bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Acute Exercise on Brain‐Derived Neurotropic Factor (BDNF) and Cognitive Performance (LB694)
Authors: Calvert Hannah , Hwang Jungyun , Kim Kiyoung , Harrison Michelle , Brothers R. , Glowacki Elizabeth , Van Dongen Daniel , Castelli Darla
Published: June 2021

PURPOSE: To investigate the effects of an acute bout of vigorous exercise on BDNF and cognitive performance in emerging adults aged 18‐25 years.

METHODS: Twenty‐nine emerging adults were recruited to assess aerobic exercise‐induced changes in BDNF and cognitive performance. At baseline (T_0), blood samples were taken to measure BDNF, and cardiorespiratory fitness (VO_2 max) was assessed on a cycle ergometer. At rest, cognitive performance was assessed via the Kaufman Brief Intelligence Test, Stroop Test and Trail Making Test (TMT) A and B , followed by 10 minutes of acute treadmill running at 85‐90% maximum heart rate . A second blood draw (T_1) immediately followed the exercise bout. Stroop and TMT were administered again once heart rate returned to 10% of baseline. BDNF was measured 30 minutes post exercise (T_2).

RESULTS: There was a significant increase in BDNF from T_0 to T_1 (p < 0.05) and a significant decrease from T_1 to T_2 ( p < 0.05). Post exercise cognitive performance improved for Stroop word (t = ‐10.36, p <0.05), color (t = ‐6.69, p <0.05), and color word (t = ‐6.16, p <0.05), and TMT A (t=4.32 p<0.001) and B (t=4.46 p<0.001). There were trending relationships between BDNF and both cognitive tests.

CONCLUSIONS: Acute exercise had a significantly positive effect on BDNF and cognition immediately after exercise. Further research is needed to determine whether cognitive performance after exercise is mediated by BDNF.
Localization of Urea Transporters UT‐A1 and UT‐B in Human Eccrine Clear Cell (LB719)
Authors: Keller Raymond , Sands Jeff
Published: June 2021

Urea, a solute classically excreted by the kidney that accumulates in kidney failure, is known to be concentrated in human sweat. Urea is also excreted in the sweat of rat eccrine footpad glands. Therefore, sweat represents an alternative route of excretion for urea. The purpose of this study was to probe for a transporter that might contribute to urea excretion in human skin and rat footpad exocrine glands. Immunohistochemistry was performed on 5 human skin and 5 Sprague‐Dawley rat footpad samples. Human skin was formalin fixed and paraffin embedded for sectioning at 5μm while rat samples were formalin fixed and cryogenically sectioned at 5μm. Polyclonal COOH‐terminal UT‐A and UT‐B antibodies were used to identify the location of UT‐A1 and UT‐B, respectively. Human and rat specimens each contained hair follicles, sebaceous glands, and eccrine glands. Immunoperoxidase staining showed that UT‐B is expressed in the plasma membrane of clear cells in the human eccrine sweat gland. The antibodies did not detect urea transporters in any rat footpad epidermal structures nor the human hair follicles or sebaceous glands. In conclusion, these results suggest the presence of UT‐B in the human eccrine gland. This suggests that UT‐B may contribute to urea secretion in sweat. Future studies are needed to determine whether uremia alters the expression of UT‐B in eccrine sweat glands.舃
Positive regulation of STIM1/Orai1‐mediated store operated calcium entry by reactive oxygen species in human mesangial cells (LB731)
Authors: Chaudhari Sarika , Wang Yanxia , Wu Peiwen , Yuan Joseph , Ma Rong
Published: June 2021

Store operated calcium entry (SOCE) plays a pivotal role in physiological responses of glomerular mesangial cells (MCs). STIM1 and Orai1 proteins are the essential components of SOCE pathway. We have previously demonstrated that STIM1and Orai1 were required for SOCE in cultured human MCs. Reactive oxygen species (ROS) can function as intracellular second messengers and as pathogenic factors in a variety of cell types. Whether and how ROS regulate the STIM1/Orai1‐dependent SOCE in MCs is unknown. The aim of the present study was to explore the effect of ROS on SOCE and the mechanism involved in cultured human MCs. Using fura‐2 fluorescence ratiometry approach, we found that the cyclopiazonic acid (CPA, 25 μM)‐stimulated SOCE was significantly enhanced in MCs with H2O2 treatment (100 μM for 5 days). Consistent with the functional data, western blot analysis of whole cell lysates showed significant increases in expressions of STIM1 and Orai1 proteins by H2O2 treatment in the range of 10‐100 μM for the same time period. However, H2O2 treatment did not affect mRNA expression levels of both STIM1 and Orai1. Furthermore, NAC (4 mM), an antioxidant, had tendency to attenuation of high glucose‐stimulated STIM1 protein expression. Taken together, our results indicate that ROS promote SOCE by increasing STIM1/Orai1 protein expression via a post‐transcriptional mechanism.

Grant Funding Source: NIH
Transcriptional profiling reveals an aberrant hepatic regenerative response underlying acetaminophen (APAP)‐induced acute liver failure (ALF) (LB84)
Authors: Rogler Leslie , Pattamanuch Nicole , Bandi Sriram , Viswanathan Preeti , Gupta Sanjeev
Published: June 2021

Acetaminophen (APAP) toxicity is the leading cause of ALF in United States. To understand mechanisms in APAP‐induced ALF, we performed transcriptional profiling of healthy livers and severely damaged explanted livers from people receiving liver transplants with Affymetrix Human Genome U133 Plus 2.0 arrays. In parallel, microRNA (miRNA) expression profiles were obtained with µParaflo® technology platform (LC Sciences.com). The most significantly down regulated gene categories were: acute phase response and LXR/RXR signaling, mitochondrial dysfunction, coagulation and complement systems, and xenobiotic metabolism. Genes involved in cholesterol and lipid metabolism or cholesterol, lipid and bile acid transport were globally down regulated. Also, hsa‐mir‐193, ‐26a, ‐23a, ‐122, ‐let7c, ‐92a were significantly down regulated. The gene expression pattern suggested activation of hepatic stellate cells. The biliary marker, KR19, was up regulated, as was the NOTCH ligand, JAG1. The proliferation markers, PCNA and Ki67, were up regulated, although growth inhibitory genes, e.g., PTCH2, TGFB1, PTTG1 and WNT signaling inhibitors, e.g., BICC1, were simultaneously up regulated. Several of these up regulated genes are targeted by miRNAs that we found were down regulated in liver with APAP toxicity. These data indicated that liver regeneration was aberrant and that miRNAs could represent suitable targets for therapeutic intervention in APAP‐induced ALF.

Grant Funding Source: NIH and NYSTEM
Circadian measurement of blood pressures and core body temperature in conscious, freely moving vervet monkeys (LB857)
Authors: Collett Jason , Hicks Megan , Beierschmitt Amy , Descanio John , Knot Harm , Osborn Jeffrey
Published: June 2021

A non‐human primate model of essential hypertension has excellent potential for understanding mechanisms of disease. Blood pressure (systolic, SBP; diastolic, mean; MBP), heart rate and core body temperature was measured in freely moving, mature Chlorocebus aethiops sabaeus (African green monkey; vervet) by telemetry (Stellar Telemetry; TSE Systems Inc.). Stellar Telemetry solid‐state pressure sensors were placed in the abdominal aorta of feral, male monkeys. 24 hour SBP, diastolic and MBP, core body temperature and heart rate were determined using different data acquisition parameters to assess system precision and reliability. Different recording parameters (n=4) yielded consistent BPs, in normotensive (MBP=104±4.35 mmHg) and hypertensive (MBP=126±7.57 mmHg) animals. Ultrasonographic examination documented effective placement of sensors within the vessel lumen. Post implant necropsy revealed no sensor induced blood pathologies. SBPs were consistent with those of monkeys measured using plethysmography. This model of hypertension in an Old World, non‐human primate is translational to human essential hypertension and allows for new directions in a genetically similar species. The use of the Stellar Telemetry system is ideal for monitoring conscious blood pressure, heart rate and body temperature in active primates to allow for natural social interactions and species‐specific behavior
Prediction of Impending Septic Shock in Children With Sepsis
Authors: Liu Ran , Greenstein Joseph L. , Fackler James C. , Bergmann Jules , Bembea Melania M. , Winslow Raimond L.
Published: June 2021

Objectives:

Sepsis and septic shock are leading causes of in-hospital mortality. Timely treatment is crucial in improving patient outcome, yet treatment delays remain common. Early prediction of those patients with sepsis who will progress to its most severe form, septic shock, can increase the actionable window for interventions. We aim to extend a time-evolving risk score, previously developed in adult patients, to predict pediatric sepsis patients who are likely to develop septic shock before its onset, and to determine whether or not these risk scores stratify into groups with distinct temporal evolution once this prediction is made.

Design:

Retrospective cohort study.

Setting:

Academic medical center from July 1, 2016, to December 11, 2020.

Patients:

Six-thousand one-hundred sixty-one patients under 18 admitted to the Johns Hopkins Hospital PICU.

Interventions:

None.

Measurements and Main Results:

We trained risk models to predict impending transition into septic shock and compute time-evolving risk scores representative of a patient’s probability of developing septic shock. We obtain early prediction performance of 0.90 area under the receiver operating curve, 43% overall positive predictive value, patient-specific positive predictive value as high as 62%, and an 8.9-hour median early warning time using Sepsis-3 labels based on age-adjusted Sequential Organ Failure Assessment score. Using spectral clustering, we stratified pediatric sepsis patients into two clusters differing in septic shock prevalence, mortality, and proportion of patients adequately fluid resuscitated.

CONCLUSIONS:

We demonstrate the applicability of our methodology for early prediction and stratification for risk of septic shock in pediatric sepsis patients. Through analyses of risk score evolution over time, we corroborate our past finding of an abrupt transition preceding onset of septic shock in children and are able to stratify pediatric sepsis patients using their risk score trajectories into low and high-risk categories.
The Implementation and Outcomes of a Nurse-Run Extracorporeal Membrane Oxygenation Program, a Retrospective Single-Center Study
Authors: Odish Mazen , Yi Cassia , Tainter Christopher , Najmaii Samira , Ovando Julio , Chechel Laura , Lipinski Jerry , Ignatyev Alex , Pile Alexander , Yeong Jang Yun , Lin Tuo , Tu Xin M. , Madani Michael , Patel Mitul , Meier Angela , Pollema Travis , Owens Robert L.
Published: June 2021

Objectives:

Due to a shortage of perfusionists and increasing utilization of extracorporeal membrane oxygenation in the United States, many programs are training nurses as bedside extracorporeal membrane oxygenation specialists (i.e., nurse-run extracorporeal membrane oxygenation). Our objective was to evaluate if a nurse-run extracorporeal membrane oxygenation program has noninferior survival to discharge and complication rates compared with a perfusionist-run extracorporeal membrane oxygenation program. Additionally, to sought to describe increases in extracorporeal membrane oxygenation capacity and the potential for cost savings by implementing a nurse-run extracorporeal membrane oxygenation program.
Early Intubation and Increased Coronavirus Disease 2019 Mortality: A Propensity Score–Matched Retrospective Cohort Study
Authors: Parish Austin J. , West Jason R. , Caputo Nicholas D. , Janus Trevor M. , Yuan Denley , Zhang John , Singer Daniel J.
Published: June 2021

Objectives:

There has been controversy about the timing and indications for intubation and mechanical ventilation in novel coronavirus disease 2019. This study assessed the effect of early intubation and mechanical ventilation on all-cause, inhospital mortality for coronavirus disease 2019 patients.

Design:

Multicenter retrospective cohort study.

Setting:

Eleven municipal hospitals in New York City from March 1, 2020, to December 1, 2020.

Patients:

Adult patients who tested positive for coronavirus disease 2019 in the emergency department were subsequently admitted. Patients with do-not-intubate orders at admission were excluded.

Interventions:

Intubation within 48 hours of triage and intubation at any point during hospital stay.

Measurements and Main Results:

Data from 7,597 coronavirus disease 2019 patients were included; of these, 1,628 (21%) were intubated overall and 807 (11%) were intubated within 48 hours of triage. After controlling for available confounders, intubation rates for coronavirus disease 2019 patients varied significantly across hospitals and decreased steadily as the pandemic progressed. After nearest neighbor propensity score matching, intubation within 48 hours of triage was associated with higher all-cause mortality (hazard ratio, 1.30 [1.15–1.48]; p < 0.0001), as was intubation at any time point (hazard ratio, 1.62 [1.45–1.80]; p < 0.0001). Among intubated patients, intubation within 48 hours of triage was not significantly associated with differences in mortality (hazard ratio, 1.09 [0.94–1.26]; p = 0.26). These results remained robust to multiple sensitivity analyses.

CONCLUSIONS:

Intubation within 48 hours of triage, as well as at any time point in the hospital course, was associated with increased mortality in coronavirus disease 2019 patients in this observational study.
Cerebrospinal Fluid Penetration of Vancomycin During Continuous Infusion Therapy in Patients With Nosocomial Ventriculitis
Authors: Tuon Felipe Francisco , Yamada Carolina Hikari , Cieslinski Juliette , dos Santos Oliveira Dayana , Ribeiro Victoria Stadler Tasca , Gasparetto Juliano , Telles Joao Paulo
Published: June 2021

Background:

This study aimed to evaluate the utility of a commercial kit used to measure serum vancomycin concentrations to determine vancomycin concentrations in cerebrospinal fluid (CSF) samples and evaluate CSF penetration when administered as a continuous high-dose infusion in patients with nosocomial ventriculitis.

Methods:

This study included patients with external ventricular drain infection who were admitted to the intensive care unit between January 2018 and September 2020. After validation, CSF samples from 33 patients were collected. All patients received 30 mg/kg of vancomycin as a loading dose followed by 60 mg/kg as a maintenance dose in continuous infusion; all CSF samples were collected at least 48 hours after the first dose.

Results:

Thirty-three patients were enrolled in this study. The median serum creatinine level was 0.66 mg/dL (0.5–0.92; n = 30), and median creatinine clearance was 119.2 mL/min (64.6–138.4; n = 13). The median serum vancomycin 24-hour area under the curve (AUC24h) was 838 mg*h/L (515–1010). The median CSF vancomycin concentration was 5.20 mg/L (1.95–12.4). Median serum vancomycin concentration was 34.9 mg/L (21.47–42.1), and median CSF/serum ratio was 18.6% (8.4–41.5). Acute renal injury occurred in 21% (n = 7) of the patients by the end of the therapy. In addition, the vancomycin CSF/serum ratio was positively correlated with the median serum creatinine level (r = 0.670; P = 0.004).

Conclusions:

Commercial vancomycin kits used to measure serum samples may be used to evaluate vancomycin concentrations in the CSF. Vancomycin penetration into CSF was 18.6%.
Lower ambulatory nocturnal SBP is associated with less cardiovascular and renal damage in normotensive hospitalized patients with chronic kidney disease
Authors: Zhang Jun , Song Jun , Zhou Liping , Zhou Wenying , Rao Jialing , Li Yuanqing , Wu Jianhao , Peng Hui , Lou Tanqi
Published: June 2021

Objective:

The impact of nocturnal blood pressure (BP) on target organ damage (TOD) in chronic kidney disease (CKD) patients with normotension has not been established. In this study, we determined whether nocturnal BP is correlated with cardiovascular and renal damage independent of the 24-h BP in CKD patients with normotension or hypertension.

Methods:

A total of 1166 hospitalized patients with CKD not requiring dialysis were enrolled in this cross-sectional study, 421 and 745 of whom had normotension and hypertension, respectively. TOD was assessed by the left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR) and presence of proteinuria. Univariate and multivariable regression analyses were used to evaluate the relationships between nocturnal BP and TOD.

Results:

In the multivariable-adjusted models, including the 24-h BP, nocturnal SBP was independently associated with the LVMI, eGFR and proteinuria in patients with normotension (P < 0.05), while the nocturnal DBP was not correlated with proteinuria. The nocturnal SBP was associated with LVMI and proteinuria, but not the eGFR in patients with hypertension. We did not demonstrate an association between nocturnal DBP and TOD in these patients. When nocturnal SBP in patients with normotension was further divided into tertiles [tertile 1 (<104 mmHg), tertile 2 (104–114 mmHg) and tertile 3 (≥114 mmHg)], multivariate analysis showed that tertile 3 was independently associated with TOD.

Conclusion:

Nocturnal SBP was shown to be an independent risk factor for TOD in patients with normotension. Targeting a nocturnal ambulatory SBP to less than 114 mmHg or even less than 104 mmHg may help prevent TOD in patients with CKD.
Emtricitabine triphosphate in dried blood spots predicts future viremia in persons with HIV and identifies mismatch with self-reported adherence
Authors: Morrow Mary , MaWhinney Samantha , Coyle Ryan P. , Coleman Stacey S. , Zheng Jia-Hua , Ellison Lucas , Bushman Lane R. , Kiser Jennifer J. , Anderson Peter L. , Castillo-Mancilla Jose R.
Published: June 2021

Objective:

Emtricitabine triphosphate (FTC-TP) in dried blood spots (DBS), a measure of short-term antiretroviral therapy (ART) adherence, is associated with viral suppression in persons with HIV (PWH). However, its ability to predict future viremia remains unknown.

Design:

Prospective, observational cohort (up to three visits in 48 weeks).

Methods:

PWH receiving TDF/FTC-based ART had DBS and HIV viral load obtained at routine clinical visits. FTC-TP in DBS was dichotomized into quantifiable vs. below the limit of quantification (BLQ). The adjusted odds ratio (aOR) of future viremia (≥20 copies/ml at next study visit) was estimated according to FTC-TP at the current visit. To assess for possible interactions, additional models adjusted for tenofovir diphosphate (TFV-DP) in DBS and 3-day self-reported adherence.

Results:

Data from 433 PWH (677 paired DBS/HIV viral load samples) were analyzed. The aOR [95% confidence interval (CI)] for future viremia for BLQ vs. quantifiable FTC-TP was 3.4 (1.8--6.5; P = 0.0002). This diminished after adjusting for TFV-DP [aOR 1.9 (0.9--4.1); P = 0.090]. Among PWH reporting 100% 3-day adherence, the odds of future viremia were 6.0 times higher [(1.8--20.3); P = 0.001] when FTC-TP was BLQ vs. quantifiable. Among participants (n = 75) reporting less than 100% adherence, BLQ FTC-TP in DBS was not predictive of future viremia [aOR 1.3 (0.4--4.6); P = 0.96].

Conclusion:

Nonquantifiable FTC-TP in DBS predicts future viremia and is particularly informative in PWH reporting perfect adherence. As point-of-care adherence measures become available, mismatches between objective and subjective measures, such as FTC-TP in DBS and self-report, could help clinicians identify individuals at an increased risk of future viremia.
Broadly neutralizing antibody responses in the longitudinal primary HIV-1 infection Short Pulse Anti-Retroviral Therapy at Seroconversion cohort
Authors: Granger Luke A. , Huettner Isabella , Debeljak Franka , Kaleebu Pontiano , Schechter Mauro , Tambussi Giuseppe , Weber Jonathan , Miro Jose M. , Phillips Rodney , Babiker Abdel , Cooper David A. , Fisher Martin , Ramjee Gita , Fidler Sarah , Frater John , Fox Julie , Doores Katie J.
Published: June 2021

Objective:

Development of immunogens that elicit an anti-HIV-1 broadly neutralizing antibody (bnAb) response will be a key step in the development of an effective HIV-1 vaccine. Although HIV-1 bnAb epitopes have been identified and mechanisms of action studied, current HIV-1 envelope-based immunogens do not elicit HIV-1 bnAbs in humans or animal models. A better understanding of how HIV-1 bnAbs arise during infection and the clinical factors associated with bnAb development may be critical for HIV-1 immunogen design efforts.

Design and methods:

Longitudinal plasma samples from the treatment-naive control arm of the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) primary HIV-1 infection cohort were used in an HIV-1 pseudotype neutralization assay to measure the neutralization breadth, potency and specificity of bnAb responses over time.

Results:

In the SPARTAC cohort, development of plasma neutralization breadth and potency correlates with duration of HIV infection and high viral loads, and typically takes 3–4 years to arise. bnAb activity was mostly directed to one or two bnAb epitopes per donor and more than 60% of donors with the highest plasma neutralization having bnAbs targeted towards glycan-dependent epitopes.

Conclusion:

This study highlights the SPARTAC cohort as an important resource for more in-depth analysis of bnAb developmental pathways.
Landfast ice: a major driver of reproductive success in a polar seabird
Authors: Labrousse Sara , Fraser Alexander D. , Sumner Michael , Le Manach Frédéric , Sauser Christophe , Horstmann Isabella , Devane Eileen , Delord Karine , Jenouvrier Stéphanie , Barbraud Christophe
Published: June 2021

In a fast-changing world, polar ecosystems are threatened by climate variability. Understanding the roles of fine-scale processes, and linear and nonlinear effects of climate factors on the demography of polar species is crucial for anticipating the future state of these fragile ecosystems. While the effects of sea ice on polar marine top predators are increasingly being studied, little is known about the impacts of landfast ice (LFI) on this species community. Based on a unique 39-year time series of satellite imagery andin situmeteorological conditions and on the world's longest dataset of emperor penguin (Aptenodytes forsteri) breeding parameters, we studied the effects of fine-scale variability of LFI and weather conditions on this species' reproductive success. We found that longer distances to the LFI edge (i.e. foraging areas) negatively affected the overall breeding success but also the fledging success. Climate window analyses suggested that chick mortality was particularly sensitive to LFI variability between August and November. Snowfall in May also affected hatching success. Given the sensitivity of LFI to storms and changes in wind direction, important future repercussions on the breeding habitat of emperor penguins are to be expected in the context of climate change.
A dynamic, ensemble learning approach to forecast dengue fever epidemic years in Brazil using weather and population susceptibility cycles
Authors: McGough Sarah F. , Clemente Leonardo , Kutz J. Nathan , Santillana Mauricio
Published: June 2021

Transmission of dengue fever depends on a complex interplay of human, climate and mosquito dynamics, which often change in time and space. It is well known that its disease dynamics are highly influenced by multiple factors including population susceptibility to infection as well as by microclimates: small-area climatic conditions which create environments favourable for the breeding and survival of mosquitoes. Here, we present a novel machine learning dengue forecasting approach, which, dynamically in time and space, identifies local patterns in weather and population susceptibility to make epidemic predictions at the city level in Brazil, months ahead of the occurrence of disease outbreaks. Weather-based predictions are improved when information on population susceptibility is incorporated, indicating that immunity is an important predictor neglected by most dengue forecast models. Given the generalizability of our methodology to any location or input data, it may prove valuable for public health decision-making aimed at mitigating the effects of seasonal dengue outbreaks in locations globally.
Higher-order organization of biomolecular condensates
Authors: Fare Charlotte M. , Villani Alexis , Drake Lauren E. , Shorter James
Published: June 2021

A guiding principle of biology is that biochemical reactions must be organized in space and time. One way this spatio-temporal organization is achieved is through liquid–liquid phase separation (LLPS), which generates biomolecular condensates. These condensates are dynamic and reactive, and often contain a complex mixture of proteins and nucleic acids. In this review, we discuss how underlying physical and chemical processes generate internal condensate architectures. We then outline the diverse condensate architectures that are observed in biological systems. Finally, we discuss how specific condensate organization is critical for specific biological functions.
Description of Acinetobacter kanungonis sp. nov., based on phylogenomic analysis
Authors: Das Lipika , Deb Sushanta , Das Subrata K.
Published: June 2021

A novel strain of a member of the genus Acinetobacter, strain PS-1T, was isolated from the skin of fresh water pufferfish (Tetraodon cutcutia) collected from Mahanadi River, India. Cells were Gram-stain-negative, aerobic, coccoid and non-motile. The predominant polar lipids were diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE) and phospholipid (PL) and the cell wall sugars were glucose, galactose and ribose. The major cellular fatty acids of PS-1T were C18 : 1ω9c (30.67 %), C16 : 1ω7c (19.54 %), C16 : 0 (15.87 %), C12 : 0 (7.35 %) and C12 : 0 3-OH (6.77 %). The genome size was 3.5 Mbp and the DNA G+C content was 41.97 %. Gene ontology study revealed that the major fraction of genes were associated with biological processes (53.99 %) followed by molecular function (30.42 %) and cellular components (15.58 %). Comparisons of 16S rRNA gene sequences revealed 97.94–97.05 % sequence similarity with the closely related type strains of species of the genus

Acinetobacter

. The average nucleotide identity (ANI) and average amino acid identity (AAI) of PS-1T with reference strains of species of the genus

Acinetobacter

with validly published names were bellow 95–96 and the corresponding in-silico DNA–DNA hybridization (DDH) values were below 70 %. A phylogenomic tree based on core genome analysis supported these results. Genotypic and phenotypic characteristics of PS-1T indicate that the strain represents a novel species of the genus

Acinetobacter

and the name Acinetobacter kanungonis sp. nov. is proposed. The type strain is PS-1T (=JCM 34131T=NCIMB 15260T)
Ketamine for the multivariate effect of PTSD: Systematic review and meta-analysis
Authors: Du Rui , Niu Kun , Lu Guofang , Shang Yulong
Published: June 2021

The aim of this systematic review and meta-analysis was to examine the efficacy, anti-effect of ketamine (intervention) for post-traumatic stress disorder (PTSD) patients during analgesia proceeding and mental illness treatment methods, in comparison with control (midazolam, opioid, saline or placebo). The bibliographic databases Cochrane, Embase, Pubmed and Web of Science were searched from inception to 23 May 2021 for randomized controlled trials, case-control and cohort studies included. For continuous and dichotomous outcomes, respectively, we calculated the mean difference using the inverse-variance method and the risk ratio with the Mantel–Haenszel method. In all, ten trials with 705 patients were included. Confirmed by meta-analysis, ketamine didn’t increase the prevalence of PTSD by a risk ratio (95 % CI) of 0.86 (0.61 to 1.20), p = 0.38 in 3 trials with 503 patients. Evidence of a difference was found in the PTSD-scales taken between ketamine and control during short durations (months), with a mean difference (95 % CI) of 2.45 (1.33 to 3.58), p < 0.001 in three trials with 65 patients. Another evidence is shown in chronic PTSD (years), with a mean difference (95 % CI) of −3.66 (−7.05 to −0.27), p = 0.03 in three trials with 91 patients. Sub-group analysis underlined the increased benefit of ketamine administration for those in whom the procedure was more than one week in the chronic PTSD group. The adoption of ketamine for the short duration of PTSD is in avoidance, but for chronic PTSD is recommended and, in the opinion of the authors, should be considered as a new therapy in view of its potential to ameliorate arousal, avoidance and dissociative symptoms, neuroticism after trauma needing more animal research and clinical trials.
Mechanosensory trichome cells evoke a mechanical stimuli–induced immune response in plants
Authors: Matsumura Mamoru , Nomoto Mika , Itaya Tomotaka , Aratani Yuri , Iwamoto Mizuki , Matsuura Takakazu , Hayashi Yuki , Kinoshita Toshinori , Mori Izumi C , Suzuki Takamasa , Betsuyaku Shigeyuki , Spoel Steven H , Toyota Masatsugu , Tada Yasuomi
Published: June 2021

Perception of pathogen-derived ligands by corresponding host receptors is a pivotal strategy in eukaryotic innate immunity. In plants, this is complemented by circadian anticipation of infection timing, promoting basal resistance even in the absence of pathogen threat. Here, we report that trichomes, hair-like structures on the epidermis, directly sense external mechanical forces caused by raindrops to anticipate waterborne infections in Arabidopsis thaliana. Exposure of leaf surfaces to mechanical stimuli initiates the concentric propagation of intercellular calcium waves away from trichomes to induce defence-related genes. Propagating calcium waves enable effective immunity against pathogenic microbes through the calmodulin-binding transcription activator 3 (CAMTA3) and mitogen-activated protein kinases. We propose a novel layer of plant immunity in which trichomes function as mechanosensory cells to detect potential risks.
TDAExplore: quantitative image analysis through topology-based machine learning
Authors: Edwards Parker , Skruber Kristen , Milićević Nikola , Heidings James B. , Read Tracy-Ann , Bubenik Peter , Vitriol Eric A.
Published: June 2021

Machine learning has greatly expanded the ability to classify images. However, many machine learning classifiers require thousands of images for training and lack quantitative descriptors of how images were grouped. We overcome these limitations with a machine learning approach based on topological data analysis, where a data set of 20-30 images is sufficient to accurately train the classifier. Our method quantifies differences between groups and identifies subcellular regions with the largest dissimilarities.
MorphVAE: Generating Neural Morphologies from 3D-Walks using a Variational Autoencoder with Spherical Latent Space
Authors: Laturnus Sophie , Berens Philipp
Published: June 2021

For the past century, the anatomy of a neuron has been considered one of its defining features: The shape of a neuron’s dendrites and axon fundamentally determines what other neurons it can connect to. These neurites have been described using mathematical tools e.g. in the context of cell type classification, but generative models of these structures have only rarely been proposed and are often computationally inefficient. Here we propose MorphVAE, a sequence-to-sequence variational autoencoder with spherical latent space as a generative model for neural morphologies. The model operates on walks within the tree structure of a neuron and can incorporate expert annotations on a subset of the data using semi-supervised learning. We develop our model on artificially generated toy data and evaluate its performance on dendrites of excitatory cells and axons of inhibitory cells of mouse motor cortex (M1) and dendrites of retinal ganglion cells. We show that the learned latent feature space allows for better cell type discrimination than other commonly used features. By sampling new walks from the latent space we can easily construct new morphologies with a specified degree of similarity to their reference neuron, providing an efficient generative model for neural morphologies.
Live Imaging Reveals the Cellular Events Downstream of SARM1 Activation
Authors: Ko Kwang Woo , Milbrandt Jeffrey , DiAntonio Aaron
Published: June 2021

SARM1 is an inducible NAD+ hydrolase that triggers axon loss and neuronal cell death in the injured and diseased nervous system. While SARM1 activation and enzyme function are well defined, the cellular events downstream of SARM1 activity but prior to axonal demise are much less well understood. Defects in calcium, mitochondria, ATP, and membrane homeostasis occur in injured axons, but the relationships among these events have been difficult to disentangle because prior studies analyzed large collections of axons in which cellular events occur asynchronously. Here we used live imaging with single axon resolution to investigate the cellular events downstream of SARM1 activity. Our studies support a model in which SARM1 NADase activity leads to an ordered sequence of events from loss of cellular ATP, to defects in mitochondrial movement and depolarization, followed by calcium influx, externalization of phosphatidylserine, and loss of membrane permeability prior to catastrophic axonal self-destruction.
Genetic and chemical inhibition of autophagy in zebrafish induced myeloproliferation
Authors: Hasan Kazi Md Mahmudul , Chen Xiang-Ke , Yi Zhen-Ni , Lau Jack Jark-Yin , Ma Alvin Chun-Hang
Published: June 2021

Autophagy is an evolutionary conserved and dynamic lysosomal degradation process for cellular homeostasis and remodelling, which is essential for the development and maintenance of different hematopoietic fates. However, the roles of autophagy in definitive hematopoiesis remain elusive. Here, we exploited zebrafish (Danio rerio) to investigate the effect of knocking-out unc-51 like autophagy activating kinase 1b and 2 (ulk1b and ulk2), homologous of human ULK1 and ULK2, respectively, on definitive hematopoiesis. Upon ulk1b or ulk2 mutation, autophagosome formation was blocked in zebrafish embryos. More importantly, pan-leukocytes (lcp1), common myeloid progenitors (spi1b), neutrophils (mpx), and macrophages (mpeg1.1) significantly elevated, while the hematopoietic stem and progenitor cell (HSPC) (myb), erythroid progenitors (gata1), and embryonic hemoglobin (hbae1.1) significantly reduced in the caudal hematopoietic tissue (CHT) of ulk1b or ulk2 mutant zebrafish embryos. On the other hand, chemically modulated autophagy induction by calpeptin, a downstream autophagy inducer for ulk complex, was insufficient to ameliorate dysregulated hematopoiesis in both ulk1b and ulk2 mutants. Conversely, autophagy inhibitor 3-Methyladenine functioned parallelly with the ulk mutants to maintain defective hematopoiesis. These observations raised a link between autophagy and definitive hematopoiesis and potentiates the fact that autophagy deficiency incorporates with myeloproliferation and anemia, which warrants the significance of autophagy in regulating definitive hematopoiesis.
Analyzing the differences in olfactory bulb mitral cell spiking with ortho- and retronasal stimulation
Authors: Craft Michelle F. , Barreiro Andrea K. , Gautam Shree Hari , Shew Woodrow L. , Ly Cheng
Published: June 2021

The majority of olfaction studies focus on orthonasal stimulation where odors enter via the front nasal cavity, while retronasal olfaction, where odors enter the rear of the nasal cavity during feeding, is understudied. The processing of retronasal odors via coordinated spiking of neurons in the olfactory bulb (OB) is largely unknown. To this end, we use multi-electrode array in vivo recordings of rat OB mitral cells (MC) in response to a food odor with both modes of stimulation, and find significant differences in evoked firing rates and spike count covariances (i.e., noise correlations). To better understand these differences, we develop a single-compartment biophysical OB model that is able to reproduce key properties of important OB cell types. Prior experiments in olfactory receptor neurons (ORN) showed retro stimulation yields slower and spatially smaller ORN inputs than with ortho, yet whether this is consequential for OB activity remains unknown. Indeed with these specifications for ORN inputs, our OB model captures the trends in our OB data. We also analyze how first and second order ORN input statistics dynamically transfer to MC spiking statistics with a phenomenological linear-nonlinear filter model, and find that retro inputs result in larger temporal filters than ortho inputs. Finally, our models show that the temporal profile of ORN is crucial for capturing our data and is thus a distinguishing feature between ortho and retro stimulation, even at the OB. Using data-driven modeling, we detail how ORN inputs result in differences in OB dynamics and MC spiking statistics. These differences may ultimately shape how ortho and retro odors are coded.

Author summary

Olfaction is a key sense for many cognitive and behavioral tasks, and is particularly unique because odors can naturally enter the nasal cavity from the front or rear, i.e., ortho- and retro-nasal, respectively. Yet little is known about the differences in coordinated spiking in the olfactory bulb with ortho versus retro stimulation, let alone how these different modes of olfaction may alter coding of odors. We simultaneously record many cells in rat olfactory bulb to assess the differences in spiking statistics, and develop a biophysical olfactory bulb network model to study the reasons for these differences. Using theoretical and computational methods, we find that the olfactory bulb transfers input statistics differently for retro stimulation relative to ortho stimulation. Furthermore, our models show that the temporal profile of inputs is crucial for capturing our data and is thus a distinguishing feature between ortho and retro stimulation, even at the olfactory bulb. Understanding the spiking dynamics of the olfactory bulb with both ortho and retro stimulation is a key step for ultimately understanding how the brain codes odors with different modes of olfaction.
Mapping the Genetic Landscape of DNA Double-strand Break Repair
Authors: Hussmann Jeffrey A. , Ling Jia , Ravisankar Purnima , Yan Jun , Cirincione Ann , Xu Albert , Simpson Danny , Yang Dian , Bothmer Anne , Cotta-Ramusino Cecilia , Weissman Jonathan S. , Adamson Britt
Published: June 2021

Cells repair DNA double-strand breaks (DSBs) through a complex set of pathways that are critical for maintaining genomic integrity. Here we present Repair-seq, a high-throughput screening approach that measures the effects of thousands of genetic perturbations on the distribution of mutations introduced at targeted DNA lesions. Using Repair-seq, we profiled DSB repair outcomes induced by two programmable nucleases (Cas9 and Cas12a) after knockdown of 476 genes involved in DSB repair or associated processes in the presence or absence of oligonucleotides for homology-directed repair (HDR). The resulting data enabled principled, data-driven inference of DSB end joining and HDR pathways and demonstrated that repair outcomes with superficially similar sequence architectures can have markedly different genetic dependencies. Systematic interrogation of these dependencies then uncovered unexpected relationships among DSB repair genes and isolated incompletely characterized repair mechanisms. This work provides a foundation for understanding the complex pathways of DSB repair and for optimizing genome editing across modalities.
CENP-N promotes the compaction of centromeric chromatin
Authors: Zhou Keda , Gebala Magdalena , Woods Dustin , Sundararajan Kousik , Edwards Garrett , Krzizike Dan , Wereszczynski Jeff , Straight Aaron F. , Luger Karolin
Published: June 2021

The histone variant CENP-A is the epigenetic determinant for the centromere, where it is interspersed with canonical H3 to form a specialized chromatin structure that nucleates the kinetochore. The arrangement of nucleosomes at the centromere into higher order structure is unknown. Here we demonstrate that the CENP-A interacting protein CENP-N promotes the stacking of CENP-A containing mono-nucleosomes and nucleosomal arrays through a previously undefined interaction between the α6 helix of CENP-N with the DNA of a neighboring nucleosome. We describe the cryoEM structures and biophysical characterization of such CENP-N mediated nucleosome stacks and nucleosomal arrays and demonstrate that this interaction is responsible for the formation of densely packed chromatin at the centromere in the cell. Our results provide first evidence that CENP-A, together with CENP-N, promotes specific chromatin higher order structure at the centromere.

One-Sentence Summary

The centromere-associated protein CENP-N promotes centromere-specific nucleosome stacking and higher order structures in vitro and in the cell.
Sensitivity to Error During Visuomotor Adaptation is Similarly Modulated by Abrupt, Gradual and Random Perturbation Schedules
Authors: Coltman Susan K. , van Beers Robert J. , Medendorp W. Pieter , Gribble Paul L.
Published: June 2021

It has been suggested that sensorimotor adaptation involves at least two processes (i.e., fast and slow) that differ in retention and error sensitivity. Previous work has shown that repeated exposure to an abrupt force field perturbation results in greater error sensitivity for both the fast and slow processes. While this implies that the faster relearning is associated with increased error sensitivity, it remains unclear what aspects of prior experience modulate error sensitivity. In the present study, we manipulated the initial training using different perturbation schedules, thought to differentially affect fast and slow learning processes based on error magnitude, and then observed what effect prior learning had on subsequent adaptation. During initial training of a visuomotor rotation task, we exposed three groups of participants to either an abrupt, a gradual, or a random perturbation schedule. During a testing session, all three groups were subsequently exposed to an abrupt perturbation schedule. Comparing the two sessions of the control group who experienced repetition of the same perturbation, we found an increased error sensitivity for both processes. We found that the error sensitivity was increased for both the fast and slow processes, with no reliable changes in the retention, for both the gradual and structural learning groups when compared to the first session of the control group. We discuss the findings in the context of how fast and slow learning processes respond to a history of errors.

New & Noteworthy

We investigated what aspects of prior experience modulate error sensitivity, within the framework of a two-state model of short-term sensorimotor adaptation. We manipulated initial training on a visuomotor adaptation reaching task using specific perturbation schedules that are thought to differentially affect fast and slow learning processes, and we tested what effect these had on subsequent adaptation. We found that sensitivity to adaptation error was similarly modulated by abrupt, gradual, and random perturbation schedules.
miR-486 is an epigenetic modulator of Duchenne muscular dystrophy pathologies
Authors: Hightower Rylie M. , Samani Adrienne , Reid Andrea L. , English Katherine G. , Lopez Michael A. , Doyle J. Scott , Conklin Michael J. , Schneider David A. , Bamman Marcas M. , Widrick Jeffrey J. , Crossman David K. , Xie Min , Jee David , Lai Eric C. , Alexander Matthew S.
Published: June 2021

Duchenne muscular dystrophy (DMD) is an X-linked progressive muscle disorder resulting in muscle weakness and cardiomyopathy. MicroRNAs have been shown to play essential roles in muscle development, metabolism, and disease pathologies. We demonstrated that miR-486 expression is reduced in DMD muscles and its expression levels correlate with dystrophic disease severity.MicroRNA-486knockout mice developed disrupted myofiber architecture, decreased myofiber size, decreased locomotor activity, increased cardiac fibrosis, and metabolic defects that were exacerbated on the dystrophicmdx5cvbackground. We integrated RNA-sequencing and chimeric eCLIP-sequencing data to identify directin vivotargets of miR-486 and associated dysregulated gene signatures in skeletal muscle. In comparison to our DMD mouse muscle transcriptomes, we identified several of these miR-486 muscle targets including known modulators of dystrophinopathy disease symptoms. Together, our studies identify miR-486 as a driver of muscle remodeling in DMD, a useful biomarker for dystrophic disease progression, and highlight chimeric eCLIP-sequencing as a useful tool to identify directin vivomicroRNA target transcripts.

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300 years of change for native fish species in the upper Danube River Basin – historical flow alterations versus future climate change
Authors: Friedrichs-Manthey Martin , Langhans Simone D. , Borgwardt Florian , Hein Thomas , Kling Harald , Stanzel Philipp , Jähnig Sonja C. , Domisch Sami
Published: June 2021

River ecosystems belong to the most threatened ecosystems on Earth. Historical anthropogenic alterations have, and future climate change will further affect river ecosystems and the species therein. While many studies assess the potential effects of expected future changes on species, little is known about the severity of these changes compared to historical alterations. Here, we used a unique 300-year time series of hydrological and climate data to assess the vulnerability of 48 native fish species in the upper Danube River Basin. We calculated species-specific vulnerability estimates relative to the reference period (1970-2000) for the periods 1800-1830, 1900-1930, and 2070-2100, including two Representative Concentration Pathways (RCP 4.5 and 8.5) and identified the environmental drivers of vulnerability estimates. Models showed that future changes under RCP 4.5 would result in moderate species vulnerability compared to historical conditions, while under RCP 8.5, the vulnerability for all species increased substantially. In addition, species vulnerability was mainly driven by hydrology in the past and is likely to be driven by temperature in the future. Our results show that future climate change would alter environmental conditions for riverine fish species at a similar magnitude as historical anthropogenic hydrological river alterations have. Shedding light on such long-term historical and possible future anthropogenic alterations provides valuable insights for prioritising conservation actions for riverine fish species.