bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of dietary salt intake in adults: A protocol for Scoping Review
Authors: Nagi Raunaq Singh , Prasad Pankaj , Kumar Sanjeev
Published: August 2021

Objective

The objective of this scoping review is to methodically review the current literature and identify the factors/determinants of dietary salt consumption in adults.

Introduction

High dietary salt intake has been identified as a risk factor for non-communicable diseases and conditions. Despite continuous and rigorous efforts, dietary salt intake still remain above the recommended adult daily dose of 5g, both locally and globally. This indicates existence of unidentified or unaddressed behavioural factors that diminish efficiency of salt reduction efforts targeted towards public.

Inclusion Criteria

This review will include global literature dealing with factors associated with dietary salt intake in adults. Qualitative, quantitative and ecological studies on behavioural, psychosocial and environmental factors associated with awareness regarding dietary salt intake and barrier to its reduction will be considered. Studies published only in English language, without any limits on date of publication will be considered for this review.

Methods

A comprehensive search across databases namely, MEDLINE, ScienceDirect, JSTOR, ERIC, DOAJ and OATD will be carried out to retrieve and identify relevant literature. Two reviewers will screen the titles followed by abstracts and subsequently full-length texts according to the inclusion and exclusion criterion, removing unrelated studies and finally compiling and extracting information from chosen studies in data extraction forms. Descriptive statistics will be used to represent the data. Thematic analysis of extracted data using deductive approach will be conducted.
COVID-19 Incidence and Hospitalization During the Delta Surge Were Inversely Related to Vaccination Coverage Among the Most Populous U.S. Counties
Authors: Harris Jeffrey E.
Published: August 2021

We tested whether COVID-19 incidence and hospitalization rates during the Delta variant-related surge were inversely related to vaccination coverage among the 112 most populous counties in the United States, together comprising 44 percent of the country’s total population. We measured vaccination coverage as the percent of the county population fully vaccinated as of July 15, 2021. We measured COVID-19 incidence as the number of confirmed cases per 100,000 population during the 14-day period ending August 12, 2021 and hospitalization rates as the number of confirmed COVID-19 admissions per 100,000 population during the same 14-day period. In log-linear regression models, a 10-percentage-point increase in vaccination coverage was associated with a 28.3% decrease in COVID-19 incidence (95% confidence interval, 16.8 - 39.7%), a 44.9 percent decrease in the rate of COVID-19 hospitalization (95% CI, 28.8 - 61.0%), and a 16.6% decrease in COVID-19 hospitalizations per 100 cases (95% CI, 8.4 - 24.8%). Inclusion of demographic covariables, as well as county-specific diabetes prevalence, did not weaken the observed inverse relationship with vaccination coverage. A significant inverse relationship between vaccination coverage and COVID-19 deaths per 100,000 during August 20 – September 16 was also observed. The cumulative incidence of COVID-19 through June 30, 2021, a potential indicator of acquired immunity due to past infection, had no significant relation to subsequent case incidence or hospitalization rates in August. Higher vaccination coverage was associated not only with significantly lower COVID-19 incidence during the Delta surge, but also significantly less severe cases of the disease.
White matter microstructure shows sex differences in late childhood: Evidence from 6,797 children
Authors: Lawrence Katherine E , Abaryan Zvart , Laltoo Emily , Hernandez Leanna M , Gandal Michael , McCracken James T , Thompson Paul M
Published: August 2021

Sex differences in white matter microstructure have been robustly demonstrated in the adult brain using both conventional and advanced diffusion-weighted magnetic resonance imaging (dMRI) approaches. However, sex differences in white matter microstructure prior to adulthood remain poorly understood; previous developmental work focused on conventional microstructure metrics and yielded mixed results. Here we rigorously characterized sex differences in white matter microstructure among over 6,000 children from the Adolescent Brain Cognitive Development (ABCD) Study who were between 9 and 10 years old. Microstructure was quantified using both the conventional model - diffusion tensor imaging (DTI) - and an advanced model, restriction spectrum imaging (RSI). DTI metrics included fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD, RD). RSI metrics included normalized isotropic, directional, and total intracellular diffusion (N0, ND, NT). We found significant and replicable sex differences in DTI or RSI microstructure metrics in every white matter region examined across the brain. Sex differences in FA were regionally specific. Across white matter regions, boys exhibited greater MD, AD, and RD than girls, on average. Girls displayed increased N0, ND, and NT compared to boys, on average, suggesting greater cell and neurite density in girls. Together, these robust and replicable findings provide an important foundation for understanding sex differences in health and disease.
Accurate predictions of individual differences in task-evoked brain activity from resting-state fMRI using a sparse ensemble learner
Authors: Zheng Ying-Qiu , Farahibozorg Seyedeh-Rezvan , Gong Weikang , Rafipoor Hossein , Jbabdi Saad , Smith Stephen
Published: August 2021

Modelling and predicting individual differences in task-evoked FMRI activity can have a wide range of applications from basic to clinical neuroscience. It has been shown that models based on resting-state activity can have high predictive accuracy. Here we propose several improvements to such models. Using a sparse ensemble leaner, we show that (i) features extracted using Stochastic Probabilistic Functional Modes (sPROFUMO) outperform the previously proposed dual-regression approach, (ii) that the shape and overall intensity of individualised task activations can be modelled separately and explicitly, (iii) training the model on predicting residual differences in brain activity further boosts individualised predictions. These results hold for both surface-based analyses of the Human Connectome Project data as well as volumetric analyses of UK-biobank data. Overall, our model achieves state of the art prediction accuracy on par with the test-retest reliability of tfMRI scans, suggesting that it has potential to supplement traditional task localisers.
Parallel pathways for rapid odor processing in lateral entorhinal cortex: Rate and temporal coding by layer 2 subcircuits
Authors: Bitzenhofer Sebastian H. , Westeinde Elena A. , Zhang Han-Xiong Bear , Isaacson Jeffry S.
Published: August 2021

Olfactory information is encoded in lateral entorhinal cortex (LEC) by two classes of layer 2 (L2) principal neurons: fan and pyramidal cells. However, the functional properties of L2 neurons are unclear. Here, we show in awake mice that L2 cells respond rapidly to odors during single sniffs and that LEC is essential for discrimination of odor identity and intensity. Population analyses of L2 ensembles reveals that while rate coding distinguishes odor identity, firing rates are weakly concentration-dependent and changes in spike timing represent odor intensity. L2 principal cells differ in afferent olfactory input and connectivity with local inhibitory circuits and the relative timing of pyramidal and fan cell spikes underlies odor intensity coding. Downstream, intensity is encoded purely by spike timing in hippocampal CA1. Together, these results reveal the unique processing of odor information by parallel LEC subcircuits and highlight the importance of temporal coding in higher olfactory areas.
Harbor porpoise losing its edges: genetic time series suggests a rapid population decline in Iberian waters over the last 30 years
Authors: Ben Chehida Yacine , Stelwagen Tjibbe , Hoekendijk Jeroen P. A. , Ferreira Marisa , Eira Catarina , Pereira Andreia T. , Nicolau Lidia , Thumloup Julie , Fontaine Michael C.
Published: August 2021

Impact of climate changes on species is expected to be especially visible at the extremities of the species distribution, where they meet sub-optimal conditions. In Mauritania and Iberia, two genetically isolated populations of harbor porpoises form a distinct ecotype and are presumably locally adapted to the upwelling waters. By analyzing the evolution of mitochondrial genetic variation in the Iberian population between two temporal cohorts (1990-2002 vs. 2012-2015), we report a dramatic decrease in genetic diversity. Phylogenetic analyses including neighboring populations identified two porpoises in southern Iberia carrying a divergent haplotype close to the Mauritanian population, yet forming a distinctive lineage. This suggests that Iberian porpoises may not be as isolated as previously thought with immigration from Mauritania or an unknown population in between, but none from the northern ecotype. The rapid decline in the Iberian mitochondrial diversity may be driven by either genetic drift, or by a dramatic decline in census population size possibly resulting from environmental stochasticity, prey depletion, or acute fishery bycatches. These results illustrate the value of genetics time series to inform demographic trends and emphasize the urgent need for conservation measures to ensure the viability of this small harbor porpoise population in Iberia.
Lacking social support is associated with structural divergences in hippocampus-default network co-variation patterns
Authors: Zajner Chris , Spreng Nathan , Bzdok Danilo
Published: August 2021

Elaborate social interaction is a pivotal asset of the human species. The complexity of people’s social lives may constitute the dominating factor in the vibrancy of many individuals’ environment. The neural substrates linked to social cognition thus appear especially susceptible when people endure periods of social isolation: here, we zoom in on the systematic inter-relationships between two such neural substrates, the allocortical hippocampus (HC) and the neocortical default network (DN). Previous human social neuroscience studies have focused on the DN, while HC subfields have been studied in most detail in rodents and monkeys. To bring into contact these two separate research streams, we directly quantified how DN subregions are coherently co-expressed with specific HC subfields in the context of social isolation. A two-pronged decomposition of structural brain scans from ∼40,000 UK Biobank participants linked lack of social support to mostly lateral subregions in the DN patterns. This lateral DN association co-occurred with HC patterns that implicated especially subiculum, presubiculum, CA2, CA3, and dentate gyrus. Overall, the subregion divergences within spatially overlapping signatures of HC-DN co-variation followed a clear segregation divide into the left and right brain hemispheres. Separable regimes of structural HC-DN co-variation also showed distinct associations with the genetic predisposition for lacking social support at the population level.
Pancreatic ductal adenocarcinoma cells employ integrin α6β4 to form hemidesmosomes and regulate cell proliferation
Authors: Humphries Jonathan D. , Zha Junzhe , Burns Jessica , Askari Janet A. , Below Christopher R. , Chastney Megan R. , Jones Matthew C. , Mironov Aleksandr , Knight David , O’Reilly Derek A. , Dunne Mark J. , Garrod David R. , Jorgensen Claus , Humphries Martin J.
Published: August 2021

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis due to its aggressive progression, late detection and lack of druggable driver mutations, which often combine to result in unsuitability for surgical intervention. Together with activating mutations of the small GTPase KRas, which are found in over 90% of PDAC tumours, a contributory factor for PDAC tumour progression is formation of a rigid extracellular matrix (ECM) and associated desmoplasia. This response leads to aberrant integrin signalling, and accelerated proliferation and invasion. To identify the integrin adhesion systems that operate in PDAC, we analysed a range of pancreatic ductal epithelial cell models using 2D, 3D and organoid culture systems. Proteomic analysis of isolated integrin receptor complexes from human pancreatic ductal epithelial (HPDE) cells predominantly identified integrin α6β4 and hemidesmosome components, rather than classical focal adhesion components. Electron microscopy, together with immunofluorescence, confirmed the formation of hemidesmosomes by HPDE cells, both in 2D and 3D culture systems. Similar results were obtained for the human PDAC cell line, SUIT-2. Analysis of HPDE cell secreted proteins and cell-derived matrices (CDM) demonstrated that HPDE cells secrete a range of laminin subunits and form a hemidesmosome-specific, laminin 332-enriched ECM. Expression of mutant KRas (G12V) did not affect hemidesmosome composition or formation by HPDE cells. Cell-ECM contacts formed by mouse and human PDAC organoids were also assessed by electron microscopy. Organoids generated from both the PDAC KPC mouse model and human patient-derived PDAC tissue displayed features of acinar-ductal cell polarity, and hemidesmosomes were visible proximal to prominent basement membranes. Furthermore, electron microscopy identified hemidesmosomes in normal human pancreas. Depletion of integrin β4 using siRNA reduced cell proliferation in both SUIT-2 and HPDE cells, reduced the number of SUIT-2 cells in S-phase, and induced G1 cell cycle arrest, indicating a requirement for α6β4-mediated adhesion for cell cycle progression and growth. Taken together, these data suggest that laminin-binding adhesion mechanisms in general, and hemidesmosome-mediated adhesion in particular, may be under-appreciated in the context of PDAC.

Proteomic data are available via ProteomeXchange with the identifiers PXD027803, PXD027823 and PXD027827.
Ethology of morphogenesis reveals the design principles of cnidarian size and shape development
Authors: Stokkermans Anniek , Chakrabarti Aditi , Wang Ling , Moghe Prachiti , Subramanian Kaushikaram , Steenbergen Petrus , Mönke Gregor , Hiiragi Takashi , Prevedel Robert , Mahadevan L. , Ikmi Aissam
Published: August 2021

During development, organisms interact with their natural habitats while undergoing morphological changes, yet it remains unclear whether the interplay between developing systems and their environments impacts animal morphogenesis. Here, we use the cnidarianNematostella vectensisas a developmental model to uncover a mechanistic link between organism size, shape and behavior. Using quantitative live imaging, including extensive behavioral profiling, combined with molecular and biophysical experiments, we demonstrate that the muscular hydraulic machinery that controls body movement directly drives larva-polyp morphogenesis. Unexpectedly, size and shape development are differentially controlled by antagonistic muscles. A simple theoretical model shows how a combination of slow-priming and fast-pumping pressures generated by muscular hydraulics acts as a global mechanical regulator that coordinates tissue remodeling. Altogether, our findings illuminate how dynamic behavioral modes in the environment can be harnessed to drive morphogenetic trajectories, establishing ethology as a critical component of organismal morphogenesis – termed ethology of morphogenesis.
GFAP splice variants fine-tune glioma cell invasion and tumour dynamics by modulating migration persistence
Authors: van Asperen Jessy V. , Uceda-Castro Rebeca , Vennin Claire , Sluijs Jacqueline , van Bodegraven Emma J. , Margarido Andreia S. , Robe Pierre A.J. , van Rheenen Jacco , Hol Elly M.
Published: August 2021

Glioma is the most common form of malignant primary brain tumours in adults. Their highly invasive nature makes the disease incurable to date, emphasizing the importance of better understanding the mechanisms driving glioma invasion. Glial fibrillary acidic protein (GFAP) is an intermediate filament protein that is characteristic for astrocyte- and neural stem cell-derived gliomas. Glioma malignancy is associated with changes in GFAP alternative splicing, as the canonical isoform GFAPα is downregulated in higher-grade tumours, leading to increased dominance of the GFAPδ isoform in the network. In this study, we used intravital imaging and anex vivobrain slice invasion model. We show that the GFAPδ and GFAPα isoforms differentially regulate the tumour dynamics of glioma cells. Depletion of either isoform increases the migratory capacity of glioma cells. Remarkably, GFAPδ-depleted cells migrate randomly through the brain tissue, whereas GFAPα-depleted cells show a directionally persistent invasion into the brain parenchyma. This study shows that distinct compositions of the GFAP-network lead to specific migratory dynamics and behaviours of gliomas.
New relationships are not necessarily more variable: female degus are more consistent with strangers, male degus are less
Authors: Thatcher Amber , Insel Nathan
Published: August 2021

When an organism explores a new environment or stimulus it varies its behavior to ensure proper sampling. As contingencies are learned, variance can give-way to routines and stereotypies. This phenomenon is common across species but has not been well studied in the social domain, in which the stimulus an animal investigates, another individual, may react negatively to unexpected behaviors. Here we investigate the effects of social familiarity on interaction variability in degus, female members of which are predisposed to form relationships with new, same-sex individuals. Degus were presented with a series of 20 minute, dyadic “reunion” sessions across days, interleaving exposures to familiar and unfamiliar same-sex conspecifics. We found that session-to-session variability in males was higher between strangers compared with cagemates, suggesting males may establish relationships by testing different social roles. In contrast, following an initial exposure, female strangers showed lower session-to-session change compared with cagemates, potentially establishing new relationships by maintaining behavioral norms. Social novelty did not appear to affect variability of interaction timing within a session. Given ecological pressures on female degus to form large, stable social networks, the data are consistent with the notion that higher behavioral variability across encounters is maladaptive for establishing cooperative peer relationships.
A human stem cell resource to decipher the biochemical and cellular basis of neurodevelopmental defects in Lowe Syndrome
Authors: Akhtar Bilal M. , Bhatia Priyanka , Acharya Shubhra , Sharma Sanjeev , Sharma Yojet , Aswathy BS , Ganapathy Kavina , Vasudevan Anil , Raghu Padinjat
Published: August 2021

Human brain development is a complex process where multiple cellular and developmental events are co-ordinated to generate normal structure and function. Alteration in any of these events can impact brain development, manifesting clinically as neurodevelopmental disorders. Human genetic disorders of lipid metabolism often present with features of altered brain function. Lowe syndrome (LS), is a X-linked recessive disease with features of altered brain function. LS results from mutations in OCRL1 that encodes a phosphoinositide 5-phosphatase enzyme. However, the cellular mechanisms by which loss of OCRL1 leads to brain defects remain unknown. Human brain development involves several cellular and developmental features not conserved in other species and understanding such mechanisms remains a challenge. Rodent models of LS have been generated, but failed to recapitulate features of the human disease. Here we describe the generation of human stem cell lines from LS patients. Further, we present biochemical characterization of lipid metabolism in patient cell lines and demonstrate their use as a “disease-in-a-dish” model for understanding the mechanism by which loss of OCRL1 leads to altered cellular and physiological brain development.
Liquid-liquid phase separation of florigen activation complex induces flowering
Authors: Taoka Ken-ichiro , Tsuji Hiroyuki , Anzawa Suai , Enomoto Mayu , Koizumi Yuka , Nakamura Juri , Tanaka Mari , Fujita Akiko , Furuita Kyoko , Kodama Takashi S. , Fujimoto Masaru , Kurokawa Kazuo , Okamoto Takashi , Fujiwara Toshimichi , Nakano Akihiko , Kojima Chojiro
Published: August 2021

Floral transition, regulated by the systemic action of the mobile florigen protein FLOWERING LOCUS T (FT), is essential for successful plant reproduction1. How FT controls downstream gene expression remains incompletely understood, although it relies on the florigen activation complex (FAC), a core component of FT function2–4. The FAC is a nucleus-localized transcriptional activator of genes encoding MADS-box transcription factors critical to reproductive development and consists of florigen FT; a scaffold 14-3-3 protein that is a key component for complex assembly; and FD, a basic leucine-zipper protein that recruits the FAC to DNA. Here we report that the FAC exhibits phase separation. In rice shoot apical meristem cells, rice florigen Heading date 3a (Hd3a) fused to the green fluorescent protein formed speckles in the nucleus. The FAC speckle is formed in a FAC-dependent manner in tobacco cells. Recombinant Hd3a, but not OsFD1, phase-separated in vitro, and this effect was enhanced in the presence of 14-3-3 protein. Furthermore, mutations affecting functionally important residues in the pocket region or C-terminal disordered region of Hd3a affected FAC phase separation, providing a biochemical framework for the protein’s effect on flowering. The ability to form condensates via phase transition represents a previously unknown mechanism for gene activation by the FAC.
A generic sequential stimulation adapter for reducing muscle fatigue during functional electrical stimulation
Authors: Ye Gongkai , Ali Saima , Bergquist Austin J. , Popovic Milos R. , Masani Kei
Published: August 2021

Background

Clinical applications of conventional functional electrical stimulation (FES) administered via a single electrode is limited by rapid onset neuromuscular fatigue. “Sequential” (SEQ) stimulation, involving rotation of pulses between multiple active electrodes, has been shown to reduce fatigue compared to conventional FES. However, there has been limited adoption of SEQ in research and clinical settings.

Methods

The SEQ adapter is a small, battery-powered device that transforms the output of any commercially available electrical stimulator into SEQ stimulation. We examined the output of the adaptor across a range of clinically relevant stimulation pulse parameters to verify the signal integrity preservation ability of the SEQ adapter. Pulse frequency, amplitude, and duration were varied across discrete states between 4-200 Hz, 10-100 mA, and 50-2000 μs, respectively.

Results

A total of 420 trials were conducted, with 80 stimulation pulses per trial. The SEQ adapter demonstrated excellent preservation of signal integrity, matching the pulse characteristics of the originating stimulator within 1% error. The SEQ adapter operates as expected at pulse frequencies up to 160 Hz, with a noted failure mode at 200 Hz.

Conclusion

The SEQ adapter represents an effective and low-cost solution to increase the utilization of SEQ in existing rehabilitation paradigms.
Prospects of raising baobab (Adansonia digitata L.) to fruiting in two years
Authors: Egbadzor Kenneth Fafa , Akuaku Jones
Published: August 2021

Baobab is a very important plant with several uses, serving as food security crop and has the potential to raise income of farmers. However, the plant is undomesticated. We have the objective of domesticating the plant and promote its cultivation and utilization. Seeds were treated with sulphuric acid for early germination and grafted with matured scions suspected to be fruiting for several years. Twenty-two of the seedlings were transplanted on the field at Ho Technical University campus. Unfortunately, only four survived bushfire and destruction by stray animals. Surprisingly, one of the four surviving trees anthesis within twenty-eight months after seed treatment (twenty months after transplanting). This is the earliest ever reported anthesis of baobab. With better agronomic practices such as supplementary irrigation, insect pest control, manuring and protection from stray animals, baobab could start fruiting within two years of planting. This would alleviate fear of long maturity period and motivate farmers to go into baobab plantation. This would help diversify agriculture in many African countries, increase income and food security and contribute towards the attainment of the sustainable development goals of the United Nations.
Analysis of migration of pathogenic drug-resistant bacteria to soils and groundwater after fertilization with sewage sludge
Authors: Stańczyk-Mazanek Ewa , Stępniak Longina
Published: August 2021

The paper discusses the analysis of the effect of using sewage sludge for fertilization on the level of soil and groundwater contamination with drug-resistant bacteria. Other sanitary contaminants in these environments were also analysed. Composted sewage sludge was introduced into the sandy soil over a period of 6 months. The examinations were conducted under conditions of a lysimetric experiment with the possibility of collecting soil leachates (in natural conditions). The following doses of sewage sludge were used: 0, 10, 20, 30 and 40 t/ha calculated per experimental object containing 10 kg of sandy soil. The research were carried out within the time frame of one year. Dactylis glomerata grass was grown on the fertilized soils. In soils and leachates from soils (which may have polluted groundwater) collected from fertilized experimental objects, the sanitary condition and quantity of drug-resistant bacteria (mainly from the families Enterobacteriaceae and Enterococcus) were analysed one year after fertilization. Their drug resistance to selected antibiotics was also analysed based on current recommendations.
An siRNA-guided Argonaute protein directs RNA Polymerase V to initiate DNA methylation
Authors: Sigman Meredith J. , Panda Kaushik , Kirchner Rachel , McLain Lauren L. , Payne Hayden , Peasari John Reddy , Husbands Aman Y. , Slotkin R. Keith , McCue Andrea D.
Published: August 2021

In mammals and plants, cytosine DNA methylation is essential for the epigenetic repression of transposable elements and foreign DNA. In plants, DNA methylation is guided by small interfering RNAs (siRNAs) in a self-reinforcing cycle termed RNA-directed DNA methylation (RdDM). RdDM requires the specialized RNA Polymerase V (Pol V), and the key unanswered question is how Pol V is first recruited to new target sites without preexisting DNA methylation. We find that Pol V follows and is dependent upon the recruitment of an AGO4-clade ARGONAUTE protein, and any siRNA can guide the ARGONAUTE protein to the new target locus independent of preexisting DNA methylation. These findings reject long-standing models of RdDM initiation and instead demonstrate that siRNA-guided ARGONAUTE targeting is necessary, sufficient and first to target Pol V recruitment and trigger the cycle of RdDM at a transcribed target locus, thereby establishing epigenetic silencing.
Transcriptomic and proteomic retinal pigment epithelium signatures of age-related macular degeneration
Authors: Senabouth Anne , Daniszewski Maciej , Lidgerwood Grace E. , Liang Helena H. , Hernández Damián , Mirzaei Mehdi , Zhang Ran , Han Xikun , Neavin Drew , Rooney Louise , Sanchez Isabel Lopez , Gulluyan Lerna , Paulo Joao A , Clarke Linda , Kearns Lisa S , Gnanasambandapillai Vikkitharan , Chan Chia-Ling , Nguyen Uyen , Steinmann Angela M , Zekanovic Rachael , Farbehi Nona , Gupta Vivek K. , Mackey David A , Bylsma Guy , Verma Nitin , MacGregor Stuart , Guymer Robyn H , Powell Joseph E. , Hewitt Alex W. , Pébay Alice
Published: August 2021

Induced pluripotent stem cells generated from patients with geographic atrophy as well as healthy individuals were differentiated to retinal pigment epithelium (RPE) cells. By integrating transcriptional profiles of 127,659 RPE cells generated from 43 individuals with geographic atrophy and 36 controls with genotype data, we identified 439 expression Quantitative Trait (eQTL) loci in cis that were associated with disease status and specific to subpopulations of RPE cells. We identified loci linked to two genes with known associations with geographic atrophy - PILRB and PRPH2, in addition to 43 genes with significant genotype x disease interactions that are candidates for novel genetic associations for geographic atrophy. On a transcriptome-only level, we identified molecular pathways significantly upregulated in geographic atrophy-RPE including in extracellular cellular matrix reorganisation, neurodegeneration, and mitochondrial functions. We subsequently implemented a large-scale proteomics analysis, confirming modification in proteins associated with these pathways. We also identified six significant protein (p) QTL that regulate protein expression in the RPE cells and in geographic atrophy - two of which share variants with cis-eQTL. Transcriptome-wide association analysis identified genes at loci previously associated with age-related macular degeneration. Further analysis conditional on disease status, implicated statistically significant RPE-specific eQTL. This study uncovers important differences in RPE homeostasis associated with geographic atrophy.
GinJinn2: Object detection and segmentation for ecology and evolution
Authors: Ott Tankred , Lautenschlager Ulrich
Published: August 2021

Proper collection and preparation of empirical data still represent one of the most important, but also expensive steps in ecological and evolutionary/systematic research. Modern machine learning approaches, however, have the potential to automate a variety of tasks, which until recently could only be performed manually. Unfortunately, the application of such methods by researchers outside the field is hampered by technical difficulties, some of which, we believe, can be avoided.

Here, we present GinJinn2, a user-friendly toolbox for deep learning-based object detection and instance segmentation on image data. Besides providing a convenient command-line interface to existing software libraries, it comprises several additional tools for data handling, pre- and postprocessing, and building advanced analysis pipelines.

We demonstrate the application of GinJinn2 for biological purposes using four exemplary analyses, namely the evaluation of seed mixtures, detection of insects on glue traps, segmentation of stomata, and extraction of leaf silhouettes from herbarium specimens.

GinJinn2 will enable users with a primary background in biology to apply deep learning-based methods for object detection and segmentation in order to automate feature extraction from image data.
Constitutive signal bias mediated by the human GHRHR splice variant 1
Authors: Cong Zhaotong , Zhou Fulai , Zhang Chao , Zou Xinyu , Zhang Huibing , Wang Yuzhe , Zhou Qingtong , Cai Xiaoqing , Liu Qiaofeng , Li Jie , Shao Lijun , Mao Chunyou , Wang Xi , Wu Jihong , Xia Tian , Zhao Lihua , Jiang Hualiang , Zhang Yan , Eric Xu H. , Cheng Xi , Yang Dehua , Wang Ming-Wei
Published: August 2021

Alternative splicing of G protein-coupled receptors has been observed, but their functions are largely unknown. Here, we report that a splice variant (SV1) of the human growth hormone releasing hormone receptor (GHRHR) is capable of transducing biased signal. Differing only at the receptor N terminus, GHRHR predominantly activates Gs while SV1 selectively couples to β-arrestins. Based on the cryo-electron microscopy structures of SV1 in the apo state or in complex with the Gs protein, molecular dynamics simulations reveal that the N termini of GHRHR and SV1 differentiate the downstream signaling pathways, Gsvs. β-arrestins. Suggested by mutagenesis and functional studies, it appears that GHRH-elicited signal bias towards β-arrestin recruitment is constitutively mediated by SV1. The level of SV1 expression in prostate cancer cells is also positively correlated with ERK1/2 phosphorylation but negatively correlated with cAMP response. Our findings imply that constitutive signal bias may be a mechanism that ensures cancer cell proliferation.

Significance Statement

The mechanism of functional changes induced by alternative splicing of GHRHR is largely unknown. Here, we demonstrate that GHRH-elicited signal bias towards β-arrestin recruitment is constitutively mediated by SV1. The cryo-electron microscopy structures of SV1 and molecular dynamics simulations reveal the different functionalities between GHRHR and SV1 at the near-atomic level, i.e., the N termini of GHRHR and SV1 differentiate the downstream signaling pathways, Gsvs. β-arrestins. Our findings provide valuable insights into functional diversity of class B1 GPCRs which may aid in the design of better therapeutic agents against certain cancers.
MultiVI: deep generative model for the integration of multi-modal data
Authors: Ashuach Tal , Gabitto Mariano I. , Jordan Michael I. , Yosef Nir
Published: August 2021

Jointly profiling the transcriptional and chromatin accessibility landscapes of single-cells is a powerful technique to characterize cellular populations. Here we present MultiVI, a probabilistic model to analyze such multiomic data and integrate it with single modality datasets. MultiVI creates a joint representation that accurately reflects both chromatin and transcriptional properties of the cells even when one modality is missing. It also imputes missing data, corrects for batch effects and is available in the scvi-tools framework: https://docs.scvi-tools.org/.
Evolutionary history of mammalian UDP-glucuronosyltransferase (UGT)1 and UGT2 families: the emergence of UGT2B subfamily in eutherians after the diversification of flowering plants
Authors: Kawai Yusuke K. , Sano Kasumi , Ikenaka Yoshinori , Nakayama Shouta M.M. , Kondo Mitsuki , Kubota Akira , Ishizuka Mayumi
Published: August 2021

The UDP-glucuronosyltransferase (UGT) gene family is responsible for the transfer of glucuronic acid to exogenous and endogenous chemicals. Based on the highly diversified number of genes, the mammalian UGT1A and UGT2B subfamily genes are believed to be involved in the conjugation reactions of xenobiotic metabolism. However, it is speculated that the UGT2 family genes are not involved in the xenobiotic metabolism of avian species due to the less diverse number of genes. In this study, we aimed to investigate the evolutionary history of mammalian UGT1 and UGT2 family genes and determine when the diversification ofUGT2Bgenes occurred. We also attempted to identify the main factors responsible for the diversification ofUGTgenes and the effect of the selection pressure on the structure of the UGT isozymes. By examining the genomic information and feeding habits of 67 species representing each mammalian family, we discovered that theUGT2Bgenes emerged in the Eutheria on or after Cretaceous period and that their number were higher in plant-eating mammals (herbivore or omnivore) than in carnivorous mammals. We also found that theUGT2Bgenes in some herbivorous mammals underwent positive selection. In contrast, the diversity of the UGT1 family genes was inherited from the common ancestor of birds and mammals. Furthermore, by predicting 3D structure of UGT enzymes, estimating selection pressure on amino acid sites, and performing molecular dynamics simulations, we showed that UGT2B and some UGT2A isozymes, which have increasing gene numbers in each mammalian species, have in common that a portion of the α-helix loosens to form a hinge-like structure, that the amino acid site at which the α-helix loosens is under positive selection, and that the α-helix loosening increases the fluctuations of the UGT2B proteins. Thus, our findings suggest that the emergence of angiosperms (flowering plants) and the occurrence of “animal–plant warfare” influenced the evolution of this gene family involved in the xenobiotic metabolism of eutherians. Furthermore, future research investigating the marsupials and birds that do not possessUGT2Bgenes is required to elucidate the mechanisms underlying the metabolism of chemical substances in these species.
Long-term translocation explains population genetic structure of a recreationally fished iconic species in Japan: Combining current knowledge with reanalysis
Authors: Kitada Shuichi
Published: August 2021

Ayu (Plecoglossus altivelis altivelis) is an important freshwater fisheries resource and popular recreational fishing species in Japan, lives for only one year, and has a single breeding season. To supplement increased recreational fishing demand for this species, huge numbers of wild-born landlocked juveniles have been translocated from Lake Biwa into most Japanese rivers for more than 100 generations. Hatchery-reared juveniles born from captive-reared parents for more than 30 generations have also been extensively released. Previous studies have reported that landlocked and amphidromous forms of Ayu easily hybridise, but survival of landlocked larvae could be very low in seawater, leading to a general consensus among scientists, hatchery managers, and commercial and recreational fishers that the reproductive success of landlocked Ayu is very low, or even 0 in translocated rivers. Despite this, limited information exists regarding the reproductive success of landlocked Ayu in translocated rivers, and no study has evaluated the effects of translocation on population structure. Demonstrating that hybridisation occurs between the two forms is central to future management and conservation of this specie. To address this issue, a comprehensive literature search was undertaken, and three published genetic data sets are analysed. Analyses provide strong evidence for very high gene flow between populations, but population structure has been retained in several regions, and several populations are nested. Allele frequencies are similar in amphidromous and landlocked forms. Genetic diversity is homogeneous in amphidromous populations. Bayesian admixture analysis infers widespread introgression in Japanese rivers, with a mean introgression proportion of 24 ± 8%. Maximum likelihood admixture graphs detect two migration events from Lake Biwa to anadromous populations. Analyses consistently indicate that hybridisation between translocated landlocked juveniles and native amphidromous Ayu occurs throughout Japanese rivers.
Exon junction complex-associated multi-adapter RNPS1 nucleates splicing regulatory complexes to maintain transcriptome surveillance
Authors: Schlautmann Lena P. , Boehm Volker , Lackmann Jan-Wilm , Altmüller Janine , Dieterich Christoph , Gehring Niels H.
Published: August 2021

The exon junction complex (EJC) is an RNA-binding multi-protein complex with critical functions in post-transcriptional gene regulation. It is deposited on the mRNA during splicing and regulates diverse processes including pre-mRNA splicing, mRNA export, mRNA translation, and nonsense-mediated mRNA decay (NMD) via various interacting peripheral proteins. The EJC-binding protein RNPS1 might serve two functions: it suppresses mis-splicing of cryptic splice sites and activates NMD in the cytoplasm. When analyzing the transcriptome-wide effects of EJC and RNPS1 knockdowns in different human cell lines, we find no evidence for RNPS1 being a globally essential NMD factor. However, various aberrant splicing events strongly suggest that the main function of RNPS1 is splicing regulation. Rescue analyses revealed that about half of these RNPS1-dependent splicing events was fully or partially rescued by the expression of the isolated RRM domain of RNPS1, whereas other splicing events are regulated by its C-terminal domain. We identified many splicing-regulatory factors, including SR proteins and U1 snRNP components, that specifically interact with the C-terminus or with the RRM of RNPS1. Thus, RNPS1 emerges as a multifunctional splicing regulator that promotes correct and efficient splicing of different vulnerable splicing events via the formation of diverse splicing-promoting complexes.
Synthesis and crystal structure of catena-poly[[hexaaqua{μ3-2-[bis(carboxylatomethyl)amino]terephthalato}dicobalt(II)] pentahydrate] containing water tapes and pentamers
Authors: Ma Jie , Zhang Wen-Zhi , Xiong Jie , Yan Chun-Yan
Published: August 2021

The title coordination polymer, {[Co2(C12H7NO8)(H2O)6]·5H2O}
n
, was crystallized at room temperature from an aqueous solution of 2-aminodiacetic terephthalic acid (H4adtp) and cobalt(II) nitrate. The asymmetric unit consists of one adtp4− ligand, one and two half CoII ions, six water ligands coordinated to CoII ions and five uncoordinated water molecules. Two of the cobalt cations lie on centres of inversion and are coordinated in octahedral O2(OH2)4 environments, whereas the other adopts a slightly distorted octahedral NO3(OH2)2 environment. The crystal structure contains parallel stacked, one-dimensional zigzag chains, {[Co2(C12H7NO8)(H2O)6]}
n
, which assemble into a three-dimensional supramolecular architecture via networks of hydrogen bonds involving the coordinated and free water molecules. One-dimensional `water tapes' are formed, containing alternating six-membered and twelve-membered rings of water molecules, together with water pentamers, in which a central uncoordinated water molecule is hydrogen bonded to two coordinated and two free water molecules in a tetrahedral arrangement.
Energetic, exergetic, exergoeconomic, environmental (4E) and sustainability performances of an unmanned aerial vehicle micro turbojet engine
Authors: Balli Ozgur , Dalkıran Alper , Karakoç Tahir Hikmet
Published: August 2021

Purpose

This study aims to investigate the aviation, energetic, exergetic, environmental, sustainability and exergoeconomic performances of a micro turbojet engine used in unmanned aerial vehicles at four different modes.

Design/methodology/approach

The engine data were collected from engine test cell. The engine performance calculations were performed for four different operation modes.

Findings

According to the results, maximum energy and exergy efficiency were acquired as 19.19% and 18.079% at Mode 4. Total cost rate was calculated as 6.757 $/h at Mode-1, which varied to 10.131 $/h at Mode-4. Exergy cost of engine power was observed as 0.249 $/MJ at Mode-1, which decreased to 0.088 $/MJ at Mode-4 after a careful exergoeconomic analysis.

Originality/value

The novelty of this work is the capability to serve as a guide for similar systems with a detailed approach in the thermodynamic, thermoeconomic and environmental assessments by prioritizing efficiency, fuel consumption and cost formation. This investigation intends to establish a design of the opportunities and benefits that the thermodynamic approach provides to turbojet engine systems.
Health status of people with autism spectrum disorder
Authors: Koceski Antonio , Trajkovski Vladimir
Published: August 2021

Purpose

The aim of this study is to determine what changes occur in the health status of people with autism spectrum disorder (ASD) compared to neurotypical controls.

Design/methodology/approach

The authors performed a comparative analysis of data collected from 72 subjects with ASD and 75 neurotypical controls aged 3–24 years using the Rochester Health Status Survey IV (RHSS-IV). A structured individual interview was conducted to compare the health status of subjects in Macedonia.

Findings

A majority of people with ASD take vitamins, supplements and use recommended drug therapies compared to the neurotypical population and experience a larger number of side effects (p = 0.000). Compared to people with neurotypical development, children with ASD have a higher prevalence of oral ulcers (31.9% vs 17.3%; p = 0.039), changes in neurological health status – epilepsy (19.4% vs 2.7%; p = 0.001) and ADD/ADHD (only persons with ASD-19.4%; p = 0.000); respiratory diseases – angina (30.5% vs 8%; p = 0.000), rhinitis and/or sinusitis (40.3% vs 17.3%; p = 0.02); changes in the gastrointestinal system – constipation (31.9% vs 10.6%; p = 0.02), intestinal inflammation (19.4% vs 8%; p = 0.043), permeable intestines (only persons with ASD – 13.9%; p = 0.000) and the presence of the fungus Candida albicans (19.4% vs 4%; p = 0.043); psychiatric disorders – sleep problems (only in people with ASD – 18%; p = 0.000) and tics (6.9% vs 2.6%; p = 0.25) and skin diseases – eczema/allergic skin rash (36.1% vs 18.7%; p = 0.02).

Originality/value

Many children with ASD have health problems. These findings support and complement the professional literature on their mutual causality.
Impacts of big data analytics management capabilities and supply chain integration on global sourcing: a survey on firm performance
Authors: Razaghi Shokouh , Shokouhyar Sajjad
Published: August 2021

Purpose

This study aims to show that management with big data analytics capability can achieve more advantages of the global sourcing process. Furthermore, this study using its conceptual attitude model aims to show that big data analytics management capability leads to an increase in firm performance by the mediating role of integration.

Design/methodology/approach

Using an online questionnaire, 158 managers from 13 Iranian companies taking advantage of the global sourcing process were surveyed. The validity of the hypotheses was evaluated using partial least squares based on structural equation modeling (PLS method).

Findings

The results of the study showed that big data analytics management capability has a positive impact on global sourcing and firm performance directly, and by the mediating role of integration.

Originality/value

Previous studies have carefully addressed the role of big data and big data analytics in firms. However, this is among a few studies addressing the role of big data analytics capability, especially management capability, in improving firms’ performance. The results of this study shed light on the fact that how global sourcing takes the best advantage of big data analytics management capability for better accomplishment of organizations’ duties. The results of this study also disclose how big data analytics management capability helps organizations with their performance and bring benefits to their units.