bluuebunny/crossref_metadata_2025_split huggingface dataset:
The First Large-Scale Wastewater Surveillance of AMR to inform Hyperlocal Antibiotic prescribing: A Study from Bengaluru, India
Authors: Roy Imon , Gowthami N , Shamsi Shoa , Unnikrishnan Nikhilesh , Shah Prerak , Prasad Ramakrishna , Satyaseela Maneesh Paul , Shridhar Varsha 
Published: August 2024

AbstractApproximately 1.2 million people died in 2019 globally due to antimicrobial resistant infections making it one of the major public health issues of the 21st century. Community level antibiotic resistance data is needed for guiding antibiotic prescriptions at the local level, which national databases may be unable to provide. We hypothesized that wastewater could have potential to detect local AMR patterns cost-effectively on a real time and longitudinal basis.Our objectives were to explore the potential of wastewater to detect local AMR patterns of specific Gram Negative bacteria against 4 key antimicrobial classes across Bengaluru city. Wastewater from 66 open storm drain sites within all eight administrative zones of Bengaluru city, in southern India, between March and April 2022 were plated on McConkey and Shigella-Salmonella agar plates. 2 colonies were randomly picked from each plate, identified using standard biochemical tests and then subcultured for antibiotic sensitivity profiles against 5 common antibiotics: ciprofloxacin (Fluoroquinolone), cefixime (3rd generation cephalosporin), piperacillin/tazobactam (TZP, beta lactam/beta lactamase inhibitor), ertapenem and meropenem (carbapenems) on Mueller-Hinton platesOf the 160 isolates selected for deeper scrutiny, 82% (132) belonged to the Enterobacteriaceae family. Of these, 95% (126) were known to cause human infections. About 28% of the clinically relevant Enterobacteriaceae isolates were susceptible to all five antibiotics tested while 12% were resistant to all five antibiotics, and the remainder had a mixed resistance profile. Our results indicate: a) drug resistant bacteria are found in significant numbers in open drains b) there is geographical variation within a city in the patterns and burden of AMR c) Wastewater could be both a method for estimating community burden of AMR. This is the first city-wide wastewater based AMR profiling in India and indicates the potential of such surveillance to provide hyperlocal community level data to influence local antibiotic prescription practices by primary care physicians and on antibiotic purchase and allocation decisions by government drug purchase committees.
Urine complement proteins are associated with kidney disease progression of type 2 diabetes in Korean and American cohorts
Authors: Yun Donghwan , Bae Sohyun , Gao Yuqian , Lopez Lauren , Han Dohyun , Nicora Carrie D. , Kim Tae Youn , Moon Kyung Chul , Kim Dong Ki , Fillmore Thomas L. , Kim Yon Su , Rosenberg Avi Z. , Wang Weijie , Sarder Pinaki , Qian Wei-Jun , Afkarian Maryam , Han Seung Seok 
Published: August 2024

AbstractBackgroundMechanisms of progression of diabetic kidney disease (DKD) are not completely understood. This study uses untargeted and targeted mass spectrometry-based proteomics in two independent cohorts on two continents to decipher the mechanisms of DKD in patients with type 2 diabetes.MethodsWe conducted untargeted mass spectrometry on urine samples collected at the time of kidney biopsy from Korean patients with type 2 diabetes and biopsy-proven diabetic nephropathy at Seoul National University Hospital (SNUH-DN cohort; n = 64). These findings were validated using targeted mass spectrometry in urine samples from a Chronic Renal Insufficiency Cohort subgroup with type 2 diabetes and DKD (CRIC-T2D; n = 282). Urinary biomarkers/pathways associated with kidney disease progression (doubling of serum creatinine, ≥50% decrease in estimated glomerular filtration rates, or the development of end-stage kidney disease) were identified.ResultsSNUH-DN patients had an estimated glomerular filtration rate (eGFR) of 55 mL/min/1.73 m2(interquartile range [IQR], 44–75) and random urine protein-to-creatinine ratio of 3.1 g/g (IQR, 1.7–7.0). Urine proteins clustered into two groups, with cluster 2 having a 4.6-fold greater hazard (95% confidence interval [CI], 1.9–11.5) of disease progression than cluster 1 in multivariable-adjusted, time-to-event analyses. Proteins in cluster 2 mapped to 10 pathways, four of the top five of which were complement or complement-related. A high complement score, constructed from urine complement protein abundance, was strongly correlated to 4 of 5 histopathologic DN features and was associated with a 2.4-fold greater hazard (95% CI, 1.0–5.4) of disease progression than a low complement score. Targeted mass spectrometry of the CRIC-T2D participants, who had an eGFR of 42 mL/min/1.73 m2(IQR, 37–49) and 24-hr urine protein of 0.48 g (IQR, 0.10–1.87), showed that the complement score similarly segregated them into rapid and slow DKD progression groups. In both cohorts, the complement score had a linear association with disease progression.ConclusionsUrinary proteomic profiling confirms the association between the complement pathway and rapid DKD progression in two independent cohorts. These results suggest a need to further investigate complement pathway inhibition as a novel treatment for DKD.
Ground nesting of soft eggs by extinct birds and a new parity mode switch hypothesis for the evolution of animal reproduction
Authors: Guimarães M. Jorge , Wang Junyou , Zhang Xuemin , Sun Qiang , Cerqueira M. Fátima , Chung Yi-Hsiu , Deng Richard , Guo Bin , Alpuim Pedro , Ma Feimin , Wang Xiaobing , Yen Tzu-Chen 
Published: August 2024

ABSTRACTNearshore ground nesting of soft eggs by extinct birds is demonstrated here, providing a new explanation for the abundance of bird fossils in early Cretaceous lacustrine environments, where humidity conditions required for soft egg incubation would have been present. This reinforces recent findings of Archaeopteryx soft eggs near Jurassic marine environments, the possibility that wings and elongated feathers developed primarily in association with nest protection on the ground and only secondarily with flight, and the origin of flight from the ground up. Notably, soft eggs preceded rigid eggs in evolution, but both crocodiles, whose ancestors seem to have antedated bird precursors, and extant birds reproduce exclusively via hard-shelled eggs. Therefore, an explanation is in order for how reproduction via soft eggs could have occurred in the bird lineage in-between two evolutionary moments of reproduction via rigid eggs. In alternative to the commonly accepted convergent evolution of viviparity and rigid eggshells, a parity mode switch hypothesis is presented here. It postulates the existence, since the rise of animals, of an inherited ancestral parity mode switch between viviparity and oviparity. This switch would have evolved to embrace hard-shelled oviparity after rigid eggshells appeared in evolution. Commitment to a particular parity mode or eggshell type may have conditioned survival of entire animal groups, especially during major extinction events, explaining, among others, the extinction of all birds that reproduced via soft eggshells.
Excluding Large Grazers Dramatically Improves Survival of Outplanted Juvenile Corals
Authors: van der Steeg Eveline , Humanes Adriana , Bythell John C. , Craggs Jamie R. , Edwards Alasdair J. , Golbuu Yimnang , Lachs Liam , Miller Margaret W. , Randle Janna L. , Guest James R. 
Published: August 2024

AbstractHigh mortality rates of juvenile corals hinder both the natural recovery of populations and the successful implementation of restoration efforts. Grazing is a significant cause of juvenile coral mortality, and grazer exclusion devices have been shown to increase juvenile coral survivorship. However, most experiments have used cages that typically alter water flow and light conditions and exclude grazers of most sizes, making it difficult to quantify the effects of large grazers alone. Here, we test whether deterring large grazers can increase the survival and growth of six-month-oldAcropora digitiferajuveniles outplanted to a shallow reef crest, using arrangements of two or four long or short masonry nails that selectively exclude larger grazers (e.g., parrotfish) while minimising abiotic changes. By the end of our study, colonies with deterrents had significantly larger planar area (almost tenfold for the most effective treatment), more branches, greater height, and enhanced survival than those without deterrents. A critical period is the first week after outplanting when colonies with deterrents had significantly less tissue loss from grazing than those without. Less tissue loss in the first week was associated with significantly higher survival over the following 14 months, with an almost threefold improvement for the most effective treatment. For heavily grazed systems, our study highlights the importance of incorporating grazing deterrents into outplant devices to counteract the negative impact of large grazers on outplanted juvenile coral survival and boost restoration success.
Origins ofde novochromosome rearrangements unveiled by coupled imaging and genomics
Authors: Cosenza Marco Raffaele , Gaiatto Alice , Erarslan Uysal Büşra , Andrades Delgado Álvaro , Sautter Nina Luisa , Jendrusch Michael Adrian , Zumalave Duro Sonia , Rausch Tobias , Halavatyi Aliaksandr , Geissen Eva-Maria , Hasenfeld Patrick , Cortes-Ciriano Isidro , Kulozik Andreas , Pepperkok Rainer , Korbel Jan O. 
Published: August 2024

AbstractChromosomal instability results in widespread structural and numerical chromosomal abnormalities (CAs) during cancer evolution1–3. While CAs have been linked to mitotic errors resulting in the emergence of nuclear atypias4–7, the underlying processes and basal rates of spontaneous CA formation in human cells remain under-explored. Here we introduce machine learning-assisted genomics-and-imaging convergence (MAGIC), an autonomously operated platform that integrates automated live-cell imaging of micronucleated cells, machine learning in real-time, and single-cell genomics to investigatede novoCA formation at scale. Applying MAGIC to near-diploid, non-transformed cell lines, we track CA events over successive cell cycles, highlighting the common role of dicentric chromosomes as an initiating event. We determine the baseline CA rate, which approximately doubles inTP53-deficient cells, and show that chromosome losses arise more rapidly than gains. The targeted induction of DNA double-strand breaks along chromosomes triggers distinct CA processes, revealing stable isochromosomes, amplification and coordinated segregation of isoacentric segments in multiples of two, and complex CA outcomes, depending on the break location. Our data contrastde novoCA spectra from somatic mutational landscapes after selection occurred. The large-scale experimentation enabled by MAGIC provides insights intode novoCA formation, paving the way to unravel fundamental determinants of chromosome instability.
Premature cleavage and polyadenylation in the minor intron of PTEN modulate its expression and generates a functional long non-coding RNA in breast cancer
Authors: Elesnawy Mariam , Elghandour Rim , Hasna Hana , Fakhroo Aisha , Al-Sulaiti Boshra , Younis Ihab 
Published: August 2024

AbstractMinor introns constitute 0.4% of all introns in human cells, but they are unique in their ability to regulate the genes in which they are embedded such that their low splicing efficiency can be a rate limiting step in gene expression. The first intron of the tumor suppressor gene, PTEN, has been documented to be a minor intron, but very little is known about its regulation. Regulation of PTEN levels in cancer cells, especially breast cancer is tightly controlled as a very small reduction in its expression can lead to tumorigenesis. Indeed, many genetic, epigenetic, post-transcriptional and post-translational mechanisms are employed to reduce PTEN levels or activities, leading to cancer. Here, we uncover a previously unexplored mechanism for modulating PTEN expression utilizing its minor intron. The minor intron of PTEN minor intron has one of the lowest splicing efficacies in breast cancer cells, causing at least 50% of PTEN pre-mRNA to retain it, and thus not produce a functional protein. We also show that, unlike other minor introns, the retained intron in PTEN pre-mRNA is not used as a molecular switch that would be spliced out when needed but is rather processed by premature cleavage and polyadenylation into a long noncoding RNA (lncRNA) that we termed PINC. Exogenous expression of PINC caused significant alterations to cellular proliferation, including breast cancer cells that harbor a genetic mutation in the PTEN gene and do not produce a functional PTEN protein. This shows that this novel lncRNA functions independently of the encoded protein of the host gene.
Prediction of Oligomeric Status of Quaternary Protein Structure by using Sequential Minimal Optimization for Support Vector Machine
Authors: Kumar Suresh 
Published: August 2024

AbstractThe prediction of quaternary structure and its function is important in pharmaceutical applications, drug design, medical or engineering applications. With the drastic rise in the number of protein sequences presented to the public database, acquiring an understanding of possible quaternary structural characteristics of their interested proteins in a timely way is essential for structural genomics research. There is a need for a method to identify quaternary attributes based on its amino acid sequence. In this study, discrimination of hetero-oligomer from non hetero-oligomer was demonstrated using amino acid composition implemented using a support vector machine with a minimum sequential optimization technique.
EnteroBase in 2025: exploring the genomic epidemiology of bacterial pathogens
Authors: Dyer Nigel P. , Päuker Birgitta , Baxter Laura , Gupta Anshul , Bunk Boyke , Overmann Jörg , Diricks Margo , Dreyer Viola , Niemann Stefan , Holt Kathryn E. , Rahman Mohammed , Brown Paul E. , Stark Richard , Zhou Zhemin , Ott Sascha , Nübel Ulrich 
Published: August 2024

ABSTRACTThis paper presents an update on the content, accessibility and analytical tools of the EnteroBase platform for web-based pathogen genome analysis. EnteroBase provides manually curated databases of genome sequence data and associated metadata from currently >1.1 million bacterial isolates, more recently includingStreptococcusspp. andMycobacterium tuberculosis. We have implemented the genome-based detection of antimicrobial resistance determinants and the new bubble plot graphical tool for visualising bacterial genomic population structures, based on pre-computed hierarchical clusters. Access to data and analysis tools is provided through an enhanced graphical user interface and a new application programming interface (RESTful API). EnteroBase is now being developed and operated by an international consortium, to accelerate the development of the platform and ensure the longevity of the resources built. EnteroBase can be accessed athttps://enterobase.warwick.ac.ukas well ashttps://enterobase.dsmz.de.GRAPHICAL ABSTRACT
Phenotypic divergence associated with genomic changes suggest local adaptation in obligate asexuals
Authors: Karapli-Petritsopoulou Athina , Heckelmann Jasmin Josephine , Anderson N. John , Franzenburg Sören , Frisch Dagmar 
Published: August 2024

AbstractLocal adaptation is a key evolutionary process that generates global biodiversity and is promoted by environmental heterogeneity. Most of the existing knowledge on adaptive capacity is focused on sexual organisms, while the adaptation potential of asexually reproducing eukaryotes as well as their vulnerability to environmental change remains unclear. Cyclical parthenogens of the keystone freshwater grazerDaphniaare known to be locally adapted with genetic differentiation related to environmental conditions even between neighbouring ponds. Similar patterns have been found in obligate parthenogenetic congeners, however studies on their local adaptation potential are rare. Here, we use respiration rate and whole genome sequencing to test the local adaptation of Arctic asexual polyploidDaphniafrom lakes with contrasting oxygen environments. The genomic data revealed the presence of two genetic clusters which differed significantly in respiration rates, suggesting molecular evolution as an adaptive mechanism. Functional enrichment pointed to differences in metabolic processes between the two genetic clusters. Our results, combining phenotypic and whole genome sequencing data, suggest that these clones are locally adapted to low oxygen concentrations and provide support for local adaptation by evolution in an obligate parthenogen.
Dynein contributes to spindle elongation during anaphase inCandida albicans
Authors: Shoukat Irsa , Allingham John S. 
Published: August 2024

AbstractBudding yeast must position the mitotic spindle at the mother-bud junction during anaphase to ensure proper chromosome segregation. Pushing and pulling forces on astral microtubules from dynein motors in the cell cortex are crucial for spindle positioning. In some higher eukaryotes and filamentous fungi, dynein also accelerates spindle elongation during anaphase, but in yeast model systems spindle elongation primarily relies on intra-spindle pushing forces from kinesin-5 motors. The pathogenic yeastCandida albicansis unique because its spindle can elongate without a functional kinesin-5. Our study helps explainC. albicans’ diminished kinesin-5 requirement by showing that its dynein, Dyn1, collaborates with its kinesin-5, Kip1, to facilitate spindle elongation. Cells lacking Kip1 activity by eitherKIP1deletion or Kip1 inhibition have more Dyn1 and astral microtubules, indicating spindle elongation happens through enhanced pulling on spindle pole body-bound astral microtubules by cortical Dyn1. When Dyn1 activity is depleted, spindle elongation speed is normal, but anaphase spindles persist for extended periods, and the number and length of astral microtubules increases. Depletion of both motors prevents spindle elongation and is lethal. The significance of astral microtubules in cells lacking either motor is highlighted by the lethal effects of microtubule-destabilizing drugs and exposure to low temperatures (8°C) that compromise microtubule stability. These findings demonstrate thatC. albicansspindle elongation involves cooperative forces from Kip1 and Dyn1 to ensure chromosome separation during cell division and thatC. albicansadapts to changes in abundance of these motors through alterations in their astral microtubule content.
Impact of a defined bacterial community including and excludingMegamonas hypermegaleon broiler cecal microbiota and resistance toSalmonellainfection
Authors: Schultz Marcolla Camila , Ju Tingting , Ten Kimberlee , Sharma Usha Sivakumar , Moeun Leakhena , Willing Benjamin P. 
Published: August 2024

AbstractIntensive broiler production practices impair the transmission of commensal microbes from hens to offspring, resulting in a lower abundance of non-spore-forming strict anaerobic bacteria. We evaluated the effects of colonization by a defined community (DC) of bacteria including and excludingMegamonas hypermegalein chicks challenged withSalmonella. Inoculation with DC resulted in higher phylogenetic diversity and the dominance of Bacteroidetes species in the cecal microbiota, with a decrease in the relative abundance ofSalmonellaandEscherichia/Shigella, as well as a lowerEnterobacteriaceaeload. Substantial shifts in microbiota composition were coupled with subtle changes in metabolites and host responses, including changes in interferon-γ, macrophage colony-stimulating factor, propionate, valerate, and isovalerate concentrations in the ceca. We identified bacterial species that were able to establish and persist after a single exposure, many of which were members of Bacteroidetes. Although co-culture withM. hypermegalereducedSalmonellacounts by 99.3%in vitro,in vivoinoculation ofM. hypermegaleincreased splenicSalmonellacounts in inoculated chicks. The use of DC containing bacteria isolates harvested from the cecal contents of mature chickens can recapitulate the changes in volatile fatty acid concentrations observed in birds colonized with complex communities, and the presence ofM. hypermegalespecifically enhances the production of propionate. Our findings suggest that the use of DC can be explored as a strategy to control disease occurrence in broiler production; however, further research is warranted to properly understand the role of individual species in the broiler cecal community aiding the formulation of appropriate DCs.ImportanceIntensive production practices can reduce beneficial gut bacteria in broiler chickens, potentially leading to higher disease risk. We investigated whether introducing a defined community (DC) of beneficial bacteria, along withM. hypermegale, could improve gut health and resistance toSalmonellain broiler chicks. Our findings show that DC increases microbial diversity and reduces the relative abundance of potential pathogens, likeSalmonellaandEscherichia/Shigella, which was coupled with subtle changes in the immune responses of the birds and higher concentration of volatile fatty acids in the ceca. This study suggests that using DC can enhance poultry health and reduce disease, providing a potential strategy to improve broiler production. However, further research is needed to understand the roles of individual bacteria and refine these bacterial communities for practical use in farming. This work holds promise for developing natural methods to enhance poultry health and safety.
Semaglutide Improves Myocardial Perfusion and Performance in a Large Animal Model of Coronary Artery Disease
Authors: Stone Christopher R. , Harris Dwight D. , Broadwin Mark , Kanuparthy Meghamsh , Nho Ju-Woo , Yalamanchili Keertana , Hamze Jad , Abid M. Ruhul , Sellke Frank W. 
Published: August 2024

AbstractObjectiveCoronary artery disease (CAD) is the leading cause of death worldwide. It imposes an enormous symptomatic burden on patients, leaving many with residual disease despite optimal procedural therapy, and up to 1/3 with debilitating angina amenable neither to procedures, nor to current pharmacologic options. Semaglutide, a glucagon-like peptide 1 agonist originally approved for management of diabetes, has garnered substantial attention for its capacity to attenuate cardiovascular risk. Although subgroup analyses in patients indicate promise, studies explicitly designed to isolate the impact of semaglutide on the sequelae of CAD, independently of comorbid diabetes or obesity, are lacking.Approach and ResultsYorkshire swine (n=17) underwent placement of an ameroid constrictor around the left circumflex coronary artery to induce CAD. Oral semaglutide was initiated postoperatively at 1.5 mg and scaled up in 2 weeks to 3 mg in treatment animals (SEM, n=8) for a total of 5 weeks, while control animals (CON, n=9) received no drug. All then underwent myocardial harvest with acquisition of perfusion and functional data using microsphere injection and pressure-volume loop catheterization. Immunoblotting, immunohistochemistry, and immunofluorescence were performed on the most ischemic myocardial segments for mechanistic elucidation. SEM animals exhibited improved left ventricular ejection fraction, both at rest and during rapid myocardial pacing (both p<0.03), accompanied by increased perfusion to the most ischemic myocardial region at rest and during rapid pacing (both p<0.03); reduced perivascular and interstitial fibrosis (both p <0.03); and apoptosis (p=0.008). These changes were associated with increased activation of the endothelial-protective AMPK pathway (p=0.005), coupled with downstream increases in endothelial nitric oxide synthase (p=0.014).ConclusionThis study is the first to reveal the capacity of oral semaglutide to augment cardiac function in the chronically ischemic heart in a highly translational large animal model, likely through AMPK-mediated improvement in endothelial function and perfusion to the ischemic myocardium.