bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell transcriptomics reveal distinct subsets of activated dendritic cells in the tumor microenvironment
Authors: To Tsun Ki Jerrick , Devalaraja Samir , Folkert Ian W. , Zhai Li , Lobel Graham P. , Haldar Malay 
Published: September 2022

AbstractDendritic cells (DCs) are rare in tumors where their heterogeneity remains unclear. To overcome the limitations of surface marker-based analyses, we utilized DC-reporter mice (Zbtb46GFP/+) to isolate tissue and tumor DCs and performed single-cell RNA sequencing (scRNA-seq). The known DC subsets were conserved across tissues, albeit at different frequencies. Activated and mature DCs formed a distinct cluster in both healthy and tumor tissues and displayed the hallmark DC migratory program (migratory DCs). We also identified a distinct subset of activated DCs in tumors that did not induce the migratory program, instead displaying signatures of interferon exposure (interferon-DCs or IFN-DCs). IFN-DCs were proficient in antigen-presentation, supported T cell proliferation, and expressed high levels of T cell-attracting chemokines. IFN-DCs further comprised of IFN1- and IFN2-DCs that were generated from CD11b+ DCs in response to type I or type II interferons respectively. We also identified IFN-DCs in scRNA-seq of human tumor-infiltrating leukocytes. These findings illustrate DC heterogeneity in tumors and suggest the existence of an interferon regulated ‘division of labor’ among activated DCs whereby the migratory DCs drive T cell priming in draining lymph nodes while the sessile IFN-DCs help recruit T cells and regulate their function in the tumor microenvironment.One Sentence SummaryTumors harbor an interferon-regulated activated sessile subset of dendritic cells.
Impact of female mate copying on male morph dynamics
Authors: Patil Srishti , Nöbel Sabine , Gokhale Chaitanya S. 
Published: September 2022

AbstractMate copying (MC), a type of non-independent mate choice, is a behaviour observed in many vertebrate and few invertebrate species. It occurs when an individual’s sexual preference gets socially inclined toward those of its conspecifics. Theoretical models and experimental studies of MC have been limited to choice between two options (or morphs). In this study we model the evolution of morphology in a population under varying extents of mate copying. Multiple morphs and multiple observations are considered and a generalisable model is presented. We quantify the level of copying needed to achieve pseudo-stable equilibria in the presence of multiple morphs. Moving closer to realistic scenarios we support our theoretical development with simulations and discuss relevance for empirical model systems.
Simulating Short-Term Synaptic Plasticity on SpiNNaker Neuromorphic Hardware
Authors: Azzalini Loïc J. , Lankarany Milad 
Published: September 2022

AbstractNeuromorphic chips are well-suited for the exploration of neuronal dynamics in (near) real-time. In order to port existing research onto these chips, relevant models of neuronal and synaptic dynamics first need to be supported by their respective development environments and validated against existing simulator backends. At the time of writing, support for short-term synaptic plasticity on neuromorphic hardware is scarce. This technical paper proposes an implementation of dynamic synapses for the SpiNNaker development environment based on the popular synaptic plasticity model by Tsodyks and Markram (TM). This extension is undertaken in the context of existing research on neuromodulation and the study of deep brain stimulation (DBS) effects on singular-neuron responses. The implementation of the TM synapse is first detailed and then, simulated for various response types. Its role in studies of DBS effect on postsynaptic responses is also reviewed. Finally, given the real-time capabilities offered by the hardware, we provide some insight to lay the groundwork for future explorations of closed-loop DBS on neuromorphic chips.
Intrinsically disordered proteins SAID1/2 condensate on SERRATE/ARS2 for dual inhibition of miRNA biogenesis in Arabidopsis
Authors: Shang Baoshuan , Wang Lin , Yan Xingxing , Li Yanjun , Li Changhao , Wu Chaohua , Wang Tian , Xiang-Guo  , Choi Sukwon , Zhang Tianru , Wang Ziying , Tong Chun-Yip , Oh Taerin , Xiao-Zhang  , Wang Zhiye , Peng Xu , Zhang Xiuren 
Published: September 2022

SummaryIntrinsically disordered proteins (IDPs) SAID1/2 are hypothetic dentin sialophosphoprotein-like proteins, but their true functions are unknown. Here, we identified SAID1/2 as negative regulators of SERRATE(SE)/ARS2, a core factor in miRNA biogenesis complex (microprocessor). Loss-of-function double mutants of said1; said2 caused pleiotropic developmental defects and thousands of differentially-expressed genes that partially overlapped with those in se. said1; said2 also displayed increased assembly of microprocessor and elevated accumulation of miRNAs. Mechanistically, SAID1/2 promotes PRP4KA-mediated phosphorylation of SE, leading to its degradation in vivo. Unexpectedly, SAID1/2 have strong binding affinity to hairpin-structured pri-miRNAs and can sequester them from SE. Moreover, SAID1/2 directly inhibit pri-miRNA processing by microprocessor in vitro. Whereas SAID1/2 did not impact SE subcellular compartmentation, the proteins themselves exhibited liquid-liquid phase condensation that is nucleated on SE. Thus, we proposed that SAID1/2 reduce miRNA production through hijacking pri-miRNAs to prevent microprocessor activity while promoting SE phosphorylation and its destabilization in Arabidopsis.
A high-throughput strategy for enhancing aptamer performance across different environmental conditions
Authors: Wan Leighton , Yoshikawa Alex , Eisenstein Michael , Soh H. Tom 
Published: September 2022

AbstractAptamers selected under specific environmental conditions (e.g., pH, ion concentration, temperature) often exhibit greatly reduced affinity when used in other contexts. This can be especially problematic for biomedical applications, in which aptamers are exposed to sample matrices with distinctive chemical properties, such as blood, sweat, or urine. We present a high-throughput screening procedure for adapting existing aptamers for use in samples whose chemical composition differs considerably from the original selection conditions. Building on prior work from our group, we have utilized a modified DNA sequencer to screen more than 106 aptamer single and double mutants for target binding under the desired assay conditions. As an exemplar, we screened mutants of a previously reported glucose aptamer that was originally selected in high-ionic strength buffer and exhibits relatively low affinity under physiological conditions. After a single round of screening, we identified aptamer mutants with ∼4-fold increased affinity under physiological conditions. Interestingly, we found that the impact of single-base substitutions was relatively modest, but observed considerably greater binding improvements among the double mutants, highlighting the importance of cooperative effects between mutations. This approach should be generalizable to other aptamers and environmental conditions for a range of applications.
Accessory-cell-free differentiation of hematopoietic stem and progenitor cells into mature red blood cells
Authors: Boccacci Yelena , Dumont Nellie , Doyon Yannick , Laganière Josée 
Published: September 2022

ABSTRACTThe culture and ex vivo engineering of red blood cells (RBCs) can help characterize genetic variants, model diseases, and may eventually spur the development of applications in transfusion medicine. In the last decade, improvements to the in vitro production of RBCs have enabled efficient erythroid progenitor proliferation and high enucleation levels from several sources of hematopoietic stem and progenitor cells (HSPCs). Despite these advances, there remains a need for refining the terminal step of in vitro human erythropoiesis — i.e., the terminal maturation of reticulocytes into erythrocytes — so that it can occur without feeder or accessory cells and animal components. Here, we describe the near-complete erythroid differentiation of cultured RBCs (cRBCs) from adult HSPCs in accessory-cell-free and animal-component-free conditions. The approach improves post-enucleation cell integrity and cell survival, and enables subsequent storage of cRBCs for up to 42 days in classical nutritive solution conditions, without any specialized equipment. We foresee that these improvements will facilitate the characterization of RBCs derived from gene-edited HSPCs.KEY POINTSErythroid progenitors were differentiated into fully mature RBCs in a medium free of accessory cellsCultured RBCs can be stored up to 42 days in a standard nutritive solution
Removal of extracellular human amyloid beta aggregates by extracellular proteases inC. elegans
Authors: Jongsma Elisabeth , María Mateos José , Ewald Collin Y. 
Published: September 2022

AbstractThe amyloid-beta (Aβ) plaques found in Alzheimer’s disease (AD) patients’ brains contain collagens and are embedded extracellularly. Several collagens have been proposed to influence Aβ aggregate formation, yet their role in clearance is unknown. To investigate the potential role of collagens in forming and clearance extracellular aggregatesin vivo, we created a transgenicCaenorhabditis elegansstrain that expresses and secretes human Aβ1-42. This secreted Aβ forms aggregates in two distinct places within the extracellular matrix. In a screen for extracellular human Aβ aggregation regulators, we identified different collagens to ameliorate or potentiate Aβ aggregation. We show that a disintegrin and metalloprotease ADM-2, an orthologue of ADAM9, reduces the load of extracellular Aβ aggregates. ADM-2 is required and sufficient to remove the extracellular Aβ aggregates. Thus, we providein-vivoevidence of collagens essential for aggregate formation and metalloprotease participating in extracellular Aβ aggregate removal.HighlightsExtracellular aggregates of amyloid beta are a hallmark of Alzheimer’s disease. Here we developed a novelC. eleganstransgenic line that secretes human amyloid beta, which forms aggregates in the extracellular matrix (ECM). We show that ECM dynamics can disturb aggregation and that ADM-2, an ortholog of Human ADAM9, is involved in removing these extracellular aggregates.
Severe fatigue as symptom of long COVID is characterized by increased expression of inflammatory genes in monocytes, increased serum pro-inflammatory cytokines, and increased CD8+ T-lymphocytes: A putative dysregulation of the immune-brain axis, the coagulation process, and auto-inflammation to explain the diversity of long COVID symptoms
Authors: Berentschot Julia C. , Drexhage Hemmo A. , Aynekulu Mersha Daniel G. , Wijkhuijs Annemarie J.M. , GeurtsvanKessel Corine H. , Koopmans Marion P.G. , Voermans Jolanda , Heijenbrok-Kal Majanka H. , Bek L. Martine , Ribbers Gerard M. , van den Berg-Emons Rita J.G. , Aerts Joachim G.J.V , Dik Willem A. , Hellemons Merel E. 
Published: September 2022

ABSTRACTBackgroundA significant proportion of patients with SARS-CoV-2 infection develops long COVID with fatigue as one of the most disabling symptoms. We performed clinical and immunologic profiling of fatigued and non-fatigued long COVID patients and age and gender matched healthy controls (HCs).MethodsWe included 37 long COVID patients with and 36 without severe fatigue and assessed inflammation-related monocyte gene expression, serum levels of inflammatory cytokines, and leukocyte and lymphocyte subsets 3-6 months after hospital discharge, and followed clinical symptoms up to one year.ResultsLong COVID with fatigue represented a severe variant with many symptoms (median 9 [IQR 5.0-10.0] symptoms) and signs of cognitive failure (41%) and depression (>24%). Symptoms persisted up to one year follow-up. Fatigued patients showed increased expression of inflammatory genes in monocytes, increased serum IL-6, TNF-α, galectin-9, and CXCL10, and increased CD8+ T-lymphocytes compared to HCs.Non-fatigued long COVID patients were arbitrarily divided in those with moderately severe disease (4 [2.5-5.0] symptoms, primarily impaired fitness, n=25) and those with mild disease (1 [1.0-2.0] symptom, n=11). Symptoms in non-fatigued long COVID patients persisted up to one year follow-up. Moderately severe patients showed reduced CD45RO-naïve CD4+T-lymphocytes and CD25+FOXP3+ regulatory CD4+T-lymphocytes and limited monocyte and serum (galectin-9) inflammation. Mild patients showed monocyte and serum (IL-6, galectin-9) inflammation and decreased CD4+T-lymphocyte subsets (T-helper 1 cells).ConclusionLong COVID with fatigue is associated with many concurrent and persistent symptoms up to one year after hospitalization and with clear signs of low grade inflammation and increased CD8+T-lymphocytes. We showed that long COVID is a clinical and immunologic heterogeneous disorder. Diagnostic tools and personalized therapies combatting the diverse immune abnormalities might be required to alleviate the persisting disabling complaints of the patients.
Single cell transcriptomics reveals correct developmental dynamics and high-quality midbrain cell types by improved hESC differentiation
Authors: Nishimura Kaneyasu , Yang Shanzheng , Lee Ka Wai , Ásgrímsdóttir Emilía Sif , Nikouei Kasra , Paslawski Wojciech , Gnodde Sabine , Lyu Guochang , Hu Lijuan , Saltó Carmen , Svenningsson Per , Hjerling-Leffler Jens , Linnarsson Sten , Arenas Ernest 
Published: September 2022

SummaryStem cell technologies provide new opportunities for modeling cells in the healthy and diseased states and for regenerative medicine. In both cases developmental knowledge as well as the quality and molecular properties of the cells are essential for their future application. In this study we identify developmental factors important for the differentiation of human embryonic stem cells (hESCs) into midbrain dopaminergic (mDA) neurons. We found that Laminin-511, and dual canonical and non-canonical WNT activation followed by GSK3β inhibition plus FGF8b, improved midbrain patterning. In addition, mDA neurogenesis and differentiation was enhanced by activation of liver X receptors and inhibition of fibroblast growth factor signaling. Moreover, single-cell RNA-sequencing analysis revealed a developmental dynamics similar to that of the endogenous human ventral midbrain and the emergence of high quality molecularly-defined midbrain cell types, including mDA neurons that become functional. Thus, our study identifies novel factors important for human midbrain development and opens the door for a future application of molecularly-defined hESC-derived midbrain cell types in Parkinson’s disease.
Accumulation of mitochondrial ROS drives reductive glutamine metabolism
Authors: Sheng Xiangpeng 
Published: September 2022

ABSTRACTHypoxia, mitochondrial defect or extracellular matrix detachment induces reductive glutamine metabolism that can produce citrate by carboxylating the glutamine-derived ketoglutarate (α-KG). Reductive carboxylation is required for maintaining redox homeostasis, lipogenesis and cancer cell growth. However, the fundamental mechanism(s) of how reductive glutamine metabolism may be controlled is not fully understood. This study here demonstrates that mitochondrial-derived reactive oxygen species (ROS) positively drives reductive carboxylation. Knockout of fatty acid synthase (FASN) causes increased mitochondrial ROS and significant reductive glutamine metabolism. Mitochondrial ROS accumulation is identified as a shared feature in cells that utilize reductive metabolism. Moreover, ROS scavenger could inhibit reductive carboxylation by decreasing ROS level in mitochondria. By contrast, ROS inducers activate reductive carboxylation via increasing mitochondrial ROS. Mitochondrial ROS level determines the degree of reductive carboxylation with a positive correlation. The results presented here not only reveal a fundamental mechanism of how reductive carboxylation is controlled, but also elucidate a critical role of ROS in reprogramming metabolism.
Three-dimensional motions of GroEL during substrate protein recognition
Authors: Stapleton Kevin , Mizobata Tomohiro , Miyazaki Naoyuki , Takatsuji Tomohiro , Kato Takayuki , Iwasaki Kenji , Standley Daron M , Kawamura Takeshi , Nakane Takanori , Takagi Junichi , Mizohata Eiichi 
Published: September 2022

AbstractGroEL is a bacterial chaperonin responsible for the assisted folding of non-native and misfolded polypeptides into biologically active proteins. The adaptive nature of the recognition mechanism of chaperonins toward client polypeptides inherently lends itself to structural heterogeneity, which hampers detailed analyses of intermolecular recognition and binding. In this report, we used single-particle cryo-EM and multiple rounds of focused mask three-dimensional classification to reveal a landscape of distinct snapshots of endogenous GroEL complexed with an unfolded substrate, the water-soluble domain of human UDP glucuronosyltransferase 1A (UGT1A), at 2.7–3.5 Å resolution. We demonstrate that UGT1A occupies the GroEL ring asymmetrically, engaging with 2–3 contiguous subunits and that a subunit bound to UGT1A exhibits a wider range of conformational dynamics, consistent with AlphaFold models. These data reveal molecular motions during initial substrate capture at near-atomic detail.
PCNA recruits cohesin loader Scc2/NIPBL to ensure sister chromatid cohesion
Authors: Psakhye Ivan , Kawasumi Ryotaro , Abe Takuya , Hirota Kouji , Branzei Dana 
Published: September 2022

AbstractSister chromatid cohesion is essential for faithful chromosome segregation and genome duplication during cell division. Failure to establish cohesion during S phase by the ring-shaped multiprotein complex cohesin leads to genomic instability1-4. Replisome-associated proteins are required to generate cohesion by two independent pathways5. One mediates conversion of cohesins bound to unreplicated DNA ahead of replication forks into cohesive entities behind them, while the second promotes cohesin de novo loading onto newly-replicated DNAs6. The latter process depends on the cohesin loader Scc2/NIPBL and the alternative PCNA loader CTF18-RFC. However, the precise mechanism of de novo cohesin loading during replication is unknown. Here we show that PCNA physically recruits yeast cohesin loader Scc2 via its C-terminal PCNA-interacting protein motif. Binding to PCNA is crucial, as scc2-pip mutant deficient in Scc2-PCNA interaction is defective in cohesion when combined with replisome mutants of the cohesin conversion pathway. Moreover, scc2-pip mutant becomes inviable without its partner Scc4/MAU2 that localizes cohesin loader to centromeres. Importantly, the role of NIPBL recruitment to PCNA for cohesion generation is conserved in vertebrate cells. Our results demonstrate that PCNA, the maestro of replication-linked functions, is also crucially involved in the cohesion establishment through de novo cohesin loading onto replicated DNA.
ADRA2B and HTR1A: An updated study of the biogenic amine receptors reveals novel conserved motifs which play key role in Mental Disorders
Authors: Papageorgiou Louis , Christou Evangelia , Louka Effrosyni , Papakonstantinou Eleni , Diakou Io , Pierouli Katerina , Dragoumani Konstantina , Bacopoulou Flora , Chrousos George P , Eliopoulos Elias , Vlachakis Dimitrios 
Published: September 2022

AbstractMental disorders are strongly connected with several psychiatric conditions including depression, bipolar disorder, schizophrenia, eating disorder and suicides. There are many biological conditions and pathways that define these complicated illnesses. For example, eating disorders are complex mental health conditions that require the intervention of geneticists, psychiatrists and medical experts in order to alleviate their symptoms. A patient with suicidal ideation should first be identified and consequently monitored by a similar team of specialists. Both genetics and epigenetics can shed light on eating disorders and suicides as they are found in the main core of such investigations. In the present study, an analysis has been performed on two specific members of the GPCR family towards drawing conclusions regarding their functionality and implementation in mental disorders. Specifically, evolutionary and structural studies on the adrenoceptor alpha 2b (ADRA2B) and the 5-hydroxytryptamine receptor 1A (HTR1A) have been carried out. Both receptors are classified in the biogenic amine receptors sub-cluster of the GPCRs and have been connected in many studies with mental diseases and malnutrition conditions. The major goal of this study is the investigation of conserved motifs among biogenic amine receptors that play an important role in this family signaling pathway, through an updated evolutionary analysis and the correlation of this information with the structural features of the HTR1A and ADRA2B. Furthermore, structural comparison of ADRA2B, HTR1A, and other members of GPCRs related with mental disorders is performed.
Influence of temperature on growth and development of dictyostelid slime moulds and its implication on the evolution of cold-tolerance
Authors: Hashimura Hidenori , Inouye Kei 
Published: September 2022

AbstractEnvironmental temperature is a major determinant of microbial life. Dictyostelids are soil amoebae capable of multicellular social behaviour upon starvation. They inhabit in a variety of environments from the tundra to the tropics, but how they have adapted to environmental temperature remains largely unknown. In this study, the effects of temperature on the growth and multicellular development of 36 dictyostelid species (58 strains/isolates) were examined. More than half of the species showed maximal growth and normal development at 28°C or above, whereas some could grow and develop at 4°C, or even at 0°C. Many of the isolates examined were from areas with temperatures far lower than their preferred range over a large part of the year. There was a significant correlation between thermal characteristics and phylogeny. Over 150 known dictyostelid species are divided into several taxonomic groups. Our phylogenetic analysis indicated that cold-tolerance evolved independently in major clades, most prominently in group 4 (genus Dictyostelium according to the new classification by Sheikh et al.), which contains many species that are often found in subarctic regions. These results suggest that ancestors that have acquired cold-tolerance expanded their ranges into cooler areas where they could proliferate and develop during summer and survive the severe winter.
Corrosion monitoring method of 304 stainless steel in a simulated marine–industrial atmospheric environment: electrochemical noise method
Authors: Hu Jiezhen , Deng Junhao , Deng Peichang , Wang Gui 
Published: September 2022

Purpose
This paper aims to study the use of electrochemical noise (EN) technology in the corrosion continuous monitoring of stainless steel (SS) in an atmospheric environment.

Design/methodology/approach
An EN electrode was designed and fabricated to acquire the EN of 304 SS in the atmospheric environment. The statistical analysis and shot noise analysis were used to analyze the EN, and the surface morphology analysis of 304 SS was used to verify the EN analysis results.

Findings
The activation state, passive film formation and pitting corrosion of 304 SS can be clearly distinguished by the amplitude and frequency change of EN. The metastable pitting corrosion and steady-state pitting corrosion can be identified with the shot noise parameters q and fn. Under the existence of chloride ion, the stability of 304 SS passive film decreases and the steady-state corrosion pits of 304 SS are more likely to form with the reduction of thin electronic layer (TEL) pH. The critical TEL pH of 304 SS corrosion is a pH between 3 and 4.

Originality/value
In an atmospheric environment, the EN technology was used in the corrosion continuous monitoring of SS.