bluuebunny/crossref_metadata_2025_split huggingface dataset:
ThepFactor Outweighs the Specific Internalizing Factor in Predicting Recurrences of Adolescent Depression
Authors: Shu Yinuo , Ao Na , Wen Xue , Cui Zaixu , Qu Diyang , Chen Runsen 
Published: August 2023

AbstractBackgroundThe early prediction of adolescent depression recurrence poses a significant challenge in the field. This study aims to investigate and compare the abilities of two psychopathology factors, namely the general psychopathology factor (p) and the specific internalizing factor, in predicting depression recurrence over a 2-year course, as well as identifying remitted depression patients from healthy adolescents. Longitudinal changes of these two factors in different trajectory groups were also tracked to examine their sensitivity to sustained remission and relapse.MethodsWe included 255 baseline-remitted depression patients and a healthy control group (n=255) matched in age, sex, and race, sourced from the Adolescent Brain Cognitive Development Study. The Linear Mixed Model was employed to differentiate between healthy controls and remitted depression patients, predict depression recurrence, and track longitudinal changes over a subsequent 2-year course using thepfactor and the specific internalizing factor respectively.ResultsThepfactor not only effectively discriminated between remitted depression patients and healthy controls, but also robustly predicted the depression recurrence over a subsequent 2-year course. The specific internalizing factor could only differentiate remitted depression patients from healthy controls. Additionally, a noteworthy longitudinal decline of thepfactor in the sustained-remission group was observed.ConclusionsPsychopathology factors serve as the inherent and enduring measurement of long-term mental health aberrations. Longitudinal results indicate that the p factor is more sensitive to respond to sustained remission than the internalizing factor. The ability of the overallpfactor to anticipate depression relapse, unlike the specific internalizing factor, suggests clinical interventions should monitor and mitigate the coincident symptoms across all dimensions to preempt relapse of adolescent depression, rather than an exclusive focus on internalizing symptoms.
Near-Infrared Photothermal Ablation of Biofilms using Protein-Functionalized Gold Nanospheres with a Tunable Temperature Response
Authors: Amarasekara Dhanush L. , Kariyawasam Chathuri S. , Hejny Madison A. , Torgall Veeresh B. , Werfel Thomas A. , Fitzkee Nicholas C. 
Published: August 2023

AbstractTemperature-responsive nanostructures with high antimicrobial efficacy are attractive for therapeutic applications against multi-drug-resistant bacteria. Here, we report temperature-responsive nanospheres (TRNs) that are engineered to undergo self-association and agglomeration above a tunable transition temperature (Tt). Temperature-responsive behavior of the nanoparticles is obtained by functionalizing citrate-capped, spherical gold nanoparticles (AuNPs) with elastin-like polypeptides (ELPs). Using protein design principles, we achieve a broad range of attainable Ttvalues and photothermal conversion efficiencies (η). Two approaches were used to adjust this range: First, by altering the position of the cysteine residue used to attach ELP to the AuNP, we attained a Ttrange from 34-42 °C. Then, functionalizing the AuNP with an additional small globular protein, we were able to extend this range to 34-50 °C. Under near-infrared (NIR) light exposure, all TRNs exhibited reversible agglomeration. Moreover, they showed enhanced photothermal conversion efficiency in their agglomerated state relative to the dispersed state. Despite their spherical shape, TRNs have a photothermal conversion efficiency approaching that of gold nanorods (η= 68±6%), yet unlike nanorods, the synthesis of TRNs requires no cytotoxic compounds. Finally, we tested TRNs for photothermal ablation of biofilms. Above Tt, NIR irradiation of TRNs resulted in a 10,000-fold improvement in killing efficiency compared to untreated controls (p < 0.0001). Below Tt, no enhanced anti-biofilm effect was observed. In conclusion, engineering the interactions between proteins and nanoparticles enables the tunable control of TRNs, resulting in a novel, anti-biofilm nanomaterial with low cytotoxicity.TOC Image
Potent induction of humoral and cellular immunity after bivalent BA.4/5 mRNA vaccination in dialysis patients with and without history of SARS-CoV-2 infection
Authors: Bronder Saskia , Mihm Janine , Urschel Rebecca , Klemis Verena , Schmidt Tina , Marx Stefanie , Abu-Omar Amina , Hielscher Franziska , Guckelmus Candida , Widera Marek , Sester Urban , Sester Martina 
Published: August 2023

AbstractKnowledge on immunogenicity of the bivalent Omicron BA.4/5 vaccine in dialysis patients and the effect of a previous infection is limited. Therefore, vaccine-induced humoral and cellular immunity was analyzed in dialysis patients and immunocompetent controls with and without prior infection.In an observational study, 33 dialysis patients and 58 controls matched for age, sex and prior infection status were recruited. Specific IgG, neutralizing antibody activity and cellular immunity towards the spike-antigen from parental SARS-CoV-2 and Omicron subvariants BA.1, BA.2 and BA.4/5 were analyzed before and 13-18 days after vaccination.The bivalent vaccine led to a significant induction of IgG, neutralizing titers, and specific CD4 and CD8 T-cell levels. Neutralizing activity towards the parental strain was highest, whereas specific T-cell levels towards parental spike and Omicron subvariants did not differ indicating substantial cross-reactivity. Dialysis patients with prior infection had significantly higher spike-specific CD4 T-cell levels with lower CTLA-4 expression compared to infection-naïve patients. When compared to controls, no differences were observed between individuals without prior infection. Among infected individuals, CD4 T-cell levels were higher in dialysis patients and neutralizing antibodies were higher in controls. Vaccination was overall well tolerated in both dialysis patients and controls with significantly less adverse events among dialysis patients.In conclusion, our study did not provide any evidence for impaired immunogenicity of the bivalent Omicron BA.4/5 vaccine in dialysis patients. Unlike in controls, previous infection of patients was even associated with higher levels of spike-specific CD4 T cells, which may reflect prolonged encounter with antigen during infection.Translational statementDialysis patients with uremic immunodeficiency are at increased risk for infectious complications after SARS-CoV-2 infection and have been shown to insufficiently respond towards the first doses of COVID-19 vaccines. Bivalent vaccines are now recommended, although knowledge on immunogenicity and on the effect of a previous infection is limited in this patient group. We show that the bivalent BA.4/5 vaccine was well tolerated and led to a pronounced induction of antibodies, neutralizing antibodies and T cells, which was overall similar in magnitude in non-infected patients and controls. Despite some differences between patients and controls with prior infection, our data do not provide any evidence towards impaired immunity in dialysis patients.
Deletion ofXistupstream sequences alters TAD interactions and leads to defects in Xist coating and expression
Authors: Majumdar S , Bammidi LS , Naik HC , Avinchal  , Baro R , Kalita A , Sundarraj N , Bariha GS , Notani D , Gayen S 
Published: August 2023

AbstractThe topological organization of the genome plays an important role in regulating gene expression. However, the connection between the two remains poorly understood. X-chromosome inactivation is a unique model system to explore the interlink between topologically associated domains (TADs) and gene expression. TADs are largely lost upon X-inactivation, and the inactive-X gets bipartitely reorganized into two large mega domains. However, the X-inactivation center (XIC) harbors two TADs – at the locus of long non-coding RNA Xist (Xist-TAD) and Tsix (Tsix-TAD). Xist is the master regulator of X-inactivation, which coat the inactive-X and facilitates heterochromatinization. Here, we deleted Xist upstream sequences (∼6 kb) near the Xist TAD’s boundary in extraembryonic endoderm stem cells (XEN), which undergo imprinted X-inactivation. This deletion led to the major rearrangement of TADs and affected the expression of genes located within Xist and Tsix TAD, specially the expression of Xist was upregulated, suggesting TADs are essential for proper transcriptional regulation. On the other hand, Xist-upstream deletion on the inactive-X resulted in dispersal of Xist coating and loss of enrichment of repressive chromatin marks on the inactive-X but no effect on X-linked gene silencing. However, we found that autosomal genes were dysregulated in Xist-upstream deleted cells, probably because of misregulation of genes located in Xist and Tsix-TAD, specially Xist. We conclude that Xist upstream sequences are necessary for proper organization of the TADs at the XIC, maintenance of Xist coating/expression and autosomal gene expression.
The Induced Fatigue on Attention Networks of Active and Inactive Individuals Effect of Exercise
Authors: Kayvani Maryam , Kavyani Akram , Soltani Sana 
Published: August 2023

AbstractBackgroundThe relationship between physical activity and cognitive functions is well established, with regular exercise improving cognitive functions. However, there is less clarity surrounding the effect of exercise-induced fatigue on attention network particularly in those with a history of continuous physical activity.AimsThis research was aimed to determine whether exercise-induced fatigue can affect cognitive functions, especially those involved in attentional control (i.e., alerting, orientation, and executive functions) and to identify any differences in attentional control between active and inactive individuals after exercise-induced fatigue.MethodsWe compared the performance of 24 physically active and inactive participants in the Attentional Network Task, which allows for the assessment of the executive, orienting and alerting networks. Under two conditions regarding exercise-induced fatigue (pre-fatigue and post-fatigue), we used sub-maximum aerobic endurance training to induce fatigue to the exhaustion point.ResultsThe results showed that fatiguing exercise improved alertness in both groups; however, the executive control network of the active group improved while the orienting and executive control networks of the inactive group performed worse.ConclusionsDepending on the participants’ degree of physical activity and the particular task used to test each of these attention networks, exercise-induced exhaustion had a different impact on different attention networks.
Projection neurons are necessary for the maintenance of the mouse olfactory circuit
Authors: Sánchez-Guardado Luis , Razavi Peyman , Wang Bo , Callejas-Marín Antuca , Lois Carlos 
Published: August 2023

ABSTRACTThe assembly and maintenance of neural circuits is crucial for proper brain function. Although the assembly of brain circuits has been extensively studied, much less is understood about the mechanisms controlling their maintenance as animals mature. In the olfactory system, the axons of olfactory sensory neurons (OSNs) expressing the same odor receptor converge into discrete synaptic structures of the olfactory bulb (OB) called glomeruli, forming a stereotypic odor map. The OB projection neurons, called mitral and tufted cells (M/Ts), have a single dendrite that branches into a single glomerulus, where they make synapses with OSNs. We used a genetic method to progressively eliminate the vast majority of M/T cells in early postnatal mice, and observed that the assembly of the OB bulb circuits proceeded normally. However, as the animals became adults the apical dendrite of remaining M/Ts grew multiple branches that innervated several glomeruli, and OSNs expressing single odor receptors projected their axons into multiple glomeruli, disrupting the olfactory sensory map. Moreover, ablating the M/Ts in adult animals also resulted in similar structural changes in the projections of remaining M/Ts and axons from OSNs. Interestingly, the ability of these mice to detect odors was relatively preserved despite only having 1-5% of projection neurons transmitting odorant information to the brain, and having highly disrupted circuits in the OB. These results indicate that a reduced number of projection neurons does not affect the normal assembly of the olfactory circuit, but induces structural instability of the olfactory circuitry of adult animals.
Empagliflozin reduces neointimal formation and vascular smooth muscle cell proliferation via the suppression of PDGF-related signaling
Authors: Chen Wei-Jan , Chang Gwo-Jyh , Hsu Yu-Juei , Chen Ying-Hwa 
Published: August 2023

AbstractObjectiveEmerging evidence has documented the beneficial effects of sodium glucose cotransporter 2 (SGLT2) inhibitors on reducing cardiovascular events. Beyond glucose regulation, the mechanisms behind their cardioprotective effects still remained unresolved. This study aims to investigate whether these benefits are mediated by their effects on vascular smooth muscle cell (VSMC) functions.Approach and ResultsTreatment of non-diabetic rats with empagliflozin (a SGLT2 inhibitor) attenuated balloon injury-induced neointimal formation in carotid arteries.In vitro, treatment of rat VSMCs with empagliflozin reduced platelet-derived growth factor (PDGF)-BB-induced proliferation and migration. Moreover, empagliflozin-treated VSMCs did not undergo apoptosis and cytosis. Notably, treating VSMCs with empagliflozinsuppressed the activation of PDGF-related signaling, such as that related to the phosphorylation of PDGF receptor b (PDGF-Rb), Akt, and STAT3. Furthermore, overactivation of PDGF-related signaling attenuated the inhibitory effects of empagliflozin on VSMC proliferation and migration. The relevantin vitrofindings were corroborated in the neointima of empagliflozin-treated rats. The fact that minimal SGLT2 was discovered in rat VSMCs and SGLT2 silencing did not alter the effect of empagliflozin supported the SGLT2-independent effect of empagliflozin on VSMC functions.ConclusionsThis study highlights the crucial role of PDGF-related signaling in mediating the beneficial effects of empagliflozin on VSMC functions and/or neointimal formation, which are independent of its effects on SGLT2 and glucose metabolism.
Robust collection and processing for label-free single voxel proteomics
Authors: Kitata Reta Birhanu , Velickovic Marija , Xu Zhangyang , Zhao Rui , Scholten David , Chu Rosalie K. , Orton Daniel J. , Chrisler William B. , Mathews Jeremy V. , Piehowski Paul D. , Liu Tao , Smith Richard D. , Liu Huiping , Wasserfall Clive H. , Tsai Chia-Feng , Shi Tujin 
Published: August 2023

ABSTRACTWith advanced mass spectrometry (MS)-based proteomics, genome-scale proteome coverage can be achieved from bulk tissues. However, such bulk measurement lacks spatial resolution and obscures important tissue heterogeneity, which make it impossible for proteome mapping of tissue microenvironment. Here we report an integrated wet collection of single tissue voxel and Surfactant-assisted One-Pot voxel processing method termed wcSOP for robust label-free single voxel proteomics. wcSOP capitalizes on buffer droplet-assisted wet collection of single tissue voxel dissected by LCM into the PCR tube cap and MS-compatible surfactant-assisted one-pot voxel processing in the collection cap. This convenient method allows reproducible label-free quantification of ∼900 and ∼4,600 proteins for single voxel from fresh frozen human spleen tissue at 20 μm × 20 μm × 10 μm (close to single cells) and 200 μm × 200 μm × 10 μm (∼100 cells), respectively. 100s-1000s of protein signatures with differential expression levels were identified to be spatially resolved between spleen red and white pulp regions depending on the voxel size. Region-specific signaling pathways were enriched from single voxel proteomics data. Antibody-based CODEX imaging was used to validate label-free MS quantitation for single voxel analysis. The wcSOP-MS method paves the way for routine robust single voxel proteomics and spatial proteomics.
High-throughput generic single-entity sequencing using droplet microfluidics
Authors: Wang Guoping , Zhao Liuyang , Shi Yu , Qu Fuyang , Ding Yanqiang , Liu Weixin , Liu Changan , Luo Gang , Li Meiyi , Bai Xiaowu , Li Luoquan , Ho Yi-Ping , Yu Jun 
Published: August 2023

SummarySingle-cell sequencing has revolutionized our understanding of cellular heterogeneity by providing a micro-level perspective over the past decades. Although heterogeneity is essential for various biological communities, the currently demonstrated platform predominantly focuses on eukaryotic cells without cell walls and their transcriptomics1,2, leaving significant gaps in the study of omics from other single biological entities such as bacteria and viruses. Due to the difficulty of isolating and acquiring their DNA3, contemporary methodologies for the characterization of generic biological entities remain conspicuously constrained, with low throughput4, compromised lysis efficiency5, and highly fragmented genomes6. Herein, we present the Generic Single Entity Sequencing platform (GSE-Seq), which boasts ample versatility, high throughput, and high coverage, and is enabled by an innovative workflow, addressing the critical challenges in single entities sequencing: (1) one-step manufacturing of massive barcodes, (2) degradable hydrogel-basedin situsample processing and whole genome amplification, (3) integrated in-drop library preparation, (4) compatible long-read sequencing. By GSE-Seq, we have achieved a significant milestone by enabling high-throughput, long-read single-entity profiling of dsDNA and ssDNA from single virus sequencing (SV-seq) and single bacteria sequencing (SB-seq) of the human gut and marine sediment for the first time. Notably, our analysis uncovered previously overlooked viral and bacterial dark matter and phage-host interactions. In summary, the presented conceptually new workflow offers a toolbox based on droplet microfluidics to tackle the persistent challenges in high-throughput profiling to generic applications, which hold immense promise for diverse biological entities, especially hard-to-lyse cells.
Machine learning approaches identify chemical features for stage-specific antimalarial compounds
Authors: van Heerden Ashleigh , Turon Gemma , Duran-Frigola Miquel , Pillay Nelisha , Birkholtz Lyn-Marié 
Published: August 2023

ABSTRACTEfficacy data from diverse chemical libraries, screened against the various stages of the malaria parasitePlasmodium falciparum, including asexual blood stage (ABS) parasites and transmissible gametocytes, serves as a valuable reservoir of information on the chemical space of compounds that are either active (or not) against the parasite. We postulated that this data can be mined to define chemical features associated with sole ABS activity and/or those that provide additional life cycle activity profiles like gametocytocidal activity. Additionally, this information could provide chemical features associated with inactive compounds, which could eliminate any future unnecessary screening of similar chemical analogues. Therefore, we aimed to use machine learning to identify the chemical space associated with stage-specific antimalarial activity. We collected data from various chemical libraries that were screened against the asexual (126 374 compounds) and sexual (gametocyte) stages of the parasite (93 941 compounds), calculated the compounds’ molecular fingerprints and trained machine learning models to recognize stage-specific active and inactiv compounds. We were able to build several models that predicts compound activity against ABS and dual-activity against ABS and gametocytes, with Support Vector Machines (SVM) showing superior abilities with high recall (90% and 66%) and low false positive predictions (15% and 1%). This allowed identification of chemical features enriched in active and inactive populations, an important outcome that could be mined for essential chemical features to streamline hit-to-lead optimization strategies of antimalarial candidates. The predictive capabilities of the models held true in diverse chemical spaces, indicating that the ML models are therefore robust and can serve as a prioritization tool to drive and guide phenotypic screening and medicinal chemistry programs.For Table of Contents Graphic Only
Interrogation of single-neuron functional connectivity in the cortex and hippocampus via fast cross-layer all-optical physiology
Authors: Liu Chi , Hao Yuejun , Zhong Yi , Kong Lingjie , Lei Bo 
Published: August 2023

AbstractThe interrogation of functional neural circuits is crucial for uncovering how the brain works during diverse behaviors. Multi-plane neurophysiological measurement systems with high temporal resolution are indispensable, especially for dissecting inter-layer functional connectivity. Here, we develop a cross-layer all-optical physiology system (CLAOP) that enables the simultaneous recording and manipulation of single-neuron activities in multiple neuronal layers, with axial intervals as large as 530 μm, at high temporal resolutions. Based on spatiotemporal multiplexing, our system enables all-optical analysis with a high frame rate up to 396 Hz and minimal time delay in inter-layer imaging and photostimulation, in both the mouse cortex and hippocampus in vivo. Combined with behavioral experiments, CLAOP provides all-optical evidence linking behavioral responses to neuronal connectivity in the primary visual cortex (V1) of live mice. Furthermore, we demonstrate that CLAOP can perturb the activity response of inter-layer cortical neurons to sensory stimuli according to their functional signatures. Overall, CLAOP provides an all-optical approach for mapping inter-layer connectivity at the single-neuron level and for modifying neuronal responses in behaving animals.