bluuebunny/crossref_metadata_2025 huggingface dataset:
High Resolution analysis of Transmission Dynamics of Sars-Cov-2 in Two Major Hospital Outbreaks in South Africa Leveraging Intrahost Diversity
Authors: James San Emmanuel , Ngcapu Sinaye , Kanzi Aquillah M , Tegally Houriiyah , Fonseca Vagner , Giandhari Jennifer , Wilkinson Eduan , Chimukangara Benjamin , Pillay Sureshnee , Singh Lavanya , Fish Maryam , Gazy Inbal , Khanyile Khulekani , Lessells Richard , de Oliveira Tulio
Published: November 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes acute, highly transmissible respiratory infection in both humans and wide range of animal species. Its rapid spread globally and devasting effects have resulted into a major public health emergency prompting the need for methodological interventions to understand and control its spread. In particular, The ability to effectively retrace its transmission pathways in outbreaks remains a major challenge. This is further exacerbated by our limited understanding of its underlying evolutionary mechanism. Using NGS whole-genome data, we determined whether inter- and intra-host diversity coupled with bottleneck analysis can retrace the pathway of viral transmission in two epidemiologically well characterised nosocomial outbreaks in healthcare settings supported by phylogenetic analysis. Additionally, we assessed the mutational landscape, selection pressure and diversity of the identified variants. Our findings showed evidence of intrahost variant transmission and evolution of SARS-CoV-2 after infection These observations were consistent with the results from the bottleneck analysis suggesting that certain intrahost variants in this study could have been transmitted to recipients. In both outbreaks, we observed iSNVs and SNVs shared by putative source-recipients pairs. Majority of the observed iSNVs were positioned in the S and ORF1ab region. AG, CT and TC nucleotide changes were enriched across SARS-COV-2 genome. Moreover, SARS-COV-2 genome had limited diversity in some loci while being highly conserved in others. Overall, Our findings show that the synergistic effect of combining withinhost diversity and bottleneck estimations greatly enhances resolution of transmission events in Sars-Cov-2 outbreaks. They also provide insight into the genome diversity suggesting purifying selection may be involved in the transmission. Together these results will help in developing strategies to elucidate transmission events and curtail the spread of Sars-Cov-2
Breadth of humoral immune responses to the C-terminus of the circumsporozoite protein is associated with protective efficacy induced by the RTS,S malaria vaccine
Authors: Chaudhury Sidhartha , MacGill Randall S. , Early Angela M. , Bolton Jessica S. , King C. Richter , Locke Emily , Pierson Tony , Wirth Dyann F. , Neafsey Daniel E. , Bergmann-Leitner Elke S.
Published: November 2020

The circumsporozoite protein (CSP) is the main surface antigen of malaria sporozoites and a prime vaccine target. Responses induced by the CSP-based RTS,S vaccine towards the polymorphic C-terminal region of P.falciparum-CSP raise concerns that vaccines using single alleles may have lower efficacy against genotypic variants. We characterized the extent of C-terminal cross-reactivity of antibodies induced by RTS,S (based on the 3D7 allele) with variants representing seven circulating field isolates through a novel HTS-multiplex assay for screening closely related peptides. Reactivity to variants showed approximately 30-fold reduction in recognition relative to 3D7. The degree of reduced cross-reactivity,ranging from 21 to 69-fold, directly correlated with the number of polymorphisms between variants and 3D7. Surprisingly, protection assessed by challenge with 3D7 parasites was strongly associated with higher C-terminal antibody breadth suggesting that C-terminal specific avidity or fine-specificity may play a role in RTS,S/AS01B-mediated protection and that breadth of C-terminal CSP-specific antibody responses may be a marker of protection.
Identifying cell type specific driver genes in autism-associated copy number loci from cerebral organoids
Authors: Lim Elaine T. , Chan Yingleong , Burns Mannix J. , Guo Xiaoge , Erdin Serkan , Tai Derek J.C. , Reichert Julia M. , Chan Ying Kai , Chiang Jessica J. , Meyers Katharina , Zhang Xiaochang , Walsh Christopher A. , Yankner Bruce A. , Raychaudhuri Soumya , Hirschhorn Joel N. , Gusella James F. , Talkowski Michael E. , Church George M.
Published: November 2020

Neuropsychiatric and neurodevelopmental disorders have been particularly challenging to study using animal models, and recently, human-derived cerebral organoids demonstrate great promise for discovering molecular processes that are important in these disorders. However, several challenges remain in achieving robust phenotyping to discover cell type specific genes. We perform RNA sequencing on 71 samples comprising of 1,420 cerebral organoids from 25 donors, and describe a framework (Orgo-Seq) to identify cell type specific driver genes, for 16p11.2 deletions and 15q11-13 duplications. We identify neuroepithelial cells as critical cell types for 16p11.2 deletions, and discover novel and previously reported cell type specific driver genes. Finally, we validated our results that mutations inKCTD13in the 16p11.2 locus lead to imbalances in the proportion of neuroepithelial cells, using CRISPR/Cas9-edited mosaic organoids. Our work presents a quantitative discovery and validation framework for identifying cell type specific driver genes associated with complex diseases using cerebral organoids.
Comprehensive mapping of tissue cell architecture via integrated single cell and spatial transcriptomics
Authors: Kleshchevnikov Vitalii , Shmatko Artem , Dann Emma , Aivazidis Alexander , King Hamish W , Li Tong , Lomakin Artem , Kedlian Veronika , Jain Mika Sarkin , Park Jun Sung , Ramona Lauma , Tuck Elizabeth , Arutyunyan Anna , Vento-Tormo Roser , Gerstung Moritz , James Louisa , Stegle Oliver , Bayraktar Omer Ali
Published: November 2020

The spatial organization of cell types in tissues fundamentally shapes cellular interactions and function, but the high-throughput spatial mapping of complex tissues remains a challenge. We present сell2location, a principled and versatile Bayesian model that integrates single-cell and spatial transcriptomics to map cell typesin situin a comprehensive manner. We show that сell2location outperforms existing tools in accuracy and comprehensiveness and we demonstrate its utility by mapping two complex tissues. In the mouse brain, we use a new paired single nucleus and spatial RNA-sequencing dataset to map dozens of cell types and identify tissue regions in an automated manner. We discover novel regional astrocyte subtypes including fine subpopulations in the thalamus and hypothalamus. In the human lymph node, we resolve spatially interlaced immune cell states and identify co-located groups of cells underlying tissue organisation. We spatially map a rare pre-germinal centre B-cell population and predict putative cellular interactions relevant to the interferon response. Collectively our results demonstrate how сell2location can serve as a versatile first-line analysis tool to map tissue architectures in a high-throughput manner.
Evolution of two-component quorum sensing systems
Authors: Giannakara Marina , Koumandou Vassiliki Lila
Published: November 2020

Quorum sensing (QS) is a cell-to-cell communication system that enables bacteria to coordinate their gene expression depending on their population density, via the detection of small molecules called autoinducers. In this way bacteria can act collectively to initiate processes like bioluminescence, virulence and biofilm formation. Autoinducers are detected by receptors, some of which are part of Two Component Signal Transduction Systems (TCS), which comprise of a (usually membrane-bound) sensor histidine kinase (HK) and a cognate response regulator (RR). Different QS systems are used by different bacterial taxa, and their relative evolutionary relationships have not been extensively studied. To address this, we used the KEGG database to identify all the QS HKs and RRs that are part of TCS and examined their conservation across microbial taxa. We compared the combinations of the highly conserved domains in the different families of receptors and response regulators using the SMART and KEGG databases, and we also carried out phylogenetic analyses for each family, and all families together. The distribution of the different QS systems across taxa, indicates flexibility in HK/RR pairing, and highlights the need for further study of the most abundant systems. For both the QS receptors and the response regulators, our analysis indicates close evolutionary relationships between certain families, highlighting a common evolutionary history which can inform future applications, such as the design of novel inhibitors for pathogenic QS systems.
Trimeric SARS-CoV-2 Spike proteins produced from CHO-cells in bioreactors are high quality antigens
Authors: Pino Paco , Kint Joeri , Kiseljak Divor , Agnolon Valentina , Corradin Giampietro , Kajava Andrey V. , Rovero Paolo , Dijkman Ronald , den Hartog Gerco , McLellan Jason S. , Byrne Patrick O. , Wurm Maria J , Wurm Florian M
Published: November 2020

The Spike protein of SARS-CoV-2 is essential for virus entry into human cells. In fact, most neutralizing antibodies against SARS-CoV-2 are directed against the Spike, making it the antigen of choice for use in vaccines and diagnostic tests. In the current pandemic context, global demand for Spike proteins has rapidly increased and could exceed hundreds of grams to kilograms annually. Coronavirus Spikes are large, heavily glycosylated, homotrimeric complexes, with inherent instability. Their poor manufacturability now threatens availability of these proteins for vaccines and diagnostic tests. Here, we outline a scalable, GMP-compliant, chemically defined process for production of a cell secreted, stabilized form of the trimeric Spike protein. The process is chemically defined and based on clonal, suspension-CHO cell populations and on protein purification via a two-step, scalable downstream process. The trimeric conformation was confirmed using electron microscopy and HPLC analysis. Binding to susceptible cells was shown using a virus-inhibition assay. The diagnostic sensitivity and specificity for detection of serum SARS-CoV-2 specific IgG1 was investigated and found to exceed that of Spike fragments (S1 and RBD). The process described here will enable production of sufficient high-quality trimeric Spike protein to meet the global demand for SARS-CoV-2 vaccines and diagnostic tests.
lra: the Long Read Aligner for Sequences and Contigs
Authors: Ren Jingwen , Chaisson Mark JP
Published: November 2020

Motivation

It is computationally challenging to detect variation by aligning long reads from single-molecule sequencing (SMS) instruments, or megabase-scale contigs from SMS assemblies. One approach to efficiently align long sequences is sparse dynamic programming (SDP), where exact matches are found between the sequence and the genome, and optimal chains of matches are found representing a rough alignment. Sequence variation is more accurately modeled when alignments are scored with a gap penalty that is a convex function of the gap length. Because previous implementations of SDP used a linear-cost gap function that does not accurately model variation, and implementations of alignment that have a convex gap penalty are either inefficient or use heuristics, we developed a method, lra, that uses SDP with a convex-cost gap penalty. We use lra to align long-read sequences from PacBio and Oxford Nanopore (ONT) instruments as well asde novoassembly contigs.

Results

Across all data types, the runtime of lra is between 52-168% of the state of the art aligner minimap2 when generating SAM alignment, and 9-15% of an alternative method, ngmlr. This alignment approach may be used to provide additional evidence of SV calls in PacBio datasets, and an increase in sensitivity and specificity on ONT data with current SV detection algorithms. The number of calls discovered using pbsv with lra alignments are within 98.3-98.6% of calls made from minimap2 alignments on the same data, and give a nominal 0.2-0.4% increase in F1 score by Truvari analysis. On ONT data with SV called using Sniffles, the number of calls made from lra alignments is 3% greater than minimap2-based calls, and 30% greater than ngmlr based calls, with a 4.6-5.5% increase in Truvari F1 score. When applied to calling variation from de novo assembly contigs, there is a 5.8% increase in SV calls compared to minimap2+paftools, with a 4.3% increase in Truvari F1 score.

Availability and implementation

Available in bioconda:https://anaconda.org/bioconda/lraand github:https://github.com/ChaissonLab/LRA

Contact

mchaisso@usc.edu,jingwenr@usc.edu
Chondrocytes in the resting zone of the growth plate are maintained in a Wnt-inhibitory environment
Authors: Hallett Shawn A. , Ono Wanida , Matsushita Yuki , Sakagami Naoko , Mizuhashi Koji , Tokavanich Nicha , Nagata Mizuki , Zhou Annabelle , Hirai Takao , Kronenberg Henry M. , Ono Noriaki
Published: November 2020

Chondrocytes in the resting zone of the postnatal growth plate are characterized by slow cell cycle progression, and encompass a population of parathyroid hormone-related protein (PTHrP)-expressing skeletal stem cells that contribute to the formation of columnar chondrocytes. However, how these chondrocytes are maintained in the resting zone remains undefined. We undertook a genetic pulse-chase approach to isolate slow cycling, label-retaining chondrocytes (LRCs) from the growth plate using a chondrocyte-specific doxycycline-controllable Tet-Off system regulating expression of histone 2B-linked GFP. Comparative RNA-seq analysis identified significant enrichment of inhibitors and activators for Wnt/β-catenin signaling in LRCs and non-LRCs, respectively. Activation of Wnt/β-catenin signaling in PTHrP+resting chondrocytes usingPthrp-creERandApc-floxed allele impaired their ability to form columnar chondrocytes. Therefore, slow-cycling chondrocytes are maintained in a canonical Wnt-inhibitory environment within the resting zone, unraveling a novel mechanism regulating maintenance and differentiation of PTHrP+skeletal stem cells of the postnatal growth plate.
Design and implementation of an intelligent framework for supporting evidence-based treatment recommendations in precision oncology
Authors: Lin Frank P.Y.
Published: November 2020

BACKGROUND

The advances in genome sequencing technologies have provided new opportunities for delivering targeted therapy to patients with advanced cancer. However, these high-throughput assays have also created a multitude of challenges for oncologists in treatment selection, demanding a new approach to support decision-making in clinics.

METHODS

To address this unmet need, this paper describes the design of a symbolic reasoning framework using the method of hierarchical task analysis. Based on this framework, an evidence-based treatment recommendation system was implemented for supporting decision-making based on a patient’s clinicopathologic and biomarker profiles.

RESULTS

This intelligent framework captures a six-step sequential decision process: (1) concept expansion by ontology matching, (2) evidence matching, (3) evidence grading and value-based prioritisation, (4) clinical hypothesis generation, (5) recommendation ranking, and (6) recommendation filtering. The importance of balancing evidence-based and hypothesis-driven treatment recommendations is also highlighted. Of note, tracking history of inference has emerged to be a critical step to allow rational prioritisation of recommendations. The concept of inference tracking also enables the derivation of a novel measure — level of matching — that helps to convey whether a treatment recommendation is drawn from incomplete knowledge during the reasoning process.

CONCLUSIONS

This framework systematically encapsulates oncologist’s treatment decisionmaking process. Further evaluations in prospective clinical studies are warranted to demonstrate how this computational pipeline can be integrated into oncology practice to improve outcomes.
Epigenetic Instability May Alter Cell State Transitions and Anticancer Drug Resistance
Authors: Saini Anshul , Gallo James M.
Published: November 2020

Drug resistance is a significant obstacle to successful and durable anti-cancer therapy. Targeted therapy is often effective during early phases of treatment; however, eventually cancer cells adapt and transition to drug-resistant cells states rendering the treatment ineffective. It is proposed that cell state can be a determinant of drug efficacy and manipulated to affect the development of anticancer drug resistance. In this work, we developed two stochastic cell state models – referenced to brain tumors - that included transcriptionally-permissive and -restrictive states based on the underlying hypothesis that epigenetic instability mitigates lock-in of drug-resistant states. One model used single-step state transitions, whereas the other considered a multi-step process to lock-in drug resistance. The latter model showed that with moderate epigenetic instability the drug-resistant cell populations were reduced, on average, by 60%, whereas a high level of epigenetic disruption reduced them by about 90%. Generation of epigenetic instability via epigenetic modifier therapy could be a viable strategy to mitigate anticancer drug resistance.
Genomic and anatomical comparisons of skin support independent adaptation to life in water by cetaceans and hippos
Authors: Springer Mark S. , Guerrero-Juarez Christian F. , Huelsmann Matthias , Collin Matthew A. , Danil Kerri , McGowen Michael R. , Oh Ji Won , Ramos Raul , Hiller Michael , Plikus Maksim V. , Gatesy John
Published: November 2020

The macroevolutionary transition from terra firma to obligatory inhabitance of the marine hydrosphere has occurred twice in the history of Mammalia: Cetacea and Sirenia. In the case of Cetacea (whales, dolphins, porpoises), molecular phylogenies provide unambiguous evidence that fully aquatic cetaceans and semiaquatic hippopotamids (hippos) are each other’s closest living relatives. Ancestral reconstructions further suggest that some adaptations to the aquatic realm evolved in the common ancestor of Cetancodonta (Cetacea+Hippopotamidae). An alternative hypothesis is that these adaptations evolved independently in cetaceans and hippos. Here, we focus on the integumentary system and evaluate these hypotheses by integrating new histological data for cetaceans and hippos, the first genome-scale data for pygmy hippopotamus, and comprehensive genomic screens and molecular evolutionary analyses for protein-coding genes that have been inactivated in hippos and cetaceans. We identified ten skin-related genes that are inactivated in both cetaceans and hippos, including genes that are related to sebaceous glands, hair follicles, and epidermal differentiation. However, none of these genes exhibit inactivating mutations that are shared by cetaceans and hippos. Mean dates for the inactivation of skin genes in these two clades serve as proxies for phenotypic changes and suggest that hair reduction/loss, the loss of sebaceous glands, and changes to the keratinization program occurred ~16 million years earlier in cetaceans (~46.5 Ma) than in hippos (~30.5 Ma). These results, together with histological differences in the integument and prior analyses of oxygen isotopes from stem hippopotamids (“anthracotheres”), support the hypothesis that aquatic adaptations evolved independently in hippos and cetaceans.
Multiscale PHATE Exploration of SARS-CoV-2 Data Reveals Multimodal Signatures of Disease
Authors: Kuchroo Manik , Huang Jessie , Wong Patrick , Grenier Jean-Christophe , Shung Dennis , Tong Alexander , Lucas Carolina , Klein Jon , Burkhardt Daniel , Gigante Scott , Godavarthi Abhinav , Israelow Benjamin , Mao Tianyang , Oh Ji Eun , Silva Julio , Takahashi Takehiro , Odio Camila D. , Casanovas-Massana Arnau , Fournier John ,   Yale IMPACT Team, Farhadian Shelli , Dela Cruz Charles S. , Ko Albert I. , Wilson F. Perry , Hussin Julie , Wolf Guy , Iwasaki Akiko , Krishnaswamy Smita
Published: November 2020

1

The biomedical community is producing increasingly high dimensional datasets, integrated from hundreds of patient samples, which current computational techniques struggle to explore. To uncover biological meaning from these complex datasets, we present an approach called Multiscale PHATE, which learns abstracted biological features from data that can be directly predictive of disease. Built on a continuous coarse graining process called diffusion condensation, Multiscale PHATE creates a tree of data granularities that can be cut at coarse levels for high level summarizations of data, as well as at fine levels for detailed representations on subsets. We apply Multiscale PHATE to study the immune response to COVID-19 in 54 million cells from 168 hospitalized patients. Through our analysis of patient samples, we identify CD16hiCD66bloneutrophil and IFNγ+GranzymeB+Th17 cell responses enriched in patients who die. Further, we show that population groupings Multiscale PHATE discovers can be directly fed into a classifier to predict disease outcome. We also use Multiscale PHATE-derived features to construct two different manifolds of patients, one from abstracted flow cytometry features and another directly on patient clinical features, both associating immune subsets and clinical markers with outcome.
A Universal Allosteric Mechanism for G Protein Activation
Authors: Knight Kevin M. , Ghosh Soumadwip , Campbell Sharon L. , Lefevre Tyler J. , Olsen Reid H. J. , Smrcka Alan V. , Valentin Natalie H. , Yin Guowei , Vaidehi Nagarajan , Dohlman Henrik G.
Published: November 2020

G proteins play a central role in signal transduction and pharmacology. Signaling is initiated by cell-surface receptors, which promote GTP binding and the dissociation of Gα from the Gβγ subunits. Structural studies have revealed the molecular basis for subunit association with receptors, RGS proteins and downstream effectors. In contrast, the mechanism of subunit dissociation is poorly understood. We used cell signaling assays, MD simulations, biochemistry and structural analysis to identify a conserved network of amino acids that dictates subunit release. In the presence of the terminal phosphate of GTP, a glycine forms a polar network with an arginine and glutamate, putting torsional strain on the subunit binding interface. This “G-R-E motif” secures GTP and, through an allosteric link, discharges the Gβγ dimer. Replacement of network residues prevents subunit dissociation, regardless of agonist or GTP binding. These findings reveal the molecular basis for the final committed step of G protein activation.

HIGHLIGHTS

Receptors promote GTP-GDP exchange and dissociation of G protein α and βγ subunits

We find an allosteric network linking the γ phosphate of GTP with release of Gβγ

The network consists of a conserved Gly-Arg-Glu “activation triad”

Triad mutations prevent subunit dissociation, regardless of agonist or GTP binding

Triad mutations are responsible for human endocrine and neurological disorders
α-Synuclein emerges as a potent regulator of VDAC-facilitated calcium transport
Authors: Rosencrans William M. , Aguilella Vicente M. , Rostovtseva Tatiana K. , Bezrukov Sergey M.
Published: November 2020

When the Parkinson’s disease (PD) related neuronal protein, alpha-synuclein (αSyn), is added to the reconstituted mitochondrial voltage-dependent anion channel (VDAC), it reversibly and partially blocks VDAC conductance by its acidic C-terminal tail. Using single-molecule electrophysiology of reconstituted VDAC we now demonstrate that, at CaCl2concentrations below 150 mM, αSyn reverses the channel’s selectivity from anionic to cationic. Importantly, we find that the decrease in channel conductance upon its blockage by αSyn is hugely overcompensated by a favorable change in the electrostatic environment for calcium, making the blocked state orders-of-magnitude more selective for calcium and thus increasing its net flux. These findings reveal a new regulatory role of αSyn, with clear implications for both normal calcium signaling and PD-associated mitochondrial dysfunction.
The selective estrogen receptor modulator tamoxifen protects against subtle cognitive decline and early markers of injury twenty-four hours after hippocampal silent infarct
Authors: Finney Caitlin A. , Shvetcov Artur , Westbrook R. Frederick , Morris Margaret J. , Jones Nicole M.
Published: November 2020

Silent infarcts (SI) are subcortical cerebral infarcts that occur in the absence of typical symptoms associated with ischemia but are linked to cognitive decline and the development of dementia. There are no approved treatments for SI, but one potential treatment is tamoxifen, a selective estrogen receptor modulator. While SI can have long-term consequences, it is critical to establish whether treatments are able to selectively target its early consequences, to avoid progression to complete injury. We induced SI in the dorsal hippocampal CA1 of rats and assessed whether tamoxifen is protective 24 hours later against cognitive deficits and injury responses to SI including gliosis, apoptosis, inflammation and changes in estrogen receptors (ERs). Hippocampal SI led to subtle cognitive impairment on the object place recognition task, an effect ameliorated by tamoxifen administration. SI did not lead to detectable hippocampal cell loss but did increase apoptosis, astrogliosis, microgliosis and inflammation. Tamoxifen protected against the effects of SI on all measures except microgliosis. SI also increased ERα and decreased ERβ in the hippocampus, which was again mitigated by tamoxifen. Exploratory data analyses using scatterplot matrices and principal component analysis indicated that the SI rats given tamoxifen were indistinguishable from sham controls. Further, SI rats were significantly different from all other groups, an effect produced by low levels of ERα and increased apoptosis, gliosis, inflammation, ERβ, and time spent with the unmoved object. The results demonstrate that tamoxifen is protective against the early cellular and cognitive consequences of hippocampal SI as early as 24 hours after injury. This effect is driven by mitigation of apoptosis, gliosis, and inflammation and normalization of ER levels in the CA1, leading to improved cognitive outcomes after hippocampal SI.
Distinct hydrogenotrophic bacteria are stimulated by elevated H2levels in upland and wetland soils
Authors: Xu Yongfeng , Teng Ying , Dong Xiyang , Wang Xiaomi , Zhang Chuwen , Ren Wenjie , Zhao Ling , Luo Yongming , Greening Chris
Published: November 2020

Background

Molecular hydrogen (H2) is a major energy source supporting bacterial growth and persistence in soil ecosystems. While recent studies have uncovered mediators of atmospheric H2consumption, far less is understood about how soil microbial communities respond to elevated H2levels produced through natural or anthropogenic processes. Here we performed microcosm experiments to resolve how microbial community composition, capabilities, and activities change in upland (meadow, fluvo-aquic soil) and wetland (rice paddy, anthrosols soil) soils following H2supplementation (at mixing doses from 0.5 to 50,000 ppmv).

Results

Genome-resolved metagenomic profiling revealed that these soils harbored diverse bacteria capable of using H2as an electron donor for aerobic respiration (46 of the 196 MAGs from eight phyla) and carbon fixation (15 MAGs from three phyla). H2stimulated the growth of several of these putative hydrogenotrophs in a dose-dependent manner, though the lineages stimulated differed between the soils; whereas actinobacterial lineages encoding group 2a [NiFe]-hydrogenases grew most in the upland soils (i.e. Mycobacteriaceae, Pseudonocardiaceae), proteobacterial lineages harboring group 1d [NiFe]-hydrogenases were most enriched in wetland soils (i.e. Burkholderiaceae). Hydrogen supplementation also influenced the abundance of various other genes associated with biogeochemical cycling and bioremediation pathways to varying extents between soils. Reflecting this, we observed an enrichment of a hydrogenotrophicNoviherbaspirillumMAG capable of biphenyl hydroxylation in the wetland soils and verified that H2supplementation enhanced polychlorinated biphenyl (PCB) degradation in these soils, but not the upland soils.

Conclusions

Our findings suggest that soils harbour different hydrogenotrophic bacteria that rapidly grow following H2exposure. In turn, this adds to growing evidence of a large and robust soil H2sink capable of counteracting growing anthropogenic emissions.
Effects of water content and mesh size on tea bag decomposition
Authors: Mori Taiki , Aoyagi Ryota , Taga Hiroki , Sakai Yoshimi
Published: November 2020

The tea bag method was developed to provide uniform litter bags that enable comparison of organic matter decomposition rates on a large scale. However, it remains uncertain whether tea bag decomposition in response to wetness is representative of that of natural litters. We performed incubation experiments to examine whether the effect of soil water on tea bag decomposition becomes inhibitory at higher water contents, as was demonstrated in natural leaf litters. In addition, we performed field studies in a mixed forest and cedar plantation in Japan to compare two litter bag mesh sizes: 0.25-mm mesh, the size previously used by a major manufacturer of tea bags (Lipton), and nonwoven bags with mesh sizes finer than 0.25 mm, which are currently produced by Lipton. Both green tea and rooibos tea exhibited higher decomposition rates at higher water contents, but decomposition was inhibited at the highest water content, consistent with conceptual models of natural litters. The nonwoven tea bags did not show lower decomposition rates, despite the finer mesh size. Rather, the nonwoven rooibos tea bags exhibited slightly higher decomposition rates than the 0.25-mm mesh bags in the cedar plantation, possibly due to a greater abundance of microorganisms that decompose litters in the nonwoven bags, due to the decrease in predation by mesofauna. Our findings provide essential information for future studies of tea bag decomposition.
Studying trajectories of multimorbidity: a systematic scoping review of longitudinal approaches and evidence
Authors: Cezard Genevieve , McHale Calum , Sullivan Frank , Bowles Juliana , Keenan Katherine
Published: November 2020

Objectives

Multimorbidity – the co-occurrence of at least two chronic diseases in an individual-is an important public health challenge in ageing societies. The vast majority of multimorbidity research takes a cross-sectional approach, but longitudinal approaches to understanding multimorbidity are an emerging research area, being encouraged by multiple funders. To support development in this research area, the aim of this study is to scope the methodological approaches and substantive findings of studies which have investigated longitudinal multimorbidity trajectories.

Design

We conducted a systematic search for relevant studies in four online databases (Medline, Scopus, Web of Science, and Embase) using pre-defined search terms and inclusion and exclusion criteria. The search was complemented by searching reference lists of relevant papers. From the selected studies we systematically extracted data on study methodology and findings, and summarised them in a narrative synthesis.

Results

We identified 34 studies investigating multimorbidity longitudinally, all published in the last decade, and predominantly in high-income countries from the Global North. Longitudinal approaches employed included constructing change variables, multilevel regression analysis (e.g. growth curve modelling), longitudinal group-based methodologies (e.g. latent class modelling), analysing disease transitions, and visualisation techniques. Commonly identified risk factors for multimorbidity onset and progression were older age, higher socio-economic and area-level deprivation, overweight, and poorer health behaviours.

Conclusion

The nascent research area employs a diverse range of longitudinal approaches that characterize accumulation and disease combinations, and to a lesser extent disease sequencing and progression. Gaps include understanding the long-term, life course determinants of different multimorbidity trajectories, and doing so in across diverse populations, including those from low and middle-income countries. This can provide a detailed picture of morbidity development, with important implications from a clinical and intervention perspective.

STRENGTHS AND LIMITATIONS OF THE STUDY

This is the first systematic review to focus on studies that take a longitudinal, rather than cross-sectional, approach to multimorbidity.

Systematic searches of online academic databases were performed using pre-defined search terms, as well as searching of reference lists, and this is reported using PRISMA guidelines.

For selected papers, data was double extracted using standardised proformas to aid narrative synthesis.

Due to the heterogeneity of the studies included, their weaknesses were described in the narrative synthesis, but we did not perform quality assessment using standardised tools.
Clustering of death receptor for apoptosis using nanoscale patterns of peptides
Authors: Wang Yang , Baars Igor , Fördös Ferenc , Högberg Björn
Published: November 2020

The nanoscale spatial organization of transmembrane tumor necrosis factor (TNF) receptors has been implied as a regulator of cellular fate. Accordingly, molecular tools that can induce specific arrangements of these receptors on cell surfaces would give us an opportunity to study these effects in detail. To achieve this, we introduce DNA origami nanostructures, that precisely scaffold the patterning of TNF-related apoptosis-inducing ligand (TRAIL)-mimicking peptides at nanoscale level. Stimulating human breast cancer cells with these patterns, we find that around 5 nm is the critical inter-ligand distance of hexagonally patterned peptides to induce death receptor clustering and a resulting apoptosis. We thus offer a strategy to reverse the non-efficacy of current ligand- and antibody-based methods for TNF superfamily (TNFRSF) activation.
A RNF12-USP26 amplification loop promotes germ cell specification and is disrupted in urogenital disorders
Authors: Segarra-Fas Anna , Bustos Francisco , Toth Rachel , Nardocci Gino , Findlay Greg M.
Published: November 2020

Ubiquitylation regulates all aspects of development, and components are frequently mutated in developmental disorders. Tonne-Kalscheuer Syndrome (TOKAS) is a X-linked multiple congenital anomaly disorder caused by mutations in the E3 ubiquitin ligase RNF12/RLIM and characterized by intellectual disability and urogenital abnormalities. However, the molecular underpinnings of TOKAS remain largely unknown. Here, we show that RNF12 catalytic activity relieves gene repression to drive a transcriptional program required for germ cell development and priming of pluripotent cells towards the germline. A major feature of the RNF12-dependent gametogenesis gene program is a transcriptional feed-forward loop featuring the deubiquitylaseUsp26/USP26.Usp26/USP26 induction stabilises RNF12 to amplify transcriptional responses, which is disrupted by RNF12 TOKAS mutations and USP26 variants identified in patients with fertility defects. In summary, we uncover remarkable synergy within a ubiquitylation cycle that controls expression of key genes required for germ cell development and is disrupted in patients with urogenital abnormalities.
The nature of mitotic forces in epithelial monolayers
Authors: Gupta Vivek K. , Nam Sungmin , Camuglia Jaclyn , Martin Judy Lisette , Sanders Erin Nicole , O’Brien Lucy Erin , Martin Adam C. , Kim Taeyoon , Chaudhuri Ovijit
Published: November 2020

Epithelial cells undergo striking morphological changes during mitosis to ensure proper segregation of genetic and cytoplasmic materials. These morphological changes occur despite dividing cells being mechanically restricted by neighboring cells, indicating the need for extracellular force generation. While forces generated during mitotic rounding are well understood, forces generated after rounding remain unknown. Here, we identify two distinct stages of mitotic force generation that follow rounding: (1) protrusive forces along the mitotic axis that drive mitotic elongation, and (2) outward forces that facilitate post-mitotic re-spreading. Cytokinetic ring contraction of the mitotic cell, but not activity of neighboring cells, generates extracellular forces that propel mitotic elongation and also contribute to chromosome separation. Forces from mitotic elongation are observed in epithelia across many model organisms. Thus, forces from mitotic elongation represent a universal mechanism that powers mitosis in confining epithelia.
Sedimentary ancient DNA shows terrestrial plant richness continuously increased over the Holocene in northern Fennoscandia
Authors: Rijal Dilli P. , Heintzman Peter D. , Lammers Youri , Yoccoz Nigel G. , Lorberau Kelsey E. , Pitelkova Iva , Goslar Tomasz , Murguzur Francisco J.A. , Salonen J. Sakari , Helmens Karin F. , Bakke Jostein , Edwards Mary E. , Alm Torbjørn , Bråthen Kari A. , Brown Antony G. , Alsos Inger G.
Published: November 2020

The effects of climate change on species richness is debated but can be informed by the past. Here, we assess the impact of Holocene climate changes and nutrients on terrestrial plant richness across multiple sites from northern Fennoscandia using new sedimentary ancient DNA (sedaDNA) data quality control methods. We find that richness increased steeply during the rapidly warming Early Holocene. In contrast to findings from most pollen studies, we show that richness continued to increase through the Middle to Late Holocene even though temperature decreased, with the regional species pool only stabilizing during the last two millennia. Furthermore, overall increase in richness was greater in catchments with higher soil nutrient availability. We suggest that richness will rapidly increase with ongoing warming, especially at localities with high nutrient availability and even in the absence of increased human activity in the region, although delays of millennia may be expected.
Modeling of symbiotic bacterial biofilm growth with an example of theStreptococcus-Veillonellasp. system
Authors: Feng Dianlei , Neuweiler Insa , Nogueira Regina , Nackenhorst Udo
Published: November 2020

We present a multi-dimensional continuum mathematical model for modeling the growth of a symbiotic biofilm system. We take a dual-species namely, theStreptococcus - Veillonellasp. biofilm system as an example for numerical investigations. The presented model describes both the cooperation and competition between these species of bacteria. The coupled partial differential equations are solved by using an integrative finite element numerical strategy. Numerical examples are carried out for studying the evolution and distribution of the bio-components. The results demonstrate that the presented model is capable of describing the symbiotic behavior of the biofilm system. However, homogenized numerical solutions are observed locally. To study the homogenization behavior of the model, numerical investigations regarding on how random initial biomass distribution influences the homogenization process are carried out. We found that a smaller correlation length of the initial biomass distribution leads to faster homogenization of the solution globally, however, shows more fluctuated biomass profiles along the biofilm thickness direction. More realistic scenarios with bacteria in patches are also investigated numerically in this study.
TNF stimulation primarily modulates transcriptional burst size of NF-κB-regulated genes
Authors: Bass Victor L. , Wong Victor C. , Bullock M. Elise , Gaudet Suzanne , Miller-Jensen Kathryn
Published: November 2020

Cell-to-cell heterogeneity is a characteristic feature of the tumor necrosis factor (TNF)-stimulated inflammatory response mediated by the transcription factor NF-κB, motivating an exploration of the underlying sources of this noise. Here we combined single-transcript measurements with computational models to study transcriptional noise at six NF-κB-regulated inflammatory genes. In the basal state, NF-κB-target genes displayed an inverse correlation between mean and noise. TNF stimulation increased transcription while maintaining noise, except for the most repressed genes. By fitting transcript distributions to a two-state model of promoter activity, we found that TNF primarily stimulated transcription by increasing burst size while maintaining burst frequency. Burst size increases were associated with enrichment of initiated-but-paused RNA polymerase II at the promoter, and blocking the release of paused RNAPII with a small molecule inhibitor decreased TNF-stimulated burst size. Finally, we used a mathematical model to show that TNF positive feedback further amplified gene expression noise resulting from burst-size mediated transcription, leading to diverse TNF functional outputs. Our results reveal potential sources of noise underlying intercellular heterogeneity in the TNF-mediated inflammatory response.
Trees and their seed networks: the social dynamics of urban fruit trees and implications for genetic diversity
Authors: Rimlinger Aurore , Avana Marie-Louise , Awono Abdon , Chakocha Armel , Gakwavu Alexis , Lemoine Taïna , Marie Lison , Mboujda Franca , Vigouroux Yves , Johnson Vincent , Vinceti Barbara , Carrière Stéphanie M. , Duminil Jérôme
Published: November 2020

Trees are a traditional component of urban spaces where they provide ecosystem services critical to urban wellbeing. In the Tropics, urban trees’ seed origins have rarely been characterized. Yet, understanding the social dynamics linked to tree planting is critical given their influence on the distribution of associated genetic diversity. This study examines elements of these dynamics (seed exchange networks) in an emblematic indigenous fruit tree species from Central Africa, the African plum tree (Dacryodes edulis, Burseraceae), within the urban context of Yaoundé. We further evaluate the consequences of these social dynamics on the distribution of the genetic diversity of the species in the city. Urban trees were planted predominantly using seeds sourced from outside the city, resulting in a level of genetic diversity as high in Yaoundé as in a whole region of production of the species. Debating the different drivers that foster the genetic diversity in planted urban trees, the study argued that cities and urban dwellers can unconsciously act as effective guardians of indigenous tree genetic diversity.
Seizing diminishing habitat conservation and restoration opportunities in the Tampa Bay, FL watershed: An urban estuary in recovery
Authors: Raulerson Gary E , Robison Douglas E , Beck Marcus W , Burke Maya C , Ries Thomas F , Saarinen Justin A , Sciarrino Christine M , Sherwood Edward T , Tomasko David A
Published: November 2020

Habitat restoration efforts should integrate past trends, current status, expected climate change and coastal development impacts, remaining realistic opportunities, and resource management community capabilities. Integrating these concepts, a new target setting approach is being implemented in the Tampa Bay region with broad transferability potential. Past changes, as determined through a three-decade habitat change analysis and over forty years of habitat restoration experience in the region, has informed the new approach. It is also primarily focused on what is possible today and the projected needs for the future, rather than focusing on or attempting to replicate past ecological conditions. Likewise, this new paradigm accounts for persistent local and global stressors – especially watershed development, sea level rise, and climate change. As such, newly established numeric targets are “place-based,” meaning that they attempt to maximize the remaining restoration and conservation “opportunity areas” within the watershed. Lastly, the approach is comprehensive in that targets for the range of critical habitats, from subtidal to uplands, are now defined. This approach represents a general framework for addressing competing interests in planning for habitat restoration that could be applied in other coastal settings where sustainable urbanization practices are desired to co-exist with natural environments.
Comprehensive studies of Head Maralla, Punjab, Pakistan vegetation for ethnopharmacological and ethnobotanical uses and their elaboration through quantitative indices
Authors: Iqbal Muhammad Sajjad , Ali Muhammad Azhar , Akbar Muhammad , Hussain Syed Atiq , Arshad Noshia , Munir Saba , Masood Hajra , Zafar Samina , Ahmad Tahira , Shaheen Nazra , Mashooq Rizwana , Sajjad Hifsa , Zahoor Munaza , Bashir Faiza , Shahbaz Khizra , Arshad Hamna , Fatima Noor , Nasir Faiza , Hashmi Ayesha Javed , Chaudhary Sofia , Waqas Ahmad , Islam Muhammad
Published: November 2020

Head Maralla is a non-recognized wetland with diversified flora that becomes focus of current studies. Whole plant or their parts are being used for treating various maladies and they are the integral part of livelihood in the area. Unique species includingOsmunda regalisis used for blood and renal diseases purifier. Wild plant resources are key to traditional ethnobotanical knowledge based practices and industrial applications. Current study reports Head Marala inhabitant’s interaction with these resources and identify priorities at species and habitat level for conservation. Four sites viz., River Tavi, Upstream Chenab, River Manawarwala Tavi and Bhalolpur were designated to record traditional knowledge through questionnaire and interviews during field trips. One hundred nineteen (119) plant species were identified belonging to 54 families, of which 87 species were of dicot, 12monocots, 05ferns, and 4 species of bryophytes. Fifty percent of the plant species were utilized as a whole for therapeutic purposes, followed by leaves which had more than 20% usage of total consumption. Ailments viz., urination (14%) followed by cough (8%), cold (7%), stomach (6%), asthma (6%), constipation (5%), laxative (5%), diarrhea (4%) etc., were associated with vegetation. Bronchial disorders, pneumonia, dyspepsia, anthelmintic and kidney stones, etc., were also among other diseases commonly cured by traditional knowledge. Fifteen percent of vegetation contributes as fodder species consumed by local community for livestock while almost 17% of local plants were utilized for industrial purposes like timber, fuel, furniture, wooden pots and sports goods. In conclusion the ecosystem of Head Maralla is a complex of aquatic, terrestrial and agricultural land that is located on climatic and geographical divides, which further add to botanical interest as included many wetland habitats with unique diversity of plants. It is suggested to devise comprehensive conservation strategies to safe indigenous knowledge in systematic way for comprehending ecological services.