bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biochemical characterization of a SusD-like protein involved in β-1,3-glucan utilization by an uncultured cow rumen
Bacteroides
Authors: Li Xiaoqian , Lippens Guy , Parrou Jean-Luc , Cioci Gianluca , Esque Jérémy , Wang Zhi , Laville Elisabeth , Potocki-Veronese Gabrielle , Labourel Aurore 
Published: July 2024

ABSTRACT

In ruminants, the rumen is a specialized stomach that is adapted to the breakdown of plant-derived complex polysaccharides through the coordinated activities of a diverse microbial community. Bacteroidota is a major phylum in this bovine rumen microbiota. They contain several clusters of genes called polysaccharide utilization loci (PULs) that encode proteins working in concert to capture, degrade, and transport polysaccharides. Despite the critical role of SusD-like proteins for efficient substrate transport, they remain largely unexplored. Here, we present the biochemical characterization of a SusD-like protein encoded by a β-glucan utilization locus from an
Escherichia coli
metagenomic clone previously isolated by functional screening of the bovine rumen microbiome. In this study, we show that clone 41O1 can grow on laminaritriose, cellotriose, and a mixture of cellobiosyl-cellobiose and glucosyl-cellotriose as sole carbon sources. Based on this, we used various
in vitro
analyses to investigate the binding ability of 41O1_SusD-like towards these oligosaccharides and the corresponding polysaccharides. We observed a clear binding affinity for β-1,6 branched β-1,3-glucans (laminarins, yeast β-glucan) and laminaritriose. Comparison of the AlphaFold2 model of 41O1_SusD-like with its closest structural homologs highlights a similar pattern of substrate recognition. In particular, three tryptophan residues are shown to be crucial for laminarin recognition. In the context of the cow rumen, we discuss the possible substrates targeted by the 41O1_PUL, such as the (1,3;1,4)-β-
d
-glucans present in cereal grains or the β-1,3- and (1,3;1,6)-β-
d
-glucans that are components of the cell wall of ruminal yeasts.

IMPORTANCE

The rumen microbiota can majorly impact overall animal health, feed efficiency, and release of harmful substances into the environment. This microbiota is involved in the fermentation of organic matter to provide the host with valuable and assimilable nutrients. Bacteroidota efficiently captures, breaks down, and imports complex polysaccharides through the concerted action of proteins encoded by polysaccharide utilization loci (PULs). Within this system, SusD-like protein has proven necessary for the active internalization of the substrate. Nevertheless, the vast majority of SusD-like proteins characterized to date originate from cultured bacteria. With regard to the diversity and importance of uncultured bacteria in the rumen, further studies are required to better understand the role of polysaccharide utilization loci in ruminal polysaccharide degradation. Our detailed characterization of the 41O1_SusD-like therefore contributes to a better understanding of the carbohydrate metabolism of an uncultured
Bacteroides
from the cow rumen.
Physical cell-cell contact elicits specific transcriptomic responses in wine yeast species
Authors: Luyt Natasha A. , de Witt Riaan N. , Divol Benoit , Patterton Hugh G. , Setati Mathabatha E. , Taillandier Patricia , Bauer Florian F. 
Published: July 2024

ABSTRACT

Fermenting grape juice provides a habitat for a well-mapped and evolutionarily relevant microbial ecosystem consisting of many natural or inoculated strains of yeasts and bacteria. The molecular nature of many of the ecological interactions within this ecosystem remains poorly understood, with the partial exception of interactions of a metabolic nature such as competition for nutrients and production of toxic metabolites/peptides. Data suggest that physical contact between species plays a significant role in the phenotypic outcome of interspecies interactions. However, the molecular nature of the mechanisms regulating these phenotypes remains unknown. Here, we present a transcriptomic analysis of physical versus metabolic contact between two wine relevant yeast species,
Saccharomyces cerevisiae
and
Lachancea thermotolerans
. The data show that these species respond to the physical presence of the other species. In
S. cerevisiae
, physical contact results in the upregulation of genes involved in maintaining cell wall integrity, cell wall structural components, and genes involved in the production of H
2
S. In
L. thermotolerans
,
HSP
stress response genes were the most significantly upregulated gene family. Both yeasts downregulated genes belonging to the
FLO
family, some of which play prominent roles in cellular adhesion. qPCR analysis indicates that the expression of some of these genes is regulated in a species-specific manner, suggesting that yeasts adjust gene expression to specific biotic challenges or interspecies interactions. These findings provide fundamental insights into yeast interactions and evolutionary adaptations of these species to the wine ecosystem.

IMPORTANCE
Within the wine ecosystem, yeasts are the most relevant contributors to alcoholic fermentation and wine organoleptic characteristics. While some studies have described yeast-yeast interactions during alcoholic fermentation, such interactions remain ill-defined, and little is understood regarding the molecular mechanisms behind many of the phenotypes observed when two or more species are co-cultured. In particular, no study has investigated transcriptional regulation in response to physical interspecies cell-cell contact, as opposed to the generally better understood/characterized metabolic interactions. These data are of direct relevance to our understanding of microbial ecological interactions in general while also creating opportunities to improve ecosystem-based biotechnological applications such as wine fermentation. Furthermore, the presence of competitor species has rarely been considered an evolutionary biotic selection pressure. In this context, the data reveal novel gene functions. This, and further such analysis, is likely to significantly enlarge the genome annotation space.
The epidemiology of intestinal protozoa in the Israeli population based on molecular stool test: a nationwide study
Authors: Peretz Avi , Azrad Maya , Ken- Dror Shifra , Strauss Merav , Sagas Dana , Parizada Miriam , Loewnthal Shulamit , Amichay Doron , Ben Horin Nili , Shenhar Yotam , Sagi Orli , Bazarsky Elina , Amit Sharon , Schwartz Eliezer 
Published: July 2024

ABSTRACT

Stool examination using microscopy was the traditional method for the diagnosis of intestinal parasites. Recently, the use of molecular tests to identify stool protozoa has become the main tool used in most clinical laboratories in Israel. This study aimed to evaluate the prevalence of intestinal parasites in Israel and to compare this prevalence in laboratories that use molecular tests vs a laboratory that uses microscopy. Samples collected from January to October 2021 at seven laboratories were analyzed by real-time PCR (RT-PCR) or by microscopy. The multiplex panel included the following pathogens:
Giardia lamblia
,
Entamoeba histolytica
,
Cryptosporidium spp.
,
Cyclospora
,
Dientamoeba fragilis
, and
Blastocystis spp
. Overall, 138,415 stool samples were tested by RT-PCR and 6,444 by microscopy. At least one protozoa species was identified in 28.4% of the PCR-tested samples compared to 4.6% of the microscopy-tested samples.
D. fragilis
was the most common PCR-identified species (29%).
D. fragilis
,
G. lamblia
, and
Cryptosporidium spp
. were mainly found in pediatric population, while
Blastocystis spp
. was most prevalent among adults (
P
< 0.001). In a sub-cohort of 21,480 samples, co-infection was found in 4,113 (19.15%) samples, with
Blastocystis spp
. and
D. fragilis
being the most common (14.9%) pair. Molecular stool testing proved more sensitive compared to microscopy.
D. fragilis
was the most commonly detected pathogen. The above profile was identified during the COVID pandemic when traveling was highly restricted and most likely represents the locally circulating protozoa.

IMPORTANCE
This study sheds light on the prevalence of stool parasites in Israel. Additionally, this study indicates that the shift from microscope analysis to molecular tests improved protozoa diagnosis.
Cyclic and Square Wave Voltammetry Analysis of MTZ Using Reactive Electrode Based on Montmorillonite and Na-Alginate
Authors: Hadjyoussef Mouna Touati , Dakhli Abir , Zayani Memia Benna 
Published: July 2024

This work describes the elaboration and the electroanalytical tests of a new electrode based on a mixture of graphite and biopolymer-modified montmorillonite nanocomposite. Initially, the nanocomposite was synthesized using sodic montmorillonite (NaMT) and sodium alginate (Naalg) extracted from Tunisian algae. The resulting nanocomposite was characterized by X-ray diffraction (XRD), infrared spectroscopy (UATR), and differential scanning calorimetry (DSC). XRD analysis revealed an increase in the basal spacing d001 and the appearance of reflections (020) and (220) of guluronan groups. Infrared spectra showed characteristic polymer bands such as symmetric and antisymmetric stretching vibrations of the carboxylic group in the nanocomposite spectra indicating the modification. Thermal analysis displayed a shift in the temperature of Naalg decomposition to a higher temperature in the nanocomposite thermogram.
The obtained nanocomposite was then used in the development of an electrode. The resulting hybrid electrode was tested for metronidazole (MTZ) analysis using cyclic voltammetry (CV) and square wave voltammetry (SWV). Various parameters including pH, scan rate, MTZ concentration, frequency, etc., were investigated. The results revealed the irreversibility of the studied molecule and indicated that the reduction mechanism involves both diffusion and adsorption behaviors. SWV showed a better sensitivity to detect MTZ than the CV technique. Promising results were obtained, suggesting prospects for this new hybrid electrode.
Facile Synthesis of U2Ti Intermetallic by Direct Electrochemical Reduction of UO2-TiO2 Composite in LiCl-Li2O Melt
Authors: Sanil N. , Shakila L. , Arunkumar V. , Kumaresan R. 
Published: July 2024

Alloys of U with Ti are of importance in nuclear industry as fuel for Gen IV fast reactors, hydrogen isotope storage medium for fusion reactors, super conductors, and also as corrosion resistant material for use in various applications. Here, preparation of U2Ti intermetallic compound was investigated by the direct electrochemical reduction of mixed oxide of UO2-TiO2 in LiCl-0.5% Li2O molten salt at 650 °C. The mixed oxide pellet of UO2-TiO2 sintered at 1500 °C was found to be a mixture of UTi2O6 and UO2 as evidenced by X-ray diffraction (XRD) analysis. Direct electro-lithiothermic reduction of UO2, TiO2, and a mixture of sintered UO2-TiO2 and UTi2O6 coupled with cyclic voltammetry of these oxides in the melt was performed to understand the electro-reduction mechanism. Potentials of reduction of these oxides in the melt, w.r.t Ni/NiO reference electrode, obtained by analysis of CV data of these oxides contained in metallic cavity electrodes and XRD analysis of partially electro-reduced oxides were used to arrive at the electro-reduction mechanism. Results indicate that U2Ti can be prepared conveniently by the electro-lithiothermic reduction of sintered pellet of UO2-TiO2 cathode by constant current electrolysis in a two-electrode cell.
Interim Phase II Results Using Panitumumab-IRDye800CW during Transoral Robotic Surgery in Patients with Oropharyngeal Cancer
Authors: Stone Logan D. , Kasten Benjamin B. , Rao Shilpa , Gonzalez Manuel. L. , Stevens Todd M. , Lin Diana , Carroll William , Greene Benjamin , Moore Lindsay S. , Fuson Andrew , James Sherin , Hartman Yolanda E. , McCammon Susan , Panuganti Bharat , Nabell Lisle M. , Li Yufeng , Li Mei , Bailey Luke , Rosenthal Eben L. , Jeyarajan Harishanker , Thomas Carissa M. , Warram Jason M. 
Published: July 2024

Abstract

Purpose:
The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has continually increased during the past several decades. Using transoral robotic surgery (TORS) significantly improves functional outcomes relative to open surgery for OPSCC. However, TORS limits tactile feedback, which is often the most important element of cancer surgery. Fluorescence-guided surgery (FGS) strategies to aid surgeon assessment of malignancy for resection are in various phases of clinical research but exhibit the greatest potential impact for improving patient care when the surgeon receives limited tactile feedback, such as during TORS. Here, we assessed the feasibility of intraoperative fluorescence imaging using panitumumab-IRDye800CW (PAN800) during TORS in patients with OPSCC.

Patients and Methods:
Twelve consecutive patients with OPSCC were enrolled as part of a nonrandomized, prospective, phase II FGS clinical trial using PAN800. TORS was performed with an integrated robot camera for surgeon assessment of fluorescence. Intraoperative and ex vivo fluorescence signals in tumors and normal tissue were quantified and correlated with histopathology.

Results:
Intraoperative robot fluorescence views delineated OPSCC from normal tissue throughout the TORS procedure (10.7 mean tumor-to-background ratio), including in tumors with low expression of the molecular target. Tumor-specific fluorescence was consistent with surgeon-defined tumor borders requiring resection. Intraoperative robot fluorescence imaging revealed an OPSCC fragment initially overlooked during TORS based on brightfield views, further substantiating the clinical benefit of this FGS approach.

Conclusions:
The results from this patient with OPSCC cohort support further clinical assessment of FGS during TORS to aid resection of solid tumors.
Dysferlin Enables Tubular Membrane Proliferation in Cardiac Hypertrophy
Authors: Paulke Nora Josefine , Fleischhacker Carolin , Wegener Justus B. , Riedemann Gabriel C. , Cretu Constantin , Mushtaq Mufassra , Zaremba Nina , Möbius Wiebke , Zühlke Yannik , Wedemeyer Jasper , Liebmann Lorenz , Gorshkova Anastasiia A. , Kownatzki-Danger Daniel , Wagner Eva , Kohl Tobias , Wichmann Carolin , Jahn Olaf , Urlaub Henning , Toischer Karl , Hasenfuß Gerd , Moser Tobias , Preobraschenski Julia , Lenz Christof , Rog-Zielinska Eva A. , Lehnart Stephan E. , Brandenburg Sören 
Published: July 2024

BACKGROUND:
Cardiac hypertrophy compensates for increased biomechanical stress of the heart induced by prevalent cardiovascular pathologies but can result in heart failure if left untreated. Here, we hypothesized that the membrane fusion and repair protein dysferlin is critical for the integrity of the transverse-axial tubule (TAT) network inside cardiomyocytes and contributes to the proliferation of TAT endomembranes during pressure overload–induced cardiac hypertrophy.

METHODS:
Stimulated emission depletion and electron microscopy were used to localize dysferlin in mouse and human cardiomyocytes. Data-independent acquisition mass spectrometry revealed the cardiac dysferlin interactome and proteomic changes of the heart in dysferlin-knockout mice. After transverse aortic constriction, we compared the hypertrophic response of wild-type versus dysferlin-knockout hearts and studied TAT network remodeling mechanisms inside cardiomyocytes by live-cell membrane imaging.

RESULTS:

We localized dysferlin in a vesicular compartment in nanometric proximity to contact sites of the TAT network with the sarcoplasmic reticulum, a.k.a. junctional complexes for Ca
2+
-induced Ca
2+
release. Interactome analyses demonstrated a novel protein interaction of dysferlin with the membrane-tethering sarcoplasmic reticulum protein juncophilin-2, a putative interactor of L-type Ca
2+
channels and ryanodine receptor Ca
2+
release channels in junctional complexes. Although the dysferlin-knockout caused a mild progressive phenotype of dilated cardiomyopathy, global proteome analysis revealed changes preceding systolic failure. Following transverse aortic constriction, dysferlin protein expression was significantly increased in hypertrophied wild-type myocardium, while dysferlin-knockout animals presented markedly reduced left-ventricular hypertrophy. Live-cell membrane imaging showed a profound reorganization of the TAT network in wild-type left-ventricular myocytes after transverse aortic constriction with robust proliferation of axial tubules, which critically depended on the increased expression of dysferlin within newly emerging tubule components.

CONCLUSIONS:
Dysferlin represents a new molecular target in cardiac disease that protects the integrity of tubule-sarcoplasmic reticulum junctional complexes for regulated excitation-contraction coupling and controls TAT network reorganization and tubular membrane proliferation in cardiomyocyte hypertrophy induced by pressure overload.
Glucagon Receptor Antagonist for Heart Failure With Preserved Ejection Fraction
Authors: Gao Chen , Xiong Zhaojun , Liu Yunxia , Wang Meng , Wang Menglong , Liu Tian , Liu Jianfang , Ren Shuxun , Cao Nancy , Yan Hai , Drucker Daniel J. , Rau Christoph Daniel , Yokota Tomohiro , Huang Jijun , Wang Yibin 
Published: July 2024

BACKGROUND:
Heart failure with preserved ejection fraction (HFpEF) is an emerging major unmet need and one of the most significant clinic challenges in cardiology. The pathogenesis of HFpEF is associated with multiple risk factors. Hypertension and metabolic disorders associated with obesity are the 2 most prominent comorbidities observed in patients with HFpEF. Although hypertension-induced mechanical overload has long been recognized as a potent contributor to heart failure with reduced ejection fraction, the synergistic interaction between mechanical overload and metabolic disorders in the pathogenesis of HFpEF remains poorly characterized.

METHOD:

We investigated the functional outcome and the underlying mechanisms from concurrent mechanic and metabolic stresses in the heart by applying transverse aortic constriction in lean C57Bl/6J or obese/diabetic B6.Cg-Lep
ob
/J (ob/ob) mice, followed by single-nuclei RNA-seq and targeted manipulation of a top-ranked signaling pathway differentially affected in the 2 experimental cohorts.

RESULTS:
In contrast to the post-transverse aortic constriction C57Bl/6J lean mice, which developed pathological features of heart failure with reduced ejection fraction over time, the post-transverse aortic constriction ob/ob mice showed no significant changes in ejection fraction but developed characteristic pathological features of HFpEF, including diastolic dysfunction, worsened cardiac hypertrophy, and pathological remodeling, along with further deterioration of exercise intolerance. Single-nuclei RNA-seq analysis revealed significant transcriptome reprogramming in the cardiomyocytes stressed by both pressure overload and obesity/diabetes, markedly distinct from the cardiomyocytes singularly stressed by pressure overload or obesity/diabetes. Furthermore, glucagon signaling was identified as the top-ranked signaling pathway affected in the cardiomyocytes associated with HFpEF. Treatment with a glucagon receptor antagonist significantly ameliorated the progression of HFpEF-related pathological features in 2 independent preclinical models. Importantly, cardiomyocyte-specific genetic deletion of the glucagon receptor also significantly improved cardiac function in response to pressure overload and metabolic stress.

CONCLUSIONS:
These findings identify glucagon receptor signaling in cardiomyocytes as a critical determinant of HFpEF progression and provide proof-of-concept support for glucagon receptor antagonism as a potential therapy for the disease.
Asymptomatic Intracranial Artery Stenosis/Occlusion in Heterozygous Familial Hypercholesterolemia: Its Frequency and Implications for Cerebrovascular and Cardiovascular Events
Authors: Funabashi Sayaka , Kataoka Yu , Hori Mika , Ogura Masatsune , Doi Takahito , Morita Yoshiaki , Kiyoshige Eri , Nishimura Kunihiro , Noguchi Teruo , Harada‐Shiba Mariko 
Published: July 2024

Background
The atherogenic characteristics of heterozygous familial hypercholesterolemia (HeFH) increase the risk of premature atherosclerotic cardiovascular disease including not only coronary artery disease but ischemic stroke. Asymptomatic intracranial artery stenosis/occlusion (IASO) is a major cause of ischemic stroke, but it has not yet been fully characterized in patients with HeFH.

Methods and Results

This study analyzed 147 clinically diagnosed subjects with HeFH who underwent magnetic resonance imaging/magnetic resonance angiography imaging for evaluation of IASO (≥50% diameter stenosis). Major adverse cerebrovascular and cardiovascular events (cardiac death, ischemic stroke, and acute coronary syndrome) were compared in patients with HeFH with and without asymptomatic IASO. Asymptomatic IASO was observed in 13.6% of patients with HeFH. The untreated low‐density lipoprotein cholesterol level (240±95 versus 244±75 mg/dL;
P
=0.67) did not differ between the 2 groups. Despite the use of lipid‐lowering therapies (statin,
P
=0.71; high‐intensity statin,
P
=0.81; ezetimibe,
P
=0.33; proprotein convertase subxilisin/kexin type 9 inhibitor,
P
=0.39; low‐density lipoprotein apheresis,
P
=0.14), on‐treatment low‐density lipoprotein cholesterol level in patients with both HeFH and IASO was still suboptimally controlled (97±62 versus 105±50 mg/dL;
P
=0.17), accompanied by a higher triglyceride level (median, 109 versus 79 mg/dL;
P
=0.001). During the 12.4‐year observational period (interquartile range, 6.2–24.6 years), asymptomatic IASO exhibited a 4.04‐fold greater likelihood of experiencing a major adverse cardiovascular event (95% CI, 1.71–9.55;
P
=0.001) in patients with HeFH. This increased risk of a major adverse cardiovascular event was consistently observed in a multivariate Cox proportional hazards model adjusting clinical characteristics (hazard ratio, 4.32 [95% CI, 1.71–10.9];
P
=0.002).

Conclusions
A total of 13.6% of Japanese subjects with HeFH presented with asymptomatic IASO. Despite lipid‐lowering therapies, patients with both HeFH and IASO more likely had elevated risk of cerebrovascular and cardiovascular events. Our findings highlight asymptomatic IASO as a phenotypic feature of HeFH‐related atherosclerosis, which ultimately affects future outcomes.