bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abandoning the Quadrupole for Mass Spectrometry Fragmentation Analysis: Towards 1,000 Hz Speeds with 100% Ion Utilization Using High Resolution Ion Mobility Precursor Isolation
Authors: DeBord Daniel , Rorrer Leonard C. , Deng Liulin , Strathmann Frederick G. 
Published: October 2024

ABSTRACTIn today’s fast-evolving landscape of omics research, tandem mass spectrometry has become a cornerstone for uncovering the complexities of biological systems. Yet, despite its essential role, the technology remains bound by the inherent limitations of quadrupole filters, which throw away up to 99% of the useful ion signal and caps the speed at which fragmentation data can be generated. These deficiencies often force compromises in data depth and accuracy, hindering breakthroughs that tie genomics, proteomics, and metabolomics together. A new technology is poised to break through these performance barriers, unlocking unprecedented capabilities in precision, sensitivity and throughput. This step-change in how mass spectrometry fragmentation analysis is performed will reshape the future of scientific discovery, pushing the boundaries of what’s possible. The solution is high resolution ion mobility (HRIM), which offers a means to quickly and efficiently isolate ions prior to fragmentation and detection by a high resolution mass spectrometer (HRMS) while also resolving challenging isomeric and isobaric compounds that lead to chimeric MS/MS spectra. HRIM isolates ions in time as a result of a high speed separation rather than acting as a filter that discards ion signal like the pervasive quadrupole mass analyzer, allowing higher sensitivity analysis to be achieved. Also, since HRIM eliminates the need to hop or sweep electronics control parameters, as is the case with a quadrupole, fragmentation spectral generation can occur at a much faster rate, upwards of 500 Hz. This whitepaper describes an IM/MS methodology first contemplated over twenty years ago and today being positioned as the fastest method for high resolution fragmentation analysis. Revisiting this concept using the latest generation ion mobility technology based on structures for lossless ion manipulation (SLIM), which is the only HRIM technology that delivers similar resolution and range of analysis as a quadrupole, realizes the full potential of this approach to deliver benefits in both speed and sensitivity for high performance MS/MS measurements. This new way of achieving ion fragmentation in complex samples is set to revolutionize the mass spectrometry space, starting in the growing field of proteomics where all researchers are seeking faster methods to achieve more comprehensive proteomic coverage. Due to the advantages of HRIM physics, we predict this will set the bar for high throughput -omics within the coming years and will eventually be as ubiquitous as the quadrupole is today.
High Prevalence of Latent Tuberculosis Infection among Persons Deprived of Liberty in a Malaysian Prison
Authors: Zhang Lu , Saifi Rumana , Kamarulzaman Adeeba , Ahmad Ahsan , Dhaliwal Sangeeth , Mohd Yukhi Saidatul Hanida , Ibrahim Nor Akma , Koh Hui Moon , Altice Frederick L. , Shenoi Sheela V. 
Published: October 2024

AbstractRising tuberculosis incidence and mortality necessitate enhanced attention to prevention in neglected high-risk venues like correctional facilities. We sought to identify prevalence and correlates of latent TB infection (LTBI) in Malaysia’s largest prison. From October 2019 to January 2023, people deprived of liberty (PDL) entering Kajang Prison underwent tuberculin skin testing, sputum examination, chest X-ray, and blood tests for HIV, HCV, and C-reactive protein (CRP); PDL with active tuberculosis were excluded. Multivariable logistic regression identified independent correlates of LTBI. Among 601 men without tuberculosis, median age was 42 (IQR 36-50) years with high prevalences of HIV (8.8%) and HCV (43.4%). LTBI prevalence was 68.2% (95%CI[64.4%-71.8%]); independent risk factors included opioid use disorder (OUD, AOR=1.95; 95%CI[1.25-3.05]), pre-incarceration homelessness (AOR=1.89; 95%CI[1.13-2.50]), and HCV (AOR=1.68; 95%CI[1.13-2.50]). Pre-incarceration cannabis use (AOR=0.69; 95%CI[0.39-0.96]) was negatively associated with LTBI, which was also found in people with HIV (AOR=0.10; 95%CI[0.01-0.51]). Among people without HIV, having OUD (AOR=2.32; 95%CI[1.48-3.68]), HCV (AOR=1.64; 95%CI[1.09-2.48]) and CRP ≥5mg/ml (AOR=1.90; 95%CI[1.04-3.65]) were independently associated with LTBI, while methamphetamine use reduced odds of LTBI (AOR=0.58; 95%CI[0.33-0.98]). LTBI prevalence in Malaysia’s largest prison was high, highlighting the need for routine screening and implementation of TB preventive therapy in high-risk settings like prisons.
Enrichment of spermatogonial stem cells and staging of the testis cycle in a dasyurid marsupial, the fat-tailed dunnart
Authors: Tarulli Gerard A. , Tatt Patrick R.S. , Howlett Rhys , Ord Sara , Shapiro Beth , Frankenberg Stephen R. , Pask Andrew J. 
Published: October 2024

AbstractThere is increasing interest in use of marsupial models in research, for use in next-generation conservation by improving fitness through genetic modification, and in de-extinction efforts. Specifically this includes dasyurid marsupials such as the Thylacine, Tasmanian devil, quolls and the small rodent-like dunnarts. Technologies for generating genetically modified Australian marsupials remains to be established. Given the need to advance research in this space, the fat-tailed dunnart (Sminthopsis crassicaudata) is being established as a model for marsupial spermatogonial stem cell isolation, modification and testicular transplantation. This species is small (60-90mm body size), polyovulatory (8-12 pups per birth), and can breed in standard rodent facilities when housed in a 12:12 light cycle. To develop the fat tailed dunnart as a model for next-generation marsupial conservation, this study aimed to enrich dunnart spermatogonial stem cells from whole testis digestions using a fluorescent dye technology and fluorescence-activated cell sorting. This approach is not dependent on antibodies or genetic reporter animals that are limiting factors when performing cell sorting on species separated from human and mouse by large evolutionary timescales. This study also assessed development of spermatogonia and spermatogenesis in the fat-tailed dunnart, by making the first definition of the cycle of the seminiferous epithelium in any dasyurid. Overall, this is the first detailed study to assess the cycle of dasyurid spermatogenesis and provides a valuable method to enrich marsupial spermatogonial stem cells for cellular, functional and molecular analysis.
Dynamic Insights into Hsp90 Inhibitor Binding: Uncovering Intermediate States and Conformational Plasticity
Authors: Sahil Mohammad , Koneru Jaya Krishna , Mondal Jagannath 
Published: October 2024

AbstractHeat shock protein 90 (Hsp90) is a vital molecular chaperone involved in protein folding, stabilization, and activation, making it a key target in cancer therapy. Tar-geting the N-terminal domain of Hsp90 (N-Hsp90) has emerged as a potential strategy for developing anticancer therapies due to its involvement in the folding and function of oncoproteins. However, the precise molecular details of how inhibitors bind to N-Hsp90 remain elusive due to inherent conformational plasticity involvingloop-inandloop-outstates of loop-4 (L4). In this work, we utilized unbiased molecular dynamics (MD) simulations coupled with Markov state modeling (MSM) and machine learning techniques to investigate the binding dynamics of the inhibitor Geldanamycin (GDM). Our findings reveal a complex two-stage binding mechanism involving the formation of a non-native intermediate state prior to the final bound state. We demonstrate that GDM binding predominantly stabilizes theloop-outconformation of N-Hsp90, chal-lenging prior beliefs and suggesting thatbothconformational selection and induced fit mechanisms are involved. Through a detailed residue-level analysis using Random For-est based ML classifiers, we quantify the relative contributions of these mechanisms, highlighting the dynamic interplay between Hsp90’s conformational states during in-hibitor binding. These findings enhance our understanding of Hsp90’s conformational plasticity and could inform the design of more effective Hsp90 inhibitors.
Mechanism of Interaction Between the Transactivation Domain of N-MYC and the DNA-Binding Surface of TFIIIC5
Authors: Leen Eoin , Yeoh Sharon , Sahak Eka , Mitchell Ellie , Wildsmith Gemma , Batchelor Matthew , Calabrese Antonio N , Büchel Gabriele , Bayliss Richard 
Published: October 2024

ABSTRACTN-myc is a member of the myc family of transcription factors, which are powerful drivers of cellular growth and consequently, important oncoproteins. N-myc interacts with many factors and complexes to affect transcription. One such complex is the RNA Polymerase III assembly factor, TFIIIC, a six-member complex that is essential for the transcription of small, structured RNA. TFIIIC and N-myc mutually restrict each other’s chromatin association, and their complex contributes to quality control in mRNA transcription. We previously demonstrated that the largely intrinsically disordered transactivation domain of N-myc interacts directly with a sub-complex of TFIIIC, τA. Structural studies by others show that DNA binding of τA is largely mediated by TFIIIC3, which suggests that TFIIIC5 is at most a secondary binding site for DNA. Here we identified the DNA binding domain of TFIIIC5 as a key binding site for N-myc. We used an integrated approach combining NMR, HDX mass spectrometry, pull-downs and biophysical assays to elucidate the molecular basis of the interaction. Two sequences in the transactivation domain of N-myc bind to the DNA binding interface of TFIIIC5. AlphaFold modelling predicts a high-confidence binding mode for the higher affinity N-myc motif that overlaps with the predicted intramolecular binding site of the C-terminal acidic plug of TFIIIC5, removal of which enhances the binding of N-myc. The same two motifs in N-myc also interact with Aurora-A kinase, which competes with N-myc for TFIIIC binding during S-phase. This model elucidates how the N-myc:TFIIIC5 interaction competes with other interactions, providing a basis for their mutual censoring function and regulation.GRAPHICAL ABSTRACT
Modelling rate-independent damping in insect exoskeleta via singular integral operators
Authors: Pons Arion 
Published: October 2024

AbstractIn insect locomotion, the transmission of energy from muscles to motion is a process within which there are many sources of dissipation. One significant but understudied source is the structural damping within the insect exoskeleton itself: the thorax and limbs. Experimental evidence suggests that exoskeletal damping shows frequency (or, rate) independence, but investigation into its nature and implications has been hampered by a lack methods for simulating the time-domain behaviour of this damping. Here, synergising and extending results across applied mathematics and seismic analysis, we provide these methods. We show that existing models of exoskeletal rate-independent damping are equivalent to an important singular integral in time: the Hilbert transform. However, these models are strongly noncausal, violating the directionality of time. We derive the unique causal analogue of these existing exoskeletal damping models, as well as an accessible approximation to them, as Hadamard finite-part integrals in time, and provide methods for simulating them. These methods are demonstrated on several current problems in insect biomechanics. Finally, we demonstrate, for the first time, that existing rate-independent damping models are not strictly dissipative: in certain circumstances they are capable of generating negative power without apparently storing energy, likely violating conservation of energy. This work resolves a key methodological impasse in the understanding of insect exoskeletal dynamics and offers new insights into the micro-structural origins of rate-independent damping as well as the directions required in order to resolve violations of causality and the conservation of energy in existing models.
Relationship as resource or burden? Associations of attachment style, relationship quality and dyadic coping with acute psychosocial stress in the presence of the romantic partner
Authors: Gallistl Mathilde , Hamann Johanna , Croy Ilona , Vrticka Pascal , Engert Veronika 
Published: October 2024

AbstractStress is a wide-spread phenomenon and associated with various detrimental health effects. A significant resource for stress buffering is social support. How social support is perceived, however, depends on a multitude of individual and interindividual factors. This study aimed to explore the stress-reducing properties of relationship-inherent variables. We investigated the association of attachment style, relationship quality and dyadic coping, with subjective and physiological stress responses to a psychosocial laboratory stressor in romantic partners. Seventy-nine couples participated, with one partner ("target") undergoing the Trier Social Stress Test and the other ("observer") observing the situation. Besides examining the role of targets’ relationship variables, we also assessed the link between observers’ relationship variables and targets’ stress reactivity. We found that both targets’ and observers’ insecure-avoidant attachment scores were associated with targets’ stress reactivity. In detail, while targets’ insecure-avoidant attachment scores were negatively associated with targets’ subjective stress experience, observers’ insecure-avoidant attachment scores were positively associated with targets’ heart rate reactivity. Further, higher insecure-avoidant attachment scores linked to lower psycho-endocrine covariance, i.e., a lower accordance between self-reported and cortisol stress responding. On the one hand, these data may suggest that under stress, insecure-avoidantly attached individuals suppress their experience of stress to preserve a sense of independence as part of their deactivating attachment strategy. The presence of an insecure-avoidantly attached partner during a stressful experience, on the other hand, seems to be a stressor rather than a source of support. Long-term, an insecure-avoidantly attached partner may negatively impact an individual’s stress-related health and wellbeing.Highlights- In a situation in which one romantic partner experienced stress (“target”) while being ob- served by their partner (“observer”), insecure-avoidant attachment of both predicted the tar- get’s stress response- Targets’ insecure-avoidant attachment was associated with lower subjective stress in the tar- gets- Observers’ insecure-avoidant attachment was related to higher heart rate reactivity in the targets- Insecure-avoidant attachment was associated with lower psycho-endocrine covariance
Vicarious Somatotopic Maps Tile Visual Cortex
Authors: Hedger Nicholas , Naselaris Thomas , Kay Kendrick , Knapen Tomas 
Published: October 2024

AbstractOur sensory systems work together to generate a cohesive experience of the world around us. Watching others being touched activates brain areas representing our own sense of touch: the visual system recruits touch-related computations to simulate bodily consequences of visual inputs. One long-standing question is how the brain implements this interface between visual and somatosensory representations. To address this question, we developed a method to simultaneously map somatosensory body part tuning and visual field tuning throughout the brain. Applying this method on ongoing co-activations during rest resulted in detailed maps of the body-part tuning in the brain’s endogenous somatotopic network. During movie watching, somatotopic tuning explains responses throughout the entire dorsolateral visual system, revealing an array of somatotopic body maps that tile the cortical surface. The tuning of these maps aligned with those of visual maps, and predicted both preferences for visual field locations and the visual-category preferences for body parts. These results reveal a mode of brain organization in which aligned visual-somatosensory topographic maps connect visual and bodily reference frames. This cross-modal interface is ideally situated to translate raw sensory impressions into more abstract formats useful for action, social cognition, and semantic processing.
Pancreatic islet α cells regulate microtubule stability in neighboring β cells to tune insulin secretion and induce functional heterogeneity in individual mouse and human islets
Authors: Ho Kung-Hsien , Barmaver Syed N. , Hu Ruiying , Yagan Mahircan , Ahmed Hamida K. , Kaverina Irina , Gu Guoqiang 
Published: October 2024

AbstractWe have reported that the microtubule (MT) network in β cells attenuates this function by withdrawing insulin secretory granules (ISGs) away from the plasma membrane. Thus, high glucose-induced MT remodeling is required for robust glucose-stimulated insulin secretion (GSIS). We now show that α-cell secreted hormones, Gcg and/or Glp1, regulate the MT stability in β cells. Activating the receptors of Gcg or Glp1 (GcgR or Glp1R) with chemical agonists induces MT destabilization in β ells in the absence of high glucose. In contrast, inhibiting these receptors with antagonists attenuates high glucose-induced MT destabilization. Supporting the significance of this regulation, the MT networks in β cells of islets with higher α/β cell ratio are less stable than those with lower α/β cell ratio. Within each individual islet, β cells that are located close to α cells show faster MTs remodeling upon glucose stimulation than those away. Consequently, islets with higher α/β cell ratio secrete more insulin in response to high glucose and plasma membrane depolarization, which is recapitulated by direct Gcg stimulation. These combined results reveal a new MT-dependent pathway by which α cells, using Gcg and or Glp1-mediated paracrine signaling, tune β-cell secretion. In addition, the different α-β cell ratios in individual islets lead to their heterogeneous secretory responses, which may be important for handling secretory function needs under different physiological conditions.HighlightsGcg sensitizes glucose-induced MT remodeling in mouse and human β cellsMT density in single islets anti-correlates with α/β cell ratioGSIS levels in single islets positively correlate with α/β cell ratioDifferent α/β cell ratio contributes to heterogeneity of single islet GSIS
National- and state-level SARS-CoV-2 immunity trends from January 2020 to December 2023: a mathematical modeling analysis
Authors: Klaassen Fayette , Swartwood Nicole A , Chitwood Melanie H , Lopes Rafael , Haraguchi Masahiko , Salomon Joshua A , Cohen Ted , Menzies Nicolas A 
Published: October 2024

AbstractIntroductionEffective immune protection against SARS-CoV-2 infection and severe COVID-19 disease continues to change due to viral evolution and waning immunity. We estimated population-level immunity to SARS-CoV-2 for each of the fifty United States (U.S.) and the District of Columbia from January 2020 through December 2023.MethodsWe updated a model of SARS-CoV-2 infections to align with the latest evidence on SARS-CoV-2 natural history and waning of immunity, and to integrate various data sources available throughout the pandemic. We used this model to produce population estimates of effective protection against SARS-CoV-2 infection and severe COVID-19 disease.ResultsOn December 30, 2023, 99.9% of the U.S. population had experienced immunological exposure to SARS-CoV-2 through infection and/or vaccination, with 99.4% (95% credible interval (CrI): 92.4-100%) having had at least one SARS-CoV-2 infection. Despite this high exposure, the average population-level protection against infection was 53.6% (95% CrI: 38.7-71.5%). Population-level protection against severe disease was 82.6% (95% CrI: 71.5-91.7%).DiscussionA new wave of SARS-CoV-2 infections and COVID-19-associated hospitalizations began near the end of 2023, with the introduction of the JN.1 variant. This upturn suggests that the U.S. population remains at risk of SARS-CoV-2 infection and severe COVID-19 disease despite the high level of cumulative exposure in the United States. This decline in effective protection is likely due to both waning and continued viral evolution.
Neural correlates of insomnia with depression and anxiety from a neuroimaging perspective: A systematic review
Authors: Peng Chen , Wang Kai , Wang Jinyu , Wassing Rick , Eickhoff Simon B. , Tahmasian Masoud , Chen Ji 
Published: October 2024

SummaryInsomnia affects a substantial proportion of the population and frequently co-occurs with mental illnesses including depression and anxiety. However, the neurobiological correlates of these disorders remain unclear. Here we review magnetic resonance imaging (MRI) studies assessing structural and functional brain associations with depressive and anxiety symptoms in insomnia disorder (ID; n=38), insomnia symptoms in depressive and anxiety disorders (n=14), and these symptoms in the general populations (n=2). The studies on insomnia disorder consistently showed overlapping (salience network: insula and anterior cingulate cortex) and differential MRI correlation patterns between depressive (thalamus, orbitofrontal cortex and its associated functional connectivity) and anxiety (functional connectivity associated with default mode network) symptoms. The insula was also consistently identified as indicating the severity of insomnia symptoms in depressive disorder. In contrast, findings for other regions related to insomnia symptoms in both depressive and anxiety disorders were generally inconsistent across studies, partly due to variations in methods and patient cohorts. In the general population, brain regions in the default mode network provided a functional link between insomnia and depressive symptoms. These findings underscore both the shared and distinct neural correlates among depression, anxiety, and insomnia, providing potential avenues for the clinical management of these conditions.
Human Satellite 3 DNA encodes megabase-scale transcription factor binding platforms
Authors: Franklin J. Matthew , Dubocanin Danilo , Chittenden Cy , Barillas Ashlie , Lee Rosa Jooyoung , Ghosh Rajarshi P. , Gerton Jennifer L. , Guan Kun-Liang , Altemose Nicolas 
Published: October 2024

AbstractEukaryotic genomes are frequently littered with large arrays of tandem repeats, called satellite DNA, which underlie the constitutive heterochromatin often found around centromeric regions. While some satellite DNA types have well-established roles in centromere biology, other abundant satellite DNAs have poorly characterized functions. For example, Human Satellite 3 (HSat3), which makes up roughly 2% of the human genome, forms enormous arrays up to tens of megabases, but these arrays play no known roles in centromere function and were almost fully excluded from genome assemblies until recently. As a result, these massive genomic regions have remained relatively understudied, and the potential functional roles of HSat3 have remained largely unknown. To address this, we performed a systematic screen for novel HSat3 binding factors. Our work revealed HSat3 arrays contain high densities of transcription factor (TF) motifs that are bound by factors related to multiple, highly conserved signaling pathways. Unexpectedly, the most enriched TFs in HSat3 belong to the Hippo pathway transcription effector family TEAD. We found that TEAD recruits the co-activator YAP to HSat3 regions in a cell-state specific manner. Using RNA polymerase-I reporter assays, targeted repression of HSat3, inducible degradation of YAP, and super-resolution microscopy, we show that HSat3 arrays can localize YAP/TEAD inside the nucleolus, where YAP regulates RNA Polymerase-I activity. Beyond revealing a direct relationship between the Hippo pathway and ribosomal DNA regulation, this work demonstrates that satellite DNA can encode multiple transcription factor binding motifs, defining a new role for these enormous genomic elements.