bluuebunny/crossref_metadata_2025_split huggingface dataset:
On-chip large-scale-integration and 2D collective modes of genetically programmed artificial cells
Authors: Ricouvier Joshua , Mostov Pavel , Shabtai Omer , Tayar Alexandra , Karzbrun Eyal , Khakimzhan Aset , Noireaux Vincent , Daube Shirley Shulman , Bar-Ziv Roy 
Published: January 2024

AbstractThe on-chip large-scale-integration of genetically programmed artificial cells capable of exhibiting collective modes is an important goal for fundamental research and technology. Here, we report assembly of a 2D layout of 1024 monolithic DNA compartments as artificial cells on a 5-millimeter square silicon chip. Homeostatic cell-free protein synthesis reactions driven by genetic circuits occur inside the compartments. We created a reaction-diffusion system with a 30x30 square lattice of artificial cells interconnected by thin capillaries for diffusion of products. Driving the system by a genetic oscillator revealed emergent collective modes of synchrony and propagating phase waves in 2D, with dynamics controlled by geometry. This demonstrates a class of nonequilibrium autonomous systems, where chemical energy consumed to make proteins induces 2D collective patterns of gene expression on multicellular scales, with applications in biological computing, sensing, and materials synthesis.
The inevitability and superfluousness of cell types in spatial cognition
Authors: Luo Xiaoliang , Mok Robert M. , Love Bradley C. 
Published: January 2024

SummaryDiscoveries of functional cell types, exemplified by the cataloging of spatial cells in the hippocampal formation, are heralded as scientific breakthroughs. We question whether the identification of cell types based on human intuitions has scientific merit and suggest that “spatial cells” may arise in non-spatial computations of sufficient complexity. We show that deep neural networks (DNNs) for object recognition, which lack spatial grounding, contain numerous units resembling place, border, and head-direction cells. Strikingly, even untrained DNNs with randomized weights contained such units and support decoding of spatial information. Moreover, when these “spatial” units are excluded, spatial information can be decoded from the remaining DNN units, which highlights the superfluousness of cell types to spatial cognition. Now that large-scale simulations are feasible, the complexity of the brain should be respected and intuitive notions of cell type, which can be misleading and arise in any complex network, should be relegated to history.
Sleep selectively and durably enhances real-world sequence memory
Authors: Diamond N.B , Simpson S. , Baena Pérez D. , Murray B. , Fogel S. , Levine B. 
Published: January 2024

AbstractSleep is thought to play a critical role in the retention of episodic memories. Yet it remains unclear whether and how sleep actively transforms memory for specific experiences. More generally, little is known about sleep’s effects on memory for multidimensional real-world experiences, both overnight and in the days to months that follow. In an exception to the law of forgetting, we showed that sleep actively and selectively improves retrieval of a one-time real-world experience (a controlled but immersive art tour) – specifically boosting memory for the order of tour items (sequential associations), but not perceptual details from the tour (featural associations). This above-baseline increase in sequence memory was not evident after a matched period of wakefulness. Moreover, the sleep-induced advantage of sequence over featural memory grew over time up to one-year post-encoding. Finally, overnight polysomnography showed that sleep-related memory enhancement was associated with the duration and neurophysiological hallmarks of slow-wave sleep previously linked to neural replay, particularly spindle-slow wave coupling. These results suggest that sleep serves a crucial and selective role in enhancing sequential organization in episodic memory at the expense of specific details, linking sleep-related neural mechanisms to the transformation and enhancement of memory for complex real-life experiences.Significance StatementSleep affects the retention of episodic memories. Yet, it remains unclear whether sleep active transforms how we remember past experiences, overnight and beyond. We investigated memory for different dimensions underlying a dynamic real-world event – sequential associations versus atemporal featural associations – before and after sleep or wakefulness, and serially up to a year later. Sleep actively and selectively enhanced sequence memory, with this preferential sequence retention growing with time. Overnight memory enhancement is associated with the duration and neurophysiological hallmarks of slow-wave sleep previously linked to sequential neural replay, particularly spindle-slow wave coupling. Our findings support an active role for sleep in transforming different aspects of real-world memory, with sequence structure coming to dominate long-term memory for dynamic real-world experiences.
SLAM/SAP signaling regulates discrete γδ T cell developmental checkpoints and shapes the innate-like γδ TCR repertoire
Authors: Mistri Somen K , Hilton Brianna M. , Horrigan Katherine J. , Andretta Emma S. , Savard Remi , Dienz Oliver , Hampel Kenneth J , Gerrard Diana L. , Rose Joshua T. , Sidiropoulos Nikoletta , Majumdar Devdoot , Boyson Jonathan E. 
Published: January 2024

AbstractDuring thymic development, most γδ T cells acquire innate-like characteristics that are critical for their function in tumor surveillance, infectious disease, and tissue repair. The mechanisms, however, that regulate γδ T cell developmental programming remain unclear. Recently, we demonstrated that the SLAM-SAP signaling pathway regulates the development and function of multiple innate-like γδ T cell subsets. Here, we used a single-cell proteogenomics approach to identify SAP-dependent developmental checkpoints and to define the SAP-dependent γδ TCR repertoire. SAP deficiency resulted in both a significant loss of an immatureGzma+Blk+Etv5+Tox2+γδT17 precursor population, and a significant increase inCd4+Cd8+Rorc+Ptcra+Rag1+thymic γδ T cells. SAP-dependent diversion of embryonic day 17 thymic γδ T cell clonotypes into the αβ T cell developmental pathway was associated with a decreased frequency of mature clonotypes in neonatal thymus, and an altered γδ TCR repertoire in the periphery. Finally, we identify TRGV4/TRAV13-4(DV7)-expressing T cells as a novel, SAP-dependent Vγ4 γδT1 subset. Together, the data suggest that SAP-dependent γδ/αβ T cell lineage commitment regulates γδ T cell developmental programming and shapes the γδ TCR repertoire.Abstract Figure
Atrial Proteomic Profiling Reveals a Switch Towards Profibrotic Gene Expression Program in CREM-IbΔC-X Mice with Persistent Atrial Fibrillation
Authors: Zhao Shuai , Hulsurkar Mohit M. , Lahiri Satadru K. , Aguilar-Sanchez Yuriana , Munivez Elda , Müller Frank Ulrich , Jain Antrix , Malovannaya Anna , Yiu Kendrick , Reilly Svetlana , Wehrens Xander H.T. 
Published: January 2024

ABSTRACTBackgroundOverexpression of the CREM (cAMP response element-binding modulator) isoform CREM-IbΔC-X in transgenic mice (CREM-Tg) causes the age-dependent development of spontaneous AF.PurposeTo identify key proteome signatures and biological processes accompanying the development of persistent AF through integrated proteomics and bioinformatics analysis.MethodsAtrial tissue samples from three CREM-Tg mice and three wild-type littermates were subjected to unbiased mass spectrometry-based quantitative proteomics, differential expression and pathway enrichment analysis, and protein-protein interaction (PPI) network analysis.ResultsA total of 98 differentially expressed proteins were identified. Gene ontology analysis revealed enrichment for biological processes regulating actin cytoskeleton organization and extracellular matrix (ECM) dynamics. Changes in ITGAV, FBLN5, and LCP1 were identified as being relevant to atrial fibrosis and remodeling based on expression changes, co-expression patterns, and PPI network analysis. Comparative analysis with previously published datasets revealed a shift in protein expression patterns from ion-channel and metabolic regulators in young CREM-Tg mice to profibrotic remodeling factors in older CREM-Tg mice. Furthermore, older CREM-Tg mice exhibited protein expression patterns that resembled those of humans with persistent AF.ConclusionsThis study uncovered distinct temporal changes in atrial protein expression patterns with age in CREM-Tg mice consistent with the progressive evolution of AF. Future studies into the role of the key differentially abundant proteins identified in this study in AF progression may open new therapeutic avenues to control atrial fibrosis and substrate development in AF.Graphical abstractGraphical abstract summarizing key findings of this paper. The atrial proteome in 9-month-old CREM- Tg mice with chronic persistent AF (perAF) was compared with age-matched WT littermates. In addition, proteome changes in these old CREM-Tg mice were compared with proteome changes previously identified in young CREM-Tg mice with paroxysmal AF (pAF). Moreover, an interspecies comparison was performed between old CREM-Tg mice and human patients with perAF. The major findings are that in pAF, key changes were identified in proteins involved in metabolism, energy production, DNA synthesis, and cell proliferation and growth. On the other hand, in mice and humans with perAF, key changes were found in the expression of proteins involved in collagen production, extracellular matrix remodeling, actin cytoskeleton organization, and tissue repair.
Single-step generation of homozygous knock-out/knock-in individuals in an extremotolerant parthenogenetic tardigrade using DIPA-CRISPR
Authors: Kondo Koyuki , Tanaka Akihiro , Kunieda Takekazu 
Published: January 2024

AbstractTardigrades are small aquatic invertebrates known for their remarkable tolerance to diverse extreme stresses. To elucidate thein vivomechanisms underlying this extraordinary resilience, the genetic manipulation methods in tardigrades have long been desired. Despite our prior success in somatic cell gene-editing by microinjecting Cas9 ribonucleoproteins (RNPs) into the body cavity of tardigrades, the generation of gene-edited individuals remained elusive.In this study, employing an extremotolerant parthenogenetic tardigrade species,Ramazzottius varieornatus, we established conditions conductive to generating gene-edited tardigrade individuals. Drawing inspiration from the direct parental CRIPSR (DIPA-CRISPR) technique employed in several insects, we simply injected a concentrated Cas9 RNP solution into the body cavity of parental females shortly before their initial oviposition. This approach yielded gene-edited G0 progeny. Notably, only a single allele was predominantly detected at the target locus for each G0 individual, indicative of homozygous mutations. Through co-injecting single-stranded oligodeoxynucleotides (ssODNs) with Cas9 RNPs, we achieved the generation of homozygously knocked-in G0 progeny and these edited-alleles were inherited by G1/G2 progeny.This establishment of a simple method for generating homozygous knock-out/knock-in individuals not only facilitatesin vivoanalyses of molecular mechanisms underpinning extreme tolerance but also opens avenues for exploring various topics, including Evo-Devo, in tardigrades.
Incidence of occult cancer in patients diagnosed with adenocarcinoma in situ by cervical punch biopsy or endocervical curettage
Authors: Kwon Byung-Su , Suh Dong Hoon , Lim Myong Cheol , Kim Kidong , Lee Chae Hyeong , Chung Hyun Hoon , Kim Yong-Beom 
Published: January 2024

AbstractObjectivesTo investigate the incidence of occult cancer in patients diagnosed with adenocarcinoma in situ through punch biopsy or endocervical curettage.MethodsWe examined the clinicopathological characteristics of patients diagnosed with adenocarcinoma in situ using punch biopsy or endocervical curettage at four institutes in the Republic of Korea from 2003 to 2011. We investigated the incidence of occult cancer in conization or hysterectomy specimens and whether the occult cancer was detected through conization.ResultsTwenty patients diagnosed with adenocarcinoma in situ through punch biopsy or endocervical curettage were enrolled. Six out of the 20 patients had occult cervical cancer, and four out of the six patients had cervical cancer at or greater than stage 1A1 with lymphovascular space invasion. Two out of four patients were diagnosed with invasive cervical cancer through conization and underwent radical hysterectomy without adjuvant radiotherapy. The other two patients underwent extrafascial hysterectomy without preoperative conization and received adjuvant radiotherapy.ConclusionA significant number of patients diagnosed with adenocarcinoma in situ through punch biopsy or endocervical curettage have occult cancer. Conization should be performed to identify occult cancer and optimize the extent of surgery.
APNet, an explainable sparse deep learning model to discover differentially active drivers of severe COVID-19
Authors: Gavriilidis George I. , Vasileiou Vasileios , Dimitsaki Stella , Karakatsoulis George , Giannakakis Antonis , Pavlopoulos Georgios A. , Psomopoulos Fotis 
Published: January 2024

AbstractMotivationComputational analyses of plasma proteomics provide translational insights into complex diseases such as COVID-19 by revealing molecules, cellular phenotypes, and signaling patterns that contribute to unfavorable clinical outcomes. Currentin silicoapproaches dovetail differential expression, biostatistics, and machine learning, but often overlook nonlinear proteomic dynamics, like post-translational modifications, and provide limited biological interpretability beyond feature ranking.ResultsWe introduce APNet, a novel computational pipeline that combines differential activity analysis based on SJARACNe co-expression networks with PASNet, a biologically-informed sparse deep learning model to perform explainable predictions for COVID-19 severity. The APNet driver-pathway network ingests co-expression and classification weights to aid result interpretation and hypothesis generation. APNet outperforms alternative models in patient classification across three COVID-19 proteomic datasets, identifying predictive drivers and pathways, including some confirmed in single-cell omics and highlighting under-explored biomarker circuitries in COVID-19.Availability and ImplementationAPNet’s R, Python scripts and Cytoscape methodologies are available athttps://github.com/BiodataAnalysisGroup/APNetContactggeorav@certh.grSupplementary informationSupplementary information can be accessed in Zenodo (10.5281/zenodo.10438830).
Polarised subcellular activation of ROPs by specific ROPGEFs drives pollen germination inArabidopsis thaliana
Authors: Bouatta Alida Melissa , Lepper Andrea , Denninger Philipp 
Published: January 2024

AbstractDuring plant fertilisation, excess male gametes compete for a limited number of female gametes. The dormant male gametophyte, encapsulated in the pollen grain, consists of two sperm cells enclosed in a vegetative cell. After reaching the stigma of a compatible flower, quick and efficient germination of the vegetative cell to a tip-growing pollen tube is crucial to ensure fertilisation success. RHO OF PLANTS (ROP) signalling and their activating ROP GUANINE NUCLEOTIDE EXCHANGE FACTORS (ROPGEFs) are essential for initiating polar growth processes in multiple cell types. However, which ROPGEFs activate pollen germination is unknown. We investigated the role of ROPGEFs in initiating pollen germination and the required cell polarity establishment. Of the five pollen-expressed ROPGEFs, we found that GEF8, GEF9, and GEF12 are required for pollen germination and male fertilisation success, asgef8;gef9;gef12triple mutants showed almost complete loss of pollen germinationin vitroand had a reduced allele transmission rate. Live cell imaging and spatiotemporal analysis of subcellular protein distribution showed that GEF8 and GEF9, but not GEF12, displayed transient polar protein accumulations at the future site of pollen germination minutes before pollen germination, demonstrating specific roles for GEF8 and GEF9 during the initiation of pollen germination. Furthermore, this novel GEF accumulation appears in a biphasic temporal manner and can shift its location. We showed that the C-terminal domain of GEF8 and GEF9 confers this protein accumulation and demonstrated that GEFs locally activate ROPs and alter Ca2+signalling, which is required for pollen tube germination. We demonstrated that GEFs do not act redundantly during pollen germination and described for the first time a polar domain with spatiotemporal flexibility, which is crucial for thede novoestablishment of a polar growth domain within a cell and, thus, for pollen function and fertilisation success.
PUFA stabilizes a conductive state of the selectivity filter in IKs channels
Authors: Golluscio Alessia , Eldstrom Jodene , Jowais Jessica J. , Perez-Rodriguez Marta E. , Cunningham Kevin P. , de la Cruz Alicia , Wu Xiaoan , Corradi Valentina , Tieleman D. Peter , Fedida David , Larsson H. Peter 
Published: January 2024

ABSTRACTIn cardiomyocytes, the KCNQ1/KCNE1 channel complex mediates the slow delayed-rectifier current (IKs), pivotal during the repolarization phase of the ventricular action potential. Mutations in IKs cause Long QT Syndrome (LQTS), a syndrome with a prolonged QT interval on the ECG, which increases the risk of ventricular arrhythmia and sudden cardiac death. One potential therapeutical intervention for LQTS is based on targeting IKs channels to restore channel function and/or the physiological QT interval. Polyunsaturated fatty acids (PUFAs) are potent activators of KCNQ1 channels and activate IKs channels by binding to two different sites, one in the voltage sensor domain (VSD) – which shifts the voltage dependence to more negative voltages– and the other in the pore domain (PD) – which increases the maximal conductance of the channels (Gmax). However, the mechanism by which PUFAs increase the Gmax of the IKs channels is still poorly understood. In addition, it is unclear why IKs channels have a very small single channel conductance and a low open probability or whether PUFAs affect any of these properties of IKs channels. Our results suggest that the selectivity filter in KCNQ1 is normally unstable, contributing to the low open probability, and that the PUFA-induced increase in Gmax is caused by a stabilization of the selectivity filter in an open-conductive state.
Defining the contribution ofTroy-positive progenitor cells to the mouse esophageal epithelium
Authors: Grommisch David , Wang Menghan , Eenjes Evelien , Svetličič Maja , Deng Qiaolin , Giselsson Pontus , Genander Maria 
Published: January 2024

AbstractProgenitor cells adapt their behavior in response to tissue demands. However, the molecular mechanisms controlling esophageal progenitor decisions remain largely unknown. Here we demonstrate the presence of aTroy(Tnfrsf19)-expressing progenitor subpopulation localized to defined regions along the mouse esophageal axis. Lineage tracing and mathematical modelling demonstrate thatTroy-positive progenitor cells are prone to undergoing symmetrical fate choices and contribute to esophageal tissue homeostasis long-term. Functionally, TROY inhibits progenitor proliferation and enables commitment to differentiation without affecting fate symmetry. WhereasTroyexpression is stable during esophageal homeostasis, progenitor cells downregulateTroyin response to tissue stress, enabling proliferative expansion of basal cells refractory to differentiation and reestablishment of tissue homeostasis. Our results demonstrate functional, spatially restricted, progenitor heterogeneity in the esophageal epithelium and identify how dynamic regulation ofTroycoordinates tissue generation.
Sequence-Dependent Conformational Transitions of Disordered Proteins During Condensation
Authors: Wang Jiahui , Sundaravadivelu Devarajan Dinesh , Kim Young C. , Nikoubashman Arash , Mittal Jeetain 
Published: January 2024

AbstractIntrinsically disordered proteins (IDPs) can form biomolecular condensates through phase separation. It is recognized that the conformation of IDPs in the dense and dilute phases as well as at the interfaces of condensates can critically impact the resulting properties associated with their functionality. However, a comprehensive understanding of the conformational transitions of IDPs during condensation remains elusive. In this study, we employ a coarse-grained polyampholyte model, comprising an equal number of oppositely charged residues—glutamic acid and lysine—whereby conformations and phase behavior can be readily tuned by altering the protein sequence. By manipulating the sequence patterns from perfectly alternating to block-like, we obtain chains with ideal-like conformations to semi-compact structures in the dilute phase, while in the dense phase, the chain conformation is approximately that of an ideal chain, irrespective of the protein sequence. By performing simulations at different concentrations, we find that the chains assemble from the dilute phase through small oligomeric clusters to the dense phase, accompanied by a gradual swelling of the individual chains. We further demonstrate that these findings are applicable to several naturally occurring proteins involved in the formation of biological condensates. Concurrently, we delve deeper into the chain conformations within the condensate, revealing that chains at the interface show a strong sequence dependence, but remain more collapsed than those in the bulk-like dense phase. This study addresses critical gaps in our knowledge of IDP conformations within condensates as a function of protein sequence.TOC graphics
Evaluating the impact of an incentive scheme to encourage pregnant people to set a quit-smoking date
Authors: Allison Seamus , Akbar M. Bilal , Allison Claire , Padley Karla , Wormall Stephen 
Published: January 2024

Purpose
This study aims to demonstrate the evaluation of an incentive scheme to encourage pregnant people to set a quit-smoking date.

Design/methodology/approach
The paper outlines a collaborative approach, working with pregnant people, clinicians, tobacco dependency practitioners and academics to gain insights into their perspectives and experiences. Quantitative and qualitative data were analysed.

Findings
The incentive scheme and appropriate support from clinicians have been shown to encourage pregnant people to set a quit date. The tobacco dependency practitioners helped remove barriers, such as the perception of the stigmatisation of smoking when pregnant. The practitioners also helped pregnant people make informed decisions to support successful behaviour change. The impact of the scheme resulted in improved infant health indicators. The scheme’s evaluation also supported establishing stakeholder knowledge exchange and learning processes.

Research limitations/implications
This is a single-site study among a relatively small group of people designed to achieve a specific evaluation objective. Caution in generalising to wider settings should be exercised.

Practical implications
This study highlights the efficacy of an incentive scheme, complemented with support from clinicians, and the significance of knowledge exchange and collaboration between stakeholders in health care with significance in similar settings.

Originality/value
The paper details the incentive scheme input, actions, output, outcomes and impact involving a wider range of stakeholders, including the emotional consequences for participants, clinicians and academics.