bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-Echo Investigations of Positive and Negative CBF and Concomitant BOLD Changes
Authors: Devi Ratnamanjuri , Lepsien Jöran , Lorenz Kathrin , Schlumm Torsten , Mildner Toralf , Möller Harald E. 
Published: September 2022

AbstractUnlike the positive blood oxygenation level-dependent (BOLD) response (PBR), commonly taken as an indication of an ‘activated’ brain region, the physiological origin of negative BOLD signal changes (i.e. a negative BOLD response, NBR), also referred to as ‘deactivation’ is still being debated. In this work, an attempt was made to gain a better understanding of the underlying mechanism by obtaining a comprehensive measure of the contributing cerebral blood flow (CBF) and its relationship to the NBR in the human visual cortex, in comparison to a simultaneously induced PBR in surrounding visual regions. To overcome the low signal-to-noise ratio (SNR) of CBF measurements, a newly developed multi-echo version of a center-out echo planar-imaging (EPI) readout was employed with pseudo-continuous arterial spin labeling (pCASL). It achieved very short echo and inter-echo times and facilitated a simultaneous detection of functional CBF and BOLD changes at 3 T with improved sensitivity. Evaluations of the absolute and relative changes of CBF and the effective transverse relaxation rate, , the coupling ratios, and their dependence on CBF at rest, CBFrest, indicated differences between activated and deactivated regions. Analysis of the shape of the respective functional responses also revealed faster negative responses with more pronounced post-stimulus transients. Resulting differences in the flow-metabolism coupling ratios were further examined for potential distinctions in the underlying neuronal contributions.HighlightsIntroduction of multi-echo center-out EPI for investigating concomitant CBF and BOLD changes in regions of positive (PBR) and negative BOLD response (NBR).ΔCBF timecourses closely follow those of with negative signals exhibiting faster responses and more pronounced post-stimulus transients.Decreases in CBF appear to warrant a larger change in NBR than CBF increases in PBR regions.Consideration of baseline CBF values is important in comparisons of relative coupling ratios (δsBOLD/δcbf) between brain regions.Discussion of potential excitatory and inhibitory neuronal feed forward control of CBF and CMRO2 in PBR and NBR.
A selective force driving metabolic genes clustering
Authors: Fondi Marco , Pini Francesco , Riccardi Christopher , Gemo Pietro , Brilli Matteo 
Published: September 2022

AbstractThe evolution of operons has puzzled evolutionary biologists since their discovery and many theories exist to explain their emergence and spreading. The presence of several plausible hypotheses dealing with operon emergence/evolution/spreading is indicative of the absence of a universal causal factor for this evolutionary process. Here, we argue that the way in which DNA replication and cell division are coupled in microbial species introduces an additional selective force that may be responsible for the clustering of functionally related genes on chromosomes. We interpret this as a preliminary and necessary step in operon formation. Specifically, we start from the observation that during DNA replication differences in copy number of genes that are found at distant loci on the same chromosome arm exist. We provide theoretical considerations suggesting that, when genes of the same metabolic process are far away on the chromosome, this results in perturbations to metabolic homeostasis. By formalizing the effect of DNA replication on metabolic homeostasis based on Metabolic Control Analysis, we show that the above situation provides a selective force that can drive the formation of gene clusters and operons. Finally, we confirmed that, in present-day genomes, this force is significantly stronger in those species where the average number of active replication forks is larger and quantify the theoretical contribution of this feature on the distribution of extant gene clusters and operons.
mtHsp70 converts mitochondrial proteostasis distress into impaired protein import
Authors: Banerjee Rupa , Trauschke Vanessa , Bertram Nils , Aretz Ina , Osman Christof , Lamb Don C. , Mokranjac Dejana 
Published: September 2022

AbstractFunctional mitochondria are essential for cell viability and depend on protein import from the cytosol. Impaired protein import initiates various well-characterized cellular programs that rescue or remove dysfunctional mitochondria. However, the molecular mechanism that underlies the initial reduction of protein import into defective mitochondria remained unknown. Here, we found that the redistribution of mtHsp70, mitochondrial chaperone that is involved in both protein import and protein folding, regulates the efficiency of protein import. During early mitochondrial stress, before rescue programs are initiated and membrane potential is affected, mtHsp70-dependent import was specifically impaired and association of mtHsp70 with the import complex reduced. Even under non-stress conditions, the majority of mtHsp70 is found in a substrate-bound state. We propose that the availability of free mtHsp70 limits protein import into mitochondria during stress.
Structural basis for membrane attack complex inhibition by CD59
Authors: Couves Emma C. , Gardner Scott , Voisin Tomas B. , Bickel Jasmine K. , Stansfeld Phillip J. , Tate Edward W. , Bubeck Doryen 
Published: September 2022

AbstractCD59 is an abundant immuno-regulatory receptor that protects human cells from damage during complement activation. Here we show how the receptor binds complement proteins C8 and C9 at the membrane to prevent insertion and polymerization of membrane attack complex (MAC) pores. We present cryoelectron microscopy structures of two inhibited MAC precursors known as C5b8 and C5b9. We discover that in both complexes, CD59 binds the pore-forming ◻-hairpins of C8 to form an intermolecular ◻-sheet that prevents membrane perforation. While bound to C8, CD59 deflects the cascading C9 ◻-hairpins, rerouting their trajectory into the membrane. Preventing insertion of C9 restricts structural transitions of subsequent monomers and indirectly halts MAC polymerization. We combine our structural data with cellular assays and molecular dynamics simulations to explain how the membrane environment impacts the dual roles of CD59 in controlling pore formation of MAC, and as a target of bacterial virulence factors which hijack CD59 to lyse human cells.
A continuous vibration-based virtual tactile motion across fingertips
Authors: Adibi Mehdi 
Published: September 2022

AbstractMotion is one of the fundamental qualities not only of vision, but also of touch. Manipulation and exploration of objects involves different forms of movement between the skin and objects. A different form of tactile motion from remote sources is through substrate vibrations, and is present in arthropods such as insects and spiders, enabling them to localise approaching preys and predators. Here, we quantify the extent to humans perceive tactile motion based on vibrations sensed by fingertips. We employed a novel stimulation paradigm in which a pair of vibrations (100 Hz) with sinusoidal envelopes (0.5 cycle/s) and various phase differences between the two vibrations were delivered to two fingertips. The phase difference between the vibrations generated perception of a virtual motion across the fingertips. The findings suggest that human tactile system possesses the sensory channel for detection of motion through substrate vibrations, which is fundamentally different from tactile motion mechanisms during active surface exploration. We propose two potential neural computations underlying processing this form of motion; one based on phase difference or time delay detection, and the second based on temporal order and interval duration processing.
RNA-deficient TDP-43 causes loss of free nuclear TDP-43 by sequestration
Authors: Keating Sean S. , Bademosi Adekunle T. , Gil Rebecca San , Walker Adam K. 
Published: September 2022

AbstractDysfunction and aggregation of the RNA-binding protein, TDP-43, is the unifying hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Mechanisms and relative contributions of concurrent TDP-43 nuclear depletion, cytoplasmic accumulation, and post-translational modification to neurodegeneration remain unresolved. We employed CRISPR/Cas9-mediated fluorescent tagging to investigate how disease-associated stressors and pathological TDP-43 alter abundance, localisation, self-assembly, aggregation, solubility, and mobility dynamics of endogenous TDP-43 over time. Oxidative stress stimulated TDP-43 liquid-liquid phase separation into droplets or spherical shell-like ‘anisosomes’, which were not formed by over-expressed wild-type TDP-43. Further, nuclear RNA-binding-ablated or acetylation-mimicking TDP-43 rapidly formed anisosomes and inclusions that readily sequestered and depleted free normal nuclear TDP-43. The majority of total endogenous TDP-43 was sequestered into anisosomes, but retained high protein mobility and solubility. However, cytoplasmic RNA-deficient TDP-43 formed large phosphorylated inclusions that occasionally sequestered endogenous TDP-43, rendering it insoluble and immobile, indicating irreversible pathological transition. These findings suggest that post-translational modification and RNA-binding deficiency exacerbate TDP-43 aggregation and dysfunction by driving sequestration, mislocalisation, and depletion of normal nuclear TDP-43 in ALS and FTD.
Identifying Lymph Node Metastasis-related Factors in Breast Cancer using Differential Modular and Mutational Structural Analysis
Authors: Liu Xingyi , Yang Bin , Huang Xinpeng , Yan Wenying , Hu Guang 
Published: September 2022

AbstractComplex diseases are generally caused by disorders of biological networks and/or mutations in multiple genes. Network theory provides useful tools to study the underlying laws governing complex diseases. Within this framework, comparisons of network topologies, including the node, edge, and community, between different disease states can highlight key factors within these dynamic processes. Here, we propose a differential modular analysis approach that integrates protein-protein interactions with gene expression profiles for modular analysis, and introduces inter-modular edges and date hubs to identify the “core network module” that quantifies the significant phenotypic variation. Then, based on this core network module, key factors including functional protein-protein interactions, pathways, and drive mutations are predicted by the topological-functional connection score and structural modeling. We applied the approach to analyze the lymph node metastasis (LNM) process in breast cancer. The functional enrichment analysis showed that both inter-modular edges and date hubs play important roles in cancer metastasis and invasion, and in metastasis hallmarks. The structural mutation analysis suggested that the LNM of breast cancer may be the outcome of the dysfunction of rearranged during transfection (RET) proto-oncogene-related interactions and the non-canonical calcium signaling pathway via an allosteric mutation of RET. We believe that the proposed method can provide new insights into disease progression such as cancer metastasis.Author summaryMetastasis is the hallmark of cancer that is responsible for the greatest number of cancer-related deaths. However, it remains poorly understood. PPI networks not only provide a static picture of cellular function and biological processes, but also have emerged as new paradigms in the study of the dynamic process of disease progression, including cancer metastasis. Herein, a network-based strategy was proposed based on the integration of expression profiles with protein interactions, by filtering with “date hubs” and “inter-modular edges”, demonstrating that different network modules may provide robust predictors to represent the dynamic mechanisms involved in metastasis formation. Furthermore, the mapping of protein structure and mutation data on the network module level provides insight into signaling mechanisms; helps understand the mechanism of disease-related mutations; and helps in drug discovery. The application of our method to study the LNM in breast cancer highlights network modules defining protein communities that respond to therapeutics, and the implications of detailed structural and mechanistic insight into oncogenic activation and how it can advance allosteric precision oncology.
Stepwise evolution ofE. coliC and ΦX174 reveals unexpected lipopolysaccharide (LPS) diversity
Authors: Dherbey Jordan Romeyer , Parab Lavisha , Gallie Jenna , Bertels Frederic 
Published: September 2022

AbstractPhage therapy is a promising method for the treatment of multi-drug-resistant bacterial infections. However, its long-term efficacy depends on understanding the evolutionary effects of the treatment. Current knowledge of such evolutionary effects is lacking, even in well-studied systems. We used the bacteriumEscherichia coliC and its bacteriophage ΦX174, which infects cells using host lipopolysaccharide (LPS) molecules. We first generated 31 bacterial mutants resistant to ΦX174 infection. Based on the genes disrupted by these mutations, we predicted that theseE. coliC mutants collectively produce eight unique LPS structures. We then developed a series of evolution experiments to select for ΦX174 mutants capable of infecting the resistant strains. During phage adaptation, we distinguished two types of phage resistance: one that was easily overcome by ΦX174 with few mutational steps (“easy” resistance), and one that was more difficult to overcome (“hard” resistance). We found that increasing the diversity of the host and phage populations could accelerate the adaptation of phage ΦX174 to overcome the hard resistance phenotype. From these experiments, we isolated 16 ΦX174 mutants that, together, can infect all 31 initially resistantE. coliC mutants. Upon determining the infectivity profiles of these 16 evolved phages, we uncovered 14 distinct profiles. Given that only eight profiles are anticipated if the LPS predictions are correct, our findings highlight that the current understanding of LPS biology is insufficient to accurately forecast the evolutionary outcomes of bacterial populations infected by phage.
From Gradient to Sectioning in CUBE: Workflow for Generating and Imaging Organoid with Localized Differentiation
Authors: Koh Isabel , Hagiwara Masaya 
Published: September 2022

AbstractAdvancements in organoid culture methods have led to a widespread availability of various in vitro mini-organs that mimic native tissues in many ways. Yet, the bottleneck remains to generate complex organoids with body axis patterning, as well as keeping the orientation of organoid samples during post-experiment analysis processes. In this paper, we present a workflow for culturing organoids with gradient using a previously developed CUBE culture device, then sectioning samples with the CUBE to retain information on the gradient direction of the sample. We show that hiPSC spheroids cultured with separate differentiation media on two opposing ends of the CUBE resulted in localized expressions of the respective differentiation markers, in contrast to homogeneous distribution of markers in controls with the same media on both ends. We also describe the processes for cryo and paraffin sectioning of gradient-cultured spheroids in CUBE to retain gradient orientation information. This workflow from gradient culture to sectioning with CUBE can provide researchers with a convenient tool to generate increasingly complex organoids and study their developmental processes in vitro.
Molecular docking: Bioactive compounds ofMimosa pudicaas an inhibitor ofCandida albicansSap 3
Authors: Gholam Gusnia Meilin , Firdausy Iman Akhyar , Artika I. Made , Abdillah Ramadhani Malik , Firmansyah Ridwan Putra 
Published: September 2022

AbstractCandida albicans(C. albicans) is a commensal microbiota that resides in humans. However, in certain cases, C. albicans can infect and cause several diseases to humans. This study aimed to investigate the interaction between Mimosa pudica bioactive compounds andC. albicansSap 3. Molecular docking analysis was carried out using YASARA structure. The procedures involved preparation of ligands and target receptor, molecular docking, data analysis and visualization. All 3D ligands were downloaded from PubChem NCBI, while target receptor was downloaded from RCSB PDB. The interaction between Mimosa pudica bioactive compounds against Sap 3 resulted in a binding energies ranges from 5,168 – 7,480 kcal/mol and most of the interactions formed were relatively strong. Furthermore, the test ligands had contact with the catalytic residues and substrate binding site pockets S1/S2/S3/S4 on the target receptor. Bioactive compounds of Mimosa pudica have relatively good interactions in inhibitingC. albicansSap 3.
An exploration of high performance computing cloud contract for SMEs: a systematic literature review
Authors: Lu Qin , Damij Nadja , Whalley Jason 
Published: September 2022

Purpose
High performance computing (HPC) is used to solve complex calculations that personal computing devices are unable to handle. HPC offers the potential for small- and medium-size enterprises (SMEs) to engage in product innovation, service improvement and the optimization of resource allocation (Borstnar and Ilijas, 2019). However, the expensive infrastructure, maintenance costs and resource knowledge gaps that accompany the use of HPC can make it inaccessible to SMEs. By moving HPC to the cloud, SMEs can gain access to the infrastructure without the requirement of owning or maintaining it, but they will need to accept the terms and conditions of the cloud contract. This paper aims to improve how SMEs access HPC through the cloud by providing insights into the terms and conditions of HPC cloud contracts.

Design/methodology/approach
This paper adopts a systematic literature review by implementing a four-step approach. A comprehensive search was undertaken and results synthesized to enable this paper’s objectives to be met.

Findings
This paper proposes that SMEs could gain competitive advantage(s) by understanding their own needs and improving their contract negotiation abilities, service management skills and risk management abilities before accepting the terms and conditions of the cloud contract. Furthermore, a checklist, service-level agreement, easily ignored elements and risk areas are presented as guidance for SMEs when reviewing their HPC cloud contract(s).

Originality/value
While HPC cloud contracts are a niche research topic, it is one of the key factors influencing the ability of SMEs to access HPC through the cloud. It is, however, by no means a level playfield with SMEs at a distinct disadvantage because of not influencing the writing up of the HPC cloud contract. The added value of the paper is that it contributes to our overall understanding of the terms and conditions of HPC cloud contracts.
Designing of cost-effective and sustainable logistics system: Whirlpool case
Authors: Yumurtacı Hüseyinoğlu Işık Özge , Kurtay Deniz , Aşar İrem , Dilmaç Serra 
Published: September 2022

Learning outcomes
In this case study, the alternative route designs were observed to significantly decrease transportation costs and the total distance traveled. This decrease in logistics requirements almost halved the annual number of shipments and the time needed for operation and documentation activities. In addition, reduced carbon emissions made this an environmentally friendly transportation model, in line with trends in society.

Case overview/synopsis
The basis for this case study was the analysis of Whirlpool Turkey’s transportation system for materials used in the production of white goods. Data obtained through fieldwork and cooperation with company consultants showed that some suppliers have high annual logistics costs. This inefficiency causes time loss and increases the total distance traveled and thus carbon emissions. In the case study, the current application created inefficiency in cost and time management, and therefore, after determining the factors that increase costs, different transportation solutions were developed accordingly.

Complexity academic level
This case is particularly designed for undergraduates in the final semester of management courses that specialize in supply chain and operation management.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 9: Operations and logistics.
Factors influencing technology adoption amongst small retailers: insights from thematic analysis
Authors: Aithal Rajesh K. , Choudhary Vikram , Maurya Harshit , Pradhan Debasis , Sarkar Dev Narayan 
Published: September 2022

PurposeThe present study aims to understand small retailers' current use of various low-cost technologies and the factors responsible for small retailers' adoption. Furthermore, these factors of adoption were mapped back to beliefs within the theory of planned behaviour (TPB), and an attempt was made to understand if some of the beliefs dominated over the others and their implications.Design/methodology/approachThe study takes a qualitative approach comprising in-depth semi-structured interviews and direct observation. The qualitative data were analysed through a thematic analysis to identify technology adoption factors.FindingsAmongst the various technologies (mobile apps), payment and procurement apps were the most widely used. The authors identified eight factors influencing technology adoption: the top being customer demand for payment apps and convenience and cost-saving for procurement apps. The study also highlights the role of the dominant beliefs in technology adoption, which managers could use to improve adoption rates.Research limitations/implicationsThe current study is a cross-sectional study and the sample was predominantly of grocery retailers, limiting the generalisability of the results.Social implicationsSmall retailers face stiff competition from organised retail and e-commerce platforms which threatens small retailers' existence. Small retailers' survival is vital as many people depend on the small retail sector for livelihood. Increased use of technology seems the only way for them to stay competitive and increase profitability. The study's outcome could help increase technology adoption amongst small retailers and increase small retailers' competitiveness.Originality/valueDespite the widespread presence of small retailers in emerging economies, few studies have examined technology adoption amongst them. This study is also the first to use the TPB theory in the small retailer technology adoption context.