bluuebunny/crossref_metadata_2025 huggingface dataset:
Essential Role of Sox2 for the Establishment and Maintenance of the Germ Cell Line
Authors: Campolo Federica , Gori Manuele , Favaro Rebecca , Nicolis Silvia , Pellegrini Manuela , Botti Flavia , Rossi Pellegrino , Jannini Emmanuele A. , Dolci Susanna
Published: April 2013

Sox2 is a pluripotency-conferring gene expressed in primordial germ cells (PGCs) and postnatal oocytes, but the role it plays during germ cell development and early embryogenesis is unknown. Since Sox2 ablation causes early embryonic lethality shortly after blastocyst implantation, we generated mice bearing Sox2-conditional deletion in germ cells at different stages of their development through the Cre/loxP recombination system. Embryos lacking Sox2 in PGCs show a dramatic decrease of germ cell numbers at the time of their specification. At later stages, we found that Sox2 is strictly required for PGC proliferation. On the contrary, Sox2 deletion in meiotic oocytes does not impair postnatal oogenesis and early embryogenesis, indicating that it is not essential for oocyte maturation or for zygotic development. We also show that Sox2 regulates Kit expression in PGCs and binds to discrete transcriptional regulatory sequences of this gene, which is known to be important for PGCs survival and proliferation. Sox2 also stimulates the expression of Zfp148, which is required for normal development of fetal germ cells, and Rif1, a potential regulator of PGC pluripotency.
PEDF promotes self-renewal of limbal stem cell and accelerates corneal epithelial wound healing
Authors: Ho Tsung-Chuan , Chen Show-Li , Wu Ju-Yun , Ho Mei-Ying , Chen Lee-Jen , Hsieh Jui-Wen , Cheng Huey-Chuan , Tsao Yeou-Ping
Published: April 2013

Limbal epithelial stem cell (LSC) transplantation is a prevalent therapeutic method for patients with LSC deficiency. The maintenance of stem cell characteristics in the process of culture expansion is critical for the success of ocular surface reconstruction. Pigment epithelial-derived factor (PEDF) increased the numbers of holoclone in LSC monolayer culture and preserved the stemness of LSC in suspension culture by evidence of ΔNp63α, Bmi-1, and ABCG2 expression. BrdU pulse-labeling assay also demonstrated that PEDF stimulated LSCs proliferation. In air-lift culture of limbal equivalent, PEDF was capable of increasing the numbers of ΔNp63α-positive cells. The mitogenic effect of PEDF was found to be mediated by the phosphorylations of p38 MAPK and STAT3 in LSCs. Synthetic 44-mer PEDF (residues 78–121) was as effective as the full length PEDF in LSC expansion in suspension culture and limbal equivalent formation, as well as the activation of p38 MAPK and STAT3. In mice subjecting to mechanical removal of cornea epithelium, 44-mer PEDF facilitated corneal wound healing. Microscopically, 44-mer PEDF advanced the early proliferative response in limbus, increased the proliferation of ΔNp63α-positive cells both in limbus and in epithelial healing front, and assisted the repopulation of limbus in the late phase of wound healing. In conclusion, the capability of expanding LSC in cell culture and in animal indicates the potential of PEDF and its fragment (e.g., 44-mer PEDF) in ameliorating limbal stem cell deficiency; and their uses as therapeutics for treating corneal wound.
Infiltration in soils with a saturated surface
Authors: Hogarth W. L. , Lockington D. A. , Barry D. A. , Parlange M. B. , Haverkamp R. , Parlange J.‐Y.
Published: April 2013

Key Points

Analytic description of infiltration in soils

Comparison of constant flux and saturated surface infiltration

Linking infiltration to soil/water properties
Regulation of stress granules and P‐bodies during RNA virus infection
Authors: Lloyd Richard E.
Published: April 2013

RNA granules are structures within cells that play major roles in gene expression and homeostasis. Two principle kinds of RNA granules are conserved from yeast to mammals: stress granules (SGs), which contain stalled translation initiation complexes, and processing bodies (P‐bodies, PBs), which are enriched with factors involved in RNA turnover. Since RNA granules are associated with silenced transcripts, viruses subvert RNA granule function for replicative advantages. This review, focusing on RNA viruses, discusses mechanisms that manipulate stress granules and P‐bodies to promote synthesis of viral proteins. Three main themes have emerged for how viruses manipulate RNA granules; (1) cleavage of key host factors, (2) control of protein kinase R (PKR) activation, and (3) redirecting RNA granule components for new or parallel roles in viral reproduction, at the same time disrupting RNA granules. Viruses utilize one or more of these routes to achieve robust and productive infection. WIREs RNA 2013, 4:317–331. doi: 10.1002/wrna.1162

This article is categorized under:

RNA in Disease and Development > RNA in Disease
Genetic Counseling Training in the Philippines
Authors: Laurino Mercy Ygona , Padilla Carmencita David
Published: April 2013

The recently established Master of Science in Genetic Counseling (MSGC) program serves a vital role in implementing and expanding genetic counseling services in the Philippines. Currently, only eight clinical geneticists practice in the Philippines, a country of approximately 94 million people, which yields a clinical‐geneticist‐to‐population‐density ratio of 1:11,750,000. The MSGC program was created to train health care providers to become crucial members of medical genetics teams being formed to meet increasing patient and healthcare provider demands. In 2011, the Board of Regents approved our proposed curriculum at the Department of Pediatrics College of Medicine, University of the Philippines Manila. As we relate how the Philippines began its efforts to implement the program and attempted to overcome the challenges the program faced, we hope we can provide an example to those interested in creating a similar MSGC program in other low‐income and middle‐income countries.
A lower bound for topological entropy of generic non-Anosov symplectic diffeomorphisms
Authors: CATALAN THIAGO , TAHZIBI ALI
Published: April 2013

We prove that a${C}^{1} $generic symplectic diffeomorphism is either Anosov or its topological entropy is bounded from below by the supremum over the smallest positive Lyapunov exponent of its periodic points. We also prove that${C}^{1} $generic symplectic diffeomorphisms outside the Anosov ones do not admit symbolic extension and, finally, we give examples of volume preserving surface diffeomorphisms which are not points of upper semicontinuity of the entropy function in the${C}^{1} $topology.
Tic Disorders and Learning Disability: Clinical Characteristics, Cognitive Performance and Comorbidity
Authors: Eapen Valsamma , Črnčec Rudi , McPherson Sarah , Snedden Corina
Published: April 2013

Tics are involuntary movements or sounds. Tourette syndrome is one of a family of tic disorders that affect around 1% of the population but which remains underrecognised in the community. In paediatric special education learning disability classes, the prevalence of individuals with tic disorders is around 20–45% — higher still in special education emotional/behavioural classes. Given the high rates of individuals with tic disorders in special education settings, as well as the unique challenges of working in an educational setting with a person with a tic disorder, it is incumbent upon professionals working in these settings to be cognisant of the possibility of tic disorders in this population. This review seeks to provide an overview of tic disorders and their association with learning and mental health difficulties. The review focuses on an exploration of factors underpinning the association between tic disorders and learning disabilities, including neurocognitive corollaries of tic disorders and the influence of common comorbidities, such as ADHD, as well as upon strategies to support individuals with tic disorders in the classroom.
On Cas A, Cassini, Comets, and King Charles
Authors: SORIA ROBERTO , BALESTRIERI RICCARDO , OHTSUKA YASUYO
Published: April 2013

We re-examine the long-standing problem of the date of the Cassiopeia A supernova (SN), in view of recent claims that it might be the 1630 ‘noon-star’ seen at the birth of King Charles II. We do not support this identification, based on the expected brightness of a Type-IIb SN (too faint to be seen in daylight), the extrapolated motion of the ejecta (inconsistent with a date earlier than 1650), the lack of any scientific follow-up observations, the lack of any mention of it in Asian archives. The origin of the 1630 noon-star event (if real) remains a mystery; there was a bright comet in 1630 June but no evidence to determine whether or not it was visible in daylight. Instead, we present French reports about a fourth-magnitude star discovered by Cassini in Cassiopeia in or shortly before 1671, which was not seen before or since. The brightness is consistent with what we expect for the Cas A SN; the date is consistent with the extrapolated motion of the ejecta. We argue that this source could be the long-sought SN.
Under-reporting of drug use among individuals with schizophrenia: prevalence and predictors
Authors: Bahorik A. L. , Newhill C. E. , Queen C. C. , Eack S. M.
Published: April 2013

Background

Illicit drug use is common in individuals with schizophrenia, and it has been suspected that many individuals under-report their use of substances, leading to significant barriers to treatment. This study sought to examine the degree to which individuals with schizophrenia disclose their use of drugs on self-rated assessments, compared to laboratory assays, and to determine the contributors of under-reported drug use in this population.

Method

A total of 1042 individuals with schizophrenia who participated in screening/baseline procedures for the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) completed self-rated assessments of substance use and laboratory drug testing. Laboratory tests assayed cannabis, cocaine and methamphetamine use; the procedures included radioimmunoassay (RIA) and urine drug screens.

Results

A significant proportion of participants tested positive for drug use on laboratory measures (n = 397; 38%), and more than half (n = 229; 58%) did not report using these drugs. Logistic regression models confirmed that patients who were most likely to conceal their use tended to be older, and presented with greater neurocognitive deficits. Patients who accurately reported drug use tended to have greater involvement with the criminal justice system. Illness severity and psychopathology were not associated with whether patients disclosed drug use.

Conclusions

Rates of under-reported drug use are considerable among individuals with schizophrenia when compared to laboratory assays, and the exclusive reliance on self-rated assessments should be used with caution. Patients who under-report their drug use are more likely to manifest neurocognitive deficits, which could be improved by interventions attempting to optimize treatment.
Trajectories of PTSD risk and resilience in World Trade Center responders: an 8-year prospective cohort study
Authors: Pietrzak R. H. , Feder A. , Singh R. , Schechter C. B. , Bromet E. J. , Katz C. L. , Reissman D. B. , Ozbay F. , Sharma V. , Crane M. , Harrison D. , Herbert R. , Levin S. M. , Luft B. J. , Moline J. M. , Stellman J. M. , Udasin I. G. , Landrigan P. J. , Southwick S. M.
Published: April 2013

Background

Longitudinal symptoms of post-traumatic stress disorder (PTSD) are often characterized by heterogeneous trajectories, which may have unique pre-, peri- and post-trauma risk and protective factors. To date, however, no study has evaluated the nature and determinants of predominant trajectories of PTSD symptoms in World Trade Center (WTC) responders.

Method

A total of 10835 WTC responders, including 4035 professional police responders and 6800 non-traditional responders (e.g. construction workers) who participated in the WTC Health Program (WTC-HP), were evaluated an average of 3, 6 and 8 years after the WTC attacks.

Results

Among police responders, longitudinal PTSD symptoms were best characterized by four classes, with the majority (77.8%) in a resistant/resilient trajectory and the remainder exhibiting chronic (5.3%), recovering (8.4%) or delayed-onset (8.5%) symptom trajectories. Among non-traditional responders, a six-class solution was optimal, with fewer responders in a resistant/resilient trajectory (58.0%) and the remainder exhibiting recovering (12.3%), severe chronic (9.5%), subsyndromal increasing (7.3%), delayed-onset (6.7%) and moderate chronic (6.2%) trajectories. Prior psychiatric history, Hispanic ethnicity, severity of WTC exposure and WTC-related medical conditions were most strongly associated with symptomatic trajectories of PTSD symptoms in both groups of responders, whereas greater education and family and work support while working at the WTC site were protective against several of these trajectories.

Conclusions

Trajectories of PTSD symptoms in WTC responders are heterogeneous and associated uniquely with pre-, peri- and post-trauma risk and protective factors. Police responders were more likely than non-traditional responders to exhibit a resistant/resilient trajectory. These results underscore the importance of prevention, screening and treatment efforts that target high-risk disaster responders, particularly those with prior psychiatric history, high levels of trauma exposure and work-related medical morbidities.
Language learning in mindbodyworld: A sociocognitive approach to second language acquisition
Authors: Atkinson Dwight
Published: April 2013

Based on recent research in cognitive science, interaction, and second language acquisition (SLA), I describe a sociocognitive approach to SLA. This approach adopts anon-cognitivistview of cognition: Instead of an isolated computational process in which input is extracted from the environment and used to build elaborate internal knowledge representations, cognition is seen asadaptive intelligence,enabling our close and sensitivealignmentto our ecosocial environment in order to survive in it. Mind, body, and world are thus functionally integrated from a sociocognitive perspective instead of radically separated.

Learning plays a major part in this scenario: If environments are ever-changing, then adaptation to them is continuous. Learning is part of our natural ability to so adapt, while retaining traces of that adaptation in the integrated mind-body-world system. Viewed in this way, SLA is adaptation to/engagement with L2 environments.

Interactionalso plays a central role in sociocognitive SLA: We learn L2s through interacting with/in L2 environments. Founded on innate, universal skills which evolutionarilyprecededlanguage and make it possible, interaction supports SLA at every turn. Having presented this argument, I illustrate it by analyzing a video clip of an EFL tutoring session, indicating various ‘sociocognitive tools’ for interactive alignment which undergird L2 development.
OCCUPATIONAL CHOICE AND THE EGALITARIAN ETHOS
Authors: Casal Paula
Published: April 2013

G. A. Cohen proposes to eradicate inequality without loss of efficiency or freedom by relying on an egalitarian ethos requiring us to undertake socially useful occupations we would rather not take, and work hard at them, without requesting differential incentive payments. Since the ethos is not legally enforced, Cohen denies it threatens our occupational freedom. Drawing on the work of Joseph Raz, the paper argues that Cohen's proposal threatens our occupational autonomy even if it leaves our legal freedom intact. It also proposes a revised ethos which respects occupational autonomy.
HOW GIFTS AND GAMBLES PRESERVE JUSTICE
Authors: Williams Andrew
Published: April 2013

This paper examines G. A. Cohen's final criticism of Ronald Dworkin's theory ofequality of resources, which targets its treatment of inequalities that arise when some individuals make luckier choices than others make. Rebutting Cohen's argument that suchoption luck inequalitiesfail to be just in an unqualified sense, the paper argues that choice does not merely render inequality legitimate but instead can sometimes make inequality just. It also examines the relationship between Cohen's criticism and the conception of equality developed in his earlier influential paper, ‘On the Currency of Egalitarian Justice’.
EPISTEMIC DEMOCRACY WITH DEFENSIBLE PREMISES
Authors: Dietrich Franz , Spiekermann Kai
Published: April 2013

The contemporary theory of epistemic democracy often draws on the Condorcet Jury Theorem to formally justify the ‘wisdom of crowds’. But this theorem is inapplicable in its current form, since one of its premises – voter independence – is notoriously violated. This premise carries responsibility for the theorem's misleading conclusion that ‘large crowds are infallible’. We prove a more useful jury theorem: under defensible premises, ‘large crowds are fallible but better than small groups’. This theorem rehabilitates the importance of deliberation and education, which appear inessential in the classical jury framework. Our theorem is related to Ladha's (1993) seminal jury theorem for interchangeable (‘indistinguishable’) voters based on de Finetti's Theorem. We also prove a more general and simpler such jury theorem.
A multidisciplinary survey on discrimination analysis
Authors: Romei Andrea , Ruggieri Salvatore
Published: April 2013

The collection and analysis of observational and experimental data represent the main tools for assessing the presence, the extent, the nature, and the trend of discrimination phenomena. Data analysis techniques have been proposed in the last 50 years in the economic, legal, statistical, and, recently, in the data mining literature. This is not surprising, since discrimination analysis is a multidisciplinary problem, involving sociological causes, legal argumentations, economic models, statistical techniques, and computational issues. The objective of this survey is to provide a guidance and a glue for researchers and anti-discrimination data analysts on concepts, problems, application areas, datasets, methods, and approaches from a multidisciplinary perspective. We organize the approaches according to their method of data collection as observational, quasi-experimental, and experimental studies. A fourth line of recently blooming research on knowledge discovery based methods is also covered. Observational methods are further categorized on the basis of their application context: labor economics, social profiling, consumer markets, and others.
New insights into the aspects of pulmonary diffusing capacity in Fontan patients
Authors: Idorn Lars , Hanel Birgitte , Jensen Annette S. , Juul Klaus , Reimers Jesper I. , Nielsen Kim G. , Søndergaard Lars
Published: April 2013

Background: Patients with a functionally univentricular heart, palliated a.m. Fontan, consequently have non-pulsatile pulmonary blood flow and are known to have a reduced pulmonary diffusing capacity. However, the cause of this reduction remains unclear. We aimed to assess the possible determinants in the aetiology of a reduced diffusing capacity and also to assess whether it could be increased. Furthermore, we aimed to search for predictors of a reduced diffusing capacity.Material and methods: A total of 87 Fontan patients (mean age 16.3 ± 7.6 years) performed advanced pulmonary function tests and maximal cycle ergometer tests. A total of 10 Fontan patients and nine matched controls performed a supine pulmonary function test after a supine rest.Results: In the sitting pulmonary function test, the mean z-scores were: diffusing capacity, 2.38 ± 1.20; pulmonary capillary blood volume, 2.04 ± 0.80; and alveolar capillary membrane diffusing capacity, 0.14 ± 0.84. In the supine compared with the sitting pulmonary function test, the diffusing capacity increased by 51.7 ± 11.9% in the Fontan group and by 23.3 ± 17.7% in the control group (p < 0.001); moreover, the pulmonary capillary blood volume increased by 48.3 ± 17.4% in the Fontan group and by 20.2 ± 13.9% in the control group (p = 0.001). In a multiple linear regression analysis including the explanatory variables of surgical data and exercise data at rest and peak exercise, the resting cardiac index was an independent predictor of the diffusing capacity (regression coefficient: 0.18, p < 0.001).Conclusions: The pulmonary diffusing capacity was reduced in Fontan patients because of a reduced pulmonary capillary blood volume, whereas the alveolar capillary membrane diffusing capacity was preserved. The diffusing capacity was highly increasable in Fontan patients compared with controls, and the resting cardiac index was an independent predictor of the diffusing capacity.
Naturalized Phenomenology: A Desideratum or a Category Mistake?
Authors: Zahavi Dan
Published: April 2013

If we want to assess whether or not a naturalized phenomenology is a desideratum or a category mistake, we need to be clear on precisely what notion of phenomenology and what notion of naturalization we have in mind. In the article I distinguish various notions, and after criticizing one type of naturalized phenomenology, I sketch two alternative takes on what a naturalized phenomenology might amount to and propose that our appraisal of the desirability of such naturalization should be more positive, if we opt for one or both of the latter alternatives.
Phenomenology, Naturalism and the Sense of Reality
Authors: Ratcliffe Matthew
Published: April 2013

Phenomenologists such as Husserl, Heidegger and Merleau-Ponty reject the kind of scientific naturalism or ‘scientism’ that takes empirical science to be epistemologically and metaphysically privileged over all other forms of enquiry. In this paper, I will consider one of their principal complaints against naturalism, that scientific accounts of things are oblivious to a ‘world’ that is presupposed by the intelligibility of science. Focusing mostly upon Husserl's work, I attempt to clarify the nature of this complaint and state it in the form of an argument. I conclude that the argument is effective in exposing naturalism's reliance upon impoverished conceptions of human experience, and that it also weakens the more general case for naturalism.
Merleau-Ponty's phenomenological critique of natural science
Authors: Baldwin Thomas
Published: April 2013

In his Phenomenology of Perception Merleau-Ponty maintains that our own existence cannot be understood by the methods of natural science; furthermore, because fundamental aspects of the world such as space and time are dependent on our existence, these too cannot be accounted for within natural science. So there cannot be a fully scientific account of the world at all. The key thesis Merleau-Ponty advances in support of this position is that perception is not, as he puts it, ‘an event of nature’. He argues that it has a fundamental intentionality which configures the perceived world as spatio-temporal in ways which are presupposed by natural science and which cannot therefore be explained by natural science.

This is a striking and original claim. When one looks in detail at the considerations Merleau-Ponty advances in support of it, however, these turn out to be either inconclusive or to draw on idealist presumptions which a contemporary naturalist will reject. So while there is much of interest and value in Merleau-Ponty's critical discussion of naturalism, he does not succeed in establishing his central claim.
TESTING FOR THE EFFICIENT MARKET HYPOTHESIS IN STOCK PRICES: INTERNATIONAL EVIDENCE FROM NONLINEAR HETEROGENEOUS PANELS
Authors: Lee Chien-Chiang , Tsong Ching-Chuan , Lee Cheng-Feng
Published: April 2013

Using international data, this paper explores whether the efficient market hypothesis for real stock prices is supported for different panels. The stationarity of a real stock price has important implications for modeling and forecasting financial activities. On a global scale, we implement the recently developed nonlinear heterogeneous panel unit root test, which allows us to account for possible nonlinearity and cross-section dependence and to identify how many and which countries of the panel contain a unit root. The primary conclusion is that the stationarity of real stock prices varies between regions and levels of economic development. Overall, our empirical results illustrate that real stock prices in these countries are a mixture of stationary (integrated of order zero) and nonstationary (integrated of order one) processes.
Nutrient intake and dietary patterns of relevance to dental health of 12-year-old Libyan children
Authors: Huew Rasmia , Maguire Anne , Waterhouse Paula , Moynihan Paula
Published: April 2013

Objective

There are few data on the dietary intake of children in Libya, and none on free sugars intake. The present study aimed to report the intake of macronutrients and eating habits of relevance to dental health in a group of Libyan schoolchildren and to investigate any gender differences for these variables.

Design

Dietary information was obtained from a randomly selected sample using an estimated 3 d food diary. Dietary data were coded using food composition tables and entered into a Microsoft®Access database. Intakes of energy, macronutrients, sugars and the amount of acidic items consumed were determined using purpose-written programs.

Setting

Benghazi, Libya.

Subjects

Schoolchildren aged 12 years.

Results

One hundred and eighty children (ninety-two boys and eighty-eight girls) completed the study. Their mean age was 12·3 (sd0·29) years. The average daily energy intake was 7·01 (sd1·54) MJ/d. The percentage contributions to energy intake from protein, fat and carbohydrate were 16 %, 30 % and 54 %, respectively. Total sugars contributed 20·4 % of the daily energy intake, and free sugars 12·6 %. The median daily intake of acidic items was 203 g/d, and of acidic drinks was 146 g/d. There were no statistically significant differences in nutrient intakes between genders. Intake of acidic items was higher in girls (P< 0·001).

Conclusions

The contribution to energy intake from macronutrients was in accordance with global nutrition guidelines. The acidic drinks intake was low compared with other populations, while free sugars intake was above the recommended threshold of 10 % of energy intake.
Increased alcohol consumption in rats after subchronic antidepressant treatment
Authors: Alén Francisco , Orio Laura , Gorriti Miguel Á , de Heras Raquel Gómez , Ramírez-López María Teresa , Pozo Miguel Ángel , de Fonseca Fernando Rodríguez
Published: April 2013

The use of antidepressants for alcoholism in humans has been a matter of controversy in recent years. Despite the existence of an important co-morbidity for depression and alcoholism, some studies suggest that the use of antidepressants could worsen the prognosis of alcoholism. However, there is a lack of studies in animal models exploring this phenomenon. In the present study, we show how the 15-d treatment with fluoxetine (10 mg/kg) or venlafaxine (50 mg/kg) affected alcohol deprivation effect (ADE) and subsequent alcohol consumption. Initially, fluoxetine reduced ADE and venlafaxine did not affect it. However, in the following days, both antidepressants increased alcohol consumption, an effect that was found to last at least 5 wk. Fluoxetine treatment was shown to cause a locomotor sensitized response to a challenge dose of amphetamine (0.5 mg/kg), indicating the presence of a supersensitive dopaminergic transmission. In summary, antidepressant treatment may increase alcohol consumption in rats after a period of alcohol deprivation and this could be related to alterations in the reward circuitry. This finding confirms in an animal model previous reports in humans that may limit the use of antidepressants for alcoholism.
Prenatal immune activation interacts with stress and corticosterone exposure later in life to modulate N-methyl-d-aspartate receptor synaptic function and plasticity
Authors: Burt Melissa A. , Tse Yiu Chung , Boksa Patricia , Wong Tak Pan
Published: April 2013

Prenatal infection is an environmental risk factor for schizophrenia while later in life, stressful events have been associated with the onset and severity of psychosis. Recent findings on the impact of stress on the N-methyl-d-aspartate receptor (NMDAR), of which hypofunctioning is implicated in schizophrenia, suggest changes in stress-induced regulation of the glutamatergic system may be related to the pathogenesis of schizophrenia. Our study aimed to test whether prenatal immune activation could interact with stress at adolescence to alter NMDAR function. We used offspring from rat dams administered bacterial lipopolysaccharide (LPS) during pregnancy (gestational days 15 and 16), an animal model expressing schizophrenia-related behavioural phenotypes. Using electrophysiological techniques, we investigated effects of stress and the stress hormone corticosterone (Cort) on NMDAR-mediated synaptic function and long-term depression (LTD) in hippocampal CA1 slices from these adolescent (aged 28–39 d) male offspring. In prenatal LPS offspring, NMDAR-mediated synaptic function and LTD were reduced and abolished, respectively, compared to prenatal saline controls. Notably, in vivo stress and in vitro Cort treatment facilitated LTD in slices from prenatal LPS rats but not prenatal saline controls. Finally, Cort enhanced NMDAR-mediated synaptic function in slices from prenatal LPS rats only. We conclude that prenatal immune activation results in NMDAR hypofunction in the hippocampus of adolescent rats but also increases responsiveness of NMDAR-mediated synaptic function and LTD towards stress. Prenatal infection could confer susceptibility to schizophrenia through modification of hippocampal NMDAR function, with hypofunction in resting conditions and heightened responsiveness to stress, thus impacting the development of the disorder.
Associations between prefrontal γ-aminobutyric acid concentration and the tryptophan hydroxylase isoform 2 gene, a panic disorder risk allele in women
Authors: Preuss Nora , Salehi Basira , van der Veen Jan Willem , Shen Jun , Drevets Wayne C. , Hodgkinson Colin , Goldman David , Hasler Gregor
Published: April 2013

Associations between the central serotonergic and γ-aminobutyric acid (GABA) systems play key roles in the prefrontal cortical regulation of emotion and cognition and in the pathophysiology and pharmacotherapy of highly prevalent psychiatric disorders. The goal of this study was to test the effects of common variants of the tryptophan hydroxylase isoform 2 (TPH2) gene on GABA concentration in the prefrontal cortex (PFC) using magnetic resonance spectroscopy. In this study involving 64 individuals, we examined the associations between prefrontal cortical GABA concentration and 12 single nucleotide polymorphisms (SNPs) spanning the TPH2 gene, including rs4570625 (−703 G/T SNP), a potentially functional TPH2 polymorphism that has been associated with decreased TPH2 mRNA expression and panic disorder. Our results revealed a significant association between increased GABA concentration in the PFC and the T-allele frequencies of two TPH2 SNPs, namely rs4570625 (−703 G/T) and rs2129575 (p⩽0.0004) and the C-allele frequency of one TPH2 SNP, namely rs1386491 (p = 0.0003) in female subjects. We concluded that rs4570625 (−703 G/T), rs2129575 and rs1386491 play a significant role in GABAergic neurotransmission and may contribute to the sex-specific dysfunction of the GABAergic system in the PFC.
Interactivity, Efficiency, and Individual Differences in Mental Arithmetic
Authors: Vallée-Tourangeau Frédéric
Published: April 2013

Thinking efficiency was examined in mental arithmetic as a function of the degree of interactivity afforded by the task. Participants carried out single-digit additions, involving either 7 or 11 numbers, as fast and as accurately as possible. They completed the sums in blocks, five from the short 7-number set first, and five from the longer 11-number set second. These sets were interpolated among a series of other tasks that measured numeracy and arithmetic skills, working memory capacity, visuo-spatial processing speed, and attention switching, in such a way as to permit the presentation of the sets twice, once with each of the sums presented on a piece of paper and participants placing their hands flat on the table and once with the sums presented as a set of manipulable tokens. Efficiency was measured as the ratio of performance over time invested. A significant interaction between condition and set size was observed: Efficiency was slightly better in the static condition for short sums but declined substantially relative to the interactive condition for long sums. Twenty-two percent of the variance in efficiency for hard sums in the static condition was explained by arithmetic skills and working memory capacity, whereas 45% of this variance was explained by arithmetic skills, working memory capacity, and attention switching skills in the interactive condition. A separate sample of 17 participants who provided concurrent verbal protocols as they solved the problems revealed that paths to solution and arithmetic strategies were substantially transformed by the opportunity to manipulate tokens.
The Sonic Hedgehog Pathway Mediates Brain Plasticity and Subsequent Functional Recovery After Bone Marrow Stromal Cell Treatment of Stroke in Mice
Authors: Ding Xiaoshuang , Li Yi , Liu Zhongwu , Zhang Jing , Cui Yisheng , Chen Xiaoguang , Chopp Michael
Published: April 2013

Bone marrow stromal cells (MSCs) improve neurologic recovery after middle cerebral artery occlusion (MCAo). To examine whether in vivo blockage of the endogenous sonic hedgehog (Shh) pathway affects grafted MSC-induced neurologic benefits, MCAo mice were administered: vehicle (control);cyclopamine (CP)—a specific Shh pathway inhibitor;MSC;and MSC and cyclopamine (MSC-CP). Neurologic function was evaluated after MCAo. Electron microscopy and immunofluorescence staining were employed to measure synapse density, protein expression of tissue plasminogen activator (tPA), and Shh in parenchymal cells in the ischemic boundary zone (IBZ), respectively. Marrow stromal cell treatment significantly enhanced functional recovery after ischemia, concurrent with increases of synaptophysin, synapse density, and myelinated axons along the IBZ, and significantly increased tPA and Shh expression in astrocytes and neurons compared with control. After treatment with MSC-CP or CP, the above effects were reversed. Co-culture of MSCs with cortical neurons confirmed the effect of Shh on MSC-mediated neurite outgrowth. Our data support the hypothesis that the Shh pathway mediates brain plasticity via tPA and thereby functional recovery after treatment of stroke with MSCs.
Molecular architecture of the human protein deacetylase Sirt1 and its regulation by AROS and resveratrol
Authors: Lakshminarasimhan Mahadevan , Curth Ute , Moniot Sebastien , Mosalaganti Shyamal , Raunser Stefan , Steegborn Clemens
Published: April 2013

Sirtuins are NAD+-dependent protein deacetylases regulating metabolism, stress responses and ageing processes. Among the seven mammalian Sirtuins, Sirt1 is the physiologically best-studied isoform. It regulates nuclear functions such as chromatin remodelling and gene transcription, and it appears to mediate beneficial effects of a low calorie diet which can partly be mimicked by the Sirt1 activating polyphenol resveratrol. The molecular details of Sirt1 domain architecture and regulation, however, are little understood. It has a unique N-terminal domain and CTD (C-terminal domain) flanking a conserved Sirtuin catalytic core and these extensions are assumed to mediate Sirt1-specific features such as homo-oligomerization and activation by resveratrol. To analyse the architecture of human Sirt1 and functions of its N- and C-terminal extensions, we recombinantly produced Sirt1 and Sirt1 deletion constructs as well as the AROS (active regulator of Sirt1) protein. We then studied Sirt1 features such as molecular size, secondary structure and stimulation by small molecules and AROS. We find that Sirt1 is monomeric and has extended conformations in its flanking domains, likely disordered especially in the N-terminus, resulting in an increased hydrodynamic radius. Nevertheless, both termini increase Sirt1 deacetylase activity, indicating a regulatory function. We also find an unusual but defined conformation for AROS protein, which fails, however, to stimulate Sirt1. Resveratrol, in contrast, activates the Sirt1 catalytic core independent of the terminal domains, indicating a binding site within the catalytic core and suggesting that small molecule activators for other isoforms might also exist.
Maternal protein restriction during pregnancy affects gene expression and immunolocalization of intestinal nutrient transporters in rats
Authors: Pinheiro Daniela F. , Pinheiro Patricia F. F. , Buratini José , Castilho Anthony C. S. , Lima Paula F. , Trinca Luiza A. , Vicentini-Paulino Maria de Lourdes M.
Published: April 2013

Intrauterine dietary restriction may cause changes in the functioning of offspring organs and systems later in life, an effect known as fetal programming. The present study evaluated mRNA abundance and immunolocalization of nutrient transporters as well as enterocytes proliferation in the proximal, median and distal segments of small intestine of rats born to protein-restricted dams. Pregnant rats were fed hypoproteic (6% protein) or control (17% protein) diets, and offspring rats were evaluated at 3 and 16 weeks of age. The presence of SGLT1 (sodium–glucose co-transporter 1), GLUT2 (glucose transporter 2), PEPT1 (peptide transporter 1) and the intestinal proliferation were evaluated by immunohistochemical techniques and the abundance of specific mRNA for SGLT1, GLUT2 and PEPT1 was assessed by the real-time PCR technique. Rats born to protein-restricted dams showed higher cell proliferation in all intestinal segments and higher gene expression of SGLT1 and PEPT1 in the duodenum. Moreover, in adult animals born to protein-restricted dams the immunoreactivity of SGLT1, GLUT2 and PEPT1in the duodenum was more intense than in control rats. Taken together, the results indicate that changes in the small intestine observed in adulthood can be programmed during the gestation. In addition, they show that this response is caused by both up-regulation in transporter gene expression, a specific adaptation mechanism, and intestinal proliferation, an unspecific adaptation mechanism.
Transgenic pig carrying green fluorescent proteasomes
Authors: Miles Edward L. , O’Gorman Chad , Zhao Jianguo , Samuel Melissa , Walters Eric , Yi Young-Joo , Sutovsky Miriam , Prather Randall S. , Wells Kevin D. , Sutovsky Peter
Published: April 2013

Among its many functions, the ubiquitin–proteasome system regulates substrate-specific proteolysis during the cell cycle, apoptosis, and fertilization and in pathologies such as Alzheimer’s disease, cancer, and liver cirrhosis. Proteasomes are present in human and boar spermatozoa, but little is known about the interactions of proteasomal subunits with other sperm proteins or structures. We have created a transgenic boar with green fluorescent protein (GFP) tagged 20S proteasomal core subunit α-type 1 (
PSMA1-GFP
), hypothesizing that the PSMA1-GFP fusion protein will be incorporated into functional sperm proteasomes. Using direct epifluorescence imaging and indirect immunofluorescence detection, we have confirmed the presence of PSMA1-GFP in the sperm acrosome. Western blotting revealed a protein band corresponding to the predicted mass of PSMA1-GFP fusion protein (57 kDa) in transgenic spermatozoa. Transgenic boar fertility was confirmed by in vitro fertilization, resulting in transgenic blastocysts, and by mating, resulting in healthy transgenic offspring. Immunoprecipitation and proteomic analysis revealed that PSMA1-GFP copurifies with several acrosomal membrane-associated proteins (e.g., lactadherin/milk fat globule E8 and spermadhesin alanine-tryptophan-asparagine). The interaction of MFGE8 with PSMA1-GFP was confirmed through cross-immunoprecipitation. The identified proteasome-interacting proteins may regulate sperm proteasomal activity during fertilization or may be the substrates of proteasomal proteolysis during fertilization. Proteomic analysis also confirmed the interaction/coimmunoprecipitation of PSMA1-GFP with 13/14 proteasomal core subunits. These results demonstrate that the PSMA1-GFP was incorporated in the assembled sperm proteasomes. This mammal carrying green fluorescent proteasomes will be useful for studies of fertilization and wherever the ubiquitin–proteasome system plays a role in cellular function or pathology.
Functional flexibility of infant vocalization and the emergence of language
Authors: Oller D. Kimbrough , Buder Eugene H. , Ramsdell Heather L. , Warlaumont Anne S. , Chorna Lesya , Bakeman Roger
Published: April 2013

We report on the emergence of functional flexibility in vocalizations of human infants. This vastly underappreciated capability becomes apparent when prelinguistic vocalizations express a full range of emotional content—positive, neutral, and negative. The data show that at least three types of infant vocalizations (squeals, vowel-like sounds, and growls) occur with this full range of expression by 3–4 mo of age. In contrast, infant cry and laughter, which are species-specific signals apparently homologous to vocal calls in other primates, show functional stability, with cry overwhelmingly expressing negative and laughter positive emotional states. Functional flexibility is a sine qua non in spoken language, because all words or sentences can be produced as expressions of varying emotional states and because learning conventional “meanings” requires the ability to produce sounds that are free of any predetermined function. Functional flexibility is a defining characteristic of language, and empirically it appears before syntax, word learning, and even earlier-developing features presumed to be critical to language (e.g., joint attention, syllable imitation, and canonical babbling). The appearance of functional flexibility early in the first year of human life is a critical step in the development of vocal language and may have been a critical step in the evolution of human language, preceding protosyntax and even primitive single words. Such flexible affect expression of vocalizations has not yet been reported for any nonhuman primate but if found to occur would suggest deep roots for functional flexibility of vocalization in our primate heritage.
Nothing gained: An explorative study of the long‐term effects of perceived maternal feeding practices on women's and men's adult BMI, body image dissatisfaction, and disordered eating
Authors: Lev‐Ari Lilac , Zohar Ada H.
Published: April 2013

The objective of the studies presented here was the prediction of adult body mass index (BMI), body image dissatisfaction, and disordered eating from recalled maternal child feeding practices. Studies 1 and 2 sampled women from the community, and found that recalled childhood feeding practices predicted both current BMI and current disordered eating. Daughters whose mothers pressured them to eat as children had lower BMIs as adults. The more a mother was concerned about her daughter's weight as a child, and the more she restricted fatty food intake, the less the woman was satisfied with her current body image. Disordered eating of adult women was positively related to their mothers' restriction of their fatty food intake as children, and negatively related to the mothers' monitoring of their food intake as children. Combining the samples and subdividing them into four BMI intervals showed that the obese women were higher on all but one of the recalled maternal child feeding practices, as well as on disordered eating and body dissatisfaction. Age was found to be positively related to BMI and drive for thinness, but not to body dissatisfaction or disordered eating, with older women having higher BMI and more drive for thinness. Study 3 sampled adult men from the community and found that recalled maternal child feeding practices predicted adult BMI and disordered eating for men, as well as for women. Considerable sex differences were found for all study variables. Recollection of maternal child feeding practices may have a formative role in the development of body image, disordered eating, and BMI for men and women, even into adulthood.
Emerging Perspectives on the Study of Social Exclusion
Authors: DeWall C. Nathan
Published: April 2013

From its beginning, the field of psychology emphasized the importance of social connections. Whether it was monkeys who preferred terrycloth mothers to wired ones, therapists who gave their clients unconditional positive regard, or establishing social relationships as a means of enabling self-actualizing, dominant psychological theories highlighted the need to have few positive and lasting relationships. Yet systematic research on the need to belong remained sparse over several decades. The past 15 years have seen the most active period of research on the need to belong in the history of psychology. This chapter outlines emerging perspectives from this pioneering period.
Evolutionary Perspectives on Interpersonal Acceptance and Rejection
Authors: Leary Mark R. , Cottrell Catherine A.
Published: April 2013

Establishing and maintaining relationships with other people was among the most crucial tasks faced by our evolutionary ancestors. As a result, human beings possess adaptations not only to seek acceptance by other people and to respond adaptively to threats of social rejection but, ironically, to avoid and reject individuals who are judged to be poor relational partners and group members. This chapter examines the interplay of these opposing inclinations, the evolved adaptations that may underlie them, and implications of an evolutionary perspective for understanding emotional and behavioral reactions to interpersonal rejection.
The Multi-Motive Model of Responses to Rejection-Related Experiences
Authors: Richman Laura Smart
Published: April 2013

This chapter describes a multimotive model of responses to rejection-related experiences. Social exclusion, like other forms of rejection, represents a threat to our need to be valued and accepted by others. In response to social exclusion, people often experience three sets of motives that promote competing behaviors: to aggress against the source of rejection, repair the relationship, and withdraw. According to the multimotive model, the ways in which the exclusion is construed determines when each of these behaviors are most likely to occur. The various construals are described in the context of different rejection-related experiences, and the model is applied to understand some of the long-term mental and physical health consequences of unrestored belonging.
The Dark Side of Divorce
Authors: Sbarra David A. , Mason Ashley E.
Published: April 2013

This chapter reviews research linking marital separation and divorce to three important outcomes in adults: mental health problems, physical health outcomes, and relational violence, including risk for homicide at the hands of an ex-partner. Following marital separation and divorce, most adults experience transient distress that abates relatively quickly over time; however, for a small percentage of people, the end of marriage represents a life-altering negative experience. This chapter catalogs a range of adverse outcomes with a focus on the potential mechanisms linking marital status and mental and physical health. The outcomes in question are discussed in terms of an overarching model for why social separations have the potential to be a particularly distressing class of negative life events, as well as methodological research highlighting the need to distinguish between social selection and social causation when considering the putative effects of marital separation and divorce.