Miracle-dz/UniFAR-FTUs huggingface dataset:
Cannabinoids modulate hippocampal memory and plasticity

Considerable evidence demonstrates that cannabinoid agonists impair whereas cannabinoid antagonists improve memory and plasticity. However, recent studies suggest that the effects of cannabinoids on learning do not necessarily follow these simple patterns, particularly when emotional memory processes are involved. We investigated the involvement of the cannabinoid system in hippocampal learning and plasticity using the fear‐related inhibitory avoidance (IA) and the non‐fear‐related spatial learning paradigms, and cellular models of learning and memory, i.e., long‐term potentiation (LTP) and long‐term depression (LTD). We found that microinjection into the CA1 of the CB1/CB2 receptor agonist WIN55,212‐2 (5 μg/side) and an inhibitor of endocannabinoid reuptake and breakdown AM404 (200 ng/side) facilitated the extinction of IA, while the CB1 receptor antagonist AM251 (6 ng/side) impaired it. WIN55,212‐2 and AM251 did not affect IA conditioning, while AM404 enhanced it, probably due to a drug‐induced increase in pain sensitivity. However, in the water maze, systemic or local CA1 injections of AM251, WIN55,212‐2, and AM404 all impaired spatial learning. We also found that i.p. administration of WIN55,212‐2 (0.5 mg/kg), AM404 (10 mg/kg), and AM251 (2 mg/kg) impaired LTP in the Schaffer collateral‐CA1 projection, whereas AM404 facilitated LTD. Our findings suggest diverse effects of the cannabinoid system on CA1 memory and plasticity that cannot be categorized simply into an impairing or an enhancing effect of cannabinoid activation and deactivation, respectively. Moreover, they provide preclinical support for the suggestion that targeting the endocannabinoid system may aid in the treatment of disorders associated with impaired extinction‐like processes, such as post‐traumatic stress disorder. © 2009 Wiley‐Liss, Inc.
Delay to Formalin Fixation Effect on HER2 Test in Breast Cancer by Dual-Color Silver-enhanced In Situ Hybridization (Dual-ISH)

Background:HER2 status is an integral part of breast cancer management. One of the variables that negatively affects HER2 test is delay to formalin fixation (DFF). The purpose of this study is to determine the effect of progressive DFF on HER2-dual color in situ hybridization (Dual-ISH). Materials and Methods:Ten palpable invasive breast cancers were included in the study. For each case, the procured tumor was divided into 8 parts and consecutively fixed after 0, 10, 30 minutes, 1, 2, 4, and 8 hours; 1 section was kept in saline and stored overnight (ON) at 4°C. Two tissue microarray blocks were constructed. Then, HER2 was tested with Dual-ISH. HER2 and CEP17 signal and HER2/CEP17 ratio was calculated in 10 cells for each core. The percentage of cells that had complete loss of signal was calculated. The percentage of cells that had nuclear bubbling and/or background staining was also calculated. Results:DFF had no statistically significant effect on HER2/CEP17 ratio, absolute number of HER2, or CEP17 signals. However, 1 case became falsely amplified in ON sample. The trend of the percentage of cells that lost signal with time of DFF was statistically significant (P<0.001), more notably after 1 hour of DFF. Nuclear bubbling and/or haze or dust was seen in 4 cases (P=0.009). These changes started to appear at 30 minutes to 1 hour DFF (P=0.025 and 0.003, respectively). Conclusions:DFF has no statistically significant effect on the HER2/CEP17 ratio tested by Dual-ISH. However, significant artifacts could occur in samples fixed after 1 hour of DFF time.
Male circumcision to prevent syphilis in 1855 and HIV in 1986 is supported by the accumulated scientific evidence to 2015: Response to Darby

ABSTRACT An article by Darby disparaging male circumcision (MC) for syphilis prevention in Victorian times (1837–1901) and voluntary medical MC programs for HIV prevention in recent times ignores contemporary scientific evidence. It is one-sided and cites outlier studies as well as claims by MC opponents that support the author's thesis, but ignores high quality randomised controlled trials and meta-analyses. While we agree with Darby that risky behaviours contribute to syphilis and HIV epidemics, there is now compelling evidence that MC helps reduce both syphilis and HIV infections. Although some motivations for MC in Victorian times were misguided, others, such as protection against syphilis, penile cancer, phimosis, balanitis and poor hygiene have stood the test of time. In the absence of a cure or effective prophylactic vaccine for HIV, MC should help lower heterosexually acquired HIV, especially when coupled with other interventions such as condoms and behaviour. This should save lives, as well as reducing costs and suffering. In contrast to Darby, our evaluation of the evidence leads us to conclude that MC would likely have helped reduce syphilis in Victorian times and, in the current era, will help lower both syphilis and HIV, so improving global public health.
Ultrastructural modifications of spine and synapse morphology by SAP97

Synaptic scaffolding proteins from membrane‐associated guanylate kinases (MAGUK) family are implicated in synapse formation and functioning. To better understand the role of one of the proteins of this family, SAP97, we studied with electron microscopy the effects of its overexpression on spine and synapse morphology in CA1 pyramidal neurons of rat organotypic hippocampal slice cultures. Dramatic spine enlargement induced by SAP97 overexpression was accompanied by marked morphological changes, with spines enwrapping and engulfing presynaptic terminals. The size and complexity of the PSD was also significantly increased. Similar to PSD‐95, SAP97 promoted formation of multi‐innervated spines (MIS). In addition, both MAGUK proteins induced multiple excitatory contacts on dendritic shafts suggesting a mechanism for shaft synapse formation. Formation of MIS and shaft synapses was blocked by the nitric oxide synthase (NOS) inhibitor L‐NAME. Immunochemistry revealed that overexpression of SAP97 was associated with overexpression of PSD‐95 and recruitment of nNOS to the synapse. These data provide evidence for both common and distinct structural alterations produced by overexpression of SAP97 and PSD‐95 and demonstrate strong interactions between these two proteins to regulate contact formation through nitric oxide signaling. © 2010 Wiley‐Liss, Inc.
Detailed descriptions of routes traveled, but not map‐like knowledge, correlates with tests of hippocampal function in older adults

We examined hippocampal contribution to remote spatial memory in older adults by correlating their performance on tests sensitive to hippocampal damage with their description of routes they traversed many times or only once, and with their map‐like knowledge of downtown Toronto. We found that performance on table‐top tests of spatial location (Smith and Milner ( 1981 ) Neuropsychologia 19:781–793) and on paired‐associate learning, and the number of Internal Details on the Autobiographical Interview (Levine et al., ( 2002 ) Psychol Aging 17:677–689), all correlated significantly with the number and type of perceptual details used in describing routes one has traversed, but not with map‐like knowledge of Toronto. No significant correlations were found with performance on tests of frontal function (WCST, phonemic fluency, and backward digit span). We conclude that the hippocampus is implicated in vivid re‐experiencing of a familiar route, but not with map‐like knowledge of a large‐scale environment. These findings are interpreted as consistent with Multiple Trace Theory's prediction that it is the degree of detail of a retrieved memory that is crucially dependent on the hippocampus. © 2010 Wiley Periodicals, Inc.
Quantitatively and qualitatively different cellular processes are engaged in CA1 during the consolidation and reconsolidation of contextual fear memory

Whether the consolidation and reconsolidation long‐term memory relies on qualitatively different molecular and cellular processes is controversial. Using a novel experimental strategy of combining intrahippocampal antisense oligodeoxynucleotides targeting BDNF or zif268 to the block consolidation or reconsolidation of contextual fear memory respectively, and Affymetrix microarray technology, we identified a comprehensive list of nonoverlapping candidate genes regulated in CA1 during the initial stages consolidation and reconsolidation. Using RT‐qPCR in subsequent validation experiments, we estimated that over 80% of the candidates reflect gene transcripts truly regulated following the acquisition or retrieval of contextual fear memory. Statistical and over‐representation bioinformatics analyses revealed that cellular processes and signaling mechanisms were differentially regulated during consolidation and reconsolidation, particularly those associated with pro‐inflammatory cytokine signaling. This predicts that the two mnemonic processes are qualitatively as well as quantitatively distinct. This experimental strategy was further validated because the cytokine interleukin 1 (IL‐1) was reciprocally regulated in CA1 after contextual fear conditioning and fear memory retrieval, and we showed for the first time that that IL‐1 receptor mediated signaling in the hippocampus was necessary for reconsolidation. © 2010 Wiley Periodicals, Inc.
The single place fields of CA3 cells: A two‐stage transformation from grid cells

Granule cells of the dentate gyrus (DG) generally have multiple place fields, whereas CA3 cells, which are second order, have only a single place field. Here, we explore the mechanisms by which the high selectivity of CA3 cells is achieved. Previous work showed that the multiple place fields of DG neurons could be quantitatively accounted for by a model based on the number and strength of grid cell inputs and a competitive network interaction in the DG that is mediated by gamma frequency feedback inhibition. We have now built a model of CA3 based on similar principles. CA3 cells receive input from an average of one active DG cell and from 1,400 cortical grid cells. Based on experimental findings, we have assumed a linear interaction of the two pathways. The results show that simulated CA3 cells generally have a single place field, as observed experimentally. Thus, a two‐step process based on simple rules (and that can occur without learning) is able to explain how grid cell inputs to the hippocampus give rise to cells having ultimate spatial selectivity. The CA3 processes that produce a single place depend critically on the competitive network processes and do not require the direct cortical inputs to CA3, which are therefore likely to perform some other unknown function. © 2010 Wiley Periodicals, Inc.
A longitudinal study of childhood obesity, weight status change, and subsequent academic performance in Taiwanese children.

BACKGROUND This study examined the association among childhood obesity, weight status change, and subsequent academic performance at 6-year follow-up. METHODS First-grade students from one elementary school district in Taichung City, Taiwan were followed for 6 years (N = 409). Academic performance was extracted from the school records at the end of each grade. Weight and height were measured at the beginning of each grade. A weight change variable was created based on each child's weight status difference at grades 1 and 6. A multivariate linear regression model for predicting academic performance at grade 6 was developed with adjustment for individual characteristics and family factors. A latent growth curve (LGC) showed the association between changes in body mass index (BMI) and in academic performance across a 6-year period. RESULTS BMI in children increased significantly across 6 years. The rate of increase in BMI over 6 years was higher for children with higher baseline BMIs than it was for children with lower baseline BMIs. However, BMI changes were not significantly associated with changes of academic performance. CONCLUSION There was no significant relationship between initial obesity or change in weight status and subsequent academic performance. It appears that either being or becoming overweight/obese did not impact academic achievement for these Taiwanese children.
A role for the CAMKK pathway in visual object recognition memory

The role of the CAMKK pathway in object recognition memory was investigated. Rats' performance in a preferential object recognition test was examined after local infusion into the perirhinal cortex of the CAMKK inhibitor STO‐609. STO‐609 infused either before or immediately after acquisition impaired memory tested after a 24 h but not a 20‐min delay. Memory was not impaired when STO‐609 was infused 20 min after acquisition. The expression of a downstream reaction product of CAMKK was measured by immunohistochemical staining for phospho‐CAMKIThr177 at 10, 40, 70, and 100 min following the viewing of novel and familiar images of objects. Processing familiar images resulted in more pCAMKI stained neurons in the perirhinal cortex than processing novel images at the 10‐ and 40‐min delays. Prior infusion of STO‐609 caused a reduction in pCAMKI stained neurons in response to viewing either novel or familiar images, consistent with its role as an inhibitor of CAMKK. The results establish that the CAMKK pathway within the perirhinal cortex is important for the consolidation of object recognition memory. The activation of pCAMKI after acquisition is earlier than previously reported for pCAMKII. © 2011 Wiley Periodicals, Inc.
Glutamate decarboxylase67 is expressed in hippocampal mossy fibers of temporal lobe epilepsy patients

Recently, expression of glutamate decarboxylase‐67 (GAD67), a key enzyme of GABA synthesis, was detected in the otherwise glutamatergic mossy fibers of the rat hippocampus. Synthesis of the enzyme was markedly enhanced after experimentally induced status epilepticus. Here, we investigated the expression of GAD67 protein and mRNA in 44 hippocampal specimens from patients with mesial temporal lobe epilepsy (TLE) using double immunofluorescence histochemistry, immunoblotting, and in situ hybridization. Both in specimens with (n = 37) and without (n = 7) hippocampal sclerosis, GAD67 was highly coexpressed with dynorphin in terminal areas of mossy fibers, including the dentate hilus and the stratum lucidum of sector CA3. In the cases with Ammon's horn sclerosis, also the inner molecular layer of the dentate gyrus contained strong staining for GAD67 immunoreactivity, indicating labeling of mossy fiber terminals that specifically sprout into this area. Double immunofluorescence revealed the colocalization of GAD67 immunoreactivity with the mossy fiber marker dynorphin. The extent of colabeling correlated with the number of seizures experienced by the patients. Furthermore, GAD67 mRNA was found in granule cells of the dentate gyrus. Levels, both of GAD67 mRNA and of GAD67 immunoreactivity were similar in sclerotic and nonsclerotic specimens and appeared to be increased compared to post mortem controls. Provided that the strong expression of GAD67 results in synthesis of GABA in hippocampal mossy fibers this may represent a self‐protecting mechanism in TLE. In addition GAD67 expression also may result in conversion of excessive intracellular glutamate to nontoxic GABA within mossy fiber terminals. © 2011 Wiley Periodicals, Inc.
Culture, myths and panic: Three decades and beyond with an HIV/AIDS epidemic in Zimbabwe

ABSTRACT Zimbabwe is going through a generalised acquired immunodeficiency syndrome (AIDS) epidemic. The first five years of the epidemic (1985-1990) were characterised by lack of medicines against human immunodeficiency virus (HIV), and an exponential increase in prevalence (65-fold) and incidence (13-fold), which were fuelled by high-risk sexual behaviour. The high HIV prevalence, mortality and stigma yielded great fear and panic in the population, which are thought to have led to confusion and hopelessness, and, in turn, increased risky sexual behaviour. The country’s government and civil society embarked on HIV awareness campaigns that are claimed to have played a central role in slowing down the epidemic since the mid-2000s. HIV-related mortality then fell by 70% between 2003 and 2013, which is attributed to high uptake of antiretroviral therapy (ART) and prevention of mother-to-child transmission (95%) prophylaxis. However, the epidemic has been characterised by a low paediatric ART coverage (35% in 2011 to 46.12% in 2013). Year 2014 saw an increase in adolescent and young adult HIV prevalence, which may be signalling a rebound of the epidemic. A more holistic approach which deals with the epidemic in its socio-political context is required to effectively lower the country’s HIV burden.
4‐ to 6‐week‐old adult‐born hippocampal neurons influence novelty‐evoked exploration and contextual fear conditioning

To explore the role of adult hippocampal neurogenesis in novelty processing, we assessed novel object recognition (NOR) in mice after neurogenesis was arrested using focal x‐irradiation of the hippocampus, or a reversible, genetic method in which glial fibrillary acidic protein‐positive neural progenitor cells are ablated with ganciclovir. Arresting neurogenesis did not alter general activity or object investigation during four exposures with two constant objects. However, when a novel object replaced a constant object, mice with neurogenesis arrested by either ablation method showed increased exploration of the novel object when compared with control mice. The increased novel object exploration did not manifest until 4–6 weeks after x‐irradiation or 6 weeks following a genetic ablation, indicating that exploration of the novel object is increased specifically by the elimination of 4‐ to 6‐week‐old adult born neurons. The increased novel object exploration was also observed in older mice, which exhibited a marked reduction in neurogenesis relative to young mice. Mice with neurogenesis arrested by either ablation method were also impaired in one‐trial contextual fear conditioning (CFC) at 6 weeks but not at 4 weeks following ablation, further supporting the idea that 4‐ to 6‐week‐old adult born neurons are necessary for specific forms of hippocampal‐dependent learning, and suggesting that the NOR and CFC effects have a common underlying mechanism. These data suggest that the transient enhancement of plasticity observed in young adult‐born neurons contributes to cognitive functions. © 2011 Wiley Periodicals, Inc.
Developmental profile of SK2 channel expression and function in CA1 neurons

We investigated the temporal and spatial expression of SK2 in the developing mouse hippocampus using molecular and biochemical techniques, quantitative immunogold electron microscopy, and electrophysiology. The mRNA encoding SK2 was expressed in the developing and adult hippocampus. Western blotting and immunohistochemistry showed that SK2 protein increased with age. This was accompanied by a shift in subcellular localization. Early in development (P5), SK2 was predominantly localized to the endoplasmic reticulum in the pyramidal cell layer. But by P30 SK2 was almost exclusively expressed in the dendrites and spines. The level of SK2 at the postsynaptic density (PSD) also increased during development. In the adult, SK2 expression on the spine plasma membrane showed a proximal‐to‐distal gradient. Consistent with this redistribution and gradient of SK2, the selective SK channel blocker apamin increased evoked excitatory postsynaptic potentials (EPSPs) only in CA1 pyramidal neurons from mice older than P15. However, the effect of apamin on EPSPs was not different between synapses in proximal or distal stratum radiatum or stratum lacunosum‐moleculare in adult. These results show a developmental increase and gradient in SK2‐containing channel surface expression that underlie their influence on neurotransmission, and that may contribute to increased memory acquisition during early development. © 2011 Wiley Periodicals, Inc.
Wnt transmembrane signaling and long‐term spatial memory

Transmembrane signaling mechanisms are critical for regulating the plasticity of neuronal connections underlying the establishment of long‐lasting memory (e.g., Linden and Routtenberg (1989) Brain Res Rev 14:279–296; Sossin (1996) Trends Neurosci 19:215–218; Mayr and Montminy (2001) Nat Rev Mol Cell Biol 2:599–609; Chen et al. (2011) Nature 469:491–497). One signaling mechanism that has received surprisingly little attention in this regard is the well‐known Wnt transmembrane signaling pathway even though this pathway in the adult plays a significant role, for example, in postsynaptic dendritic spine morphogenesis and presynaptic terminal neurotransmitter release (Inestrosa and Arenas (2010) Nat Rev Neurosci 11:77–86). The present report now provides the first evidence of Wnt signaling in spatial information storage processes. Importantly, this Wnt participation is specific and selective. Thus, spatial, but not cued, learning in a water maze selectively elevates the levels in hippocampus of Wnt 7 and Wnt 5a, but not the Wnt 3 isoform, indicating behavioral selectivity and isoform specificity. Wnt 7 elevation is subfield‐specific: granule cells show an increase with no detectable change in CA3 neurons. Wnt 7 elevation is temporally specific: increased Wnt signaling is not observed during training, but is seen 7 days and, unexpectedly, 30 days later. If the Wnt elevation after learning is activity‐dependent, then it may be possible to model this effect in primary hippocampal neurons in culture. Here, we evaluate the consequence of potassium or glutamate depolarization on Wnt signaling. This represents, to our knowledge, the first demonstration of an activation‐dependent elevation of Wnt levels and surprisingly an increased number of Wnt‐stained puncta in neurites suggestive of trafficking from the cell body to neuronal processes, probably dendrites. It is proposed that Wnt signaling pathways regulate long‐term information storage in a behavioral‐, cellular‐, and isoform‐specific manner. © 2011 Wiley Periodicals, Inc.
Understanding how Afghan women utilise a gender transformative and economic empowerment intervention: A qualitative study

ABSTRACT The processes through which women's economic empowerment interventions are envisaged to improve women's health are strongly embedded in notions of building women's agency and autonomy. Yet despite the ubiquity of such interventions, there remains incredibly little qualitative work exploring how women actually utilise interventions to reshape their lives and wellbeing. Drawing on 9 focus groups discussions among 52 women who participated in the Women for Women International intervention in Afghanistan, an economic strengthening and social empowerment intervention, we explore processes of change. Data showed women learnt new skills around numeracy and animal husbandry; they perceived themselves to have become more respected within the household setting; they invested cash they received for intervention attendance in businesses, primarily their husband's or family's, and saved cash. Women did not, however, report their relationships to have been radically restructured. Rather women described incremental changes in their relationships within their household and used what they gained from the intervention to secure and sustain this. This conceptualisation of agency and empowerment reflects approaches to understanding agency, which move away from ‘action-oriented’ understandings, to ones that recognise ‘distributed agency’ as pathways to change through interventions.