bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome analysis of hepatic injury caused by delayed resuscitation following severe burns in rats
Authors: Liu Zhaoxing , Li Dawei , Yang Jianqiu , Liu Xinzhu , Zhang Bohan , Zang Yu , Zhang Wen , Song Yaoyao , Niu Yuezeng , Shen Chuanan
Published: June 2023

BACKGROUND

Delayed resuscitation (DR) can induce hepatic reperfusion injury after severe burns. The underlying molecular mechanisms of DR-induced hepatic injury remain unidentified. This study sought to predict candidate genes and molecular pathways in a DR-induced hepatic injury preclinical model.

METHODS

Rats were randomized into three groups: the sham injury (Sham) group; the DR group, which had third-degree burns covering 30% of the body surface area and DR; and the early resuscitation (ER) group, in which ER was administered. The liver tissue was harvested for the purpose of evaluating hepatic injury and performing transcriptome sequencing. Differentially expressed genes (DEGs) for DR versus Sham and ER versus DR were analyzed respectively. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Ingenuity Pathway Analysis were used. The DEGs and critical module genes were intersected to obtain critical genes. Immune infiltration and competing endogenous RNA networks were also analyzed. Validation was conducted using quantitative real-time polymerase chain reaction.

RESULTS

Hepatic injury was evident in DR rats. There were 2,430 DEGs between DR and Sham and 261 DEGs between ER and DR. Differentially expressed genes were mostly enriched in metabolic process for DR versus Sham, and immune and inflammatory processes for ER versus DR. Four critical genes (Tff3, C1galt1, Cd48, and MGC105649) were obtained by screening. Five immune cells were significantly different between DR and Sham, and seven immune cells were significantly different between ER and DR in immunoassays. Three critical genes, 75 miRNAs, 7 lncRNAs, and 197 edges constituted the mRNA-miRNA-lncRNA linkages, which included C1galt1-rno-miR-330-5p-Pvt1, among others.

CONCLUSION

This is the first attempt to perform a high-throughput analysis of gene expression profiles in DR-induced hepatic injury. It shows that immunity and inflammation-related RNAs and pathways play an important role in the progression of hepatic injury. It also provides insight into some important RNAs and regulatory targets related to disease.
Prolonging the therapeutic window for valproic acid treatment in a swine model of traumatic brain injury and hemorrhagic shock
Authors: Jin Guang , Ho Jessie W. , Keeney-Bonthrone Toby Philip , Pai Manjunath P. , Wen Bo , Ober Rebecca Ariel , Dimonte Deanna , Chtraklin Kiril , Joaquin Theodore Alan , Latif Zoya , Vercruysse Claire , Alam Hasan B.
Published: June 2023

BACKGROUND

It has previously been shown that administration of valproic acid (VPA) can improve outcomes if given within an hour following traumatic brain injury (TBI). This short therapeutic window (TW) limits its use in real-life situations. Based upon its pharmacokinetic data, we hypothesized that TW can be extended to 3 hours if a second dose of VPA is given 8 hours after the initial dose.

METHOD

Yorkshire swine (40–45 kg; n = 10) were subjected to TBI (controlled cortical impact) and 40% blood volume hemorrhage. After 2 hours of shock, they were randomized to either (1) normal saline resuscitation (control) or (2) normal saline–VPA (150 mg/kg × two doses). First dose of VPA was started 3 hours after the TBI, with a second dose 8 hours after the first dose. Neurologic severity scores (range, 0–36) were assessed daily for 14 days, and brain lesion size was measured via magnetic resonance imaging on postinjury day 3.

RESULTS

Hemodynamic and laboratory parameters of shock were similar in both groups. Valproic acid–treated animals had significantly less neurologic impairment on days 2 (16.3 ± 2.0 vs. 7.3 ± 2.8) and 3 (10.9 ± 3.6 vs. 2.8 ± 1.1) postinjury and returned to baseline levels 54% faster. Magnetic resonance imaging showed no differences in brain lesion size on day 3. Pharmacokinetic data confirmed neuroprotective levels of VPA in the circulation.

CONCLUSION

This is the first study to demonstrate that VPA can be neuroprotective even when given 3 hours after TBI. This expanded TW has significant implications for the design of the clinical trial.
Precision Automated Critical Care Management: Closed-loop critical care for the treatment of distributive shock in a swine model of ischemia-reperfusion
Authors: Ganapathy Aravindh S. , Patel Nathan T.P. , Wiley Aidan P. , Lane Magan R. , Jordan James E. , Johnson M. Austin , Adams Jason Y. , Neff Lucas P. , Williams Timothy K.
Published: June 2023

BACKGROUND

Goal-directed blood pressure management in the intensive care unit can improve trauma outcomes but is labor-intensive. Automated critical care systems can deliver scaled interventions to avoid excessive fluid or vasopressor administration. We compared a first-generation automated drug and fluid delivery platform, Precision Automated Critical Care Management (PACC-MAN), to a more refined algorithm, incorporating additional physiologic inputs and therapeutics. We hypothesized that the enhanced algorithm would achieve equivalent resuscitation endpoints with less crystalloid utilization in the setting of distributive shock.

METHODS

Twelve swine underwent 30% hemorrhage and 30 minutes of aortic occlusion to induce an ischemia-reperfusion injury and distributive shock state. Next, animals were transfused to euvolemia and randomized into a standardized critical care (SCC) of PACC-MAN or an enhanced version (SCC+) for 4.25 hours. SCC+ incorporated lactate and urine output to assess global response to resuscitation and added vasopressin as an adjunct to norepinephrine at certain thresholds. Primary and secondary outcomes were decreased crystalloid administration and time at goal blood pressure, respectively.

RESULTS

Weight-based fluid bolus volume was lower in SCC+ compared with SCC (26.9 mL/kg vs. 67.5 mL/kg, p = 0.02). Cumulative norepinephrine dose required was not significantly different (SCC+: 26.9 μg/kg vs. SCC: 13.76 μg/kg, p = 0.24). Three of 6 animals (50%) in SCC+ triggered vasopressin as an adjunct. Percent time spent between 60 mm Hg and 70 mm Hg, terminal creatinine and lactate, and weight-adjusted cumulative urine output were equivalent.

CONCLUSION

Refinement of the PACC-MAN algorithm decreased crystalloid administration without sacrificing time in normotension, reducing urine output, increasing vasopressor support, or elevating biomarkers of organ damage. Iterative improvements in automated critical care systems to achieve target hemodynamics in a distributive-shock model are feasible.
Damage-control resuscitation in pediatric trauma: What you need to know
Authors: Russell Robert T. , Leeper Christine M. , Spinella Philip C.
Published: June 2023

Damage-control resuscitation (DCR) consists of rapid control of bleeding, avoidance of hemodilution, acidosis, and hypothermia; early empiric balanced transfusions with red blood cells, plasma and platelets, or whole blood when available, and the use of intravenous or mechanical hemostatic adjuncts when indicated. The principles used in pediatric and adult trauma patients are quite similar. There are very important recognized physiologic differences in children with traumatic hemorrhagic shock that warrant slight variations in DCR. In pediatric trauma patients, early physiologic signs of shock may be different from adults and the early recognition of this is critical to enable prompt resuscitation and utilization of damage control principles. This review details the current principles of pediatric DCR based on the best available literature, expert consensus recommendations, and also describes a practical guide for implementation of DCR strategies for pediatric trauma patients.
Estimating the fitness cost and benefit of antimicrobial resistance from pathogen genomic data
Authors: Helekal David , Keeling Matt , Grad Yonatan H. , Didelot Xavier
Published: June 2023

Increasing levels of antibiotic resistance in many bacterial pathogen populations are a major threat to public health. Resistance to an antibiotic provides a fitness benefit when the bacteria are exposed to this antibiotic, but resistance also often comes at a cost to the resistant pathogen relative to susceptible counterparts. We lack a good understanding of these benefits and costs of resistance for many bacterial pathogens and antibiotics, but estimating them could lead to better use of antibiotics in a way that reduces or prevents the spread of resistance. Here, we propose a new model for the joint epidemiology of susceptible and resistant variants, which includes explicit parameters for the cost and benefit of resistance. We show how Bayesian inference can be performed under this model using phylogenetic data from susceptible and resistant lineages and that by combining data from both we are able to disentangle and estimate the resistance cost and benefit parameters separately. We applied our inferential methodology to several simulated datasets to demonstrate good scalability and accuracy. We analysed a dataset of
Neisseria gonorrhoeae
genomes collected between 2000 and 2013 in the USA. We found that two unrelated lineages resistant to fluoroquinolones shared similar epidemic dynamics and resistance parameters. Fluoroquinolones were abandoned for the treatment of gonorrhoea due to increasing levels of resistance, but our results suggest that they could be used to treat a minority of around 10% of cases without causing resistance to grow again.
Thomas Willis' iatrochemistry and the activity of matter
Authors: Clericuzio Antonio
Published: June 2023

This article presents a comprehensive study of Thomas Willis' chemistry and matter theory. Willis' medical and chemical views rest on the assumption that matter is both active and endowed with life. He resorted to chemical principles, which he interpreted in corpuscular terms, to account for physiological processes, including those occurring in the brain and in the nervous system. He combined anatomical research with the chemical investigation of organic fluids, giving a central role to spirits, which he saw as active particles of matter. Willis deployed analogies between chemical apparatuses (and processes) and physiological phenomena, as attested by his study of the brain and of the nervous system. He saw muscular motion, sensation and imagination as the result of chemical reactions triggered by animal spirits, i.e. by volatile and active corpuscles generated by the distillation of blood in the cerebral cortex. Furthermore, he posited that elementary forms of reasoning are reducible to matter, namely to the activity of animal spirits.
Copper-doped ZnO-ZrO
2
solid solution catalysts for promoting methanol synthesis from CO
2
hydrogenation
Authors: Song Fujiao , Cheng Wenqiang , Yu Yang , Cao Yan , Xu Qi
Published: June 2023

Copper-doped ZnO-ZrO
2
solid solution catalysts were synthesized via co-precipitation for promoting CH
3
OH synthesis via hydrogenation of CO
2
. Various testing methods were applied to investigate the effect of various copper contents on the catalysts. The catalytic performance was evaluated by a fixed bed reactor. XRD, HRTEM and Raman spectra collectively indicated that a ZnO-ZrO
2
solid solution catalyst with 3% Cu had a higher Cu dispersion, while the H
2
-TPR results confirmed that a catalyst with 3% Cu had more Cu active sites under low temperature H
2
pretreatment. When the copper content increased to 5% and 10%, the catalyst showed a better Cu crystallinity and a worse Cu dispersion, which could have a negative effect. Therefore, the CO
2
conversion and methanol yield with a 3% CuZnO-ZrO
2
catalyst at 5 MPa, 250°C and 12 000 ml/(g h) increased by 8.6% and 7.6%, respectively. Moreover, the CH
3
OH selectivity and catalytic stability of the solid solution catalyst were better than those of the traditional CZA catalyst.
Variation in foraging activity influences area-restricted search behaviour by bottlenose dolphins
Authors: Fernandez-Betelu Oihane , Iorio-Merlo Virginia , Graham Isla M. , Cheney Barbara J. , Prentice Simone M. , Cheng Rachael Xi , Thompson Paul M.
Published: June 2023

Area-restricted search (ARS) behaviour is commonly used to characterize spatio-temporal variation in foraging activity of predators, but evidence of the drivers underlying this behaviour in marine systems is sparse. Advances in underwater sound recording techniques and automated processing of acoustic data now provide opportunities to investigate these questions where species use different vocalizations when encountering prey. Here, we used passive acoustics to investigate drivers of ARS behaviour in a population of dolphins and determined if residency in key foraging areas increased following encounters with prey. Analyses were based on two independent proxies of foraging: echolocation buzzes (widely used as foraging proxies) and bray calls (vocalizations linked to salmon predation attempts). Echolocation buzzes were extracted from echolocation data loggers and bray calls from broadband recordings by a convolutional neural network. We found a strong positive relationship between the duration of encounters and the frequency of both foraging proxies, supporting the theory that bottlenose dolphins engage in ARS behaviour in response to higher prey encounter rates. This study provides empirical evidence for one driver of ARS behaviour and demonstrates the potential for applying passive acoustic monitoring in combination with deep learning-based techniques to investigate the behaviour of vocal animals.
Environmental and molecular regulation of asexual reproduction in the sea anemoneNematostella vectensis
Authors: Al-Shaer Layla , Leach Whitney , Baban Noor , Yagodich Mia , Gibson Mathew C. , Layden Michael J.
Published: June 2023

Cnidarians exhibit incredible reproductive diversity, with most capable of sexual and asexual reproduction. Here, we investigate factors that influence asexual reproduction in the burrowing sea anemoneNematostella vectensis,which can propagate asexually by transverse fission of the body column. By altering culture conditions, we demonstrate that the presence of a burrowing substrate strongly promotes transverse fission. In addition, we show that animal size does not affect fission rates, and that the plane of fission is fixed along the oral–aboral axis of the polyp. Homeobox transcription factors and components of the TGFβ, Notch, and FGF signalling pathways are differentially expressed in polyps undergoing physal pinching suggesting they are important regulators of transverse fission. Gene ontology analyses further suggest that during transverse fission the cell cycle is suppressed, and that cell adhesion and patterning mechanisms are downregulated to promote separation of the body column. Finally, we demonstrate that the rate of asexual reproduction is sensitive to population density. Collectively, these experiments provide a foundation for mechanistic studies of asexual reproduction inNematostella,with implications for understanding the reproductive and regenerative biology of other cnidarian species.
Bullying as an advertisement of social dominance in common waxbills
Authors: Beltrão Patrícia , Gomes Ana Cristina R. , Cardoso Gonçalo C.
Published: June 2023

Bullying consists of preferentially attacking individuals lowest in the dominance hierarchy, and its functions are unclear because the most subordinate individuals do not pose social challenges to the aggressor. Instead, conflict is expected mostly between individuals of similar dominance rank or socially distant (i.e. weakly associated), among whom dominance relationships may not be well established. A possible function of bullying is that it may be used as a low-risk strategy of showing-off dominance to relevant third parties. To study this hypothesis, we monitored aggressions during feeding, the composition of audiences, dominance hierarchy and social network of common waxbills (
Estrilda astrild
) in an open-air mesocosm, and tested (i) whether their aggressions show a pattern of bullying, and (ii) whether audience effects influence aggressiveness. Waxbills showed bullying, most often attacking the lowest ranking individuals rather than socially distant individuals or those of similar dominance rank, and aggressions increased when the audience included socially distant individuals, indicating a signalling function of bullying. Showing-off dominance in the presence of socially distant individuals may be a strategy to manage dominance hierarchies, avoiding direct fights with potentially dangerous opponents in the audience. We suggest that bullying is a safe manner of managing dominance hierarchies, by signalling dominance status to potential opponents.
Characterization of three Francisella tularensis genomes from Oklahoma, USA
Authors: Narayanan Sai , Couger Brian , Bates Haley , Gupta Sushim Kumar , Malayer Jerry , Ramachandran Akhilesh
Published: June 2023

Francisella tularensis

, the causative agent for tularaemia, is a Tier 1 select agent, and a pan-species pathogen of global significance due to its zoonotic potential. Consistent genome characterization of the pathogen is essential to identify novel genes, virulence factors, antimicrobial resistance genes, for studying phylogenetics and other features of interest. This study was conducted to understand the genetic variations among genomes of

F. tularensis

isolated from two felines and one human source. Pan-genome analysis revealed that 97.7 % of genes were part of the core genome. All three

F. tularensis

isolates were assigned to sequence type A based on single nucleotide polymorphisms (SNPs) in sdhA. Most of the virulence genes were part of the core genome. An antibiotic resistance gene coding for class A beta-lactamase was detected in all three isolates. Phylogenetic analysis showed that these isolates clustered with other isolates reported from Central and South-Central USA. Assessment of large sets of the

F. tularensis

genome sequences is essential in understanding pathogen dynamics, geographical distribution and potential zoonotic implications.
Evaluation of the diagnostic performance of the urine dipstick test for the detection of urinary tract infections in patients treated in Kenyan hospitals
Authors: Maina John , Mwaniki John , Mwiti Franklin , Kiiru Susan , Katana Japhet , Wanja Fredrick , Mukaya Joel , Khasabuli Osborn , Asiimwe Benon , Gillespie Stephen , Stelling John , Mshana Stephen , Holden Matthew , Sabiiti Wilber , Kiiru John ,   HATUA consortium
Published: June 2023

Introduction. Culture is the gold-standard diagnosis for urinary tract infections (UTIs). However, most hospitals in low-resource countries lack adequately equipped laboratories and relevant expertise to perform culture and, therefore, rely heavily on dipstick tests for UTI diagnosis.

Research gap. In many Kenyan hospitals, routine evaluations are rarely done to assess the accuracy of popular screening tests such as the dipstick test. As such, there is a substantial risk of misdiagnosis emanating from inaccuracy in proxy screening tests. This may result in misuse, under-use or over-use of antimicrobials.

Aim. The present study aimed to assess the accuracy of the urine dipstick test as a proxy for the diagnosis of UTIs in selected Kenyan hospitals.

Methods. A hospital-based cross-sectional method was used. The utility of dipstick in the diagnosis of UTIs was assessed using midstream urine against culture as the gold standard.

Results. The dipstick test predicted 1416 positive UTIs, but only 1027 were confirmed positive by culture, translating to a prevalence of 54.1 %. The sensitivity of the dipstick test was better when leucocytes and nitrite tests were combined (63.1 %) than when the two tests were separate (62.6 and 50.7 %, respectively). Similarly, the two tests combined had a better positive predictive value (87.0 %) than either test alone. The nitrite test had the best specificity (89.8 %) and negative predictive value (97.4 %) than leucocytes esterase (L.E) or both tests combined. In addition, sensitivity in samples from inpatients (69.2 %) was higher than from outpatients (62.7 %). Furthermore, the dipstick test had a better sensitivity and positive predictive value among female (66.0 and 88.6 %) than male patients (44.3 and 73.9 %). Among the various patient age groups, the dipstick test’s sensitivity and positive predictive value were exceptionally high in patients ≥75 years old (87.5 and 93.3 %).

Conclusion. Discrepancies in prevalence from the urine dipstick test and culture, the gold standard, indicate dipstick test inadequacy for accurate UTI diagnosis. The finding also demonstrates the need for urine culture for accurate UTI diagnosis. However, considering it is not always possible to perform a culture, especially in low-resource settings, future studies are needed to combine specific UTI symptoms and dipstick results to assess possible increases in the test’s sensitivity. There is also a need to develop readily available and affordable algorithms that can detect UTIs where culture is not available.
Production of xylanase by Aspergillus niger GIO and Bacillus megaterium through solid-state fermentation
Authors: Fasiku Samuel Adedayo , Bello Mobolaji Akeem , Odeniyi Olubusola Ayoola
Published: June 2023

Xylanase breaks xylan down to xylose, which is used in industries such as pulp and paper, food and feed, among others. The utilization of wastes for xylanase production is economical, hence this work aimed at producing xylanase through solid-state fermentation and characterizing the enzyme. Xylanase-producing strains of

Bacillus megaterium

and Aspergillus niger GIO were inoculated separately in a 5 and 10 day solid fermentation study on maize straw, rice straw, sawdust, corn cob, sugarcane bagasse, conifer litters, alkaline-pretreated maize straw (APM) and combined alkaline and biological-pretreated maize straw, respectively. The best substrate was selected for xylanase production. The crude enzyme was extracted from the fermentation medium and xylanase activity was characterized using parameters such as temperature, cations, pH and surfactants. Among different substrates, the highest xylanase activity of 3.18 U ml−1 was recorded when A. niger GIO was grown on APM. The xylanase produced by A. niger GIO and

B. megaterium

had the highest activities (3.67 U ml−1 and 3.36 U ml−1) at 40 °C after 30 and 45 min of incubation, respectively. Optimal xylanase activities (4.58 and 3.58 U ml−1) of A. niger GIO and

B. megaterium

, respectively, were observed at pH 5.0 and 6.2. All cations used enhanced xylanase activities except magnesium ion. Sodium dodecyl sulfate supported the highest xylanase activity of 6.13 and 6.90 U ml−1 for A. niger GIO and

B. megaterium

, respectively. High yields of xylanase were obtained from A. niger GIO and

B. megaterium

cultivated on APM. The xylanase activities were affected by pH, temperature, surfactants and cations.
HNF4α regulates acyl chain remodeling and ether lipid accumulation in hepatic steatosis
Authors: Von Bank Helaina , Geoghegan Gisela , Jain Raghav , Kotulkar Manasi , Hurtado-Thiele Mae , Gonzalez Paula , Kirsh Charlie , Chevalier Autumn , Huck Ian , Scheuler Kathryn , Attie Alan , Keller Mark , Apte Udayan , Simcox Judith
Published: June 2023

Hepatocyte nuclear factor 4α (HNF4α) is an established transcriptional master regulator of differentiation, maintenance, and metabolism. Polymorphisms in HNF4α are linked to several diseases in humans including diabetes and nonalcoholic fatty liver disease (NAFLD). Identifying novel regulation of lipid metabolism by HNF4α would inform on NAFLD development and progression. We directly assessed HNF4α activity through chromatin immunoprecipitation (ChIP)-sequencing and integration of untargeted lipidomics. Direct regulation by HNF4α can be difficult to assess due to the role of HNF4α in liver homeostasis; to rapidly disrupt activity, mice were exposed to cold stress which induces hepatic steatosis in several hours. Cold exposure shifted HNF4α activity with differential genome occupancy of more than 50% of HNF4α binding sites. Focusing on HNF4α binding to promoter with active transcription determined that HNF4α directly regulates fatty acid desaturation, ether lipid synthesis, and peroxisomal biogenesis in response to cold exposure. Integration of lipidomics found that cold exposure increases the very long chain polyunsaturated fatty acid composition of the hepatic lipid pool, including ether lipids, in an HNF4α dependent manner. Because portions of ether lipid synthesis are in the peroxisome and peroxisomal biogenesis is directly HNF4α regulated, we analyzed peroxisomal abundance and found increases with cold exposure that are ablated with loss of HNF4α. This peroxisomal regulation was independent of PPARα— a known regulator of peroxisomes and lipid metabolism—since loss of HNF4α was not rescued by PPARα overexpression. These data determined that regulation of hepatic steatosis by HNF4α is more complex than triglyceride accumulation and includes acyl chain modifications, ether lipid synthesis, and peroxisomal oxidation.
Can higher aggressiveness effectively compensate for a virulence deficiency in plant pathogen? A case study ofPuccinia triticina’s fitness evolution in a diversified varietal landscape
Authors: Fontyn Cécilia , Meyer Kevin JG , Boixel Anne-Lise , Picard Corentin , Destanque Adrien , Marcel Thierry C , Suffert Frédéric , Goyeau Henriette
Published: June 2023

Plant resistances impose strong selective pressure on plant pathogen populations through the deployment of resistance genes, which leads to the emergence of new virulences. The pathogen adaptation also involves other parasitic fitness traits, especially aggressiveness components. A previous study on Puccinia triticina, the causal agent of wheat leaf rust, revealed that the distribution frequency of virulences in the French pathogen population cannot be fully explained by the major resistance genes deployed in the landscape. From 2012 to 2015, two dominant pathotypes (distinguished by their combination of virulences) were equally frequent despite the theoretical advantage conferred to one pathotype (166 317 0) by its virulence to Lr3, frequent in the cultivated landscape, whereas the other (106 314 0) is avirulent to this gene. To explain this apparent contradiction, we assessed three components of aggressiveness — infection efficiency, latency period and sporulation capacity — for 23 isolates representative of the most frequent genotype within each pathotype (106 314 0-G2 and 166 317 0-G1, identified by their combination of microsatellite markers). We tested these isolates on seedlings of Michigan Amber, a ‘naive’ wheat cultivar that has never been grown in the landscape, Apache, a ’neutral‘ cultivar with no selection effect on the landscape-pathotype pattern, and several cultivars that were frequently grown. We found that 106 314 0-G2 was more aggressive than 166 317 0-G1, with a consistency for the three components of aggressiveness. Our results show that aggressiveness plays a significant role in driving evolution in pathogen populations by acting as a selective advantage, even offsetting the disadvantage of lacking virulence towards a major Lr gene. Higher aggressiveness represents a competitive advantage that is likely even more pronounced when exhibited at the landscape scale as the expression of its multiple components is amplified by the polycyclic nature of epidemics.
Type 4 pili mediated natural competence inFusobacterium nucleatum
Authors: Sanders Blake E. , Umana Ariana , Nguyen Tam T.D. , Williams Kevin J. , Yoo Christopher C. , Casasanta Michael A. , Wozniak Bryce , Slade Daniel J.
Published: June 2023

Many bacterial species naturally take up DNA from their surroundings and recombine it into their chromosome through homologous gene transfer (HGT) to aid in survival and gain advantageous functions. Herein we present the first characterization of Type 4 pili mediated natural competence inFusobacterium nucleatum, which are Gram-negative, anaerobic bacteria that participate in a range of infections and diseases including periodontitis, preterm birth, and cancer. We bioinformatically identified components of the Type 4 conjugal pilus machinery and show this is a conserved system within theFusobacteriumgenus. We next validate Type 4 pili in natural competence inF. nucleatumstrain 23726 and show that gene deletions in key components of pilus deployment (pilQ)and cytoplasmic DNA import (comEC)abolish DNA uptake and chromosomal incorporation. We next show that natural competence may require nativeF. nucleatumDNA methylation to bypass restriction modification systems and allow subsequent genomic homologous recombination. In summary, this proof of principle study provides the first characterization of natural competence inFusobacterium nucleatumand highlights the potential to exploit this DNA import mechanism as a genetic tool to characterize virulence mechanisms of an opportunistic oral pathogen.
Host Gastric Corpus Microenvironment FacilitatesAscaris SuumLarval Hatching And Infection in a Murine Model
Authors: Wu Yifan , Adeniyi-Ipadeola Grace , Adkins-Threats Mahliya , Seasock Matthew , Suarez-Reyes Charlie , Fujiwara Ricardo , Bottazzi Maria Elena , Song Lizhen , Mills Jason C. , Weatherhead Jill E.
Published: June 2023

Ascariasis (roundworm) is the most common parasitic helminth infection globally and can lead to significant morbidity in children including chronic lung disease. Children become infected withAscarisspp. via oral ingestion of eggs. It has long been assumed thatAscarisegg hatching and larval translocation across the gastrointestinal mucosa to initiate infection occurs in the small intestine. Here, we show thatA. suumlarvae hatched in the host stomach in a murine model. Larvae utilize acidic mammalian chitinase (AMCase; acid chitinase;Chia) from chief cells and acid pumped by parietal cells to emerge from eggs on the surface of gastric epithelium. Furthermore, antagonizing AMCase and gastric acid in the stomach decreases parasitic burden in the liver and lungs and attenuates lung disease. GivenAscariseggs are chitin-coated, the gastric corpus would logically be the most likely organ for egg hatching, though this is the first study directly evincing the essential role of the host gastric corpus microenvironment. These findings point towards potential novel mechanisms for therapeutic targets to prevent ascariasis and identify a new biomedical significance of AMCase in mammals.
Elevated Expression ofsrpRiPPs Across Bacterial Phyla in Marine Sponges
Authors: Waterworth Samantha C. , Rees Evan R. , Clark Chase M. , Carlson Skylar , Miller Ian J. , Puglisi Melany , Kwan Jason C.
Published: June 2023

We investigated transcriptional activity, at a genome-resolved level, of bacterial communities in twoS. officinalisand twoI. felixsponges, both of which are considered high microbial abundance (HMA) sponges that harbor similar bacterial communities. Overlap of metatranscriptional data on genome-resolved metagenomic data showed that genome bins classified within the Chloroflexota and Poribacteria phyla were the most abundant and transcriptionally active. However, abundant bins in general were not the most transcriptionally active, instead less abundant bins of the same phyla were most active indicating that numerical dominance does not imply transcriptional dominance. We found that although some primary metabolic functions appeared upregulated, they were not obviously attributable to any particular bacterial species. However, assessment of transcription levels of biosynthetic gene clusters (BGCs) encoding secondary metabolites revealed a high transcription of ribosomally synthesized and post-translationally modified peptides (RiPPs) in genome bins across diverse bacterial phyla, most of which were likelysrpRiPPs encoding brominated azol(in)e-containing compounds. However, the ecological role of these compounds remains elusive.

IMPORTANCE

Marine sponges and bacteria have formed close associations over several million years with many bacteria performing specialized functions within their sponge host. Previous studies have either assessed the genomes of a given sponge or the expression profile for a sponge holobiont as a whole. Here, we present the first genome-resolved transcriptomic study which gives us a snapshot of the transcriptional activity of individual bacteria in the context of four different sponge holobionts. Using this approach we found that the numerically dominant bacteria were not the most transcriptionally active and that relatively high expression of a ubiquitous biosynthetic gene cluster was evident in many different bacterial phyla in all four sponge samples.
Structured Ethical Review for Wastewater-Based Testing
Authors: Bowes Devin A. , Darling Amanda , Driver Erin M. , Kaya Devrim , Maal-Bared Rasha , Lee Lisa M. , Goodman Kenneth , Adhikari Sangeet , Aggarwal Srijan , Bivins Aaron , Bohrerova Zuzana , Cohen Alasdair , Duvallet Claire , Elnimeiry Rasha A. , Hutchison Justin M. , Kapoor Vikram , Keenum Ishi , Ling Fangqiong , Sills Deborah , Tiwari Ananda , Vikesland Peter , Ziels Ryan , Mansfeldt Cresten
Published: June 2023

Wastewater-based testing (WBT) for SARS-CoV-2 has rapidly expanded over the past three years due to its ability to provide a comprehensive measurement of disease prevalence independent of clinical testing. The development and simultaneous application of the field blurred the boundary between measuring biomarkers for research activities and for pursuit of public health goals, both areas with well-established ethical frameworks. Currently, WBT practitioners do not employ a standardized ethical review process (or associated data management safeguards), introducing the potential for adverse outcomes for WBT professionals and community members. To address this deficiency, an interdisciplinary group developed a framework for a structured ethical review of WBT. The workshop employed a consensus approach to create this framework as a set of 11-questions derived from primarily public health guidance because of the common exemption of wastewater samples to human subject research considerations. This study retrospectively applied the set of questions to peer- reviewed published reports on SARS-CoV-2 monitoring campaigns covering the emergent phase of the pandemic from March 2020 to February 2022 (n=53). Overall, 43% of the responses to the questions were unable to be assessed because of lack of reported information. It is therefore hypothesized that a systematic framework would at a minimum improve the communication of key ethical considerations for the application of WBT. Consistent application of a standardized ethical review will also assist in developing an engaged practice of critically applying and updating approaches and techniques to reflect the concerns held by both those practicing and being monitored by WBT supported campaigns.

Abstract Figure

Synopsis

Development of a structured ethical review facilitates retrospective analysis of published studies and drafted scenarios in the context of wastewater-based testing.
Exploring the Role of Chat GPT in patient care (diagnosis and Treatment) and medical research: A Systematic Review
Authors: Garg Ravindra Kumar , Urs Vijeth L , Agrawal Akshya Anand , Chaudhary Sarvesh Kumar , Paliwal Vimal , Kar Sujita Kumar
Published: June 2023

Background

ChatGPT(Chat Generative Pre-trained Transformer) is an artificial intelligence (AI) based on a natural language processing tool developed by OpenAI (California, USA). This systematic review examines the potential of Chat GPT in diagnosing and treating patients and its contributions to medical research.

Methods

In order to locate articles on ChatGPT’s use in clinical practise and medical research, this systematic review used PRISMA standards and conducted database searches across several sources. Selected records were analysed using ChatGPT, which also produced a summary for each article. The resultant word document was transformed to a PDF and handled using ChatPDF. The review looked at topics pertaining to scholarly publishing, clinical practise, and medical research.

Results

We reviewed 118 publications. There are difficulties and moral conundrums associated with using ChatGPT in therapeutic settings and medical research. Patient inquiries, note writing, decision-making, trial enrolment, data management, decision support, research support, and patient education are all things that ChatGPT can help with. However, the solutions it provides are frequently inadequate and inconsistent, presenting issues with its originality, privacy, accuracy, bias, and legality. When utilising ChatGPT for academic writings, there are issues with prejudice and plagiarism, and because it lacks human-like characteristics, its authority as an author is called into question.

Conclusions

ChatGPT has limitations when used in research and healthcare. Even while it aids in patient treatment, concerns regarding accuracy, authorship, and bias arise. Currently, ChatGPT can serve as a “clinical assistant” and be a huge assistance with research and scholarly writing.
Mapping factors that may influence attrition and retention of midwives: a scoping review protocol
Authors: Moncrieff Gill , Cheyne Helen , Downe Soo , Maxwell Margaret
Published: June 2023

Introduction

An appropriately staffed midwifery workforce is essential for the provision of safe and high-quality maternity care. However, there is a global and national shortage of midwives. Understaffed maternity services are frequently identified as contributing to unsafe care provision and adverse outcomes for mothers and babies. While there is a need to recruit midwives through pre-registration midwifery programmes, this is associated with cost and resource implications, and is counteracted to a large extent by the high number of midwives leaving the workforce. It is increasingly recognised that there is a critical need to attend to retention in midwifery in order to develop and maintain safe staffing levels. The objective of this review is to collate and map factors that have been found to influence attrition and retention in midwifery.

Methods and analysis

Joanna Briggs Institute guidance for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews will be used to guide the review process and reporting of the review. CINAHL, MEDLINE, PsycINFO, and Scopus databases will be used to carry out the search for relevant literature. Results will be screened against inclusion criteria. Data will be extracted using a pre-formed data extraction tool and findings will be presented in narrative, tabular, and graphical formats.

Ethics and dissemination

The review will collate data from existing research, therefore ethics approval is not required. Findings will be published in journals, presented at conferences, and will be translated into infographics and other formats for online dissemination.

Strengths and limitations of this study

This will be the first review to systematically map the factors found to influence midwives’ decision to stay in or leave their role as a midwife

Scoping reviews provide a rigorous and structured method through which to collate and map evidence on a given topic

This protocol and the full review will follow Joanna Briggs Institute guidance for scoping reviews and will be reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews

The review will be of relevance to other high income countries but is unlikely be relevant for low and middle income countries
Hormonal steroids bind theNeisseria gonorrhoeaemultidrug resistance regulator, MtrR, to induce a multidrug binding efflux pump and stress-response sigma factor
Authors: Hooks Grace M. , Ayala Julio C. , Beggs Grace A. , Perfect John R. , Schumacher Maria A. , Shafer William M. , Brennan Richard G.
Published: June 2023

Overexpression of the multidrug efflux pump MtrCDE, a critical factor of multidrug-resistance inNeisseria gonorrhoeae, the causative agent of gonorrheae, is repressed by the transcriptional regulator, MtrR (multiple transferable resistance repressor). Here, we report the results from a series ofin vitroexperiments to identify innate, human inducers of MtrR and to understand the biochemical and structural mechanisms of the gene regulatory function of MtrR. Isothermal titration calorimetry experiments reveal that MtrR binds the hormonal steroids progesterone, β-estradiol, and testosterone, all of which are present at significant concentrations at urogenital infection sites as well as ethinyl estrogen, a component of some birth control pills. Binding of these steroids results in decreased affinity of MtrR for cognate DNA, as demonstrated by fluorescence polarization-based assays. The crystal structures of MtrR bound to each steroid provided insight into the flexibility of the binding pocket, elucidated specific residue-ligand interactions, and revealed the conformational consequences of the induction mechanism of MtrR. Three residues, D171, W136 and R176 are key to the specific binding of these gonadal steroids. These studies provide a molecular understanding of the transcriptional regulation by MtrR that promotesN. gonorrhoeaesurvival in its human host.
Taphonomic damage obfuscates interpretation of the retroarticular region of theAsteriornismandible
Authors: Crane Abi , Benito Juan , Chen Albert , Musser Grace , Torres Christopher R. , Clarke Julia A. , Lautenschlager Stephan , Ksepka Daniel T. , Field Daniel J.
Published: June 2023

Asteriornis maastrichtensis, from the latest Cretaceous of Belgium, is among the oldest known crown bird fossils, and its three-dimensionally preserved skull provides the most substantial insights into the cranial morphology of early crown birds to date. Phylogenetic analyses recoveredAsteriornisas a total-group member of Galloanserae (the clade uniting Galliformes and Anseriformes. One important feature supporting this placement was enlargement of the retroarticular processes, which form elongate caudal extensions of the mandible in extant Galloanserae. Here, we reinterpret the jaw ofAsteriornisand illustrate that the caudalmost portion of the mandibles are in fact not preserved. Instead, the caudal extremities of both the left and right mandibular rami extend to the surface of the fossil block containing the holotype skull, where they have eroded away. The originally identified retroarticular process of the right mandible—which exhibits a morphology and orientation strikingly similar to the retroarticular processes of certain extant and fossil galloanserans, including the early Palaeogene total-clade anseriformsConflictoandNettapterornis—instead represents a twisted and caudally displaced medial process. Nonetheless, anatomical comparisons with extant taxa reveal that we are unable to exclude the possibility thatAsteriornisexhibited robust retroarticular processes comparable to those of extant Galloanserae. In light of the reinterpreted morphology of theAsteriornismandible, we update the original anatomical character matrix used to investigate its phylogenetic relationships, and our revised phylogenetic analyses continue to support its position as a total-group galloanseran, as initially interpreted. We demonstrate additional morphological traits of the mandible supporting this phylogenetic position and provide new data on the nature and distribution of retroarticular processes among early crown birds.
Including the Invisible Fraction in Whole Population Studies: a Guide to the Genetic Sampling of Unhatched Bird Eggs
Authors: Morland Fay , Patel Selina , Santure Anna W. , Brekke Patricia , Hemmings Nicola
Published: June 2023

Early embryo mortality has recently been proven to be a significant component of avian reproductive failure. Due to the difficulty in distinguishing eggs which have suffered early embryo mortality from unfertilised eggs, this cause of reproductive failure has historically been underestimated and overlooked. We describe methods for recognising and collecting undeveloped, unhatched eggs from wild bird populations, identifying and isolating embryonic material in unhatched eggs, and efficiently extracting DNA from those samples. We test these methods on unhatched eggs collected from the field which have undergone post-mortem incubation. We obtained DNA yields from early-stage embryos that are sufficient for a wide range of molecular techniques, including microsatellite genotyping for parentage analysis and sex-typing. The type of tissue sample taken from the egg affected downstream DNA yields and microsatellite amplification rates. Species-specific microsatellite markers had higher amplification success rates than cross-species markers. We make key recommendations for each stage of the sampling and extraction process and suggest improvements potential and protocol modifications. Genetic and possibly genomic analysis of embryos that die early in development has the potential to advance many fields. The methods described here will allow a more in-depth exploration of the previously overlooked causes of early embryo mortality in wild populations of birds, including threatened species.
ALS-causing SOD1 mutations H46R and G85R form similar novel amyloid fibril structures and promote ferroptosis in cells
Authors: Wang Li-Qiang , Ma Yeyang , Zhang Mu-Ya , Yuan Han-Ye , Li Xiang-Ning , Xia Wencheng , Zhao Kun , Huang Xi , Chen Jie , Zou Liangyu , Li Dan , Wang Zhengzhi , Le Weidong , Liu Cong , Liang Yi
Published: June 2023

More than two hundred genetic mutations of Cu, Zn-superoxide dismutase (SOD1) have been identified in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by the selective death of motor neurons through ferroptosis. Two ALS-causing SOD1 mutations, H46R and G85R, are metal-binding region mutants with reduced affinity for metal ions. Here, we generated amyloid fibrils from the apo forms of H46R and G85R under reducing conditions and determined their structures using cryo-EM. We built models for the fibril cores, comprising residues 85−153 for H46R and 82−153 for G85R. These mutations disrupt crucial interactions in the wild-type SOD1 fibril, resulting in amyloid fibrils with distinct structures compared to the wild-type fibril. Remarkably, H46R and G85R form similar novel amyloid fibril structures. The fibril cores display a serpentine fold containing seven or eight β-strands, which are stabilized by a hydrophobic cavity. In the G85R fibril core, Arg85 and Asp101 form a salt bridge for stabilization. We demonstrate that fibril seeds from H46R and G85R cause more severe mitochondrial impairment and significantly promote ferroptosis in neuronal cells, compared with those from wild-type SOD1. Our findings reveal how different SOD1 mutations can result in similar amyloid fibril structures and contribute to ALS pathology.
Tools for Quantitative Analysis of Calcium Signaling Data Using Jupyter-Lab Notebooks
Authors: Rugis John , Chaffer James , Sneyd James , Yule David
Published: June 2023

Calcium signaling data analysis has become increasing complex as the size of acquired datasets increases. In this paper we present a Ca2+signaling data analysis method that employs custom written software scripts deployed in a collection of Jupyter-Lab “notebooks” which were designed to cope with this complexity. The notebook contents are organized to optimize data analysis workflow and efficiency. The method is demonstrated through application to several different Ca2+signaling experiment types.