bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinguishing medication‐free subjects with unipolar disorder from subjects with bipolar disorder: state matters
Authors: Rive Maria M , Redlich Ronny , Schmaal Lianne , Marquand André F , Dannlowski Udo , Grotegerd Dominik , Veltman Dick J , Schene Aart H , Ruhé Henricus G
Published: November 2016

Objectives

Recent studies have indicated that pattern recognition techniques of functional magnetic resonance imaging (fMRI) data for individual classification may be valuable for distinguishing between major depressive disorder (MDD) and bipolar disorder (BD). Importantly, medication may have affected previous classification results as subjects with MDD and BD use different classes of medication. Furthermore, almost all studies have investigated only depressed subjects. Therefore, we focused on medication‐free subjects. We additionally investigated whether classification would be mood state independent by including depressed and remitted subjects alike.

Methods

We applied Gaussian process classifiers to investigate the discriminatory power of structural MRI (gray matter volumes of emotion regulation areas) and resting‐state fMRI (resting‐state networks implicated in mood disorders: default mode network [DMN], salience network [SN], and lateralized frontoparietal networks [FPNs]) in depressed (n=42) and remitted (n=49) medication‐free subjects with MDD and BD.

Results

Depressed subjects with MDD and BD could be classified based on the gray matter volumes of emotion regulation areas as well as DMN functional connectivity with 69.1% prediction accuracy. Prediction accuracy using the FPNs and SN did not exceed chance level. It was not possible to discriminate between remitted subjects with MDD and BD.

Conclusions

For the first time, we showed that medication‐free subjects with MDD and BD can be differentiated based on structural MRI as well as resting‐state functional connectivity. Importantly, the results indicated that research concerning diagnostic neuroimaging tools distinguishing between MDD and BD should consider mood state as only depressed subjects with MDD and BD could be correctly classified. Future studies, in larger samples are needed to investigate whether the results can be generalized to medication‐naïve or first‐episode subjects.
Conspiracy suspicions as a proxy for beliefs in conspiracy theories: Implications for theory and measurement
Authors: Wood Michael J.
Published: November 2016

Research on the psychology of conspiracy theories has shown recent steps towards a standardization of measures. The present article seeks to continue that trend by presenting the Flexible Inventory of Conspiracy Suspicions (FICS), a questionnaire template that can be adapted to measure suspicions of a conspiracy around nearly any topic of public interest. Compared to conspiracy belief measures that ask about specific theories on a given topic, the FICS is worded in such a way as to provide relatively stable validity across time and cultural context. Using a hybrid approach incorporating classical test theory and Rasch scaling, three questionnaire studies on Mechanical Turk demonstrate the validity of the FICS in measuring conspiracy suspicions regarding 9/11, vaccine safety, and US elections, with good psychometric properties in most situations. However, the utility of the FICS is limited in the case of climate change due to the existence of two opposing conspiracy theories that share essentially no common assumptions (‘climate change is a hoax’ vs. ‘there is a conspiracy to make people believe that climate change is a hoax’). The results indicate that the FICS is a reliable and valid measure of conspiracy suspicions within certain parameters, and suggest a three‐level model that differentiates general conspiracist ideation, relatively vague conspiracy suspicions, and relatively specific conspiracy beliefs.
αvβ3 integrins negatively regulate cellular forces by phosphorylation of its distal NPXY site
Authors: Milloud Rachel , Destaing Olivier , de Mets Richard , Bourrin‐Reynard Ingrid , Oddou Christiane , Delon Antoine , Wang Irène , Albigès‐Rizo Corinne , Balland Martial
Published: November 2016

Background information

Integrins are key receptors that allow cells to sense and respond to their mechanical environment. Although they bind the same ligand, β1 and β3 integrins have distinct and cooperative roles in mechanotransduction.

Results

Using traction force microscopy on unconstrained cells, we show that deleting β3 causes traction forces to increase, whereas the deletion of β1 integrin results in a strong decrease of contractile forces. Consistently, loss of β3 integrin also induces an increase in β1 integrin activation. Using a genetic approach, we identified the phosphorylation of the distal NPXY domain as an essential process for β3 integrin to be able to modulate traction forces. Loss of β3 integrins also impacted cell shape and the spatial distribution of traction forces, by causing forces to be generated closer to the cell edge, and the cell shape.

Conclusions

Our results emphasize the role of β3 integrin in spatial distribution of cellular forces. We speculate that, by modulating its affinity with kindlin, β3 integrins may be able to locate near the cell edge where it can control β1 integrin activation and clustering.

Significance

Tensional homeostasis at the single cell level is performed by the ability of β3 adhesions to negatively regulate the activation degree and spatial localization of β1 integrins. By combining genetic approaches and new tools to analyze traction distribution and cell morphology on a population of cells we were able to identify the molecular partners involved in cellular forces regulation.
Mitochondrial VDAC2 and cell homeostasis: highlighting hidden structural features and unique functionalities
Authors: Maurya Svetlana Rajkumar , Mahalakshmi Radhakrishnan
Published: November 2016

ABSTRACT

Voltage‐dependent anion channels (VDACs) are the gateway to mitochondrial processes, interlinking the cytosolic and mitochondrial compartments. The mitochondrion acts as a storehouse for cytochrome c, the effector of apoptosis, and hence VDACs become intricately involved in the apoptotic pathway. Isoform 1 of VDAC is abundant in the outer mitochondrial membrane of many cell types, while isoform 2 is the preferred channel in specialized cells including brain and some cancer cells. The primary role of VDACs is metabolite flux. The pro‐ and anti‐apoptotic role of VDAC1 and VDAC2, respectively, are secondary, and are influenced by external factors and interacting proteins. Herein, we focus on the less‐studied VDAC2, and shed light on its unique functions and features. VDAC2, along with sharing many of its functions with VDAC1, such as metabolite and Ca2+ transport, also has many delineating functions. VDAC2 is closely engaged in the gametogenesis and steroidogenesis pathways and in protection from oxidative stress as well as in neurodegenerative diseases like Alzheimer's and epilepsy. A closer examination of the functional pathways of VDACs indicates that the unique functions of VDAC2 are a result of the different interactome of this isoform. We couple functional differences to the structural and biophysical evidence obtained for the VDACs, and present a testament of why the two VDAC isoforms with >90% sequence similarity, are functionally diverse. Based on these differences, we suggest that the VDAC isoforms now be considered as paralogs. An in‐depth understanding of VDAC2 will help us to design better biomolecule targets for cancer and neurodegenerative diseases.
Synthesis and preliminary evaluation of a 99mTc‐labeled folate‐PAMAM dendrimer for FR imaging
Authors: Song Manli , Guo Zhide , Gao Mengna , Shi Changrong , Xu Duo , You Linyi , Wu Xiaowei , Su Xinhui , Zhuang Rongqiang , Pan Weimin , Liu Ting , Zhang Xianzhong
Published: November 2016

Folate receptor is an ideal target for tumor‐specific diagnostic and therapeutic. The aim of this study was to synthesize 99mTc‐labeled folate‐polyamidoamine dendrimer modified with 2‐hydrazinonicotinic acid (99mTc‐HP3FA) for FR imaging. The 99mTc‐HP3FA conjugate was prepared using N‐tris‐(hydroxymethyl)‐methylglycine and trisodium triphenylphosphine‐3,3′,3″‐trisulfonate as coligands. Physicochemical properties, in vitro cell uptake study, and in vivo micro‐single‐photon emission computed tomography/CT imaging were performed. The radiolabeled 99mTc‐HP3FA conjugate was prepared with high radiolabeling yield, good stability, and water solubility (logP = −1.70 ± 0.21). In cell uptake study, the radiolabeled conjugate showed high uptakes in the FR‐abundant KB cells and could be blocked significantly by excess folic acid. The 7721 cells which served as control group substantially had no uptakes. The results of micro‐single‐photon emission computed tomography/CT imaging exhibited that high accumulation of activity was found in FR‐overexpressed KB tumor, and the tumor‐to‐muscle ratio was approximately 25.78, while, using free FA as inhibitor, the uptakes of 99mTc‐HP3FA in KB tumor and kidney were obviously inhibited. In summary, a new radiocompound was synthesized successfully with specific FR targeting ability. The feasibility of 99mTc‐HP3FA for early diagnosis of FR‐positive tumors with non‐invasive single‐photon emission computed tomography imaging was demonstrated and the possibility of imaging‐guided drug delivery based on multifunctional polyamidoamine will be studied in the future.
Teenage Mothers Today: What We Know and How It Matters
Authors: Mollborn Stefanie
Published: November 2016

Over the past two decades, births to U.S. teenagers have fallen and no longer follow overall fertility patterns. Yet the unique challenges faced by teenage mothers and their families justify continued research. Across disciplines, newer work has furthered our understanding of teenage motherhood today. In this article, I highlight four areas of progress: processes of selection into teenage motherhood, the broader consequences of teenage childbearing beyond the socioeconomic realm, heterogeneity of effects, and the application of life course principles. Emerging societal trends such as complex family structures, a stalled recovery from the recession for families of low socioeconomic status, and a rapidly evolving political environment for reproductive health care continue to challenge the lives of teenage mothers. Given that the consequences for teenagers of becoming mothers may change, continued research is needed. Shifts in policy to favor supporting teenage mothers and addressing the causes of both teenage pregnancy and social disadvantage may help improve the lives of these mothers and their families.
Children's Sympathy, Guilt, and Moral Reasoning in Helping, Cooperation, and Sharing: A 6‐Year Longitudinal Study
Authors: Malti Tina , Ongley Sophia F. , Peplak Joanna , Chaparro Maria P. , Buchmann Marlis , Zuffianò Antonio , Cui Lixian
Published: November 2016

This study examined the role of sympathy, guilt, and moral reasoning in helping, cooperation, and sharing in a 6‐year, three‐wave longitudinal study involving 175 children (Mage 6.10, 9.18, and 12.18 years). Primary caregivers reported on children's helping and cooperation; sharing was assessed behaviorally. Child sympathy was assessed by self‐ and teacher reports, and self‐attributed feelings of guilt–sadness and moral reasoning were assessed by children's responses to transgression vignettes. Sympathy predicted helping, cooperation, and sharing. Guilt–sadness and moral reasoning interacted with sympathy in predicting helping and cooperation; both sympathy and guilt–sadness were associated with the development of sharing. The findings are discussed in relation to the emergence of differential motivational pathways to helping, cooperation, and sharing.
Young Children Want to See Others Get the Help They Need
Authors: Hepach Robert , Vaish Amrisha , Grossmann Tobias , Tomasello Michael
Published: November 2016

Children's instrumental helping has sometimes been interpreted as a desire to complete action sequences or to restore the physical order of things. Two‐year‐old children (n = 51) selectively retrieved for an adult the object he needed rather than one he did not (but which equally served to restore the previous order of things), and those with greater internal arousal (i.e., pupil dilation) were faster to help. In a second experiment (n = 64), children's arousal increased when they witnessed an adult respond inappropriately to another adult's need. This was not the case in a nonsocial control condition. These findings suggest that children's helping is not aimed at restoring the order of things but rather at seeing another person's need fulfilled.
Staphylococcus aureus‐derived membrane vesicles exacerbate skin inflammation in atopic dermatitis
Authors: Jun S. H. , Lee J. H. , Kim S. I. , Choi C. W. , Park T. I. , Jung H. R. , Cho J. W. , Kim S. H. , Lee J. C.
Published: November 2016

Background

Skin colonization or infection with Staphylococcus aureus is known to trigger aggravation of atopic dermatitis (AD). However, the exact mechanisms by which S. aureus can worsen AD are unknown.

Objective

We investigated whether and how S. aureus‐derived membrane vesicles (MVs) contribute to worsening of AD.

Methods

Immunohistochemical and immunoelectron microscopic analyses were performed to detect staphylococcal protein A (SPA) in the epidermis of AD lesions. HaCaT cells were treated with S. aureus MVs and were analysed for the expression of cytokine genes. Immunopathology and cytokine gene profiles were analysed after topical application of S. aureus MVs to AD‐like skin lesions in a mouse model.

Results

The MV component SPA was detected in the keratinocytes as well as in the intercellular space of the epidermis of AD lesions colonized with S. aureus. Intact MVs from S. aureus delivered their components to keratinocytes and stimulated pro‐inflammatory cytokine gene expression in vitro. A knock‐down of Toll‐like receptor 2 or nucleotide‐binding oligomerization domain 2 using small interfering RNAs suppressed interleukin‐8 gene expression. Topical application of intact S. aureus MVs to AD‐like skin lesions in the mouse model induced massive infiltration of inflammatory cells and the resulting eczematous dermatitis. This inflammatory reaction was associated with a mixed Th1/Th2 immune response and enhanced expression of chemokine genes in AD‐like skin lesions.

Conclusions and Clinical Relevance

This study showed the importance of S. aureus MVs as a potent mediator for worsening of AD among many exogenous worsening factors of AD. Thus, S. aureus MVs may be regarded as one of the therapeutic targets for the management of AD aggravation.
Emerging ocular biomarkers of Alzheimer disease
Authors: van Wijngaarden Peter , Hadoux Xavier , Alwan Mostafa , Keel Stuart , Dirani Mohamed
Published: November 2016

Interest in reliable biomarkers of Alzheimer disease, the leading cause of dementia, has been fuelled by challenges in diagnosing the disease and monitoring disease progression as well as the response to therapy. A range of ocular manifestations of Alzheimer disease, including retinal and lens amyloid‐beta accumulation, retinal nerve fiber layer loss, and retinal vascular changes, have been proposed as potential biomarkers of the disease. Herein, we examine the evidence regarding the potential value of these ocular biomarkers of Alzheimer disease.
A novel method for treatment of chronic anal fissure: adipose‐derived regenerative cells – a pilot study
Authors: Andjelkov K. , Sforza M. , Barisic G. , Soldatovic I. , Hiranyakas A. , Krivokapic Z.
Published: November 2016

Aim

The purpose of this study was to investigate the safety and feasibility of autologous adipose‐derived regenerative cells (ADRC) in the treatment of chronic anal fissure.

Method

A prospective pilot study was conducted in six patients with chronic anal fissures at the First Surgical Clinic, Clinical Center of Serbia and at the BelPrime Clinic, Belgrade, Serbia. All patients were candidates for surgical treatment. The average duration of symptoms was 24 months. Pain assessment was quantified using a visual analogue scale and bowel continence was assessed using the Wexner incontinence score. Both were assessed before treatment and during each postoperative outpatient visit. Liposuction was performed under local or general anaesthesia. Extraction of ADRC was achieved with a closed automated medical device. The fat and ADRC were injected subcutaneously into the edge of the fissure. The rest of the pellet was infiltrated into the internal anal sphincter. The study has been registered at ClinicalTrials.gov (NCT02628522).

Results

Complete healing of the anal fissure and the disappearance of symptoms was achieved in all patients. The average time to complete pain cessation was 33.7 ± 15.0 days. All fissures healed after 3 months and remained healed 12 months after the procedure. There were no complications related to the procedure.

Conclusion

The application of ADRC may be an alternative to lateral sphincterotomy and a reliable procedure which avoids faecal incontinence.
Imitation, Inspiration, and Creation: Cognitive Process of Creative Drawing by Copying Others' Artworks
Authors: Okada Takeshi , Ishibashi Kentaro
Published: November 2016

To investigate the cognitive processes underlying creative inspiration, we tested the extent to which viewing or copying prior examples impacted creative output in art. In Experiment 1, undergraduates made drawings under three conditions: (a) copying an artist's drawing, then producing an original drawing; (b) producing an original drawing without having seen another's work; and (c) copying another artist's work, then reproducing that artist's style independently. We discovered that through copying unfamiliar abstract drawings, participants were able to produce creative drawings qualitatively different from the model drawings. Process analyses suggested that participants' cognitive constraints became relaxed, and new perspectives were formed from copying another's artwork. Experiment 2 showed that exposure to styles of artwork considered unfamiliar facilitated creativity in drawing, while styles considered familiar did not do so. Experiment 3 showed that both copying and thoroughly viewing artwork executed using an unfamiliar style facilitated creativity in drawing, whereas merely thinking about alternative styles of artistic representation did not do so. These experiments revealed that deep encounters with unfamiliar artworks—whether through copying or prolonged observation—change people's cognitive representations of the act of drawing to produce novel artwork.
Mismatch between Habitat Science and Habitat Directive: Lessons from the French (Counter) Example
Authors: Jeanmougin Martin , Dehais Camille , Meinard Yves
Published: November 2016

The European Habitat Directive encompasses a conservation policy devoted to conserve habitats rather than single species. This ambition has strong ecological justifications, and inspires other initiatives such as the IUCN red list of ecosystems. Evaluating this policy is therefore pivotal to identify and reproduce best practices. However, the habitat aspect of this policy has so far not been systematically assessed. To make up for this lacuna, we take advantage of decision‐aiding methodologies to introduce a new normative framework. According to this framework, a conservation policy is positively evaluated if it contributes to conservation, is science‐based, operational, and legitimate. Based on an exploration of the published literature and unpublished reports and databases, we identify knowledge gaps plaguing the European habitat conservation policy. We argue that, due to these knowledge gaps, the contribution of this policy to the conservation of habitats is unproven, it is not science‐based, not operational and not legitimate. Our study draws heavily on the French implementation. Analyzing this example, we highlight knowledge gaps that carry lessons for European conservation policies as a whole, but also for conservation initiatives focused on habitats in a broader geographical and political context. We then identify concrete means to strengthen habitats conservation policies.
The contribution of alcohol use and other lifestyle factors to socioeconomic differences in all‐cause mortality in a Swedish cohort
Authors: Sydén Lovisa , Landberg Jonas
Published: November 2016

Introduction and Aims

A relationship between socioeconomic position (SEP) and mortality has been found in high‐income countries. One possible explanation is socioeconomic differentials in health behaviours. The aim was to investigate to what degree the association between SEP and all‐cause mortality is explained by differences in alcohol use and other lifestyle factors.

Design and Methods

The study was based on data from a large public health survey from Stockholm County in 2002, with 5 year follow‐up for all‐cause mortality. Proportional hazard models estimated the effect of education, occupational class and income on all‐cause mortality, before and after adjusting for alcohol use (both separate and combined effects of levels and patterns of drinking), smoking, physical activity and body mass index.

Results

The prevalence of lifestyle factors showed a marked social gradient. All three SEP indicators showed higher mortality for the most disadvantaged SEP group than in the least disadvantaged group. Adjusting for a combined measure of alcohol use attenuated the SEP differences in mortality by a fifth, whereas adjusting for volume of consumption resulted in considerably smaller attenuations. Adjusting for smoking resulted in attenuations of 6–18%. In the fully adjusted model, physical activity and body mass index did not account for the socioeconomic differences in mortality beyond that of alcohol and smoking.‬

Discussion and Conclusions

Irrespective of whether SEP is defined by education, occupational class or income, the unequal distribution of hazardous alcohol use and smoking contributes to a notable proportion of the socioeconomic differences in mortality in Sweden. [Sydén L, Landberg J. The contribution of alcohol use and other lifestyle factors to socioeconomic differences in all‐cause mortality in a Swedish cohort. Drug Alcohol Rev 2016;00:000‐000]
Mother still knows best: Maternal influence uniquely modulates adolescent reward sensitivity during risk taking
Authors: Guassi Moreira João F. , Telzer Eva H.
Published: November 2016

Adolescent decision‐making is highly sensitive to input from the social environment. In particular, adult and maternal presence influence adolescents to make safer decisions when encountered with risky scenarios. However, it is currently unknown whether maternal presence confers a greater advantage than mere adult presence in buffering adolescent risk taking. In the current study, 23 adolescents completed a risk‐taking task during an fMRI scan in the presence of their mother and an unknown adult. Results reveal that maternal presence elicits greater activation in reward‐related neural circuits when making safe decisions but decreased activation following risky choices. Moreover, adolescents evidenced a more immature neural phenotype when making risky choices in the presence of an adult compared to mother, as evidenced by positive functional coupling between the ventral striatum and medial prefrontal cortex. Our results underscore the importance of maternal stimuli in bolstering adolescent decision‐making in risky scenarios.
Seeing behind the surface: communicative demonstration boosts category disambiguation in 12‐month‐olds
Authors: Kovács Ágnes M. , Téglás Ernő , Gergely György , Csibra Gergely
Published: November 2016

In their first years, infants acquire an incredible amount of information regarding the objects present in their environment. While often it is not clear what specific information should be prioritized in encoding from the many characteristics of an object, different types of object representations facilitate different types of generalizations. We tested the hypotheses that 1‐year‐old infants distinctively represent familiar objects as exemplars of their kind, and that ostensive communication plays a role in determining kind membership for ambiguous objects. In the training phase of our experiment, infants were exposed to movies displaying an agent sorting objects from two categories (cups and plates) into two locations (left or right). Afterwards, different groups of infants saw either an ostensive or a non‐ostensive demonstration performed by the agent, revealing that a new object that looked like a plate can be transformed into a cup. A third group of infants experienced no demonstration regarding the new object. During test, infants were presented with the ambiguous object in the plate format, and we measured generalization by coding anticipatory looks to the plate or the cup side. While infants looked equally often towards the two sides when the demonstration was non‐ostensive, and more often to the plate side when there was no demonstration, they performed more anticipatory eye movements to the cup side when the demonstration was ostensive. Thus, ostensive demonstration likely highlighted the hidden dispositional properties of the target object as kind‐relevant, guiding infants’ categorization of the foldable cup as a cup, despite it looking like a plate. These results suggest that infants likely encode familiar objects as exemplars of their kind and that ostensive communication can play a crucial role in disambiguating what kind an object belongs to, even when this requires disregarding salient surface features.
Coconut milk and probiotic milk as storage media to maintain periodontal ligament cell viability: an in vitro study
Authors: Saini Divya , Gadicherla Prahlad , Chandra Prakash , Anandakrishna Latha
Published: November 2016

Background/Aim

The viability of periodontal ligament (PDL) cells is a significant determinant of the long‐term prognosis of replanted avulsed teeth. A storage medium is often required to maintain the viability of these cells during the extra‐alveolar period. Many studies have been carried out to search for the most suitable storage medium for avulsed teeth, but an ideal solution has not yet been found. The purpose of the study was to compare and analyze the ability of coconut milk and probiotic milk to maintain PDL cell viability.

Methodology

In an in vitro setting, 69 caries free human premolars with normal periodontium that had been extracted for orthodontic purposes were randomly divided into two experimental groups on the basis of storage media used (i.e., coconut milk or probiotic milk) and a Hanks’ balanced salt solution (HBSS) control group (23 samples per group). Immediately after extraction, the teeth were stored dry for 20 min and then immersed for 30 min in one of the storage media. The teeth were then subjected to collagenase–dispase assay and labeled with 0.5% trypan blue staining solution for determination of cell viability. The number of viable cells was counted under a light microscope and statistically analyzed using anova and post hoc Tukey test (P ≤ 0.05).

Results

Statistical analysis demonstrated there was a significant difference (P < 0.001) between coconut milk and probiotic milk as well as HBSS in maintaining cell viability. However, there was no significant difference between probiotic milk and HBSS in ability to maintain PDL cell viability (P > 0.05).

Conclusion

Coconut milk may not be suitable as an interim transport media due to poor maintenance of cell viability. However, probiotic milk was able to maintain PDL cell viability as well as HBSS.
Electrophysiological correlates of decision making impairment in multiple sclerosis
Authors: Azcárraga‐Guirola Elisa , Rodríguez‐Agudelo Yaneth , Velázquez‐Cardoso Julia , Rito‐García Yamel , Solís‐Vivanco Rodolfo
Published: November 2016

Although previous studies have shown that patients with multiple sclerosis (MS) may exhibit impaired decision making (DM), the specific neuro‐cognitive processes that underlie this deficiency remain unknown. Inefficient DM may occur due to poor option assessment or a deficit in the evaluation of choice outcomes. This study uses, for the first time, the event‐related potential (ERP) technique to analyze these DM subprocesses in patients with MS. Sixteen MS patients and nineteen control subjects performed a DM task based on the Iowa Gambling Task while a digital EEG was recorded. The P3b was analyzed as an index of option assessment, and both the feedback‐related negativity (FRN) and P3b were considered markers for choice outcome evaluation. We found that MS patients made a larger number of unfavorable choices during the DM task (P = 0.02), with no differences between groups for reaction times. There were no significant differences in P3b for option assessment between the groups. In the control group, the type of feedback (gain, loss, or nothing) modified the FRN (F = 3.72, P = 0.033) and the P3b (F = 3.15, P = 0.059). This effect was not observed in the MS group. Also, FRN latencies were shorter in the MS group compared to controls (P = 0.047). Finally, lesions in temporal regions revealed by MRI were associated with DM both in behavioral and electrophysiological terms. We conclude that the DM impairment of patients with MS may be due to a deficit in their evaluation of choice outcomes or a general alteration in emotional reactivity.
Sex differences in depolarizing actions of GABAA receptor activation in rat embryonic hypothalamic neurons
Authors: Mir Franco R. , Carrer Hugo F. , Cambiasso María J.
Published: November 2016

GABAA receptor activation exerts trophic actions in immature neurons through depolarization of resting membrane potential. The switch to its classical hyperpolarizing role is developmentally regulated. Previous results suggest that a hormonally biased sex difference exists at the onset of the switch in hypothalamic neurons. The aim of this work was to evaluate sex differences in GABAA receptor function of hypothalamic neurons before brain masculinization by gonadal hormones. Hypothalamic cells were obtained from embryonic day 16 male and female rat foetuses, 2 days before the peak of testosterone production by the foetal testis, and grown in vitro for 9 days. Whole‐cell and perforated patch‐clamp recordings were carried out in order to measure several electrophysiological parameters. Our results show that there are more male than female neurons responding with depolarization to muscimol. Additionally, among cells with depolarizing responses, males have higher and longer lasting responses than females. These results highlight the relevance of differences in neural cell sex irrespective of exposure to sex hormones.
Structural studies of protein arginine methyltransferase 2 reveal its interactions with potential substrates and inhibitors
Authors: Cura Vincent , Marechal Nils , Troffer‐Charlier Nathalie , Strub Jean‐Marc , van Haren Matthijs J. , Martin Nathaniel I. , Cianférani Sarah , Bonnefond Luc , Cavarelli Jean
Published: November 2016

PRMT2 is the less‐characterized member of the protein arginine methyltransferase family in terms of structure, activity, and cellular functions. PRMT2 is a modular protein containing a catalytic Ado‐Met‐binding domain and unique Src homology 3 domain that binds proteins with proline‐rich motifs. PRMT2 is involved in a variety of cellular processes and has diverse roles in transcriptional regulation through different mechanisms depending on its binding partners. PRMT2 has been demonstrated to have weak methyltransferase activity on a histone H4 substrate, but its optimal substrates have not yet been identified. To obtain insights into the function and activity of PRMT2, we solve several crystal structures of PRMT2 from two homologs (zebrafish and mouse) in complex with either the methylation product S‐adenosyl‐L‐homocysteine or other compounds including the first synthetic PRMT2 inhibitor (Cp1) studied so far. We reveal that the N‐terminal‐containing SH3 module is disordered in the full‐length crystal structures, and highlights idiosyncratic features of the PRMT2 active site. We identify a new nonhistone protein substrate belonging to the serine‐/arginine‐rich protein family which interacts with PRMT2 and we characterize six methylation sites by mass spectrometry. To better understand structural basis for Cp1 binding, we also solve the structure of the complex PRMT4:Cp1. We compare the inhibitor–protein interactions occurring in the PRMT2 and PRMT4 complex crystal structures and show that this compound inhibits efficiently PRMT2. These results are a first step toward a better understanding of PRMT2 substrate recognition and may accelerate the development of structure‐based drug design of PRMT2 inhibitors.

Database

All coordinates and structure factors have been deposited in the Protein Data Bank: zPRMT21‐408‐SFG = 5g02; zPRMT273‐408‐SAH = 5fub; mPRMT21‐445‐SAH = 5ful; mPRMT21‐445‐Cp1 = 5fwa, mCARM1130‐487‐Cp1 = 5k8v.
Structure of the transmembrane domain ofHIV‐1 envelope glycoprotein
Authors: Chen Bing , Chou James J.
Published: November 2016

HIV‐1 envelope spike (Env) is a heavily glycosylated, type I membrane protein that mediates fusion of viral and cell membranes to initiate infection. It is also a primary target of neutralizing antibodies and thus an important candidate for vaccine development. We have recently reported a nuclear magnetic resonance structure of the transmembrane (TM) domain ofHIV‐1 Env reconstituted in a membrane‐like environment. TakingHIV‐1 as an example, we discuss here how aTMdomain can anchor, stabilize, and modulate a viral envelope spike and how its high‐resolution structure can contribute to understanding viral membrane fusion and to immunogen design.
Diagnostic concordance of breast pathologists: lessons from the National Health Service Breast Screening Programme Pathology External Quality Assurance Scheme
Authors: Rakha Emad A , Ahmed Mohamed A , Aleskandarany Mohammed A , Hodi Zsolt , Lee Andrew H S , Pinder Sarah E , Ellis Ian O
Published: November 2016

Aims

Previous concordance studies examining accuracy of breast diagnosis by pathologists, typically targeting difficult, histologically challenging breast lesions using artificial and restrictive environments, have reported aberrantly high levels of diagnostic discordance. The results of these studies may be misinterpreted by non‐pathologists and raise concerns relating to routine practice. This study aims to assess the diagnostic agreement among UK breast pathologists.

Methods

Two hundred and forty consecutive breast lesions, submitted by participants from their routine practice, included in the UK National Health Service Breast Screening Programme (NHSBSP) breast pathology EQA scheme during the last 10 years were reviewed. An average of approximately 600 participants viewed each case. Data on diagnostic categories (benign, atypical, in‐situ malignant and invasive malignant) were collected. In this study, benign and atypical diagnoses were grouped together.

Results

The overall diagnostic agreement level was in the almost perfect range. Thirty‐five cases (14.6%) showed diagnostic concordance of ≤95%. Reasons for discordance included one or more of: (1) scheme methodology limitations such as: (i) miscoding of certain lesions (e.g. phyllodes tumours and lobular neoplasia) (n = 7) and (ii) variable representation of the index lesion on glass slides (n = 18); and (2) diagnostically challenging cases that may be interpreted more easily using immunohistochemistry (n = 28). These latter included benign and malignant papillary lesions (n = 12), complex sclerosing lesions (n = 7), intraductal epithelial proliferative lesions (n = 6) and an unusual special tumour type (n = 1). Further review identified pathologists’ misinterpretation in 13 cases (5.4%), with an average discordance rate of only 4.2%.

Conclusions

The performance of breast pathologists is high. Exclusion of the effect of the scheme methodology limitations highlights further the high performance rate and identifies true diagnostically challenging entities. These difficult cases may benefit from additional diagnostic work‐up and second opinions.
Moisture sensing studies of CuO‐ZnO nanocomposites
Authors: Rajput Vijay , Pandey Narendra
Published: November 2016

This paper reports the characterization and humidity sensing studies of CuO–ZnO nanocomposites prepared by solid‐state reaction method. The electrical resistance of nanocomposites continuously decreased when relative humidity (RH) was increased from 10% to 95% RH. Nanocomposites with 1 wt% of CuO in ZnO showed the best results with a sensitivity of 29.95 MΩ/%RH. This sample also showed low hysteresis and high reproducibility. This sample had an average particle and crystallite size of 200 nm and 70 nm, respectively. Measurement of crystallite size by both the methods, that is, Scherer's formula and Williamson and Hall method matched with an error of ±4%.
Climate hindcasts: exploring the disjunct distribution of Diopatra biscayensis
Authors: Wethey David S. , Woodin Sarah A. , Berke Sarah K. , Dubois Stanislas F.
Published: November 2016

The ecosystem engineer onuphid polychaete Diopatra biscayensis has a continuous population in the Bay of Biscay from the Cantabria coast in Spain to southern Brittany in France. A group of disjunct populations also are found in the English Channel, separated from the Biscay population by more than 400 coastal kilometers. It remains unclear whether D. biscayensis is native to the Bay of Biscay; it is also debated whether the disjunct populations in the English Channel are relics of a formerly continuous population, or the product of recent introductions through aquaculture. Here, we use climate hindcasts to explore hypotheses about the D. biscayensis historical distribution in Europe. If D. biscayensis is native, its range would have been restricted to southern Iberia and the Mediterranean during the Last Glacial Maximum (21,000 BP). However, the species is completely absent from both regions today, further supporting its interpretation as a non‐native species. If it was historically present in Europe, the climate hindcasts are congruent with range contraction in the Last Glacial Maximum (21,000 BP), expansion in the Mid‐Holocene Warm Period (6000 BP), and contraction again in the past 1000 years (850–1850), prior to the first reports of D. biscayensis on the Spanish and French Atlantic coasts. However, the simulations do not support there being climatic refugia along the English Channel coast that would account for the existence of relic populations. Taken together, the evidence suggests that D. biscayensis has been introduced to the Bay of Biscay, and that disjunct populations in the English Channel are the result of recent transport through human activities, perhaps aquaculture.
Population and reproductive dynamics of the polychaete Pygospio elegans in a boreal estuary complex
Authors: Thonig Anne , Knott K. Emily , Kesäniemi Jenni Emilia , Winding Hansen Benni , Banta Gary Thomas
Published: November 2016

Pygospio elegans is an opportunistic, wide‐spread spionid polychaete that reproduces asexually via fragmentation and can produce benthic and pelagic larvae, hence combining different developmental modes in one species. We documented the density, size distribution, and reproductive activity of P. elegans at four sites in the Danish Isefjord‐Roskilde Fjord estuary complex, where all modes of reproduction were reported. We compared population dynamics of this species to environmental parameters such as salinity, temperature, and sediment characteristics (grain size, sorting, porosity, water content, organic content, C/N). We observed that new cohorts—resulting either from sexual or asexual reproduction—appeared in spring and fall, and old ones disappeared in late summer and winter. Sexual reproduction occurred from September until May, and although their timing was variable, there were two reproductive peaks at three sites. At those sites, we also observed a switch in larval developmental mode. Asexual reproduction peaked in April. While the seasonal dynamics can be related to temperature to a large extent, the differences in population dynamics among sites also correlated with sediment structure and salinity. Populations from sites with coarse and heterogeneous sediment had high levels of sexual reproduction. At the site with lower salinity, intermediate and benthic larvae were present during winter in contrast to pelagic larvae found at the other sites. However, we could not identify one clear environmental factor determining the mode of development. At present, it remains unclear to what degree genetic background contributes to mode of development. Hence, whether the differences in developmental mode are the result of genetically different cohorts will be further investigated.
When does speech sound disorder matter for literacy? The role of disordered speech errors, co‐occurring language impairment and family risk of dyslexia
Authors: Hayiou‐Thomas Marianna E. , Carroll Julia M. , Leavett Ruth , Hulme Charles , Snowling Margaret J.
Published: November 2016

Background

This study considers the role of early speech difficulties in literacy development, in the context of additional risk factors.

Method

Children were identified with speech sound disorder (SSD) at the age of 3½ years, on the basis of performance on the Diagnostic Evaluation of Articulation and Phonology. Their literacy skills were assessed at the start of formal reading instruction (age 5½), using measures of phoneme awareness, word‐level reading and spelling; and 3 years later (age 8), using measures of word‐level reading, spelling and reading comprehension.

Results

The presence of early SSD conferred a small but significant risk of poor phonemic skills and spelling at the age of 5½ and of poor word reading at the age of 8. Furthermore, within the group with SSD, the persistence of speech difficulties to the point of school entry was associated with poorer emergent literacy skills, and children with ‘disordered’ speech errors had poorer word reading skills than children whose speech errors indicated ‘delay’. In contrast, the initial severity of SSD was not a significant predictor of reading development. Beyond the domain of speech, the presence of a co‐occurring language impairment was strongly predictive of literacy skills and having a family risk of dyslexia predicted additional variance in literacy at both time‐points.

Conclusions

Early SSD alone has only modest effects on literacy development but when additional risk factors are present, these can have serious negative consequences, consistent with the view that multiple risks accumulate to predict reading disorders.
Ixekizumab treatment improves fingernail psoriasis in patients with moderate‐to‐severe psoriasis: results from the randomized, controlled and open‐label phases of UNCOVER‐3
Authors: van de Kerkhof P. , Guenther L. , Gottlieb A.B. , Sebastian M. , Wu J.J. , Foley P. , Morita A. , Goldblum O. , Zhang L. , Erickson J. , Ball S. , Rich P.
Published: November 2016

Background

Fingernail psoriasis is difficult to treat.

Objective

The objective was to evaluate the effect of ixekizumab, a monoclonal antibody selectively targeting IL‐17A, on fingernail psoriasis.

Methods

This Phase 3, double‐blind trial (UNCOVER‐3) randomized patients to placebo, etanercept (50‐mg twice weekly), or 80 mg ixekizumab as one injection every 4 (IXE Q4W) or 2 weeks (IXE Q2W) after a 160‐mg starting dose. At Week 12, ixekizumab patients received open‐label IXE Q4W through Week 60; placebo patients received a 160‐mg starting ixekizumab dose and etanercept patients a 4‐week placebo washout before starting IXE Q4W. Efficacy was assessed by mean per cent Nail Psoriasis Severity Index (NAPSI) improvement at Weeks 12 and 60.

Results

Of 1346 patients in the UNCOVER‐3 trial, this subgroup analysis included only patients with baseline fingernail psoriasis: 116 (60.1%) placebo, 236 (61.8%) etanercept, 228 (59.1%) IXE Q4W and 229 (59.5%) IXE Q2W. At Week 12, greater mean per cent NAPSI improvements were achieved in IXE Q4W (36.7%) and IXE Q2W (35.2%) vs. placebo (−34.3%, P < 0.001 each comparison) and etanercept (20.0%, P = 0.048 vs. Q4W, P = 0.072 vs. Q2W). At Week 60, mean per cent NAPSI improvement was >80% regardless of initial treatment. At Week 12 (nonresponder imputation), complete resolution (NAPSI = 0) was achieved in 19.7% (IXE Q4W), 17.5% (IXE Q2W), 4.3% (placebo, P < 0.001 each comparison) and 10.2% (etanercept, P < 0.05 each comparison) of patients. By Week 60, >50% of patients achieved complete resolution.

Conclusions

At Week 12, significant improvements in fingernail psoriasis were achieved with ixekizumab therapy. With IXE Q4W maintenance dosing, additional improvement was demonstrated through 60 weeks, and >50% of patients achieved complete resolution.

Registered at clinicaltrials.gov: NCT01646177
Molecular Phylogeny and Taxonomy of a New Freshwater Hymenostomatid from Northeastern China, with the Establishment of a New Genus Anteglaucoma gen. n. (Protista, Ciliophora, Oligohymenophorea)
Authors: Pan Xuming , Shi Zihan , Wang Chundi , Bourland William A. , Chen Ying , Song Weibo
Published: November 2016

The morphology, infraciliature and SSU rDNA sequence of a new freshwater hymenostomatid ciliate, Anteglaucoma harbinensis gen. nov., spec. nov., collected from a farmland pond in Harbin, China, were investigated. The new genus Anteglaucoma is characterized as follows: small to medium‐sized Glaucomidae with oral apparatus in anterior one‐third of cell; paroral membrane composed of almost longitudinally arranged dikinetids; three adoral membranelles nearly equal in length and arranged almost longitudinally in parallel; silverline pattern tetrahymenid. The improved diagnosis of family Glaucomidae Corliss 1971 is provided based on the previous and present work. The type species Anteglaucoma harbinensis spec. nov. is defined by having 32–35 somatic kineties; four or five postoral kineties; membranelle 1 and membranelle 2 having five or six kinetosomal rows, membranelle 3 having three kinetosomal rows; single macronuclear nodule; contractile vacuole on average 15% from posterior body end; locomotion characterized by crawling with a rather hectic jerking motion; freshwater habitat. Phylogenetic analyses show that Anteglaucoma clusters in the family Glaucomidae and groups with the genera Glaucoma. The molecular and morphological data indicate that Glaucomidae is related to the family Bromeliophryidae in the phylogenetic trees.