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In India, across over 6,50,000 villages and 2,50,000 panchayats represented by 3 million panchayat members. Approx 40% population is living below poverty line, illiteracy rate is more than 25-30% and digital literacy is almost no-existent among more than 90% of India's population.
While the country boasts the world's second fastest-growing mobile market, it is lagging behind when it comes to internet connectivity. Connecting the community and its members to the world through the Internet is becoming increasingly essential for community vitality for the development and social progress in recent years.
According to the IAMAI report, there were about 30,000,000 internet users in rural India in December 2011. The 50 per cent spike leading to the expected 45,000,000 by December 2012 is primarily driven by mobile internet access, community centers and cyber cafes. However, within rural communities, the task to empower using ICT can still be challenging, but many of us have been dedicating time and energies to empower trouble torn community.
NDLM: INTRODUCTION
In a country with more than 6,50,000 villages, where more than half of its population live in rural areas and off-the-map villages. Most are remote and too isolated to benefit from the country's impressive economic progress. Yet there's a growing desire among people in rural India to be part of its modernization process. But, the last-mile delivery has always been a challenge for India. Increasingly the government with the support of NGOs is looking at better ways to reach remote, rural India.
As per the NSSO Level and Pattern of Consumer Expenditure Report 2011, only 3.5 households in 1000 rural households in rural India had internet connectivity at home in 2009-2010. And there are close to 90,000 rural info kiosks (Common Service Centres, Community Information Resource Centres and others) in India, and around 5452 CSCs are located in the state. However, these kiosks lack internet connectivity and services to delivery at people's doorsteps. To make India digitally literate, it is important 3.5 million people to be digitally literate.
For this purpose, the Universal Services Obligation Fund (USOF) has established Bharat Broadband Network Ltd. (BBNL) to roll out the National Optical Fiber Network (NOFN) plan. BBNL will lay out the optic fiber cable terminating in each of the 250,000 gram panchayats in the country, providing 100 MBPs link to be used as information highway to be utilized diversely by all kind of stakeholders to ensure that digital inclusion has reached in all villages across the country. For this, BBNL has identified three pilot blocks – Arain (Rajasthan); Naogang (North Tripura) and Pravada (Visakhapatnam) where the fiber connectivity would be reached and the same would be available for usage free for a month and later on do costing of the project.
With a hope and desire to light up the rural communities and to complement the objectives of NOFN plan, Digital Empowerment Foundation (DEF) supported by with Intel Corporation as a part of the National Digital Literacy Mission has launched Follow the Fibre Programme (FtF) to help rural communities conquer this challenge of digital illiteracy.
About NDLM
National Digital Literacy Mission Programme is a dynamic and integrated platform of digital literacy awareness, education and capacity programmes that will help rural communities to take lead in the global digital economy and help them in maintaining the competitiveness and also shape a technologically empowered society. NDLM is an effort to complement the objectives of National Optic Fibre Netowrk (NOFN) plan to transform one from each household as digitally literate. Under NDLM, we pledge to work with multi-stakeholder to Digitally Literate at least One adult from each of 147 million rural household of India.
DLM will be an ecosystem of digital literacy awareness, education and training that will help India take a lead in the global digital economy and help us maintain the competitiveness and also shape a technologically empowered society. DLM is an effort to extend NOFN objectives to empower rural citizens by making them digitally literate.
The vision of Digital Literacy Mission (DLM) is to create multi-stakeholder, consortium and work with government and their various schemes and agendas to showcase in some of those panchayats constituencies that how making them digitally literate can change the scenario of governance, empowerment, social inclusion, educational approach and employment.
Why NDLM?
To empower rural communities with capacity building & training programmes and make them digitally literate
To facilitate deployment of rural citizen services through digital means
To create a digital data house at every rural community level to make them economically viable
To generate social, cultural and economic advantages for rural communities with two information and content gateway

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Home » India » Newborn baby dragged out of OT and killed by stray dog in UP hospital
Newborn baby dragged out of OT and killed by stray dog in UP hospital
Hospital administration rejected the allegations leveled by Kanchan's family and claimed that her baby was stillborn
By AuthorPTI | Published: 14th Jan 2020 6:18 pm
Farrukhabad: A newborn baby was allegedly dragged out of an operation theatre of a private hospital here and killed by a stray dog, police said on Tuesday.
The incident took place at Akash Ganga Hospital on Monday. The baby's mother, Kanchan, was admitted to the hospital earlier in the day, they said.
Kanchan's family alleged that they were never showed the baby boy and he was dragged out of the operation theatre and killed by a stray dog owing to complete negligence on the part of hospital staff, the police said.
An FIR has been filed against a doctor and the hospital administration on a complaint by Kanchan's husband, Ravi, they said. Superintendent of Police Anil Kumar Misra said a probe is underway and "action will be taken on the basis of the investigation report".
On Monday night, Chief Medical Officer Dr Chandra Shekhar and City Magistrate Sunil Kumar Singh visited the hospital and sealed it, the police said. CCTV camera recordings have also been seized, they said.
The hospital administration rejected the allegations leveled by Kanchan's family and claimed that her baby was stillborn.


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Związek Księgarzy Polskich – stowarzyszenie właścicieli i pracowników księgarń polskich. Zostało założone w roku 1908 jako efekt pierwszego zjazdu polskich księgarzy z zaboru rosyjskiego, który odbył się 9–10 grudnia 1907. Po uzyskaniu przez Polskę niepodległości weszły do niego lokalne organizacje z wszystkich trzech zaborów. Został rozwiązany w roku 1950, a następnie reaktywowany w roku 1956 pod nazwą Stowarzyszenie Księgarzy Polskich.

Tablica pamiątkowa poświęcona polskim księgarzom
Na ścianie Kamienicy Busserowskiej w Warszawie, po wschodniej stronie (zwanej stroną Barssa) Rynku Starego Miasta, znajduje się tablica pamiątkowa poświęcona polskim księgarzom. Wykonana z żeliwa tablica ufundowana została przez Związek Bojowników o Wolność i Demokrację. Napis na tablicy:

Przypisy

Bibliografia

Stowarzyszenia w Warszawie

Stowarzyszenia zawodowe

redpajama_set_name: RedPajamaWikipedia


Brian retired from the University of Guelph (veterinary medicine and agriculture) in 2001 and relocated to Comox on Vancouver Island. He began his study with acclaimed artists in Canada and the US including full-time study at the Jeffrey Watts Atelier in California, drawing and painting from life. He continues to study with exceptional artists.
Brian paints full time in oils and acrylics. His interest is the Canadian landscape, including painting on location (plein air). He has won competitions and awards for both his studio and plein air paintings.
Brian's paintings have been featured in Arabella Magazine, South West Art Magazine and Plein Air Magazine's Plein Air Today. He is also featured in the North Light Books: The Best of Acrylic Painters, 2014, 2015 and 2016.
His paintings have sold across Canada, and internationally. He is represented by galleries in BC, Alberta and Ontario.
Brian and his wife Cathy share their time between Courtenay BC. (winter) and Collingwood, Ontario (summer).
To view Brian's paintings or for information on his Galleries and workshops visit www.brianbuckrell.com.


Single-origin black tea from Darjeeling, with a hint of spice.
Growing high upon the mountains, Darjeeling tea is famously delicate and nuanced — much less common as a base for chai. Honouring the superb natural flavour of this luxury tea, we keep it simple: star anise, green cardamom, and cracked peppercorns add a gentle kick of spice.
Illusory and ephemeral as its meaning, MAYA is a tea that implies that not all is as it seems.
Darjeeling tea is well-known for its unique and nuanced character, as it is commonly described as "the champagne of tea." Much like a fine wine, a high-quality tea is influenced by factors such as region, climate, terroir, and production style.
The tea base for MAYA comes from a small farm in Darjeeling, grown at an altitude of 2000 meters, which results in a refreshingly light and flowery tea. Hand-crafted by its growers, and harvested in the "first flush" (or, the most prized spring harvest season) of 2017, the leaves are of high grade, and are quite exceptional without the addition of milk or sugar.
So as to not overpower the character of the original leaves, a careful balance of spices lightly enhances the flavour, adding an extra level of depth to this luxury tea.


The Lambarene Schweitzer Fellows Award is available to third-year medical students. You must attend a medical school in the New England or New York area and have a working knowledge of French to be eligible for this award. Recipients of this award agree to carry out a health-related community service project of at least 200 hours in collaboration with a local community agency.


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Fermor, Patrick Michael Leigh, 1915 (author)
Correspondence between Patrick Leigh Fermor, Joan Leigh Fermor and NGA, 1990-08-07 - 1996-09-25
Reference Code: GBR/0272/NGA/5/1/592
Scope and Contents This file comprises:-3 autograph letters signed and 2 autograph postcards signed from Patrick Leigh Fermor to NGA. 7 Aug. 1990 - 31 Jan. 19952 autograph letters signed from Joan Leigh Fermor to NGA. 11 Nov. and 9 Feb. [no year]4 carbon typed letters from NGA. 26 Nov. 1990 - 25 Sept. 1996Photocopy from 'The Canturian' (school magazine of the King's School, Canterbury). UndatedPhotocopy of typescript transcript of letters between Philip Toynbee and Patrick Leigh Fermor....
Dates: 1990-08-07 - 1996-09-25
Conditions Governing Access: From the Fonds: Some files are closed because they contain personal information. Most files which are marked as restricted access can be read with the written permission of the author. All other files may be consulted in the Archive Centre following the standard registration procedures.
Found in: Archive Centre, King's College, Cambridge / GBR/0272/NGA, Annan: The Papers of Noel Gilroy Annan / Correspondence / Correspondence with individuals
Letters from Patrick and Joan Leigh Fermor to GHWR, 1975 - 1994
Reference Code: GBR/0272/GHWR/3/147
43 autograph letters signed, 4 autograph postcards signed and 1 telegram. The file also contains several photocopied typescript pieces of travel writing and personal reminiscence by Patrick Leigh Fermor.
Conditions Governing Access: From the Fonds: The majority of the Rylands Papers are readily available to scholars in the Archive Centre. Record consultation is by appointment. Personal letters of living authors may only be consulted with their written permission. Some material is reserved in view of its sensitivity. There is no access to such material for the time being.
Found in: Archive Centre, King's College, Cambridge / GBR/0272/GHWR, Rylands: The Papers of George Humphrey Wolferstan Rylands / Correspondence
Letters from Patrick Leigh Fermor to Frances Partridge, 1960-07-19 - 1994-11-16
Reference Code: GBR/0272/FCP/6/1/53
7 autograph letters signed. The file includes a photocopy of sketches with a poem entitled 'Voix d'Outretombe' by Patrick Leigh Fermor.
Conditions Governing Access: From the Sub-Series: Certain letters are closed under the terms of the Data Protection Act (1998) because they contain sensitive information about living individuals. Researchers may apply in writing to the Archivist to see the closed material, stating the intended use and precise nature of the information requested. The Archivist and Frances Partridge's Literary Executor will then consider whether non-sensitive parts of the letter may be made available, and they will consult the author if necessary. Please be aware that this decision may take several weeks and may incur photocopying charges. A statement to this effect is given with each closed file.
Found in: Archive Centre, King's College, Cambridge / GBR/0272/FCP, Partridge: The Papers of Frances Catherine Partridge / Correspondence / Correspondence
Letters from Patrick Leigh Fermor to JDH, 1954 - 1955
Reference Code: GBR/0272/JDH/26/59
3 autograph letters signed.
Found in: Archive Centre, King's College, Cambridge / GBR/0272/JDH, Hayward: The Papers of John Davy Hayward / Correspondence and related papers


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Yazidi women kept as slaves by IS appeal to UN to intervene in their fight for compensation
Kaamil Ahmed
Photograph: Maya Alleruzzo/AP
Five Yazidi women held as slaves by an Islamic State fighter are appealing to the UN to intervene in their case for compensation in a move lawyers hope will help fix a "lawless" global system that is failing torture survivors.
The women, captured in Iraq in 2014, were taken to Syria as slaves by IS fighters, including the Australian citizen Khaled Sharrouf, who was pictured standing next to his young son holding a severed human head.
The women, in a case due to be filed next week, want the UN's Committee Against Torture to remind Australia of its obligation to provide survivors of violence with redress under the UN's torture convention, which the country has ratified. The Australian authorities have so far denied all requests for compensation.
Lawyers had argued that the women were entitled to compensation under New South Wales law because Sharrouf was born in Sydney and NSW was his last known place of residence. The NSW Victims Rights and Supports Act entitles survivors to $10,000 and other means of support. However, the Australian courts, including the high court, ruled against the women.
Related: 'Still going through hell': the search for Yazidi women seven years on
Philippe Sands KC, one of the lawyers leading the case, said the purpose of taking the complaint to the UN committee is to end the impunity of western governments who have pledged to support Yazidis in their quest for justice.
"You've got a situation of utter lawlessness in which western governments who have committed to rooting it out seem unwilling to take responsibility to provide the institutional and financial mechanisms to deliver on that commitment. If there's a gap, and unless that gap is filled, you have impunity and more lawlessness," said Sands.
"The legal framework as it stands seems incapable of delivering, so this application is intended to fill that gap and seek to recognise the responsibility of a state like Australia to ensure that justice is done for the victims."
In their complaint to the UN, the women argue that Sharrouf's crimes were of universal jurisdiction, and Australia's obligation to act under the torture convention is not limited by territory. They also state that Australia had failed to prevent Sharrouf from leaving the country, despite previous arrests for terror offences.
Yasmin Waljee, the international pro bono partner at the law firm Hogan Lovells, which is representing the women, said the women cannot be compensated by IS or the perpetrator, as Sharrouf is presumed to have been killed in a 2017 US airstrike. Waljee said the case highlighted how difficult it is for survivors to access compensation, even when their abuse had been widely condemned.
"We've got women who experienced sexual violence and violence generally as part of this horrific movement which the world condemned, and yet they've left the victims on their own without any remedy," said Waljee. "It's shocking – you're dealing with post-traumatic stress, suicides, all sorts of horrendous long-term impacts."
Waljee said survivors have short and long-term needs – like healthcare, mental health support and accommodation – that require money. While a positive ruling from the UN committee cannot compel Australia to provide compensation, she said, a finding that the government had breached the convention against torture would be "a move forward" in international law.
"It is important that the experience of these courageous women is widely recognised, documented and remembered. If we don't draw these issues into the light, there's no hope that improvements will ever be made," said Waljee. "The world condemned this movement [IS] and continues to condemn it, but then doesn't try to support the victims in any way."
Lawyers believe the outcome of this case can have implications for survivors of violence in other conflicts, especially those by non-state militias.
Erin Rosenberg, senior legal adviser to the DRC-based Mukwege Foundation, said: "Right now in the Democratic Republic of the Congo, for example, one of the most vicious and brutal is a non-state actor, M23. It's crucial that victims could be provided with redress even when the perpetrator is a terrorist or militia."
Rosenberg, who previously worked at the international criminal court, said that international justice is too focused on prosecuting individuals for crimes against humanity and does not offer enough support for victims. The need for compensation is recognised by most countries but, in reality, few are willing to pay.
"We see a lot of rhetoric from a lot of states about the idea of a victim-centred approach, ensuring victims are provided with redress and able to rebuild their lives, but these talking points are often deprioritised when it comes down to the nuts and bolts of paying," she said.
Democratic Arizona governor to keep migrant busing program
Democratic Arizona Gov. Katie Hobbs is defending her decision to continue her Republican predecessor's program to transport migrants out of border communities. Hobbs said in an interview with The Arizona Republic published Wednesday that her focus would be on ensuring that the state's continued payment of migrants' travel costs is "efficient and humane." "We just wanted to make sure that we were addressing this issue and, as I talked about many times in the campaign, in a way that was the best use of taxpayer resources and something that wasn't a political stunt," Hobbs told the newspaper Tuesday.
Fox News host jokingly suggests Mike Pence could have 'destroyed' classified documents
Fox News host jokingly suggests Mike Pence could have 'destroyed' classified documentsSource: The Five, Fox News
Eldorado Gold (TSE:ELD) Shareholders Will Want The ROCE Trajectory To Continue
If you're looking for a multi-bagger, there's a few things to keep an eye out for. Typically, we'll want to notice a...
'I'm my own psychologist': Sabalenka tames her inner tiger
A year ago, Aryna Sabalenka's serve was in pieces and she was having to scrape through fraught battles in Australia as her fragile emotions were laid painfully bare.The shaky serve that haunted her so badly 12 months ago has been rock-solid, broken just six times in Melbourne.
Mexico's Indigenous rappers find rare spotlight – on Wakanda soundtrack
A new generation of Mexico's Indigenous musicians like Pat Boy are using rap to combat prejudice, revive ancient languages and reignite pride
Julia Fox Goes Viral For Relatable Apartment Tour
Julia Fox posted an apartment tour on TikTok and peopleare loving how relatable it is.
Major updates announced for Mazda UK's top-selling SUV model
Staff set to train in the 'ancient art of Japanese hospitality'
Welby told me gay marriage progress will be 'glacial', says Sandi Toksvig
Comedian says C of E's position is 'untenable' after meeting archbishop of Canterbury
Photos show wrecked cars on streets of Penilee after fire attacks
PHOTOS show the damage caused to several cars following fire attacks in the early hours of this morning.


For small businesses using virtualization, there is no question that the technology provides substantial, measurable benefits for their organizations. Of those that have virtualized, 79 percent say small businesses can see significant benefits from server virtualization, and 65 percent say server virtualization has significantly improved their organization's IT ROI. On average, they are saving 18 percent of their IT budget due to server virtualization implementation.


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Enriched Environment Experience Overcomes Learning Deficits and Depressive-Like Behavior Induced by Juvenile Stress
Yana Ilin,
Affiliation Department of Psychology, The Institute for the Study of Affective Neuroscience (ISAN), University of Haifa, Mount Carmel, Haifa, Israel
Gal Richter-Levin
* E-mail: galrichterlevin@gmail.com
Yana Ilin Gal Richter-Levin
Mood disorders affect the lives and functioning of millions each year. Epidemiological studies indicate that childhood trauma is predominantly associated with higher rates of both mood and anxiety disorders. Exposure of rats to stress during juvenility (JS) (27–29 days of age) has comparable effects and was suggested as a model of induced predisposition for these disorders. The importance of the environment in the regulation of brain, behavior and physiology has long been recognized in biological, social and medical sciences. Here, we studied the effects of JS on emotional and cognitive aspects of depressive-like behavior in adulthood, on Hypothalamic-Pituitary-Adrenal (HPA) axis reactivity and on the expression of cell adhesion molecule L1 (L1-CAM). Furthermore, we combined it with the examination of potential reversibility by enriched environment (EE) of JS – induced disturbances of emotional and cognitive aspects of behavior in adulthood. Three groups were tested: Juvenile Stress –subjected to Juvenile stress; Enriched Environment – subjected to Juvenile stress and then, from day 30 on to EE; and Naïves. In adulthood, coping and stress responses were examined using the elevated plus-maze, open field, novel setting exploration and two way shuttle avoidance learning. We found that, JS rats showed anxiety- and depressive-like behaviors in adulthood, altered HPA axis activity and altered L1-CAM expression. Increased expression of L1-CAM was evident among JS rats in the basolateral amygdala (BLA) and Thalamus (TL). Furthermore, we found that EE could reverse most of the effects of Juvenile stress, both at the behavioral, endocrine and at the biochemical levels. The interaction between JS and EE resulted in an increased expression of L1-CAM in dorsal cornu ammonis (CA) area 1 (dCA1).
Citation: Ilin Y, Richter-Levin G (2009) Enriched Environment Experience Overcomes Learning Deficits and Depressive-Like Behavior Induced by Juvenile Stress. PLoS ONE 4(1): e4329. https://doi.org/10.1371/journal.pone.0004329
Editor: Bernhard Baune, James Cook University, Australia
Received: September 11, 2008; Accepted: October 9, 2008; Published: January 30, 2009
Copyright: © 2009 Ilin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was supported by the EU's PROMEMORIA grant #512012 to GRL, and by a grant from The Institute for the Study of Affective Neuroscience (ISAN) (2007) to GRL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Mood disorders affect the lives and functioning of millions each year. A greater understanding of the neural circuits underlying mood in both normal and abnormal affective states has been identified as one of the critical needs in the field of mood disorders research [1].
Stress, particularly when uncontrollable, excessive and/or prolonged, can produce a myriad of emotional and cognitive alterations [2]–[4]. In some individuals, stress can eventually trigger or exacerbate mood disorders, among which depression and bipolar disorders appear to be particularly linked to aversive life experiences [5]. Chronic stress procedures are currently widely used in experimental animals (mainly rodents) to model depression [6]–[9].
Many of the hormones secreted during stress have been shown to affect learning and memory processes [3], [10], [11]. Thus, stress has been shown to affect synaptic plasticity [3], [12], particularly hippocampal plasticity, dendrite morphology, neurotoxicity and neurogenesis within the dentate gyrus [13], [14]. Stress diminishes hippocampal synaptic plasticity, producing morphological changes in dendritic development, and decreasing neurogenesis in the dentate granule cells. Stress effects on the hippocampal formation and on memory involve other neural structures (e.g., hypothalamus) and neuromodulators (norepinephrine and γ-aminobutric acid (GABA)) [12].
Also, numerous studies have demonstrated that early-life stressful experiences affect both acute and long-term development of neuroendocrine, cognitive and behavioral systems. Exposure to stress or trauma during early childhood may disturb the formation of functional brain pathways, in particular, of the limbic circuits [15]–[18].
Previous findings from our group indicate that an exposure of rats to a relatively brief stressful experience during juvenility (27–29 days of age) has profound and long-lasting behavioral effects [19], [20]. In addition, a short-term juvenile exposure to variable stressors produced two types of impaired avoidance learning reminiscent of symptoms of both mood and anxiety disorders [20], [21].
The importance of the environment in the regulation of brain, behavior and physiology has long been recognized in biological, social and medical sciences [22]. Animals maintained under enriched conditions (EE) have clearly been shown to have reduced aggression [23], reduction of anxiety, fear and excitability [24]–[27], reduction of stress [28]–[30], brain function [31], [32] and better learning abilities [33] than those maintained under standard conditions. However, most of these studies have been carried out in animals with no history of early insults.
Several studies have demonstrated that cell adhesion molecules (CAMs) are involved in corticosterone (CORT) actions in memory and neuroplasticity. Relevant to the current study, the expression levels of a member of the immunoglobulin superfamily, L1-CAM, are considered to be regulated through glucocorticoid-mediated pathways [34]. Moreover, L1-CAM, has been implicated not only in cell interactions during nervous system development, but also in synaptic plasticity and memory formation in the adult brain [35]–[42]. During early development it promotes neurite outgrowth and fasciculation [43], axon pathfinding [44] and myelination [45].
Recent clinical and preclinical work has highlighted L1-CAM as particularly susceptible to showing alterations in stress-related disorders and depression [46]–[50].
Here, we studied the effects of stress during juvenility (JS) (27–29 days of age) on emotional and cognitive aspects of depressive-like behavior in adulthood, on HPA axis reactivity and on the expression of L1-CAM. Furthermore, we combined it with the examination of potential reversibility by enriched environment of JS – induced disturbances of emotional and cognitive aspects of behavior in adulthood.
Alterations in expression level of L1-CAM was checked in the prefrontal cortex (PFC), basolateral amygdala (BLA), dorsal cornu ammonis (CA) area 1 (dCA1) and thalamus (TL). This areas were chosen because they share extensive anatomic connections [51] and found to be affected by early life stress [52]–[54].
The exposure to JS resulted in both mood and anxiety symptoms. Furthermore, EE could reverse most of the effects of JS, at the behavioral, endocrine and at the biochemical levels.
Significant differences (p<0.05) were observed between the body weight gain of the three groups (Naïve, JS and JS+EE). Repeated measure analysis for lingering body weight gain revealed a significant main effect for each measure [WL = 0.005; F(1,174) = 17355.34; p<0.001] and for groups [F(2,114) = 3.84; p<0.024]. Post-hoc Tukey analysis at 30 post natal day (PND) indicated that in comparison with Naïve (unexposed) rats, juvenile-stressed rats (from both groups JS and JS+EE) exhibited less body weight gain when examined 24 h after the exposure to stress. However, one week later (38 PND) this difference was observed only for JS group, there was no difference between Naïve and JS+EE groups. However, later on during the maturation process (at 45, 52, and 59 PND), this difference was no more evident. These results indicate that though the stressor affected body weight gain in the short run, in the long run juvenile-stressed rats (from both groups JS and JS+EE) continued to develop normally in terms of their body weight gain (Figure 1).
Figure 1. Body weight.
JS (n = 39) and JS+EE (n = 39) exhibited less body weight gain when examined 24 h after the exposure to stress compared to Naïve group (n = 48). However, one week later (38 PND) this difference was observed only for the JS group. There was no difference between Naïve and JS+EE groups. Later on during the maturation process (at 45, 52, and 59 PND), this difference was no longer evident. *JS significantly different from Naïve (p<0.05); #JS+EE significantly different from Naïve (p<0.05).
Behavioral Assessments in Adulthood
Animals were tested in the open field (OF) and elevated plus-maze (EPM) at 60 PND, after 1 month in different housing environments. Significant differences in behavioral parameters (activity and anxiety-like behavior) were observed. At the next, 61 PND, day animals were subjected to the TWS avoidance task. Learning abilities of the animals were also affected by the manipulations.
One-way ANOVA revealed a significant effect of group on time spent in the open arena of the OF [F(2,51) = 12.75, p<0.001]. Post-hoc Tukey testing indicated that the time spent in the open arena of the OF of the JS group was significantly lower than that of the Naïve and JS+EE groups. The time spent in the open arena of the JS+EE group was significantly higher than that of the Naïves and JS. The time spent in the open arena of the Naïve group was significantly higher than that of the JS, while being significantly lower than that of the JS+EE group (Figure 2A).
Figure 2. Open Field (OF) Test.
(A) Time spent in the open arena. Time spent in the open arena of the OF of the JS (n = 17) group was significantly shorter than that of the Naïve (n = 20) and JS+EE (n = 17) groups. Time spent in the open arena of the JS+EE group was significantly longer than that of the Naïves and JS. Time spent in the open arena of the Naïve group was significantly longer than that of the JS, while being significantly shorter than that of the JS+EE group. (B) The locomotor activity in the OF. The number of center square crossing of the JS group was significantly lower than that of the Naïve and JS+EE groups. The number of center square crossing of the JS+EE group was significantly higher than that of the Naïves and JS. The number of center square crossing of the Naïve group was significantly higher than that of the JS, while being significantly lower than that of the JS+EE group. There was no difference between the groups in the number of periphery square crossing and total locomotor activity (total number of squares crossed) in the OF. *significantly different from all other groups (p<0.05).
One-way ANOVA revealed a significant effect of group on the number of center square crossing [F(2,51) = 16.54, p<0.001]. Post-hoc Tukey testing indicated that the number of center square crossing of the JS group was significantly lower than that of the Naïve and JS+EE groups. The number of center square crossing of the JS+EE group was significantly higher than that of the Naïves and JS. The number of center square crossing of the Naïve group was significantly higher than that of the JS, while being significantly lower than that of the JS+EE group (Figure 2B).
One-way ANOVA for the number of periphery square crossing showed no significant effect for groups [F(2,51) = 1.87, N.S.] (Figure 2B).
One-way ANOVA for the locomotor activity (total number of squares crossed) showed no significant effect for groups [F(2,51) = 0.92, N.S.] (Figure 2B).
One-way ANOVA revealed a significant effect of group on time spent in the open arms of the EPM [F(2,87) = 8.82, p<0.001]. Post-hoc Tukey testing indicated that the time spent in the open arms of the JS group was significantly lower than that of the Naïve and JS+EE groups. There was no significant difference between JS+EE and Naïve groups (Figure 3A).
Figure 3. Elevated Plus Maze (EPM).
(A) Time spent in the open arms. Time spent in the open arms of the JS (n = 29) group was significantly shorter than that of the Naïve (n = 31) and JS+EE (n = 30) groups. There was no significant difference between JS+EE and Naïve groups. (B) The locomotor activity in the EPM. The line crossing in the open arms of the JS group was significantly lower than that of the JS+EE group. Line crossing in the closed arms of the JS+EE group was significantly higher than that of the Naïve and JS groups. Total line crossing of the JS+EE group was significantly higher than that of the Naïve and JS groups. *significantly different from all other groups (p<0.05); &significantly different from JS+EE group (p<0.05); #significantly different from Naïve group (p<0.05).
One-way ANOVA revealed a significant effect of group on line crossing in the open arms of the EPM [F(2,87) = 4.32, p<0.016]. Post-hoc Tukey testing indicated that the line crossing in the open arms of the JS group was significantly lower than that of the JS+EE group (Figure 3B).
One-way ANOVA revealed a significant effect of group on line crossing in the closed arms of the EPM [F(2,87) = 10.07, p<0.001]. Post-hoc Tukey testing indicated that the line crossing in the closed arms of the JS+EE group was significantly higher than that of the Naïve and JS groups (Figure 3B).
One-way ANOVA revealed a significant effect of group on total line crossing in the EPM [F(2,87) = 8.89, p<0.001]. Post-hoc Tukey testing indicated that the total line crossing of the JS+EE group was significantly higher than that of the Naïve and JS groups (Figure 3B).
Novel-setting exploration
One-way ANOVA revealed a significant effect of group on novel setting exploration [F(2,116) = 12.32, p<0.001]. Post-hoc Tukey testing indicated that the exploratory behavior of the JS group was significantly lower than that of the Naïve and JS+EE groups. The exploratory behavior of the JS+EE group was significantly higher than that of the Naïves and JS. The exploratory behavior of the Naïve group was significantly higher than that of the JS, while being significantly lower than that of the JS+EE group (Figure 4).
Figure 4. Exploration of a novel setting.
Exploratory behavior of the JS (n = 38) group was significantly lower than that of the Naïve (n = 41) and JS+EE (n = 40) groups. The exploratory behavior of the JS+EE group was significantly higher than that of the Naïves and JS. The exploratory behavior of the Naïve group was significantly higher than that of the JS, while being significantly lower than that of the JS+EE group. *significantly different from all other groups (p<0.05).
Two-way shuttle (TWS) avoidance task
Avoidance responses.
One-way ANOVA revealed a significant effect of group on percent of avoidance responses during TWS avoidance task [F(2,24) = 3.79, p<0.037]. Post-hoc Tukey testing indicated that percent of avoidance responses of the JS+EE group was significantly higher than that of the Naïve and JS groups (Figure 5A).
Figure 5. Two-Way Shuttle (TWS) Avoidance learning.
(A) Avoidance responses. Percent of avoidance responses of the JS+EE (n = 8) group was significantly higher than that of the Naïve (n = 10) and JS (n = 8) groups. (B) Escape responses. Percent of escape responses of the JS+EE group was significantly lower than that of the Naïve and JS groups. (C) No Escape responses. Percent of no escape responses of the JS group was significantly higher than that of the Naïve and JS+EE groups. *significantly different from all other groups (p<0.05); #significantly different from Naïve group (p<0.05).
Escape responses.
One-way ANOVA revealed a significant effect of group on percent of escape responses during TWS avoidance task [F(2,24) = 3.96, p<0.033]. Post-hoc Tukey testing indicated that percent of escape responses of the JS+EE group was significantly lower than that of the Naïve and JS groups (Figure 5B).
No Escape responses.
One-way ANOVA revealed a significant effect of group on percent of no escape responses during TWS avoidance task [F(2,24) = 6.75, p<0.005]. Post-hoc Tukey testing indicated that percent of no escape responses of the JS group was significantly higher than that of the Naïve and JS+EE groups (Figure 5C).
Endocrine and Molecular Assessments in Adulthood
At PND 60, between 10:00 and 12:00 h, Naïve, JS and JS+EE groups of animals, without previous history of testing, were taken directly from their home-cages for brain and trunk blood collection.
Concentrations of corticosterone
One-way ANOVA revealed a significant effect of group on basal CORT concentration [F(2,23) = 6.14, p<0.007]. Post-hoc Tukey testing indicated basal CORT concentration of the JS group was significantly higher than that of the Naïve and JS+EE groups (Figure 6).
Figure 6. Serum corticosterone concentration.
Basal CORT concentration of the JS (n = 9) group was significantly higher than that of the Naïve (n = 10) and JS+EE (n = 8) groups. *significantly different from all other groups (p<0.05).
L1-CAM expression
L1-CAM expression was measured at 60 PND in the prefrontal cortex (PFC), basolateral amygdala (BLA), dorsal cornu ammonis (CA) area 1 (dCA1) and thalamus (TL) (Figure 7). Expression levels are depicted as the ratio between the total L1-CAM expression level and β-actin levels in each brain area (i.e. L1-CAM/β-actin), normalized to the Naïve group.
Figure 7. L1-CAM expression at post natal day 60.
(A) L1-CAM expression was measured at 60 PND in the PFC, BLA, dCA1 and TL (Naïve (n = 10); JS+EE (n = 8); JS+EE (n = 8)). Expression levels are depicted as the ratio between the total L1-CAM expression level and β-actin levels in each brain area (i.e. L1-CAM/β-actin), normalized to the Naïve group. In the PFC: no difference between the groups for L1-CAM expression levels. In the BLA: L1-CAM expression levels of the JS group was significantly higher than that of the Naïve group. In the dCA1: L1-CAM expression levels of the JS+EE group was significantly higher than that of the Naïve group. In the TL: L1-CAM expression levels of the JS group was significantly higher than that of the Naïve and JS+EE groups. (B) L1-CAM representative immunoblots. Bottom rows: β-actin; Top Rows: L1-CAM. *significantly different from all other groups (p<0.05); #significantly different from Naïve group (p<0.05).
In the PFC.
One-way ANOVA for L1-CAM expression levels in the PFC showed no significant effect for the group [F(2,26) = 0.17, N.S.].
In the BLA.
One-way ANOVA for L1-CAM expression levels in the BLA revealed significant effect for the group [F(2,23) = 4.22, p<0.027]. Post-hoc Tukey testing indicated that L1-CAM expression levels of the JS group was significantly higher than that of the Naïve group.
In the dCA1.
One-way ANOVA for L1-CAM expression levels in the dCA1 revealed significant effect for the group [F(2,23) = 4.30, p<0.026]. Post-hoc Tukey testing indicated that L1-CAM expression levels of the JS+EE group was significantly higher than that of the Naïve group.
In the TL.
One-way ANOVA for L1-CAM expression levels in the TL revealed significant effect for the group [F(2,25) = 6.09, p<0.007]. Post-hoc Tukey testing indicated that L1-CAM expression levels of the JS group was significantly higher than that of the Naïve and JS+EE groups.
Social/Environmental stress in early life such as maternal separation, isolation, poverty, etc. is not avoidable in many children. Cognitive deficits progressively emerging with development are the results of complex interactions between genetic and environmental factors [55]–[57], and evidence suggests that EE experience can attenuate or reverse a variety of cognitive deficits [58].
This study was designed to experimentally investigate the effects of EE during adolescents on JS rats. We found that, JS rats showed anxiety- and depressive-like behaviors in adulthood, altered HPA axis activity and L1-CAM expression pattern through limbic system areas and the thalamus. Furthermore, we found that EE could reverse most of the effects of JS, both at the behavioral, endocrine and at the biochemical levels.
Our JS protocol resulted in a variety of behavioral changes in the rodents that might be regarded as behavioral correlates of depressive-like symptoms in humans. In our experiment rats were compared in the following tests: (1) OF and EPM tests for the assessment of anxiety level as one of the possible components of depressive state [24], [59]; (2) novel-setting exploration as motivational/hedonic state measure [60]–[62]; (3) TWS avoidance task for revealing a possible sign for cognitive disturbances or learned helplessness (LH) behavior, as an analogue of impaired coping state in depression [63], [64].
Exposure to the JS transiently delayed body weight gain. In comparison with Naïve rats, both juvenile-stressed rats (JS and JS+EE) exhibited less body weight gain when examined 24 h after the exposure (at 30 PND), indicating that both groups were affected in the same way by the stressors. However, one week later, 37 PND, JS rats continued to show less body weight gain than Naïve animals, while JS+EE rats were no longer different from Naïves. This finding indicates that the EE protocol started to have an impact already from the first week.
However, later, during the maturation process, the body weight gain difference was no longer evident, indicating that our variable stress procedure affected body weight gain in the short run; in the long run both JS groups (JS and JS+EE) continued to develop normally in terms of their body weight gain. The same pattern of weight changes was found also by Brunson et. al. [65].
The emotional consequence of exposure to JS was examined in both the OF and the EPM. High anxiety levels of the JS group were found in both tests. In the OF there was a decrease in the time spent in the central arena and center square crossing by JS rats compared to Naïve and JS+EE rats. These findings confirm previous findings of high anxiety level of JS rats even 1 month after the exposure to the stress protocol [19], [20]. EE not only reversed high anxiety levels of JS, but reduced them even below the levels of Naïve animals.
Similar results were obtained in the EPM. JS reduced time spent in open arms (as indicated both by time in open arms and open arms crossing). Exposure of animals to the EE condition during 1 month after JS completely reversed this effect. In fact, EE in JS animals increased total exploratory behavior even beyond that of Naïve animals.
The initial activity of a rat placed in a novel surrounding (e.g. novel setting exploration) can be taken as an indicator of its emotional and motivational state [60]. It is assumed that a novel context/situation reflects both the stress and the rewarding component of novelty. It has been proposed that reduced sensitivity to rewards in rodents might be homologous to human anhedonia [66]. In rats, decreased exploratory activity in a novel environment might reflect decreased motivation or drive, a behavior representing "refractory loss of interest" [60], [67] and may also be related to an hedonic deficit, since novelty is rewarding [61], [62]. In our model JS rats exhibited reduced novel-setting exploration compared to Naïve and JS+EE rats. This reduced exploratory activity may represent the loss of interest in new stimulating situations and may imply the presence of motivational deficits. In contrast, novel-setting exploration of the JS+EE rats not only was higher from JS rats but was also higher from Naïve rats.
During TWS avoidance task JS rats were not different from Naïve-controls in the total number of avoidance or escape responses, but showed significantly more No Escape responses. The increased rates of escape failure (no escape responses) during this task that we found among JS rats may also imply an emotional disruption. Such increases in escape failures were suggested to correspond to learned helplessness, representing, in animals, depressive symptoms of non-responsiveness [68]. EE completely reversed this effect. Furthermore, EE increased total number of avoidance responses even beyond that of Naïve-controls. Improved learning and memory by EE is one of the most consistent findings in the literature [69], [70]. The present results confirm this finding and extend its validity by showing that this effect even overcomes the effects of JS.
Furthermore, exposure to stressors during juvenility affected the HPA axis baseline activity. Analysis of basal circulating CORT levels revealed elevated levels in the JS group, as compared to Naïve and JS+EE groups. Serum corticosterone was used as the traditional anxiety/stress marker [71]. This result provides independent support to indicate that the JS group indeed experienced significantly higher levels of anxiety than either of the other groups. This finding is in agreement with reported physiological abnormality of resting level titers of the hormone in depressed humans [68], [72], [73]. EE reversed also this effect of JS.
Overall, JS appears to trigger anxiety- and depressive-like behaviors; EE was found to be able to reverse these effects. Moreover, EE not only reversed most of JS-induced disruptions but rather, in some parameters made the animals less anxious, more motivated and with better learning abilities compared also with Naïve animals.
L1-CAM, together with other members of the L1 subfamily, is critical for several early development processes like axon outgrowth, fasciculation, neuronal migration and survival [46], [74]–[76]. Furthermore, L1-CAM restriction throughout post-weaning and to adulthood developmental phase also affected stress responsiveness and cognitive functions in adulthood [77], suggesting a key role for L1-CAM in development related processes during adolescence.
In the current study, exposure to stressors during juvenility altered the expression levels of L1-CAM throughout the monitored brain regions. Increased expression of L1-CAM was evident among JS rats in the BLA and thalamus. In the thalamus, EE completely reversed this effect, while in the BLA it only reduced it.
Exposure to stressors during juvenility affected the HPA axis baseline activity as was indicated by elevated basal CORT levels. The amygdala shares extensive anatomic connections with the thalamus [51]. Both these areas serve as feedback sites of HPA regulation in stressed animals [78], so that alteration of L1-CAM expression by JS and by EE could be related to the alterations found in CORT levels under these conditions.
Individual variations in L1-CAM mRNA levels were positively correlated with plasma CORT concentrations and anxiety-like behaviors [38]. It was suggested that chronic-stress induced increased L1-CAM levels may contribute to the chronic stress-associated emotional and cognitive impairments [39], [80]. In addition, in the adult brain, L1-CAM regulation is affected by continuous increased CORT levels or chronic stress exposure [39]. Thus, elevated basal levels of CORT could explain the observed amygadalar and thalamic L1-CAM alterations.
Since L1-CAM was implicated in repair processes in the adult lesioned CNS [81]–[83], chronic-stress induced increased L1-CAM levels were suggested to represent the activation of a neuroprotective mechanism [39], [41], [84]. However, early life stress could disrupt the information processing in the cortex and thalamus of the developing brain, and limbic system particularly, of juvenile rats leading to cognitive and affective disorders. Controversially, the limbic system is most probably modified by EE [24]. Thus, EE experience could rescue the early life induced development disruptions by triggering the release of nerve growth factors, activating neurotransmitter receptors, or enhancing neurogenesis [69], [85], [86].
The interaction between JS and EE resulted in an increased expression of L1-CAM in dCA1, beyond that of Naïve-controls and JS rats. EE has been found to have profound and long-lasting neural and physiological consequences on the hippocampus. EE has been shown to induce higher hippocampal expression of glucocorticoid type II receptor mRNA [87]; enhanced hippocampal field potentials [88], [89]; and hippocampal neurogenesis in adult animals [32], [69]. Thus, L1-CAM increased levels in the dCA1 area could reflect neuroprotective mechanism and the neurogenesis that occurred through interaction between JS and EE.
EE was also found to improve the acquisition and long-term retention of a two-way active avoidance [70]. These changes could be correlated with the behavioral effects of EE compared to controls. It is thus tempting to suggest that these alterations in an area (CA1) associated with the behavior are relevant to the behavioral effects of EE. Further experiments are required to clarify this possibility
In conclusion, our data show that JS applied in rats induces a broad spectrum of behavioral changes reminiscent of depressive symptoms in humans. These results may be helpful for elucidating cellular and molecular mechanisms involved in cognitive deficits and affective disorders caused by early life stress. On the other hand, our findings suggest that EE may be useful to prevent these devastating effects in young adults following childhood stress.
Male Sprague Dawley rats (SD), 22 days old, weighing 35–49 g were purchased from Harlan (Jerusalem, Israel) and habituated in the Brain and Behavior Research laboratory facilities for five days. Three animals were housed per cage in 75×55×15 cm Plexiglas cages in temperature-controlled (23±1°C) animal quarters on a 12∶12 light-dark cycle (lights on 07:00–19:00 hours). They had ad libitum access to standard Purina rodent chow pellets and water.
All procedures and tests were approved by the Institutional Animal Care Committee and adhered to the guidelines of the US Institute of Laboratory Animal Research's Guide for the Care and Use of Laboratory Animals.
Three groups of SD rats were used
JS subjected to variable stress at post natal days (PND) 27–29
JS+EE subjected to variable stress at 27–29 PND and at 30 PND were transfered to EE housing conditions.
Naïve rats.
Juvenile stress procedure
We have designed a juvenile short-term variable stressor protocol [20] in which rats were exposed to a different stressor every day for three days (see below). Stress exposure took place during juvenility (ages 27–29 days) at approximately midday (12:00–14:00) in designated experimental rooms (a different room each day) away from the vivarium.
Day 1. (aged 27 d) Forced swim: 10 min forced swim in an opaque circular water tank (diameter 0.5 m; height: 0.5 m; water depth 0.4 m), water temperature 22±2°C (adapted from Avital et. al. [90]).
Day 2. (aged 28 d) Elevated platform: three 30 min trials; ITI (Inter-Trial Interval): 60 min in the home cage. Elevated platform: 12×12 cm at a height of 70 cm above floor level, located in the middle of a small closet-like room (adapted from [91].
Day 3 (aged 29 d) Restraint stress: Rats were placed in a metal mesh restraining box (11×5×4 cm) that prevented forward-backward movement and limited side-to-side mobility, but did not discomfort the animal in any other way. Rats remained in the restraining box for 2 hrs at 25°C under dim illumination.
Protocols were applied in parallel to rats in the stress groups, so as not to isolate any rat in its home cage. Upon completion of the each of the stress procedures, rats were returned to their home cage.
Environmental Enrichment procedure
Enriched Environment was defined in terms of combination of physical environment and partially social housing conditions. Therefore, animals were housed in larger and higher cages provided with differently shaped plastic containers, colored platforms and suspended objects. The objects were changed twice a week. Once a week all animals from this group were taken together to another enriched box with different objects, wheel, one apple, carrot, cucumber and 50 g of granola.
For both housing conditions: standard and EE, the sawdust of the cage was changed once a week in association with measurement of animals body weight. Rats were put in standard and EE cages at the age 30 PND and maintained in their housing conditions throughout all the experimental assessment.
In the present study in order to prevent the tests from influencing one another, different rats were used for each of the following experiments: (1) behavioral measurements; (2) corticosterone concentrations and L1-CAM expression.
In adulthood, 60–61 PND, coping and stress responses were examined using the open field test, elevated plus-maze test, the novel-setting exploratory behavior, two-way shuttle (TWS) avoidance task.
Open field test (OF).
The apparatus is a quadrant box, 90 cm length with 30 cm wall, divided into 15×15 cm squares. Animal was placed in the center of the field and the following variables were recorded for 5 min: the number of squares crossed and center square entries. The open field was cleaned after each rat. The test room had a dim illumination (40 W) for decreasing the aversiveness of the test.
Elevated plus-maze test (EPM).
The apparatus is elevated 80 cm above a floor and exposed to dim illumination. It consists of two opposite open arms (45×10 cm) and two opposite closed arms of the same size with walls 10 cm high. The arms are connected by a central square (10×10 cm). Each rat was placed on the central-platform facing an open arm and was allowed to explore the maze for 5 min. Each test was videotaped and scored by an independent observer. Arm entry was defined as entering an arm with all four paws. The following terms were used: durations in open arms, open and closed arm crossing and total crossing of all arms.
Novel-setting exploration.
Rats were placed in the two-way shuttle avoidance apparatus described below, although it was in an inoperative mode, and were allowed to explore both compartments for a total of 10 min. Crossingover between compartments provided an index of exploratory behavior.
Two-way shuttle (TWS) avoidance task.
Immediately after the exploratory behavior assessment a training session began. Apparatus: The TWS box, placed in a dimly-lit, ventilated, sound-attenuated cupboard, is a rectangular chamber (60×26×28 cm) divided by an opaque partition with a small flap passage (10×8 cm) that connects two equal sized, side-by-side, cube-shaped compartments. Both metal grid floors of the compartments are weight sensitive and electrifiable. Micro-switches transmit information about the location of the rat to a computer control and data collection program. This program controls both conditioned stimulus (CS) presentations (a tone produced by loudspeakers located on the distal walls of the compartments) and unconditioned stimulus (US) – electric shock deliveries (to the animals' feet through the compartment floor, by a Solid State Shocker/Distributor, Coulbourn Instruments Inc. Lehigh Valley, PA, USA). The TWS avoidance task: One session comprises of 80 "trace conditioning" trials. CS: 10 s tone presentation; US: immediately following the termination of the CS an electric shock (1.2 mA) will be delivered for a maximum of 10 s; ITI: (randomly varying) 30±12 s. Rats could perform one of the following behaviors: (1) Avoidance - shuttling to the adjacent chamber of the apparatus while the tone was on, thus avoiding the shock altogether; (2) Escape - shuttling to the other compartment after the shock began, thus reducing exposure to the shock; (3) No Escape - not shuttling to the adjacent chamber, thus receiving the full length of the shock.
Corticosterone (CORT) radioimmunoassay
Trunk blood was collected into plastic tubes following decapitation between 10:00 and 12:00 h. Samples were centrifuged at 3000 rpm for 20 min at 4°C. Approximately 1 ml of serum from each rat was collected into 1.5 ml Eppendorf tubes and stored at −80°C. The tubes were numbered, but not labeled, so that analysis of CORT levels was blind to the experimental procedure followed. CORT levels were assessed using DSL/10/81000 ELISA kits (DSL, Texas). The sensitivity of the CORT assay was 12.5 µg/L. Within-assay variation was less than 10% at 100 µg/L, and between-assay variation was less than 15% at 100 µg/L.
The CORT serum concentrations were used to further corroborate basal stress levels.
Brain extraction
At the PND 60 animals were taken from their home cages and sacrificed, their brains was extracted, immediately frozen in isoproponol and stored at −80°C. Bilateral tissue punches with seventeen-gauge needle of prefrontal cortex (PFC), basolateral amygdala (BLA), dorsal cornu ammonis (CA) area 1 (dCA1) and thalamus (TL) were obtained from ∼1.5 mm coronal sections cut in a cryostat at −20°C. The coronal sections were approximately +4.0 (PFC), −1.8 (BLA) and −2.0 (dCA1 and TL) from bregma, respectively [92].
The tissues were immediately homogenized in an ice-cold glass/Teflon homogenizer (885502-0019; KONTES GLASS COMPANY, Vineland, NJ, USA) using 50 Teflon/glass mortar strokes in 300 µl of ice-cold NP-40 lysis buffer (20 mM Tris HCl, 20 mM EDTA, 1% NP-40, 137 mM NaCl, 10% glycerol, pH 8), with freshly added with the following protease inhibitors: 0.1 mM sodium orthovanadate, 1 µg/ml leupeptine, 1.6 µg/ml aprotinin and 5 mM NaF and 1 µg/ml protease inhibitor cocktail P2714 (from Sigma). 30 µl of each lysate were saved for further protein concentration by Bradford analysis. The regions were immediately homogenized with ice cold sodium dodecyl sulfate (SDS) sample buffer (20% glycerol, 10% β-mercaptoethanol and 20% SDS, 2.33 gr bromophenol blue in 62.5 mM Tris-HCl, pH 6.8) was added to each remaining lysate, thoroughly mixed and denatured 5 min at 95°C. The denatured proteins were stored at −80°C for further analysis.
Immunoblot analysis
Protein concentration was monitored using Bradford assay, and equal amounts of loaded protein were verified using β-actin staining (1∶1000, II - α-Goat 1∶10000, BIOCHEM; 10% acrylamide). No differences were observed between the groups in β-actin concentrations in any of the examined regions. Individual samples from each region of each rat (20 µg) were loaded onto 7.5% SDS-PAGE gels. Following electrophoresis gels were transferred by wet transfer tanks to nitrocellulose membranes and stained against L1-CAM: (α-NCAM-L1-(C-20) Santa Cruz-SC-1508-1∶1000, II - α-Goat 1∶10000, BIOCHEM). The membranes were developed using the enhanced chemiluminescence light (ECL) (Amersham, Piscataway, NJ) reaction with a charge coupled device (CCD) camera (XRS BioRad).
Densitometric analysis of L1-CAM and β-actin immunoreactivity was conducted using Quantity One 1-D Analysis software. Each sample was measured relative to the background, and expression levels were calculated as the Optical Density (OD) ratio between the β-actin and L1-CAM of each sample.
The results were normalized to Naïve group values.
The results are expressed as means±SEM. For statistical analysis, a one-way ANOVA test was applied. For post-hoc comparisons, the Tukey contrast test was used with an α level of 0.05, unless otherwise noted.
Conceived and designed the experiments: GRL. Performed the experiments: YI. Analyzed the data: YI GRL. Wrote the paper: YI GRL.
1. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, et al. (2002) Neurobiology of depression. Neuron 34(1): 13–25.
2. de Kloet ER, Oitzl MS, Joels M (1999) Stress and cognition: are corticosteroids good or bad guys? Trends Neurosci 22(10): 422–426.
3. Kim JJ, Diamond DM (2002) The stressed hippocampus, synaptic plasticity and lost memories. Nat Rev Neurosci 3(6): 453–462.
4. Roozendaal B (2002) Stress and memory: opposing effects of glucocorticoids on memory consolidation and memory retrieval. Neurobiol Learn Mem 78(3): 578–595.
5. Gold PW, Chrousos GP (2002) Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Mol Psychiatry 7(3): 254–275.
6. McEwen BS (2001) Plasticity of the hippocampus: adaptation to chronic stress and allostatic load. Ann N Y Acad Sci 933: 265–277.
7. Rygula R, Abumaria N, Flugge G, Fuchs E, Ruther E, et al. (2005) Anhedonia and motivational deficits in rats: impact of chronic social stress. Behav Brain Res 162(1): 127–134.
8. Fuchs E (2005) Social stress in tree shrews as an animal model of depression: an example of a behavioral model of a CNS disorder. CNS Spectr 10(3): 182–190.
9. Wilner W (2005) The lone ranger as a metaphor for the psychoanalytic movement from conscious to unconscious experience. Psychoanal Rev 92(5): 759–776.
10. Diamond DM, Park CR, Heman KL, Rose GM (1999) Exposing rats to a predator impairs spatial working memory in the radial arm water maze. Hippocampus 9(5): 542–552.
11. Akirav I, Richter-Levin G (1999) Biphasic modulation of hippocampal plasticity by behavioral stress and basolateral amygdala stimulation in the rat. J Neurosci 19(23): 10530–10535.
12. McEwen BS (1999) Stress and hippocampal plasticity. Annu Rev Neurosci 22: 105–122.
13. McEwen BS (2002) The neurobiology and neuroendocrinology of stress. Implications for post-traumatic stress disorder from a basic science perspective. Psychiatr Clin North Am 25(2): 469–494, ix.
14. McEwen BS (2002) Protective and damaging effects of stress mediators: the good and bad sides of the response to stress. Metabolism 51: 6 Suppl 12–4.
15. Heim C, Nemeroff CB (2001) The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies. Biol Psychiatry 49(12): 1023–1039.
16. Heim C, Plotsky PM, Nemeroff CB (2004) Importance of studying the contributions of early adverse experience to neurobiological findings in depression. Neuropsychopharmacology 29(4): 641–648.
17. Nemeroff CB (2004) Neurobiological consequences of childhood trauma. J Clin Psychiatry 65: Suppl 118–28.
18. Gutman DA, Nemeroff CB (2002) Neurobiology of early life stress: rodent studies. Semin Clin Neuropsychiatry 7(2): 89–95.
19. Avital A, Richter-Levin G (2005) Exposure to juvenile stress exacerbates the behavioural consequences of exposure to stress in the adult rat. Int J Neuropsychopharmacol 8(2): 163–173.
20. Tsoory M, Richter-Levin G (2006) Learning under stress in the adult rat is differentially affected by 'juvenile' or 'adolescent' stress. Int J Neuropsychopharmacol 9(6): 713–728.
21. Tsoory M, Cohen H, Richter-Levin G (2007) Juvenile stress induces a predisposition to either anxiety or depressive-like symptoms following stress in adulthood. Eur Neuropsychopharmacol 17(4): 245–256.
22. Pryce C, Mohammed A, Feldon J (2002) Environmental manipulations in rodents and primates. Insights into pharmacology, biochemistry and behaviour. Pharmacol Biochem Behav 73(1): 1–5.
23. Armstrong KR, Clark TR, Peterson MR (1998) Use of Corn-Husk Nesting Material to Reduce Aggression in Caged Mice. Contemp Top Lab Anim Sci 37(4): 64–66.
24. Chapillon P, Manneche C, Belzung C, Caston J (1999) Rearing environmental enrichment in two inbred strains of mice: 1. Effects on emotional reactivity. Behav Genet 29(1): 41–46.
25. Engellenner WJ, Goodlett CR, Burright RG, Donovick PJ (1982) Environmental enrichment and restriction: effects on reactivity, exploration and maze learning in mice with septal lesions. Physiol Behav 29(5): 885–893.
26. Hansen LT, Berthelsen H (2000) The effect of environmental enrichment on the behaviour of caged rabbits (Oryctolagus cuniculus). Appl Anim Behav Sci 68(2): 163–178.
27. Sharp J, Zammit T, Azar T, Lawson D (2003) Stress-like responses to common procedures in individually and group-housed female rats. Contemp Top Lab Anim Sci 42(1): 9–18.
28. Chamove AS (1989) Cage design reduces emotionality in mice. Lab Anim 23(3): 215–219.
29. Van Loo PL, Van der Meer E, Kruitwagen CL, Koolhaas JM, Van Zutphen LF, et al. (2004) Long-term effects of husbandry procedures on stress-related parameters in male mice of two strains. Lab Anim 38(2): 169–177.
30. Huang-Brown KM, Guhad FA (2002) Chocolate, an effective means of oral drug delivery in rats. Lab Anim (NY) 31(10): 34–36.
31. Bennett EL, Diamond MC, Krech D, Rosenzweig MR (1964) Chemical and Anatomical Plasticity Brain. Science 146: 610–619.
32. Kempermann G, Kuhn HG, Gage FH (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386(6624): 493–495.
33. Patterson-Kane EG, Hunt M, Harper DN (1999) Behavioral indexes of poor welfare in laboratory rats. J Appl Anim Welf Sci 2(2): 97–110.
34. Wakabayashi Y, Uchida S, Funato H, Matsubara T, Watanuki T, et al. (2008) State-dependent changes in the expression levels of NCAM-140 and L1 in the peripheral blood cells of bipolar disorders, but not in the major depressive disorders. Prog Neuropsychopharmacol Biol Psychiatry 32(5): 1199–1205.
35. Dityatev A, Dityateva G, Schachner M (2000) Synaptic strength as a function of post- versus presynaptic expression of the neural cell adhesion molecule NCAM. Neuron 26(1): 207–217.
36. Welzl H, Stork O (2003) Cell adhesion molecules: key players in memory consolidation? News Physiol Sci 18: 147–150.
37. Schachner M (1997) Neural recognition molecules and synaptic plasticity. Curr Opin Cell Biol 9(5): 627–634.
38. Venero C, Tilling T, Hermans-Borgmeyer I, Herrero AI, Schachner M, et al. (2004) Water maze learning and forebrain mRNA expression of the neural cell adhesion molecule L1. J Neurosci Res 75(2): 172–181.
39. Sandi C (2004) Stress, cognitive impairment and cell adhesion molecules. Nat Rev Neurosci 5(12): 917–930.
40. Knafo S, Barkai E, Libersat F, Sandi C, Venero C (2005) Dynamics of olfactory learning-induced up-regulation of L1 in the piriform cortex and hippocampus. Eur J Neurosci 21(2): 581–586.
41. Sandi C, Merino JJ, Cordero MI, Touyarot K, Venero C (2001) Effects of chronic stress on contextual fear conditioning and the hippocampal expression of the neural cell adhesion molecule, its polysialylation, and L1. Neuroscience 102(2): 329–339.
42. Merino JJ, Cordero MI, Sandi C (2000) Regulation of hippocampal cell adhesion molecules NCAM and L1 by contextual fear conditioning is dependent upon time and stressor intensity. Eur J Neurosci 12(9): 3283–3290.
43. Fischer G, Kunemund V, Schachner M (1986) Neurite outgrowth patterns in cerebellar microexplant cultures are affected by antibodies to the cell surface glycoprotein L1. J Neurosci 6(2): 605–612.
44. Cohen NR, Taylor JS, Scott LB, Guillery RW, Soriano P, et al. (1998) Errors in corticospinal axon guidance in mice lacking the neural cell adhesion molecule L1. Curr Biol 8(1): 26–33.
45. Wood PM, Schachner M, Bunge RP (1990) Inhibition of Schwann cell myelination in vitro by antibody to the L1 adhesion molecule. J Neurosci 10(11): 3635–3645.
46. Kenwrick S, Watkins A, De Angelis E (2000) Neural cell recognition molecule L1: relating biological complexity to human disease mutations. Hum Mol Genet 9(6): 879–886.
47. Fransen E, Van Camp G, Vits L, Willems PJ (1997) L1-associated diseases: clinical geneticists divide, molecular geneticists unite. Hum Mol Genet 6(10): 1625–1632.
48. Laifenfeld D, Karry R, Klein E, Ben-Shachar D (2005) Alterations in cell adhesion molecule L1 and functionally related genes in major depression: a postmortem study. Biol Psychiatry 57(7): 716–725.
49. Laifenfeld D, Karry R, Grauer E, Klein E, Ben-Shachar D (2005) Antidepressants and prolonged stress in rats modulate CAM-L1, laminin, and pCREB, implicated in neuronal plasticity. Neurobiol Dis 20(2): 432–441.
50. Laifenfeld D, Klein E, Ben-Shachar D (2002) Norepinephrine alters the expression of genes involved in neuronal sprouting and differentiation: relevance for major depression and antidepressant mechanisms. J Neurochem 83(5): 1054–1064.
51. Price JL, Carmichael ST, Drevets WC (1996) Networks related to the orbital and medial prefrontal cortex; a substrate for emotional behavior? Prog Brain Res 107: 523–536.
52. Leventopoulos M, Ruedi-Bettschen D, Knuesel I, Feldon J, Pryce CR, et al. (2007) Long-term effects of early life deprivation on brain glia in Fischer rats. Brain Res 1142: 119–126.
53. Ichise M, Vines DC, Gura T, Anderson GM, Suomi SJ, et al. (2006) Effects of early life stress on [11C]DASB positron emission tomography imaging of serotonin transporters in adolescent peer- and mother-reared rhesus monkeys. J Neurosci 26(17): 4638–4643.
54. Becker K, Abraham A, Kindler J, Helmeke C, Braun K (2007) Exposure to neonatal separation stress alters exploratory behavior and corticotropin releasing factor expression in neurons in the amygdala and hippocampus. Dev Neurobiol 67(5): 617–629.
55. Matsumoto M, Togashi H, Konno K, Koseki H, Hirata R, et al. (2008) Early postnatal stress alters the extinction of context-dependent conditioned fear in adult rats. Pharmacol Biochem Behav 89(3): 247–252.
56. Mattson MP, Chan SL (2001) Dysregulation of cellular calcium homeostasis in Alzheimer's disease: bad genes and bad habits. J Mol Neurosci 17(2): 205–224.
57. Rice CJ, Sandman CA, Lenjavi MR, Baram TZ (2008) A novel mouse model for acute and long-lasting consequences of early life stress. Endocrinology.
58. Guilarte TR, Toscano CD, McGlothan JL, Weaver SA (2003) Environmental enrichment reverses cognitive and molecular deficits induced by developmental lead exposure. Ann Neurol 53(1): 50–56.
59. Hogg S (1996) A review of the validity and variability of the elevated plus-maze as an animal model of anxiety. Pharmacol Biochem Behav 54(1): 21–30.
60. Katz RJ, Roth KA, Carroll BJ (1981) Acute and chronic stress effects on open field activity in the rat: implications for a model of depression. Neurosci Biobehav Rev 5(2): 247–251.
61. Bevins RA, Bardo MT (1999) Conditioned increase in place preference by access to novel objects: antagonism by MK-801. Behav Brain Res 99(1): 53–60.
62. Bardo MT, Dwoskin LP (2004) Biological connection between novelty- and drug-seeking motivational systems. Nebr Symp Motiv 50: 127–158.
63. Overmier JB, Seligman ME (1967) Effects of inescapable shock upon subsequent escape and avoidance responding. J Comp Physiol Psychol 63(1): 28–33.
64. Seligman ME, Maier SF (1967) Failure to escape traumatic shock. J Exp Psychol 74(1): 1–9.
65. Brunson KL, Kramar E, Lin B, Chen Y, Colgin LL, et al. (2005) Mechanisms of late-onset cognitive decline after early-life stress. J Neurosci 25(41): 9328–9338.
66. Willner P, Muscat R, Papp M (1992) Chronic mild stress-induced anhedonia: a realistic animal model of depression. Neurosci Biobehav Rev 16(4): 525–534.
67. Roth KA, Katz RJ (1979) Stress, behavioral arousal, and open field activity–a reexamination of emotionality in the rat. Neurosci Biobehav Rev 3(4): 247–263.
68. Pryce CR, Ruedi-Bettschen D, Dettling AC, Weston A, Russig H, et al. (2005) Long-term effects of early-life environmental manipulations in rodents and primates: Potential animal models in depression research. Neurosci Biobehav Rev 29(4–5): 649–674.
69. van Praag H, Kempermann G, Gage FH (2000) Neural consequences of environmental enrichment. Nat Rev Neurosci 1(3): 191–198.
70. Escorihuela RM, Tobena A, Fernandez-Teruel A (1994) Environmental enrichment reverses the detrimental action of early inconsistent stimulation and increases the beneficial effects of postnatal handling on shuttlebox learning in adult rats. Behav Brain Res 61(2): 169–173.
71. Mello DM, Marcinichen DR, Madruga D, Branco R, Paschoalini MA, et al. (2007) Involvement of NK1 receptors in metabolic stress markers after the central administration of substance P. Behav Brain Res 181(2): 232–238.
72. Holsboer F (2000) The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 23(5): 477–501.
73. Wong ML, Kling MA, Munson PJ, Listwak S, Licinio J, et al. (2000) Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: relation to hypercortisolism and corticotropin-releasing hormone. Proc Natl Acad Sci U S A 97(1): 325–330.
74. Maness PF, Schachner M (2007) Neural recognition molecules of the immunoglobulin superfamily: signaling transducers of axon guidance and neuronal migration. Nat Neurosci 10(1): 19–26.
75. Brummendorf T, Kenwrick S, Rathjen FG (1998) Neural cell recognition molecule L1: from cell biology to human hereditary brain malformations. Curr Opin Neurobiol 8(1): 87–97.
76. Hortsch M (2000) Structural and functional evolution of the L1 family: are four adhesion molecules better than one? Mol Cell Neurosci 15(1): 1–10.
77. Law JW, Lee AY, Sun M, Nikonenko AG, Chung SK, et al. (2003) Decreased anxiety, altered place learning, and increased CA1 basal excitatory synaptic transmission in mice with conditional ablation of the neural cell adhesion molecule L1. J Neurosci 23(32): 10419–10432.
78. Jaferi A, Bhatnagar S (2006) Corticosterone can act at the posterior paraventricular thalamus to inhibit hypothalamic-pituitary-adrenal activity in animals that habituate to repeated stress. Endocrinology 147(10): 4917–4930.
79. Roozendaal B, Brunson KL, Holloway BL, McGaugh JL, Baram TZ (2002) Involvement of stress-released corticotropin-releasing hormone in the basolateral amygdala in regulating memory consolidation. Proc Natl Acad Sci U S A 99(21): 13908–13913.
80. Sandi C, Bisaz R (2007) A model for the involvement of neural cell adhesion molecules in stress-related mood disorders. Neuroendocrinology 85(3): 158–176.
81. Styren SD, Miller PD, Lagenaur CF, DeKosky ST (1995) Alternate strategies in lesion-induced reactive synaptogenesis: differential expression of L1 in two populations of sprouting axons. Exp Neurol 131(2): 165–173.
82. Jucker M, D'Amato F, Mondadori C, Mohajeri H, Magyar J, et al. (1996) Expression of the neural adhesion molecule L1 in the deafferented dentate gyrus. Neuroscience 75(3): 703–715.
83. Brook GA, Houweling DA, Gieling RG, Hermanns T, Joosten EA, et al. (2000) Attempted endogenous tissue repair following experimental spinal cord injury in the rat: involvement of cell adhesion molecules L1 and NCAM? Eur J Neurosci 12(9): 3224–3238.
84. Venero C, Tilling T, Hermans-Borgmeyer I, Schmidt R, Schachner M, et al. (2002) Chronic stress induces opposite changes in the mRNA expression of the cell adhesion molecules NCAM and L1. Neuroscience 115(4): 1211–1219.
85. Pham TM, Ickes B, Albeck D, Soderstrom S, Granholm AC, et al. (1999) Changes in brain nerve growth factor levels and nerve growth factor receptors in rats exposed to environmental enrichment for one year. Neuroscience 94(1): 279–286.
86. Rampon C, Jiang CH, Dong H, Tang YP, Lockhart DJ, et al. (2000) Effects of environmental enrichment on gene expression in the brain. Proc Natl Acad Sci U S A 97(23): 12880–12884.
87. Mohammed AH, Henriksson BG, Soderstrom S, Ebendal T, Olsson T, et al. (1993) Environmental influences on the central nervous system and their implications for the aging rat. Behav Brain Res 57(2): 183–191.
88. Sharp PE, McNaughton BL, Barnes CA (1985) Enhancement of hippocampal field potentials in rats exposed to a novel, complex environment. Brain Res 339(2): 361–365.
89. Sharp PE, Barnes CA, McNaughton BL (1987) Effects of aging on environmental modulation of hippocampal evoked responses. Behav Neurosci 101(2): 170–178.
90. Avital A, Richter-Levin G, Leschiner S, Spanier I, Veenman L, et al. (2001) Acute and repeated swim stress effects on peripheral benzodiazepine receptors in the rat hippocampus, adrenal, and kidney. Neuropsychopharmacology 25(5): 669–678.
91. Maroun M, Richter-Levin G (2003) Exposure to acute stress blocks the induction of long-term potentiation of the amygdala-prefrontal cortex pathway in vivo. J Neurosci 23(11): 4406–4409.
92. Paxinos G, Watson C (1996) The Rat Brain in Stereotaxic Coordinate, Compact Third Edition. New York: Academic Press.
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"Sweat and tears roll down your face. Your enemies lie in a heap on the floor and yet, more of them still come rolling over the horizon. Your weapons lie shattered beside you, destroyed by your own hand for failing you when you needed them most. Despair and rage fill you, but you steel yourself and prepare to fight on."
It could be a scene from a Dark Souls game, or it could be a scene from your living room whilst playing. Either way, fans of the series know these feelings well, and that is why they love these games.
For too long, gaming fans have begged video game developers to stop making games too easy. They remember the good old days of lives, and impossible jumps, and the sheer panic of being on the brink of having to start six hours of gameplay from the beginning again. But in the world of big-budget modern gaming, developers have verged towards safety, to coddling gamers with infinite saves and barely taxing challenges: the diaper generation of gaming. But the Dark Souls games are aimed squarely at those who are all grown up, and love a challenge.
Without yet having a Dark Souls 3 release date, we look ahead to what fans of the series would love to see in the next iteration.


Actress Jada Pinkett Smith says things are moving in a good direction in Hollywood following the #OscarsSoWhite controversy last year.
The 45-year-old "Girls Trip" star, however, says there is still a long way to go, reported Contactmusic.
Asked if things are better in Hollywood, she says, "I definitely think so. I think things are moving in a good direction. We have a lot of work to do, a lot of work to do - a lot of work to do.
"Like, I did a movie like 'Bad Moms'. 'Bad Moms' was majority white women. And just the way in which the studio handled that movie, in my opinion, was very different than this movie.


text:
Atlas Van Lines named a new service provider for The PGA of America
PGA of America
Series: PGA
Published: Tuesday, November 08, 2011 | 3:54 p.m.
PALM BEACH GARDENS, Fla. (Nov. 8, 2011) -- Atlas Van Lines, one of the world's largest moving companies, has been named a new service provider through 2014 for The PGA of America.
With national headquarters in Evansville, Ind., Atlas Van Lines has become the exclusive transport for PGA-owned operations trailers used at the Senior PGA Championship presented by KitchenAid, the PGA Professional National Championship, PGA Championship and the U.S.-based Ryder Cup.
"It is with a great deal of pride that The PGA of America welcomes Atlas Van Lines, one of the most trusted names in the moving industry, as a service provider for our premier spectator and member championships, and our member professionals," said PGA President Allen Wronowski. "Just as The PGA of America proudly promotes its brand, we welcome the expertise of Atlas Van Lines and its agents, who represent a commitment to quality service."
Under the service provider agreement, Atlas Van Lines also will provide favorable pricing programs for PGA employee relocations, PGA members, employees, Section staff and club members at PGA-staffed facilities. In addition, Atlas will provide a dedicated account manager and PGA member moves will be managed by Atlas agents, many of whom are recipients of Atlas' highest honor, the Milton M. Hill Quality award. Milton M. Hill Quality award winners are recognized for their commitment to quality and professionalism.
Founded in 1948, Atlas Van Lines is a member of Atlas World Group, comprising a family of companies that deliver transportation and related services globally through a network of quality agents and select service partners.
"We are proud to join The PGA of America in a partnership that will allow Atlas to extend our brand and services with an organization that maintains such an excellent reputation," said Jack Griffin, president and COO of Atlas Van Lines.
About Atlas Van Lines
Atlas Van Lines, a national moving company, is the largest subsidiary of Atlas World Group, an Evansville, Ind.-based company. Atlas World Group companies employ nearly 700 people throughout North America. Nearly 500 Atlas interstate moving agents in the United States and Canada specialize in corporate relocation, household moving services and in the specialized transportation of high-value items such as electronics, fine art, new fixtures and furniture. Visit atlasvanlines.com for further information.
About The PGA of America
Celebrating its 95th year, The PGA of America has maintained a twofold mission of its founders: to establish and elevate the standards of the profession and to grow interest and participation in the game of golf.
By establishing and elevating the standards of the golf profession through world-class education, career services, marketing and research programs, The PGA enables its professionals to maximize their performance in their respective career paths and showcases them as experts in the game and in a multi-billion dollar golf industry.
By creating and delivering dramatic world-class championships and exciting and enjoyable promotions that are viewed as the best of their class in the golf industry, The PGA of America elevates the public's interest in the game, the desire to play more golf, and ensures accessibility to the game for everyone, everywhere. The PGA of America brand represents the very best in golf.
Home » Atlas Van Lines named a new service provider for The PGA of America


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Visiting elderly parents is an important factor in their mental health and even helps to ward off dementia, it has been found. The English Longitudinal Study of Ageing (ELSA) discovered that families with "reliable, approachable and understanding" relationships are key to preventing Alzheimer's disease.
While having spouses and children that are caring is beneficial, having a bad relationship or no contact with grown up children can have the opposite effect. Those who are critical of their parents and unreliable "can be a source of intense interpersonal stress, which may have a negative impact on both physical and mental health of older adults," the study's authors stated.
The research was carried out over a significant timeframe, with 10,055 assessed in 2002 and deemed Alzheimer's-free. At intervals of two years, they were then interviewed again over the course of a decade and their cognitive decline reported. They also completed questionnaires to establish the level of social support from family.
Answering six questions and ranking them on a scale of one to four allowed researchers to discern which category they fitted into. Just one point more in the social support scale correlated to a 17 per cent drop in the instantaneous risk of developing dementia, the study found. In the opposite direction, a negative support score of just one point difference saw the risk rise by 31 per cent.
Between 2004-2012, 3.4 per cent of the study's participants developed some form of dementia. The research sample was made up of 5,475 men and 4,580 women, all of whom were over the age of 50 and living in England.
Dr Mizanur Khondoker, a senior lecturer in medical statistics at UEA's Norwich Medical School, said: "It is well known that having a rich network of close relationships, including being married and having adult children, is related to a reduced risk of cognitive decline and developing dementia.
This latest research, which was published in the Journal of Alzheimer's Disease, adds to the body of evidence on social relationships and dementia risk. It underlines the importance of the quality of interactions, as opposed to quantity and is something that all children with elderly relatives should bear in mind.
Scientists from the University of East Anglia (UEA), University College London (UCL), London Metropolitan University, and the University of Nottingham all worked together on the study. It highlights the importance of a collaborative approach in tackling Alzheimer's and dementia.
At present, there is no cure for the conditions and the best approach is to lead a healthy lifestyle in a bid to stave off the onset. As more is known about Alzheimer's and dementia, it is hoped that medication can be developed to reverse the effects. In the meantime, the number of people suffering in the UK is increasing all the time and expected to reach two million by 2051.


text:
Al Capp Residence
122 Beacon Street
Boston, MA 02116 United States
When Alfred Gerald Caplin was nine years old, he lost his left leg in a trolley car accident near his hometown of New Haven, CT. Socially shunned and indignant, his father introduced him to drawing as a kind of refuge, and young Al found his life's calling.
After briefly attending a series of art schools — including the Boston Museum School of Fine Arts — Caplin left for New York to pursue a career as a cartoonist in the depths of the Great Depression. While apprenticing with Ham Fisher, creator of the "Joe Palooka" comic strip, Caplin spent his nights on a story concept about his teenage trips hitchhiking across the mountain towns of West Virginia. In August 1934, he sold and published the first Li'l Abner comic strip — under the name "Al Capp" — to immediate acclaim.
Li'l Abner features a panoply of characters and storylines, rooted in the backwater hamlet of Dogpatch, and centered around the loutish but good-natured Li'l Abner Yokum. Dogpatch residents are visited by unseemly city slickers and government officials, and sometimes travel themselves to far-flung locales like Hollywood or the Moon. In its 40+ year run, Li'l Abner became one of the most successful comic strips in history, appearing in over 900 papers in 28 countries and inspiring themed movies, plays, amusement parks, and merchandise.
Capp is credited with transforming the comic strip genre into a vehicle for social commentary and satire. His strips parodied cultural icons like The Beatles and Senator Joseph McCarthy, and introduced phrases like "double whammy" and "Sadie Hawkins" into the mainstream lexicon. John Steinbeck once compared Capp to Cervantes and claimed that he "may very possibly be the best writer in the world today."
Coinciding with the "golden age" of the American comic strip, Capp's famed cartoon bolstered him into the limelight. He was a controversial though sympathetic presence on TV shows, radio broadcasts, and university campuses, and often volunteered to meet with veterans who had lost a limb. Although his political ideologies leaned left, he was unsettled by the turbulence of the 1960s, which often played out in his neighborhood of Cambridge, where he lived with his wife, Catherine Camerino.
A lifelong smoker, Capp's health began to fail in the '70s as he battled bouts of emphysema, and his condition worsened after the tragic deaths of his daughter and granddaughter. He passed away in 1979 and is buried in Mount Prospect Cemetery in Amesbury, MA.