bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum levels of the novel adipokine isthmin-1 are associated with obesity in pubertal boys
Authors: Ruiz-Ojeda Francisco Javier , Anguita-Ruiz Augusto , Rico Maria C. , Leis Rosaura , Bueno Gloria , Gil-Campos Mercedes , Gil Ángel , Aguilera Concepción M
Published: March 2022

Purpose

The aims of this study were; 1) to evaluate if there is an association between the serum levels of the novel insulin-like adipokine isthmin-1 (ISM1) and obesity-related phenotypes in a population of Spanish children, 2) to investigate the plausible molecular alterations behind the alteration of the serum levels of this protein in children with obesity.

Methods

The study population is a sub-cohort of the PUBMEP research project, consisting of a cross-sectional population of 119 pubertal children with overweight (17 boys, 19 girls), obesity (20 boys, 25 girls) and normal weight (17 boys, 21 girls). All subjects were classified into experimental groups according to their sex, obesity and insulin resistance (IR) status. They counted on anthropometry, glucose, and lipid metabolism, inflammation and cardiovascular biomarkers as well as ISM1 serum levels measured. This population was intended as a discovery population in which to elucidate the relationship between obesity and ISM1 levels in children. Furthermore, the study population had blood whole-genome DNA methylation allowing deepening into the obesity-ISM1 molecular relationship.

Results

Higher serum levels of ISM1 were observed in boys with obesity when compared with normal-weight (P=0.004), and overweight (P=0.007). ISM1 serum levels were positively associated with BMI Z-score (P=0.005), and negatively with myeloperoxidase (MPO) (p=0.043) in boys. Nevertheless, we did not find associations between ISM1 serum levels and metabolic outcomes in girls, indicating a putative sexual dimorphism. DNA methylation levels in two-enhancer-related CpG sites of ISM1 (cg03304641 and cg14269097) were associated with serum levels of ISM1 in children.

Discussion

We report an unprecedented study that provides a major step forward showing that ISM1 is robustly associated with obesity in pubertal boys, elucidating how this protein might be of special relevance as a new biomarker of obesity in children.
Evidence of co-infection during Delta and Omicron variants of concern co-circulation, weeks 49-2021 to 02-2022, France
Authors: Combes Patricia , Bisseux Maxime , Bal Antonin , Marin Pierre , Archimbaud Christine , Brebion Amélie , Chabrolles Hélène , Regagnon Christel , Lafolie Jérémy , Destras Gregory , Simon Bruno , Josset Laurence , Henquell Cécile , Mirand Audrey
Published: March 2022

We report evidence of Delta/Omicron SARS-CoV-2 co-infections during the fifth wave of COVID-19 pandemics in France for 7 immunocompetent and epidemiologically unrelated patients. These co-infections were detected by PCR assays targeting SARS-CoV-2 S-gene mutations K417N and L452R and confirmed by whole genome sequencing which allowed the proportion estimation of each subpopulation. For 2 patients, the analyses of longitudinal samples collected 7 to 11 days apart showed that Delta or Omicron can outcompete the other variant during dual infection.
Daily tenofovir disoproxil fumarate/emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a double-blind placebo controlled randomized trial in healthcare workers
Authors: Polo R , García-Albéniz X , Terán C , Morales M , Rial-Crestelo D , Garcinuño MA , García del Toro M , Hita C , Gómez-Sirvent JL , Buzón L , Díaz de Santiago A , Pérez Arellano JL , Sanz J , Bachiller P , Martínez Alfaro E , Díaz-Brito V , Masiá M , Hernández-Torres A , Guerra J , Santos J , Arazo P , Muñoz L , Arribas JR , Martínez de Salazar P , Moreno S , Hernán MA , Del Amo J
Published: March 2022

Objective

To assess the effect of hydroxychloroquine (HCQ), Tenofovir disoproxil fumarate/Emtricitabine (TDF/FTC), and their combination as pre-exposure prophylaxis on the risk of symptomatic COVID-19.

Methods

EPICOS is a double-blind, placebo-controlled randomized trial conducted in 51 hospitals in Spain, Bolivia, and Venezuela. Healthcare workers with negative SARS-CoV-2 IgM/IgG test were randomly assigned to: daily TDF/FTC plus HCQ for 12 weeks, TDF/FTC plus HCQ placebo, HCQ plus TDF/FTC placebo and TDF/FTC placebo plus HCQ placebo. The primary outcome was laboratory-confirmed, symptomatic COVID-19. We also studied any (symptomatic or asymptomatic) COVID-19 infection. We compared group-specific 14-week risks via differences and ratios with 95% confidence intervals (CI).

Results

Of 1002 individuals screened, 926 (92.4%) were eligible; 64.2% recruited in Spain, 22.3% in Bolivia, and 13.6% in Venezuela. Median age was 38 years (range 18 - 68), 62.5% were female, 62.3% worked at inpatient care, and comorbidities were rare. Compared with the placebo group, 14-week risk ratios (95% CI) of symptomatic COVID-19 were 0.39 (0.00, 1.98) for TDF+HCQ, 0.34 (0.00, 2.06) for TDF, and 0.49 (0.00, 2.29) for HCQ. Corresponding risk ratios of any COVID-19 were 0.51 (0.21, 1.00) for TDF+HCQ, 0.81 (0.44, 1.49) for TDF, and 0.73 (0.41, 1.38) for HCQ. Adverse events were generally mild.

Conclusion

A beneficial effect of TDF/FTC and HCQ, alone or in combination, as pre-exposure prophylaxis for COVID-19 cannot be ruled out but effect estimates are imprecise because the target sample size was not met. These findings support launching randomized trials of TDF/FTC for the early treatment of COVID-19.
Vaccine Breakthrough Infection with the SARS-CoV-2 Delta or Omicron (BA.1) Variant Leads to Distinct Profiles of Neutralizing Antibody Responses
Authors: Seaman Michael S. , Siedner Mark J. , Boucau Julie , Lavine Christy L. , Ghantous Fadi , Liew May Y. , Mathews Josh , Singh Arshdeep , Marino Caitlin , Regan James , Uddin Rockib , Choudhary Manish C. , Flynn James P. , Chen Geoffrey , Stuckwisch Ashley M. , Lipiner Taryn , Kittilson Autumn , Melberg Meghan , Gilbert Rebecca F. , Reynolds Zahra , Iyer Surabhi L. , Chamberlin Grace C. , Vyas Tammy D. , Vyas Jatin M. , Goldberg Marcia B. , Luban Jeremy , Li Jonathan Z. , Barczak Amy K. , Lemieux Jacob E.
Published: March 2022

There is increasing evidence that the risk of SARS-CoV-2 infection among vaccinated individuals is variant-specific, suggesting that protective immunity against SARS-CoV-2 may differ by variant. We enrolled vaccinated (n = 39) and unvaccinated (n = 11) individuals with acute, symptomatic SARS-CoV-2 Delta or Omicron infection and performed SARS-CoV-2 viral load quantification, whole-genome sequencing, and variant-specific antibody characterization at the time of acute illness and convalescence. Viral load at the time of infection was inversely correlated with antibody binding and neutralizing antibody responses. Increases in antibody titers and neutralizing activity occurred at convalescence in a variant-specific manner. Across all variants tested, convalescent neutralization titers in unvaccinated individuals were markedly lower than in vaccinated individuals. For individuals infected with the Delta variant, neutralizing antibody responses were weakest against BA.2, whereas infection with Omicron BA.1 variant generated a broader response against all tested variants, including BA.2.
Quantifying the Effect Size of Exposure-Outcome Association Using δ-score: Application to Environmental Chemical Mixture studies
Authors: Midya Vishal , Liao Jiangang , Gennings Chris , Colicino Elena , Teitelbaum Susan L. , Wright Robert O. , Valvi Damaskini
Published: March 2022

Epidemiologists often study the associations between a set of exposures and multiple biologically relevant outcomes. Frequently used scale and context dependent regression coefficients may not offer practically meaningful comparison and can further complicate the interpretation when these outcomes do not have similar units. Additionally, while scaling up a hypothesis driven study based on preliminary data, epidemiologists face a major uncertainty of how large the sample size should be. Frequently used p-value based sample size calculation emphasizes on precision and might lead to very large sample size for small or moderate effect sizes. This is not only costly but also might allow detection of irrelevant effects. Here we introduced a new concept “δ-score” by modifying Cohen’s f2. δ-score is scale independent and under a new hypothesis testing framework quantifies the maximum Cohen’s f2 with certain optimal properties. We also introduced “Sufficient sample size”, which is the sample size required to attain the δ-score. Finally, we demonstrated the utility of δ-score and sufficient sample size using data on adults from 2017–2018 US National Health and Nutrition Examination Survey for association between mixture of Per-and poly-fluoroalkyl substances and metals with serum high-density and low-density lipoprotein-cholesterols.
An observational study of the association between COVID-19 vaccination rates and entry into the Australian ‘Million Dollar Vax’ competition
Authors: Jun Dajung , Scott Anthony
Published: March 2022

Objectives

To examine the association between financial incentives from entry into a vaccine competition with the probability of vaccination for COVID-19.

Design

A cross-sectional study with adjustment for covariates using logistic regression

Setting

October and November 2021, Australia.

Participants

2,375 respondents of the Taking the Pulse of the Nation Survey

Primary and secondary outcome measures

The proportion of respondents who had any vaccination, a first dose only, or second dose after the competition opened.

Results

Those who entered the competition were 2.27 (95% CI 1.73 to 2.99) times more likely to be vaccinated after the competition opened on October 1st than those who did not enter—an increase in the probability of having any dose of 0.16 (95 % CI 0.10 to 0.21) percentage points. This increase was mostly driven by those receiving second doses. Entrants were 2.39 (95% CI 1.80 to 3.17) times more likely to receive their second dose after the competition opened.

Conclusions

Those who entered the Million Dollar Vax competition were more likely to receive a vaccination after the competition opened compared to those who did not enter the competition, with this effect dominated by those receiving second doses.

Strengths and limitations of this study

We use a nationally representative sample of individual self-reported vaccination status and timings.

We distinguish between the association between competition entry and first and second doses.

We adjust for a rich set of individual characteristics associated with vaccination status, and examine the factors influencing competition entry

The strong association for second dose vaccinations may reflect some individuals who had already scheduled their second dose after the competition opened, potentially leading to an overestimate of the association.
Introducing riskCommunicator: an R package to obtain interpretable effect estimates for public health
Authors: Grembi Jessica A. , Rogawski McQuade Elizabeth T.
Published: March 2022

Common statistical modeling methods do not necessarily produce the most relevant or interpretable effect estimates to communicate risk. Overreliance on the odds ratio and relative effect measures limit the potential impact of epidemiologic and public health research. We created a straightforward R package, calledriskCommunicator, to facilitate the presentation of a variety of effect measures, including risk differences and ratios, number needed to treat, incidence rate differences and ratios, and mean differences. TheriskCommunicatorpackage uses g-computation with parametric regression models and bootstrapping for confidence intervals to estimate effect measures in time-fixed data. We demonstrate the utility of the package using data from the Framingham Heart Study to estimate the effect of prevalent diabetes on the 24-year risk of cardiovascular disease or death.

The absolute 24-year risk of cardiovascular disease or death was 30% (95% confidence interval (CI): 22, 38) higher among subjects with diabetes compared to subjects without diabetes at baseline. The relative 24-year risk was 55% (95% CI: 40, 70) higher. Because the outcome was common (41.8%), the odds ratio (4.55) is highly inflated compared to the risk ratio (1.55). An expected 4 additional persons would need to have diabetes at baseline to observe an increase in the number of cases of cardiovascular disease or death by 1 over 24 years of follow-up.

The package promotes the communication of public-health relevant effects and is accessible to a broad range of epidemiologists and health researchers with little to no expertise in causal inference methods or advanced coding.
Self-Care, Health Literacy and Their Associations Amongst Patients with Chronic Kidney Disease (CKD) in Primary Care
Authors: Ho Han-Kwee , Koh Eileen Yi-Ling , Chua Wan-Ching , S/O Meyappan Meykkumar , Chung Ray Ern , Marie-Pamerlyn Pereira Emma , Zhai Chenlu , Lim Leon Jian-Ying , Abdullah Adina , Tan Ngiap-Chuan
Published: March 2022

Aim

The study objective was to determine the levels of self-care (including domains of behaviour, motivation, self-efficacy) and health literacy, and study their associations amongst patients with chronic kidney disease (CKD) in primary care setting in Singapore.

Method

A cross-sectional, questionnaire-based study was conducted in one public-sector primary care clinic. Participants aged 21 to 80 years with hypertension were recruited from the clinic CKD register with 5,500 patients. Self-care profile (including behaviour, motivation and self-efficacy) were measured using Hypertension Self-Care Profile (HTN-SCP, range 0-240, domain range 0-80). Health literacy was measured using Short-Form Health Literacy Scale (HLS-SF12, range 0-50, limited literacy ≤33).

Results

A total of 347 out of 354 randomly selected patients consented to participate in the study. Two hundred and eighty-nine fully-completed responses were analysed. The mean self-care (HTN-SCP) score was 182.7 (SD 23.2), while mean scores were 55.3 (SD 8.6), 63.3 (SD 8.7), 64.0 (SD 9.3), for behaviour, self-efficacy and motivation domains respectively. The mean health literacy score was 36.1 (SD 7.7), and 31.1% of participants had limited health literacy. Limited health literacy was associated with self-efficacy (OR= −7.2, 95%CI=−9.1 to −5.2, p<0.001), motivation (OR= −6.1, 95%CI=−8.3 to −3.9, p<0.001) and behaviour (OR= −4.5, 95%CI=−6.6 to −2.4, p<0.001). Self-care was not associated with age, CKD status, household income and education but was associated with gender and limited health literacy. In the final regression model only limited health literacy was associated with self-care scores (Adjusted beta −17.4, p<0.001).

Conclusion

One-third of the patients with CKD in primary care had limited health literacy. Self-care was not associated with age, gender, CKD status, household income or education. Limited health literacy was associated with self-care, with strongest association with self-efficacy, followed by motivation and behaviour. More targeted approach can be adopted to improve self-care and health literacy amongst patients with CKD.
Estimating relative generation times and relative reproduction numbers of Omicron BA.1 and BA.2 with respect to Delta in Denmark
Authors: Ito Kimihito , Piantham Chayada , Nishiura Hiroshi
Published: March 2022

The Omicron variant is the most transmissible variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) we had so far. The BA.1 and BA.2 sublineages of Omicron are circulating in Europe and it is urgent to evaluate the transmissibility of these sub-lineages. Using a mathematical model describing trajectories of variant frequencies that assumes a constant ratio in generation times and a constant ratio in effective reproduction numbers among variants, trajectories of variant frequencies in Denmark from November 22, 2021 to February 26, 2022 were analyzed. We found that the generation times of Omicron BA.1 and BA.2 are 0.60 (95%CI: 0.59–0.62) and 0.51 (95%CI: 0.50–0.52) of the length of that of Delta, respectively. We also found that the effective reproduction number of Omicron BA.1 is 1.99 (95% CI: 1.98–2.02) times and that of Omicron BA.2 is 2.51 (95% CI: 2.48– 2.55) times larger than the effective reproduction number of Delta. The generation times of Omicron BA.2 is 0.85 (95% CI:0.84–0.86) the length of that of BA.1 and that the effective reproduction number of Omicron BA.2 is 1.26 (95% CI:1.25–1.26) times larger than that of Omicron BA.1. These estimates on the ratio of generation times and the ratio of effective reproduction numbers has epidemiologically important implications. The duration of quarantine for people who contacted with an Omicron BA.1 and BA.2 patient can be reduced to 60% and 51% of that for Delta, respectively. The control measures against Omicron BA.1 and BA.2 need to reduce contacts between infectious and susceptible people respectively by 50% (95% CI: 49–50%) and 60% (95% CI: 60–61%) compared to that against Delta to achieve the same effect on their control.
Monitoring and understanding household clustering of SARS-CoV-2 cases using surveillance data in Fulton County, Georgia
Authors: Liu Carol Y. , Smith Sasha , Chamberlain Allison T. , Gandhi Neel R. , Khan Fazle , Williams Steve , Shah Sarita
Published: March 2022

Background

Households are important for SARS-CoV-2 transmission due to high intensity exposure in enclosed living spaces over prolonged durations. Using contact tracing, the secondary attack rate in households is estimated at 18-20%, yet no studies have examined COVID-19 clustering within households to inform testing and prevention strategies. We sought to quantify and characterize household clustering of COVID-19 cases in Fulton County, Georgia and further explore age-specific patterns in household clusters.

Methods

We used state surveillance data to identify all PCR- or antigen-confirmed cases of COVID-19 in Fulton County, Georgia. Household clustered cases were defined as cases with matching residential address with positive sample collection dates within 28 days of one another. We described proportion of COVID-19 cases that were clustered, stratified by age and over time and explored trends in age of first diagnosed case within clusters and age patterns between first diagnosed case and subsequent household cases.

Results

Between 6/1/20–10/31/21, there were 106,233 COVID-19 cases with available address reported in Fulton County. Of these, 31,449 (37%) were from 12,955 household clusters. Children were more likely to be in household clusters than any other age group and children increasingly accounted for the first diagnosed household case, rising from 11% in February 2021 to a high of 31% in August 2021. Bubble plot density of age of first diagnosed case and subsequent household cases mirror age-specific patterns in household social mixing.

Discussion

One-third of COVID-19 cases in Fulton County were part of a household cluster. High proportion of children in household clusters reflects higher probability of living in larger homes with caregivers or other children. Increasing probability of children as the first diagnosed case coincide with temporal trends in vaccine roll-out among the elderly in March 2021 and the return to in-person schooling for the Fall 2021 semester. While vaccination remains the most effective intervention at reducing household clustering, other household-level interventions should also be emphasized such as timely testing for household members to prevent ongoing transmission.
Large haploblocks underlie rapid adaptation in an invasive weed
Authors: Battlay Paul , Wilson Jonathan , Bieker Vanessa C. , Lee Christopher , Prapas Diana , Petersen Bent , Craig Sam , van Boheemen Lotte , Scalone Romain , de Silva Nissanka P. , Sharma Amit , Konstantinović Bojan , Nurkowski Kristin A. , Rieseberg Loren H. , Connallon Tim , Martin Michael D. , Hodgins Kathryn A.
Published: March 2022

Adaptation is the central feature and leading explanation for the evolutionary diversification of life. Adaptation is also notoriously difficult to study in nature, owing to its complexity and logistically prohibitive timescale. We leverage extensive contemporary and historical collections ofAmbrosia artemisiifolia—an aggressively invasive weed and primary cause of pollen-induced hayfever—to track the phenotypic and genetic causes of recent local adaptation across its native and invasive ranges in North America and Europe, respectively. Large haploblocks— indicative of chromosomal inversions—contain a disproportionate share (26%) of genomic regions conferring parallel adaptation to local climates between ranges, are associated with rapidly adapting traits, and exhibit dramatic frequency shifts over space and time. These results highlight the importance of large-effect standing variants in rapid adaptation, which have been critical toA. artemisiifolia’s global spread across vast climatic gradients.
Organoid-based human stomach micro-physiological system to recapitulate the dynamic mucosal defense mechanism
Authors: Jeong Hye-Jin , Park Ji-Hyeon , Kang Joo H. , Kong Seong-Ho , Park Tae-Eun
Published: March 2022

Several stomach diseases are attributed to the dysregulation of physiological function of gastric mucosal barrier by pathogens. Gastric organoids are a promising tool to develop treatment strategies for gastric infections. However, their functional features of in vivo gastric mucosal barrier and host-microbe interactions are limited due to the lack of physiological stimuli. Herein, we describe the first human stomach micro-physiological system (hsMPS) with physiologically relevant gastric mucosal defense system based on the combination of organoid and MPS technology. A fluid flow enhanced epithelial-mesenchymal interaction in the hsMPS enables functional maturation of gastric epithelial cells, which allows for the recreation of mesh-like mucus layer containing high level of mucus protective peptides and well-developed epithelial junctional complexes. Furthermore, gastroprotection mechanisms against Helicobacter pylori are successfully demonstrated in our system. Therefore, hsMPS represents a new in vitro tool for research where gastric mucosal defense mechanism is pivotal for developing therapeutic strategies.
Partial gene suppression improves identification of cancer vulnerabilities when CRISPR-Cas9 knockout is pan-lethal
Authors: Krill-Burger J. Michael , Dempster Joshua M. , Borah Ashir A. , Paolella Brenton R. , Root David E. , Golub Todd R. , Boehm Jesse S. , Hahn William C. , McFarland James M. , Vazquez Francisca , Tsherniak Aviad
Published: March 2022

Hundreds of genome-wide loss-of-function screens have been performed, as part of efforts such as The Cancer Dependency Map, to create a catalog of genetic dependencies in a diverse set of cancer contexts. In recent years, large-scale screening efforts have shifted perturbation technology from RNAi to CRISPR-Cas9, due to the superior efficacy and specificity of CRISPR-Cas9-mediated approaches. However, questions remain about the extent to which partial suppression of gene targets could result in selective dependency across cell lines, potentially revealing a larger set of targetable cancer vulnerabilities than can be identified using CRISPR knockout alone. Here, we use CRISPR-Cas9 and RNAi screening data for more than 400 shared cell lines to represent knockout and partial suppression genetic perturbation modalities and evaluate the utility of each for therapeutic target discovery and the inference of gene function. We find that CRISPR screens identify more dependencies, and yield more accurate predictive models and co-dependency relationships overall. However, RNAi outperforms CRISPR in identifying associations (omics, drug, co-dependencies) with genes that are common dependencies for most cell lines (pan-dependencies). As pan-dependencies occur frequently in the CRISPR dataset (~2,000 genes), using results from both RNAi and CRISPR analyses facilitates the discovery of predictive models and associated co-dependencies for a wider range of gene targets than could be detected using either dataset alone. These findings can aid in the interpretation of contrasting results obtained from CRISPR and RNAi screens and reinforce the importance of partial gene suppression methods in building a cancer dependency map.
An initial assessment of the sustainability of waterbird harvest in the United Kingdom
Authors: Ellis Matthew B. , Cameron Tom C.
Published: March 2022

There is a need to assess the sustainability of wild bird harvest in the United
Kingdom (UK), and more widely, across Europe. Yet data on populations and harvest sizes are limited.

We used a Demographic Invariant Method (DIM) to estimate Potential Excess Growth (PEG) for populations of UK wintering waterbirds and calculated a Sustainable Harvest Index (SHI) for each. We compared this with population trends and conservation classifications (e.g. Birds of Conservation Concern; BoCC) to assess the sustainability of harvests and the utility of these classifications.

Our approach found evidence for potential overharvest of mallard Anas platyrhynchos, Eurasian teal Anas crecca, gadwall Mareca strepera, Canada geese Branta canadensis, greylag geese Anser anser and woodcock Scolopax rusticola. Whether DIM methods predict overharvest is highly dependent on estimates of maximum population growth rates inferring PEG. We found estimates of maximum population growth to be variable across a range of different methods.

We found no relationship between SHI and short-term wintering trends or conservation classification under the UK’s BoCC framework. There was however a positive relationship between SHI and long-term wintering trends.

Policy Implications: Our results suggest that UK based harvest is unlikely to be a major determinant of population trends for the majority of UK overwintering waterbirds, but harvest rates for some species may exceed that required to maintain stationary population growth. The lack of a relationship between conservation classifications and SHI strongly suggests that such conservation classifications are not an appropriate tool for making decisions about harvest management. Instead, our assessment provides the basis for a framework to make evidence-based decisions on sustainable harvest levels in the face of incomplete data. There is currently no clear policy instrument in the UK to support such a framework via controls on either harvest effort or mortality of waterfowl.
PIF4/HEMERA-mediated daytime thermosensory growth requires the Mediator subunit MED14
Authors: Bajracharya Abhishesh , Xi Jing , Grace Karlie F. , Bayer Eden E. , Grant Chloe A. , Clutton Caroline H. , Baerson Scott R. , Agarwal Ameeta K. , Qiu Yongjian
Published: March 2022

While moderately elevated ambient temperatures do not trigger stress responses in plants, they do significantly stimulate the growth of specific organs through a process known as thermomorphogenesis. The basic helix-loop-helix transcription factor PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) plays a central role in regulating thermomorphogenetic hypocotyl elongation in various plant species, including Arabidopsis thaliana. Although it is well known that PIF4 promotes plant thermosensory growth by activating genes involved in the biosynthesis and signaling of the phytohormone auxin, the detailed molecular mechanism of such transcriptional activation is not clear. Our previous studies demonstrated that HEMERA (HMR), a transcriptional co-activator of PIF4, promotes the thermo-induced expression of PIF4 target genes through its nine-amino-acid transactivation domain (9aaTAD). In this report, we investigate the role of the Mediator complex in the PIF4/HMR-mediated thermoresponsive gene expression. Through the characterization of various mutants of the Mediator complex, a tail subunit named MED14 is identified as an essential factor for thermomorphogenetic hypocotyl growth. MED14 is required for the thermal induction of PIF4 target genes but has a marginal effect on the levels of PIF4 and HMR. Further transcriptomic analyses confirm that the expression of numerous PIF4/HMR-dependent, auxin-related genes requires MED14 at warm temperatures. Moreover, PIF4 and HMR physically interact with MED14 and both are indispensable for the association of MED14 with the promoters of these thermoresponsive genes. Taken together, these results unveil an important thermomorphogenetic mechanism, in which PIF4 and HMR recruit the Mediator complex to activate auxin-related growth-promoting genes when plants sense moderate increases in ambient temperature.

One-sentence summary

The Mediator subunit MED14 promotes thermomorphogenesis by interacting with PHYTOCHROME-INTERACTING FACTOR 4 and HEMERA to induce the expression of growth-promoting genes at elevated temperatures.
Rapid quantification of polyhydroxyalkanoates accumulated in living cells based on green fluorescence protein labeled phasin: The qPHA method
Authors: Liu Xu , Li Dianjie , Yan Xu , Zhang Zonghao , Zheng Shuang , i Jingpeng Zhang , Wu Fuqing , Li Fangting , Chen Guo-Qiang
Published: March 2022

Polyhydroxyalkanoates (PHA), are microbial polyesters with possibility to replace non-biodegradable petro-plastics. No rapid in situ PHA quantitation method has been available for the past 40 years to replace the traditional method which is complicated, time and labor consuming. Quantification of PHA in living cells were finally developed from fluorescence intensities generated from green fluorescence protein (GFP) fused with the Halomonas bluephagenesis phasin proteins attached on the PHA granules. Phasins PhaP1 and PhaP2 were used to fuse with GFP which reflects PHA accumulation with an R-square over 0.9, respectively. Also, a standard correlation was established to calculate PHA contents based on the fluorescence and cell density recorded via a microplate reader with R-square over 0.95 when grown on various substrates, respectively. The PhaP2-GFP containing H. bluephagenesis was applied successfully to quantify PHA synthesis in a 7.5 L fermenter with high precision. The method is named qPHA.
The order Axinellida (Porifera: Demospongiae) in California
Authors: Turner Thomas L. , Pankey M. Sabrina
Published: March 2022

Sponges are common and diverse in California, but they have received little study in the region, and the identities of many common species remain unclear. Here we combine fresh collections and museum vouchers to revise the order Axinellida for California. Seven new species are described:Endectyon (Endectyon) hispitumulus, Eurypon curvoclavus, Aulospongus viridans, Aulospongus lajollaensis, Halicnemia litorea,Halicnemia montereyensis, andHalicnemia weltoni. One new combination is also described, and two existing species are reduced to junior synonyms, resulting in a total of 13 species; a dichotomous key to differentiate them is provided. DNA data from 9 of the 13 species is combined with publicly available data to produce updated global phylogenies for the order.
Engineering chimeric antigen receptor neutrophils from human pluripotent stem cells for targeted cancer immunotherapy
Authors: Chang Yun , Syahirah Ramizah , Wang Xuepeng , Jin Gyuhyung , Torregrosa-Allen Sandra E. , Elzey Bennett D. , Hummel Sydney N , Wang Tianqi , Lian Xiaojun , Deng Qing , Broxmeyer Hal E. , Bao Xiaoping
Published: March 2022

Neutrophils, the most abundant white blood cells in the circulation, are closely related to cancer development and progression. Primary neutrophils from healthy donors present potent cytotoxicity against different human cancer cell lines through direct contact and via the generation of reactive oxygen species (ROS). However, due to their short half-life and resistance to genetic modification, neutrophils have not yet been engineered with widely used chimeric antigen receptors (CARs) to enhance their anti-tumor cytotoxicity for targeted immunotherapy. Here, we genetically engineered human pluripotent stem cells (hPSCs) with different synthetic CARs and successfully differentiated them into functional neutrophils by implementing a novel chemically-defined differentiation platform. Neutrophils expressing the chlorotoxin (CLTX)-T-CAR presented specific cytotoxicity against glioblastoma (GBM) cells both in monolayer and 3D cultures. In a GBM xenograft mouse model, systematically-administered CLTX-T-CAR neutrophils also displayed enhanced anti-tumor activity and prolonged animal survival compared with peripheral blood-neutrophils, hPSC-neutrophils and CLTX-NK-CAR natural killer (NK) cells. Collectively, we established a new platform for production of CAR-neutrophils, paving the way to myeloid cell-based therapeutic strategies that would complement and boost current cancer treatment approaches.
Confluence and tight junction dependence of volume regulation in epithelial tissue
Authors: Chmiel Theresa A. , Gardel Margaret L.
Published: March 2022

Epithelial cell volume regulation is a key component to tissue stability and dynamics. In particular, how cells respond to osmotic stresses is of significant physiological interest in kidney epithelial tissue. For individual mammalian cells, it is well established that Na-K-2Cl cotransporter (NKCC) channels mediate cell volume homeostasis in response to hyperosmotic stress. However, whether mature epithelium respond similarly is not well known. Here we show that while small colonies of MDCK epithelial cells behave similarly to single cells and exhibit volume homeostasis that is dependent on the NKCC channel function, mature epithelial tissue does not. Instead, the cell volume decreases by 33% when confluent monolayers or acini formed from MDCK are subjected to hyperosmotic stress. We show that the tight junction protein, ZO-1, and Rho-associated kinase (ROCK) are essential for osmotic regulation of cell volume in mature epithelium. Since these both are known to be essential for tight junction assembly, this strongly suggest a role for tight junctions in changing volume response in mature epithelium. Thus, tight junctions act either directly or indirectly in osmotic pressure response of epithelial tissue to suppress volume homeostasis common to isolated epithelial cells.
A chromosome-scale hybrid genome assembly of the extinct Tasmanian tiger (Thylacinus cynocephalus)
Authors: Feigin Charles , Frankenberg Stephen , Pask Andrew
Published: March 2022

The extinct Tasmanian tiger or thylacine (Thylacinus cynocephalus) was a large marsupial carnivore native to Australia. Once ranging across parts of the mainland, the species remained only on the island of Tasmania by the time of European colonization. It was driven to extinction in the early 20th century and is an emblem of native species loss in Australia. The thylacine was a striking example of convergent evolution with placental canids, with which it shared a similar skull morphology. Consequently, it has been the subject of extensive study. While the original thylacine assemblies published in 2018 enabled the first exploration of the species’ genome biology, further progress is hindered by the lack of high-quality genomic resources. Here, we present a new chromosome-scale hybrid genome assembly for the thylacine, which compares favorably with many recent de novo marsupial genomes. Additionally, we provide homology-based gene annotations, characterize the repeat content of the thylacine genome and show that, consistent with demographic decline, the species possessed a low rate of heterozygosity even compared to extant, threatened marsupials.

Significance

The lack of high-quality genomes for extinct species inhibits research into their biology. Moreover, marsupials are underrepresented among sequenced genomes. Here, we present a new, chromosome-scale thylacine genome. This high-quality assembly is a valuable new resource for studies on marsupial carnivores.
The dynamics of protein localisation to restricted zones within Drosophila mechanosensory cilia
Authors: Xiang Wangchu , zur Lage Petra , Newton Fay G. , Qiu Guiyun , Jarman Andrew P.
Published: March 2022

The Drosophila chordotonal neuron cilium is the site of mechanosensory transduction. The cilium has a 9+0 axoneme structure and is highly sub-compartmentalised, with proximal and distal zones harbouring different TRP channels and the proximal zone axoneme also being decorated with axonemal dynein motor complexes. The activity of the dynein complexes is essential for mechanotransduction. We investigate the localisation of TRP channels and dynein motor complexes during ciliogenesis. Differences in timing of TRP channel localisation correlate with order of construction of the two ciliary zones. Dynein motor complexes are initially not confined to their target proximal zone, but complexes beyond the proximal zone are later cleared, perhaps by retrograde transport. Differences in transient distal localisation of ODAs and IDAs are consistent with previous suggestions from unicellular eukaryotes of differences in processivity during intraflagellar transport. Stable localisation depends on the targeting of their docking proteins in the proximal zone. For outer dynein arm (ODA) complexes, we characterise an ODA docking complex (ODA-DC) that is targeted directly to the proximal zone. Interestingly, the subunit composition of the ODA-DC in chordotonal neuron cilia appears to be different from the predicted ODA-DC in Drosophila sperm.
Powering single-cell analyses in the browser with WebAssembly
Authors: Lun Aaron , Kancherla Jayaram
Published: March 2022

We present kana, a web application for interactive single-cell ‘omics data analysis in the browser. Like, literally, in the browser: kana leverages web technologies such as WebAssembly to efficiently perform the relevant computations on the user’s machine, avoiding the need to provision and maintain a backend service. The application provides a streamlined one-click workflow for the main steps in a typical single-cell analysis, starting from a count matrix and finishing with marker detection. Results are presented in an intuitive web interface for further exploration and iterative analysis. Testing on public datasets shows that kana can analyze over 100,000 cells within 5 minutes on a typical laptop.
Cophylogeny and specificity between cryptic coral species (Pocilloporaspp.) at Mo’orea and their symbionts (Symbiodiniaceae)
Authors: Johnston Erika C. , Cunning Ross , Burgess Scott C.
Published: March 2022

The congruence between phylogenies of tightly associated groups of organisms (cophylogeny) reflects evolutionary links between ecologically important interactions. However, despite being a classic example of an obligate symbiosis, tests of cophylogeny between scleractinian corals and their photosynthetic algal symbionts have been hampered in the past because both corals and algae contain genetically unresolved and morphologically cryptic species. Here, we studied co-occurring, crypticPocilloporaspecies from Mo’orea, French Polynesia, that differ in their relative abundance across depth. We constructed new phylogenies of the hostPocillopora(using genomic loci, complete mitochondrial genomes, and thousands of single nucleotide polymorphisms) and their Symbiodiniaceae symbionts (using ITS2 and psbAncrmarkers) and tested for cophylogeny. The analysis supported the presence of fivePocilloporaspecies on the fore-reef at Mo’orea that mostly hosted eitherCladocopium latusorumorC. pacificum.OnlyPocilloporaspecies hostingC. latusorum,and that have similar relative abundances across depths, also hosted taxa fromSymbiodiniumandDurusdinium.In general, theCladocopiumphylogeny mirrored thePocilloporaphylogeny. WithinCladocopiumspecies, lineages also differed in their associations withPocilloporahaplotypes, except those showing evidence of nuclear introgression, and with depth in the two most commonPocilloporaspecies. We also found evidence for a newPocilloporaspecies (haplotype 10), that has so far only been sampled from French Polynesia, that warrants formal identification. The linked phylogenies of thesePocilloporaandCladocopiumspecies and lineages suggest that symbiont speciation is driven by niche diversification in the host, but there is still evidence for symbiont flexibility in rare cases.
Single-cell Spatial Proteomic Imaging for Human Neuropathology
Authors: Vijayaragavan Kausalia , Cannon Bryan J , Tebaykin Dmitry , Bossé Marc , Baranski Alex , Oliveria JP , Mrdjen Dunja , Corces M. Ryan , McCaffrey Erin F , Greenwald Noah F , Sigal Yari , Khair Zumana , Bruce Trevor , Rajaraman Anusha , Bukhari Syed A , Montine Kathleen S. , Angelo R. Michael , Montine Thomas J. , Bendall Sean C.
Published: March 2022

Neurodegenerative disorders are characterized by phenotypic changes and hallmark proteopathies. Quantifying these in archival human brain tissues remains indispensable for validating animal models and understanding disease mechanisms. We present a framework for nanometer-scale, spatial proteomics with multiplex ion beam imaging (MIBI) for capturing neuropathological features. MIBI facilitated simultaneous, quantitative imaging of 36 proteins on archival human hippocampus from individuals spanning cognitively normal to dementia. Customized analysis strategies identified cell types and proteopathies in the hippocampus across stages of Alzheimer’s disease (AD) neuropathologic change. We show microglia-pathologic tau interactions in hippocampal CA1 subfield, in AD dementia. Data driven, sample independent creation of spatial proteomic regions identified persistent neurons in pathologic tau neighborhoods expressing mitochondrial protein MFN2, regardless of cognitive status, suggesting a survival advantage. Our study revealed unique insights from multiplexed imaging and data-driven approaches for neuropathologic analysis and serves as a baseline for mechanistic and interventional understanding in human neurodegeneration.
Precocious sperm exchange in the simultaneously hermaphroditic nudibranch,Berghia stephanieae
Authors: Taraporevala Neville F. , Lesoway Maryna P. , Goodheart Jessica A. , Lyons Deirdre C.
Published: March 2022

Sexual systems vary greatly across molluscs. This diversity includes simultaneous hermaphroditism, with both sexes functional at the same time. Most nudibranch molluscs are thought to be simultaneous hermaphrodites, but detailed studies of reproductive development and timing remain rare as most species cannot be cultured in the lab. The aeolid nudibranch,Berghia stephanieae, is one such species that can be cultured through multiple generations on the benchtop. We studiedB. stephanieaereproductive timing to establish when animals first exchange sperm and how long sperm can be stored. We isolated age- and size-matched individuals at sequential timepoints to learn how early individuals exchange sperm. Individuals isolated at 13 weeks post laying (wpl) can produce fertilized eggs. This is 6 weeks before animals first lay egg masses, indicating that sperm exchange occurs well before individuals are capable of laying eggs. Our results indicate that male gonads become functional for animals between 6 mm (~9 wpl) and 9 mm (~15 wpl) in length. That is much smaller (and sooner) than the size (and age) of individuals at first laying (12-19 mm; ~19 wpl), indicating that male and female functions do not develop simultaneously. We also tracked the number of fertilized eggs in each egg mass, which remained steady for the first 10-15 egg masses, followed by a decline to near-to-no fertilization. This large, novel dataset provides insights into precise timing of the onset of functionality of the male and female reproductive systems inB. stephanieae. These data contribute to a broader understanding of reproductive development and the potential for understanding evolution of diverse sexual systems in molluscs.
Connectomic Analysis of the Drosophila Lateral Neuron Clock Cells Reveals the Synaptic Basis of Functional Pacemaker Classes
Authors: Shafer O.T. , Gutierrez G.J. , Li K. , Mildenhall A. , Spira D. , Marty J. , Lazar A.A. , Fernandez M.P.
Published: March 2022

The circadian clock orchestrates daily changes in physiology and behavior to ensure internal temporal order and optimal timing across the day. In animals, a central brain clock coordinates circadian rhythms throughout the body and is characterized by a remarkable robustness that depends on synaptic connections between constituent neurons. The clock neuron network of Drosophila, which shares network motifs with clock networks in the mammalian brain yet is built of many fewer neurons, offers a powerful model for understanding the network properties of circadian timekeeping. Here we report an assessment of synaptic connectivity within a clock network, focusing on the critical lateral neuron (LN) clock neuron classes. Our results reveal that previously identified anatomical and functional subclasses of LNs represent distinct connectomic types. Moreover, we identify a small number of clock cell subtypes representing highly synaptically coupled nodes within the clock neuron network. This suggests that neurons lacking molecular timekeeping likely play integral roles within the circadian timekeeping network. To our knowledge, this represents the first comprehensive connectomic analysis of a circadian neuronal network.
Relationships among evolutionary distance, the variance–covariance matrix, multidimensional scaling, and principal component analysis
Authors: Misawa Kazuharu
Published: March 2022

Principal component analyses (PCAs) are often used to visualize patterns of genetic variation in human populations. Previous studies showed a close correspondence between genetic and geographic distances. In such PCAs, the principal components are eigenvectors of the data’s variance-covariance matrix, which is obtained by a genetic relationship matrix (GRM). However, it is difficult to apply GRM to multiallelic sites. In this paper, I showed that a PCA from GRM is equivalent to multidimensional scaling (MDS) from nucleotide differences. Therefore, a PCA can be conducted using nucleotide differences. The new method provided in this study provides a straightforward method to predict the effects of different demographic processes on genetic diversity.