bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initiation of fibronectin fibrillogenesis is an enzyme-dependent process
Authors: Melamed Shay , Zaffryar-Eilot Shelly , Nadjar-Boger Elisabeth , Aviram Rohtem , Zhao Huaning , Yaseen-Badarne Wesal , Kalev-Altman Rotem , Sela-Donenfeld Dalit , Lewinson Oded , Astrof Sophie , Hasson Peleg , Wolfenson Haguy 
Published: November 2022

SummaryFibronectin fibrillogenesis and mechanosensing both depend on integrin-mediated force transmission to the extracellular-matrix. However, force transmission is in itself dependent on fibrillogenesis, and fibronectin fibrils are found in soft embryos where high forces cannot be applied, suggesting that force cannot be the sole initiator of fibrillogenesis. Here we identify a nucleation step prior to force transmission, driven by fibronectin oxidation mediated by lysyl-oxidase enzyme family members. This oxidation induces fibronectin clustering that promotes early adhesion, alters cellular response to soft matrices, and enhances force transmission to the matrix. In contrast, absence of fibronectin oxidation abrogates fibrillogenesis, perturbs cell-matrix adhesion, and compromises mechanosensation. Moreover, fibronectin oxidation promotes cancer cells colony formation in soft agar as well as collective and single-cell migration. These results reveal a force-independent enzyme-dependent mechanism that initiates fibronectin fibrillogenesis, establishing a critical step in cell adhesion and mechanosensing.
Consumption of the non-nutritive sweetener stevia for 12 weeks does not alter the composition of the gut microbiota
Authors: Singh Gurdeep , McBain Andrew J , McLaughlin John T , Stamataki Nikoleta S 
Published: November 2022

AbstractThe use of non-nutritive sweeteners (NNS) as an alternative to caloric sugars has increased in recent years. Stevia is a NNS that has demonstrated beneficial effects on appetite and energy intake. However, the impact on the gut microbiome is not well understood. Therefore, we investigated how regular consumption of stevia, for up to 12 weeks, impacts upon the human gut microbiome. Healthy subjects with a normal body mass index participated in the study; the stevia group (n= 14) were asked to consume five drops of stevia, twice daily, compared against control participants (n= 13). Faecal samples collected before and after treatment were analysed by 16S sequencing. Stevia did not cause significant changes in the beta or alpha diversity when compared to the control groups. When relative abundances of taxa were investigated, no clear differences could be detected. Conversely, random forest analysis could correctly associate the gut microbiome with control and stevia groups with an average of 75% accuracy, suggesting that there are intrinsic patterns that could discriminate between control and stevia use. However, large-scale changes in the gut microbiome were not apparent in this study and therefore, our data suggest that stevia does not significantly impact the gut microbiome.
CHRRT: boosting coordinate hit-and-run with rounding by thinning
Authors: Jadebeck Johann F. , Wiechert Wolfgang , Nöh Katharina 
Published: November 2022

AbstractThinning is a sub-sampling technique to reduce the memory footprint of Markov chain Monte Carlo. Despite being commonly used, thinning is rarely considered efficient. For sampling convex polytopes uniformly, a highly relevant use-case in systems biology, we here demonstrate that thinning generally boosts computational and, thereby, sampling efficiencies of the widely used Coordinate Hit-and-Run with Rounding (CHRR) algorithm. We benchmark CHRR with thinning (CHRRT) with simplices and constrained-based metabolic networks with up to thousands of dimensions. With appropriate thinning, CHRRT offers a substantial increase in computational efficiency compared to unthinned CHRR, in our examples of up to three orders of magnitude, as measured by the effective sample size per time (ESS/t). Our experiments reveal that the performance gain of CHRRT by optimal thinning grows substantially with polytope (effective model) dimension. Based on our experiments, we provide practically useful advice for tuning thinning to efficient and effective use of compute resources. Besides allocating computational resources optimally to permit sampling convex polytopes uniformly to convergence in a fraction of time, exploiting thinning unlocks investigating hitherto intractable models under limited computational budgets. CHRRT thereby paves the way to keep pace with progressing model sizes within the existing constraint-based reconstruction and analysis (COBRA) tool set. Sampling and evaluation pipelines are available athttps://jugit.fz-juelich.de/IBG-1/ModSim/fluxomics/chrrt.
A cell circuit approach to dissect fibroblast-macrophage interactions in the tumor microenvironment
Authors: Mayer Shimrit , Milo Tomer , Isaacson Achinoam , Halperin Coral , Miyara Shoval , Stein Yaniv , Pevsner-Fischer Meirav , Tzahor Eldad , Alon Uri , Scherz-Shouval Ruth 
Published: November 2022

AbstractThe tumor microenvironment (TME) is composed of various nonmalignant cell types that interact with each other and with cancer cells, impacting all aspects of cancer biology. The TME is complex and heterogeneous, and thus simplifying systems and concepts are needed. Here we provide a tractable experimental system and powerful mathematical circuit concepts to identify the main molecular interactions that govern the composition of the TME. We focus on two major components of the TME - cancer associated fibroblasts (CAFs) and tumor associated macrophages (TAMs), define their interactions and verify our predictions in mouse and human breast cancer. We measure the population dynamics starting from many initial conditions of co-cultures of macrophages and organ-derived fibroblasts from mammary, lung, and fat, and explore the effects of cancer-conditioned medium on the circuits. We define the circuits and their inferred parameters from the data using a mathematical approach, and quantitatively compare the cell circuits in each condition. We find that while the homeostatic steady-states are similar between the organs, the cancer-conditioned medium profoundly changes the circuit. Fibroblasts in all contexts depend on autocrine secretion of growth factors whereas macrophages are more dependent on external cues, including paracrine growth factors secreted from fibroblasts and cancer cells. Transcriptional profiling reveals the molecular underpinnings of the cell circuit interactions and the primacy of the fibroblast autocrine loop. The same fibroblast growth factors are shared by the co-cultures and mouse and human breast cancer. The cell circuit approach thus provides a quantitative account of cell interactions in the cancer microenvironment.
Representational geometries reveal differential effects of response correlations on population codes in neurophysiology and functional magnetic resonance imaging
Authors: Cheng Zi-Jian , Zhang Wen-Hao , Zhang Ru-Yuan 
Published: November 2022

ABSTRACTTwo sensory neurons usually display trial-by-trial response correlations given the repeated representations of an identical stimulus. The effects of such response correlations on population-level sensory coding have been the focal contention in computational neuroscience over the past few years. In the meantime, multivariate pattern analysis (MVPA) has been the leading analysis approach in functional magnetic resonance imaging (fMRI), but the effects of response correlations in voxel populations remain underexplored. Here, instead of conventional MVPA analysis, we calculate linear Fisher information of population responses in human visual cortex and hypothetically remove response correlations between voxels. We found that voxelwise response correlations generally enhance stimulus information, a result standing in stark contrast to the detrimental effects of response correlations reported in neurophysiological literature. By voxel-encoding modeling, we further show that these two seemingly opposite effects actually can coexist. Furthermore, we use principal component analysis to decompose stimulus information in population responses onto different principal dimensions in a high representational space. Interestingly, response correlations simultaneously reduce and enhance information on high- and low-variance principal dimensions, respectively. The relative strength of the two antagonistic effects within the same computational framework produces the apparent discrepancy in the effect of response correlations in neuronal and voxel populations. Our results suggest that multivariate fMRI data contain rich statistical structures that are directly related to sensory information representation, and the general computational framework to analyze neuronal and voxel population responses can be applied in many types of neural measurements.
Divergent impacts ofC9orf72repeat expansion on neurons and glia in ALS and FTD
Authors: Li Junhao , Jaiswal Manoj K , Chien Jo-Fan , Kozlenkov Alexey , Zhou Ping , Gardashli Mahammad , Pregent Luc J. , Engelberg-Cook Erica , Dickson Dennis W. , Belzil Veronique V. , Mukamel Eran A , Dracheva Stella 
Published: November 2022

AbstractNeurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), are strongly influenced by inherited genetic variation, but environmental and epigenetic factors also play key roles in the course of these diseases. A hexanucleotide repeat expansion in theC9orf72(C9) gene is the most common genetic cause of ALS and FTD. To determine the cellular alterations associated with the C9 repeat expansion, we performed single nucleus transcriptomics (snRNA-seq) and epigenomics (snATAC-seq) in postmortem samples of motor and frontal cortices from C9-ALS and C9-FTD donors. We found pervasive alterations of gene expression across multiple cortical cell types in C9-ALS, with the largest number of affected genes in astrocytes and excitatory neurons. Astrocytes increased expression of markers of activation and pathways associated with structural remodeling. Excitatory neurons in upper and deep layers increased expression of genes related to proteostasis, metabolism, and protein expression, and decreased expression of genes related to neuronal function. Epigenetic analyses revealed concordant changes in chromatin accessibility, histone modifications, and gene expression in specific cell types. C9-FTD patients had a distinct pattern of changes, including loss of neurons in frontal cortex and altered expression of thousands of genes in astrocytes and oligodendrocyte-lineage cells. Overall, these findings demonstrate a context-dependent molecular disruption in C9-ALS and C9-FTD, resulting in distinct effects across cell types, brain regions, and disease phenotypes.One Sentence SummaryC9orf72-associated ALS and FTDshowed a distinct pattern of transcriptome changes, with the largest number of affected genes in C9-ALS in astrocytes and excitatory neurons in upper and deep layers.
Microlenses fabricated by two-photon laser polymerization for cell imaging with non-linear excitation microscopy
Authors: Marini M. , Nardini A. , Vázquez R. Martínez , Conci C. , Bouzin M. , Collini M. , Osellame R. , Cerullo G. , Kariman B.S. , Farsari M. , Kabouraki E. , Raimondi M.T. , Chirico G. 
Published: November 2022

AbstractNon-linear excitation microscopy offers several advantages for in-vivo imaging compared to conventional confocal techniques. However, tissue penetration can still be an issue due to scattering and spherical aberrations induced on focused beams by the tissue. The use of low numerical aperture objectives to pass through the outer layers of the skin, together with high dioptric power microlenses implanted in-vivo close to the observation volume, can be beneficial to the reduction of optical aberrations. Here, we develop and test on fibroblast cell culture plano-convex microlenses to be used for non-linear imaging of biological tissue. The microlenses can be used as single lenses or multiplexed in an array. A thorough test of the lenses wavefront is reported together with the modulation transfer function and wavefront profile. We could retrieve magnified fluorescence images through the microlenses coupled to commercial confocal and two-photon excitation scanning microscopes. The signal-to-noise ratio of the images is not substantially affected by the use of the microlenses and the magnification can be adjusted by changing the relative position of the microlens array to the microscope objective and the immersion medium. These results are opening the way to the application of implanted micro-optics for optical in-vivo inspection of biological processes.
Suppression of insulin stimulated muscle glucose uptake by non-caloric sweetener sucralose and its reversal by an antidiabetic nutraceutical supplement
Authors: Arpitha Reddy R.N , Saranya K , Battula Sanjana , Kadiyala Gopi , Iyer Subramanian , Vangala Subrahmanyam , Chandran Satish , Saxena Uday 
Published: November 2022

AbstractNon caloric sweeteners (NCS) have been used for decades now as sugar substitutes in foods and beverages. The market for such products has grown immensely over time. There are human studies which report their negative effects on glucose metabolism with various results of disturbances in glucose metabolism, weight gain etc.No studies to the best of our knowledge have directly addressed the impact of the NCS on muscle glucose uptake. Muscle tissue can account for over 70 percent of whole-body glucose uptake. Therefore, we examined directly the effect of NCS on muscle cell glucose uptake. We find that aspartame moderately increased insulin stimulated glucose uptake by muscle cells in vitro. But sucralose, saccharin and stevia suppressed insulin stimulated glucose uptake.Sucralose is one of the most often used sweetener in foods and beverages globally it is important to understand its effects on glucose metabolism. Therefore, we explored the mechanism of its inhibition of glucose uptake by using an anti-diabetic nutraceutical which is known to target insulin mediated glucose uptake and metabolism pathways. We show here that the nutraceutical is able to relieve the suppression by sucrose in muscle uptake by a novel mechanism of action. We propose that such nutraceuticals may be useful to combine with sucralose containing products to offset negative effects of the NCS on glucose metabolism.
ECOLE: Learning to call copy number variants on whole exome sequencing data
Authors: Mandiracioglu Berk , Ozden Furkan , Kaynar Gun , Yilmaz Mehmet Alper , Alkan Can , Ercument Cicek A. 
Published: November 2022

AbstractCopy number variants (CNV) are shown to contribute to the etiology of several genetic disor­ders. Accurate detection of CNVs on whole exome sequencing (WES) data has been a long sought-after goal for use in clinics. This was not possible despite recent improvements in performance because algo­rithms mostly suffer from low precision and even lower recall on expert-curated gold standard call sets. Here, we present a deep learning-based somatic and germline CNV caller for WES data, named ECOLE. Based on a variant of the transformer architecture, the model learns to call CNVs per exon, using high-confidence calls made on matched WGS samples. We further train and fine-tune the model with a small set of expert calls via transfer learning. We show that ECOLE achieves high performance on human ex­pert labeled data for the first time with 68.7% precision and 49.6% recall. This corresponds to precision and recall improvements of 18.7% and 30.8% over the next best-performing methods, respectively. We also show that the same fine-tuning strategy using tumor samples enables ECOLE to detect RT-qPCR validated variations in bladder cancer samples without the need for a control sample. ECOLE is available athttps://github.com/ciceklab/ECOLE.
Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies
Authors: Planas Delphine , Bruel Timothée , Staropoli Isabelle , Guivel-Benhassine Florence , Porrot Françoise , Maes Piet , Grzelak Ludivine , Prot Matthieu , Mougari Said , Planchais Cyril , Puech Julien , Saliba Madelina , Sahraoui Riwan , Fémy Florent , Morel Nathalie , Dufloo Jérémy , Sanjuán Rafael , Mouquet Hugo , André Emmanuel , Hocqueloux Laurent , Simon-Loriere Etienne , Veyer David , Prazuck Thierry , Péré Hélène , Schwartz Olivier 
Published: November 2022

AbstractConvergent evolution of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 lineages has led to the emergence of several new subvariants, including BA.2.75.2, BA.4.6. and BQ.1.1. The subvariants BA.2.75.2 and BQ.1.1 are expected to become predominant in many countries in November 2022. They carry an additional and often redundant set of mutations in the spike, likely responsible for increased transmissibility and immune evasion. Here, we established a viral amplification procedure to easily isolate Omicron strains. We examined their sensitivity to 6 therapeutic monoclonal antibodies (mAbs) and to 72 sera from Pfizer BNT162b2-vaccinated individuals, with or without BA.1/BA.2 or BA.5 breakthrough infection. Ronapreve (Casirivimab and Imdevimab) and Evusheld (Cilgavimab and Tixagevimab) lost any antiviral efficacy against BA.2.75.2 and BQ.1.1, whereas Xevudy (Sotrovimab) remained weakly active. BQ.1.1 was also resistant to Bebtelovimab. Neutralizing titers in triply vaccinated individuals were low to undetectable against BQ.1.1 and BA.2.75.2, 4 months after boosting. A BA.1/BA.2 breakthrough infection increased these titers, which remained about 18-fold lower against BA.2.75.2 and BQ.1.1, than against BA.1. Reciprocally, a BA.5 breakthrough infection increased more efficiently neutralization against BA.5 and BQ.1.1 than against BA.2.75.2. Thus, the evolution trajectory of novel Omicron subvariants facilitated their spread in immunized populations and raises concerns about the efficacy of most currently available mAbs.
Spatial localization ability of planarians identified through a light maze paradigm
Authors: Qian Renzhi , yan Yuan , Pei Yu , Zhang Yixuan , Chi Yuanwei , Chen Yuxuan , Hao Kun , Xu Zhen , Yang Guang , Shao Zilun , Wang Yuhao , Li Xinran , Lu Chenxu , Zhang Xuan , Chen Kehan , Zhang Wenqiang , Wang Baoqing , Ying Zhengxin , Huang Kaiyuan 
Published: November 2022

AbstractSpatial localization ability is crucial for free-living animals to fit the environment. As shown by previous studies, planarians can be conditioned to discriminate directions. However, due to their simplicity and primitiveness, they had never been considered to have true spatial localization ability to retrieve locations of objects and places in the environment. Here, we introduce a light maze training paradigm to demonstrate that a planarian worm can navigate to a former recognized place from the start point, even if the worm is transferred into a newly produced maze. This finding identifies the spatial localization ability of planarians for the first time, which provides clues for the evolution of spatial learning. Since the planarians have a primitive brain with simple structures, this paradigm can also provide a simplified model for a detailed investigation of spatial learning.
Examining the influence of price-quality inference and consumer attitudes on the inclination to buy non-deceptive counterfeit goods: evidence from South Africa
Authors: Ndofirepi Takawira Munyaradzi , Chuchu Tinashe , Maziriri Eugine , Nyagadza Brighton 
Published: November 2022

PurposeThe market for counterfeit goods worldwide has continued to grow significantly over the years, attracting the curiosity of researchers in the marketing field. This study aimed to analyse the influence of price-quality inference and attitudes towards economic rewards of purchasing counterfeit products on the intentions to purchase non-deceptive counterfeit products.Design/methodology/approachThe research adopted a quantitative methodology and utilised the cross-sectional survey method to collect data from a sample of 381 respondents comprising university students. The data was then analysed using the computer software Smart PLS 4.FindingsThe results established that the respondents’ price-quality inference of counterfeit products was positively associated with the attitudes towards economic rewards of purchasing counterfeit products and intention to purchase counterfeit products. Furthermore, the study revealed that attitudes towards economic rewards of purchasing counterfeit products partially mediated the influence of price-quality inference on customer intention to acquire non-deceptive counterfeit goods. A multigroup analysis of the proposed relationship did not find any statistically significant differences in the pattern of results concerning the gender groups.Research limitations/implicationsThe significance of the study findings is hampered by the singular focus on university students as a reference point for young people’s perceptions of counterfeit goods in South Africa. The study, however, presents verifiable evidence that marketers and brand managers of genuine products may utilise to develop intervention measures to sway young African consumers away from counterfeits and towards genuine brands.Originality/valueThis is one of the few studies in the literature that addresses young adults’ deliberate purchasing of non-deceptive counterfeits in South Africa, an important consumer market in Africa.
Venturing and managing disruptive digital innovations: financial management concept motivated propositions
Authors: Imam Tasadduq 
Published: November 2022

Purpose
There are uncertainties concerning how innovators can successfully venture into disruptive innovations and how incumbents can react to the emergence of such innovations. Disruptive digital innovations, which use information technology to disrupt business contexts and can evolve rapidly to either successes or failures, have unique challenges. The literature has largely remained silent concerning these. Also, existing studies often focus on innovations originating in developed economies and just on successful cases. There is a lack of comparative focus on successful and failure cases emerging across economies. The purpose of this paper is to fill these gaps.

Design/methodology/approach
This paper assesses the evolution of disruptive digital innovations in various contexts through a financial management-motivated conceptual framework. Contrary to existing works, this paper focuses on both successful and failure cases and regards the influence of various stakeholders further to innovators and incumbents to explain the successes or failures of the innovation.

Findings
There are some common success factors for disruptive digital innovation. These include an inherent focus on social value, alignment to financiers' interests and rivals' actions and strategic collaborations to create a synergy effect.

Research limitations/implications
Innovators can cause effective digital disruption by focusing on social and financial values. Success can also largely depend on strategic partnerships rather than actions by an individual entity. Thus, venturing and managing disruptive digital innovation is not an isolated but a social process.

Originality/value
This paper recommends propositions for innovators and incumbents to venture into and confront disruptive digital innovations effectively. Its originality lies in focusing on both successful and failure cases, unexplored in literature, to develop the propositions.