bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypic expansion in DDX3X – a common cause of intellectual disability in females
Authors: Wang Xia , Rosenfeld Jill A. , Bacino Carlos A. , Scaglia Fernando , Immken LaDonna , Harris Jill M. , Hickey Scott E. , Mosher Theresa M. , Slavotinek Anne , Zhang Jing , Beuten Joke , Leduc Magalie S. , He Weimin , Vetrini Francesco , Walkiewicz Magdalena A. , Bi Weimin , Xiao Rui , Shao Yunru , Gezdirici Alper , Jiang Yunyun , Hansen Adam W. , Pehlivan Davut , Piard Juliette , Muzny Donna M. , Hanchard Neil , Belmont John W. , van Maldergem Lionel , Gibbs Richard A. , Eldomery Mohammad K. , Akdemir Zeynep C. , Harel Tamar , Posey Jennifer E. , Adesina Adekunle M. , Chen Shan ,   members of the UDN, Lee Brendan , Lupski James R. , Eng Christine M. , Xia Fan , Yang Yaping , Graham Brett H. , Moretti Paolo 
Published: March 2018

AbstractDe novo variants in DDX3X account for 1-3% of unexplained intellectual disability (ID), one of the most common causes of ID, in females. Forty-seven patients (44 females, 3 males) have been described. We identified 29 additional individuals carrying 27 unique DDX3X variants in the setting of complex clinical presentations including developmental delay or ID. In addition to previously reported manifestations, rare or novel phenotypes were identified including respiratory problems, congenital heart disease, skeletal muscle mitochondrial DNA depletion, and late-onset neurologic decline. Our findings expand the spectrum of DNA variants and phenotypes associated with DDX3X disorders.
Active information sampling varies across the cardiac cycle
Authors: Kunzendorf Stella , Klotzsche Felix , Akbal Mert , Villringer Arno , Ohl Sven , Gaebler Michael 
Published: March 2018

AbstractPerception and cognition oscillate with fluctuating bodily states. For example, visual processing has been shown to change with alternating cardiac phases. Here, we study the heartbeat’s role for active information sampling—testing whether humans implicitly act upon their environment so that relevant signals appear during preferred cardiac phases.During the encoding period of a visual memory experiment, participants clicked through a set of emotional pictures to memorize them for a later recognition test. By self-paced key press, they actively prompted the onset of shortly (100-ms) presented pictures. Simultaneously recorded electrocardiograms allowed us to analyse the self-initiated picture onsets relative to the heartbeat. We find that self-initiated picture onsets vary across the cardiac cycle, showing an increase during cardiac systole, while memory performance was not affected by the heartbeat. We conclude that active information sampling integrates heart-related signals, thereby extending previous findings on the association between body-brain interactions and behaviour.
Sensory Deprivation Independently Regulates Neocortical Feedforward and Feedback Excitation-Inhibition Ratio
Authors: Miska Nathaniel J. , Richter Leonidas M.A. , Cary Brian A. , Gjorgjieva Julijana , Turrigiano Gina G. 
Published: March 2018

SUMMARYBrief (2-3d) monocular deprivation (MD) during the critical period induces a profound loss of responsiveness within layer 4 of primary visual cortex (V1). This has largely been ascribed to long-term depression (LTD) at thalamocortical synapses onto pyramidal neurons, while a contribution from intracortical inhibition has been controversial. Here we used optogenetics to probe feedforward thalamocortical and feedback intracortical excitation-inhibition (E-I) ratios following brief MD. While thalamocortical inputs onto pyramidal neurons were depressed, there was stronger depression onto PV+ interneurons, which shifted the thalamocortical-evoked E-I ratio toward excitation. In contrast, feedback intracortical E-I ratio was shifted toward inhibition, and a computational model of layer 4 demonstrated that these opposing shifts produced an overall suppression of layer 4 excitability. Thus, feedforward and feedback E-I ratios onto the same postsynaptic target can be independently regulated by visual experience, and enhanced feedback inhibition is the primary driving force behind loss of visual responsiveness.
Cell-type heterogeneity in adipose tissue is associated with complex traits and reveals disease-relevant cell-specific eQTLs
Authors: Glastonbury Craig A. , Alves Alexessander Couto , El-Sayed Moustafa Julia S. , Small Kerrin S. 
Published: March 2018

AbstractAdipose tissue is comprised of a heterogeneous collection of cell-types which can differentially impact disease phenotypes. We investigated cell-type heterogeneity in two population-level subcutaneous adipose tissue RNAseq datasets (TwinsUK, N =766 and GTEx, N=326). We find that adipose cell-type composition is heritable and confirm the positive association between macrophage proportion and obesity (BMI), but find a stronger BMI-independent association with DXA-derived body-fat distribution traits. Cellular heterogeneity can confound ‘omic analyses, but is rarely taken into account in analysis of solid-tissue transcriptomes. We benchmark the impact of adipose tissue cell-composition on a range of standard analyses, including phenotypegene expression association, co-expression networks and cis-eQTL discovery. We applied G x Cell Type Proportion interaction models to identify 26 cell-type specific eQTLs in 20 genes, including 4 autoimmune disease GWAS loci, demonstrating the potential of in silico deconvolution of bulk tissue to identify cell-type restricted regulatory variants.
Dynamic Construction of Reduced Representations in the Brain for Perceptual Decision Behavior
Authors: Zhan Jiayu , Ince Robin A. A. , van Rijsbergen Nicola , Schyns Philippe G. 
Published: March 2018

AbstractCurrent models propose that the brain uses a multi-layered architecture to reduce the high dimensional visual input to lower dimensional representations that support face, object and scene categorizations. However, understanding the brain mechanisms that support such information reduction for behavior remains challenging. We addressed the challenge using a novel information theoretic framework that quantifies the relationships between three key variables: single-trial information randomly sampled from an ambiguous scene, source-space MEG responses and perceptual decision behaviors. In each observer, behavioral analysis revealed the scene features that subtend their decisions. Independent source space analyses revealed the flow of these and other features in cortical activity. We show where (at the junction between occipital cortex and ventral regions), when (up until 170 ms post stimulus) and how (by separating task-relevant and irrelevant features) brain regions reduce the high-dimensional scene to construct task-relevant feature representations in the right fusiform gyrus that support decisions. Our results inform the occipito-temporal pathway mechanisms that reduce and select information to produce behavior.
Role of anterograde motor Kif5b in clathrin-coated vesicle uncoating and clathrin-mediated endocytosis
Authors: Ni Yan-Xiang , Xue Wen-Qian , Zhou Nan , Yung Wing-Ho , Lin Rao-Zhou , Kao Richard Yi-Tsun , Duan Zhi-Gang , Tang Xu-Ming , Liu Meng-Fei , Zhang Wen , Qi Shuang , Lu Xi-Bin , Hu Jian-jiang , Chung Sookja , Song You-Qiang , Huang Jian-Dong 
Published: March 2018

SummaryKif5b-driven anterograde transport and clathrin-mediated endocytosis (CME) are responsible for opposite intracellular trafficking, contributing to plasma membrane homeostasis. However, whether and how the two trafficking processes coordinate remain unclear. Here, we show that Kif5b directly interacts with clathrin heavy chain (CHC) at a region close to that for uncoating catalyst (Hsc70) and preferentially localizes on large clathrin-coated vesicles (CCVs). Uncoatingin vitrois decreased for CCVs from the cortex ofkif5bconditional knockout (mutant) mouse and facilitated by adding CHC-binding Kif5b fragments, while cell peripheral distribution of CHC or Hsc70 keeps unaffected by Kif5b depletion. Furthermore, cellular entry of vesicular stomatitis virus that internalized into large CCV is inhibited in cells by Kif5b depletion or introducing a dominant-negative Kif5b fragment. These findings showed a new role of Kif5b in CCV uncoating and CME, indicating Kif5b as a molecular knot connecting anterograde transport to CME.
Identify and Predict Environmental Change Effects On Tiger Mosquitos,Aedes Polynesiensis
Authors: Grziwotz Florian , Strauß Jakob Friedrich , Hsieh Chih-hao , Telschow Arndt 
Published: March 2018

SummaryTo control mosquito populations for managing vector-borne diseases, a critical need is to identify and predict their response to causal environmental variables. However, most existing attempts rely on linear approaches based on correlation, which cannot apply in complex, nonlinear natural systems, because correlation is neither a necessary nor sufficient condition for causation. Appling empirical dynamic modelling that acknowledges nonlinear dynamics on nine subpopulations of tiger mosquitos from three neighbouring reef islets of the Raiatea atoll, we identified temperature, precipitation, dew point, air pressure, and mean tide level as causal environmental variables. Interestingly, responses of subpopulations in close proximity (100-500 m) differed with respect to their causal environmental variables and the time delay of effect, highlighting complexity in mosquito-environment causality network. Moreover, we demonstrated how to explore the effects of changing environmental variables on number and strength of mosquito outbreaks, providing a new framework for pest control and disease vector ecology.
Chromosome compartmentalization replacement during stem cell differentiation
Authors: Eidelman Y.A. , Slanina S.V. , Pyatenko V.S. , Andreev S.G. 
Published: March 2018

ABSTRACTIn this paper, changes in a large-scale 3D structure of chromosomes during stem cell differentiation is studied. The polymer coarse-grained model of a human interphase chromosome is introduced which reproduces the experimental Hi-C contact maps in chromosomes 12, 17 for both embryonic stem and differentiated cells with high accuracy. Model based analysis of Hi-C data suggests a mechanism of establishment of preferential long-range chromosomal contacts and compartmentalization replacement during cell stem differentiation. The model provides the conceptual basis for integration of data on the dynamics of chromatin interactions, the 3D structure of chromosomes and gene expression during stem cell differentiation or reprogramming.
A re-examination of responding on ratio and regulated-probability interval schedules
Authors: Pérez Omar D. , Aitken Michael R.F. , Milton Amy L. , Dickinson Anthony 
Published: March 2018

AbstractThe higher response rates observed on ratio than on matched interval reward schedules has been attributed to the differential reinforcement of longer inter-response times (IRTs) on the interval contingency. Some data, however, seem to contradict this hypothesis, showing that the difference is still observed when the role of IRT reinforcement is neutralized by using a regulated-probability interval schedule (RPI). Given the mixed evidence for these predictions, we re-examined this hypothesis by training three groups of rats to lever press under ratio, interval and RPI schedules across two phases while matching reward rates within triads. At the end of the first phase, the master ratio and RPI groups responded at similar rates. In the second phase, an interval group yoked to the same master ratio group of the first phase responded at a lower rate than the RPI group. Post-hoc analysis showed comparable reward rates for master and yoked schedules. The experienced response-outcome rate correlations were likewise similar, and approached zero as training progressed. We discuss these results in terms of dual-system theories of instrumental conditioning.
Genome-wide prediction of synthetic rescue mediators of resistance to targeted and immunotherapy
Authors: Das Avinash , Lee Joo Sang , Zhang Gao , Wang Zhiyong , Iglesias-Bartolome Ramiro , Tian Tian , Wei Zhi , Miao Benchun , Nair Nishanth Ulhas , Ponomarova Olga , Friedman Adam A. , Amzallag Arnaud , Moll Tabea , Kasumova Gyulnara , Greninger Patricia , Egan Regina K. , Damon Leah J. , Frederick Dennie T. , Wagner Allon , Cheng Kuoyuan , Park Seung Gu , Robinson Welles , Gardner Kevin , Boland Genevieve , Hannenhalli Sridhar , Herlyn Meenhard , Benes Cyril , Gutkind J. Silvio , Flaherty Keith , Ruppin Eytan 
Published: March 2018

ABSTRACTMost patients with advanced cancer eventually acquire resistance to targeted therapies, spurring extensive efforts to identify molecular events mediating therapy resistance. Many of these events involvesynthetic rescue (SR) interactions, where the reduction in cancer cell viability caused by targeted gene inactivation is rescued by an adaptive alteration of another gene (therescuer). Here we perform a genome-wide prediction of SR rescuer genes by analyzing tumor transcriptomics and survival data of 10,000 TCGA cancer patients. Predicted SR interactions are validated in new experimental screens. We show that SR interactions can successfully predict cancer patients’ response and emerging resistance. Inhibiting predicted rescuer genes sensitizes resistant cancer cells to therapies synergistically, providing initial leads for developing combinatorial approaches to overcome resistance proactively. Finally, we show that the SR analysis of melanoma patients successfully identifies known mediators of resistance to immunotherapy and predicts novel rescuers.
Transdiagnostic multimodal neuroimaging in psychosis: structural, resting-state, and task MRI correlates of cognitive control
Authors: Lerman-Sinkoff Dov B. , Kandala Sridhar , Calhoun Vince D. , Barch Deanna M. , Mamah Daniel T. 
Published: March 2018

AbstractBackgroundPsychotic disorders, including schizophrenia and bipolar disorder, are associated with impairments in regulation of goal-directed behavior, termed cognitive control. Cognitive control related neural alterations have been studied in psychosis. However, studies are typically unimodal and relationships across modalities of brain function and structure remain unclear. Thus, we performed transdiagnostic multimodal analyses to examine cognitive control related neural variation in psychosis.MethodsStructural, resting, and working memory task imaging and behavioral data for 31 controls, 27 bipolar, and 23 schizophrenia patients were collected and processed identically to the Human Connectome Project (HCP), enabling identification of relationships with prior multimodal work. Two cognitive control related independent components (ICs) derived from the HCP using multiset canonical correlation analysis + joint independent component analysis (mCCA+jICA) were used to predict performance in psychosis. de novo mCCA+jICA was performed, and resultant IC weights were correlated with cognitive control.ResultsA priori ICs significantly predicted cognitive control in psychosis (3/5 modalities significant). De novo mCCA+jICA identified an IC correlated with cognitive control that also discriminated groups. Structural contributions included insular, somatomotor, cingulate, and visual regions; task contributions included precentral, posterior parietal, cingulate, and visual regions; and resting-state contributions highlighted canonical network organization. Follow-up analyses suggested de novo correlations with cognitive control were primarily influenced by schizophrenia patients.ConclusionsA priori components partially predicted performance in transdiagnostic psychosis and de novo analyses identified novel contributions in somatomotor and visual regions in schizophrenia. Together, results suggest joint contributions across modalities related to cognitive control across the healthy-to-psychosis spectrum.
Human sensory Long-Term Potentiation (LTP) predicts visual memory performance and is modulated by the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism
Authors: Spriggs M.J. , Thompson C.S. , Moreau D , McNair N.A. , Wu C.C. , Lamb Y.N. , McKay N.S. , King R.O.C. , Antia U. , Shelling A.N. , Hamm J.P. , Teyler T.J. , Russell B.R. , Waldie K.W. , Kirk I.J. 
Published: March 2018

BackgroundLong-Term Potentiation (LTP) is recognised as a core neuronal process underlying long-term memory. However, a direct relationship between LTP and human memory performance is yet to be demonstrated. The first aim of the current study was thus to assess the relationship between LTP and human long-term memory performance. With this also comes an opportunity to explore factors thought to mediate the relationship between LTP and long-term memory, and to gain additional insight into variations in memory function and memory decline. The second aim of the current study was to explore the relationship between LTP and memory in groups differing with respect to BDNF Val66Met; a single nucleotide polymorphism implicated in memory function.Methods28 participants (15 female) were split into three genotype groups (Val/Val, Val/Met, Met/Met) and were presented with both an EEG paradigm for inducing LTP-like enhancements of the visually-evoked response, and a test of visual memory.ResultsThe magnitude of LTP 40 minutes after induction was predictive of long-term memory performance. Additionally, the BDNF Met allele was associated with both reduced LTP and reduced memory performance.ConclusionsThe current study not only presents the first evidence for a relationship between sensory LTP and human memory performance, but also demonstrates how targeting this relationship can provide insight into factors implicated in variation in human memory performance. It is anticipated that this will be of utility to future clinical studies of disrupted memory function.
Structural view on the role of WT1’s zinc finger 1 in DNA binding
Authors: Yengo Raymond K. , Nurmemmedov Elmar , Thunnissen Marjolein M 
Published: March 2018

AbstractThe WT1 protein is a transcription factor that controls genes involved in cell proliferation, differentiation and apoptosis. It has become increasing apparent that WT1 can act both as a tumor suppressor and oncogene in a tissue specific manner. This opposing role of WT1 is linked to its underlying transcriptional regulatory function, which involves the specific binding to its regulatory elements on gene promoters. WT1 binds DNA using it C-terminal domain made up of 4 C2H2-typ zinc fingers. This same zinc finger domain is used to bind RNA and proteins and it is still not clear how each zinc finger contributes to this promiscuous binding behavior. The molecular details of DNA binding by zinc finger 2 to 4 have been described but it remains to be determined whether or not zinc finger 1 binds DNA and if so whether it exhibits any DNA binding specificity. We present the X-ray structures of zinc finger 1 to 3 bound to a 9 bp and an 8 bp DNA. The two structures refined to 1.7 Å, show no DNA binding specificity for zinc finger 1. The only DNA interactions involving zinc finger 1 are crystal-packing interactions with a symmetry related molecule. In the structure of zinc finger 1 to 3 bound to the 9 bp DNA we observe a shift in the DNA binding positions for zinc fingers 2 and 3. These structures provide molecular detail into the WT1-DNA interaction showing that zinc finger 1 only modestly contributes to DNA binding affinity through transient interactions. The dislocation of zinc finger 2 and 3 emphasizes the importance of zinc finger 4 for maintaining gene transcriptional specificity.
The interval transfer of a frozen‐thawed embryo is more successful than a fresh embryo transfer for women undergoing IVF with recurrent implantation failure after cleavage stage embryo biopsy
Authors: Pontré Jennifer C. , Ryan John P. , Tan Andy , Hart Roger J. 
Published: March 2018

BackgroundRecurrent implantation failure (RIF) is repeated unsuccessful embryo transfers (ETs).AimsTo identify predictive embryonic markers of implantation in RIF, following pre‐implantation genetic screening (PGS) of cleavage stage embryos, after accounting for male and female factors.Materials and MethodsRetrospective analysis of RIF patients undergoing PGS after correction of modifiable causes.ResultsEighty‐four patients underwent 140 in vitro ferilisation cycles. Forty‐one cycles were excluded: 12 (no embryo for transfer), four (double ETs) and 25 (no biopsy). Sixty‐three patients underwent 99 single euploid ETs (48 fresh, 51 frozen) resulting in 11 biochemical pregnancies, 36 clinical pregnancies (CP), and six miscarriages and 30 live births (LB). Frozen ET was more successful than fresh; respective live birth rate (LBR) and clinical pregnancy rate (CPR), 39.2% versus 20.8%, (P = 0.02), 45.1% versus 27.1% (P = 0.04).LBR and CPR were lower when 5–6 blastomeres were present at embryo biopsy, compared to embryos with ≥7 blastomeres: 15.4% versus 32.6% (P = 0.185) and 15.4% versus 39.5% (P = 0.074) respectively. Serum β human chorionic gonadotropin (βhCG) concentration was greater when a more developed embryo was biopsied (r = 0.448, P = 0.017 and r = 0.476, P = 0.118, fresh and frozen transfers, respectively).Embryo morphokinetic analysis demonstrated faster development to blastocyst stage when more cells were present at biopsy: mean 103.3, 102.2 and 96.0 h for biopsy at the 5–6, 7–8 or ≥9 cell stage respectively (P = 0.040 for difference between 7–8 cells vs ≥9).ConclusionsAfter cleavage stage biopsy, frozen ET was more successful than fresh ET. Chance of conception and serum βhCG concentration correlated with number of cells present at time of biopsy.
Education: The Heart of the Matter
Authors: Morriss Wayne W. , Milenovic Miodrag S. , Evans Faye M. 
Published: March 2018

There are inadequate numbers of anesthesia providers in many parts of the world. Good quality educational programs are needed to increase provider numbers, train leaders and teachers, and increase knowledge and skills. In some countries, considerable external support may be required to develop self-sustaining programs. There are some key themes related to educational programs in low- and middle-income countries:
(1) Programs must be appropriate for the local environment—there is no “one-size-fits-all” program. In some countries, nonuniversity programs may be appropriate for training providers.
(2) It is essential to train local teachers—a number of short courses provide teacher training. Overseas attachments may also play an important role in developing leadership and teaching capacity.
(3) Interactive teaching techniques, such as small-group discussions and simulation, have been incorporated into many educational programs. Computer learning and videoconferencing offer additional educational possibilities.
(4) Subspecialty education in areas such as obstetric anesthesia, pediatric anesthesia, and pain management are needed to develop leadership and increase capacity in subspecialty areas of practice. Examples include short subspecialty courses and clinical fellowships.
(5) Collaboration and coordination are vital. Anesthesiologists need to work with ministries of health and other organizations to develop plans that are matched to need. External organizations can play an important role.
(6) Excellent education is required at all levels. Training guidelines could help to standardize and improve training. Resources should be available for research, as well as monitoring and evaluation of educational programs.