bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unfolded Von Willebrand Factor Binds Protein S and Reduces Anticoagulant Activity
Authors: Sim Martha M.S. , Mollica Molly Y. , Alfar Hammodah R. , Hollifield Melissa , Chung Dominic W. , Fu Xiaoyun , Gandhapudi Siva , Coenen Daniëlle M. , Prakhya Kanakanagavalli Shravani , Mahmood Dlovan F. D , Banerjee Meenakshi , Peng Chi , Li Xian , Thornton Alice C. , Porterfield James Z. , Sturgill Jamie L. , Sievert Gail A. , Barton-Baxter Marietta , Zheng Ze , Campbell Kenneth S. , Woodward Jerold G. , López José A. , Whiteheart Sidney W. , Garvy Beth A. , Wood Jeremy P. 
Published: February 2024

AbstractProtein S (PS), the critical plasma cofactor for the anticoagulants tissue factor (TF) pathway inhibitor (TFPI) and activated protein C (APC), circulates in two functionally distinct pools: free (anticoagulant) or bound to complement component 4b-binding protein (C4BP) (anti-inflammatory). Acquired free PS deficiency is detected in several viral infections, but its cause is unclear. Here, we identified a shear-dependent interaction between PS and von Willebrand Factor (VWF) by mass spectrometry. Consistently, plasma PS and VWF comigrated in both native and agarose gel electrophoresis. The PS/VWF interaction was blocked by TFPI but not APC, suggesting an interaction with the C-terminal sex hormone binding globulin (SHBG) region of PS. Microfluidic systems, mimicking arterial laminar flow or disrupted turbulent flow, demonstrated that PS stably binds VWF as VWF unfolds under turbulent flow. PS/VWF complexes also localized to platelet thrombi under laminar arterial flow. In thrombin generation-based assays, shearing plasma decreased PS activity, an effect not seen in the absence of VWF. Finally, free PS deficiency in COVID-19 patients, measured using an antibody that binds near the C4BP binding site in SHBG, correlated with changes in VWF, but not C4BP, and with thrombin generation. Our data suggest that PS binds to a shear-exposed site on VWF, thus sequestering free PS and decreasing its anticoagulant activity, which would account for the increased thrombin generation potential. As many viral infections present with free PS deficiency, elevated circulating VWF, and increased vascular shear, we propose that the PS/VWF interaction reported here is a likely contributor to virus-associated thrombotic risk.Key PointsVon Willebrand Factor (VWF) binds Protein S (PS) in a shear-dependent manner, reducing the free PS pool and its anticoagulant activity.The PS/VWF complex forms under turbulent flow conditions, is stable in whole blood, and localizes to growing platelet thrombi.
Evaluating Bacterial Viability in Faecal Microbiota Transplantation: A Comparative Analysis of In Vitro Cultivation and Membrane Integrity Methods
Authors: Cibulková Ivana , Řehořová Veronika , Wilhelm Marek , Soukupová Hana , Hajer Jan , Duška František , Daňková Helena , Cahová Monika 
Published: February 2024

AbstractBackgroundFaecal microbiota transplantation (FMT) is a developing therapy for disorders related to gut dysbiosis. Despite its growing application, standardized protocols for FMT filtrate preparation and quality assessment remain undeveloped. The viability of bacteria in the filtrate is crucial for FMT’s efficacy and for validating protocol execution. We compared two methods—in vitro cultivation and membrane integrity assessment—for their accuracy, reproducibility, and clinical applicability in measuring bacterial viability in frozen FMT stool filtrate.MethodsBacterial viability in stool filtrate was evaluated using (i) membrane integrity through fluorescent DNA staining with SYTO9 and propidium iodide, followed by flow cytometry; and (ii) culturable bacteria counts (colony-forming units, CFU) under aerobic or anaerobic conditions.ResultsWe refined the bacterial DNA staining protocol integrated with flow cytometry for stool samples. Both the membrane integrity-based and cultivation-based methods exhibited significant variability in bacterial viability across different FMT filtrates, without correlation. The cultivation-based method showed a mean coefficient of variance of 17%, ranging from 5.3% to 52.9%. Conversely, the membrane integrity approach yielded highly reproducible results, with a median coefficient of variance for viable cells of 0.9%, ranging from 8.5% to 0.04%.ConclusionBacterial viability assessment using cultivation-dependent methods produces inconsistent outcomes. In contrast, the membrane integrity method offers robust and precise data, making it a viable option for routine faecal material evaluation in FMT.
Diversity ofVibrio choleraeO1 through the human gastrointestinal tract during cholera
Authors: Lypaczewski Patrick , Chac Denise , Dunmire Chelsea N. , Tandoc Kristine M. , Chowdhury Fahima , Khan Ashraful I. , Bhuiyan Taufiqur , Harris Jason B. , LaRocque Regina C. , Calderwood Stephen B. , Ryan Edward T. , Qadri Firdausi , Shapiro B. Jesse , Weil Ana A. 
Published: February 2024

ABSTRACTVibrio choleraeO1 causes the diarrheal disease cholera, and the small intestine is the site of active infection. During cholera, cholera toxin is secreted fromV. choleraeand induces a massive fluid influx into the small intestine, which causes vomiting and diarrhea. Typically,V. choleraegenomes are sequenced from bacteria passed in stool, but rarely from vomit, a fluid that may more closely represents the site of active infection. We hypothesized that theV. choleraeO1 population bottlenecks along the gastrointestinal tract would result in reduced genetic variation in stool compared to vomit. To test this, we sequencedV. choleraegenomes from ten cholera patients with paired vomit and stool samples. Genetic diversity was low in both vomit and stool, consistent with a single infecting population rather than co-infection with divergentV. choleraeO1 lineages. The number of single nucleotide variants decreased between vomit and stool in four patients, increased in two, and remained unchanged in four. The number of genes encoded in theV. choleraegenome decreased between vomit and stool in eight patients and increased in two. Pangenome analysis of assembled short-read sequencing demonstrated that the toxin-coregulated pilus operon more frequently contained deletions in genomes from vomit compared to stool. However, these deletions were not detected by PCR or long-read sequencing, indicating that interpreting gene presence or absence patterns from short-read data alone may be incomplete. Overall, we found thatV. choleraeO1 isolated from stool is genetically similar toV. choleraerecovered from the upper intestinal tract.IMPORTANCEVibrio choleraeO1, the bacterium that causes cholera, is ingested in contaminated food or water and then colonizes the upper small intestine and is excreted in stool. ShedV. choleraegenomes are usually studied, butV. choleraeisolated from vomit may be more representative of whereV. choleraecolonizes in the upper intestinal epithelium.V. choleraemay experience bottlenecks, or large reductions in bacterial population sizes or genetic diversity, as it passes through the gut. Passage through the gut may select for distinctV. choleraemutants that are adapted for survival and gut colonization. We did not find strong evidence for such adaptive mutations, and instead observed that passage through the gut results in modest reductions inV. choleraegenetic diversity, and only in some patients. These results fill a gap in our understanding of theV. choleraelife cycle, transmission, and evolution.
A tension-induced morphological transition shapes the avian extra-embryonic territory
Authors: Michaut Arthur , Chamolly Alexander , Villedieu Aurélien , Corson Francis , Gros Jérôme 
Published: February 2024

The segregation of the extra-embryonic lineage is one of the earliest events and a key step in amniote development. Whereas the regulation of extra-embryonic cell fate specification has been extensively studied, little is known about the morphogenetic events underlying the formation of this lineage. Here, taking advantage of the amenability of avian embryos to live and quantitative imaging, we investigate the cell- and tissue-scale dynamics of epiboly, the process during which the epiblast expands to engulf the entire yolk. We show that tension arising from the outward migration of the epiblast border on the vitelline membrane stretches extra-embryonic cells, which reversibly transition from a columnar to squamous morphology. The propagation of this tension is strongly attenuated in the embryonic territory, which concomitantly undergoes fluid-like motion, culminating in the formation of the primitive streak. We formulate a simple viscoelastic model in which the tissue responds elastically to isotropic stress but flows in response to shear stress, and show that it recapitulates the flows and deformation of both embryonic and extra-embryonic tissues. Together, our results clarify the mechanical basis of early avian embryogenesis and provide a framework unifying the divergent mechanical behaviors observed in the contiguous embryonic and extra-embryonic territories that make up the epiblast.HighlightsThe extra-embryonic region expands radially during epibolyCell area increase accounts for the rapid extra-embryonic expansionEpiboly-induced tension reversibly stretches extra-embryonic cellsA simple viscoelastic model recovers the morphogenesis of the entire epiblast
Label free, capillary-scale blood flow mappingin vivoreveals that low intensity focused ultrasound evokes persistent dilation in cortical microvasculature
Authors: Shen YuBing , Jethe Jyoti V. , Reid Ashlan P. , Hehir Jacob , Amaral Marcello Magri , Ren Chao , Hao Senyue , Zhou Chao , Fisher Jonathan A. N. 
Published: February 2024

AbstractNon-invasive, low intensity focused ultrasound (FUS) is an emerging neuromodulation technique that offers the potential for precision, personalized therapy. An increasing body of research has identified mechanosensitive ion channels that can be modulated by FUS and support acute electrical activity in neurons. However, neuromodulatory effects that persist from hours to days have also been reported. The brain’s ability to provide targeted blood flow to electrically active regions involve a multitude of non-neuronal cell types and signaling pathways in the cerebral vasculature; an open question is whether persistent effects can be attributed, at least partly, to vascular mechanisms. Using a novelin vivooptical approach, we found that microvascular responses, unlike larger vessels which prior investigations have explored, exhibit persistent dilation following sonication without the use of microbubbles. This finding and approach offers a heretofore unseen aspect of the effects of FUSin vivoand indicate that concurrent changes in neurovascular function may partially underly persistent neuromodulatory effects.
Genome-wide transcriptional silencing and mRNA stabilization allow the coordinated expression of the meiotic program in mice
Authors: Bellutti Laura , Pen Edith Chan Sock , Guerquin Marie-Justine , Messiaen Sébastien , Llano Elena , Cluzet Victoria , Dereli Ihsan , Rolland Antoine , Martini Emmanuelle , Tóth Attila , Pendás Alberto M. , Chalmel Frederic , Livera Gabriel 
Published: February 2024

ABSTRACTThe transcriptional dynamic of mammalian cells when these transit from the ubiquitous mitotic to a meiotic specific program is key to understand this switch central to sexual reproduction. By quantifying active RNA polymerase II and nascent transcripts using single cell dataset and ethynyl-uridine pool-down with sorted cells from synchronised testes, we detailed the transcriptional activity of murine male germ cells. When spermatogonia differentiate, transcription slows down, reaching minimal activity at meiotic entry and resumes during pachytene stage. This event, we termed EMLT (for early meiotic low transcription), is distinct from the silencing of sex chromosomes as it is independent of Setdb1 though it is accompanied by the same chromatin mark, H3K9me3. EMLT is delayed in Stra8KO but occurs in mutants altering meiotic chromosome structure or DSB formation or repair. By comparing transcript abundance and neotranscription we unveil a massive event of mRNA stabilization that parallels EMLT. Altogether our data indicate that meiosis is initiated with a nearly silent genome and we propose that the stabilization of transcripts at that time facilitates the meiotic entry by synchronising the expression of several meiotic sub-programs.
BMP9 and BMP10 coordinate liver cellular crosstalk to maintain liver health
Authors: Zhao Dianyuan , Huang Ziwei , Li Xiaoyu , Wang Huan , Hou Qingwei , Wang Yuyao , Yan Fang , Yang Wenting , Liu Di , Yi Shaoqiong , Han Chunguang , Hao Yanan , Tang Li 
Published: February 2024

AbstractThe liver is the largest solid organ in the body and is primarily composed of HCs, ECs, KCs, and HSCs, which spatially interact and cooperate with each other to maintain liver homeostasis. However, the complexity and molecular mechanisms underlying the crosstalk between these different cell types remain to be revealed. Here, we generated mice with conditional deletion ofBmp9/10in different liver cell types and demonstrated that HSCs were the major source of BMP9 and BMP10 in the liver. Using transgenic ALK1 (receptor for BMP9/10) reporter mice, we found that ALK1 is expressed on KCs and ECs other than HCs and HSCs, and BMP9/10 secreted by HSCs promotes the differentiation of KCs and ECs and maintain their identity.Pdgfbexpression was significantly upregulated in KCs and ECs after BMP9 and BMP10 deletion, ultimately leading to HSCs activation and liver fibrosis. ECs express several angiocrine factors, such as BMP2, BMP6, Wnt2 and Rspo3, to regulate hepatocyte iron metabolism and metabolic zonation. We found that these angiocrine factors were significantly decreased in ECs fromBmp9/10HSC-KOmice, which further resulted in liver iron overload and disruption of HC zonation. In summary, we demonstrated that HSCs play a central role in mediating liver cell‒cell crosstalk via the production of BMP9/10, highlighting the important role of intercellular interaction in organ development and homeostasis.
Glial expression ofDrosophila UBE3Acauses spontaneous seizures modulated by 5-HT signaling
Authors: Sleep Megan , Landaverde Saul , Lacoste Andrew , Tan Selene , Schuback Reid , Reiter Lawrence T. , Iyengar Atulya 
Published: February 2024

AbstractMisexpression of the E3 ubiquitin ligaseUBE3Ais thought to contribute to a range of neurological disorders. In the context of Dup15q syndrome, excess genomic copies ofUBE3Ais thought to contribute to the autism, muscle tone and spontaneous seizures characteristic of the disorder. In aDrosophilamodel of Dup 15q syndrome, it was recently shown glial-driven expression of theUBE3Aorthologdube3aled to a “bang-sensitive” phenotype, where mechanical shock triggers convulsions, suggesting glialdube3aexpression contributes to hyperexcitability in flies. Here we directly compare the consequences of glial- and neuronal-drivendube3aexpression on motor coordination and neuronal excitability in Drosophila. We utilized IowaFLI tracker and developed a hidden Markov Model to classify seizure-related immobilization. Both glial and neuronal drivendube3aexpression led to clear motor phenotypes. However, only glial-drivendube3aexpression displayed spontaneous immobilization events, that were exacerbated at high-temperature (38 °C). Using a tethered fly preparation we monitored flight muscle activity, we found glial-drivendube3aflies display spontaneous spike discharges which were bilaterally synchronized indicative of seizure activity. Neither control flies, nor neuronal-dube3aoverexpressing flies display such firing patterns. Prior drug screen indicated bang-sensitivity in glial-drivendube3aexpressing flies could be suppressed by certain 5-HT modulators. Consistent with this report, we found glial-drivendube3aflies fed the serotonin reuptake inhibitor vortioxetine and the 5HT2Aantagonist ketanserin displayed reduced immobilization and spike bursting. Together these findings highlight the potential for glial pathophysiology to drive Dup15q syndrome-related seizure activity.
Pre-vaccination carriage prevalence ofStreptococcus pneumoniaeserotypes among internally displaced people in Somaliland
Authors: van Zandvoort Kevin , Ibrahim Hassan Abdirahman , Bobe Mohamed , Pell Casey L. , Ahmed Mohammed Saed , Ortika Belinda D. , Ibrahim Saed , Abdi Mohamed Ismail , Karim Mustapha A , Eggo Rosalind M , Yusuf Sulieman , Hinds Jason , Soleman Saed Mohamood , Cummings Rachael , McGowan Catherine , Mulholland Kim , Hergeeye Mohamed Abdi , Satzke Catherine , Checchi Francesco , Flasche Stefan 
Published: February 2024

AbstractPopulations affected by humanitarian crises likely experience high burdens of pneumococcal disease. Streptococcus pneumoniae carriage estimates are essential to understand pneumococcal transmission dynamics and the potential impact of pneumococcal conjugate vaccines (PCV). Over 100 million people are forcibly displaced worldwide, yet here we present only the second pneumococcal carriage estimates for a displaced population.In October 2019, we conducted a cross-sectional survey among internally displaced people (IDP) living in Digaale, a permanent IDP camp in Somaliland where PCV has not been implemented. We collected nasopharyngeal swab samples from 453 residents which were assessed for presence of pneumococci and serotyped using DNA microarray.We found that pneumococcal carriage prevalence was 36% (95%CI 31 – 40) in all ages, and 70% (95%CI 64 – 76) in children under 5. The three most common serotypes were vaccine serotypes 6B, 19F, and 23. We estimated that the serotypes included in the 10-valent PNEUMOSIL vaccine were carried by 41% (95%CI 33 – 49) of all pneumococcal carriers and extrapolated that they caused 52% (95%CI 35 – 72) of invasive pneumococcal disease. We found some evidence that pneumococcal carriage was associated with recent respiratory symptoms, the total number of physical contacts made, and with malnutrition in children under 5. Through linking with a nested contact survey we projected that pneumococcal exposure of children under 2 was predominantly due to contact with children aged 2-5 (39%; 95%CI 32 – 48) and 6-14 (25%; 95%CI 18 – 33).These findings suggest considerable potential for direct and indirect protection against pneumococcal disease in Digaale through PCV use in children and potentially adolescents.
Thermal and magnetoelastic properties of the van der Waals ferromagnet
Fe3−δGeTe2
: Anisotropic spontaneous magnetostriction and ferromagnetic magnon excitations
Authors: Kremer Reinhard K. , Brücher Eva 
Published: February 2024

By determining the lattice parameters as a function of temperature of the hexagonal van der Waals ferromagnet Fe2.92(1)Ge1.02(3)Te2 we obtain the temperature dependence of the spontaneous in-plane magnetostriction in the ferromagnetic and the linear thermal expansion coefficients in the paramagnetic state. The spontaneous magnetostriction is clearly seen in the temperature dependence of the in-plane lattice parameter a(T), but less well pronounced perpendicular to the planes along c. Below TC the spontaneous magnetostriction follows a power law M(T)3/2 of the magnetization and leads to an expansion of the hexagonal layers. Extrapolating to T→ 0 K we obtain a spontaneous in-plane saturation magnetostriction of λsp,a(T→0)≈−220×10−6. In the paramagnetic state the linear thermal expansion coefficients amount to 13.9(1)×10−6K−1 and to 23.2(2)×10−6K−1 for the in-plane and out-of-plane direction, respectively, indicating a linear volume thermal expansion coefficient of 50.8(4)×10−6K−1 which we use to estimate the volume thermal expansion contribution to the heat capacity determined at constant pressure. A Sommerfeld-type linear term in the low-temperature heat capacities can be quantitatively ascribed to two-dimensional (2D) ferromagnetic magnon excitations.

Published by the American Physical Society
2024
Sparse Random Hamiltonians Are Quantumly Easy
Authors: Chen Chi-Fang , Dalzell Alexander M. , Berta Mario , Brandão Fernando G. S. L. , Tropp Joel A. 
Published: February 2024

A candidate application for quantum computers is to simulate the low-temperature properties of quantum systems. For this task, there is a well-studied quantum algorithm that performs quantum phase estimation on an initial trial state that has a non-negligible overlap with a low-energy state. However, it is notoriously hard to give theoretical guarantees that such a trial state can be prepared efficiently. Moreover, the heuristic proposals that are currently available, such as with adiabatic state preparation, appear insufficient in practical cases. This paper shows that, for most random sparse Hamiltonians, the maximally mixed state is a sufficiently good trial state, and phase estimation efficiently prepares states with energy arbitrarily close to the ground energy. Furthermore, any low-energy state must have non-negligible quantum circuit complexity, suggesting that low-energy states are classically nontrivial and phase estimation is the optimal method for preparing such states (up to polynomial factors). These statements hold for two models of random Hamiltonians: (i) a sum of random signed Pauli strings and (ii) a random signed d-sparse Hamiltonian. The main technical argument is based on some new results in nonasymptotic random matrix theory. In particular, a refined concentration bound for the spectral density is required to obtain complexity guarantees for these random Hamiltonians.

Published by the American Physical Society
2024
Model-free low-power observer based robust trajectory tracking control of UAV quadrotor with unknown disturbances
Authors: Siddiqui Muhammad Nabeel , Zhu Xiaolu , Rasool Hanad , Afzal Muhammad Bilal , Ahmed Nigar 
Published: February 2024

Purpose
The purpose of this paper is to design an output-feedback algorithm based on low-power observer (LPO), robust chattering-free controller and nonlinear disturbance observer (DO) to achieve trajectory tracking of quadrotor in the Cartesian plane.

Design/methodology/approach
To achieve trajectory tracking control, firstly the decoupled rotational and translational model of quadrotor are modified by introducing backstepped state-space variables. In the second step, robust integral sliding mode control is designed based on the proportional-integral-derivative (PID) technique. In the third step, a DO is constructed. In next step, the measurable outputs, i.e. rotational and translational state variables, are used to design the LPO. Finally, in the control algorithm all state variables and its rates are replaced with its estimates obtained using the state-observer.

Findings
The finding includes output-feedback control (OFC) algorithm designed by using a LPO. A modified backstepping model for rotational and rotational systems is developed prior to the design of integral sliding mode control based on PID technique. Unlike traditional high-gain observers (HGO), this paper used the LPO for state estimation of quadrotor systems to solve the problem of peaking phenomenon in HGO. Furthermore, a nonlinear DO is designed such that it attenuates disturbance with unknown magnitude and frequency. Moreover, a chattering reduction criterion has been introduced to solve the inherited chattering issue of controllers based on sliding mode technique.

Practical implications
This paper presents input and output data-driven model-free control algorithm. That is, only input and output of the quadrotor model are required to achieve the trajectory tracking control. Therefore, for practical implementation, the number of on-board sensor is reduced.

Originality/value
Although extensive research has been done for designing OFC algorithms for quadrotor, LPO has never been implemented for the rotational and translational state estimations of quadrotor. Furthermore, the mathematical model of rotational and translational systems is modified by using backstepped variables followed by the controller designed using PID and integral sliding mode control technique. Moreover, a DO is developed for attenuation of disturbance with unknown bound, magnitude and frequency.