bluuebunny/crossref_metadata_2025 huggingface dataset:
A continental scale analysis reveals widespread root bimodality
Authors: Lu Mingzhen , Wang Sili , Malhotra Avni , Tumber-Dávila Shersingh Joseph , Weintraub-Leff Samantha , McCormack Luke , Wang Xingchen Tony , Jackson Robert B.
Published: September 2022

Summary paragraph

Recent studies of plant fine roots have greatly advanced our understanding of their geometric properties and symbiotic relationships, but knowledge of how these roots are spatially distributed across the soil matrix lags far behind. An improved understanding of broad-scale variability in root vertical distribution is critical for understanding plant-soil-atmosphere interactions and their influence on the land carbon sink. Here we analyze a continental-scale dataset of plant roots reaching 2-meters depth, spanning 19 ecoclimatic domains ranging from Alaskan tundra to Puerto Rican neotropical forest. Contrary to the common expectation that fine root abundance decays exponentially with increasing soil depth, we found surprising root bimodality at ~20% of 44 field sites —a secondary peak of fine root biomass far beneath the soil surface. All of the secondary root peaks were observed deeper than 60cm (with 33% below 1m), far deeper than the sampling depth commonly used in ecosystem studies and forestry surveys. We demonstrate that root bimodality is more likely in places with relatively low total fine root biomass, and is more frequently associated with shrubland vegetation but less with grassland. Further statistical analyses revealed that the secondary peak of root biomass coincided with unexpected high soil nitrogen contents at depth. By linking roots and nutrient distributions, we further demonstrate that deep soil nutrients tend to be underexploited by plant rooting systems, yet root bimodality offers a unique mechanism by which fine roots can tap into soil resources in the deep. Our findings suggest that empirical practices have often systematically overlooked root dynamics in deep soils, and as a result the current-generation global climate and vegetation models have relied on overly simplistic assumptions for plant rooting distribution.
An intragenic FAT1 regulatory element deleted in muscular dystrophy patients drives muscle and mesenchyme expression during development
Authors: Caruso Nathalie , Zimmermann Angela K , Nigam Tarana , Becker Celine , Lipson Karelia , Helmbacher Françoise
Published: September 2022

Fat1 is an atypical cadherin playing multiple roles that influence tissue morphogenesis. During mouse development Fat1 is required to modulate muscle morphogenesis through complementary activities in myogenic cells, muscle-associated connective tissue, and motor neurons, ablation of which leads to regionalized muscle phenotypes. We previously identified copy number variants (CNV) deleting an intragenic conserved non-coding element (CNE) in the human FAT1 locus, that were enriched among muscular dystrophy patients with symptoms resembling those of Facioscapulohumeral Dystrophy (FSHD), compared to healthy individuals. Since such deletions of a putative cis-regulatory element had the potential to cause tissue-specific depletion of FAT1, they were postulated to act as symptom modifiers. However, activity of this CNE has not been functionally explored so far. To investigate the possible regulatory activity of this Fat1-CNE, we engineered transgenic mice in which it drives expression of a bi-cistronic reporter comprising the CRE-recombinase (Cre) and a myristilated-tdTomato fluorescent protein. The tissue-specific pattern of cre and tomato expression indicates that this enhancer has bipotential character, and drives expression in skeletal muscle and in muscle-associated mesenchymal cells. We extended our analysis of one of the transgenic lines, which exhibits enhanced expression in mesenchymal cells at extremities of subsets of muscles matching the map of Fat1-dependent muscles. This transgenic line exhibits highly selective CRE-mediated excision in scattered cells within the Tomato-positive territory hotspots. This represents a novel tool to genetically explore the diversity of muscle-associated mesenchymal lineages.
Ancient DNA Reveals China as a Historical Genetic Melting Pot in Tiger Evolution
Authors: Sun Xin , Liu Yue-Chen , Tiunov Mikhail P. , Gimranov Dmitry O. , Zhuang Yan , Han Yu , Driscoll Carlos A. , Pang Yu-Hong , Li Chunmei , Pan Yan , Velasco Marcela Sandoval , Gopalakrishnan Shyam , Yang Rui-Zheng , Li Bao-Guo , Jin Kun , Xu Xiao , Uphyrkina Olga , Huang Yan-Yi , Wu Xiao-Hong , Gilbert M. Thomas P. , O’Brien Stephen J. , Yamaguchi Nobuyuki , Luo Shu-Jin
Published: September 2022

The contrast between the tiger’s (Panthera tigris) 2-3 My age and extant tigers’ coalescence approximately 110,000 years ago suggests an ancient demographic bottleneck. Here we collected over 60 extinct specimens across mainland Asia and generated whole genome sequences from a 10,600-year-old Russian Far East (RFE) specimen (RUSA21, 8ξ coverage), 14 South China tigers (0.1-12ξ), three Caspian tigers (4-8ξ), plus 17 new mitogenomes. RUSA21 clustered within modern Northeast Asian phylogroups and partially derived from an extinct Late Pleistocene lineage. While some 8,000-10,000-year-old RFE mitogenomes are basal to all tigers, one 2,000-year-old specimen resembles present Amur tigers. The Caspian tiger likely dispersed from an ancestral Northeast Asian population and experienced gene flow from southern Bengal tigers. Lastly, genome-wide monophyly supported the South China tiger as a distinct subspecies, albeit with mitochondrial paraphyly, hence resolving its longstanding taxonomic controversy. The distribution of mitochondrial haplogroups corroborated by biogeographical modeling suggested Southwest China was a Late Pleistocene refugium for a relic basal lineage. As suitable habitat returned, Eastern China became a genetic melting pot to foster divergent lineages to merge into South China tigers and other subsequent northern subspecies to develop. Genomic information retrieved from ancient tigers hence sheds light on the species’ full evolutionary history leading to nine modern subspecies and resolves the natural history of surviving tigers.
First mitogenome phylogeny of the sun bear Helarctos malayanus reveals a deep split between Indochinese and Sundaic lineages
Authors: Kunde Miriam N. , Barlow Axel , Klittich Achim , Yakupova Aliya , Patel Riddhi P. , Fickel Jörns , Förster Daniel W.
Published: September 2022

The sun bear Helarctos malayanus is one of the most endangered ursids, and to date classification of sun bear populations has been based almost exclusively on geographic distribution and morphology. The very few molecular studies focusing on this species were limited in geographic scope. Using archival and non-invasively collected sample material, we have added a substantial number of complete or near-complete mitochondrial genome sequences from sun bears of several range countries of the species’ distribution. We here report 32 new mitogenome sequences representing sun bears from Cambodia, Thailand, Peninsular Malaysia, Sumatra and Borneo. Reconstruction of phylogenetic relationships revealed two matrilines that diverged ∼290 thousand years ago: one restricted to portions of mainland Indochina (China, Cambodia, Thailand; “Mainland clade”), and one comprising bears from Borneo, Sumatra, Peninsular Malaysia but also Thailand (“Sunda clade”). Generally recent coalescence times in the mitochondrial phylogeny suggest that recent or historical demographic processes have resulted in a loss of mtDNA variation. Additionally, analysis of our data in conjunction with shorter mtDNA sequences revealed that the Bornean sun bear, classified as a distinct subspecies (H. m. euryspilus), does not harbour a distinctive matriline. Further molecular studies of H. malayanus are needed, which should ideally include data from nuclear loci.
DNA methylation supports accelerated biological age in Type 2 Diabetes which can be reversed with pharmacological treatments: Retrospective Cohort Study
Authors: Cortez Briana N. , Pan Hui , Aguayo-Mazzucato Cristina
Published: September 2022

Background

Biological age (BA) closely depicts age-related changes at a cellular level. Type 2 Diabetes mellitus (T2D) accelerates BA when calculated using clinical biomarkers. However, there is a large spread of individual BA within these groups and it is unclear what clinical biomarkers correlate with different speeds of aging and whether pharmacological treatment of diabetes alter BA. We hypothesized that accelerated BA would be seen at the DNA methylation (DNAm) level, the gold standard to determine BA, and biomarkers and treatments would correlate the rate of BA in T2D.

Methods

Publicly available DNAm samples were obtained from the GEO NCBI database and the NHANES 2017-2018 and ACCORD Cohorts were used for our analysis. We used the DNA Methylation Phenotypic Age algorithm and the Klemera and Doubal (KDM) methods to calculate BA with DNA methylation and clinical biomarkers, respectively.

Results

DNAm showed increased BA in whole blood and pancreatic islets in T2D in aging-related pathways, such as DNA damage and inflammation. Using the NHANES and ACCORD Trial cohorts, we found that avoidance of fried and fatty foods, and vigorous activity correlated with decreased BA in T2D. Cardiovascular, glycemic, and inflammatory biomarkers associated with the rate of aging in DM. Intensive blood pressure and T2D treatment associated with a greater deceleration in the speed of aging as compared to the standard.

Conclusions

Overall, we show that certain tissues age faster in people with T2D and this strongly associates with blood glucose control, inflammation and cardiovascular health. Effective treatment of the disease can decelerate aging and decrease BA suggesting the latter as a novel and integrated index to evaluate and follow people with T2D.

Funding

This study was supported by Institutional Startup Funds to C.A.M. (Joslin Diabetes Center) and NIH grants P30 DK036836 Joslin Diabetes Research Center (Bioinformatic Core).
Rapid learning of neural circuitry from holographic ensemble stimulation enabled by model-based compressed sensing
Authors: Triplett Marcus A. , Gajowa Marta , Antin Benjamin , Sadahiro Masato , Adesnik Hillel , Paninski Liam
Published: September 2022

Discovering how neural computations are implemented in the cortex at the level of monosynaptic connectivity requires probing for the existence of synapses from possibly thousands of presynaptic candidate neurons. Two-photon optogenetics has been shown to be a promising technology for mapping such monosynaptic connections via serial stimulation of neurons with single-cell resolution. However, this approach is limited in its ability to uncover connectivity at large scales because stimulating neurons one-by-one requires prohibitively long experiments. Here we developed novel computational tools that, when combined, enable learning of monosynaptic connectivity from high-speed holographic neural ensemble stimulation. First, we developed a model-based compressed sensing algorithm that identifies connections from postsynaptic responses evoked by stimulation of many neurons at once, considerably increasing the rate at which the existence and strength of synapses are screened. We show that this model-based approach, explicitly incorporating known biophysics of optogenetic mapping experiments, is critical for accurately determining synaptic connectivity using compressed sensing. Second, we developed a deep learning method that isolates the postsynaptic response evoked by each stimulus, allowing stimulation to rapidly switch between ensembles without waiting for the postsynaptic response to return to baseline. We then validated our approach by performing large-scale connectivity mapping experiments in slices from layer 2/3 of mouse primary visual cortex. Together, our system increases the throughput of monosynaptic connectivity mapping by an order of magnitude over existing approaches, enabling the acquisition of connectivity maps at speeds needed to discover the synaptic circuitry implementing neural computations.
Improving 3D Edge Detection for Visual Inspection of MRI Coregistration and Alignment
Authors: Rorden Chris , Newman-Norlund Roger , Drake Chris , Glen Daniel R. , Fridriksson Julius , Hanayik Taylor , Taylor Paul A.
Published: September 2022

Detecting and visualizing edges is important in several neuroimaging and medical imaging applications. For example, it is common to use edge maps to ensure the automatic alignment of low-resolution functional MRI images to match a high-resolution structural image has been successful. Specifically, software toolboxes like FSL and AFNI generate volumetric edge maps that can be particularly useful for visually assessing the alignment of datasets, overlaying the edge map of one on the other. Therefore, edge maps play a crucial role in quality assurance. Popular methods for computing edges are based on either the first derivative of the image as in FSL, or a variation of the Canny Edge detection method as implemented in AFNI. The crucial algorithmic parameter for adjustment for each of these methods relates to the image intensity. However, image intensity is relative and can be quite variable in most neuroimaging modalities. Further, the existing approaches do not necessarily generate a closed edge/surface, which can reduce the ability to determine the correspondence between a represented edge and another image. We suggest that using the second derivative (difference of Gaussian, or DoG) of the image to generate edges resolves both these issues. This method primarily operates by specifying a spatial scale of interest (which is typically known in medical imaging) rather than a contrast scale, and creates closed surfaces by definition. We describe some convenient implementation features (for both efficiency and visual quality) developed here, and we provide open source implementations of this method as both online and high performance portable code. Finally, we include this method as part of both the AFNI and FSL software packages.
Optimal energy and redox metabolism in the cyanobacteriumSynechocystissp. PCC 6803
Authors: Kugler Amit , Stensjö Karin
Published: September 2022

Cyanobacteria represent an attractive platform for the sustainable production of chemicals and fuels. However, the obtained rates, yields, and titers are below those required for commercial application. Carbon metabolism alone cannot achieve maximal accumulation of end-products, since an efficient production of target molecules entails energy and redox balance, in addition to carbon flow. The interplay between cofactor regeneration and heterologous metabolite overproduction in cyanobacteria is not fully explored. Here, we applied stoichiometric metabolic modelling of the cyanobacteriumSynechocystissp. PCC 6803, in order to investigate the optimality of energy and redox metabolism, while overproducing bio-alkenes - isobutene, isoprene, ethylene and 1-undecene. Our network-wide analysis indicates that the rate of NADP+ reduction, rather than ATP synthesis, controls ATP/NADPH ratio, and thereby chemical production. The simulation implies that energy and redox balance necessitates gluconeogenesis, and that acetate metabolism via phosphoketolase serves as an efficient carbon- and energy-recycling pathway. Furthermore, we show that an auxiliary pathway, composed of serine, one-carbon and glycine metabolism, supports cellular redox homeostasis and ATP cycling, and that theSynechocystismetabolism is controlled by few key reactions carrying a high flux. The study also revealed non-intuitive metabolic pathways to enhance isoprene, ethylene and 1-undecene production. We conclude that metabolism of ATP and NAD(P)H is entwined with carbon and nitrogen metabolism, and cannot be assessed in isolation. We envision that the presented here in-depth metabolic analysis will guide the a priori design ofSynechocystisas a host strain for an efficient manufacturing of target products.
Dynamic Transcriptomic Network Responses to Divergent Acute Exercise Challenges in Young Adults
Authors: Lavin Kaleen M , Graham Zachary A , McAdam Jeremy S , O’Bryan Samia M , Drummer Devin , Bell Margaret B , Kelley Christian J , Lixandrão Manoel E , Peoples Brandon , Tuggle S. Craig , Seay Regina S , Van Keuren-Jensen Kendall , Huentelman Matthew J , Pirrotte Patrick , Reiman Rebecca , Alsop Eric , Hutchins Elizabeth , Antone Jerry , Bonfitto Anna , Meechoovet Bessie , Palade Joanna , Talboom Joshua S , Sullivan Amber , Aban Inmaculada , Peri Kalyani , Broderick Timothy J , Bamman Marcas M
Published: September 2022

Acute exercise elicits dynamic transcriptional changes that, when repeated, form the fundamental basis of adaptations in health, resilience, and performance. While moderate-intensity endurance training combined with conventional resistance training (traditional, TRAD) is often prescribed and recommended by public health guidance, high-intensity training combining maximal-effort intervals with intensive, limited-rest resistance training is a time-efficient alternative that may be used tactically (HITT) to seek whole body health benefits. Mechanisms of action of these distinct doses are incompletely characterized and have not been directly compared. We assessed transcriptome-wide responses in skeletal muscle and circulating extracellular vesicles (EVs) to a single exercise bout in young adults randomized to TRAD (n=21, 12M/9F, 22±3y) or HITT (n=19, 11M/8F, 22±2y). Next-generation sequencing captured small, long, and circular RNA in muscle and EVs. Analysis identified differentially expressed transcripts (|log2FC|>1, FDR≤0.05) immediately (h0, EVs only), h3, and h24 post-exercise within and between exercise doses. Additionally, all apparently responsive transcripts (FDR<0.2) underwent singular value decomposition to summarize data structures into latent variables (LVs) to deconvolve molecular expression circuits and inter-regulatory relationships. LVs were compared across time and exercise dose. TRAD generally elicited a stronger, more consistent transcriptional response than HITT, but considerable overlap and key differences existed. Findings reveal shared and unique molecular responses to divergent exercise stimuli and lay groundwork toward establishing relationships between protein-coding genes and lesser-understood transcripts that serve regulatory roles in response to exercise. Future work should advance the understanding of these circuits and whether they repeat in other populations or following other types of exercise/stress.

NEW AND NOTEWORTHY

We examined small and long transcriptomics in skeletal muscle and serum-derived extracellular vesicles before and after a single exposure to traditional combined exercise (TRAD) and high-intensity tactical training (HITT). Across 40 young adults, we found more consistent protein-coding gene responses to TRAD, whereas HITT elicited differential expression of microRNA enriched in brain regions. Follow-up analysis revealed relationships and temporal dynamics across transcript networks, highlighting potential avenues for research into mechanisms of exercise response and adaptation.
Effects of social presence on behavioural, neural and physiological aspects of empathy for pain
Authors: Petereit Pauline , Weiblen Ronja , Perry Anat , Krämer Ulrike M.
Published: September 2022

In mediated interactions (e.g. video calls), less information is available about the other. To investigate how this affects our empathy for one another, we conducted an EEG study, in which thirty human participants observed one of 5 targets undergoing painful electric stimulation, once in a direct interaction and once in a live, video-mediated interaction. We found that observers were as accurate in judging others’ pain and showed as much affective empathy via video as in a direct encounter. While mu suppression, a common neural marker of empathy, was not sensitive to others’ pain, theta responses to others’ pain as well as skin conductance coupling between participants were reduced in the video-mediated condition. We conclude that physical proximity with its rich social cues is important for nuanced physiological resonance with the other’s experience. More studies are warranted to confirm these results and to understand their behavioural significance for remote social interactions.
Large scale production of human blastoids amenable to modeling blastocyst development and maternal-fetal crosstalk
Authors: Yu Leqian , Ezashi Toshihiko , Wei Yulei , Duan Jialei , Logsdon Deirdre , Zhan Linfeng , Nahar Asrafun , Arteaga Carlos A. Pinzon , Liu Lizhong , Stobbe Caitlen , Katz-Jaffe Mandy , Schoolcraft William B , Wang Lei , Tan Tao , Hon Gary C. , Yuan Ye , Wu Jun
Published: September 2022

Recent advances in human blastoids generated from naïve pluripotent stem cells have opened a new avenue for modelling early human development and implantation. Despite the success, however, existing protocols have several limitations, e.g., the use of custom-built microwell arrays impedes wide adoption by the research community, and mass production of human blastoids is hampered by low-output or low-efficiency methods. To address these issues, here we developed an optimized protocol based on commercially available microwell plates, which enabled efficient generation of high-fidelity human blastoids at a large scale. Leveraging on the improved protocol, we identified MAPK. PI3K/AKT and mTOR signaling pathways were activated in both blastoids and blastocyst, and discovered endometrial stromal effects in promoting trophoblast cell survival, proliferation and syncytialization during extended co-culture with blastoids. Our optimized protocol will facilitate broader use of human blastoids as an accessible, perturbable, scalable, tractable, and ethical model for human blastocysts.
Oncogenic Kras induces spatiotemporally specific tissue deformation through converting pulsatile into sustained ERK activation
Authors: Xin Tianchi , Gallini Sara , Gonzalez David , Gonzalez Lauren E. , Regot Sergi , Greco Valentina
Published: September 2022

Tissue regeneration and maintenance rely on coordinated stem cell behaviors. This orchestration can be impaired by oncogenic mutations leading to tissue architecture disruption and ultimately cancer formation. However, it is still largely unclear how oncogenes perturb stem cells’ functions to break tissue architecture. Here, we used intravital imaging and a novel signaling reporter to investigate the mechanisms by which oncogenic Kras mutation causes tissue disruption in the hair follicle. Through longitudinally tracking the same hair follicles in live mice, we found that KrasG12D, a mutation that can lead to squamous cell carcinoma, induces epithelial tissue deformation in a spatiotemporally specific manner. This tissue architecture abnormality is linked with a spatial dysregulation of stem cell proliferation as well as abnormal migration during hair follicle growth. By using a reporter mouse that allows us to capture real-time ERK signal dynamics at the single cell level, we discovered that KrasG12D, but not a closely related mutation HrasG12V, converts the pulsatile ERK signal fluctuation in the stem cells into sustained activation. Furthermore, by combining drug treatment with longitudinal imaging, we demonstrated that temporary inhibiting ERK signal reverts the KrasG12D-induced tissue deformation, suggesting that sustained ERK activation leads to tissue architecture disruption in Kras mutant hair follicles. Altogether, our work suggests that oncogenic mutations induce tissue abnormalities when spatiotemporally specific conditions are met, which allows mutant stem cells to disturb local cell coordination through altering dynamic signal communications.
Control of alveolar macrophage differentiation by Siah1a/2 ubiquitin ligases limits carcinogen-induced lung adenocarcinoma
Authors: Scortegagna Marzia , Du Yuanning , Bradley Linda M. , Wang Kun , Ruppin Eytan , Murad Rabi , Ronai Ze’ev A.
Published: September 2022

Tumor microenvironment components, including T and myeloid cells, play important roles in lung adenocarcinoma (LADC) progression and response to therapy. Here, we identify a role for Siah1a/2 ubiquitin ligases in controlling alveolar macrophage (AM) differentiation and urethane-induced LADC. Genetic ablation of Siah1a/2 in AMs enriched their immature state, coinciding with increased pro-tumorigenic and inflammatory gene signatures and abundance of Siah1a/2 substrates NRF2 and β-catenin. Urethane administration to mice enriched the population of monocytic and immature-like AMs, which were more prevalent in the lungs of mice carrying Siah1a/2-ablated macrophages. While resembling transitional profibrotic macrophages often seen in lung fibrosis, enrichment of immature AMs coincided with the development of more frequent and larger lung tumors in urethane-treated mice harboring Siah1a/2 ablated macrophages compared with controls. Gene expression signature of Siah1a/2 ablated immature-like AMs is associated with increased infiltration of CD14+ immune cells and worse survival of LADC patients. Our findings identify Siah1a/2 as gatekeepers of cancer development by controlling AM differentiation and profibrotic phenotypes contributing to carcinogen-induced lung cancer.
Widespread convergent evolution of alpha-neurotoxin resistance in African mammals
Authors: Drabeck Danielle H. , Holt Jennifer , McGaugh Suzanne E.
Published: September 2022

Convergent evolution is central to the study of adaptation and has been used to understand both the limits of evolution and the diverse patterns and processes which result in adaptive change. Resistance to snake venom α-neurotoxins (αNTXs) is a case of widespread convergence having evolved several times in snakes, lizards, and mammals. Despite extreme toxicity of αNTXs, substitutions in its target, the nicotinic acetylcholine receptor (nAChR), prevent αNTX binding and render species resistant. Recently, the published meerkat (Herpestidae) genome revealed that meerkats have the same substitutions in nAChR as the venom resistant Egyptian mongoose (Herpestidae), suggesting that venom-resistant nAChRs may be ancestral to Herpestids. Like the mongoose, many other species of feliform carnivores prey on venomous snakes, though their venom resistance has never been explored. To evaluate the prevalence and ancestry of αNTX resistance in mammals, we generate a dataset of mammalian nAChR utilizing museum specimens and public datasets. We find five instances of convergent evolution within feliform carnivores, and an additional eight instances across all mammals sampled. Tests of selection show that these substitutions are evolving under positive selection. Repeated convergence suggests that this adaptation played an important role in the evolution of mammalian physiology and potentially venom evolution.
Genotypic variation in tolerance to salinity in Pakistani okra (Abelmoschus esculentus L.) varieties as assessed at seed germination, seedling growth and biochemical characters
Authors: Ullah Hayat , Jan Tour , Wahid Fazal , Zahoor Muhammad , Uddin Shahab , Bibi Shabana
Published: September 2022

Salt stress is one of the major abiotic stresses that causes reduction in crops yield. Okra (Abelmoschus esculentus L.) is a high-value nutraceutical vegetable because its various parts are used for different purposes. This study was conducted to calculate the salt tolerance among thirteen okra varieties. Different salt (NaCl) levels: 0, 50, 75 and 100 mM were selected to measure the response of the okra varieties to stress. The experimental data showed that all varieties were affected by salt level with a differential variation in their stress response, demonstrating the presence of genetic variability. Five varieties: “NAYAB-F1”, “Arka anamika”, “MALAV-27”, “Sarhad Green” and 051-F1 showed germination at all stress levels (0, 50, 75 and 100 mM), six varieties: “Feveeri Green”, “Punjab Selection”, “Local Multani”, “Shehzadi”, “Green Star” and “Hunza” showed germination at (0, 50 and 75 mM) and two: “Anmol” and “Sabz Pari” showed germination at (0 and 50 mM). As a result of salt stress, germination percentage (PG), leaf fresh and dry weight (LFW and LDW), shoot fresh and dry weight (SFW and SDW), root fresh and dry weight (RFW and RDW) were significantly reduced with increasing stress level. Based on the performance of variety to salt stress, five varieties were selected for biochemical analysis, concentrating on the determination of osmolytes. The values of sugar and proline were affected both by the varieties and salt levels. Variety “NAYAB-F1” showed higher sugar and proline content at all stress levels compared to varieties “Arka anamika”, “MALAV-27”, “051-F1” and Sarhad Green. Correspondingly, in the stressed seedling a decreasing trend in chlorophyll “a” and “b” were noted depending on the varieties and stress concentrations. After a series of experiment, it has been concluded that varieties “NAYAB-F1”, “Arka anamika”, “MALAV-27”, “Sarhad Green” and “051-F1” were recommended as salt tolerant varieties and could be utilized in the breeding program of salt tolerant okra.
Systematic investigation of allelic regulatory activity of schizophrenia-associated common variants
Authors: McAfee Jessica C. , Lee Sool , Lee Jiseok , Bell Jessica L. , Krupa Oleh , Davis Jessica , Insigne Kimberly , Bond Marielle L. , Phanstiel Douglas H. , Love Michael I. , Stein Jason L. , Kosuri Sriram , Won Hyejung
Published: September 2022

Genome-wide association studies (GWAS) have successfully identified 145 genomic regions that contribute to schizophrenia risk, but linkage disequilibrium (LD) makes it challenging to discern causal variants. Computational finemapping prioritized thousands of credible variants, ∼98% of which lie within poorly characterized non-coding regions. To functionally validate their regulatory effects, we performed a massively parallel reporter assay (MPRA) on 5,173 finemapped schizophrenia GWAS variants in primary human neural progenitors (HNPs). We identified 439 variants with allelic regulatory effects (MPRA-positive variants), with 71% of GWAS loci containing at least one MPRA-positive variant. Transcription factor binding had modest predictive power for predicting the allelic activity of MPRA-positive variants, while GWAS association, finemap posterior probability, enhancer overlap, and evolutionary conservation failed to predict MPRA-positive variants. Furthermore, 64% of MPRA-positive variants did not exhibit eQTL signature, suggesting that MPRA could identify yet unexplored variants with regulatory potentials. MPRA-positive variants differed from eQTLs, as they were more frequently located in distal neuronal enhancers. Therefore, we leveraged neuronal 3D chromatin architecture to identify 272 genes that physically interact with MPRA-positive variants. These genes annotated by chromatin interactome displayed higher mutational constraints and regulatory complexity than genes annotated by eQTLs, recapitulating a recent finding that eQTL- and GWAS-detected variants map to genes with different properties. Finally, we propose a model in which allelic activity of multiple variants within a GWAS locus can be aggregated to predict gene expression by taking chromatin contact frequency and accessibility into account. In conclusion, we demonstrate that MPRA can effectively identify functional regulatory variants and delineate previously unknown regulatory principles of schizophrenia.
Prevalence and risk factors for long COVID after mild disease: a longitudinal study with a symptomatic control group
Authors: Cazé Ana Beatriz C , Cerqueira-Silva Thiago , Bomfim Adriele Pinheiro , de Souza Gisley Lima , Andrade Azevedo Amanda Canário , Aguiar Brasil Michelle Queiroz , Rúbia Santos Nara , Khouri Ricardo , Dan Jennifer , Bandeira Antonio Carlos , de Goes Cavalcanti Luciano Pamplona , Barral-Netto Manoel , Prado Barral Aldina Maria , Barbosa Cynara Gomes , Boaventura Viviane Sampaio
Published: September 2022

Background

There is limited data on the prevalence and risk factors for long COVID, with a shortage of prospective studies with appropriate control groups and adequate sample size. We therefore performed a prospective study to determine the prevalence and risk factors for long COVID.

Methods

We recruited patients age ≥ 15 years who were clinically suspected of having acute SARS-CoV-2 infection from September 2020 to April 2021. Nasopharyngeal swabs were collected for RT-PCR 3-5 days post symptom onset. Clinical and sociodemographic characteristics were collected using structured questionnaires from persons positive and negative for SARS-COV-2. Follow-up was performed by telephone interview to assess early outcomes and persistent symptoms. For COVID-19 cases, 5D-3L EuroQol questionnaire was used to assess the impact of symptoms on quality of life.

Results

We followed 814 participants (412 COVD-19 positive and 402 COVID-19 negative persons) of whom the majority (741 / 814) had mild symptoms. Both the COVID-19 positive and the COVID-19 negative groups had similar sociodemographic and clinical characteristics, except for the rate of hospitalization (15.8% vs 1.5%, respectively). One month after disease onset, 122 (29.6%) individuals reported residual symptoms in the COVID-19 positive group or the long COVID group versus 24 (6%) individuals in the COVID-19 negative group. In the long COVID group, fatigue, olfactory disorder, and myalgia were the most frequent symptoms which occurred in the acute phase. Compared to recovered patients, female sex, older age and having > 5 symptoms during the acute phase were risk factors for long COVID. Quality of life was evaluated in 102 out of 122 cases of long COVID with 57 (55.9%) reporting an impact in at least one dimension of the EuroQol 5D-3L questionnaire.

Conclusion

In this prospective study consisting predominantly of patients with mild disease, the persistence of symptoms after acute disease was highly associated with long COVID-19 (29.6% vs 6% of COVID negative group). The risk factors for long COVID were older age, female sex, and polysymptomatic acute disease.
Research and Diagnostic Algorithmic Rules (RADAR) for mood disorders, recurrence of illness, suicidal behaviors, and the patient’s lifetime trajectory
Authors: Maes Michael , Moraes Juliana Brum , Congio Ana , Vargas Heber Odebrecht , Nunes Sandra Odebrecht Vargas
Published: September 2022

The top-down DSM/ICD categories of mood disorders are inaccurate, and their dogmatic nature precludes both deductive (as indisputable) and inductive (as top-down) remodeling of case definitions. In trials, psychiatric rating scale scores employed as outcome variables are invalid and rely on folk psychology-like narratives. Using machine learning techniques we developed a new precision nomothetic model of mood disorders with a recurrence of illness (ROI) index, a new endophenotype class, namely Major Dysmood Disorder (MDMD), characterized by increased ROI, a more severe phenome, and more disabilities Nonetheless, our previous studies did not compute Research and Diagnostic Algorithmic Rules (RADAR) to diagnose MDMD and score ROI, lifetime (LT), and current suicidal behaviors, as well as the phenome of mood disorders. Here we provide rules to compute bottom-up RADAR scores for MDMD, ROI, lifetime (LT) and current suicidal SI and SA, the phenome of mood disorders, and the lifetime trajectory of mood disorder patients from a family history of mood disorders and substance abuse to adverse childhood experiences, ROI, and the phenome. We also demonstrate how to plot the 12 major scores in a single RADAR graph, which displays all features in a two-dimensional plot. These graphs allow the characteristics of a patient to be displayed as an idiomatic fingerprint, allowing one to estimate the key traits and severity of the illness at a glance. Consequently, biomarker research into mood disorders should use our RADAR scores to examine pan-omics data, which should be used to enlarge our precision models and RADAR graph.
Distinct origins and transmission pathways ofblaKPCEnterobacterales across three U.S. states
Authors: Lapp Zena , Octaria Rany , O’Malley Sean M. , Nguyen Tu Ngoc , Wolford Hannah , Crawford Ryan , Moore Christina , Vagnone Paula Snippes , Noel Diane , Duffy Nadezhda , Pirani Ali , Thomas Linda S. , Pattee Brittany , Pearson Claire , Bulens Sandra N. , Hoffman Sophie , Kainer Marion , Anacker Melissa , Meek James , See Isaac , Chan Allison , Lynfield Ruth , Maloney Meghan , Hayden Mary K. , Snitkin Evan , Slayton Rachel B.
Published: September 2022

Background

Carbapenem-resistant Enterobacterales (CRE) are among the most concerning antibiotic resistance threats due to high rates of multidrug resistance, transmissibility in healthcare settings, and high mortality rates. We evaluated the potential for regional genomic surveillance to trackblaKPC-carrying CRE (KPC-CRE) transmission across healthcare facilities in three U.S. states.

Methods

Clinical isolates were collected from Connecticut (CT; 2017-2018), Minnesota (MN; 2012-2018), and Tennessee (TN; 2016-2017) through the U.S. Centers for Disease Control and Prevention’s Multi-site Gram-negative Surveillance Initiative and additional surveillance. KPC-CRE isolates were whole-genome sequenced, and case report data on patient comorbidities, healthcare utilization, and interfacility patient transfer were extracted.

Findings

In CT, most KPC-CRE isolates showed evidence of importation from outside the state, with limited local transmission. In MN, cases were mainly from sporadic importation and transmission ofblaKPC-carryingKlebsiella pneumoniae(KPC-Kp) ST258, and clonal expansion of an imported epidemic lineage ofblaKPC-carryingEnterobacter hormaechei(KPC-Ec) ST171 primarily at a single focal facility and its satellite facilities. In TN, KPC-Kp ST258, and more recently emerged KPC-Kp ST307 and KPC-Eh ST114 were most common, with largely non-overlapping facility networks mediating the spread of ST258 versus ST307 and ST114.

Conclusions

The underlying processes driving KPC-CRE burden can differ substantially across regions, and different STs can spread via distinct pathways within a region. Integrating genomic and epidemiological data from regional surveillance, and information on interfacility patient transfers, can provide insights to target interventions.
Stakeholders’ perspectives on the feasibility of adopting a Healthy Nail Salon Recognition Program in Philadelphia: A qualitative study
Authors: Nguyen Duong T , Nguyen Chau , Pintor Jessie , Huynh Tran B
Published: September 2022

Background

The California Healthy Nail Salon Recognition Program is a statewide initiative to incentivize nail salons to adopt safer practices such as use of safer nail products without certain harmful chemicals, installation of ventilation systems, proper personal protective equipment use, and staff training. This public policy intervention is in response to the call to protect nail care workers, mostly women of color, who bear disproportionate burden of chemical exposure at work. Because there is interest from the community to adopt similar program in the Greater Philadelphia region, we conducted this formative research to document stakeholders’ perspectives on the feasibility of adopting the Healthy Nail Salon Recognition Program in Philadelphia.

Methods

We conducted semi-structured interviews with a purposive sample of 31 stakeholders in Philadelphia in 2021. Using the Consolidated Framework for Implementation Science as our theoretical framework, we developed the interview guide and analyzed the data using qualitative research method to identify key facilitators and barriers.

Results

Key facilitating themes were perceived need and benefits of program to improve workers’ health and working conditions, and willingness of stakeholders to leverage their organizational resources. Barriers included perceived high cost and time commitment from salon owners and employees, lack of funding and implementation leaders at the city government, community members’ willingness to be visible and advocate for the program affected by the stigmas of being immigrant workers, fear of interacting with authorities, as well as the impact of COVID-19 pandemic. Our results suggest successful adoption of the Healthy Nail Salon Recognition Program in Philadelphia will require outreach within the community to raise awareness of the benefits of the program and close partnership with community-based organizations to facilitate mutual understanding between the authority and the ethnically diverse nail salon communities.
Neutralizing antibodies following three doses of BNT162b2 vaccine, breakthrough infection, and symptoms during the Omicron predominant wave
Authors: Yamamoto Shohei , Matsuda Kouki , Maeda Kenji , Horii Kumi , Okudera Kaori , Oshiro Yusuke , Inamura Natsumi , Takeuchi Junko S. , Konishi Maki , Ozeki Mitsuru , Mizoue Tetsuya , Sugiyama Haruhito , Aoyanagi Nobuyoshi , Mitsuya Hiroaki , Sugiura Wataru , Ohmagari Norio
Published: September 2022

Background

Data on the role of immunogenicity following the third vaccine dose against Omicron infection and coronavirus disease 2019 (COVID-19)-compatible symptoms of infection are limited.

Methods

First we examined vaccine effectiveness (VE) of the third-dose against the second dose during the Omicron wave among the staff at a tertiary hospital in Tokyo. In a case-control study of a cohort of third vaccine recipients, we compared the pre-infection levels of live-virus neutralizing antibodies (NAb) against Omicron between breakthrough cases and their controls, who had close contact with COVID-19 patients. Among these cases, we examined the association between pre-infection NAb levels and the number of COVID-19-compatible symptoms experienced during the Omicron wave.

Results

Among the 1456 participants for VE analysis, 60 (4%) breakthrough infections occurred during the Omicron wave (January to March 2022). The third-dose VE for infection, relative to the second dose was 54.6% (95% CI: 14.0–76.0). Among the recipients of the third vaccine, pre-infection NAb levels against Omicron did not significantly differ between the cases and controls. Among the cases, those who experienced COVID-19-compatible symptoms had lower pre-infection NAb levels against Omicron than those who did not.

Conclusions

The third vaccine dose was effective in decreasing the risk of severe acute respiratory syndrome coronavirus 2 infection during the Omicron wave compared with the second dose. Among third-dose recipients, higher pre-infection NAb levels may not be associated with a lower risk of Omicron infection. Contrarily, they may be associated with fewer symptoms of infection.

The third vaccine dose reduced SARS-CoV-2 infection risk during the Omicron wave. Higher neutralizing antibody levels may not reduce Omicron infection risk in third-dose patients. On the contrary, it may be associated with fewer symptoms of infection.
Estimation of mRNA COVID-19 Vaccination Effectiveness in Tokyo for Omicron Variants BA.2 and BA.5 -Effect of Social Behavior-
Authors: Kodera Sachiko , Niimi Yuki , Rashed Essam A. , Yoshinaga Naoki , Toyoda Masashi , Hirata Akimasa
Published: September 2022

Variability of COVID-19 vaccination effectiveness (VE) should be assessed with a resolution of a few days assuming that VE is influenced by public behavior and social activity. Here the VE for the Omicron variants (BA.2 and BA.5) is numerically derived for Japan’s population for the second and third vaccination doses. We then evaluated the daily VE variation caused by our social behavior from the daily data reports for Tokyo. The vaccination effectiveness for Omicron variants (BA.1, BA.2, and BA.5) are derived from the data of Japan and Tokyo with a computational approach. In addition, the effect of different parameters regarding human behavior on VE is assessed using daily data in Tokyo. The individual VE for the Omicron BA.2 in Japan was 61% (95%CI: 57%–65%) for the vaccination second dose from our computation, whereas that for the third dose was 86% (95% CI: 84%–88%). The individual BA.5 VE for the second and third doses are 37% (95% CI: 33%–40%) and 63% (95% CI: 61%–65%). The reduction of daily VE from estimated value was close correlated to the number of tweets related to social gathering in Twitter. The number of tweets considered here would be one of new candidates for VE evaluation and surveillance affecting the viral transmission.
TandemAligner: a new parameter-free framework for fast sequence alignment
Authors: Bzikadze Andrey V. , Pevzner Pavel A.
Published: September 2022

The recent advances in “complete genomics” revealed the previously inaccessible genomic regions (such as centromeres) and enabled analysis of their associations with diseases. However, analysis of variations in centromeres, immunoglobulin loci, and other extra-long tandem repeats (ETRs) faces an algorithmic bottleneck since there are currently no tools for accurate sequence comparison of ETRs. Counterintuitively, the classical alignment approaches, such as the Smith-Waterman algorithm, that work well for most sequences, fail to construct biologically adequate alignments of ETRs. This limitation was overlooked in previous studies since the ETR sequences across multiple genomes only became available in the last year. We present TandemAligner — the first parameter-free sequence alignment algorithm that introduces a sequence-dependent alignment scoring that automatically changes for any pair of compared sequences. We apply TandemAligner to various human centromeres and primate immunoglobulin loci, arrive at the first accurate estimate of the mutation rates in human centromeres, and quantify the extremely high rate of large insertions/duplications in centromeres. This extremely high rate (that the standard alignment algorithms fail to uncover) suggests that centromeres represent the most rapidly evolving regions of the human genome with respect to their structural organization.
An R-R-type MYB transcription factor promotes nonclimacteric pepper fruit ripening pigmentation
Authors: Yang Ningzuo , Song Jiali , Chen Changming , Sun Binmei , Zhang Shuanglin , Cai Yutong , Zheng Xiongjie , Cao Bihao , Chen Guoju , Jin Dan , Li Bosheng , Bian Jianxin , Lei Jianjun , He Hang , Zhu Zhangsheng
Published: September 2022

Carotenoids act as phytohormones and volatile compound precursors that influence plant development and confer characteristic colours, affecting both the aesthetic and nutritional value of fruits. Carotenoid pigmentation in ripening fruits is highly dependent on developmental trajectories. Transcription factors incorporate developmental and phytohormone signalling to regulate the biosynthesis process. In contrast to the well-established pathways regulating ripening-related carotenoid biosynthesis in climacteric fruit, carotenoid regulation in nonclimacteric fruit is poorly understood. Capsanthin is the primary carotenoid of nonclimacteric pepper (Capsicum) fruit; its biosynthesis is tightly associated with fruit ripening, and it confers red pigment to the ripening fruit. In this study, using a weighted gene coexpression network and expression analysis, we identified an R-R-type MYB transcription factor, DIVARICATA1, and demonstrated that it is tightly associated with the levels of carotenoid biosynthetic genes (CBGs) and capsanthin accumulation. DIVARICATA1 encodes a nucleus-localized protein that functions primarily as a transcriptional activator. Functional analyses demonstrated that DIVARICATA1 positively regulates CBG transcript levels and capsanthin contents by directly binding to and activating the CBG promoter transcription. Furthermore, the association analysis revealed a significant positive association between DIVARICATA1 transcription level and capsanthin content. Abscisic acid (ABA) promotes capsanthin biosynthesis in a DIVARICATA1-dependent manner. Comparative transcriptomic analysis of DIVARICATA1 in pepper and its orthologue in a climacteric fruit, tomato, suggests that its function might be subject to divergent evolution among the two species. This study illustrates the transcriptional regulation of capsanthin biosynthesis and offers a novel target for breeding peppers with high red colour intensity.