bluuebunny/crossref_metadata_2025 huggingface dataset:
Dorsal and ventral striatal functional connectivity shift with the medial frontal gyrus in internet gaming disorder: Potential mechanisms underlying addictive engagement
Authors: Dong Guang-Heng , Dong Haohao , Wang Min , Zhang Jialin , Zhou Weiran , Zheng Yanbin , Potenza Marc N.
Published: August 2020

Background

Animal models suggest transitions from non-addictive to addictive behavioral engagement are associated with ventral-to-dorsal striatal shifts. However, few studies have examined such features in humans, especially in internet gaming disorder (IGD), a behavioral addiction.

Methods

Four-hundred-and-eighteen subjects (174 with IGD; 244 with recreational game use (RGU)) were recruited. Resting-state fMRI data were collected and functional connectivity (FC) analyses were performed based on ventral and dorsal striatal seeds. Correlations and follow-up spectrum dynamic causal model (spDCM) analyses were performed to examine relationships between ventral/dorsal striatum to medial frontal gyrus (MFG) and IGD severity. Longitudinal data from 40 subjects (22 IGD; 18 RGU) were also analysed to investigate further.

Results

Interactions were observed between group (IGD, RGU) and striatal regions (ventral, dorsal). IGD relative to RGU subjects showed lower ventral-striatum-to-MFG (mostly involving supplementary motor area (SMA)) and higher dorsal-striatum-to-MFG functional connectivity. spDCM revealed that left dorsal-striatum-to-MFG connectivity was correlated with IGD severity. Longitudinal data further support for ventral-to-dorsal striatal MFG relationships in IGD.

Conclusions

Consistent with animal models of substance addictions, ventral-to-dorsal striatal transitions in involvement coritico-striatal circuitry may underlie IGD and its severity. These findings suggest possible neurobiological mechanisms that may be targeted in treatments for IGD.
Data-Driven Development of a Small-Area COVID-19 Vulnerability Index for the United States
Authors: Amram Ofer , Amiri Solmaz , Thorn Emily L. , Mansfield Jacob J. , Mellacheruvu Pranav , Monsivais Pablo
Published: August 2020

As the COVID-19 pandemic continues to surge in the United States, it has become clear that infection risk is higher in certain populations, particularly socially and economically marginalized groups. Social risk factors, together with other demographic and community characteristics, may reveal local variations and inequities in COVID risk that could be useful for targeting testing and interventions. Yet to date, rates of infection and estimations of COVID risk are typically reported at the county and state level. In this study we develop a small area vulnerability index based on publicly-available sociodemographic data and 668,428 COVID diagnoses reported in 4,803 ZIP codes in the United States (15% of all ZIP codes). The outcome was COVID-19 diagnosis rates per 100,000 people by ZIP code. Explanatory variables included sociodemographic characteristics obtained from the 2018 American Community Survey 5-year estimates. Bayesian multivariable techniques were used to capture complexities of spatial data and spatial autocorrelation and identify individual risk factors and derive their respective weights in the index. COVID-19 diagnosis rates varied from zero to 29,508 per 100,000 people. The final vulnerability index showed that higher population density, higher percentage of noninsured, nonwhite race and Hispanic ethnicity were positively associated with COVID-19 diagnosis rates. Our findings indicate disproportionate risk of COVID-19 infection among some populations and validate and expand understanding of these inequities, integrating several risk factors into a summary index reflecting composite vulnerability to infection. This index can provide local public health and other agencies with evidence-based metrics of COVID risk at a geographical scale that has not been previously available to most US communities.
SARS-CoV-2 antibody responses in children with MIS-C and mild and severe COVID-19
Authors: Anderson Elizabeth M. , Diorio Caroline , Goodwin Eileen C. , McNerney Kevin O. , Weirick Madison E. , Gouma Sigrid , Bolton Marcus J. , Arevalo Claudia P. , Chase Julie , Hicks Philip , Manzoni Tomaz B. , Baxter Amy E. , Andrea Kurt P. , Burudpakdee Chakkapong , Lee Jessica H. , Vella Laura A. , Henrickson Sarah E. , Harris Rebecca M. , John Wherry E. , Bates Paul , Bassiri Hamid , Behrens Edward M. , Teachey David T. , Hensley Scott E.
Published: August 2020

SARS-CoV-2 antibody responses in children remain poorly characterized. Here, we show that pediatric patients with multisystem inflammatory syndrome in children (MIS-C) possess higher SARS-CoV-2 spike IgG titers compared to those with severe coronavirus disease 2019 (COVID-19), likely reflecting a longer time since onset of infection in MIS-C patients.
BiG-SLiCE: A Highly Scalable Tool Maps the Diversity of 1.2 Million Biosynthetic Gene Clusters
Authors: Kautsar Satria A. , van der Hooft Justin J. J. , de Ridder Dick , Medema Marnix H.
Published: August 2020

Background

Genome mining for Biosynthetic Gene Clusters (BGCs) has become an integral part of natural product discovery. The >200,000 microbial genomes now publicly available hold information on abundant novel chemistry. One way to navigate this vast genomic diversity is through comparative analysis of homologous BGCs, which allows identification of cross-species patterns that can be matched to the presence of metabolites or biological activities. However, current tools suffer from a bottleneck caused by the expensive network-based approach used to group these BGCs into Gene Cluster Families (GCFs).

Results

Here, we introduce BiG-SLiCE, a tool designed to cluster massive numbers of BGCs. By representing them in Euclidean space, BiG-SLiCE can group BGCs into GCFs in a non-pairwise, near-linear fashion. We used BiG-SLiCE to analyze 1,225,071 BGCs collected from 209,206 publicly available microbial genomes and metagenome-assembled genomes (MAGs) within ten days on a typical 36-cores CPU server. We demonstrate the utility of such analyses by reconstructing a global map of secondary metabolic diversity across taxonomy to identify uncharted biosynthetic potential. BiG-SLiCE also provides a "query mode" that can efficiently place newly sequenced BGCs into previously computed GCFs, plus a powerful output visualization engine that facilitates user-friendly data exploration.

Conclusions

BiG-SLiCE opens up new possibilities to accelerate natural product discovery and offers a first step towards constructing a global, searchable interconnected network of BGCs. As more genomes get sequenced from understudied taxa, more information can be mined to highlight their potentially novel chemistry. BiG-SLiCE is available viahttps://github.com/medema-group/bigslice.
Neuroimmune circuits involved in β-lactoglobulin-induced food allergy
Authors: Lemos Luísa , Assis Helder Carvalho , Alves Juliana Lima , Reis Daniela Silva , Canesso Maria Cecilia Campos , Moreira Thais Garcias , Miranda Barbara Kaori Sato , Batista Luara Augusta , de Souza Gomes Lenzi Julia Ariana , Moraes Muiara Aparecida , Pereira Luciana Melo , Aguiar Daniele Cristina , Souza Bruno Rezende , Cara Denise Carmona , Gomes-Santos Ana Cristina , Faria Ana Maria Caetano
Published: August 2020

Cow’s milk allergy is the most prevalent food allergy that usually begins early in life and β- lactoglobulin (BLG) is the milk component with the highest allergenicity. It has been described that ovalbumin (OVA)-induced food allergy in mice is associated with anxiety and aversive behavior. However, it is yet to be determined whether altered behavior is a general component of food allergy or whether it is specific for some types of allergens. Thus, we investigated behavioral and neuroimmune circuits triggered by allergic sensitization to BLG. We found a neuroimmune conflict between aversion and reward in a model of food allergy induced to BLG. Mice sensitized to BLG did not present aversive behavior when the allergen was used for sensitization and oral challenge. Mice allergic to BLG preferred to drink the allergen-containing solution over water even though they presented high levels of specific IgE, inflammatory cells in the intestinal mucosa and significant weight loss. When sensitized to OVA and orally challenged with the same antigen, mice had display neuron activation in the amygdala suggesting an anxiety-related sensation. On the other hand, OVA-sensitized mice showed preference to consume a mixture of BLG and OVA during oral challenge in spite of their aversion to OVA. Consumption of OVA-BLG solution was associated with neuron activation in the nucleus accumbens, suggesting a reward sensation. Thus, the aversive behavior observed in food allergy to OVA does not apply to all antigens and some allergens may induce preference rather than aversion. Our study provides new insights into the neuroimmune conflicts regarding preference and avoidance to a common antigen associated with food allergy.
Probing the Hidden Sensitivity of Intrinsically Disordered Proteins to their Chemical Environment
Authors: Moses David , Yu Feng , Ginell Garrett M. , Shamoon Nora M. , Koenig Patrick S. , Holehouse Alex S. , Sukenik Shahar
Published: August 2020

Intrinsically disordered proteins and protein-regions (IDRs) make up roughly 30% of the human proteome and play vital roles in a wide variety of biological processes. Given a lack of persistent tertiary structure, all of the residues in an IDR are, to some extent, solvent exposed. This extensive surface area, coupled with the absence of strong intramolecular contacts, makes IDRs inherently sensitive to their chemical environment. Despite this sensitivity, our understanding of how IDR structural ensembles are influenced by changes in their chemical environment is limited. This is particularly relevant given a growing body of evidence showing that IDR function is linked to the underlying structural ensemble. We develop and use a combined experimental, computational, and analytical framework for high-throughput characterization of IDR sensitivity we call solution space scanning. Our framework reveals that IDRs show sequence-dependent sensitivity to solution chemistry, with complex behavior that can be interpreted through relatively simple polymer models. Our results imply that solution-responsive IDRs are ubiquitous and can provide an additional layer of biological regulation.
Mapping quantitative trait loci and predicting candidate genes for leaf angle in maize
Authors: Zhang Ning , Huang Xueqing
Published: August 2020

Leaf angle of maize is a fundamental determinant of plant architecture and an important trait influencing photosynthetic efficiency and crop yields. To broaden our understanding of the genetic mechanisms of leaf angle formation, we constructed an F3:4recombinant inbred lines (RIL) population derived from a cross between a model inbred line (B73) with expanded leaf architecture and an elite inbred line (Zheng58) with compact leaf architecture to map QTL for leaf angle. A sum of 8 QTL were detected on chromosome 1, 2, 3, 4 and 8. Single QTL explained 4.3 to 14.2% of the leaf angle variance. Additionally, some important QTL were confirmed through a heterogeneous inbred family(HIF) approach. Furthermore, twenty-four candidate genes for leaf angle were predicted through whole-genome resequencing and expression analysis in qLA02-01and qLA08-01 regions. These results will be helpful to elucidate the genetic mechanism of leaf angle formation in maize and benefit to clone the favorable allele for leaf angle or develop the novel maize varieties with ideal plant architecture through marker-assisted selection.
Characterization of CRISPR/Cas9 RANKL knockout mesenchymal stem cell clones based on single-cell printing technology and emulsion coupling assay as a low-cellularity workflow for single-cell cloning
Authors: Groß Tobias , Jeney Csaba , Halm Darius , Finkenzeller Günter , Stark G. Björn , Zengerle Roland , Kolaty Peter , Zimmermann Stefan
Published: August 2020

The homogeneity of the genetically modified single-cells is a necessity for many applications such as cell line development, gene therapy, and tissue engineering and in particular for regenerative medical applications. The lack of tools to effectively isolate and characterize CRISPR/Cas9 engineered cells is considered as a significant bottleneck in these applications. Especially the incompatibility of protein detection technologies to confirm protein expression changes without a preconditional large-scale clonal expansion, creates a gridlock in many applications. To ameliorate the characterization of engineered cells, we propose an improved workflow, including single-cell printing/isolation technology based on fluorescent properties with high yield, a genomic edit screen (surveyor assay), mRNA rtPCR assessing altered gene expression and a versatile protein detection tool called emulsion-coupling to deliver a high-content, unified single-cell workflow. The workflow was exemplified by engineering and functionally validating RANKL knockout immortalized mesenchymal stem cells showing altered bone formation capacity of these cells. The resulting workflow is economical, without the requirement of large-scale clonal expansions of the cells with overall cloning efficiency above 30% of CRISPR/Cas9 edited cells. Nevertheless, as the single-cell clones are comprehensively characterized at an early, highly parallel phase of the development of cells including DNA, RNA, and protein levels, the workflow delivers a higher number of successfully edited cells for further characterization, lowering the chance of late failures in the development process.

Author summary

I completed my undergraduate degree in biochemistry at the University of Ulm and finished my master's degree in pharmaceutical biotechnology at the University of Ulm and University of applied science of Biberach with a focus on biotechnology, toxicology and molecular biology. For my master thesis, I went to the University of Freiburg to the department of microsystems engineering, where I developed a novel workflow for cell line development. I stayed at the institute for my doctorate, but changed my scientific focus to the development of the emulsion coupling technology, which is a powerful tool for the quantitative and highly parallel measurement of protein and protein interactions. I am generally interested in being involved in the development of innovative molecular biological methods that can be used to gain new insights about biological issues. I am particularly curious to unravel the complex and often poorly understood protein interaction pathways that are the cornerstone of understanding cellular functionality and are a fundamental necessity to describe life mechanistically.
Role of neutrophil extracellular traps in regulation of lung cancer invasion and metastasis: Structural Insights from a Computational Model
Authors: Lee Junho , Lee Donggu , Lawler Sean , Kim Yangjin
Published: August 2020

Lung cancer is one of the leading causes of cancer-related deaths worldwide and is characterized by hijacking immune system for active growth and aggressive metastasis. Neutrophils, which in their original form should establish immune activities to the tumor as a first line of defense, are undermined by tumor cells to promote tumor invasion in several ways. In this study, we investigate the mutual interactions between the tumor cells and the neutrophils that facilitate tumor invasion by developing a mathematical model that involves taxis-reaction-diffusion equations for the critical components in the interaction. These include the densities of tumor and neutrophils, and the concentrations of signaling molecules and structure such as neutrophil extracellular traps (NETs). We apply the mathematical model to a Boyden invasion assay used in the experiments to demonstrate that the tumor-associated neutrophils can enhance tumor cell invasion by secreting the neutrophil elastase. We show that the model can both reproduce the major experimental observation on NET-mediated cancer invasion and make several important predictions to guide future experiments with the goal of the development of new anti-tumor strategies. Moreover, using this model, we investigate the fundamental mechanism of NET-mediated invasion of cancer cells and the impact of internal and external heterogeneity on the migration patterning of tumour cells and their response to different treatment schedules.

Author summary

When cancer patients are diagnosed with tumours at a primary site, the cancer cells are often found in the blood or already metastasized to the secondary sites in other organs. These metastatic cancer cells are more resistant to major anti-cancer therapies, and lead to the low survival probability. Until recently, the role of neutrophils, specifically tumor-associated neutrophils as a member of complex tumor microenvironment, has been ignored for a long time due to technical difficulties in tumor biology but these neutrophils are emerging as an important player in regulation of tumor invasion and metastasis. The mutual interaction between a tumor and neutrophils from bone marrow or in blood induces the critical transition of the naive form, called the N1 type, to the more aggressive phenotype, called the N2 TANs, which then promotes tumor invasion. In this article, we investigate how stimulated neutrophils with different N1 and N2 landscapes shape the metastatic potential of the lung cancers. Our simulation framework is designed for boyden invasion chamber in experiments and based on a mathematical model that describes how tumor cells interact with neutrophils and N2 TANs can promote tumor cell invasion. We demonstrate that the efficacy of anti-tumor (anti-invasion) drugs depend on this critical communication and N1 → N2 landscapes of stimulated neutrophils.
Multi-environment phenotyping ofC. elegansfor robust evaluation of physical performance
Authors: Hewitt Jennifer E. , Laranjeiro Ricardo , Norouzi Masoud , Ellwood Rebecca , Antebi Adam , Szewczyk Nathaniel J. , Driscoll Monica , Vanapalli Siva A.
Published: August 2020

Determining the physical performance of humans using several measures is essential to evaluating the severity of diseases, understanding the role of environmental factors, and developing therapeutic interventions. Development of analogous measures of physical performance in model organisms can help in identifying conserved signaling pathways and prioritizing drug candidates. In this study, we propose a multi-environment phenotyping (MEP) approach that generates a comprehensive set of measures indicative of physical performance inC. elegans. We challengeC. elegansin different mechanical environments of burrowing, swimming, and crawling, each of which places different physiological demands on the animals to generate locomotory forces. Implementation of the MEP approach is done using three established assays corresponding to each environment–a hydrogel-based burrowing assay, the CeleST swim assay, and the NemaFlex crawling strength assay. Using this approach, we study individuals and show that these three assays report on unique aspects of nematode physiology, as phenotypic measures obtained from different environments do not correlate with one another. Analysis of a subset of genes representative of oxidative stress, glucose metabolism, and fat metabolism show differential expression depending on the animal’s environment, suggesting that each environment evokes a response with distinct genetic requirements. To demonstrate the utility of the MEP platform, we evaluate the response of a muscular dystrophy model ofC. elegans dys-1to drug interventions of prednisone, melatonin and serotonin. We find that prednisone, which is the current treatment standard for human Duchenne muscular dystrophy, confers benefits in all three assays. Furthermore, while the tested compounds improve the physical performance ofdys-1, these compounds are not able to fully restore the measures to wild-type levels, suggesting the need for discovery efforts to identify more efficacious compounds that could be aided using the MEP platform. In summary, the MEP platform’s ability to robustly defineC. eleganslocomotory phenotypes demonstrates the utility of the MEP approach toward identification of candidates for therapeutic intervention, especially in disease models in which the neuromuscular performance is impaired.
Two forms of isometric muscle function: Interpersonal motor task supports a distinction between a holding and a pushing isometric muscle action
Authors: Schaefer Laura V , Bittmann Frank N
Published: August 2020

In sports and movement sciences isometric muscle function is measured by pushing against a stable resistance. However, subjectively one can hold or push isometrically. Several investigations suggest a distinction of those forms. The aim of this study was to investigate, whether or not these two forms of isometric muscle action can be distinguished by objective parameters in an interpersonal setting. 20 subjects were grouped in 10 same sex pairs, in which one partner should perform the pushing isometric muscle action (PIMA) and the other partner executed the holding isometric muscle action (HIMA). The partners were coupled by an interface including a strain gauge and an acceleration sensor. The mechanical oscillations of the triceps brachii (MMGtri) muscle, its tendon (MTGtri) and the abdominal muscle (MMGobl) were recorded by piezoelectric-sensor-based measurement system (mechanomyography (MMG); mechanotendography (MTG)). Each partner performed three 15s (80% MVIC) and two fatiguing trials (90% MVIC) during PIMA and HIMA, respectively (tasks changed in the couple). Regarded parameters to compare PIMA and HIMA were (1) the mean frequency, (2) the normalized mean amplitude, (3) the amplitude variation, (4) the power in the frequency range of 8 to 15 Hz and (5) a special power-frequency ratio and the number of task failures during HIMA or PIMA (partner who quit the task).

A “HIMA failure” occurred in 87.5% of trials (p<0.000). No significant differences between PIMA and HIMA were found for the mean frequency and normalized amplitude. The MMGobl showed a significantly higher values of the amplitude variation (15s:p0.013; fatigue:p=0.007) and of the power-frequency-ratio (15s:p= 0.040; fatigue:p= 0.002) during HIMA and a higher power in the range of 8 to 15 Hz during PIMA (15s:p=0.001; fatigue:p=0.011). MMGtri and MTGtri showed no significant differences.

Based on the findings it is suggested that a holding and a pushing isometric muscle action can be distinguished objectively, whereby a more complex neural control is assumed for HIMA.
Acoustic niche partitioning in two tropical wet forest bird communities
Authors: Hart Patrick J. , Paxton Kristina , Ibanez Thomas , Tredinnick Grace , Sebastián-González Esther , Tanimoto-Johnson Ann
Published: August 2020

When acoustic signals sent from individuals overlap in frequency and time, acoustic interference and signal masking may occur. Under the acoustic niche hypothesis (ANH), signaling behavior has evolved to minimize overlap with other calling individuals through selection on signal structure and the sender’s ability to adjust the timing of signals. In this study, we examine the fine-scale use of acoustic space and the relevance of the acoustic niche hypothesis in two montane tropical wet forest bird communities (Costa Rica and Hawai’i) that vary in bird species richness. We used a null model approach to test the prediction that there are differences between observed and expected signal overlap in both communities. As predicted under ANH, we found much lower overlap of acoustic signals than expected by chance. In addition, spectral and temporal overlap between different signals was far more common in Hawaii than Costa Rica. These findings constitute strong support that there is competition for acoustic space in signaling communities, and this has resulted in temporal and spectral partitioning of the soundscape.
Influenza virus inhibits respiratory syncytial virus (RSV) infection via a two-wave expression of interferon-induced protein with tetratricopeptide (IFIT) proteins
Authors: Drori Yaron , Jacob-Hirsch Jasmine , Pando Rakefet , Glatman-Freedman Aharona , Friedman Nehemya , Mendelson Ella , Mandelboim Michal
Published: August 2020

Influenza viruses and respiratory syncytial virus (RSV) are respiratory viruses that primarily circulate worldwide during the autumn and winter seasons. Seasonal surveillance shows that RSV infection generally precedes influenza. However, in the last four winter seasons (2016-2020) an overlap of the morbidity peaks of both viruses was observed in Israel, and was paralleled by significantly lower RSV infection rates. To investigate whether the influenza virus inhibits RSV we performed coinfection of Human cervical carcinoma (HEp2) cells or mice with influenza and RSV and we observed that the influenza inhibited RSV growth, both in vitro and in vivo. Mass spectrometry analysis of mouse lungs infected with influenza identified a two-wave pattern of protein expression upregulation, which included members of the interferon-induced protein with tetratricopeptide (IFITs) family. Interestingly, in the second peak of upregulation, influenza viruses were no longer detectable in mouse lungs. We also observed that knockdown and overexpression of IFITs in HEp2 cells affected RSV multiplicity. In conclusion, influenza infection inhibits RSV infectivity via upregulation of IFIT proteins in a two-wave modality. Understanding of the interaction between influenza and RSV viruses and immune system involvement will contribute to the development and optimization of future treatment strategies against these viruses.

Author Summary

Respiratory syncytial virus (RSV) and influenza viruses are both respiratory viruses associated with morbidity and mortality worldwide. RSV is usually detected in October, with a clear peak in December, whereas influenza virus arrives in November and peaks in January. In the last four seasons, influenza infection overlapped with that of RSV in Israel, which resulted in decreased morbidity of RSV suggesting that influenza virus inhibits RSV infection. To identify the mechanism responsible for the influenza inhibition of RSV we performed experiments in culture and in mice. We observed that influenza infection results in two wave modality of inhibition of RSV infection. Using mass spectrometry perfornmed on lungs from infected mice we show that influenza infection induces the expression of (IFIT) family of proteins which also showed a two-wave modality. Using knockdown and overexpression experiments we showed that indeed the IFTIs inhibits RSV infection. Our study provides new insights on the interaction between influenza and RSV viruses and immune system involvement and contribute to the development of future treatment strategies against these viruses.
Physiological, Biochemical and Microstructural Changes in Rice (Oryza sativaL.) under Varying pH Levels
Authors: Ekta  , Singh Anil Kumar , Pandey Dev Mani
Published: August 2020

Soil acidification exerts detrimental effects on rice plant leading to severe reduction in its yield. In the present study, we investigated the physiological, biochemical and microstructural changes in the leaves of rice cultivars, namely, Jhilli Dhan (JD) and Gora Dhan (GD), under varying pH conditions (pH 6.5, 5.5, 4.5 and 3.5). Seedlings were grown at varying pH levels for 14 days under controlled conditions. Root and shoot growth and chlorophyll content were found to be decreased with increasing acidity, whereas electrolyte leakage was increased with increasing acidity. Overall, seedling growth was significantly reduced at pH 3.5, while, it was maximum at pH 6.5 treatment, which might be the result of cumulative altered physiological parameters. Further, biochemical parameters, namely total soluble sugar (TSS), proline content and lipid peroxidation were found to be positively correlated with acidity. Microstructural changes were observed through Swept-Source Optical Coherence Tomography (SS-OCT) and Field Emission Scanning Electron Microscope (FESEM). The thickness between different layers of leaves was found to be disintegrating at low pH conditions and the thickness of parenchyma cells was reduced significantly. FESEM analysis revealed changes in characteristics of stomata under acidic stress. The understanding of physiological, biochemical and microstructural changes in rice leaves under varying pH conditions may help in developing rice with improved tolerance towards soil acidity stress.
Characterization of Onion Seedlots into Different Storability Groups with 4 Parameter Hill Function (4-PHF)
Authors: Kumar Sunil , Basu Sudipta , Anand Anjali , Aravind J.
Published: August 2020

Onion varieties were classified into different storability groups by comparing two approaches (i)germination and vigor indices (conventional germination parameters) (ii)variables extracted from 4 Parameter Hill Function (4-PHF), after mimicking ageing conditions with accelerated ageing (42 °C and 100% RH). The study revealed that in comparison to evaluation using conventional germination parameters, the parameters extracted using 4-PHF provided realistic characterization of varieties as good, medium and poor storers. Time related parameters like time to maximum germination rate (TMGR), time to 50% germination (T50), difference between time at germination onset (lag) and 50% germination (Dlag-50), uniformity (U) along with germination percent (a) and area under curve (AUC) were decisive in identification of the varieties to a storage category which was misinterpreted with exclusive use of conventional approach. The distinction between good and medium storers was not of much significance but shift of varieties like Bhima Super, Pusa Red and Agrifound Light Red from poor to good performance cluster could be detected exclusively through 4-PHF analysis. Curve fittings highlightedAUCas the most crucial parameter contributing towards clustering of the varieties in different storability groups. Our study is the first reported research of using 4-PHF mathematical function for seedlot characterization into different storability groups.
Unveiling sex-based differences in the effects of alcohol abuse: a comprehensive functional meta-analysis of transcriptomic studies
Authors: Ferrer Franc Casanova , Pascual María , Hidalgo Marta R. , Malmierca-Merlo Pablo , Guerri Consuelo , García-García Francisco
Published: August 2020

The abuse of alcohol, one of the most popular psychoactive substances, can cause several pathological and psychological consequences, including alcohol use disorder (AUD). An impaired ability to stop or control alcohol intake despite adverse health or social consequences characterize AUD. While AUDs predominantly occur in men, growing evidence suggests the existence of distinct cognitive and biological consequences of alcohol dependence in women. The molecular and physiological mechanisms participating in these differential effects remain unknown. Transcriptomic technology permits the detection of the biological mechanisms responsible for such sex-based differences, which supports the subsequent development of novel personalized therapeutics to treat AUD. We conducted a systematic review and meta-analysis of transcriptomics studies regarding alcohol dependence in humans with representation from both sexes. For each study, we processed and analyzed transcriptomic data to obtain a functional profile of pathways and biological functions and then integrated the resulting data by meta-analysis to characterize any sex-based transcriptomic differences associated with AUD. Global results of the transcriptomic analysis revealed the association of decreased tissue regeneration, embryo malformations, altered intracellular transport, and increased rate of RNA and protein replacement with female AUD patients. Meanwhile, our analysis indicated that increased inflammatory response and blood pressure and a reduction in DNA repair capabilities associated with male AUD patients. In summary, our functional meta-analysis of transcriptomic studies provides evidence for differential biological mechanisms that AUD patients of differing sex.

Abstract Figure
Continued topographical learning- and relearning-dependent activity in the resting state after post-training sleep and wake
Authors: Deantoni Michele , Villemonteix Thomas , Balteau Evelyne , Schmidt Christina , Peigneux Philippe
Published: August 2020

Continuation of experience-dependent neural activity during offline periods of sleep and wakefulness is a critical element of memory consolidation. Using functional magnetic resonance imaging (fMRI), offline consolidation effects have been evidenced probing behavioral and neurophysiological changes during memory retrieval, i.e. in the context of task practice. Resting state fMRI (rfMRI) further allows investigating the offline evolution of recently learned information, without confounding task-related effects. In the present study, we used rfMRI to investigate offline changes in functional connectivity (FC) and Amplitude of Low Frequency Fluctuation (ALFF) associated with learning and relearning in a spatial navigation task, following an episode of post-training wake or sleep, respectively. Resting state activity was measured immediately (i) before and (ii) after topographical learning in a virtual town, (iii) 4 days later after regular sleep (RS) vs. sleep deprivation (SD) on the first post-learning night, and (iv) after topographical re-learning in an extended town encompassing the initial map. Task (navigation)-based fMRI activity was also recorded on Day 1 and Day 4 during target retrieval. Our results highlight the continuation of navigation-related activity in the subsequent resting state, as evidenced by changes in FC and ALFF in task-related neural networks. Behavioural performance was not modulated by post-training SD vs RS. However, in line with prior reports, post-training SD was associated with increased FC between navigation-related brain structures when faced to the task of learning a novel but related environment in the extended version of the city at Day 4. These results suggest the use of compensatory resources to link novel information with SD-related less efficiently consolidated memory traces.
Disentangling semantic composition and semantic association in the left temporal lobe
Authors: Li Jixing , Pylkkänen Liina
Published: August 2020

Although composing two words into a complex representation (e.g., “coffee cake”) is conceptually different from forming associations between a pair of words (e.g., “coffee, cake”), the brain regions supporting semantic composition have also been implicated for associative encoding. Here, we adopted a two-word magnetoencephalography (MEG) paradigm which varies compositionality (“French/Korean cheese” vs. “France/Korea cheese”) and strength of association (“France/French cheese” vs. “Korea/Korean cheese”) between the two words. We collected MEG data while 42 English speakers (24 females) viewed the two words successively in the scanner, and we applied both univariate regression analyses and multivariate pattern classification to the source estimates of the two words. We show that the left anterior and middle temporal lobe (LATL; LMTL) are distinctively modulated by semantic composition and semantic association. Specifically, the LATL is mostly sensitive to high-association compositional phrases, while the LMTL responds more to low-association compositional phrases. Pattern-based directed connectivity analyses further revealed a continuous information flow from the anterior to the middle temporal region, suggesting that the integration of adjective and noun properties originated earlier in the LATL is consistently delivered to the LMTL when the complex meaning is newly encountered. Taken together, our findings shed light into a functional dissociation within the left temporal lobe for compositional and distributional semantic processing.

Significance Statement

Prior studies on semantic composition and associative encoding have been conducted independently within the subfields of language and memory, and they typically adopt similar two-word experimental paradigms. However, no direct comparison has been made on the neural substrates of the two processes. The current study relates the two streams of literature, and appeals to audiences in both subfields within cognitive neuroscience. Disentangling the neural computations for semantic composition and association also offers insight into modeling compositional and distributional semantics, which has been the subject of much discussion in Natural Language Processing and cognitive science.
Cleavage Site Specificity for Processing of Farnesylated Prelamin A by the Zinc Metalloprotease ZMPSTE24
Authors: Babatz Timothy D. , Spear Eric D. , Xu Wenxin , Sun Olivia L. , Nie Laiyin , Carpenter Elisabeth P. , Michaelis Susan
Published: August 2020

The integral membrane zinc metalloprotease ZMPSTE24 is important for human health and longevity. ZMPSTE24 performs a key proteolytic step in maturation of prelamin A, the precursor of the nuclear scaffold protein lamin A. Mutations in the genes encoding either prelamin A or ZMPSTE24 that prevent cleavage cause the premature aging disease Hutchinson Gilford Progeria Syndrome (HGPS) and related progeroid disorders. ZMPSTE24 has a novel structure, with seven transmembrane spans that form a large water-filled membrane chamber whose catalytic site faces the chamber interior. Prelamin A is the only known mammalian substrate for ZMPSTE24, however, the basis of this specificity remains unclear. To define the sequence requirements for ZMPSTE24 cleavage, we mutagenized the eight residues flanking the prelamin A scissile bond (TRSY↓LLGN) to all other 19 amino acids, creating a library of 152 variants. We also replaced these eight residues with sequences derived from putative ZMPSTE24 cleavage sites from amphibian, bird, and fish prelamin A. Cleavage of prelamin A variants was assessed using anin vivoyeast assay that provides a sensitive measure of ZMPSTE24 processing efficiency. We found that residues on the C-terminal side of the cleavage site are most sensitive to changes. Consistent with other zinc metalloproteases, including thermolysin, ZMPSTE24 preferred hydrophobic residues at the P1’ position (Leu647), but in addition, showed a similar, albeit muted, pattern at P2’. Our findings begin to define a consensus sequence for ZMPSTE24 that helps to clarify how this physiologically important protease functions and may ultimately lead to identifying additional substrates.
Promoterless Transposon Mutagenesis Drives Solid Cancers via Tumor Suppressor Inactivation
Authors: Aiderus Aziz , Contreras-Sandoval Ana M. , Meshey Amanda L. , Newberg Justin Y. , Ward Jerrold M. , Swing Deborah , Copeland Neal G. , Jenkins Nancy A. , Mann Karen M. , Mann Michael B.
Published: August 2020

A central challenge in cancer genomics is the systematic identification of single and cooperating tumor suppressor genes driving cellular transformation and tumor progression in the absence of oncogenic driver mutation(s). Multiplein vitroandin vivogene inactivation screens have enhanced our understanding of the tumor suppressor gene landscape in various cancers. However, these studies are limited to single or combination gene effects, specific organs, or require sensitizing mutations. In this study, we developed and utilized aSleeping Beautytransposon mutagenesis system that functions only as a gene trap to exclusively inactivate tumor suppressor genes. Using whole body transposon mobilization in wild type mice, we observed that cumulative gene inactivation can drive tumorigenesis of solid cancers. We provide a quantitative landscape of the tumor suppressor genes inactivated in these cancers, and show that despite the absence of oncogenic drivers, these genes converge on key biological pathways and processes associated with cancer hallmarks.
Simultaneous smoothing and detection of topological units of genome organization from sparse chromatin contact count matrices with matrix factorization
Authors: Lee Da-Inn , Roy Sushmita
Published: August 2020

The three-dimensional (3D) organization of the genome plays a critical role in gene regulation for diverse normal and disease processes. High-throughput chromosome conformation capture (3C) assays, such as Hi-C, SPRITE, GAM, and HiChIP, have revealed higher-order organizational units such as topologically associating domains (TADs), which can shape the regulatory landscape governing downstream phenotypes. Analysis of high-throughput 3C data depends on the sequencing depth, which directly affects the resolution and the sparsity of the generated 3D contact count map. Identification of TADs remains a significant challenge due to the sensitivity of existing methods to resolution and sparsity. Here we present GRiNCH, a novel matrix-factorization-based approach for simultaneous TAD discovery and smoothing of contact count matrices from high-throughput 3C data. GRiNCH TADs are enriched in known architectural proteins and chromatin modification signals and are stable to the resolution, and sparsity of the input data. GRiNCH smoothing improves the recovery of structure and significant interactions from low-depth datasets. Furthermore, enrichment analysis of 746 transcription factor motifs in GRiNCH TADs from developmental time-course and cell-line Hi-C datasets predicted transcription factors with potentially novel genome organization roles. GRiNCH is a broadly applicable tool for the analysis of high throughput 3C datasets from a variety of platforms including SPRITE and HiChIP to understand 3D genome organization in diverse biological contexts.
The Role of Colony Temperature in the Entrainment of Circadian Rhythms of Honey Bee Foragers
Authors: Giannoni-Guzmán Manuel A. , Rivera Emmanuel , Aleman-Rios Janpierre , Moreno Alexander M. Melendez , Ramos Melina Perez , Pérez-Claudio Eddie , Loubriel Darimar , Moore Darrell , Giray Tugrul , Agosto-Rivera Jose L.
Published: August 2020

Honey bees utilize their circadian rhythms to accurately predict the time of day. This ability allows foragers to remember the specific timing of food availability and its location for several days. Previous studies have provided strong evidence toward light/dark cycles being the primary Zeitgeber for honey bees. Work in our laboratory described large individual variation in the endogenous period length of honey bee foragers from the same colony and differences in the endogenous rhythms under different constant temperatures. In this study, we further this work by examining temperature inside the honey bee colony. By placing temperature and light data loggers at different locations inside the colony we measured temperature at various locations within the colony. We observed significant oscillations of temperature inside the hive, that show seasonal patterns. We then simulated the observed temperature oscillations in the laboratory and found that using the temperature cycle as a Zeitgeber, foragers present large individual differences in the phase of locomotor rhythms with respect to temperature. Moreover, foragers successfully synchronize their locomotor rhythms to these simulated temperature cycles. Advancing the cycle by six hours, resulted in changes in the phase of activity in some foragers in the assay. The results shown in this study highlight the importance of temperature as a potential Zeitgeber in the field. Future studies will examine the possible functional and evolutionary role of the observed phase differences of circadian rhythms.
Shift work dynamics and division of labor: honeybee foraging and fanning tasks
Authors: Giannoni-Guzmán Manuel A. , Giray Tugrul , Agosto-Rivera Jose L.
Published: August 2020

In complex societies common social needs such as vigilance, care giving, resource gathering, and production are attended around the clock. In humans, these services are constantly provided using a shift work strategy where different individuals, or groups of individuals perform their tasks at different times of the day. However, shift work strategy in job organization in other social organisms remains unclear. Previous studies in honeybees for two jobs support shift work for only pollen foragers and not for nursing behavior. Here we examined shift work dynamics for three types of jobs performed by honeybee foragers. Specifically, we studied pollen foragers, non-pollen foragers and bees fanning at the entrance of the colony, a job important for orientation and temperature control. Major features of the observed shift work were: 1) individuals can be divided into early and late shifts; 2) there are constant workers; 3) based on job, shift work is performed by fewer or greater number of individuals; 4) shift work of an individual is plastic and may change with age; 5) foraging and fanning shifts are coupled yet dissociable. This study adds to the findings that shift work is not exclusive to modern human societies and that a natural form of shift work exists in honeybees. These results suggest that shift work in honeybees is a feature of worker division of labor. Future studies aiming to further understand the structure, function and mechanism of this natural form of shift work in honey bees not only could have an impact on agriculture but also may provide insight into alternative forms of shift work strategies that may reduce the various health problems associated with shift work in humans.
Vesicle capture by discrete self-assembled clusters of membrane-bound Munc13
Authors: Li Feng , Sundaram Venkat Kalyana , Gatta Alberto T. , Coleman Jeff , Krishnakumar Shyam S. , Pincet Frederic , Rothman James E.
Published: August 2020

Munc13 is a large banana-shaped soluble protein that is involved in the regulation of synaptic vesicle docking and fusion. Recent studies suggested that multiple copies of Munc13 form nanoassemblies in active zones of neurons. However, it is not known if such clustering is an inherent self-assembly property of Munc13 or whether Munc13 clusters indirectly by multivalent binding to synaptic vesicles or specific plasma membrane domains at docking sites in the active zone. The functional significance of putative Munc13 clustering is also unknown. Here we report that nano-clustering is an inherent property of Munc13, and is indeed required for vesicle binding to bilayers containing Munc13. Pure Munc13 reconstituted onto supported lipid bilayers assembled into clusters containing from 2 to ∼20 copies as revealed by a combination of quantitative TIRF microscopy and step-wise photobleaching. Surprisingly, only clusters a minimum of 6 copies of Munc13 were capable of efficiently capturing and retaining small unilamellar vesicles. The C-terminal C2C domain of Munc13 is not required for Munc13 clustering, but is required for efficient vesicle capture.