bluuebunny/crossref_metadata_2025_split huggingface dataset:
MODL-34. A SERIES OF EGFR-MUTANT MODELS OF GLIOBLASTOMA THAT RECAPITULATES PATIENT TUMOR HETEROGENEITY AND RESPONSE TO TREATMENT
Authors: Grausam Katie , Pacheco David Rincon Fernandez , Hatanaka Emily , Shiao Stephen , Breunig Joshua 
Published: November 2023

Abstract
Glioblastoma (GBM) is the most common and aggressive brain cancer, with a treatment regimen that has remained disappointingly unaltered for the last few decades. Preclinical testing of immunotherapy has generated promising results, sometimes leading to elimination of the tumor over time in mouse models; however, when tested clinically, patients show limited responses with no impact on patient survival. Current mouse models (e.g., GL261) for preclinical testing involve orthotopic transplantation of a cell line with tumor mutations not commonly found in patient tumors. Most of these models elicit a strong anti-tumor immune response which is typically not found clinically. Single cell sequencing has revealed that different mutations in GBM are associated with differences in the aggressiveness and composition of the tumor immune microenvironment. We therefore developed an immunocompetent, autochthonous platform for generating mouse models of GBM using combinations of clinically-relevant mutations, including mutant EGFR driving tumor growth and various single guide RNAs with CRISPR-Cas9 to elicit loss of function of tumor suppressor genes. Histopathology from tumors in mice mirrors the typical features of GBM, while single-cell RNA sequencing identified expression patterns similar to patients with different driver combinations altering expression patterns in ways that mimic their human counterparts, including the heterogeneity that is the hallmark of GBM. The immune cell population of these tumors was composed of predominantly microglia, with a small population of peripherally derived immune cells. Finally, treatment studies of radiation and anti-PD-1 using this new mouse model do not result in long-term survival, similar to human trials of these agents, paving the way for more accurate preclinical testing. In conclusion, using this unique modeling system that more closely resembles human tumors genetically and immunologically, we can better explore the mechanisms of therapeutic resistance and identify more relevant targets to improve outcomes in this challenging disease.
MODL-40. CLONAL ARCHITECTURE, TRANSCRIPTIONAL CELLULAR STATES AND IN-VITRO DRUG RESPONSE IN GLIOBLASTOMA
Authors: Song Youjin , Miller-Michlits Yelyzaveta , Greutter Lisa , Kiesel Barbara , Loetsch-Gojo Daniela , Redl Vivian , Gesperger Johanna , Breu Jana , Nam Do-Hyun , Widhalm Georg , Sa Jason K , Woehrer Adelheid 
Published: November 2023

Abstract
Seventy-five multiregional tumors from 20 representative GBM patients (female/male ratio = 0.75, median age= 63 ys) were profiled using deep whole-exome sequencing with a nominal coverage of &gt; 300x. The clonal complexity of each individual tumor was measured by calculating the molecular distance using the Euclidean distance of all possible paired regions based on somatic mutational profiles. Among them, fresh tumor slices of 4 patients were cultured in minimal essential media and treated with 4.2 Gy plus 200 µM temozolomide for 48 hours. Spatial Transcriptomics was performed on matched tumor slices with and without treatment. Molecular characterization of multiregional tumors revealed two patterns of evolutionary trajectory, linear and branched (linear: 8 cases, branched: 8 cases) among 16 patients. Tumors with branched evolution demonstrated considerable levels of molecular divergence, determined by high molecular distance and a low number of mutations that were shared among all regions. In-vitro drug response varied considerably between patients based on cell proliferation (minus 0.5 to 13.8 %), apoptotic rates (30.1 to 44.4 %), and cell viability (minus 7.8 to 34.1 %). Under treatment pressure an increase of mesenchymal cellular states with peculiar redistribution of transcriptional patterns and increased clonal complexity was observed. In sum, we report on an ongoing study in glioblastoma that seeks to link the clonal architecture with spatially-resolved transcriptional patterns and in-vitro drug response. Our study will provide new insights into the clinical relevance of the clonal composition of this deadly cancer.
Recent progress in MnBi2nTe3n+1 intrinsic magnetic topological insulators: crystal growth, magnetism and chemical disorder
Authors: Hu Chaowei , Qian Tiema , Ni Ni 
Published: November 2023

ABSTRACT
The search for magnetic topological materials has been at the forefront of condensed matter research for their potential to host exotic states such as axion insulators, magnetic Weyl semimetals, Chern insulators, etc. To date, the MnBi2nTe3n+1 family is the only group of materials showcasing van der Waals-layered structures, intrinsic magnetism and non-trivial band topology without trivial bands at the Fermi level. The interplay between magnetism and band topology in this family has led to the proposal of various topological phenomena, including the quantum anomalous Hall effect, quantum spin Hall effect and quantum magnetoelectric effect. Among these, the quantum anomalous Hall effect has been experimentally observed at record-high temperatures, highlighting the unprecedented potential of this family of materials in fundamental science and technological innovation. In this paper, we provide a comprehensive review of the research progress in this intrinsic magnetic topological insulator family, with a focus on single-crystal growth, characterization of chemical disorder, manipulation of magnetism through chemical substitution and external pressure, and important questions that remain to be conclusively answered.
Ultrasound-guided Fat Graft of the Obliques–Serratus Complex
Authors: Flores González Emanuel Armando , Babaitis Ricardo , Viaro Mauricio Schneider , Manzaneda Cipriani Raul Martin , Duran Vega Hector , Ramírez Guerrero Oliver René , Brito Toledo Patricia , Vázquez Apodaca Raquel Aracely , Gracida Mancilla Noe Isaias 
Published: November 2023

Background:
The idea of the anterolateral thoracic musculature in men during the contour procedure is very limited, particularly in terms of surgical techniques that improve its appearance and aesthetics. Therefore, this study aimed to describe a technique of deep definition liposuction with intramuscular grafting of the serratus external oblique muscle complex.

Methods:
A retrospective case series of a total of 11 cases of male patients aged between 29 and 60 years in the year 2022 is presented. These patients underwent body contouring surgery and subsequently underwent ultrasound-guided intramuscular fat grafting in the serratus external oblique complex. As part of the study, measurements were taken before and immediately after surgery. The data were stored in a database and analyzed with the statistical software SPSS, v23.0.

Results:
The patients were aged between 29 and 60 years, with a mean age of 38.3 years (±8.5). All cases had a body mass index of 30. Results were matched preinfiltration and postinfiltration; These results were subjected to statistical validation using the Student t test for related samples, and statistically significant differences were obtained in all the measures tested.

Conclusions:
The technique of fat grafting in the oblique-serratus complex allows for increasing muscle thickness. The measurements were made only immediately after the infiltration; it is important in the future to show the long-term follow-up. No adverse events occurred during the study.
Transcriptional profiling ofDrosophilamale-specific P1 (pC1) neurons
Authors: Ahmed Osama M. , Crocker Amanda , Murthy Mala 
Published: November 2023

AbstractInDrosophila melanogaster, the P1 (pC1) cluster of male-specific neurons both integrates sensory cues and drives or modulates behavioral programs such as courtship, in addition to contributing to a social arousal state. The behavioral function of these neurons is linked to the genes they express, which underpin their capacity for synaptic signaling, neuromodulation, and physiology. Yet, P1 (pC1) neurons have not been fully characterized at the transcriptome level. Moreover, it is unknown how the molecular landscape of P1 (pC1) neurons acutely changes after flies engage in social behaviors, where baseline P1 (pC1) neural activity is expected to increase. To address these two gaps, we use single cell-type RNA sequencing to profile and compare the transcriptomes of P1 (pC1) neurons harvested from socially paired versus solitary male flies. Compared to control transcriptome datasets, we find that P1 (pC1) neurons are enriched in 2,665 genes, including those encoding receptors, neuropeptides, and cell-adhesion molecules (dprs/DIPs). Furthermore, courtship is characterized by changes in∼300 genes, including those previously implicated in regulating behavior (e.g.DopEcR, Octβ3R, Fife, kairos, rad). Finally, we identify a suite of genes that link conspecific courtship with the innate immune system. Together, these data serve as a molecular map for future studies of an important set of higher-order and sexually-dimorphic neurons.
scDrugPrio: A framework for the analysis of single-cell transcriptomics to address multiple problems in precision medicine in immune-mediated inflammatory diseases
Authors: Schäfer Samuel , Smelik Martin , Sysoev Oleg , Zhao Yelin , Eklund Desiré , Lilja Sandra , Gustafsson Mika , Heyn Holger , Julia Antonio , Kovács István A. , Loscalzo Joseph , Marsal Sara , Zhang Huan , Li Xinxiu , Gawel Danuta , Wang Hui , Benson Mikael 
Published: November 2023

AbstractBackgroundIneffective drug treatment is a major problem for many patients with immune-mediated inflammatory diseases (IMIDs). Important reasons are the lack of systematic solutions for drug prioritisation and repurposing based on characterisation of the complex and heterogeneous cellular and molecular changes in IMIDs.MethodsHere, we propose a computational framework, scDrugPrio, which constructs network models of inflammatory disease based on single-cell RNA sequencing (scRNA-seq) data. scDrugPrio constructs detailed network models of inflammatory diseases that integrate information on cell type-specific expression changes, altered cellular crosstalk and pharmacological properties for the selection and ranking of thousands of drugs.ResultsscDrugPrio was developed using a mouse model of antigen-induced arthritis and validated by improved precision/recall for approved drugs, as well as extensivein vitro, in vivo,andin silicostudies of drugs that were predicted, but not approved, for the studied diseases. Next, scDrugPrio was applied to multiple sclerosis, Crohn’s disease, and psoriatic arthritis, further supporting scDrugPrio through prioritisation of relevant and approved drugs. However, in contrast to the mouse model of arthritis, great interindividual cellular and gene expression differences were found in patients with the same diagnosis. Such differences could explain why some patients did or did not respond to treatment. This explanation was supported by the application of scDrugPrio to scRNA-seq data from eleven individual Crohn’s disease patients. The analysis showed great variations in drug predictions between patients, for example, assigning a high rank to anti-TNF treatment in a responder and a low rank in a nonresponder to that treatment.ConclusionWe propose a computational framework, scDrugPrio, for drug prioritisation based on scRNA-seq of IMID disease. Application to individual patients indicates scDrugPrio’s potential for personalised network-based drug screening on cellulome-, genome-, and drugome-wide scales. For this purpose, we made scDrugPrio into an easy-to-use R package (https://github.com/SDTC-CPMed/scDrugPrio).
Multidimensional behavioral profiles associated with resilience and susceptibility after inescapable stress
Authors: de Oliveira-Júnior Benedito Alves , Marques Danilo Benette , Rossignoli Matheus Teixeira , Prizon Tamiris , Leite João Pereira , Ruggiero Rafael Naime 
Published: November 2023

ABSTRACTStress-related neuropsychiatric disorders are complex conditions that are difficult to diagnose and treat due to the variety of symptoms they present with. While animal models have been instrumental in understanding their underlying mechanisms, there is an ongoing debate about the validity of behavioral measures to address specific disorders. Here, we conducted an extensive ethological characterization of behavioral variables associated with anxiety and depression and employed a multidimensional approach to investigate stress susceptibility in male Wistar rats. The rats underwent inescapable footshocks (IS) or no-shocks (NS), followed by a comprehensive battery of behavioral tests over several days. Our study identified phenotypically distinct clusters, including fully characterized stress-susceptible and stress-resilient subpopulations, along with intermediate phenotypes. Reduced time in elevated plus maze open arms, diminished sucrose preference and increased escape failures consistently differentiated susceptible from resilient rats. Behavior in the forced swim test was unrelated to stress susceptibility. In conclusion, our study sheds light on the relationships between classical behavioral measures in animal models of depression, highlighting distinct patterns that differentiate susceptibility from resilience. It emphasizes the importance of a multidimensional assessment of behavioral responses in animal models for a better understanding of stress-related neuropsychiatric disorders.HIGHLIGHTSClustering of features reveals a correlation pattern that separates behavioral variables associated with susceptibility from those associated with resilience to stressMultidimensional patterns of covariation among behavioral measures distinguish helpless from non-helpless individuals and indicate independence from forced swim test behavior.Clustering of individuals discriminates stressed subjects and reveals multidimensional behavioral phenotypes of resilience and susceptibility, indicating different stress-coping strategies.
Antisense transcription from a neighboring gene interferes with the expression of mNeonGreen as a functionalin vivofluorescent reporter in the chloroplast ofChlamydomonas reinhardtii
Authors: Navarrete Axel , Pollak Bernardo 
Published: November 2023

ABSTRACTAlthough over 30 years have passed sinceChlamydomonas reinhardtiichloroplast transformation was first achieved, robust genetic engineering of the chloroplast still remains a challenging task. The glass-bead transformation method has enabled simple and accessible chloroplast transformation of theC. reinhardtiiTN72 strain, allowing generation of marker-free transplastomic strains for low-cost experimentation. However, lack of functionalin vivofluorescent reporters limit research and widespread development of chloroplast engineering. Here, we developed a chloroplast codon-optimised mNeonGreen fluorescent reporter, which can be detectedin vivothrough fluorescence microscopy and fluorometry, by context-aware construct engineering, leading up to a ∼6-fold increase in fluorescence. We found evidence for chloroplast post-transcriptional regulation of gene expression derived from formation of antisense pairing of mRNAs due to transcriptional readthrough of the convergent adjacent gene, which was validated through detection of the double-stranded RNA. In addition, engineering approaches were used to modulate transcriptional readthrough, allowing a better understanding of context effects that are relevant for heterologous expression. Finally, we characterised a suite of regulatory parts for transgene expression in a sense-transcriptional context regarding to the selectable marker, achieving up to ∼2-fold increase in mNeonGreen fluorescence levels regarding to the control, with the use of PrrnS,5’atpAand 3’rbcLendogenous regulatory sequences from the chloroplast ofC. reinhardtii. This work provides new tools for studying basic aspects of the molecular biology in the chloroplast inC. reinhardtii, as well as evidence for fundamental processes of gene regulation that may enable developing rules for more efficient chloroplast engineering.
Cellular COPI components promote geminivirus infections by facilitating the chloroplast localization of viral C4/AC4 proteins
Authors: Zhao Wenhao , Ji Yinghua , Zhou Yijun , Wang Xiaofeng 
Published: November 2023

AbstractGeminiviruses are a family of viruses that infect numerous crops and cause extensive agricultural losses worldwide. During viral infection, geminiviral C4/AC4 proteins relocate from the plasma membrane (PM) to chloroplasts, where they inhibit chloroplast-mediated host defense, including the biosynthesis of salicylic acid (SA). However, how are C4/AC4 proteins transported to chloroplasts is unknown. We report here that the Coat Protein I (COPI) components play a critical role in redistributing Tomato yellow leaf curl virus (TYLCV) C4 protein to chloroplasts. TYLCV C4 interacts with the β subunit of COPI, and the coexpression of both inNicotiana benthamianacells promotes the enrichment of C4 in chloroplasts, which also occurs during TYLCV infection and is blocked by an inhibitor of the COPI pathway. Overexpression of COPI components promotes but knockdown of gene expression inhibits TYLCV infection. The COPI pathway plays similar roles in C4/AC4 transport and infections of other geminiviruses, including Beet curly top virus and East African cassava mosaic virus. Our results identify an unconventional role of the COPI pathway in protein trafficking to chloroplasts during geminiviruses infections in plants, and suggest a broad-spectrum antiviral strategy in controlling geminiviruses by manipulating COPI components.
Dynamic RNA Polymerase II Recruitment Drives Differentiation of the Intestine under the direction of HNF4
Authors: Vemuri Kiranmayi , Kumar Sneha , Chen Lei , Verzi Michael P. 
Published: November 2023

SUMMARYTerminal differentiation requires a massive restructuring of the transcriptome. During intestinal differentiation, the expression patterns of nearly 4000 genes are altered as cells transition from progenitor cells in crypts to differentiated cells in villi. We identified dynamic recruitment of RNA Polymerase II (Pol II) to gene promoters as the primary driver of transcriptomic shifts during intestinal differentiationin vivo. Changes in enhancer-promoter looping interactions accompany dynamic Pol II recruitment and are dependent upon HNF4, a pro-differentiation transcription factor. Using genetic loss-of-function, ChIP-seq and IP mass spectrometry, we demonstrate that HNF4 collaborates with chromatin remodelers and loop-stabilizing proteins and facilitates Pol II recruitment at hundreds of genes pivotal to differentiation. We also explore alternate mechanisms which drive differentiation gene expression and find pause-release of Pol II and post-transcriptional mRNA stability regulate smaller subsets of differentially expressed genes. These studies provide insights into the mechanisms of differentiation in a renewing adult tissue.HIGHLIGHTSDynamic recruitment of Pol II largely drives the vast transcriptomic changes seen during differentiation of mouse intestinal epithelium.Smaller groups of differentiated genes are subject to regulation through Pol II pause-release and post-transcriptional mechanisms such as differences in mRNA stability.IP-mass spectrometry analysis identifies the first interactome of HNF4 in the differentiated small intestine, finding interactions with chromatin looping and chromatin remodeling proteins.HNF4 transcription factors play a critical role in recruiting Pol II to the promoters of essential intestinal differentiation genes.
Combinatorialin silicoapproach for cancer-associated 4Fe-4S protein discovery
Authors: Tam Winnie W. L. , Cheng Michael H. W. , Mo Xiaoyong , He Bei-Bei , Ngo Ulrike F. M. , Yuen Nicholas M. H. , Yau Angela Y. L. , Wu Nicholas C. , Tse Edmund C. M. 
Published: November 2023

AbstractIron-sulfur (Fe-S) proteins play vital roles in multiple cellular processes, including mediating redox balance as well as DNA replication and repair. Given the role of Fe-S cofactors in genome maintenance, mutations in such metalloproteins could be associated with cancer. Nevertheless, only a few cancer-associated Fe-S proteins have been identified.In vitro, Fe-S cluster is susceptible to degradation in oxic environment. It could also be replaced by other metal ions during protein purification, mis-labelled as zinc finger or Zn-containing proteins.In silico, bioinorganic Fe-S cluster lacks unique sequence characteristics that distinguish itself from other metal-coordination sites, making motif prediction based solely on protein sequence difficult. Thus, in this study, three traits have been employed to discover putative cancer-associated 4Fe-4S proteins. Here, we have analyzed the human proteome via a three-pronged approach: (i) the presence of a triamino acid motif, (ii) the geometric arrangements of the cysteines, and (iii) the mutations of cancer-associated cysteines. In addition to MUTYH, a known 4Fe-4S human DNA glycosylase, 21 novel proteins were discovered as potential cancer-associated 4Fe-4S proteins. While 6 receptor proteins and 3 growth factors have been identified as potential targets in this study, 5 histone lysine methyltransferases with SET domains were also predicted to contain 4Fe-4S metallocofactors. This work provides insights for rational adjustments in experimental design and novel cancer biomarker discovery.
GENTANGLE: integrated computational design of gene entanglements
Authors: Martí Jose Manuel , Hsu Chloe , Rochereau Charlotte , Blazejewski Tomasz , Nisonoff Hunter , Leonard Sean P. , Kang-Yun Christina S. , Chlebek Jennifer , Ricci Dante P. , Park Dan , Wang Harris , Listgarten Jennifer , Jiao Yongqin , Allen Jonathan E. 
Published: November 2023

AbstractSummaryThe design of two overlapping genes in a microbial genome is an emerging technique for adding more reliable control mechanisms in engineered organisms for increased safety. The design of functional gene pairs is a challenging procedure and computational design tools are used to improve the efficiency to deploy successful designs in genetically engineered systems. GENTANGLE (Gene Tuples ArraNGed in overLapping Elements) is a high performance containerized pipeline for the computational design of two overlapping genes translated in different reading frames of the genome. This new software package can be used to design and test gene entanglements for microbial engineering projects using arbitrary sets of user specified gene pairs.Availability and ImplementationThe GENTANGLE source code and its submodules are freely available on GitHub athttps://github.com/BiosecSFA/gentangle. The DATANGLE (DATA for genTANGLE) repository contains related data and results, and is freely available on GitHub athttps://github.com/BiosecSFA/datangle. The GENTANGLE repository wiki contains detailed instructions on how to use the container and the different components of software and data, including reproducing the results. The code is licensed under the GNU Affero General Public License version 3 (https://www.gnu.org/licenses/agpl.html).Contactmartimartine1@llnl.govandallen99@llnl.gov