bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-intensity focused ultrasound in treatment of primary breast cancer: a systematic review and meta-analysis
Authors: Alikarami Sogol , Harandi Hamid , Jahanshahi Ali , Zakavi Seyed Sina , Frounchi Negin , Mahalleh Mehrdad , Momtazmanesh Sara 
Published: September 2024

AbstractsBackgroundIn recent years, the tumor management strategies have focused on less invasive methods, aiming to yield optimal efficacy while minimizing further complications and enhancing the overall outcome of patients. High-intensity focused ultrasound (HIFU), a known thermal ablative technique, has shown promising results in breast cancer treatment. Therefore, we performed this systematic review and meta-analysis to assess the clinical, histopathologic, immunologic, and radiologic outcomes of HIFU ablative therapy and its complications in patients with primary breast cancer.MethodsWe searched PubMed and Scopus databases to identify the eligible articles. Data extraction was conducted by two independent authors. A random effect model was employed to pool the proportion of remaining tumor after HIFU therapy in breast cancer. Pooled CD4/CD8 ratio mean difference between HIFU and radical mastectomy was, measured using a fixed-effect model.ResultsWe included 26 studies and 677 participants in the systematic review. Tumor necrosis rates varied, with 4 studies reporting less than 50% complete necrosis and 5 more than 50%. Two studies observed HIFU-induced disturbances in microvasculature of the targeted tissue. Six noted no contrast enhancement in successfully treated areas, two observed a thin rim indicating necrosis or fibrosis, and four reported a persistent enhancement in MRI images associated with a residual viable tumor. The weighted proportion of patients with residual tumor was 58.45 (95% C: 45.48 – 71.42). The CD4/CD8 ratio was higher in the HIFU group, with a weighted mean difference of 0.6 (95% CI: 0.41 – 0.78). The most prevalent side effects were pain (47.14%) and skin burn (2.59%).ConclusionsHIFU is a relatively safe procedure for treatment of breast cancer as an independent or conjugated therapy and its effectiveness is promising regarding histopathological response, immunological reactivity, and vascular damage in the targeted area.
ATP-dependent remodeling of chromatin condensates uncovers distinct mesoscale effects of two remodelers
Authors: Moore Camille , Wong Emily , Kaur Upneet , Chio Un Seng , Zhou Ziling , Ostrowski Megan , Wu Ke , Irkliyenko Iryna , Wang Sean , Ramani Vijay , Narlikar Geeta J 
Published: September 2024

AbstractATP-dependent chromatin remodeling enzymes mobilize nucleosomes, but how such mobilization affects chromatin condensation is unclear. Here, we investigate effects of two major remodelers, ACF and RSC using chromatin condensates and single-molecule footprinting. We find that both remodelers inhibit the formation of condensed chromatin. However, the remodelers have distinct effects on pre-formed chromatin condensates. ACF spaces nucleosomes without de-condensing the chromatin, explaining how ACF maintains nucleosome organization in transcriptionally repressed genomic regions. In contrast, RSC catalyzes ATP-dependent de-condensation of chromatin. Surprisingly, RSC also drives micron-scale movements of entire condensates. These newly uncovered activities of RSC explain its central role in transcriptional activation. The biological importance of remodelers may thus reflect both their effects on nucleosome mobilization and the corresponding consequences on chromatin dynamics at the mesoscale.
Curriculum Learning: sequential acquisition of task complexity enhances neuronal discriminability
Authors: Shujah Maria , Joshi Suyash , Nakamura Mari , Barkat Tania Rinaldi 
Published: September 2024

AbstractCurriculum Learning (CL) is a strategy where concepts with increasing complexity are acquired sequentially. Despite its widespread application, its putative neural mechanisms are poorly understood. In this study, using a multi-staged Go/No-Go auditory discrimination paradigm for mice, we show that CL improves and accelerates learning in a unidirectional way. By combining behavioral data within vivoelectrophysiological recordings of the auditory cortex, we demonstrate that neuronal discriminability is enhanced with sequential training. This improvement suggests that CL involves a convergence of common discriminable features in the auditory stimuli shared across tasks of different complexity. Our findings uncover specific properties of CL at the level of neuronal discriminability, distinguishing it from other forms of learning strategies.
Human CCR4-NOT globally regulates gene expression and is a novel silencer of retrotransposon activation
Authors: Kulkarni Shardul , Morrissey Alexis , Sebastian Aswathy , Giardine Belinda , Smith Courtney , Akinniyi Oluwasegun T. , Keller Cheryl A. , Arnaoutov Alexei , Albert Istvan , Mahony Shaun , Reese Joseph C. 
Published: September 2024

AbstractCCR4-NOT regulates multiple steps in gene regulation and has been well studied in budding yeast, but much less is known about the human complex. Auxin-induced degradation was used to rapidly deplete the scaffold subunit CNOT1, and CNOT4, to characterize the functions of human CCR4-NOT in gene regulation. Depleting CNOT1 increased RNA levels and caused a widespread decrease in RNA decay. In contrast, CNOT4 depletion only modestly changed steady-state RNA levels and, surprisingly, led to a global acceleration in mRNA decay. Further, depleting either subunit resulted in a global increase in RNA synthesis. In contrast to most of the genome, the transcription of KRAB-Zinc-Finger-protein (KZNFs) genes, especially those on chromosome 19, was repressed. KZNFs are transcriptional repressors of retrotransposable elements (rTEs), and consistent with the decreased KZNFs expression, rTEs, mainly Long Interspersed Nuclear Elements (LINEs), were activated. These data establish CCR4-NOT as a global regulator of gene expression and a novel silencer of rTEs.
Shox2 is necessary for normal thalamic spindle function
Authors: Febbo Isabella , Maroteaux Matthieu , Yu Diankun , Warkins Valerie , Martinez LA , Anderson AE , Galazo MJ , Schrader LA 
Published: September 2024

AbstractThe cellular identity of thalamocortical neurons (TCNs), namely their firing properties, dictates brain-wide activity patterns, such as sleep spindles. Transcription factors are critical to the determination of cellular identity. Previously, we discovered that a subset of TCNs express the transcription factor, Shox2, and, in a globalShox2KO, established that TCNs within the anterior nucleus of the thalamus rely on the expression ofShox2to regulate key ion channels that are necessary to maintain their firing properties. From this, we hypothesized thatShox2expression, through the regulation of firing properties of TCNs, is critical for the thalamocortical circuit to generate spindle oscillations. We exploited the somatosensory thalamocortical circuit to investigate this by creating a primary somatosensory thalamus (VB)Shox2knockdown mouse model. We delivered Cre into the VB of P21 Shox2fl/flmice using viral infection and comparedin vitro, patch-clamp recordings fromShox2+andShox2knockdown TCNs, finding thatShox2expression is indeed critical to maintain burst and tonic firing properties of VB TCNs. Since Shox2 is important developmentally and firing from TCNs to cortex during development structures the circuit, we performed ultrasound-guided P3 injections at P3 to generate an early-stage, Shox2 VB knockdown, but found no changes in the layer four, barrel map (VB cortical target). Despite this, Shox2 knockdown mice exhibit reduced sleep-spindle EEG density. Further, key behaviors associated with spindles and proper VB thalamic function—memory consolidation and somatosensory perception—are significantly impaired. These results indicate that the impact on spindle function is likely due to cell autonomous changes to TCNs rather than circuit changes, confirming our hypothesis thatShox2is necessary for normal thalamic spindle function and implicating a potential role forShox2in autism and schizophrenia pathologies.
Small mammals in biodiversity hotspot harbor viruses of epidemic potential
Authors: Feng Yun , Kuang Guopeng , Pan Yuanfei , Wang Jing , Yang Weihong , Wu Wei-chen , Pan Hong , Wang Juan , Han Xi , Yang Lifen , Xin Gen-yang , Shan Yong-tao , Gou Qin-yu , Liu Xue , Guo Deyin , Liang Guodong , Holmes Edward C. , Gao Zihou , Shi Mang 
Published: September 2024

ABSTRACTMetagenomic sequencing has transformed our understanding of viral diversity in wildlife and its threat to human health. Despite this progress, many studies have lacked systematic and ecologically informed sampling, which has left numerous potentially emergent viruses undiscovered, and the drivers of their ecology and evolution poorly understood. We conducted an extensive analysis of viruses in the lung, spleen, and gut of 1,688 animals from 38 mammalian species across 428 sites in Yunnan, China—a hotspot for zoonotic diseases. We identified 162 mammalian viral species, including 102 novel species and 24 posing potential risks to humans due to their relationships with known pathogens associated with serious diseases and their ability to cross major host species barriers. Our findings offer an in-depth view of virus organotropism, cross-species transmission, host sharing patterns, and the ecological factors influencing viral evolution, all of which are critical for anticipating and mitigating future zoonotic outbreaks.
Effects Of Extrinsic Reward Based Skill Learning On Motor Plasticity
Authors: Yadav Goldy , Vassiliadis Pierre , Dubuc Cecile , Hummel Friedhelm C. , Derosiere Gerard , Duque Julie 
Published: September 2024

ABSTRACTHuman motor skill acquisition is improved by performance feedback and coupling such feedback with extrinsic reward (such as money) can enhance skill learning. However, the neurophysiology underlying such behavioral effect is unclear. To bridge this gap, we assessed the effects of reward on multiple forms of motor plasticity during skill learning. Sixty-five healthy participants divided in three groups performed a pinch-grip skill task with sensory feedback only, sensory and reinforcement feedback or both feedback coupled with an extrinsic monetary reward during skill training. To probe motor plasticity, we applied transcranial magnetic stimulation on the left primary motor cortex at rest before, during and after training in the three groups. We evaluated the amplitude and variability of corticospinal output, GABA-ergic short-intracortical inhibition and use-dependent plasticity before training and at two time points during and after training. At the behavioral level, monetary reward accelerated skill learning. In parallel, corticospinal output became less variable early on during training in the presence of extrinsic reward. Interestingly, this effect was particularly pronounced for participants who were more sensitive to reward, as evaluated in an independent questionnaire. Other measures of motor excitability remained comparable across groups. These findings highlight that a mechanism underlying the benefit of reward on motor skill learning is the fine tuning of early-training resting-state corticospinal variability.SIGNIFICANCE STATEMENTSkill acquisition is enhanced in the presence of reward. Despite its potential clinical relevance for motor rehabilitation, the underlying neurophysiological mechanisms remain largely unexplored. Specifically, whether reward affects the plasticity of motor cortex in the context of skill learning is unclear. We show that reward reduces the variability of corticospinal output at an early stage during training and that this effect correlates with individual sensitivity to reward. Our results suggest that a key mechanism underlying the beneficial effect of reward on motor skill learning may be an increase in the stability of motor output in response to training during early stages of skill learning.
Astrocyte ezrin defines resilience to stress-induced depressive behaviours in mice
Authors: Lin Si-Si , Zhou Bin , Liu Si-Le , Ren Xing-Ying , Guo Jing , Tong Jing-Lin , Chen Bin-Jie , Jiang Ruo-Tian , Semyanov Alexey , Yi Chenju , Niu Jianqin , Illes Peter , Li Baoman , Tang Yong , Verkhratsky Alexei 
Published: September 2024

AbstractAstrocyte atrophy is the main histopathological hallmark of major depressive disorder (MDD) in humans and in animal models of depression. Here we demonstrated that manipulating with ezrin expression specifically in astrocytes significantly increases the resilience of mice to chronic unpredictable mild stress (CUMS). Overexpression of ezrin in astrocytes from prefrontal cortex (PFC) rescued depressive-like behaviours induced by CUMS, whereas down-regulation of ezrin in astrocytes from PFC increased mice susceptibility to CUMS and promoted depressive-like behaviours. These behavioural changes correlated with astrocytic morphology. Astrocytes from PFC of mice sensitive to CUMS demonstrated significant atrophy; similar atrophy was found in astrocytes from animals with down-regulated ezrin expression. To the contrary morphology remains unchanged astrocytes in animals resistant to CUMS and in animals with astrocytic overexpression of ezrin. Morphological changes also correlated with ezrin immunoreactivity which was low in mice with depressive-like behaviours and high in mice resistant to stress. We conclude that Ezrin-dependent morphological remodelling of astrocytes defines the sensitivity of mice to stress: high ezrin expression renders them stress resilient, whereas low ezrin expression promotes depressive-like behaviour in response to chronic stress.
A High Frequency of Detection of Recombinant Koala Retrovirus (recKoRV) in Victorian Koalas Suggests Historic Integration of KoRV
Authors: Zheng Louize , Legione Alistair R 
Published: September 2024

AbstractRecombinant koala retrovirus (recKoRV) is a recently discovered variant of koala retrovirus (KoRV), which likely emerged due to the insertion of another retrovirus (likely Phascolarctos endogenous retrovirus) into the backbone of KoRV. KoRV endogenisation was thought to be ongoing in Victoria based on the low prevalence of the virus based on molecular detection of thepolgene, however recKoRV was not incorporated into the previous KoRV diagnostic test results. In this study, a new 5’-region-based PCR assay was developed, capable of detecting both intact KoRV and recKoRV. Using this assay, 319 archived DNA samples from 287 Victorian koalas were retested to investigate KoRV endogenisation. We found a 98.3% (282/287) of these samples were positive for the KoRV-5’ fragment, the majority of which were KoRV-polnegative (222/287) on prior testing. Our findings demonstrate extensive KoRV integration into the Victorian koala populations, suggestive of a historic presence of KoRV in Victorian koalas. This finding makes biological sense relative to the translocation history of Victorian koalas, compared to the prior paradigm of ongoing endogenisation, and provides new epidemiological and practical management implications.
The two-component system ArlRS is essential for wall teichoic acid glycoswitching inStaphylococcus aureus
Authors: Kuijk Marieke M. , Tusveld Emma , Lehmann Esther , van Dalen Rob , Lasa Iñigo , Ingmer Hanne , Pannekoek Yvonne , van Sorge Nina M. 
Published: September 2024

AbstractStaphylococcus aureusis among the leading causes of hospital-acquired infections. Critical toS. aureusbiology and pathogenesis are the cell wall-anchored glycopolymers wall teichoic acids (WTA). Approximately one-third ofS. aureusisolates decorates WTA with a mixture of α1,4- and β1,4-N-acetylglucosamine (GlcNAc), which requires the dedicated glycosyltransferases TarM and TarS, respectively. Environmental conditions, such as high salt concentrations, affect the abundance and ratio of α1,4- and β1,4-GlcNAc WTA decorations, thereby impacting biological properties such as antibody binding and phage infection. To identify regulatory mechanisms underlying WTA glycoswitching, we screened 1,920S. aureusmutants (Nebraska Transposon Mutant Library) by immunoblotting for differential expression of WTA-linked α1,4- or β1,4-GlcNAc using specific monoclonal antibody Fab fragments. Three two-component systems (TCS), GraRS, ArlRS, and AgrCA, were among the 230 potential hits. Using isogenic TCS mutants, we demonstrated that ArlRS is essential for WTA β1,4-GlcNAc decoration through regulation oftarMbut nottarS. ArlRS regulatedtarMexpression through the transcriptional regulator MgrA, which was responsive to Mg2+, but not Na+. Importantly, ArlRS-mediated regulation of WTA glycosylation affectedS. aureusinteraction with the innate receptor langerin and lysis by β1,4-GlcNAc-dependent phages. Since WTA represents a promising target for future immune-based treatments and vaccines, our findings provide important insight to align targeting strategies with theS. aureusWTA glycosylation patterns during infection.ImportanceStaphylococcus aureusis a common colonizer of mucosal surfaces, but is also a frequent cause of severe infections in humans. Development of antibiotic resistance complicates treatment ofS. aureusinfections, increasing the need for antibiotic alternatives such as vaccines and therapies with bacterial viruses also known as phages. Wall teichoic acids (WTA) are abundantly-expressed glycosylated structures of theS. aureuscell wall that have gained attention as a promising target for new treatments. Importantly, WTA glycosylation patterns show variation depending on environmental conditions, thereby impacting phage binding and interaction with host factors, such as antibodies and innate pattern-recognition receptors. Here, we show that the two-component system ArlRS through its effector MgrA is involved in regulation of WTA glycosylation by responding to environmental changes in Mg2+concentration. These findings may support the design of new treatment strategies that target WTA glycosylation patterns ofS. aureusduring infection.
Disrupted development of sensory systems and the cerebellum in a zebrafishebf3amutant
Authors: Dang Nghi D. P. , Conklin Claire L. , Truong Thinh Q. , Vivian Michael D. , Wang Jun , Thomas Holly R. , Parant John M. , Yeo Nan Cher , Thyme Summer B. 
Published: September 2024

AbstractMutations in the transcription factorEBF3results in a neurodevelopmental disorder, and studies in animal models indicate that it has a critical role in neuronal differentiation. The molecular pathways and neuron types disrupted by its loss, however, have not been thoroughly investigated. Nor have the outcomes of these changes on behavior and brain activity. Here, we generated and characterized a zebrafishebf3aloss-of-function mutant. We discovered morphological and neural phenotypes, including an overall smaller brain size, particularly in the hypothalamus, cerebellum, and hindbrain. Brain function was also compromised, with activity strongly increased in the cerebellum and abnormal behavior at baseline and in response to visual and acoustic stimuli. From RNA-sequencing of developing larvae, notable changes included significant downregulation of genes that mark olfactory sensory neurons, the lateral line, and cerebellar Purkinje neurons. This study sets the stage for determining which downstream pathways underlie the emergence of the observed phenotypes and establishes multiple strong phenotypes that could form the basis of a drug screen.
A cell and transcriptome atlas of the human arterial vasculature
Authors: Zhao Quanyi , Pedroza Albert , Sharma Disha , Gu Wenduo , Dalal Alex , Weldy Chad , Jackson William , Li Daniel Yuhang , Ryan Yana , Nguyen Trieu , Shad Rohan , Palmisano Brian T. , Monteiro João P. , Worssam Matthew , Berezwitz Alexa , Iyer Meghana , Shi Huitong , Kundu Ramendra , Limbu Lasemahang , Kim Juyong Brian , Kundaje Anshul , Fischbein Michael , Wirka Robert , Quertermous Thomas , Cheng Paul 
Published: September 2024

SUMMARYVascular beds show different propensities for different vascular pathologies, yet mechanisms explaining these fundamental differences remain unknown. We sought to build a transcriptomic, cellular, and spatial atlas of human arterial cells across multiple different arterial segments to understand this phenomenon. We found significant cell type-specific segmental heterogeneity. Determinants of arterial identity are predominantly encoded in fibroblasts and smooth muscle cells, and their differentially expressed genes are particularly enriched for vascular disease-associated loci and genes. Adventitial fibroblast-specific heterogeneity in gene expression coincides with numerous vascular disease risk genes, suggesting a previously unrecognized role for this cell type in disease risk. Adult arterial cells from different segments cluster not by anatomical proximity but by embryonic origin, with differentially regulated genes heavily influenced by developmental master regulators. Non-coding transcriptomes across arterial cells contain extensive variation in lnc-RNAs expressed in cell type- and segment-specific patterns, rivaling heterogeneity in protein coding transcriptomes, and show enrichment for non-coding genetic signals for vascular diseases.
Absence of biofilm adhesin proteins changes surface attachment and cell strategy forDesulfovibrio vulgarisHildenborough
Authors: Pete Pickens C. , Wang Dongyu , Pan Chongle , De León Kara B. 
Published: September 2024

AbstractUbiquitous in nature, biofilms provide stability in a fluctuating environment and provide protection from stressors. Biofilms formed in industrial processes are exceedingly problematic and costly. While biofilms of sulfate-reducing bacteria in the environment are often beneficial because of their capacity to remove toxic metals from water, in industrial pipelines, these biofilms cause a major economic impact due to their involvement in metal and concrete corrosion. The mechanisms by which biofilms of sulfate-reducing bacteria form, however, is not well understood. Our previous work identified two proteins, named by their gene loci DVU1012 and DVU1545, as adhesins in the model sulfate-reducing bacterium,Desulfovibrio vulgarisHildenborough. Both proteins are localized to the cell surface and the presence of at least one of the proteins, with either being sufficient, is necessary for biofilm formation to occur. In this study, differences in cell attachment and early biofilm formation in single deletion mutants of these adhesins were identified. Cells lacking DVU1012 had a different attachment strategy from wild-type and ΔDVU1545 cells, more often attaching as single cells than aggregates, which indicated that DVU1012 was more important for cell-to-cell attachment. ΔDVU1545 cells had increased cell attachment compared to wild-type cells when grown in static cultures. To date, comparisons of theD. vulgarisHildenborough have been made to the large adhesion protein (Lap) system in environmental pseudomonads. Yet, we and others have shown distinct mechanistic differences in the systems. We propose to name these proteins inD. vulgarisHildenborough biofilm formation system (Bfs) to facilitate comparisons.ImportanceBiofilms of sulfate-reducing bacteria contribute to biocorrosion, costing the U.S. hundreds of millions of dollars annually. In contrast, these biofilms can be used to bioremediate toxic heavy metals and to generate bioelectricity. As one of the most abundant groups of organisms on Earth, it is pertinent to better understand mechanistically how the biofilms of sulfate-reducing bacteria form so we may use this knowledge to help in efforts to mitigate biocorrosion, to promote bioremediation, and to produce clean energy. This study shows that the absence of either one of two biofilm adhesins impacts surface colonization by a sulfate-reducing bacterium, and that these two biofilm adhesins differ in their effect on cell attachment compared to other well-documented bacteria such asPseudomonasspecies.