bluuebunny/crossref_metadata_2025 huggingface dataset:
The Research of Acellular Pancreatic Bioscaffold as a Natural 3-Dimensional Platform In Vitro
Authors: Wang Xin , Li Yue-Guang , Du Yue , Zhu Ji-Ye , Li Zhao
Published: August 2018

Objective

The aim of the study was to investigate the biochemical and functional properties of a rat acellular pancreatic bioscaffolds (APBs).

Methods

Fresh pancreata from 10 rats were soaked and perfused through portal veins using Easy-Load Digital Drive peristaltic pumps. The histological structure, extracellular matrix composition, and the DNA content of the APBs were evaluated. Biocompatibility studies had also been performed. The proliferation and differentiation of AR42J pancreatic acinar cells were assessed.

Results

The pancreatic tissue became translucent after decellularization. There were no visible vascular endothelial cells, cellular components, or cracked cellular debris. The extracellular matrix components were not decreased after decellularization (P> 0.05); however, the DNA content was decreased significantly (P< 0.05). The subcutaneous implantation sites showed low immunological response and low cytotoxicity around the APB. The proliferation rate was higher and the apoptosis rate was lower when AR42J cells were cultured on APB (P< 0.05). The gene expression and the protein expression were higher for the APB group (P< 0.001).

Conclusions

Our findings support the biological utility of whole pancreas APBs as biomaterial scaffolds, which provides an improved approach for regenerative medicine.
Disability in amyotrophic lateral sclerosis compared with traumatic brain injury using the World Health Organization Disability Assessment Schedule 2.0 and the International Classification of Functioning minimal generic set
Authors: Tarvonen-Schröder Sinikka , Kaljonen Anne , Laimi Katri
Published: August 2018

We compared the functioning of two neurological patient groups, amyotrophic lateral sclerosis (ALS) and traumatic brain injury (TBI), using brief and validated International Classification of Functioning (ICF)-based tools. A 12-item World Health Organization Disability Assessment Schedule (WHODAS 2.0) questionnaire was mailed to ALS and TBI patients and their significant others 2 weeks before their appointment at an outpatient clinic of a university hospital. In addition, a neurologist filled in the ICF minimal generic set. Two years after diagnosis, no significant differences between the two diagnosis groups were found in overall functioning or in working ability using either patient or proxy WHODAS or physician-rated minimal generic set. In single items, however, clear differences were found. Patients and significant others rated household activities, mobility, and self-care as more impaired in the group with ALS, and learning, concentrating, and maintaining friendships in the group with TBI. There were no differences between the two diagnosis groups in the WHODAS items emotional functions, engaging in community, relating with strangers, or in working ability. Both brief ICF-based generic scales, WHODAS and the ICF generic set, could show differences between these patient groups with severe disability. The results of this study should promote assessment of disability with WHODAS 2.0 in ALS and TBI.
A comparison of the usability of a standard and an age-friendly smartphone launcher: experimental evidence from usability testing with older adults
Authors: Petrovčič Andraž , Šetinc Mojca , Burnik Tomaž , Dolničar Vesna
Published: August 2018

Age-friendly smartphone launchers are tools designed to enhance smartphone handling among older adults with cognitive and functional limitations. Although evidence exists about the positive effects of age-friendly smartphone launchers on older adults’ usability performance in general, little is known about how the design and interface complexity of these launchers affect their interface usability effectiveness and efficiency compared with standard Android smartphone interfaces. Thus, in this study, a randomized crossover experiment involving 50 older smartphone users, aged 60 years and above, was guided by the principles of summative usability testing to assess whether an age-friendly launcher performs better than a standard Android launcher performs and to investigate the relationship between the user interface complexity and usability performance of launchers. The results of usability tests in which each participant solved 10 tasks on both launchers indicate that the two tested launchers had comparable effectiveness (i.e. completeness with which participants achieved the test tasks’ goals), whereas the age-friendly launcher marginally outperformed its standard Android counterpart in terms of efficiency (i.e. the amount of time used by participants to solve the test tasks). The results also demonstrate that lower user interface complexity is associated with higher effectiveness and efficiency, suggesting that age-friendly smartphone launchers might lead to higher adoption rates of smartphones among older adults if interface designers could reduce their cognitive complexity by limiting the number of steps and alternative paths for task completion.
The baseline speed of 10-m gait predicts ambulatory discharge for hospitalized frail elderly after DOPPO rehabilitation
Authors: Uehara Akifumi , Obata Hiroaki , Watanabe Hiroshi , Izumi Yuki , Suzuki Yorio , Izumi Tohru
Published: August 2018

The discharge of elderly patients from hospital on the basis of their independent gait program (DOPPO) is a new rehabilitation strategy for physically frail hospitalized elderly that aims to recover independent gait and to achieve ambulatory discharge. We retrospectively investigated baseline determinants of physical measures associated closely with the 6-min walking distance (6MWD) after DOPPO. Participants were 137 consecutive elderly inpatients, irrespective of the causative disease (mean age: 82±7 years; 76 women), who had a Short Physical Performance Battery (SPPB) score of less than 12 and low independent walking capacity. The rehabilitation comprised muscle stretching, muscle strengthening, balance training, and endurance exercise, including walking. The exercises were gradually increased until the goal of ambulatory discharge was attained. The SPPB, isometric knee-extension muscle strength (IKEMS), functional reach test (FRT), one-leg stance time (OLST), and the 10-m gait speed (TMGS) were measured, before and after the DOPPO intervention, and their association with the 6MWD was evaluated. All participants achieved ambulatory discharge, requiring on average 35±19 hospital days and 32±18 h of rehabilitation. The SPPB, IKEMS, FRT, OLST, and TMGS improved. The SPPB scores increased from 7.1 at baseline to 9.2 at discharge. Eighty-eight patients completed the 6MWD. The SPPB, IKEMS, FRT, OLST, and TMGS were strongly associated with the 6MWD. Only the baseline TMGS and SPPB predicted the 6MWD, with a cut-off TMGS value of 0.84 m/s providing the best prediction of achieving a distance of more than 300 m on the 6MWD. Thus, the baseline TMGS is the best prediction of the ambulatory outcome after the present DOPPO rehabilitation.
Therapeutic electrical stimulation and immune status in healthy men
Authors: Novak Primož , Kopitar Andreja N. , Vidmar Gaj , Ihan Alojz , Štefančič Martin
Published: August 2018

In physical and rehabilitation medicine, there are few reports on the effects of therapeutic low-frequency electrical stimulation on the immune response of the organism, even though electrical stimulation is used widely in clinical practice and sports medicine. The aim of our study was to examine the possible immunological consequences of moderate transcutaneous neuromuscular electrical stimulation (NMES) for quadriceps muscle strengthening in healthy individuals. The study included twelve healthy male adult volunteers (mean age 42 years) without contraindications for electrical stimulation. At the beginning and immediately after a 20-min session of NMES of quadriceps muscles, peripheral blood was collected to analyse the biochemical blood components (creatinine, creatine kinase, estimated glomerular filtration rate, cortisol), differential white blood cell count and immunological parameters. The intensity of NMES was set at maximum tolerance, eliciting on average about one-sixth of the maximum voluntary isometric contraction of the same leg. No statistically significant differences in the average group level were found in any of the measured biochemical blood components, white blood cell count or immunological parameters after the NMES session. On an individual level, the changes in creatine kinase, estimated glomerular filtration rate, basophils and some immunological parameters correlated with changes in the cortisol level. We can conclude that moderate transcutaneous low-frequency electrical stimulation for quadriceps muscle strengthening used in our study did not induce essential changes in immune status in healthy men.
Staff’s Experiences of Preparing and Caring for Children With Cancer and Their Families During the Child’s Radiotherapy
Authors: Ångström-Brännström Charlotte , Lindh Viveca , Nyholm Tufve , Lindh Jack , Engvall Gunn
Published: August 2018

Background

Approximately one-third of children diagnosed with cancer are treated with radiotherapy (RT). Staff experiences of preparing and distracting the children and their families during a child’s RT are sparsely described.

Objective

The aim of this study was to describe staff experiences of preparing and caring for children with cancer and their families during the child’s RT.

Intervention/Methods

Semistructured interviews with staff were performed at 3 Swedish RT centers. The interviews were analyzed using inductive qualitative content analysis.

Results

The analysis revealed 5 categories summarizing the staff members’ experiences. These include the following: experiences of various emotions; care for the child and the child’s family; commitments before, during, and after RT; organizational issues; and experiences of the intervention and suggestions for improvement.

Conclusions

The preparatory intervention facilitated the ability of staff members to conduct their work, although the intervention should be specifically tailored to each child. Meeting children and their families and providing care to both during RT were challenging. The staff strived to provide optimal care for each child and family. Interdisciplinary teamwork and organizational acceptance for the importance of preparation and distraction were essential.

Implications for Practice

A future challenge will be to provide opportunities for all staff involved in the treatment of children with cancer to develop their skills continuously in order to provide high-quality preparation and distraction to all children undergoing RT, regardless of the geographical location of the RT center.
Extracellular Matrix and Adhesion Molecule Gene Expression in the Normal and Injured Murine Intervertebral Disc
Authors: Zhang Yejia , Tian Zuozhen , Ashley Jason W. , Wang Luqiang , Tower Robert J. , Wei Yulong , Qin Ling , Yang Shuying , Enomoto-Iwamoto Motomi
Published: August 2018

Objective

The aim of the study was to determine the transcription profile of the mouse nucleus pulposus and annulus fibrosus with an unbiased method. Furthermore, pathophysiological relevance of selected genes was demonstrated in the mouse tail intervertebral disc injury model.

Design

Paired normal mouse nucleus pulposus and annulus fibrosus tissue from C57BL/6j mice was examined by a polymerase chain reaction array. Key gene expression in the normal and injured intervertebral discs was confirmed by real-time polymerase chain reaction.

Results

Among the 84 genes studied, 63 were expressed higher in annulus fibrosus than in nucleus pulposus; only four genes were expressed higher in nucleus pulposus than in annulus fibrosus (n= 4,P≤ 0.05). Real-time polymerase chain reaction confirmed that cadherin (cdh) 2 gene expression was higher in nucleus pulposus than in annulus fibrosus, and type I collagen (col1) gene expression was higher in the annulus fibrosus than in nucleus pulposus (n= 8,P< 0.01). One week after tail intervertebral disc injury, cdh2 gene expression decreased, while col1 expression increased (n= 8,P< 0.01).

Conclusions

This is the first study to examine the relative expression of 84 genes in normal mouse nucleus pulposus and annulus fibrosus. Key genes in the normal and injured mouse intervertebral discs were confirmed with real-time polymerase chain reaction. This information should be useful for studying the mouse model of intervertebral disc degeneration and guide future cell therapy approaches.
Heme oxygenase-1 inducer and carbon monoxide–releasing molecule enhance the effects of gabapentinoids by modulating glial activation during neuropathic pain in mice
Authors: Godai Kohei , Kanmura Yuichi
Published: August 2018

Introduction:

Neuropathic pain is one of the most difficult-to-treat symptoms. Although gabapentinoids are classified as first-line drugs, they have only modest efficacy.

Objectives:

The aim of this study was to investigate whether treatment with the heme oxygenase-1 (HO-1) inducer cobalt protoporphyrin IX (CoPP) or the carbon monoxide–releasing molecule tricarbonyldichlororuthenium (II) dimer (CORM-2) can enhance the antinociceptive effects produced by gabapentinoids in mice with neuropathic pain.

Methods:

Neuropathic pain was induced by spared nerve injury (SNI) of the sciatic nerve. The mechanical threshold was tested using von Frey filaments. The expression of spinal HO-1, HO-2, the Ca2+ channel α2δ1 subunit, microglial markers, and M1 or M2 microglial markers was examined using reverse transcription polymerase chain reaction.

Results:

Treatment with CoPP or CORM-2 alleviated mechanical allodynia induced by SNI. CoPP or CORM-2 enhanced the antiallodynic effects of gabapentinoids (pregabalin or gabapentin) during SNI-induced mechanical allodynia. HO-1 inhibitor tin protoporphyrin IX (SnPP) prevented the antiallodynic effects of gabapentinoids (pregabalin or gabapentin) during SNI-induced mechanical allodynia. CoPP or CORM-2 increased HO-1 and Ca2+ channel α2δ1 subunit gene expression and the decreased gene expression of microglial markers, M1 microglial marker, or tumor necrosis factor in the ipsilateral spinal dorsal horn of mice with SNI. SnPP prevented HO-1 induction and glial inhibition, which were produced by gabapentinoids during SNI-induced mechanical allodynia.

Conclusions:

This study suggests that HO-1 plays crucial roles in the antiallodynic effects of gabapentinoids. Gabapentinoids attenuate the glial activation induced by SNI and some of these effects are mediated by HO-1.
Sacral Soft Tissue Deformations When Using a Prophylactic Multilayer Dressing and Positioning System
Authors: Peko Cohen Lea , Levy Ayelet , Shabshin Nogah , Neeman Ziv , Gefen Amit
Published: August 2018

PURPOSE:

The sacrum is the most common location of pressure injuries (PIs) in bedridden patients. The purpose of this study was to measure the effect of specific pressure preventive devices on sacral skeletal muscle, subcutaneous fat, and skin tissue deformations.

SUBJECTS AND SETTING:

The sample comprised 3 healthy adults residing in a community setting in Tel Aviv, Israel.

DESIGN:

Descriptive, comparative design.

METHODS:

Tissue thickness changes of 3 healthy adults were measured using magnetic resonance imaging (MRI) in weight-bearing sacral skin, subcutaneous fat, and muscle. Changes in tissue thickness were compared under the following conditions: (1) lying supine on a rigid surface (unpadded MRI table), (2) lying on a standard foam mattress, (3) lying on a mattress after application of a prophylactic multilayer dressing, and (4) lying on a standard foam mattress with a prophylactic multilayer dressing and a positioning system. One-way analysis of variance and post hoc Tukey-Kramer multiple pairwise comparisons were used to compare outcomes.

RESULTS:

The mattress, the prophylactic multilayer dressing, and the turning and positioning device when applied together resulted in significantly lower deformation levels of each of the soft tissue layers (ie, skin, subcutaneous fat, and muscle separately) as well as of the total soft tissue bulk, with respect to the rigid MRI table (P < .05).

CONCLUSION:

Study findings suggest that a combination of preventive interventions may reduce the risk of developing a sacral PI.
Exchange of amino acids in the H1-haemagglutinin to H3 residues is required for efficient influenza A virus replication and pathology in Tmprss2 knock-out mice
Authors: Lambertz Ruth L. O. , Pippel Jan , Gerhauser Ingo , Kollmus Heike , Anhlan Darisuren , Hrincius Eike R. , Krausze Joern , Kühn Nora , Schughart Klaus
Published: August 2018

The haemagglutinin (HA) of H1N1 and H3N2 influenza A virus (IAV) subtypes has to be activated by host proteases. Previous studies showed that H1N1 virus cannot replicate efficiently in Tmprss2−/−
knock-out mice whereas H3N2 viruses are able to replicate to the same levels in Tmprss2−/−
as in wild type (WT) mice. Here, we investigated the sequence requirements for the HA molecule that allow IAV to replicate efficiently in the absence of TMPRSS2. We showed that replacement of the H3 for the H1-loop sequence (amino acids 320 to 329, at the C-terminus of HA1) was not sufficient for equal levels of virus replication or severe pathology in Tmprss2−/−
knock-out mice compared to WT mice. However, exchange of a distant amino acid from H1 to H3 sequence (E31D) in addition to the HA-loop substitution resulted in virus replication in Tmprss2−/−
knock-out mice that was comparable to WT mice. The higher virus replication and lung damage was associated with increased epithelial damage and higher mortality. Our results provide further evidence and insights into host proteases as a promising target for therapeutic intervention of IAV infections.
Taxonogenomics reveal multiple novel genomospecies associated with clinical isolates of Stenotrophomonas maltophilia
Authors: Patil Prashant P. , Kumar Sanjeet , Midha Samriti , Gautam Vikas , Patil Prabhu B.
Published: August 2018

Stenotrophomonas maltophilia has evolved as one of the leading multidrug-resistant pathogens responsible for a variety of nosocomial infections especially in highly debilitated patients. As information on the genomic and intraspecies diversity of this clinically important pathogen is limited, we sequenced the whole genome of 27 clinical isolates from hospitalized patients. Phylogenomic analysis along with the genomes of type strains suggested that the clinical isolates are distributed over the Stenotrophomonas maltophilia complex (Smc) within the genus Stenotrophomonas. Further genome-based taxonomy coupled with the genomes of type strains of the genus Stenotrophomonas allowed us to identify five cryptic genomospecies, which are associated with the clinical isolates of S. maltophilia and are potentially novel species. These isolates share a very small core genome that implies a high level of genetic diversity within the isolates. Recombination analysis of core genomes revealed that the impact of recombination is more than mutation in the diversification of clinical S. maltophilia isolates. Distribution analysis of well-characterized antibiotic-resistance and efflux pump genes of S. maltophilia across multiple novel genomospecies provided insights into its antibiotic-resistant ability. This study supports the existence of multiple cryptic species within the Smc besides S. maltophilia, which are associated with human infections, and highlights the importance of genome-based approaches to delineate bacterial species. This data will aid in improving clinical diagnosis and for understanding species-specific clinical manifestations of infection due to Stenotrophomonas species.
Discrete or indiscrete? Redefining the colour polymorphism of the land snailCepaea nemoralis
Authors: Davison Angus , Jackson Hannah J. , Murphy Ellis W. , Reader Tom
Published: August 2018

Biologists have long tried to describe and name the different phenotypes that make up the exuberant colour polymorphism of the land snailCepaea nemoralis. Traditionally, the view is that the ground colour is one of a few major colour classes, either yellow, pink or brown, but in practise it is frequently difficult to distinguish the colours, and consistently define different shades of the same colour. To understand whether colour variation is continuous, and to investigate how the variation may be perceived by an avian predator, we applied psychophysical models of colour vision to shell reflectance measures. The main finding is that both achromatic and chromatic variation are indiscrete, being continuously distributed over many perceptual units, with the major axis of chromatic variation representing differences in saturation, or purity of colour. Nonetheless, clustering analysis based on the density of the distribution revealed three groups, roughly corresponding to human-perceived yellow, pink and brown shells. There is also large-scale geographic variation between these morphs across Europe, and some covariance between shell colour and banding patterns. Although further studies are necessary to understand the evolutionary origins and impact of natural selective upon this variation, the observation of continuous variation in colour is intriguing, given that the underlying supergene that determines colour should prevent phenotypes from “dissolving” into continuous trait distributions.
Decision-making through integration of sensory evidence at prolonged timescales
Authors: Waskom Michael L. , Kiani Roozbeh
Published: August 2018

When multiple pieces of information bear on a decision, the best approach is to combine the evidence provided by each one. Evidence integration models formalize the computations underlying this process [1–3], explain human perceptual discrimination behavior [4–11], and correspond to neuronal responses elicited by discrimination tasks [12–17]. These findings indicate that evidence integration is key to understanding the neural basis of decision-making [18–21]. Evidence integration has most often been studied with simple tasks that limit the timescale of deliberation to hundreds of milliseconds, but many natural decisions unfold over much longer durations. Because neural network models imply acute limitations on the timescale of evidence integration [22–26], it is unknown whether current computational insights can generalize beyond rapid judgments. Here, we introduce a new psychophysical task and report model-based analyses of human behavior that demonstrate evidence integration at long timescales. Our task requires probabilistic inference using brief samples of visual evidence that are separated in time by long and unpredictable gaps. We show through several quantitative assays how decision-making can approximate a normative integration process that extends over tens of seconds without accruing significant memory leak or noise. These results support the generalization of evidence integration models to a broader class of behaviors while posing new challenges for models of how these computations are implemented in biological networks.
Parallelized analysis of spatial gene expression patterns by database integration
Authors: Miyamoto Daisuke , Ikeno Hidetoshi , Okamura-Oho Yuko , Sato Akira , Furuichi Teiichi , Okumura Yoshihiro , Yamaguchi Yoko , Kanzaki Ryohei
Published: August 2018

We developed a computational framework for automated integration of a large number of two-dimensional (2D) images with three-dimensional (3D) image datasets located in the standard 3D coordinate. We applied the framework to 2,810 para-sagittal sectioned mouse brain 2D images of in situ hybridization (ISH), archived in the BrainTx database (http://www.cdtdb.neuroinf.jp). We registered the ISH images into the mouse standard coordinate space for MR images, Waxholm space (WHS, https://www.nitrc.org/projects/incfwhsmouse) by linearly transforming them into each of a series of para-sagittal MR image slices, and identifying the best-fit slice by calculating the similarity metric value (δ). Transformed 2D images were compared with 3D gene expression image datasets, which were made using a microtomy-based microarray assay system, Transcriptome Tomography, and archived in the ViBrism DB (http://vibrism.neuroinf.jp): the 3D images are located in the WHS.

We first transformed ISH images of 10 regionally expressed genes and compared them to signals of corresponding 3D expression images in ViBrism DB for evaluating the integration schema: two types of data, produced with different modalities and originally located in different dimensions, were successfully compared after enhancing ISH signals against background noise. Then, for the massive transformation of BrainTx database images, we parallelized our framework, using the IPython cluster package, and implemented it on the PC cluster provided for the Brain Atlasing Hackathon activity hosted by Neuroinformatics Japan Center in Japan. We could identify the best-fit positions for all of the ISH images. All programs were made available through the GitHub repository, at the web site of neuroinformatics/bah2016_registration (https://github.com/neuroinformatics/bah2016_registration).
Neuropsychiatric Phenotypes and a Distinct Constellation of ASD Features in 3q29 Deletion Syndrome: Results from the 3q29 Registry
Authors: Pollak Rebecca M , Murphy Melissa M , Epstein Michael P , Zwick Michael E , Klaiman Cheryl , Saulnier Celine A ,   the Emory 3q29 Project, Mulle Jennifer G
Published: August 2018

Background

The 1.6 Mb 3q29 deletion is associated with neurodevelopmental and psychiatric phenotypes, including increased risk for autism spectrum disorder (ASD) and a 20-40-fold increased risk for schizophrenia. However, the phenotypic spectrum of the deletion, particularly with respect to ASD, remains poorly described.

Methods

We ascertained individuals with 3q29 deletion syndrome (3q29Del, “cases”, n=93, 58.1% male) and typically developing controls (n=64, 51.6% male) through the 3q29 registry (https://3q29deletion.patientcrossroads.org). Self-report of neuropsychiatric illness was evaluated for 93 cases. Subsets of participants were evaluated with the Social Responsiveness Scale (SRS, n=48 cases, 56 controls), Social Communication Questionnaire (SCQ, n=33 cases, 46 controls), Autism Spectrum Screening Questionnaire (ASSQ, n=24 cases, 35 controls), and Achenbach Behavior Checklists (n=48 cases, 57 controls).

Results

3q29Del cases report a higher prevalence of autism diagnoses versus the general population (29.0% vs. 1.47%, p<2.2E-16). Notably, 3q29 deletion confers a greater influence on risk for ASD in females (OR=41.8, p=4.78E-05) than in males (OR=24.6, p=6.06E-09); this is aligned with the reduced male:female bias from 4:1 in the general population to 2:1 in our study sample. Although 71% of cases do not report a diagnosis of ASD, there is evidence of significant social disability (3q29Del SRST-score=71.8, control SRST-score=45.9, p=2.16E-13). Cases also report increased frequency of generalized anxiety disorder compared to controls (28.0% vs. 6.2%, p=0.001), which is mirrored by elevated mean scores on the Achenbach DSM-oriented sub-scales (p<0.001). Finally, cases show a distinct constellation of ASD features on the SRS as compared to idiopathic ASD, with substantially elevated Restricted Interests and Repetitive Behaviors, but only mild impairment in Social Motivation.

Conclusions

Our sample of 3q29Del is significantly enriched for ASD diagnosis, especially among females, and features of autism may be present even when an ASD diagnosis is not reported. Further, the constellation of ASD features in this population is distinct from idiopathic ASD, with substantially less impaired social motivation. Our study implies that ASD evaluation should be the standard of care for individuals with 3q29Del. From a research perspective, the distinct ASD subtype present in 3q29Del is an ideal entry point for expanding understanding of ASD.
Multi-modal regulation ofC. eleganshermaphrodite spermatogenesis by the GLD-1-FOG-2 complex
Authors: Hu Shuang , Ryan Lauren E. , Kaymak Ebru , Freeberg Lindsay , Lo Te-Wen , Kuersten Scott , Ryder Sean P. , Haag Eric S.
Published: August 2018

Proper germ cell sex determination inCaenorhabditisnematodes requires a network of RNA-binding proteins (RBPs) and their target mRNAs. In some species, changes in this network enabled limited XX spermatogenesis, and thus self-fertility. InC. elegans, one of these selfing species, the global sex-determining genetra-2is regulated in germ cells by a conserved RBP, GLD-1, via the 3’ untranslated region (3’UTR) of its transcript. AC. elegans-specific GLD-1 cofactor, FOG-2, is also required for hermaphrodite sperm fate, but how it modifies GLD-1 function is unknown. Germline feminization ingld-1andfog-2null mutants has been interpreted as due to cell-autonomous elevation of TRA-2 translation. Consistent with the proposed role of FOG-2 in translational control, the abundance of nearly all GLD-1 target mRNAs (includingtra-2)is unchanged infog-2mutants. Epitope tagging reveals abundant TRA-2 expression in somatic tissues, but an undetectably low level in wild-type germ cells. Loss ofgld-1function elevates germline TRA-2 expression to detectable levels, but loss offog-2function does not. A simple quantitative model oftra-2activity constrained by these results can successfully sort genotypes into normal or feminized groups. Surprisingly,fog-2andgld-1activity enable the sperm fate even when GLD-1 cannot bind to thetra-23’ UTR. This suggests the GLD-1-FOG-2 complex regulates uncharacterized sites withintra-2, or other mRNA targets. Finally, we quantify the RNA-binding capacities of dominant missense alleles of GLD-1 that act genetically as “hyperrepressors” oftra-2activity. These variants bind RNA more weaklyin vitrothan does wild-type GLD-1. These results indicate thatgld-1andfog-2regulate germline sex via multiple interactions, and that our understanding of the control and evolution of germ cell sex determination in theC. eleganshermaphrodite is far from complete.
Foxp1 controls neural stem cell competence and bias towards deep layer cortical fates
Authors: Pearson Caroline Alayne , Moore Destaye M. , Tucker Haley O. , Dekker Joseph D. , Hu Hui , Miquelajáuregui Amaya , Novitch Bennett G.
Published: August 2018

The laminar architecture of the mammalian neocortex depends on the orderly generation of distinct neuronal subtypes by apical radial glia (aRG) during embryogenesis. We identify critical roles for Foxp1 in maintaining RG identity and gating the temporal competency for early neurogenesis. High levels of Foxp1 are associated with early aRG and are required to promote proliferation and influence cell division symmetry, favoring aRG expansion and production of early born neurons. The potent pro-progenitor functions of Foxp1 are revealed through its ability to preserve a population of cells with aRG identity throughout development and extend the early neurogenic period into postnatal life. Foxp1 further promotes the formation of cells resembling basal RG (bRG), a progenitor group implicated in the increased size and complexity of the human cortex. Consistent with this role, we show that FOXP1 is associated with the initial formation and expansion of bRG during human corticogenesis.

HIGHLIGHTS

Foxp1 is transiently expressed by aRG during the early phase of corticogenesis

Foxp1 promotes self-renewing vertical cell divisions and aRG maintenance

Foxp1 gates the time window of deep layer neurogenesis

Ectopic Foxp1 expression can elicit bRG formation
Allele-specific RNA imaging shows that allelic imbalances can arise in tissues through transcriptional bursting
Authors: Symmons Orsolya , Chang Marcello , Mellis Ian A. , Kalish Jennifer M. , Bartolomei Marisa S. , Raj Arjun
Published: August 2018

Extensive cell-to-cell variation exists even among putatively identical cells, and there is great interest in understanding how the properties of transcription relate to this heterogeneity. Differential expression from the two gene copies in diploid cells could potentially contribute, yet our ability to measure from which gene copy individual RNAs originated remains limited, particularly in the context of tissues. Here, we demonstrate quantitative, single molecule allele-specific RNA FISH adapted for use on tissue sections, allowing us to determine the chromosome of origin of individual RNA molecules in formaldehyde-fixed tissues. We used this method to visualize the allele-specific expression ofXistand multiple autosomal genes in mouse kidney. By combining these data with mathematical modeling, we evaluated models for allele-specific heterogeneity, in particular demonstrating that apparent expression from only one of the alleles in single cells can arise as a consequence of low-level mRNA abundance and transcriptional bursting.
Inferring metabolite interactomes via molecular structure informed Bayesian graphical model selection with an application to coronary artery disease
Authors: Trainor Patrick J. , Mitchell Joshua M. , Carlisle Samantha M. , Moseley Hunter N.B. , DeFilippis Andrew P. , Rai Shesh N.
Published: August 2018

Introduction

While the generation of reference genomes facilitates the elucidation of gene-phenome associations, reference models of the metabolome that are specific to organism, sample type (e.g. plasma, serum, urine, cell-culture), and state (including disease), remain uncommon. In studying heart disease in humans, a reference model describing the relationships between metabolites in plasma has not been determined but would have great utility as a reference for comparing acute disease states such as myocardial infarction.

Materials and Methods

We present a methodology for deriving probabilistic models that describe the partial correlation structure of metabolite distributions (“interactomes”) from metabolomics data. As determining partial correlation structures requires estimating p*(p-1)/2 parameters for p metabolites, the dimension of the search space for parameter values is immense. Consequently, we have developed a Bayesian methodology for the penalized estimation of model parameters in which the magnitude of penalization is drawn from probability distributions with hyperparameters linked to molecular structure similarity. In our work, structural similarity was determined as the Tanimoto coefficient of algorithmically-generated “atom colors” that capture the local structure around each atom within each structure. A Gibbs sampler (a Markov chain Monte Carlo technique) was implemented for simulating the posterior distribution of model parameters. We have made software for implementing this methodology publicly available via the R package BayesianGLasso.

Results / Conclusions

First, we demonstrate robust performance of our methodology (sensitivity, specificity, and measures of accuracy) for recovering the true underlying partial correlation structure over simulated datasets (with simulated metabolite abundances and simulated known structural similarity). We then present an interactome model for stable heart disease inferred from non-targeted mass spectrometry data via this methodology. Inspection of the local graph topology about cholate reveals probabilistic interactions with other primary bile acids, secondary bile acids, and many steroid hormones sharing the same precursors.
Extracting allelic read counts from 250,000 human sequencing runs in Sequence Read Archive
Authors: Tsui Brian , Dow Michelle , Skola Dylan , Carter Hannah
Published: August 2018

The Sequence Read Archive (SRA) contains over one million publicly available sequencing runs from various studies using a variety of sequencing library strategies. These data inherently contain information about underlying genomic sequence variants which we exploit to extract allelic read counts on an unprecedented scale. We reprocessed over 250,000 human sequencing runs (>1000 TB data worth of raw sequence data) into a single unified dataset of allelic read counts for nearly 300,000 variants of biomedical relevance curated by NCBI dbSNP, where germline variants were detected in a median of 912 sequencing runs, and somatic variants were detected in a median of 4,876 sequencing runs, suggesting that this dataset facilitates identification of sequencing runs that harbor variants of interest. Allelic read counts obtained using a targeted alignment were very similar to read counts obtained from whole genome alignment. Analyzing allelic read count data for matched DNA and RNA samples from tumors, we find that RNA-seq can also recover variants identified by WXS, suggesting that reprocessed allelic read counts can support variant detection across different library strategies in SRA. This study provides a rich database of known human variants across SRA samples that can support future meta-analyses of human sequence variation.
Infection of theBiomphalaria glabrata vector snailbySchistosoma mansoniparasites drives snail microbiota dysbiosis
Authors: Portet Anaïs , Toulza Eve , Lokmer Ana , Huot Camille , Duval David , Galinier Richard , Gourbal Benjamin
Published: August 2018

Host-associated microbiota cari affect the fitness of its host i η a number of ways, including the modification of host-parasite interactions and thus the outcome of disease.Biomphalaria glabratais the vector snail of the trematodeSchistosoma mansoni,the agent of human schistosomiasis, causing hundreds of thousands of deaths every year. Here, we present the first study of the snail bacterial microbiota in response toSchistosomainfection. To examine the interplay betweenB. glabrata, S. mansoniand snail microbiota, snails were infected and the microbiota composition was analysed by massive 16S rDNA amplicon sequencing approach. We characterized theBiomphalariabacterial microbiota at the individual level in both naive and infected snails. Sympatric and allopatric strains of parasites were used for infections and re­infections to analyse the modification or dysbiosis of snail microbiota in different host-parasite co-evolutionary contexts. Concomitantly, using RNAseq data, we investigated the link between bacterial microbiota dysbiosis and snail anti-microbial peptide immune response. This work paves the way for a better understanding of snail/schistosome interaction, and would have critical consequences in terms of snail control strategies for fighting schistosomiasis disease in the field.
“ER-Ca2+ sensor STIM regulates neuropeptides required for development under nutrient restriction in Drosophila”
Authors: Megha  , Wegener Christian , Hasan Gaiti
Published: August 2018

Neuroendocrine cells communicate via neuropeptides to regulate behaviour and physiology. This study examines how STIM (Stromal Interacting Molecule), an ER-Ca2+ sensor required for Store-operated Ca2+ entry, regulates neuropeptides required for Drosophila development under nutrient restriction (NR). We find two STIM-regulated peptides, Corazonin and short Neuropeptide F, to be required for NR larvae to complete development. Further, a set of secretory DLP (Dorso lateral peptidergic) neurons which co-express both peptides was identified. Partial loss of dSTIM caused peptide accumulation in the DLPs, and reduced systemic Corazonin signalling. Upon NR, larval development correlated with increased peptide levels in the DLPs, which failed to occur when dSTIM was reduced. Comparison of systemic and cellular phenotypes associated with reduced dSTIM, with other cellular perturbations, along with genetic rescue experiments, suggested that dSTIM primarily compromises neuroendocrine function by interfering with neuropeptide release. Under chronic stimulation, dSTIM also appears to regulate neuropeptide synthesis.
Genome Wide Meta-Analysis identifies new loci associated with cardiac phenotypes and uncovers a common genetic signature shared by heart function and Alzheimer’s disease
Authors: Sáez MªEugenia , González-Pérez Antonio , Hernández-Olasagarre Begoña , Beà Aida , Moreno-Grau Sonia , Rojas Itziar de , Monté Gemma , Orellana Adela , Valero Sergi , Comella Joan X. , Sanchis Daniel , Ruiz Agustín ,   For the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2018

Aims

Echocardiography has become an indispensable tool for the study of heart performance, improving the monitoring of individuals with cardiac diseases. Diverse genetic factors associated with echocardiographic measures of heart structure and functions have been previously reported. The impact of several apoptotic genes in heart development identified in experimental models prompted us to assess their potential association with indicators of human cardiac function. This study started with the aim to investigate the possible association of variants of apoptotic genes with echocardiographic traits and to identify new genetic markers associated with cardiac function.

Methods and results

Genome wide data from different studies were obtained from public repositories. After quality control and imputation, association analyses confirm the role of caspases and other apoptosis related genes with cardiac phenotypes. Moreover, enrichment analysis showed an over-representation of genes, including some apoptotic regulators, associated with Alzheimer’s disease (AD). We further explored this unexpected observation which was confirmed by genetic correlation analyses.

Conclusions

Our findings show the association of apoptotic gene variants with echocardiographic indicators of heart function and reveal a novel potential genetic link between echocardiographic measures in healthy populations and cognitive decline later on in life. These findings may have important implications for preventative strategies combating Alzheimer’s disease.
TP promotes malignant progression in hepatocellular carcinoma through pentose Warburg effect
Authors: Zhang Qiang , Qin Yuan , Zhao Jianmin , Tang Yuanhao , Hu Xuejiao , Zhong Weilong , Li Mimi , Zong Shumin , Li Meng , Tao Honglian , Zhang Zhen , Chen Shuang , Liu Huijuan , Yang Lan , Zhou Honggang , Liu Yanrong , Sun Tao , Yang Cheng
Published: August 2018

Tumor progression is dependent on metabolic reprogramming. Metastasis and vasculogenic mimicry (VM) are typical tumor progression. The relationship of metastasis, VM and metabolic reprogramming is not clear. In this study, we identified the novel role of Twist1, a VM regulator, in the transcriptional regulation of the expression of thymidine phosphorylase (TP). We demonstrated that TP promoted extracellular thymidine metabolization into ATP and amino acids through pentose Warburg effect by coupling the pentose phosphate pathway and glycolysis. Moreover, Twist1 relied on TP-induced metabolic reprogramming to promote hepatocellular carcinoma (HCC) metastasis and VM formation mediated by VE-Cad, VEGFR1, and VEGFR2 in vitro and in vivo. TP inhibitor tipiracil reduced promotion effect of TP enzyme activity on HCC VM formation and metastasis. Our findings demonstrate that TP, transcriptionally activated by Twist1, promotes HCC VM formation and metastasis through pentose Warburg effect, contributing to tumor progression.
Calcium negatively regulates secretion from dense granules inToxoplasma gondii
Authors: Katris Nicholas J , McFadden Geoffrey I , Dooren Giel G. van , Waller Ross F
Published: August 2018

Apicomplexan parasites includingToxoplasma gondiiandPlasmodiumspp. manufacture a complex arsenal of secreted proteins used to interact with and manipulate their host environment. These proteins are organised into three principle exocytotic compartment types according to their functions: micronemes for extracellular attachment and motility, rhoptries for host cell penetration, and dense granules for subsequent manipulation of the host intracellular environment. The order and timing of these events during the parasite’s invasion cycle dictates when exocytosis from each compartment occurs. Tight control of compartment secretion is, therefore, an integral part of apicomplexan biology. Control of microneme exocytosis is best understood, where cytosolic intermediate molecular messengers cGMP and Ca2+act as positive signals. The mechanisms for controlling secretion from rhoptries and dense granules, however, are virtually unknown. Here, we present evidence that dense granule exocytosis is negatively regulated by cytosolic Ca2+, and we show that this Ca2+-mediated response is contingent on the function of calcium-dependent protein kinasesTgCDPK1 andTgCDPK3. Reciprocal control of micronemes and dense granules provides an elegant solution to the mutually exclusive functions of these exocytotic compartments in parasite invasion cycles and further demonstrates the central role that Ca2+signalling plays in the invasion biology of apicomplexan parasites.
Structure of the Macrobrachium rosenbergii Nodavirus: A new genus within the Nodaviridae?
Authors: Ho Kok Lian , Gabrielsen Mads , Beh Poay Ling , Kueh Chare Li , Thong Qiu Xian , Streetley James , Tan Wen Siang , Bhella David
Published: August 2018

Macrobrachium rosenbergii nodavirus (MrNV) is a pathogen of freshwater prawns that poses a threat to food-security and causes significant economic losses in the aquaculture industries of many developing nations. A detailed understanding of the MrNV virion structure will inform the development of strategies to control outbreaks. The MrNV capsid has also been engineered to display heterologous antigens, thus knowledge of its atomic resolution structure will benefit efforts to develop tools based on this platform. Here we present an atomic-resolution model of the MrNV capsid protein, calculated by cryogenic electron microscopy (cryoEM) of MrNV virus-like particles (VLPs) produced in insect cells, and three-dimensional image reconstruction at 3.3 Å resolution. CryoEM of MrNV virions purified from infected freshwater prawn post-larvae yielded a 6.6 Å resolution structure confirming the biological relevance of the VLP structure.

Our data revealed that unlike other known nodaviruses structures, which have been shown to assemble capsids having trimeric spikes, MrNV assembles a T=3 capsid with dimeric spikes. We also found a number of surprising similarities between the MrNV capsid structure and that of the Tombusviridae. 1. An extensive network of N-terminal arms lines the capsid interior forming long-range interactions to lace together asymmetric units. 2. The capsid shell is stabilised by three pairs of Ca2+ ions in each asymmetric unit. 3. The protruding spike domain exhibits a very similar fold to that seen in the spikes of the tombusviruses. These structural similarities raise questions concerning the correct taxonomic classification of MrNV.