not too surprising as, physiologically, both yeasts are stimulated to enter meiosis by nutritional limitation, while induction of fruit body development and meiosis in Coprinopsis cinerea is largely controlled by illumination and temperature).
However, a 'core meiotic transcriptome' of 75 genes was conserved between the three fungi. Ascomycetes and basidiomycetes are thought to have diverged in evolution about 500 to 900 million years ago, with Saccharomyces cerevisiae and Schizosaccharomyces pombe diverging from one another shortly after. Conservation of the core meiotic transcriptome between these three fungi implies that the essential transcriptional programme of meiosis has persisted through at least half a billion years of evolution, and potentially for up to a billion years (Burns et al., 2010).
the 'target of rapamycin' (TOR) signalling pathway, which integrates both intracellular and extracellular signals and serves as a central regulator of cell metabolism.
All of which is consistent with the idea that sensing of nutrient levels and environmental conditions are important in this developmental transition. Interestingly, over 100 of the up-regulated genes were found to be unique to mushroom forming basidiomycetes, highlighting the novelty of fruit body development in these fungi (Cheng et al., 2013).
The transcriptomes of stage 1 primordia and vegetative mycelium of Coprinopsis cinerea were also studied by Plaza et al. (2014), but these authors paid attention to regulation of the expression of defence genes as well as the conserved transcriptional patterns of sexual reproduction. Comparing their results with analogous data from Laccaria bicolor and Schizophyllum commune revealed a conserved transcriptional circuitry in basidiomycete fruit bodies consisting of nearly 70 genes involved in mushroom development and function. They also found evidence for a role of the 'Velvet protein regulon' in sexual development of basidiomycetes, as a velvet domain-containing protein was found to be up-regulated in all three fungi. The four velvet proteins VeA, VelB, VelC, and VosA were originally identified in Aspergillus nidulans and shown to form a family of fungal regulators that couple together light-regulated processes, control of secondary metabolism, growth and differentiation. Velvet proteins share a region of about 150 amino acids, the velvet domain, which lacks sequence homology to any other proteins (Bayram et al., 2008; Ahmed et al., 2014). These velvet regulators are present in most clades of the fungal kingdom from chytrids to basidiomycetes.
Muraguchi et al. (2015) extended the investigation of the transcriptome during fruit body development in Coprinopsis cinerea by using high-throughput sequencing of cDNA libraries from 13 developmental points (nine developmental stages, but from stage 6 (onset of meiosis) cap and stipe tissues were analysed separately; see Table 12.1). The analysis revealed changes in expression of many differentially expressed genes between two succeeding developmental stages and between vegetative mycelium and each developmental stage. GO analysis of differentially expressed genes (DEGs) in each transition revealed an overall developmental framework and many notable cellular events; these results are summarised in Fig. 28 and Table 1 [CLICK HERE to download a PDF of these two items].
Fig. 28. Summary of major transcriptional events during morphogenetic transitions during fruit body development in Coprinopsis cinerea. The cartoon diagrams of fruiting across the centre run from vegetative mycelium at left to autolysing mature fruit body at right, and are placed on an average time scale with time zero being set by the illumination cycle that triggers primordium maturation.
The nine developmental stages selected to investigate the transcriptome are shown with numbers in circles (cap and stipe tissue samples were taken separately from 24 h onwards). Developmental and cellular events in each stage and tissue are shown in Table 12.1.
The study identified differentially expressed gene sets using GO enrichment analysis [http://geneontology.org/page/go-enrichment-analysis]; that is, sets of gene sequences of related function that are up-regulated or down-regulated in pairwise comparisons between two succeeding developmental stages, and between vegetative mycelium and each individual developmental stage. The program does this by statistically determining which sequence(s) are over-represented (or under-represented) in each member of the pair relative to the other.
Notable transcriptional programme events are depicted in the text labels. Events detected by up-regulated differentially expressed genes are indicated in the upper part with upward red arrows; down-regulated differentially expressed gene sets are shown in the lower part with downward blue arrows. Sets which featured a mix of both up-regulated and downregulated gene sequences of related function are indicated with asterisks and bidirectional green arrows. Taken from Muraguchi et al. (2015) under Creative Commons licence https://creativecommons.org/licenses/by/4.0/.
2, sets which featured a mix of both up-regulated and downregulated differentially expressed gene sequences of related function are indicated with this bidirectional arrow and green text.
*, indicates that only the first 3,000 genes were analysed.
Data from Muraguchi et al. (2015) [https://doi.org/10.1371/journal.pone.0141586].
CLICK HERE to download a PDF version of this Table (with its associated figure).
Looking at the discussion so far you can see that the conclusions from the pregenomics era have been broadly confirmed by genome systems analysis, though expanded and given their quantitative context (Table 1). Several hundred to a thousand genes are preferentially expressed at different stages in development of the fruit body. Various signalling pathways have been implicated including cAMP-PKA, MAPK and TOR, the fungus-specific velvet protein regulon and the FunK1 kinases, which are only found in multicellular ascomycete and basidiomycete fungi. Considering the accounts given above (Section 12.11) of the cycles of glycogen accumulation and translocation in different fruit body tissues it is interesting to see in Fig. 28 that the category 'polysaccharide metabolic process' is a set that featured a mix of both up-regulated and down-regulated transcripts. Indeed, transcriptional profiling is beginning to unravel this 'glycogen regulatory circuit' by showing that glycogen synthase kinase 3 (GSK-3) activity is essential for fruit body formation in Coprinopsis cinerea by directly affecting expression of fruit body induction genes together with genes in downstream cellular processes (Chan et al., 2018); and experimental inhibition of GSK-3 expression can control fruit body development (Chang et al., 2018b).
Similarly, the importance attached to enzymes involved in ammonium scavenging and the urea cycle (Section 12.11) fits well with the up-regulation of transcripts in the category 'cellular amino acid biosynthetic process'. There are several other features of Fig. 28 that confirm deductions from the pre-genomics era, particularly the up-regulation of 'transport' transcripts in both cap and stipe between stages 5 and 6/7, and then again between 6/7 and 8/9, and yet again between 8/9 and 10/11 all confirm the presumed rapid translocation of metabolites and water during fruit body maturation. Perhaps not quite so obvious is that the up-regulation of transcripts in the 'extracellular matrix' category fits well with what was known about the importance of the extracellular matrix to hyphal knot formation; and the up-regulation of 'proteasome complex' in the stipe between stages 6/7 and 8/9, with the implication that protein degradation is important to the stipe at these stages for some reason is compatible with what is known about the biochemistry of the Coprinopsis stipe which, unusually, does not accumulate sugars or polyols and is likely, therefore to use the carbon skeletons of amino acids derived from protein degradation as energy source. Furthermore, the conclusion that differentiation of fungal multicellular structures is genetically compartmentalised with normal morphogenesis being made up of several-to-many developmental subroutines (see above in this Section) are equivalent to the transcriptional clusters, transcriptional waves of differential gene expression and differentially expressed gene sets detected in these different studies of the transcriptional programme of the Coprinopsis cinerea genome.
Muraguchi et al. (2015) also observed dramatic changes in gene expression of some transcription factor networks, and several examples of natural antisense transcripts (NATs) that are likely to be involved in developmental regulation of fruiting. NATs are widespread in eukaryotes; they are RNAs that are complementary to other ('sense') RNA transcripts. Evidence indicates that sense and antisense transcripts interact, suggesting a role for NATs in the regulation of gene expression (Wight & Werner, 2013). MicroRNAs (miRNAs) are about 22 nucleotides in length and have essential roles in post-transcriptional regulation of gene expression in animals and plants. Although little studied in fungi, microRNAs have been associated with early fruit body development in Coprinopsis cinerea, where Lau et al. (2018) established their potential targets and demonstrated differential miRNA expression during the early developmental stages of the mushroom, suggesting their involvement in regulating development in this fungus.
Krizsán et al. (2019a & b) constructed a reference atlas of mushroom formation based on comparisons of developmental transcriptome data of more than 200 whole genomes belonging to six species of Agaricomycetes (Armillaria ostoyae, Coprinopsis cinerea, Lentinus tigrinus, Phanerochaete chrysosporium, Rickenella mellea and Schizophyllum commune). 12,003 to 17,822 expressed genes were detected in the six species of which 938 to 7,605 were developmentally regulated. Importantly, nearly 300 conserved gene families in more than 70 functional groups contained developmentally regulated genes. These data outline the major multicellularity-related and developmental processes of mushrooms, including the role of transcriptional reprogramming, gene coexpression networks (called 'modules' by the authors but corresponding to the developmental subroutines discussed above), and alternative splicing. Many of the developmentally regulated sequences were expanded in multicellular plants and/or animals too, implying convergent evolution towards solutions to the challenges imposed by complex multicellularity within independently evolving lineages. Data relating to the evolutionary age distribution of developmentally regulated genes suggested that most developmental gene families are older than fruit body formation; the sequences falling into three groups (a) genes shared by all living species, (b) genes shared by the Dikarya (Ascomycota and Basidiomycota), and (c) species-specific genes.
Another promising technique for detecting transcriptional regulatory relationships on a genome-wide scale that is beginning to be applied to fungal development is the analysis of expression Quantitative Trait Loci (eQTL). A quantitative trait locus (QTL) is a DNA segment associated with a particular phenotype, which varies across a population in a manner attributed to polygenic control (presumed to be the product of two or more genes together with their environment). The approach is essentially a metagenomic statistical analysis of variation in the phenotype of interest that can reveal the genetic architecture of that trait; that is, whether phenotype is controlled by many genes of small effect, or by a few genes of large effect. Expression quantitative trait loci (eQTLs) are genomic loci that describe the variation in expression levels of mRNA molecules. Analysis of eQTLs can recognise potential regulatory factors of gene expression and could identify master regulators in the genome (Michaelson et al., 2009; Liseron-Monfils & Ware, 2015; Cheng et al., 2016; Chang et al., 2018a).
Because the current interpretation of the mechanism of gravity perception in the Coprinopsis cinerea fruit body is that cytoskeletal interactions communicated to the transmembrane domains of a sugar transporter change its substrate specificity to cause a 6-deoxy hexose sugar growth regulator to be transported asymmetrically (see Sections 9.8 and 12.9), it is significant that the eQTL network analysis of Chang et al. (2018a) identified a sugar transporter as an 'eQTL hotspot'. Such hotspots are believed to regulate expression of several genes, and the sugar transporter identified as a hotspot in this study regulated the expression of at least 12 associated genes. One of those associated genes specifies a Zn-finger protein (which can bind DNA, RNA, proteins or small molecules) and another is a pyranose dehydrogenase enzyme with broad substrate tolerance for oxidation of different sugars. The transporter is thought to interact with the pyranose dehydrogenase via a transcription factor.
We already knew about the extensive use of transcription factors to direct transcription to specific genes in fungi (see above, Sections 2.4; 5.4; 5.13; 6.7; 8.5; 9.4), particularly the homeodomain proteins of the mating type factors (Bobola & Merabet, 2017; Vonk & Ohm, 2018), so add those to the list of fungal regulators. We should also add to that list of regulators translational triggering and feedback fixation, discovered in the 1990s in research on Aspergillus nidulans conidiophores (Section 9.4), which solve the problems of how to respond to a transient signal, and how to maintain that response when the signal has dissipated. The mechanism involves a genetic sequence, in this case the brlA locus, that codes for an RNA transcript containing overlapping reading frames (Fig. 9.9). Alternative splicing of precursor mRNA is now established as an essential mechanism to increase the complexity of gene expression that plays an important role in cellular differentiation and development in eukaryotes (Wang et al., 2015). Alternative splicing is common in higher plants and animals and increases the coding capacity from a limited set of genes. Grützmann et al. (2014) claim that alternative splicing is also a common phenomenon in fungi, and that, on average, about 6.0% of genes in ascomycetes, and 8.6% of basidiomycete genes show alternative splicing (Cryptococcus neoformans had the extraordinary rate of 18%), and that this process is associated with multicellular complexity, dimorphic switching, stress response and pathogenic virulence.
Fungal mycelia, fruit body primordia and mature fruit bodies are attractive sources of food to small animals including molluscs, arthropods and nematodes (Section 11.2; Fig. 11.11), and it is well known that mushrooms produce defence proteins and secondary metabolites to deter such predators and other competitors. Plaza et al. (2014) revealed the existence of two different sets of fungal defence proteins in the proteomes of fruit body primordia of Coprinopsis cinerea. One of the primordium-specific proteins is toxic to insects and nematodes and the expression pattern of these proteins correlates with the type of antagonists with which these tissues are confronted. For instance, cytoplasmic lectins, also referred to as fruit body lectins due to their specific expression pattern, have been shown to be toxic to nematodes, insect larvae and amoebae (Bleuler-Martínez et al., 2011; see Section 15.6). In contrast, vegetative mycelia secrete antibacterial peptides which deter competing bacteria. Known as defensins, these are found in vertebrates, higher plants and invertebrates as well as saprotrophic fungi (Wu et al., 2014). Defensins have therapeutic promise; plectasin, isolated from the ascomycete Pseudoplectania nigrella, is especially active against Streptococcus pneumoniae, including strains resistant to conventional antibiotics. Genome editing techniques are now available to manipulate production of potentially useful metabolites like these (Doudna & Sontheimer, 2014; and see Section 18.14), and a novel method of high-throughput CRISPR/Cas9-based genome editing of Coprinopsis cinerea using cryopreserved protoplasts has been reported (Sugano et al., 2017).
Surprisingly, there is no mention in any of these studies of homologues of sequences of the animal signalling mechanisms known as Wnt, Hedgehog, Notch and TGF-α, all of which are essential and highly conserved components of normal development in animals. Systematic mining of fungal genomes for these sequences established that all were absent from the fungal genomes, just as they are absent from plants (Moore et al., 2005). Subsequently, a fully comprehensive data-mining exercise searched for homologies to all developmental sequences in all sequenced genomes, animal, fungal and plant that were then available (Moore & Meškauskas, 2006; 2009). The outcome was that homology between the genomes of fungi and other eukaryotes was limited to 78 sequences involved in the architecture of the eukaryotic cell. This survey demonstrated that there was no evidence in fungal genomes of Wnt, Hedgehog, Notch, TGF, p53, which are all crucial animal regulators, nor of the plant control sequences SINA, or NAM. All of which leads to the conclusion that the unique cell biology of filamentous fungi has caused them to evolve control of their multicellular development in a radically different fashion from that in animals and plants.
In this Section we have focussed on the developmental biology of Coprinopsis cinerea but as we indicate above in this Section '…there are over 1000 fungal genomes listed as complete in at least draft form in the Mycocosm portal…' We can't prolong this discussion any further, so to ease you into the world of fungal genomics we've put together a list of publications (open access text favoured, so you should be able to obtain the full texts) in the following Resources Box.
MycoCosm is a fungal genomics portal (http://jgi.doe.gov/fungi), developed by the US Department of Energy Joint Genome Institute to support integration, analysis and dissemination of fungal genome sequences and other 'omics' data by providing interactive web-based tools. MycoCosm also promotes and facilitates user community participation through the nomination of new species of fungi for sequencing, and the annotation and analysis of resulting data. View the current list on the following page, and links to publications about the sequences: https://genome.jgi.doe.gov/fungi/fungi.info.html.
Grigoriev, I.V., Nikitin, R., Haridas, S., Kuo, A., Ohm, R., Otillar, R., Riley, R., Salamov, A., Zhao, X., Korzeniewski, F., Smirnova, T., Nordberg, H., Dubchak, I. & Shabalov, I. (2014). MycoCosm portal: gearing up for 1000 fungal genomes. Nucleic Acids Research, 42: D699-D704. DOI: https://doi.org/10.1093/nar/gkt1183.
We have prepared a list of published papers (additional to those cited in the text) that will ease you into the world of fungal genomics. The list has been put together favouring these criteria: (a) open access publishing; and (b) illustrating different approaches.
And check out this special issue of the journal Fungal Genetics and Biology (Volume 89, pages 1-156, April 2016) entitled The Era of Synthetic Biology in Yeast and Filamentous Fungi at https://www.sciencedirect.com/journal/fungal-genetics-and-biology/vol/89/suppl/C.
Lewin, H.A., Robinson, G.E., Kress, W.J., Baker, W.J., Coddington, J., Crandall, K.A., Durbin, R., Edwards, S.V., Forest, F., Gilbert, M.T.P., Goldstein, M.M., Grigoriev, I.V., Hackett, K.J., Haussler, D., Jarvis, E.D., Johnson, W.E., Patrinos, A., Richards, S., Castilla-Rubio, J.C., van Sluys, M.-A., Soltis, P.S., Xu, X., Yang, H. & Zhang, G. (2018). Earth BioGenome Project: Sequencing life for the future of life. Proceedings of the National Academy of Sciences of the United States of America, 115: 4325-4333. DOI: https://doi.org/10.1073/pnas.1720115115.
See also the Earth BioGenome Project website at https://www.earthbiogenome.org/ and the Darwin Tree of Life Project at https://www.sanger.ac.uk/news/view/genetic-code-66000-uk-species-be-sequenced.


text:
Trump's CEQ Appointee Hartnett-White Would Put Environment, Public Health on Dangerous Footing
By Ken Kimmell
Global Research, October 18, 2017
Union of Concerned Scientists 13 October 2017
Theme: Environment, Law and Justice, Poverty & Social Inequality
Featured image: Kathleen Hartnett-White
President Trump has nominated Kathleen Hartnett-White to lead the Council on Environmental Quality (CEQ). A former chair of the Texas Commission on Environmental Quality, Hartnett-White is now affiliated with an oil industry-funded think tank in Austin.
Below is a statement by Ken Kimmell, president of the Union of Concerned Scientists.
"The Council on Environmental Quality has a critical role in making sure federal policy is carried out in accordance with laws that protect our health, safety and the environment. Her record and public statements place her far out of the mainstream, and raise grave doubts about her fitness for this position.
"There's strong evidence that Kathleen Hartnett-White favors private over public interests. At the Texas Commission on Environmental Quality, Hartnett-White often put industry preferences ahead of public health—pushing for a lax ozone standard, approving pollution-intensive coal plants and lowballing fines for companies that violate state laws. Her work at the Texas Public Policy Foundation is funded by fossil fuel companies, creating potential conflicts of interest for her future work at CEQ.
"Most egregiously, she has been vocal in denying the science of climate change. In fact, she has said that the overwhelming acceptance of the evidence for climate change is 'more like the dogmatic claims of ideologues and clerics than scientific conclusions,' that renewable energy is 'parasitic' and 'a false hope,' and that carbon dioxide 'has no adverse environmental impacts on people.'
"Nominating Hartnett-White fits a disturbing pattern of this administration: putting people at agencies with responsibilities they have questioned and in jobs they are unwilling to fulfill. Much like Environmental Protection Agency Administrator Scott Pruitt, Hartnett-White has a clear record of fighting to undermine the very laws she would be charged with overseeing.
"We have already seen the damage that officials such as Pruitt can cause when they are allowed to head agencies whose missions they oppose. We do not need yet another fox to guard the henhouse. It is time for Senators to draw the line and say no to this nominee."
The original source of this article is Union of Concerned Scientists
Copyright © Ken Kimmell, Union of Concerned Scientists, 2017
Articles by: Ken Kimmell

redpajama_set_name: RedPajamaCommonCrawl


I am not satisfied with the price compared to the price, and it works well. I was so satisfied that I ordered one more.
The caustic rain is really good. But I think the durability is a little weak. This is the second purchase, but the first one broke the blade.
Arrive in two days after purchase, delivery is completely satisfied! I would like to add one line to the fact that this product can be purchased easily at a convenience store like CU as an optional cartridge.
I received three days to order. I bought it for a subs and I like it.
I just bought it and tried it. The price is also good and I can not smell it!
The price is cheap, but the weight is not so good.
It was very super quick delivery. There is an advantage that smoking is quicker than icecourse.
The blades are not sold separately.
Hello, Thank you for your return.
We are checking the goods in stock.
We will accept the return of your order as soon as it is confirmed.
As a result of confirming the shipper, we are checking the business again with the invoice number you have stated that it is not yet in stock. Please check again and reply again. Thank you.
If you do not know when the power is turned off and when the power button is turned off, you will not hear anything.
We are in the process of inquiring to the shipper side of your inquiry part.
We may contact you directly from the shipper.
We'll respond to you again.
I contacted your shipper and contacted you directly.
It is said to guide. Please accept the number you do not know.
If you have not received a call, please contact us at 070-7864-8732.
You can call the shipper. Thank you.
The sound continues to sound the same. I am sensitive.
I would like to talk on the phone, but are you so busy?
If you would like to return to Quiten, please let us know.
Pack the item as you received it first.
You can send it to us by cash.
After confirming the commodity is insured, I will return the return of the Kyuten.
Is it possible to send a courier back to the place where I received it, or is it just me?
Can I send it this way?
Please send us the photo you sent us.
Please send it by cash.
We will proceed with the return of goods if confirmed.
When it's done, is the money coming in?
I would like to return to Kyutin.
I will return the stock as soon as the receipt and inspection.
Once we accept the return, we will contact you.
Thank you for your refund.
We have processed the return authorization. If you check your order, you will be returned. Thank you.
When will the refund money come in?
If you have any questions about refunds, please contact us.
Please contact us if you have any questions about refunds. Thank you.
I want to exchange it, but can I just return it?
We will deliver the contents so that we can proceed with the return of goods to the manufacturer. We will proceed to acceptance after receipt and return.
Please send us your payment by return address and send the invoice number.
I will proceed with refund after confirmation.
Please be sure to accept returns as soon as possible.
I tried it, but I can not. ㅠ ㅠ ㅠ I thought it would take a long time to exchange it.
The commodity will proceed with exchange processing.
We will ship the goods to you after confirming that you send us your payment by cash.
I have written 3 times and it's broken. It's not a bad one. I turn on the power. I press 5 times and 3 times. The green light is on and the red light is blinking. The battery is 100 pro. Why are you doing this?
I am sorry for the inconvenience first of you.
We are in the process of submitting inquiries to the sending company.
Please accept it and we will respond once again to the processing result.
I gave you a call, but I answer in my absence.
It is said. Reseat the heating chip normally.
If you still can not do it, please send me a message once again.
We will contact you again after confirmation.


text:
Colleagues gather to honor Eyewitness News anchor Diana Williams
NEW YORK (WABC) -- It was quite a gathering at Channel 7 Tuesday night as a special celebration was held to thank our friend and colleague Diana Williams for her decades of work as a journalist, both in the field and on the anchor desk.
Diana is retiring on Thursday after the 5:00 news following 29 years here at WABC-TV.
Colleagues current and past, and from other stations in New York City, all came together to honor Diana and her family.
Be sure to join us Wednesday and Thursday as we continue to celebrate Diana's career and thank her for her service to the viewers of Eyewitness News for so many years.
Diana, an award-winning reporter and anchor for WABC-TV's top-rated Eyewitness News at 5:00, joined the Eyewitness News Team in 1991.
Before that, she worked at WNEV-TV in Boston and started her career at WBTV-TV in Charlotte, North Carolina - a career spanning 40 years in broadcasting.


Not a phrase that comes to mind in our house when it comes to Christmas decorations.
Like thousands of families around the world we finally put up our Christmas tree on Sunday 1st December. Lots of friends hadn't even held out until December this year with trees popping up in my Facebook news feed from mid November. Now - I LOVE Christmas but I do think you need to wait until December before putting up the tree.
This year we bought a new fake tree. A 7ft beast - I love it.
Long gone is the colour coordinated themed tree of our childless days - now our tree is covered in lots of homemade ornaments from nursery and school and lots of garish glittery baubles.
I really can't stand it when people who have kids won't let them decorate the tree - unless you are Christian and are celebrating a religious holiday then Christmas really is for the children and I love that Miss R has expressed her creativity on the tree.
Not to be outdone both girls decided they would like a tree in their bedrooms. Miss R has plenty of space but poor Miss L has a tiny room - but she loves her little tacky tree and decorated it ALL herself. Can you tell?!
Miss R's tree on the left and Little Miss L's tree on the right. Tasteful huh?!


text:
by Erinn Burgess
U.S. Army Garrison Rheinland-Pfalz Installation Management Command Directorate
Fraud committed by Soldiers can result in a loss of thousands of dollars to the U.S. government every year. That's why U.S. Army Garrison Rheinland-Pfalz is taking measures to combat this crime before it begins.
Interactive training finds signs of adolescent drug, alcohol abuse
Story and photos by Mary Ann Davis
What can adults learn from a cluttered teen bedroom? That's what "Hidden iN Plain Sight" participants found out Feb. 13 at Kaiserslautern Middle School. Hidden iN Plain Sight is designed to help the U.S. Army Garrison Rheinland-Pfalz adult community spot the warning signs of at-risk behavior by providing a hands-on training exhibit of a typical teenager's bedroom for parents, educators, unit leadership, law enforcement and concerned adult community members to recognize common items that may be indicative of substance abuse.
The 435th AGOW and 435th AEW celebrate 75th anniversary
by Jeffrey McGovern, PhD
435th Air Ground Operations Wing and 435th Air Expeditionary Wing historian
Seventy-five years ago this month the U.S. Army Air Forces activated the 435th Troop Carrier Group at Bowman Field, Kentucky. When the Airmen of the 435th and four assigned troop carrier squadrons — the 75th, 76th, 77th and 78th — assembled for the first time February 25, 1943, they unknowingly began an odyssey that continues to reverberate today. The moment established today's 435th Air Ground Operations Wing and 435th Air Expeditionary Wing. It marked the start of a journey where the Airmen of yesterday continue to inspire the Airmen of today.
by Dr. (Maj.) Jonathan Harmon 86th Dental Squadron
Growing up, I had a misguided idea of how to take care of my teeth. I suppose I just had a different definition of what was expected. For example, I thought it was acceptable to drink five sodas every day. At our house, it was normal to substitute fruit snacks for fruit. I even thought it was okay to only brush your teeth when your sister mocked you for having bad breath.
Soldiers helping Soldiers
Was ist los? — Feb. 23, 2018
by Petra Lessoing
The following is a list of performances and events happening in the KMC and nearby locations. Dates are subject to change.
German-American Stammtisch highlights topics, starts discussions
by Petra Lessoing 86th Airlift Wing Public Affairs
The German-American Stammtisch is a monthly get-together of Americans and Germans living in the KMC. They meet at 6:30 p.m. every first Tuesday of the month at the Paradox restaurant in Ramstein-Miesenbach. Actually, a "Stammtisch" is a table, at a restaurant or pub, where guests come regularly to sit down to have a drink and talk.
Women's club holds Pfennig Bazaar March 2 to 4
The German-American and International Women's Club Kaiserslautern will sponsor its annual Pfennig Bazaar March 2 to 4 in the event hall of the Kaiserslautern Gartenschau.
Mark your Calendar — Feb. 23, 2018
Events A MOM2MOM KMC Open House will be noon to 2 p.m. Sunday at the Kaiserslautern Military Community Center. It is a community fair with games for children, food and prizes. Spring Bazaar: Be sure to visit the Spring Bazaar March 9 to 11 at Kleber Fitness Center, Kleber Kaserne, […]
USAFE Band visits Kosovo, celebrates 10th anniversary of independence
Story and photos by Maj. Tristan Hinderliter
U.S. Air Forces in Europe and Air Forces Africa Public Affairs
PRISTINA, Kosovo — The U.S. Air Forces in Europe Band returned Feb. 19 from a six-day trip to Kosovo to celebrate the country's 10th anniversary of independence, capping a whirlwind trip that included building partnerships with the Kosovo Security Forces and outreach events across the country.


Pedantic Soldiers Review finally got hold of some ROSPAKS Greek Hoplites (only 36 years late !).
The box/bag is rather cheaply produced.
It contains 24 figures, 12 standing to attention and 12 attacking with an overarm thrust. All have to be fitted with their shield, provided on separate sprues, and the attackers need their spear-arms gluing in place.
First is the initial disappointment that there were not 100 individually posed and sculpted figures in this pack which cost 50 pence. How manufacturers can justify not giving many hundreds of hours of sculpting work away almost free we fail to understand. Why don't we just give in and also discuss plastic 28mm? We have no answer for that other than we only review figures we think are OK and are about 1/72 scale and 28mm manufacturers may shoot back.
We are presented with two different 'hoplites' . The Classical Greek warriors known for wearing so little that they could hop around all over the place and their opponents. These look just the job with their lack of water bottles, cigarette pouches and other field kit.
We were disappointed that none of the spears were sufficiently sharp to pierce a scaled-down shield or corselet. An omission easily corrected in future sets. The sprues were sufficiently sharp to give a nasty wound as we removed the figures, though.
Imagine our horror when we discovered that under their chitons the figures are not equipped with standard underpants as depicted in Fishing Eagle Publications 'Cool Twats No.37 '300 Spartans (Leatherwear edition)'. Rospaks should step up their game with the next productions.
The helmets seem to be Atheno-Thracian rather than the more prevalent Sparto-Dorian. But buyers can live with this as they tend to be less fussy than us.
Finally some prototypes finisehd of N-Guage ships.
Hemioliai - Hat legionaries for scale.
The ships await epibatai - on the way from Magister Militum.


text:
Anggun — song chords
Anggun was born on April, 29 1974 in Jakarta to the family of the famous Indonesian musician Darto Singo. Anggun's international success started in France where she recorded albums that were released in more than 30 countries making her one of the most popular Asian stars. Anggun's songs, in other languages, can be heard not only in the international charts, but in film soundtracks (for example, The Transporter 2, Gia, etc.) In 2003 the singer was rewarded by the Minister of Culture of France for her services to the country and in 2011 Anggun was announced as France's representative at the 2012 Eurovision International Song Contest in Azerbaijan.
Performer's official web site - www.anggun.com
Echo (You and I)
🎸 A


Those who choose AMARA are opting for a smooth management in all relocation matters.
This is made possible by your individual relocation contract with fixed-price guarantee, which guarantees both costs and legal certainty. The contract is prepared in accordance to your concrete plans and drafted in a meeting with a customer adviser of the AMARA member company of your choice. An agreed fixed price forms an essential part of this contract. Moreover, all offers submitted by AMARA members are binding for their companies. For you, this means guaranteed time, delivery, and price.
AMARA member companies conduct furniture transports and forwarding business exclusively on the basis of the "General Austrian Forwarders' Terms and Conditions" and the "Transportation Terms and Conditions for Furniture Removals" (BBMT).
The BBMT rules govern the rights and obligations between customers and furniture movers/forwarders. They apply to the transport of removal items in the furniture van (furniture trailer, swap body, container, lift van) within Austria and abroad. The provider undertakes toward the customer to conduct the transport in a professional manner and to use trained personnel and suitable materials and means of transport.
We regularly offer legal training courses for our members, thus providing clarity on the current legal situation. You will directly benefit from your customer adviser's expertise during the personal meeting.


text:
Перуштица () — община в Болгарии. Входит в состав Пловдивской области. Население составляет 5344 человека.

Состав общины
В составе общины — один населённый пункт:
 Перуштица

Общины Пловдивской области

redpajama_set_name: RedPajamaWikipedia


Kora National Park in Coast Province – Kenya is one of the national parks in the country that travelers from all across the globe visit to experience its wildlife.
Tagged as a wilderness park, this provides you with the opportunity to view some of the country's most magnificent animals.
Kora National Park in Coast Province – Kenya is approximately two hundred and eighty kilometers off the northeastern section of Nairobi and about one hundred and twenty-five kilometers off Mount Kenya.
The easiest way to reach Kora National Park in Coast Province – Kenya is via Thika heading towards Mwingi. From here, ply the north-eastern route going towards Kyuso village.
From there, ply the route going to the national park which is around eighty or so kilometers off.
You can also reach the park through the bridge that connects Meru National Park with Kora National Park.
Lush vegetation surrounds Kora National Park in Coast Province – Kenya. Visiting the park, you may come across several wild animals such as caracals, hippos, cheetahs, elephants, hyenas, leopards, genets and various antelopes.
But perhaps one of the most awe-inspiring sights to visit here are the huts that used to be the homes of George Adamson, a British wildlife conservationist; and his aide.
Adamson was murdered by Somali bandits back in 1983 when he tried to help a tourist visiting the park. He is buried in the park alongside his lion friend he calls Boy.
There are also various bird species in the park that you can see around the park.
In 1973, Kora National Park in Coast Province – Kenya was designated as a reserve. Following the death of George Adamson, the reserve was designated as a national park in the year 1990.
The park has an area of approximately one thousand seven hundred and eighty-eight square kilometers.
Comprised of dense woodland and scrub, sixty-five kilometers of the park is bounded by the Tana River on its northern side.
The eastern side is bounded by the Mwitamyisi River.
Park entry fees for foreign visitors are pegged at USD50 for adults and USD25 for kids and students during low season and USD60 for adults and USD30 for kids and students during peak season.
Public campsites charge USD15 for adults and USD10 for kids per day.
Fees are per person and valid for twenty-four hours. Student fees are for those aged 18 up to 23 years old. To avail of student fees a valid school identification card must be presented.
Children's fees are for kids aged three years up to seventeen years old.


"On the Way to Emmaus" — a project of the iconographer, Seraphim O'Keefe. This Icon will be located above the entrance to our church, welcoming people as they enter. We will provide updates as this work progresses.


text:
Idea: Monetary Incentive for Students
Elena DellaValle
Students at The University of Akron work on their coursework.
By Elena DellaValle, Guest Writer
How exciting would it be if universities paid students for their good grades? Think about it; college can be a challenging experience, so receiving money for hard-earned A's would be a tangible incentive in addition to the feeling of accomplishment from getting a good grade.
The University of Akron already has a similar concept in effect called the Akron Guarantee Scholarship, which ensures the yearly renewal of students' scholarships if they maintain at least a 2.0 GPA. The guarantee will total $3,500 as they progress through their sophomore, junior and senior years.
"This enhanced scholarship offers important advantages to prospective students. It rewards steady academic progress toward graduation with automatic scholarship increases along the way," Matthew J. Wilson, the president of The University of Akron, said on the school's website.
The Akron Guarantee Scholarship rewards students for their success and so would the concept of paying students for their good grades.
South High Community School, a high school in Massachusetts, gave the reward idea a try back in 2009 as part of the National Math and Science Initiative. The high school opened up their advanced placement courses to all students, and the students who scored a 3 or higher on the exam earned a $100 reward. For context, a 3 is considered good because it's equivalent to a C or better, which is a passing grade.
Joe Nystrom, a math teacher at the low-income school, now teaches advanced placement statistics to eight times as many students as he used to because of the motivation to earn a reward for good test scores. If this idea worked in 2009, it should certainly work in 2017, right?
Here's how the concept of paying college students for their good grades would work: For every exam, a student receives an A on within a semester, he or she would receive $25. The maximum number of exams the concept would apply to is five, so if a student takes five exams within one semester and earns an A on all of them, he or she would receive $125 at the end of that semester. If the student receives another five A's on exams in the next semester, a total of $250 would be given to the student at the end of one school year. The reason for the limit of earning money on up to five exams is for financial reasons so the opportunity can extend to all students.
That sounds wonderful, doesn't it?
"I would have loved to have this incentive during my senior year. Receiving $25 for each A on up to five exams doesn't seem like a lot, but it's enough when you're a college student," Savannah Hudson, a senior who graduates from the University in December, said.
There is, however, a catch to this new concept. It would only apply to students during their senior year of college. The reason for this limitation is because it would set a goal for students to work their way up to their senior year and have the opportunity to take advantage of the incentive.
It could also lessen the rate of college dropouts because it would give incoming students something to look forward to and it could make them work harder during their freshman, sophomore and junior years.
Dr. Val Pipps, a professor at the University, said, "I believe we should try ideas like this for a couple of reasons. This gives a student an incentive to go to class and to pay attention—to strive to do well. The money can help with expenses. Maybe incomes in the form of reduced tuition for the class in which the A was received. Anything the University can do to help offset costs should be studied. If this did work for upperclassmen and women, then let others have a shot."
Furthermore, the concept would benefit the universities that implement it. It could generate more revenue since additional students might be interested and want to attend the participating colleges. It may also lead to higher graduation rates and a better overall ranking for the universities.
The new concept would create motivated students and proud faculty members at universities across the country.


Aryans Group of Colleges established in the year 2007 is among the most reputed chain of institutes in this region. The 20 acre campus is situated near Chandigarh in a lush green and a pollution free environment. Aryans Group of Colleges is organizing 'Aryans 43rd Job Fest' on 6th June 2017. More than 15 renowned Companies are expected to visit the Job fair. It is good Opportunity for Job aspirants.
Chandigarh, Punjab. Are you looking for jobs in Mumbai, Bangalore, Noida, Hyderabad, Pune?


text:
Somalia's Drought Raises a Thorny Issue—Talking to Al-Shabab
By Conor Gaffey On 3/26/17 at 3:10 AM EDT
Internally displaced Somali families rest as they flee from drought-stricken parts of the Lower Shabelle region before entering makeshift camps in Somalia's capital Mogadishu on March 17. Many Somalis suffering from the drought are living under al-Shabab, which controls many rural parts of southern Somalia. Feisal Omar/Reuters
World Somalia Drought Somalia famine Somalia elections
Updated | Just hours after Somalia's new prime minister named his first cabinet at the presidential compound in Mogadishu Tuesday, a massive explosion occurred just a few hundred yards away.
Footage of the aftermath of the blast shared on social media showed several burnt-out vehicles and a crater-like dent in the ground where the explosion occurred outside Somalia's national theater. Somali police said that at least 10 people were killed in the blast, which happened when a suicide attacker rammed a car bomb into a security checkpoint.
On Wednesday, a familiar foe claimed responsibility for the attack: Al-Shabab, an extremist militant group affiliated to al-Qaeda, which is waging war on the Western-backed federal government.
The assault is the latest obstacle to meaningful engagement between the new Somali government and Al-Shabab, at a time when analysts and diplomats have said it is most needed: the current drought in Somalia, which is at risk of escalating into famine, is part of what a senior U.N. official recently called the "worst humanitarian crisis since the creation of the United Nations" in 1945.
Somalia's government is barely a month old: The new president, Mohamed Abdullahi Farmajo, was only inaugurated on February 22, and the cabinet ministers appointed Tuesday have not yet been approved by Parliament. And yet the challenge facing it is huge. Not even six years after a famine that claimed the lives of more than a quarter of a million people, Somalia is again at risk of human disaster on an enormous scale. Some 6.2 million people are in need of humanitarian assistance, and the United Nations is appealing for $825 million to avert a catastrophe in the Horn of Africa country. There are increasing reports of Somalis across the country starving to death, along with pictures of skeletal livestock, left to perish without pasture. As clean water becomes more scarce, Somalis are turning to unsafe water sources, resulting in cholera outbreaks.
The new government has formed a National Drought Response Committee and has urged Somalis in the diaspora to donate; the committee's chairman tells Newsweek that around $2 million has already been raised, and a further $3 million in donations has been pledged. Aid has started to come from the international community, and the United Nations has also been active in opening drought relief centers in some of the worst-affected areas.
But any national response in Somalia is being hampered by the fact that the government does not control all its territory—Al-Shabab still controls significant portions of Somalia, particularly in the South and in rural areas. Former Somali president Hassan Sheikh Mohamud told Newsweek in September 2016 that the militants held around 10 percent of territory in the country.
Analysts say that, even in areas that Al-Shabab does not fully control, the militant group still exerts a semi-territorial presence that can deter government or humanitarian actors. The chairperson of the National Drought Response Committee, outgoing Deputy Prime Minister Mohamed Omar Arteh, has publicly stated that some of the areas worst-affected by the drought are under Al-Shabab's control. Finally, the ongoing conflict between the militant group and the Somali security forces, backed by an African Union mission, has played a role in food shortages in Somalia by displacing many and halting agriculture.
This poses a conundrum for the government, U.N. and other humanitarian actors—to open channels of communication with an extremist militant group in order to ensure aid reaches civilians; or to keep the lines down, potentially risking the fate of a substantial swathe of the Somali population.
Somali President Mohamed Abdullahi Mohamed, known as Farmajo, makes an address in Mogadishu after he was elected president on February 8. Despite allegations of corruption and a limited electorate, Mohammed says Somalia's recent elections constituted a step forward for the country. MUSTAFA HAJI ABDINUR/AFP/Getty
The U.N.'s top official in Somalia has already indicated that the drought might necessitate a change of tact with the militants. "The drought is highlighting the need to engage with Al-Shabab, because al-Shabab controls areas where large numbers of people live," said Michael Keating, the special representative of the U.N. Secretary-General in Somalia, at a talk at U.S. think tank the International Peace Institute in January. (Keating did add a caveat to his statement about engaging with the militants: "We are not there yet.")
Keating was unavailable when contacted for further comment by Newsweek , but the U.N.'s deputy humanitarian coordinator in Somalia, Vincent Lelei, says it has had "no contacts with Al-Shabab militants regarding the drought response thus far" and that there were no plans to coordinate efforts with the group. Lelei added that Al-Shabab "has not provided access directly to U.N. humanitarian agencies to reach people affected by the drought in areas under its control."
Somalia's new president has shown an eagerness to offer Al-Shabab members another path. In his inaugural speech, President Farmajo outlined a strategy for winning over disaffected youth and promised a "good life" to militants who dropped their weapons. But this has not yet translated into open communication between government officials and the militant group.
"We are not [communicating with Al-Shabab and we don't intend to do so...There are no channels of communication," Mohamed Omar Arteh, the chairman of the National Drought Response Committee and outgoing deputy prime minister, tells Newsweek from Mogadishu. But this does not mean that civilians in Al-Shabab-controlled areas are not receiving aid, Arteh says. The committee, he adds, is using "networks" to ensure that those in need are given supplies, while other government sources tell Newsweek that religious and traditional elders are being used as intermediaries with the militants.
"If I explain what we do then it might jeopardize the whole operation," says Arteh. "[But] the most important thing for us is to deliver and that is what we are trying to achieve, to try to reach every Somali and provide the support and aid that they require, wherever they are and regardless of which authority they are under."
A volunteer serves internally displaced Somali people with cooked food from the United Nations World Food Programme initiative at the Sorrdo camp in Hodan district of Somalia's capital Mogadishu on March 11. More than 6 million Somalis are in need of aid due to the drought. Feisal Omar/Reuters
Nevertheless, given the severity of the drought and the limited access to Al-Shabab areas, Somalis living under the militants are likely to be at greater risk, says Abdirashid Hashi, the director of Somalia's first think tank, the Heritage Institute for Policy Studies.
"If the situation is as dire as it is now, then you can imagine that in the areas that Al-Shabab controls, where they are the only ones helping [civilians]...the situation is much worse," Hashi says.
Besides, for Al-Shabab, the drought appears to represent a propaganda opportunity. Sagging white bags of rice, flour and sugar, topped with yellow jerry cans of palm oil, are pictured neatly stacked in piles in the sparse, dry dustlands of southern Somalia in images shared on pro-Al-Shabab social media channels. A video shows a Somali man allegedly saying: "Al-Shabab has provided us with food aid, may Allah bless them." The militant group has its own welfare wing, the Al-Ihsaan Charity Organization—and its own drought emergency committee, whose chairman told Reuters that civilians living under the group's authority "are free" to leave for new pastures in search of food. He also criticized international aid agencies for "talking" while "dying people need action to save them."
Both the U.N. and Somali government sources told Newsweek that anecdotal evidence suggested the militants were providing some degree of drought response, though the images and videos have not been independently verified.
Al-Shabab recruits walk through the Somali capital of Mogadishu, March 5, 2012. The Al-Qaeda affiliate has called for attacks on Western countries, including the United States. A U.S. soldier was killed during an operation targeting the group. Mohamed Abdiwahab/AFP/Getty Images
Al-Shabab's publicity drive may point to an awareness that their response to the 2011 famine did not endear them to Somalis. The group obstructed humanitarian agencies from delivering aid to those under their authority: A 2013 study by U.K.-based think tank the Overseas Development Institute and the Heritage Institute in Mogadishu found that the militants charged exorbitant registration fees of up to $10,000 for aid agencies to work in their areas. In other cases, Al-Shabab simply burned food aid and even killed charity workers. The famine resulted in 260,000 deaths, and the militants lost face over reports that its fighters kept food aid for themselves in many cases rather than distributing to the needy.
Al-Shabab has not indicated any desire to negotiate with the federal government, and any talks would be complicated and delicate. The group does include some moderate elements, and there have been several cases of Al-Shabab fighters renouncing violence for politics, which may be a promising sign for the government's plan to deliver an effective drought response.
But a hardcore of the group remains, as the continued suicide and car bombings in and around Mogadishu attest: Two explosions were reported in the capital on Friday, causing an unknown number of casualties, although the group has not yet claimed responsibility.
The devastating impact of the drought, however, may force Somalia to consider the previously inconsiderable: In some areas, like Somaliland—which is not under al-Shabab control— 80 percent of livestock have reportedly perished.
"In order to operate in these areas, you need to have contact with Al-Shabab, so I'm supportive of that, I think it's worth a try," says Al-Shabab expert Stig Jarle Hansen, a research fellow on Harvard University's international security program. "[The drought] is now an emergency, so it's actually worth the risk."
This article originally misspelled the last name of Mohamed Omar Arteh, the chairman of the National Drought Response Committee.
Somalia's Drought Raises a Thorny Issue—Talking to Al-Shabab | World
Boris Johnson Makes Unannounced Trip to Somalia
Somalia: Why We Must Act Now to Prevent a New Famine
Al-Shabab Executes Four 'Spies' in Somalia
Somalia Embraces the Audacity of Change


NEW BEDFORD, Mass. — Southcoast Health announced today that it has been recognized as one of the finalists for the Boston Business Journal's seventh-annual Healthiest Employers program, which will be held Thursday, Aug. 3, at Community Rowing Inc. in Boston, Mass.
The Healthiest Employers finalists are chosen through an assessment process consisting of 75 scored questions that are completed by the participating companies. Honorees will be highlighted in a special section of the Boston Business Journal on Aug. 3, while each company's scores and final rankings will be revealed at the event on the same day.
"We are excited and honored to be one of the finalists selected this year. It shows that our employee wellness program, HealthQuest, ranks with the best of the best. This is an excellent reflection of Southcoast Health's commitment to the health of their employees and the communities in which we serve," said Kris Aimone, Wellness Coordinator for Southcoast Health.
In partnership with its third-party research and survey manager, Springbuk, the Boston Business Journal evaluated nominee initiatives in the following six categories: leadership commitment, foundational components, strategic planning, communication and marketing, programming and interventions, and reporting and analysis.
The Boston Business Journal, is the leading source for business news, research and events in the greater Boston area.


text:
Westmont Magazine An Entrepreneur with Energy
Rudy Sains Jr. '84 didn't realize he was an entrepreneur until he started a business. Willing to take risks and comfortable not knowing what work was coming in, he has thrived as president of Heritage Energy Group LLC.
Based in Irvine, Calif., the 16-year old business has provided Title 24 energy calculations in accordance with California state law. All new construction must meet certain energy efficiency ratings, and Heritage does the analysis and produces the required documentation.
Heritage Energy Group specializes in residential analysis and consults primarily with large, tract-home builders. His role focuses on administration and special projects; his employees do most of the analysis. Even when the company must do two weeks of work in one week, Rudy takes pride in meeting deadlines.
"We get it done when we say we will get it done," he says. "In Southern California, demand for housing still exceeds the supply, and builders are very busy. It's typical to promise something you can't deliver, but we don't do that. I like the challenge of providing a service rather than a product. It keeps me focused on what clients expect and what I can do to keep them coming back. Some customers have been with me since day one."
Acquiring a competitor added stability to Heritage and broadened the customer base. Instead of seeing this move as risky, Rudy considered it a challenge and an opportunity. "Some people fear these things, but I understand the risk financially and look at it from a business standpoint. I've learned that I think like an entrepreneur. I didn't know that about myself 10 years ago."
One of the benefits of owning a business is the flexibility it provides. "I get to take my kids to school and coach their sports teams," he explains. "My wife, Cheri, and I consider stewardship of our kids our highest priority." Their four children range in age from 3 to 10 years. The couple met when they both worked with the high school program at Calvary Church in Santa Ana, Calif.
Rudy has also had time to volunteer for Westmont as an alumni chapter leader in Orange County with Doug '84 and Sandy Heinrichs '85 Mathews. "It was great to be involved and learn more about Westmont," he says. "It stirred up my pride as an alum."
His best college experience was going to Europe with Professors Paul Wilt and Ed Bouslough. An economics and business major, he played on the junior varsity basketball team and got involved in Potter's Clay as a translator when one of his teammates discovered he was fluent in Spanish.
"God has given me great opportunities," he says. "I was blessed to go to Westmont, and I love running a business. I stopped worrying about next month's work years ago. God provides."
During college, Rudy developed an appreciation for community and the friendships that develop between like-minded people. He sought that same kind of community after he graduated, and found it at Calvary Church. "Friendships with families at church have been an asset to our parenting and a blessing in our lives," he says. "And I will always value my Westmont friends."


This is associate completely superb recording by Nicol Williamson and aimed toward hard- & soft-core Tolkein fans. i'd say that it'd be cherished by anyone ages ten and over. Williamson plays all of the characters and his talent is such one is aware of United Nations agency every character is simply by the assorted voices that he uses (Smaug is fantastic, as is Gollum). Nicol Williamson – The Hobbit Audiobook Online Free.
Because I simply have the L-P record and not have a turntable, i have not been ready to hear the albums for regarding twenty years, therefore i actually hope that somebody can transfer the recording to a CD – presently. regardless of the value once it will eventually start are going to be worthwhile. it'll be fantastic to take a seat within the dark, with a glass of wine and also the phonephone unplugged, and listen for the 3 or four hours that the story unfolds.
While this can be associate emended reading of The imaginary creature it's still my all time favorite rendition. Williamson will a wonderful form of voices and on the occasion once music is employed, it continually will a pretty job of setting the tone. My family wont to hear this on container for long automobile rides and currently I play it for my children (8 and 6) and that they am fond of it too! Nicol Williamson – The Hobbit Audiobook Download Free.
The narration is entirely by Nicol Williamson and his use of regional British accents and tones brings the characters alive in an exceedingly approach that nothing else even approaches.
I was introduced to the story of Bilbo Baggins when i used to be eight years previous and even currently, at age 62, it will bring a tear or 2 to my eyes. My better half and that i 1st detected this narrated version in 1978 once an exponent loaned Pine Tree State his boxed set and being attentive to it once more carried U.S.A. back to those early years of our wedding. The Hobbit Audiobook Free.
Decca/Argo do not seem to have an interest in re-releasing this on CD that could be a pity, therefore if you'll line up of a vinyl copy do therefore and do not accept something nevertheless the Nicol Williamson version – if you are doing, you'll be rather discomfited. Nicol Williamson – The Hobbit Audio Book Online Free.


text:
Plymouth historic district added to National Register of Historic Places
Plymouth historic district added to National Register of Historic Places; Downtown Mansfield Historic District approved for nomination.
Plymouth historic district added to National Register of Historic Places Plymouth historic district added to National Register of Historic Places; Downtown Mansfield Historic District approved for nomination. Check out this story on mansfieldnewsjournal.com: https://www.mansfieldnewsjournal.com/story/news/2018/12/18/plymouth-ohio-historic-district-now-national-register-historic-places/2339714002/
Lou Whitmire, Mansfield News Journal Published 3:25 p.m. ET Dec. 18, 2018 | Updated 3:37 p.m. ET Dec. 18, 2018
The Plymouth Historic District was added to National Register of Historic Places.(Photo: Jason J. Molyet/News Journal)Buy Photo
MANSFIELD - The Plymouth Historic District earlier this month was added to National Register of Historic Places.
The Ohio Historic Site Preservation Advisory Board also voted on Dec. 7 to recommend that the proposed Downtown Mansfield Historic District be nominated to the National Register of Historic Places.
Doug Dickson, a trustee with the Plymouth Historical Society who spearheaded the Plymouth effort, said the district being created will hopefully get merchants to fix up their buildings and get some tax credits to help them do just that.
"There's a lot more work ahead but we have a lot to communicate to business owners about the tax credits. The Historic District is a big deal for a small village like Plymouth," he said. "We want to work on making this village full of specialty stores."
Dickson said a lot of people have been involved: the mayor, council, Plymouth Chamber and many other organizations and members of the historical society trustees. Without the help of the Ohio History Connection (formerly the Ohio Historical Society) it wouldn't have been possible, he added.
Any Plymouth merchant interested in more information regarding tax credits may call 614-298-2000.
"I'm excited and we're very happy for the support of the many agencies in Richland County," he said. "Alan Wigton, president of the Richland County Historical Society, was a big help promoting Plymouth with the initial needed preservation funds. He deserves a lot of credit for this."
Nathalie Wright, a Columbus-based historic preservation consultant, Wednesday said, "The village has historic integrity and if you're just buzzing through the town on the state routes, you might not notice but if you stop, there are a lot of great buildings still intact, including the 5-7 West Broadway building. You rarely see one of the early wood frame buildings still standing."
Wright said the downtown's oldest building is the 1848 Beelman Furniture building at 26 Plymouth St. "It at one time had a porch on it. It was a factory in the 1870s. When you're standing on Plymouth Street it looks quite a lot like the building at 5-7 West Broadway St.," she said, allowing a visitor to imagine what the town looked like in days gone-by.
Old Plymouth Locomotives Buildings in Plymouth, Ohio
Old Plymouth Locomotive Buildings, Plymouth Ohio Jake Furr/ News Journal
She said many of the buildings in the district, like 10 and 16 West Broadway St., are in the Italianate style popular from the 1860s to the 1880s.
Also intriguing are the storefronts with cast iron columns still visible.
Many of the buildings have the original windows which from a preservation standpoint is awesome. They can be repaired to be functional again and energy efficient, Wright said.
Also, even Plymouth's street and public square configuration is interesting, as it reflects War of 1812 road development.
A summary paragraph about that from the nomination, noted:
"Plymouth is significant in illustrating 19th century road networks, village squares and post-War of 1812 settlement patterns in north central Ohio. The 1825 town plat itself remains intact and reflects Plymouth's early settlement along the military and stagecoach roads. The Public Square and all of the principle streets seen on the original plat are still extant today, including the street names. Even the route of Beall's military road, which itself followed an existing Wyandot trail, is still evident as Trux Street/Ohio. 603. The angled roads have not been straightened to conform to a standard grid, and conforming to them created several irregular lots within the village plat. Diagonal blocks in the commercial center continue to reflect Plymouth's historic streetscape."
The Plymouth Historic District is roughly bounded by Dix, Trux, Mills and New Railroad Streets.
Downtown Mansfield Historic District
The proposed district is roughly bounded by Fifth Street to the north, Diamond Street to the east, Second Street to the south and Mulberry Street to the west.
Mansfield Mayor Tim Theaker said it is actually great news for those individuals in the downtown who want to continue to develop and possibly get tax credits to help in the development of their buildings. It's something that is actually going to be an asset to the downtown area," Theaker said.
According to the announcement:
"The proposed historic district reflects Mansfield's growth and development from the 1860s to 1968. Central Park, or the square, a focal point of the district, is a feature of the original plan of Mansfield, which was settled in 1808. Mansfield evolved from a rural county seat to an early railroad junction starting in the 1840s, then into a regional center of commerce and manufacturing from the late 19th century through the 1960s. Buildings in the proposed district date from the 1860s, when the former H.L. Reed Co. on the square was completed, to 1968, when the fifth Richland County Courthouse, also on the square, was finished in a style known as New Formalism, favored at the time for major public buildings like Lincoln Center and the Kennedy Center. The historic district includes nearly 100 downtown buildings illustrating a variety of Victorian and later architectural styles, many by noted Mansfield architects such as Vernon Redding, Althouse & Jones and Thomas G. Zaugg."
Owners or long-term tenants who rehabilitate income-producing properties listed in the National Register can qualify for a 20 percent federal income tax credit if the work they do follows the Secretary of the Interior's Standards for Rehabilitation, guidelines used nationwide for repairs and alterations to historic buildings. A similar 25 percent state income tax credit is also offered through the Ohio Development Services Agency, with assistance provided by the Ohio History Connection's State Historic Preservation Office and the Ohio Department of Taxation, according to information provided by the Ohio History Connection.
lwhitmir@nncogannettt.com
Read or Share this story: https://www.mansfieldnewsjournal.com/story/news/2018/12/18/plymouth-ohio-historic-district-now-national-register-historic-places/2339714002/