bluuebunny/crossref_metadata_2025 huggingface dataset:
Lean Management Systems in Health Care: A Review of the Literature
Authors: Winner Laura E. , Reinhardt Erica , Benishek Lauren , Marsteller Jill A.
Published: February 2022

Background and Objectives:

Many health care organizations now employ Lean tools to improve value in health care, yet reports of their effectiveness vary. This variation may be explained by the context in which Lean is implemented, whether as a tool or as a management system. This article reports on a structured literature review conducted to understand the evidence base for the impact of Lean Management System implementation in health care.

Methods:

A search of PubMed, Scopus, Emerald, EMBASE, CINAHL, and Business Source Complete databases was conducted in November 2017 and repeated in July 2020 to assess the evidence for the impact of Lean Management Systems in health care from 2000 to July 2020. Articles were included if they (1) reported on a Lean Management System or (2) reported on Lean Management System components as described by Mann1 (ie, leader standard work, visual controls, daily accountability process, and discipline).

Results:

A total of 52 articles met the inclusion criteria. Although all articles described some combination of leader standard work, visual management, and daily accountability as part of their Lean Management System, only a handful described use of all 3 components together. Only one explicitly mentioned the fourth component, discipline, required to consistently apply the first 3. The majority reported on single-unit or department implementations and most described daily huddles at the unit level that included review of key performance indicators, identification of improvement opportunities, and problem solving. The role of the leader in a Lean Management System was described a coach and a mentor. Barriers to adoption such as insufficient training and increased workload for nurses were noted along with the importance of relevance to the local context for unit teams to find value in huddle boards and huddles. As yet, evidence of Lean Management System effectiveness in driving health care improvement is absent due to weak study designs and lack of statistical rigor.

Conclusion:

Well-designed research on Lean Management Systems in health care is lacking. Despite increasing adoption of Lean Management Systems over the past 10 years and anecdotal reports of its effectiveness, very few articles provide quantitative data. Those that do report unit-level implementation only, little use of a comprehensive package of Lean Management Systems elements, and weaker study designs and statistical methods. More rigorous study designs and robust statistical analysis are needed to evaluate effectiveness of Lean Management Systems in health care. This represents a rich area for future health care management research.
Steatotic Hepatitis Presenting as a Huge Hypermetabolic Liver Mass
Authors: Doroudinia Abtin , Karam Mehrdad Bakhshayesh , Ghadimi Niloufar , Yousefi Farhad
Published: February 2022

FDG PET/CT scan is a diagnostic imaging modality for oncologic patients, but with false-positive findings in inflammatory diseases. In this interesting case, we present a 24-year-old woman with history of giant cell tumor of the bone (lumbar vertebrae) who underwent whole-body FDG PET/CT scan for treatment response evaluation. FDG PET/CT scan demonstrated a large hypermetabolic tumoral mass lesion in segment VI/VII of the right hepatic lobe. A range of malignant versus benign lesions should be considered as differential diagnoses, including metastasis, primary cholangiocarcinoma, hepatocellular carcinoma, focal nodular hyperplasia, and infection. Final diagnosis of “steatotic hepatitis” after CT-guided biopsy was established.
Evaluation of Variability in Operative Efficiency in Plastic Surgery Procedures
Authors: Boson Alexis L. , Ross Evan , Popp Daniel , Tapking Christian , Ramirez Arianna , Branski Ludwik , Phillips Linda G. , Wolf Steven E.
Published: February 2022

Background

As the cost of healthcare rises, it is imperative to assess value delivered to patients and impact on the economic viability of institutions. We aimed to characterize plastic surgery operative time management and identified areas for efficiency improvement.

Methods

Procedures from a US academic plastic surgery division from September 2017 to August 2018 were reviewed. Times were categorized into preparation (patient in room to incision), procedure (incision to closure), exit (closure to patient exiting room), and turnover (patient out of room to next patient in room). Median and interquartile ranges were calculated. Procedures were classified by relative value units (RVUs) for comparison of procedure complexities and resources. Components were plotted against RVUs; r
2 values were calculated.

Results

We analyzed 522 cases; 69 were excluded for missing data, primary surgeon not a plastic surgeon, emergent cases, or burn procedures; a total of 453 cases were analyzed. Median and interquartile range (in minutes) for preparation was (34, 18 minutes; 23% of total), procedure (53, 75 minutes; 36% of total), exit (30, 27 minutes; 20% of total), and turnover (30, 26 minutes; 20% of total). Normalized to RVUs, preparation demonstrated the most variability (r
2 = 0.19), followed by exit (r
2 = 0.38), and procedure (r
2 = 0.57). Average work RVUs per month was 678.1 ± 158.7. Average work RVUs per OR hour was 7.2.

Conclusions

The largest component with greatest variability was preparation for surgery in the OR. Improved efficiency by decreasing variability increases the value of healthcare delivered to patients and OR throughput.
Phylogenomic and comparative analyses support the reclassification of several Komagataeibacter species as novel members of the Novacetimonas gen. nov. and bring new insights into the evolution of cellulose synthase genes
Authors: Brandão Pedro R. , Crespo Maria T. B. , Nascimento Francisco X.
Published: February 2022

The genus

Komagataeibacter

harbours bacteria presenting the ability to produce increased levels of crystalline nanocellulose, as well as strains used in the industrial production of fermented products and beverages. Still, most of the studies of this biotechnologically relevant genus were conducted based on limited phenotypic methodologies and taxonomical classifications. In this work, a detailed analysis of the currently described genus

Komagataeibacter

was conducted based on phylogenomic analysis, unveiling the phylogenomic relationships within the genus and allowing a detailed phylogenetic analysis of biotechnologically important genes such as those involved in cellulose biosynthesis (bcs genes). Phylogenomic and comparative genomic analysis revealed that several type strains formed an independent genomic group from those of other

Komagataeibacter

, prompting their reclassification as members of a novel genus, hereby termed Novacetimonas gen. nov. The results support the reclassification of

Komagataeibacter hansenii

,

Komagataeibacter cocois

,

Komagataeibacter maltaceti

and

Komagataeibacter pomaceti

as novel members of the genus Novacetimonas. The Novacetimonas hansenii species is the proposed representative of the novel genus. Importantly, phylogenetic analysis based on cellulose biosynthesis genes (bcsABCD, bcsAB2XYC2, bcsAB3C3, bcsAB4), showed that the evolutionary history of these genes is closely related to the strain’s phylogenomic/taxonomic classification. Hence, the robust taxonomic classification of these bacteria will allow the better characterization and selection of strains for biotechnological applications.
Effect of a single dose of oral iron on pancreatic beta-cell function in healthy individuals: a before-and-after (pre-post) study
Authors: Venkatesan Padmanaban , Ramaswamy Jagadish , Vanitha S , Jacob Molly , Varghese Joe
Published: February 2022

Introduction

Althoughin vitroand animal studies have shown that iron loading in pancreatic beta-cells impaired insulin secretion, no human studies have documented the acute effects of oral iron on beta-cell insulin secretory capacity. In this study, we determined beta-cell insulin secretory capacity at baseline and after a single oral dose of iron (ferrous sulphate, 120 mg elemental iron) in healthy male individuals.

Methods

Fifteen healthy male volunteers underwent an oral glucose tolerance test (OGTT) to document baseline glucose tolerance and insulin secretion kinetics (baseline OGTT). One week later, the same subjects underwent a second OGTT, two hours after an oral dose of ferrous sulfate (120 mg of elemental iron) (post-iron OGTT). Changes in disposition index, insulin secretion kinetics, glucose tolerance, insulin clearance, and iron-related parameters in serum were determined.

Results

Compared to baseline OGTT, the areas under the curve (AUC) for serum iron and transferrin saturation increased by 125% and 118% respectively, in the post-iron OGTT. The disposition index decreased by 20% (p=0.009) and the AUC for glucose concentrations increased by 5.7% (p<0.001) during the post-iron OGTT. The insulin secretion rate was marginally lower during the first hour (−3.5%, p=0.63), but became significantly higher during the second hour (22%, p=0.005) of the post-iron OGTT. Concentrations of glucose, insulin and C-peptide in blood were significantly higher at 120 min of the post-iron OGTT.

Conclusion

The decrease in disposition index and glucose tolerance observed after the oral dose of iron points to an acute iron-induced impairment in pancreatic beta-cell insulin secretory capacity.
SpecDB: A Relational Database for Archiving Biomolecular NMR Spectra Data
Authors: Fraga Keith J. , Huang Yuanpeng J. , Ramelot Theresa A. , Swapna G.V.T. , Anak Kendary Arwin Lashawn , Li Ethan , Korf Ian , Montelione Gaetano T.
Published: February 2022

NMR is a valuable experimental tool in the structural biologist’s toolkit to elucidate the structures, functions, and motions of biomolecules. The progress of machine learning, particularly in structural biology, reveals the critical importance of large, diverse, and reliable datasets in developing new methods and understanding in structural biology and science more broadly. Protein NMR research groups produce large amounts of data, and there is renewed interest in organizing this data to train new, sophisticated machine learning architectures to improve biomolecular NMR analysis pipelines. The foundational data type in NMR is the free-induction decay (FID). There are opportunities to build sophisticated machine learning methods to tackle long-standing problems in NMR data processing, resonance assignment, dynamics analysis, and structure determination using NMR FIDs. Our goal in this study is to provide a lightweight, broadly available tool for archiving FID data as it is generated at the spectrometer, and grow a new resource of FID data and associated metadata. This study presents a relational schema for storing and organizing the metadata items that describe an NMR sample and FID data, which we call Spectra Database (SpecDB). SpecDB is implemented in SQLite and includes a Python software library providing a command-line application to create, organize, query, backup, share, and maintain the database. This set of software tools and database schema allow users to store, organize, share, and learn from NMR time domain data. SpecDB is freely available under an open source license at https://github.rpi.edu/RPIBioinformatics/SpecDB.

Abstract Figure
Time-dependent Role of Bisphosphonates on Atherosclerotic Plaque Calcification
Authors: Nik Amirala Bakhshian , Ng Hooi Hooi , Russo Manuel Garcia , Iacoviello Francesco , Shearing Paul R. , Bertazzo Sergio , Hutcheson Joshua D.
Published: February 2022

Atherosclerotic plaque calcification directly contributes to the leading cause of morbidity and mortality by affecting the plaque vulnerability and rupture risk. Small microcalcifications can increase plaque stress and promote rupture, whereas large calcifications can stabilize plaques. Drugs that target bone mineralization may lead to unintended consequences on ectopic plaque calcification and cardiovascular outcomes. Bisphosphonates, common anti-osteoporotic agents, elicited unexpected cardiovascular events in clinical trials. Here, we investigated the role of bisphosphonates treatment and timing on the disruption or promotion of vascular calcification and bone mineral in a mouse model of atherosclerosis. We started the bisphosphonate treatment either before plaque formation, at early plaque formation times associated with the onset of calcification, or at late stages of plaque development. Our data indicate that long term bisphosphonate treatment (beginning prior to plaque development) leads to higher levels of plaque calcification, with a narrower mineral size distribution. When given later in plaque development, we measured a wider distribution of mineral size. These morphological alterations may associate with higher risk of plaque rupture by creating stress foci. Yet, bone mineral density positively correlated with the duration of bisphosphonate treatment.
Behavioral signatures of Y-like neuronal responses in human vision
Authors: Ramirez Ana L. , Thompson Lowell W. , Rosenberg Ari , Baker Curtis L.
Published: February 2022

Retinal ganglion cells initiating the magnocellular/Y-cell visual pathways respond nonlinearly to high spatial frequencies (SFs) and temporal frequencies (TFs). This nonlinearity is implicated in the processing of contrast modulation (CM) stimuli in cats and monkeys, but its contribution to human visual perception is not well understood. Here, we evaluate human psychophysical performance for CM stimuli, consisting of a high SF grating carrier whose contrast is modulated by a low SF sinewave envelope. Subjects reported the direction of motion of CM envelopes or luminance modulation (LM) gratings at different eccentricities. The performance on SF (for LMs) or carrier SF (for CMs) was measured for different TFs (LMs) or carrier TFs (CMs). The best performance for LMs was at lower TFs and SFs, decreasing systematically with eccentricity. However, performance with CMs was bandpass with carrier SF, largely independent of carrier TF, and at the highest carrier TF (20 Hz) decreased minimally with eccentricity. Since the nonlinear subunits of Y-cells respond better at higher TFs compared to the linear response components and respond best at higher SFs that are relatively independent of eccentricity, these results suggest that behavioral tasks employing CM stimuli might reveal nonlinear contributions of retinal Y-like cells to human perception.
Reconstructing cell interactions and state trajectories in pancreatic cancer stromal tumoroids
Authors: Okuda Ryo , Gjeta Bruno , Popovic Doris , Maynard Ashley , Yu Qianhui , He Zhisong , Santel Malgorzata , Seimiya Makiko , Morinaga Soichiro , Miyagi Yohei , Yamaguchi Tomoyuki , Ueno Yasuharu , Taniguichi Hideki , Treutlein Barbara , Camp J. Gray
Published: February 2022

Interlineage communication within a cancer microenvironment can augment cancer cell behaviour and impact response to therapy. Patient-derived cancer organoids provide an opportunity to explore cancer cell biology, however it is a major challenge to generate a complex cancer microenvironment in vitro. Here, we established a stromal tumoroid culture system modeling pancreatic ductal adenocarcinoma (PDAC) that reconstitutes multilineage interactions between cancer, endothelial, and fibroblast cells and recapitulates several aspects of primary tumors. Whole-mount immunohistochemistry on cleared tumoroids reveals organized vessel, desmoplastic fibroblast, and glandular cancer cell phenotypes that emerge over time. Time-course scRNA-seq measurements show that tumoroid formation activates fibroblasts, altering the extracellular matrix (ECM) composition and inducing cancer cell signal-response signatures and metabolic state change. Comparison between tumoroids with normal or cancer associated fibroblasts (CAFs) reveals different ECM compositions, as well as differential effects on cancer cell behaviors and metabolism. We identify Syndecan 1 (SDC1) and Peroxisome proliferator-activated receptor gamma (PPARG) as receptor and metabolic nodes involved in cancer cell response to CAF signals, and blocking SDC1 disrupts cancer cell growth within the tumoroid. Tumoroids from multiple PDAC patients revealed co-existence of subpopulations associated with classical and basal phenotypes, and CAF-induced migration behaviors emerged in certain patient tumoroids. Comparisons between patient tumoroids revealed a multigene migration signature that develops over time reflecting a stress response mechanism that correlates with worse clinical outcome. Altogether, stromal tumoroids can be used to explore dynamic and reciprocal interactions between cancer, CAF and endothelial cell states, and our data provides new inroads into the discovery of personalized pancreatic cancer therapies.
The impacts of anesthetic regimens on the middle cerebral artery occlusion outcomes in male rats
Authors: Mousavi Seyedeh Maryam , Karimi-Haghighi Saeideh , Chavoshinezhad Sara , Pandamooz Sareh , Belém-Filho Ivaldo Jesus Almeida , Keshavarz Somaye , Bayat Mahnaz , Hooshmandi Etrat , Jaberi Abbas Rahimi , Salehi Mohammad Saied , Borhani-Haghighi Afshin
Published: February 2022

Objectives

The middle cerebral artery occlusion (MCAO) model was introduced more than three decades ago to simulate human stroke. Till now, it is the most common platform to investigate stroke-induced pathological changes as well as discover new drugs and treatments. Induction of general anesthesia is mandatory to induce this model, and different laboratories are using various anesthetic drugs, which might affect MCAO results. Therefore, the present study was designed to compare the impacts of several widely used anesthetic regimens on the MCAO outcomes.

Materials and Methods

Here, adult male rats were anesthetized by isoflurane inhalation, intraperitoneal injection of chloral hydrate, intraperitoneal injection of ketamine-xylazine, or subcutaneous administration of ketamine-xylazine, then subjected to 30 min MCAO. Mortality rate, body weight change, infarct size, as well as cognitive and neurological performance were evaluated up to three days after the surgery.

Results

Our findings revealed chloral hydrate caused the highest, while subcutaneous ketamine-xylazine led to the lowest mortality rate. Meanwhile, there were no significant differences in the body weight loss, infarct size, cognitive impairments, and neurological deficits among the experimental groups.

Conclusions

Based on the current results, we proposed that subcutaneous injection of ketamine-xylazine could be an effective anesthetic regimen in the rat model of MCAO with several advantages such as low mortality, cost-effectiveness, safety, ease of administration, and not requiring specialized equipment.
Unbiased pangenome graphs
Authors: Garrison Erik , Guarracino Andrea
Published: February 2022

Motivation

Pangenome variation graphs model the mutual alignment of collections of DNA sequences. A set of pairwise alignments implies a variation graph, but there are no scalable methods to generate such a graph from these alignments. Existing related approaches depend on a single reference, a specific ordering of genomes, or ade Bruijnmodel based on a fixedk-mer length. A scalable, self-contained method to build pangenome graphs without such limitations would be a key step in pangenome construction and manipulation pipelines.

Results

We design theseqwishalgorithm, which builds a variation graph from a set of sequences and alignments between them. We first transform the alignment set into an implicit interval tree. To build up the variation graph, we query this tree-based representation of the alignments to reduce transitive matches into single DNA segments in a sequence graph. By recording the mapping from input sequence to output graph, we can trace the original paths through this graph, yielding a pangenome variation graph. We present an implementation that operates in external memory, using disk-backed data structures and lock-free parallel methods to drive the core graph induction step. We demonstrate that our method scales to very large graph induction problems by applying it to build pangenome graphs for several species.

Availability

seqwishis published as free software under the MIT open source license. Source code and documentation are available athttps://github.com/ekg/seqwish.seqwishcan be installed via Biocondahttps://bioconda.github.io/recipes/seqwish/README.htmlor GNU Guixhttps://github.com/ekg/guix-genomics/blob/master/seqwish.scm.

Contact

egarris5@uthsc.edu
The invasive land flatworm Obama nungara in La Réunion, a French island in the Indian Ocean, the first report of the species for Africa
Authors: Justine Jean-Lou , Marie Amandine Delphine , Gastineau Romain , Fourcade Yoan , Winsor Leigh
Published: February 2022

The land flatworm Obama nungara, a species originating from South America and already invasive in many European countries, is recorded from La Réunion, a French island in the Indian Ocean. This is the first record of O. nungara from this locality and also the first record of the species for Africa. Two specimens were collected, one from Petite France (commune of Saint Paul) and one from La Plaine des Grègues (commune of Saint Joseph); the two localities are widely separated, one in the Western part and one in the South-eastern part of the island. This suggests that the species is already present in several locations in La Réunion. The sightings were communicated to us in 2021, but it is likely that the species is already present since 2020. A molecular analysis of the specimen from Petite France showed that it had the same cox1 haplotype as specimens previously recorded from several countries of Europe; it is hypothesized that the species was imported from Europe, probably from France. We mapped climatic suitability of the species in La Réunion and found that O. nungara could potentially invade a large part of the island. One record was apparently associated with the transport of plates of travertine, a construction material which has numerous cavities, suitable for the transport and survival of adult or cocoons of land flatworms.
Therapeutic resistance in acute myeloid leukemia cells is mediated by a novel ATM/mTOR pathway regulating oxidative phosphorylation
Authors: Park Hae J. , Gregory Mark A. , Zaberezhnyy Vadym , Goodspeed Andrew , Jordan Craig T. , Kieft Jeffrey S. , DeGregori James
Published: February 2022

While leukemic cells are susceptible to various therapeutic insults, residence in the bone marrow microenvironment typically confers protection from a wide range of drugs. Thus, understanding the unique molecular changes elicited by the marrow is of critical importance towards improving therapeutic outcomes. In the present study, we demonstrate that aberrant activation of oxidative phosphorylation serves to induce therapeutic resistance in FLT3 mutant human AML cells challenged with FLT3 inhibitor drugs. Importantly, our findings show that AML cells are protected from apoptosis following FLT3 inhibition due to marrow-mediated activation of ATM, which in turn up-regulates oxidative phosphorylation via mTOR signaling. mTOR is required for the bone marrow stroma-dependent maintenance of protein translation, with selective polysome enrichment of oxidative phosphorylation transcripts, despite FLT3 inhibition. To investigate the therapeutic significance of this finding, we tested the mTOR inhibitor everolimus in combination with the FLT3 inhibitor quizartinib in primary human AML xenograft models. While marrow resident AML cells were highly resistant to quizartinib alone, the addition of everolimus induced profound reduction in tumor burden and prevented relapse. Taken together, these data provide a novel mechanistic understanding of marrow-based therapeutic resistance, and a promising strategy for improved treatment of FLT3 mutant AML patients.
Gut Microbiome Contributes to Cold-climate Adaptation in Lizards
Authors: Chen Jun-Qiong , Zhang Lu-Wen , Zhao Ru-Meng , Wu Hai-Xia , Lin Long-Hui , Li Peng , Li Hong , Qu Yan-Fu , Ji Xiang
Published: February 2022

The metabolic cold-climate adaption hypothesis predicts that animals from cold environments have relatively high metabolic rates compared with their warm-climate counterparts. However, studies testing this hypothesis are sparse. Here, we compared gut microbes between two cold-climate lizard species of the genusPhrynocephalusto test the hypothesis that gut microbiota can help lizards adapt to cold environments by promoting metabolism and absorption efficiency. We kept lizards at 24°C and 30°C for 25 d, and then collected their fecal samples to analyze and compare the microbiota based on 16S rRNA gene sequencing technology. The gut microbiota was mainly composed of Proteobacteria, Firmicutes, Bacteroidetes, and Verrucomicrobia at the phylum level in both species (Proteobacteria > Firmicutes > Verrucomicrobiota inP. erythrurus, and Bacteroidota > Proteobacteria > Firmicutes inP. przewalskii). Further analysis revealed that the gut microbiota contributed to the host’s cold adaptation, but with differences in the relative abundance of these contributory bacteria between the two species. KEGG analysis revealed that the gut microbiota primarily played roles in metabolism, genetic information processing, cellular processes, and environmental information processing in both species. Furthermore, genes related to metabolism were more abundant inP. erythrurusat 24 °C than in other species × temperature combinations, indicating the role of gut microbiota in long-term cold-climate adaptation. Our finding that gut microbiome contributes to cold-climate adaptation in both species but more evidently inP. erythrurususing colder habitats thanP. przewalskiithroughout a year confirms the gut microbiota’s role in the cold-climate adaptation in lizards.

IMPORTANCE

This study proves that temperature affects the composition and relative abundance of the gut microbiota in twoPhrynocephaluslizards in a species-specific manner. Both species harbor specific gut microbiota with significant roles in cold-climate adaptation. Specifically,P. erythrurushas a higher Proteobacteria ratio and relative abundance of metabolism-related microbial genes in the gut thanP. przewalskii. Given thatP. erythrurususes colder habitats thanP. przewalskiithroughout a year, these results suggest that gut microbiota contributes to cold-climate adaptation in both species lizards but more evidently inP. erythrurus. This study provides evidence linking gut microbiome with cold adaptation. The co-evolution mechanism between gut microbiota and their hosts in extreme environments will provide new insights into animal adaptation.
Hand Hygiene Products and Adverse Skin Reactions: A Comparison between Health Care and Non-Health Care Workers
Authors: Roy Simanta , Saha Aishik Dipta , Iktidar Mohammad Azmain , Chowdhury Sreshtha , Tanvir Syed Md. Sayeem , Hawlader Mohammad Delwer Hossain
Published: February 2022

Background

Since December 2019, a deadly coronavirus epidemic has swept the globe. Due to the significant risk of infection, frontline health workers had to use Personal Protective Equipment, including hand hygiene products, to keep their hands hygienic. The present study aims to compare adverse skin responses between Health Care Worker (HCW) and Non-Health Care Worker (NHCW).

Materials and Methods

A descriptive, cross-sectional study of HCW and NHCW throughout the country was executed. A self-structured questionnaire was utilized to gather data from 404 HCWs and 826 NHCWs during a two-month period using multistage sampling. STATA (v16) was used to analyse the data.

Results

41.87% of the study participants experienced adverse skin reactions, which were more prevalent among HCW (65.10%) than NHCW (30.51%). The most often reported skin condition was skin dryness (34.39%), followed by skin peeling (11.71%). Users of alcohol-based hand sanitizers (ABHS) were more likely to get itch (8.13%), whereas soap water users were more likely to suffer skin peeling (35.74%) and rash (7.46%). There was a significant (p<0.001) association between occupation and adverse skin responses, with HCW being 3.5 times more likely to have adverse skin manifestations than NHCW.

Conclusion

The research showed that health care workers had a greater prevalence of skin conditions than the overall population. Hand hygiene guidelines for frontline employees should be equipped with instructions on how to protect oneself from these adverse skin manifestations, since frequent use constitutes a significant risk factor. Above all, health care professionals and the general population should be educated on good hand hygiene practices.
The C. elegans ASPP homolog APE-1 is a junctional protein phosphatase 1 modulator
Authors: Beacham Gwendolyn M. , Wei Derek T. , Beyrent Erika , Zhang Ying , Zheng Jian , Camacho Mari M. K. , Florens Laurence , Hollopeter Gunther
Published: February 2022

How serine/threonine phosphatases are spatially and temporally tuned by regulatory subunits is a fundamental question in cell biology. Ankyrin repeat, SH3 domain, proline-rich-region-containing proteins (ASPPs) are protein phosphatase 1 (PP1) binding partners associated with cardiocutaneous diseases. ASPPs localize PP1 to cell-cell junctions, but how ASPPs localize and whether they regulate PP1 activity in vivo is unclear. Through a C. elegans genetic screen, we find that loss of the ASPP homolog, APE-1, suppresses a pathology called ‘jowls,’ providing us with an in vivo assay for APE-1 activity. Using structure-function analysis, we discover that APE-1’s N-terminal half directs the APE-1–PP1 complex to intercellular junctions. Additionally, we isolated mutations in highly conserved residues of APE-1’s ankyrin repeats that suppress jowls yet do not preclude PP1 binding, implying ASPPs do more than simply localize PP1. Indeed, in vivo reconstitution of APE-1 suggests the ankyrin repeats modulate phosphatase output, a function we find to be conserved among vertebrate homologs.
An electrophysiological and kinematic model ofParamecium, the “swimming neuron”
Authors: Elices Irene , Kulkarni Anirudh , Escoubet Nicolas , Pontani Léa-Laetitia , Prevost Alexis Michel , Brette Romain
Published: February 2022

Parameciumis a large unicellular organism that swims in fresh water using cilia. When stimulated by various means (mechanically, chemically, optically, thermally), it often swims backward then turns and swims forward again in a new direction: this is called the avoiding reaction. This reaction is triggered by a calcium-based action potential. For this reason, several authors have calledParameciumthe “swimming neuron”. Here we present an empirically constrained model of its action potential based on electrophysiology experiments on live immobilized paramecia, together with simultaneous measurement of ciliary beating using particle image velocimetry. Using these measurements and additional behavioral measurements of free swimming, we extend the electrophysiological model by coupling calcium concentration to kinematic parameters, turning it into a swimming model. In this way, we obtain a model of autonomously behavingParamecium. Finally, we demonstrate how the modeled organism interacts with an environment, can follow gradients and display collective behavior. This work provides a modeling basis for investigating the physiological basis of autonomous behavior ofParameciumin ecological environments.

Author Summary

Behavior depends on a complex interaction between a variety of physiological processes, the body and the environment. We propose to examine this complex interaction in an organism consisting of a single excitable and motile cell,Paramecium. The behavior ofParameciumis based on trial and error: when it encounters an undesirable situation, it backs up and changes direction. This avoiding reaction is triggered by an action potential. Here we developed an empirically constrained biophysical model ofParamecium’s action potential, which we then coupled to its kinematics. We then demonstrate the potential of this model in investigating various types of autonomous behavior, such as obstacle avoidance, gradient-following and collective behavior.
Finding coarse and fine scale population structure in a coastal species: population demographics meets genomics
Authors: Catarino Diana , Jorde Per Erik , Rogers Lauren , Albretsen Jon , Jahnke Marlene , Sodeland Marte , Mellerud Ida , Andre Carl , Knutsen Halvor
Published: February 2022

Population genetic studies often focus on patterns at a regional scale and use spatially aggregated samples to draw inferences about population structure and drivers, potentially masking ecologically relevant population sub-structure and dynamics. In this study we use a multidisciplinary approach combining genomic, demographic, and habitat data with an oceanographic particle drift model, to unravel the patterns of genetic structure at different scales in the black goby (Gobius niger) along the Norwegian coast. Using a high-density sampling protocol, we observed restricted gene flow both at a surprisingly fine (kms) and large (100s km) scale. Our results showed a pattern of isolation by distance related to the level of exposure along the Skagerrak coast, where sheltered sampling stations had an overall level of genetic divergence about three times higher (FST =0.0046) than levels observed among exposed samples (FST =0.0015). These results were corroborated by demographic analyses which showed that population-fluctuations decrease in synchrony with distance at much smaller scales for sheltered samples (20 km) than for exposed sites (80 km), suggesting higher population connectivity among exposed sites. We also found a pronounced genetic discontinuity between populations along the Norwegian west and east coasts, with a sharp “break” around the southern tip of Norway, likely driven both by lack of habitat and by oceanographic features.
An efficient early-pooling protocol for environmental DNA metabarcoding
Authors: Ushio Masayuki , Furukawa Saori , Murakami Hiroaki , Masuda Reiji , Nagano Atsushi J.
Published: February 2022

Environmental DNA (eDNA) metabarcoding, a method that applies high-throughput sequencing and universal primer sets to eDNA analysis, has been a promising approach for efficient, comprehensive biodiversity monitoring. However, significant money-, labor-, and time-costs are still required for performing eDNA metabarcoding. In the present study, we assessed the performance of an “early-pooling” protocol (a protocol based on the 1st PCR indexing) to reduce the experimental costs of the library preparation for eDNA metabarcoding. Specifically, we performed three experiments to test the effects of 1st PCR and 2nd PCR indexing protocols on the community composition revealed by eDNA metabarcoding, of post-1st-PCR exonuclease purification on index-hopping, and of the number of PCR replicates and eDNA template volume on the number of detected OTUs. By analyzing 204 eDNA libraries from 3 natural aquatic ecosystems and 1 mock eDNA sample, we show that (i) the 1st PCR indexing does not cause clear biases in the outcomes of eDNA metabarcoding, (ii) post-1st-PCR exonuclease purification reduces the risk of index-hopping, and (iii) increasing the eDNA template volume can increase the number of detected OTUs and reduce the variations in detected community compositions, as can increasing the number of the 1st PCR replicates. Our results show that an early-pooling protocol with post-1st-PCR exonuclease purification and an increased amount of DNA template will reduce the risk of index-hopping, the costs for consumables and reagents, and the handling time in the library preparation, and that it produces comparable results to a 2nd-PCR-indexing protocol. Therefore, once a target metabarcoding region is determined and a set of indexed-1st-PCR primers is prepared, the early-pooling protocol provides a cost-, labor-, and time-efficient way to process a large number of samples.
Task-specific effects of biological sex and sex hormones on object recognition memories in a 6-hydroxydopamine-lesion model of Parkinson’s disease in adult male and female rats
Authors: Pinizzotto Claudia C. , Patwardhan Aishwarya , Aldarondo Daniel , Kritzer Mary F.
Published: February 2022

Many patients with Parkinson’s disease (PD) experience impairments in cognition and memory with few therapeutic options currently available to mitigate them. This has fueled interest in determining how factors including biological sex and sex hormones might modulate higher order function in PD. Previous studies have investigated this in female rats and in gonadally intact and gonadectomized males, with and without hormone replacement, that received bilateral neostriatal 6-hydroxydopamine (6-OHDA) lesions to model PD. Barnes maze and What Where When Episodic-like memory testing showed that 6-OHDA lesions disrupted spatial working and episodic memory functions in both sexes, and that in males, androgen-sensitive behaviors could be rescued in subjects where circulating androgen levels were diminished. Here we tested similar animal groups using the Novel Object Preference (NOP) and Object-in-Place (OiP) tasks. This revealed two entirely different patterns of sex and sex hormone influence. First, for both tasks, 6-ODHA lesions impaired object discrimination in males but not females. Further, for the NOP task, 6-OHDA lesions disrupted discrimination in males rats independently of hormone status. And finally, 6-OHDA lesions impaired OiP performance in males regardless of whether androgen levels were high or low but had no effect on discrimination in gonadectomized rats given 17β-estradiol. Together with previous findings, these data identify the impacts of sex and sex hormones on cognition and memory in PD as behavioral task/behavioral domain specific. This specificity could explain why a cohesive clinical picture of endocrine impacts on higher order function in PD has remained elusive.

HIGHLIGHTS

6-OHDA lesions impair Novel Object performance in male but not female rats.

6-OHDA lesions impair Object-in-Place performance in male but not female rats.

Gonadectomy has no effect on 6-OHDA-induced deficits in Novel Object Preference.

Estrogen replacement prevents 6-OHDA-induced Object-in-Place deficits in males.
Perinatal Oxycodone Exposure Causes Long Term Sex-Dependent Changes in Sensory and Reward Processing in Adult Mice
Authors: Minakova Elena , Mikati Marwa O. , Madasu Manish K. , Conway Sineadh M. , Baldwin Justin W. , Swift Raylynn G. , McCullough Katherine B. , Dougherty Joseph D. , Maloney Susan E. , Al-Hasani Ream
Published: February 2022

In utero opioid exposure is associated with lower weight and a Neonatal Opioid Withdrawal Syndrome (NOWS) at birth, along with longer-term adverse neurodevelopmental outcomes and mood disorders. While NOWS is sometimes treated with continued opioids, clinical studies have not addressed if long-term neurobehavioral outcomes are worsened with continued postnatal exposure to opioids. In addition, pre-clinical studies comparing in utero only opioid exposure to continued post-natal opioid administration for withdrawal mitigation are lacking. Therefore, we implemented a rodent perinatal opioid exposure model of Oxycodone (Oxy) exposure for comparison of long-term consequences of Oxy exposure until birth (Short Oxy) to the impact of continued postnatal opioid exposure (Long Oxy) spanning gestation through birth and lactation. Short Oxy exposure was associated with a sex-specific increase in weight gain trajectory in adult male mice. Long Oxy exposure caused an increased weight gain trajectory in adult males, sex-dependent changes in morphine conditioned place preference, and alterations in nociceptive processing in females. Importantly, there was no evidence of long-term social behavioral deficits, anxiety, hyperactivity, or memory deficits following Short or Long Oxy exposure. Our findings suggest that offspring with prolonged opioid exposure experienced some long-term sequelae compared to pups with opioid cessation at birth. These results highlight the potential long-term consequences of opioid administration as a mitigation strategy for clinical NOWS symptomology and suggest alternatives should be explored.
A possible way to relate the effects of SARS-CoV-2 induced changes in transferrin to severe COVID-19 associated diseases
Authors: Telek Elek , Ujfalusi Zoltán , Kemenesi Gábor , Zana Brigitta , Jakab Ferenc , Lukács András , Hild Gábor
Published: February 2022

The potentially life-threatening Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is responsible for the coronavirus pandemic in 2019 (COVID-19). The transferrin as an essential component of iron-metabolism was suggested to be a link between iron transport associated diseases and COVID-19 infection.

The effect of SARS-CoV-2 on human whole blood was studied by differential scanning calorimetry. The analysis and deconvolution of the thermal transition curves showed that the Tm of transferrin related second peak decreased by 5.16 °C (6.4%) in the presence of SARS-CoV-2 virus. The ratio of the under-curve area of the two main peaks was greatly affected while the total enthalpy of the heat denaturation was nearly unchanged in the presence of the virus.

Based on the results it is possible to conclude that SARS-CoV-2 through binding to transferrin can influence it’s Fe3+ uptake by inducing thermodynamic changes. Transferrin may stay in iron-free apo-conformational state, which probably depends on the SARS-CoV-2 concentration.

SARS-CoV-2 might induce disturbance in the erythropoiesis due to the free iron overload generated iron toxicity. As a late consequence iron toxicity related hepatocellular carcinoma can even develop.

Our work can support the basic role of transferrin in COVID-19 related severe diseases.
Comparative sub-cellular proteome analyses reveals metabolic differentiation and production of effector-like molecules in the dieback phytopathogen Phytophthora cinnamomi
Authors: Andronis Christina E. , Jacques Silke , Lipscombe Richard , Tan Kar-Chun
Published: February 2022

Phytopathogenic oomycetes pose a significant threat to global biodiversity and food security. The proteomes of these oomycetes likely contain important factors that contribute to their pathogenic success, making their discovery crucial for elucidating pathogenicity. Oomycetes secrete effector proteins that overcome or elicit a defence response in susceptible hosts. Phytophthora cinnamomi is a root pathogen that causes dieback in a wide variety of crops and a range of native vegetation world-wide. Virulence proteins produced by P. cinnamomi are not well defined and a large-scale approach to understand the biochemistry of this pathogen has not been documented. Here, soluble mycelial, zoospore and secreted proteomes were obtained and label-free quantitative proteomics was used to compare the composition of protein content of the three sub-proteomes by matching the MS/MS data to a sequenced P. cinnamomi genome. Mass spectra matched to a total of 4635 proteins, validating 17.7% of the predicted gene set of the P. cinnamomi genome. The mycelia were abundant in transporters for nutrient acquisition, metabolism and cellular proliferation. The zoospores had less metabolic related ontologies than the mycelia but were abundant in energy generating, motility and signalling associated proteins. Virulence-associated proteins were identified in the secretome such as candidate effector and effector-like proteins, which interfere with the host immune system. These include hydrolases, cell wall degrading enzymes, putative necrosis-inducing proteins and elicitins. The secretome elicited a hypersensitive response on the roots of a model host and thus suggests evidence of effector activity.

Significance

Phytophthora cinnamomi is a phytopathogenic oomycete that causes dieback disease in native vegetation and several horticultural crops such as avocado, pineapple and macadamia. Whilst this pathogen has significance world-wide, its pathogenicity and virulence have not been described in depth. We carried out comparative label-free proteomics of the mycelia, zoospores and secretome of P. cinnamomi. This study highlights the differential metabolism and cellular processes between the sub-proteomes. Proteins associated with metabolism, nutrient transport and cellular proliferation were over represented in the mycelia. The zoospores have a specialised proteome showing increased energy generation geared towards motility. Candidate effectors and effector-like secreted proteins were also identified, which can be exploited for genetic resistance. This demonstrates a better understanding of the biology and pathogenicity of P. cinnamomi infection that can subsequently be used to develop effective methods of disease management
Discovery of Novel Trans-Ancestry and Ancestry-Specific Gene Loci for Total Testosterone in a Multi-Ancestral Analysis of Men in the Million Veteran Program
Authors: Pagadala Meghana S. , Jasuja Guneet K. , Palnati Madhuri , Lynch Julie , Anglin Tori , Chang Nelson , Deka Rishi , Lee Kyung Min , Agiri Fatai Y. , Seibert Tyler M. , Rose Brent S. , Carter Hannah , Panizzon Matthew S. , Hauger Richard L.
Published: February 2022

Utilizing data from the Million Veteran Program (MVP), we investigated the genetic determinants underlying total testosterone levels via a multi-ancestral analysis of 124,593 individuals of European (n=88,385), African (n=25,235) and Hispanic (n=10,973) ancestry. We identified 46 trans-ancestry variants and 17 ancestry-specific variants, of which 14 trans-ancestry variants and 15 ancestry-specific variants are novel associations with testosterone. Results implicate genes regulating testosterone shared across ancestral groups, which include SHBG, JMJD1C, FXR2, SENP3, TNFSF12-TNFSF13 while implicating genes such as MSN, DMD, VSIG4, CHEK2, TKTL1 that may underlie ancestry-group differences in testosterone regulation. We also linked testosterone variants on the X chromosome with differential risk of chronic kidney disease and hereditary hemolytic anemias in African and Hispanic ancestry groups, respectively. Lastly, we constructed a polygenic score from our 46 trans-ancestry variants and associated it with testicular dysfunction, hyperlipidemia, gout and prostate cancer with stronger prostate cancer associations in Hispanic and African ancestry groups compared to the European ancestry group. These findings provide insight into ancestry-specific androgen regulation and identify novel variants for disease risk stratification in patients.