bluuebunny/crossref_metadata_2025_split huggingface dataset:
Respiratory Complex I Regulates Dendritic Cell Maturation in Explant Model of Human Tumor Immune Microenvironment
Authors: Turpin Rita , Liu Ruixian , Munne Pauliina M. , Peura Aino , Rannikko Jenna H. , Philips Gino , Boeckx Bram , Salmelin Natasha , Hurskainen Elina , Suleymanova Ilida , Vuorinen Elisa M. , Lehtinen Laura , Mutka Minna , Kovanen Panu E. , Niinikoski Laura , Meretoja Tuomo , Mattson Johanna , Mustjoki Satu , Saavalainen Päivi , Goga Andrei , Lambrechts Diether , Pouwels Jeroen , Hollmén Maija , Klefström Juha 
Published: May 2023

ABSTRACTCombining cytotoxic chemotherapy or novel anticancer drugs with T-cell modulators holds great promise in treating advanced cancers. However, the response varies depending on the tumor immune microenvironment (TIME). Therefore, there is a clear need for pharmacologically tractable models of the TIME to dissect its influence on mono- and combination treatment response at the individual level. Here we establish a Patient-Derived Explant Culture (PDEC) model of breast cancer, which retains the immune contexture of the primary tumor, recapitulating cytokine profiles and CD8+ T cell cytotoxic activity. We explored the immunomodulatory action of a synthetic lethal BCL2 inhibitor venetoclax + metformin drug combinationex vivo, discovering metformin cannot overcome the lymphocyte-depleting action of venetoclax. Instead, metformin promotes dendritic cell maturation through inhibition of mitochondrial complex I, increasing their capacity to co-stimulate CD4+ T cells and thus facilitating anti-tumor immunity. Our results establish PDECs as a feasible model to identify immunomodulatory functions of anticancer drugs in the context of patient-specific TIME.
Schistosoma haematobiumandSchistosoma bovisfirst generation hybrids undergo large gene expressions remodeling consistent with species compatibility
Authors: Mathieu-Bégné Eglantine , Kincaid-Smith Julien , Chaparro Cristian , Allienne Jean-François , Rey Olivier , Boissier Jérôme , Toulza Eve 
Published: May 2023

AbstractWhen two species hybridize, the two parental genomes are brought together and some alleles might interact for the first time. To the date, the extent of the transcriptomic changes in first hybrid generations, along with their functional outcome constitute an important knowledge gap especially in non-model organisms. Here we explored the molecular and functional outcomes of hybridization in first-generation hybrid between the blood fluke parasitesS. haematobiumandS. bovis. To this aim we fist assembled a hybrid reference transcriptome allowing us to measure gene expression in both parental species and hybrids to further described and quantified the profiles of gene expression encountered in hybrids. We identified large-scale gene expression remodeling since up to 55% of genes were differentially expressed in hybrids compared to at least one of the parental species. We further showed that intermediate level of expression in hybrids compared to parental species was the most prevalent expression profile (38% of genes) in agreement withS. haematobium x S. bovishigh genomic compatibility and limited divergence. Also, among the differentially expressed genes of each of the identified profiles (intermediate, under-, over-expressed, or matching the expression of one of the parental species), only a few biological processes were found enriched without patterns being consistent through crosses and sexes. Our findings suggest that hybrid heterosis could be due to change in expression of a large portion of random genes which affect various biological processes.Author SummaryWhen two species manage to produce a viable offspring, due to different parental genetic material, new allelic interactions might arise. We do not know much about how genes are expressed in such hybrids compared to their parental species and especially for non-model species. Here we gene expressions in first generation hybrids of two blood flukes’ parasitesSchistosoma haematobiumandS. bovis.We quantified and categorized gene differentially expressed in first generation hybrids. We showed that more than half the genes of the hybrids were differentially expressed compared to at least one of their parental species, hence showing major gene expression remodeling occurring during hybridization. However, the most common hybrid expression pattern was intermediate level of expression compared to parental species and various but no specific biological processes were associated with hybrids differentially expressed genes. We hypothesized that becauseS. haematobiumandS. bovisremain very compatible, when hybridizing many non-specific genes can have their expression level remodeled hence impacting the overall molecular machinery of the offspring while still sustaining highly operational hybrids.
The Upstream Sequence Transcription Complex Dictates Nucleosome Positioning and Promoter Accessibility at piRNA Genes in theC. elegansGerm Line
Authors: Sanchez Nancy , Gonzalez Lauren E , Reinke Valerie 
Published: May 2023

ABSTRACTThe piRNA pathway is a conserved germline-specific small RNA pathway that ensures genomic integrity and continued fertility. InC. elegansand other nematodes, Type-I piRNA precursor transcripts are expressed from over 10,000 small, independently regulated genes clustered within two discrete domains of 1.5 and 3.5 MB on Chromosome IV. These large clusters likely play a significant role in promoting germline-specific expression of piRNAs, but the underlying mechanisms are unclear. By examining the chromatin environment specifically in isolated germ nuclei, we demonstrate that piRNA clusters are located in closed chromatin, and confirm the enrichment for the inactive histone modification H3K27me3. We further show that the piRNA biogenesis factor USTC (Upstream Sequence Transcription Complex) plays two roles – it promotes a strong association of nucleosomes throughout the piRNA clusters, and it organizes the local nucleosome environment to direct the exposure of individual piRNA genes. Overall, this work reveals new insight into how chromatin state coordinates transcriptional regulation over large genomic domains, which has implications for understanding global genome organization in the germ line.
RBM3 enhances cold resistance by regulating thermogenic gene expressions
Authors: Nakamura Junnosuke , Uno Megumi , Taketomi Takumi , Yadav Manoj Kumar , Tsuruta Fuminori 
Published: May 2023

AbstractMammals are thermostatic animals capable of regulating their body temperature within a precise range, irrespective of ambient temperature conditions. However, the precise mechanisms by which a body temperature is controlled dependent on ambient temperature are still unclear. Here, we report that RNA binding motif protein 3 (RBM3), one of the cold-responsive proteins, regulates body temperature via expressing thermogenic genes during the late-postnatal period. The body temperature inRbm3knockout (KO) juvenile mice was unstable and increased vulnerability to cold exposure. In addition,Rbm3KO mice exhibited increased lipid droplets in brown adipose tissue (BAT) and abnormal histology. The single-cell RNA-seq (scRNA-seq) analysis revealed that RBM3 is highly expressed in proliferating and differentiating cells in BAT. Moreover, RBM3 was necessary for upregulating thermogenic genes after cold shock. Notably, RBM3 interacted with UCP1 mRNAin vivo, thereby stabilizing its mRNA levels. Lastly, RBM3 regulated neuronal activity in the dorsomedial hypothalamic nucleus (DMH) under a cold environment. These data suggest that RBM3 regulates thermogenesis in juvenile mice through both upregulating thermogenic genes in BAT and activating DMH neurons after cold exposure.
Spatial biology of Ising-like synthetic genetic networks
Authors: Simpson Kevin , L’Homme Alfredo , Keymer Juan , Federici Fernán 
Published: May 2023

AbstractBackgroundUnderstanding how spatial patterns of gene expression emerge from the interaction of individual gene networks is a fundamental challenge in biology. Developing a synthetic experimental system with a common theoretical framework that captures the emergence of short- and long-range spatial correlations (and anti-correlations) from interacting gene networks could serve to uncover generic scaling properties of these ubiquitous phenomena.ResultsHere, we combine synthetic biology, statistical mechanics models and computational simulations to study the spatial behavior of synthetic gene networks (SGNs) inEscherichia coliquasi-2D colonies growing on hard agar. Guided by the combined mechanisms of the contact process lattice simulation and two-dimensional Ising model (CPIM), we describe the spatial behavior of bi-stable and chemically-coupled SGNs that self-organize into patterns of long-range correlations with power-law scaling or short-range anti-correlations. These patterns, resembling ferromagnetic and anti-ferromagnetic configurations of the Ising model near critical points, maintain their scaling properties upon changes in growth rate and cell shape.ConclusionsOur findings shed light on the spatial biology of coupled and bistable gene networks in growing cell populations. This emergent spatial behavior could provide insights into the study and engineering of self-organizing gene patterns in eukaryotic tissues and bacterial consortia.
SARS-CoV-2 introductions to the island of Ireland
Authors: Rice Alan M. , Troendle Evan P. , Bridgett Stephen , Nejad Behnam Firoozi , McKinley Jennifer M. ,   The COVID-19 Genomics UK consortium,   National SARS-CoV-2 Surveillance & Whole Genome Sequencing (WGS) Programme, Bradley Declan T. , Fairley Derek , Bamford Connor G. G. , Skvortsov Timofey , Simpson David A. 
Published: May 2023

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had an unprecedented impact on the people of Ireland as waves of infection spread across the island during the global coronavirus disease 2019 (COVID-19) pandemic. Viral whole-genome sequencing (WGS) has provided insights into SARS-CoV-2 molecular mechanisms of pathogenicity and evolution and contributed to the development of anti-virals and vaccines. High levels of WGS have enabled effective SARS-CoV-2 genomic surveillance on the island of Ireland, leading to the generation of a sizeable data set with potential to provide additional insights into viral epidemiology. Because Ireland is an island, accurate documentation of travel rates to and from other regions, both by air and by sea, are available. Furthermore, the two distinct political jurisdictions on the island allow comparison of the impact of varying public health responses on viral dynamics, including SARS-CoV-2 introduction events.Using phylogenomic analysis incorporating sample collection date and location metadata, we describe multiple introduction and spreading events for all major viral lineages to the island of Ireland during the period studied (March 2020–June 2022). The majority of SARS-CoV-2 introductions originated from England, with frequent introductions from USA and northwestern Europe. The clusters of sequences predicted to derive from discrete introduction events (“introduction clusters”) vary greatly in size, with some involving only one or two cases and others comprising thousands of samples. When introduction cluster samples are mapped sequentially by collection date, they appear predominantly in previously affected or adjacent areas. This mirroring of the phylogenetic relationships by the geospatiotemporal propagation of SARS-CoV-2 validates our analytic approach. By downsampling, we estimate the power to detect introductions to Ireland as a function of sequencing levels. Per capita normalisation of both sequencing levels and detected introductions accounts for biases due to differing sequencing efforts and total populations. This approach showed similar rates of introductions for all major lineages into Northern Ireland (NI) and Republic of Ireland (RoI) with the exception of Delta, which was higher in NI which is likely attributable to higher travel per capita. However, there were similar rates of Delta infection within NI and RoI, suggesting that although travel restrictions will reduce risk of introducing novel variants to the region, they may not substantially decrease total incidence.Our generalisable methodology to study introduction dynamics and optimal sequencing levels will assist public health authorities to select the most appropriate control measures and viral sequencing strategy.
AT7867 promotes pancreatic progenitor differentiation of human iPSCs and accelerates diabetes reversal
Authors: Cuesta-Gomez Nerea , Verhoeff Kevin , Dadheech Nidheesh , Pawlick Rena , Marfil-Garza Braulio , Razavy Haide , Shapiro A.M. James 
Published: May 2023

SummaryGeneration of pure pancreatic progenitor cells (PPs) is critical for clinical translation of stem cell derived islets. Herein, we performed PP differentiation with and without AKT/P70 inhibitor AT7867 and characterized the resulting cells at protein and transcript levelin vitroandin vivoupon transplantation into diabetic mice. AT7867 treatment increased the percentage of PDX1+NKX6.1+(-AT7867: 50.9% [IQR 48.9%-53.8%]; +AT7867: 90.8% [IQR 88.9%-93.7%];p=0.0021) and PDX1+GP2+PP cells (-AT7867: 39.22% [IQR 36.7%-44.1%; +AT7867: 90.0% [IQR 88.2%-93.6%];p=0.0021). Transcriptionally, AT7867 treatment significantly upregulatedPDX1(p=0.0001),NKX6.1(p=0.0005) andGP2(p=0.002) expression compared to controls, while off-target markersPODXL(p<0.0001) andTBX2(p <0.0001) were significantly downregulated. Transplantation of AT7867 treated PPs resulted in faster hyperglycemia reversal in diabetic mice compared to controls (time and group:p<0.0001). Overall, our data shows that AT7867 enhances PP cell differentiation leading to accelerated diabetes reversal.
When Do Visual Category Representations Emerge in Infants’ Brains?
Authors: Yan Xiaoqian , Tung Sarah , Fascendini Bella , Chen Yulan Diana , Norcia Anthony M. , Grill-Spector Kalanit 
Published: May 2023

AbstractOrganizing the continuous stream of visual input into categories like places or faces is important for everyday function and social interactions. However, it is unknown when neural representations of these and other visual categories emerge. Here we used steady state evoked potential electroencephalography to measure cortical responses in infants at 3-4 months, 4-6 months, 6-8 months, and 12-15 months, when they viewed controlled, gray-level images of faces, limbs, corridors, characters, and cars. We found that distinct responses to these categories emerge at different ages. Reliable brain responses to faces emerge first, at 4-6 months, followed by limbs and places around 6-8 months. Between 6-15 months response patterns become more distinct, such that a classifier can decode what an infant is looking at from their brain responses. These findings have important implications for assessing typical and atypical cortical development as they not only suggest that category representations are learned, but also that representations of categories that may have innate substrates emerge at different times during infancy.
High-speed TIRF and 2D super-resolution structured illumination microscopy with large field of view based on fiber optic components
Authors: Ortkrass Henning , Schürstedt Jasmin , Wiebusch Gerd , Szafranska Karolina , Mccourt Peter , Huser Thomas 
Published: May 2023

AbstractSuper-resolved structured illumination microscopy (SR-SIM) is among the most flexible, fast, and least perturbing fluorescence microscopy techniques capable of surpassing the optical diffraction limit. Current custom-built instruments are easily able to deliver two-fold resolution enhancement at video-rate frame rates, but the cost of the instruments is still relatively high, and the physical size of the instruments based on the implementation of their optics is still rather large. Here, we present our latest results towards realizing a new generation of compact, cost-efficient, and high-speed SR-SIM instruments. Tight integration of the fiber-based structured illumination microscope capable of multi-color 2D- and TIRF-SIM imaging, allows us to demonstrate SR-SIM with a field of view of up to 150 × 150 μm2and imaging rates of up to 44 Hz while maintaining highest spatiotemporal resolution of less than 100 nm. We discuss the overall integration of optics, electronics, and software that allowed us to achieve this, and then present the fiberSIM imaging capabilities by visualizing the intracellular structure of rat liver sinusoidal endothelial cells, in particular by resolving the structure of their trans-cellular nanopores called fenestrations.
DeCOIL: Optimization of Degenerate Codon Libraries for Machine Learning-Assisted Protein Engineering
Authors: Yang Jason , Ducharme Julie , Johnston Kadina E. , Li Francesca-Zhoufan , Yue Yisong , Arnold Frances H. 
Published: May 2023

ABSTRACTWith advances in machine learning (ML)-assisted protein engineering, models based on data, biophysics, and natural evolution are being used to propose informed libraries of protein variants to explore. Synthesizing these libraries for experimental screens is a major bottleneck, as the cost of obtaining large numbers of exact gene sequences is often prohibitive. Degenerate codon (DC) libraries are a cost-effective alternative for generating combinatorial mutagenesis libraries where mutations are targeted to a handful of amino acid sites. However, existing computational methods to optimize DC libraries to include desired protein variants are not well suited to design libraries for ML-assisted protein engineering. To address these drawbacks, we present DEgenerate Codon Optimization for Informed Libraries (DeCOIL), a generalized method which directly optimizes DC libraries to be useful for protein engineering: to sample protein variants that are likely to have both high fitness and high diversity in the sequence search space. Using computational simulations and wet-lab experiments, we demonstrate that DeCOIL is effective across two specific case studies, with potential to be applied to many other use cases. DeCOIL offers several advantages over existing methods, as it is direct, easy-to-use, generalizable, and scalable. With accompanying software (https://github.com/jsunn-y/DeCOIL), DeCOIL can be readily implemented to generate desired informed libraries.Abstract Figure
Structural snapshots of hyaluronan formation reveal principles of length control and secretion
Authors: Górniak Ireneusz , Stephens Zachery , Erramilli Satchal K. , Gawda Tomasz , Kossiakoff Anthony A. , Zimmer Jochen 
Published: May 2023

ABSTRACTHyaluronan (HA) is an essential component of the vertebrate extracellular matrix. It is a heteropolysaccharide of alternatingN-acetylglucosamine (GlcNAc) and glucuronic acid (GlcA) units reaching several megadaltons in healthy tissues. HA is synthesized and secreted in a coupled reaction by HA-synthase (HAS). Here, structural snapshots of HAS provide important insights into HA biosynthesis, from substrate recognition to HA elongation and translocation. We reveal a loop insertion mechanism for substrate binding, monitor the extension of a GlcNAc primer with GlcA, and capture the opening of a secretion channel that coordinates a nascent HA polymer. Further, we identify HA-interacting residues that control HA product lengths. Integrating structural and biochemical analyses, we propose a mechanism for HA length control based on finely tuned enzymatic processivity and catalytic rates.
Process decomposition of expanded rural housing at the rural–urban fringe: evidence from 27,034 buildings in Pudong New Area, Shanghai, China
Authors: Cai Yin Ying , Xie Jin , Huntsinger Lynn 
Published: May 2023

PurposeFaced with the challenges of rural population decline, combined with the widespread expansion of homesteads in rural areas, local Chinese governments hope to strictly control and minimize rural housing land. Accurately decomposing the process of rural housing expansion and revealing its driving factors will be helpful for land-use regulation by the government.Design/methodology/approachIn this study, an unusually rich dataset of rural housing registration from Pudong New Area in Shanghai is employed. The study aimed to decompose the fragmented accumulation process and its expansion determinants on rural housing assets. The dataset covers all samples of rural households and housing plots at 72 surveyed villages in six towns.FindingsHousing offers profitable capital and earning assets to villagers at the urban fringe, so they have a powerful incentive to build and expand more. The results of this analysis showed that the expansion of rural housing is largely due to the haphazard construction of auxiliary rooms by villagers, especially on plots of arable land that are adjacent to their houses that have been stealthily converted into auxiliary rooms and sheds. Low costs and weak penalties have led to an increase in rent-seeking expansions to rural houses. Houses with the smaller initial areas, families with more laborers and household heads, and the proximity of villages to downtown with convenient living services were the main driving factors for expanding houses. A concerted effort is needed to control the disorganized and unlicensed expansion of housing. This effort should include formulating areas for free use by villagers, high taxes on overused areas, serious penalties for unlicensed housing expansion and effective land-use planning.Research limitations/implicationsAn understanding of the expansion status and control measures related to rural houses in Shanghai provides an important reference that can help to guide the formulation of rural housing policies, and the sustainable development of cities worldwide. Of course, this study cannot generalize about housing distribution and expansion status worldwide based on the study area in China, because China's land tenure policies are unique. But land registry data exists that makes research like this feasible. There is a need to carefully examine the detailed housing distribution in each country before it can be decided on how best to address the disorderly increase in rural housing stock, and promote the reduction of rural residential expansion.Originality/valueFirst, the process of rural housing expansion by using an unique dataset which covers ten thousands of samples is revealed. Second, the results have policy implications for reducing the amount of idle and inefficiently rural homestead. The focus is on rural housing growth and its driving factors in Shanghai, and the villagers' motivations for housing expansion are explored.
Fabrizex: creating a technology platform for global supply chains
Authors: Aserkar Rajiv 
Published: May 2023

Subject area
Supply Chain Management, Technology, Procurement, Supply Chain Finance

Learning outcomes
The key learning objectives are as follows: to gain critical insights into e-commerce supply chains of fashion garments; understand the importance of digitization to manage the risks due to supply chain disruptions; evaluate the role of digitization to improve supply chain performance; understand the importance of supply chain finance in maintaining a healthy buyer–supplier relationship; and appreciate the role of supply chain digitization to transform a regional supply chain into a global supply chain.

Case overview/synopsis
This case highlights the challenges faced by fashion garments industry due to fragmented nature of their supply chains, where the manufacturing base was in the east and most of the consumers in the west. Digitization can create a bridge to integrate these supply chains to drive out their inefficiency, fragility and vulnerability to disruptions.

Complexity academic level
The case could be discussed in 90 min of an Operations Management, Supply Chain Management and Technology Management class at MBA or Executive MBA level.

Supplementary Material
Teaching notes are available for educators only.

Subject code
CSS 9: Operations and Logistics.