julilili42/papers huggingface dataset:
Fragmentation in the massive G31.41+0.31 protocluster
2021-04-20

Context. ALMA observations at 1.4 mm and ~0.′′2 (~750 au) angular resolution of the Main core in the high-mass star-forming region G31.41+0.31 have revealed a puzzling scenario. On the one hand, the continuum emission looks very homogeneous and the core appears to undergo solid-body rotation, suggesting a monolithic core stabilized by the magnetic field; on the other hand, rotation and infall speed up toward the core center, where two massive embedded free-free continuum sources have been detected, pointing to an unstable core having undergone fragmentation. Aims. To establish whether the Main core is indeed monolithic or if its homogeneous appearance is due to a combination of large dust opacity and low angular resolution, we carried out millimeter observations at higher angular resolution and different wavelengths. Methods. We carried out ALMA observations at 1.4 mm and 3.5 mm that achieved angular resolutions of ~0.′′1 (~375 au) and ~0.′′075 (~280 au), respectively. VLA observations at 7 mm and 1.3 cm at even higher angular resolution, ~0.′′05 (~190 au) and ~0.′′07 (~260 au), respectively, were also carried out to better study the nature of the free-free continuum sources detected in the core. Results. The millimeter continuum emission of the Main core has been clearly resolved into at least four sources, A, B, C, and D, within 1′′, indicating that the core is not monolithic. The deconvolved radii of the dust emission of the sources, estimated at 3.5 mm, are ~400–500 au; their masses range from ~15 to ~26 M⊙; and their number densities are several 109 cm−3. Sources A and B, located closer to the center of the core and separated by ~750 au, are clearly associated with two free-free continuum sources, likely thermal radio jets, and are brightest in the core. The spectral energy distribution of these two sources and their masses and sizes are similar and suggest a common origin. Source C has not been detected at centimeter wavelengths, while source D has been clearly detected at 1.3 cm. Source D is likely the driving source of an E–W SiO outflow previously detected in the region, which suggests that the free-free emission might be coming from a radio jet. Conclusions. The observations have confirmed that the Main core in G31 is collapsing, that it has undergone fragmentation, and that its homogeneous appearance previously observed at short wavelengths is a consequence of both high dust opacity and insufficient angular resolution. The low level of fragmentation together with the fact that the core is moderately magnetically supercritical, suggests that G31 could have undergone a phase of magnetically regulated evolution characterized by a reduced fragmentation efficiency, eventually leading to the formation of a small number of relatively massive dense cores.
Perfluorinated Phthalocyanines on Cu(110) and Cu(110)-(2 × 1)O: The Special Role of the Central Cobalt Atom
2021-04-20

Interface properties of CoPcF16 on Cu(110) and Cu(110)-(2 × 1)O were investigated by X-ray photoemission spectroscopy (XPS), ultraviolet photoemission spectroscopy (UPS), X-ray absorption spectroscopy (XAS), and scanning tunneling microscopy (STM). The results are compared to FePcF16 on Cu(110)-(2 × 1)O. A charge transfer from both substrates to the central Co ion of CoPcF16 is observed. Unlike to FePcF16 and related molecules, the strong interaction between CoPcF16 molecules of the first layer and the Cu(110) substrate is only partially suppressed by oxygen termination. The special nature of the electronic structure of the Co ion in Co phthalocyanines is discussed. The analysis of the fluorine Auger parameter enables the discussion of initial and final state effects of core level binding energy shifts in photoemission. A bidirectional charge transfer also involving the macrocycle of CoPcF16 molecules is concluded.
A shuttle-vector system allows heterologous gene expression in the thermophilic methanogenMethanothermobacter thermautotrophicusΔH
2021-04-20

Abstract Thermophilic Methanothermobacter spp. are used as model microbes to study the physiology and biochemistry of the conversion of hydrogen and carbon dioxide into methane ( i.e ., hydrogenotrophic methanogenesis), because of their short doubling times and robust growth with high growth yields. Yet, a genetic system for these model microbes was missing despite intense work for four decades. Here, we report the establishment of tools for genetic modification of M. thermautotrophicus . We developed the modular Methanothermobacter vector system, which provided shuttle-vector plasmids (pMVS) with exchangeable selectable markers and replicons for both Escherichia coli and M. thermautotrophicus . For M. thermautotrophicus , a thermostable neomycin-resistance cassette served as the selectable marker for positive selection with neomycin, and the cryptic plasmid pME2001 from Methanothermobacter marburgensis served as the replicon. The pMVS-plasmid DNA was transferred from E. coli into M. thermautotrophicus via interdomain conjugation. After the successful validation of DNA transfer and positive selection in M. thermautotrophicus , we demonstrated heterologous gene expression of a thermostable β-galactosidase-encoding gene ( bgaB ) from Geobacillus stearothermophilus under the expression control of four distinct synthetic and native promoters. In quantitative in-vitro enzyme activity assays, we found significantly different β-galactosidase activity with these distinct promoters. With a formate dehydrogenase operon-encoding shuttle vector, we allowed growth of M. thermautotrophicus on formate as the sole growth substrate, while this was not possible for the empty vector control. These genetic tools provide the basis to investigate hypotheses from four decades of research on the physiology and biochemistry of Methanothermobacter spp. on a genetic level. Significance Statement The world economies are facing permanently increasing energy demands. At the same time, carbon emissions from fossil sources need to be circumvented to minimize harmful effects from climate change. The power-to-gas platform is utilized to store renewable electric power and decarbonize the natural gas grid. The microbe Methanothermobacter thermautotrophicus is already applied as the industrial biocatalyst for the biological methanation step in large-scale power-to-gas processes. To improve the biocatalyst in a targeted fashion, genetic engineering is required. With our shuttle-vector system for heterologous gene expression in M. thermautotrophicus , we set the cornerstone to engineer the microbe for optimized methane production, but also for production of high-value platform chemicals in power-to-x processes.
Loss-of-function variants in the KCNQ5 gene are associated with genetic generalized epilepsies
2021-04-20

ABSTRACT Objective De novo missense variants in KCNQ5 , encoding the voltage-gated K + channel K V 7.5, have been described as a cause of developmental and epileptic encephalopathy (DEE) or intellectual disability (ID). We set out to identify disease-related KCNQ5 variants in genetic generalized epilepsy (GGE) and their underlying mechanisms. Methods 1292 families with GGE were studied by next-generation sequencing. Whole-cell patch-clamp recordings, biotinylation and phospholipid overlay assays were performed in mammalian cells combined with docking and homology modeling. Results We identified three deleterious heterozygous missense variants, one truncation and one splice site alteration in five independent families with GGE with predominant absence seizures, two variants were also associated with mild to moderate ID. All three missense variants displayed a strongly decreased current density indicating a loss-of-function (LOF). When mutant channels were co-expressed with wild-type (WT) K V 7.5 or K V 7.5 and K V 7.3 channels, three variants also revealed a significant dominant-negative effect on WT channels. Other gating parameters were unchanged. Biotinylation assays indicated a normal surface expression of the variants. The p.Arg359Cys variant altered PI(4,5)P 2 - interaction, presumably in the non-conducting preopen-closed state. Interpretation Our study indicates that specific deleterious KCNQ5 variants are associated with GGE, partially combined with mild to moderate ID. The disease mechanism is a LOF partially with dominant-negative effects through functional, rather than trafficking deficits. LOF of K V 7.5 channels will reduce the M-current, likely resulting in increased excitability of K V 7.5- expressing neurons. Further studies on a network level are necessary to understand which circuits are affected and how the variants induce generalized seizures.
Faculty Opinions recommendation of A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis.
2021-04-20

Stromal cells in adult bone marrow that express leptin receptor (LEPR) are a critical source of growth factors, including stem cell factor (SCF), for the maintenance of haematopoietic stem cells and early restricted progenitors1-6. LEPR+ cells are heterogeneous, including skeletal stem cells and osteogenic and adipogenic progenitors7-12, although few markers have been available to distinguish these subsets or to compare their functions. Here we show that expression of an osteogenic growth factor, osteolectin13,14, distinguishes peri-arteriolar LEPR+ cells poised to undergo osteogenesis from peri-sinusoidal LEPR+ cells poised to undergo adipogenesis (but retaining osteogenic potential). Peri-arteriolar LEPR+osteolectin+ cells are rapidly dividing, short-lived osteogenic progenitors that increase in number after fracture and are depleted during ageing. Deletion of Scf from adult osteolectin+ cells did not affect the maintenance of haematopoietic stem cells or most restricted progenitors but depleted common lymphoid progenitors, impairing lymphopoiesis, bacterial clearance, and survival after acute bacterial infection. Peri-arteriolar osteolectin+ cell maintenance required mechanical stimulation. Voluntary running increased, whereas hindlimb unloading decreased, the frequencies of peri-arteriolar osteolectin+ cells and common lymphoid progenitors. Deletion of the mechanosensitive ion channel PIEZO1 from osteolectin+ cells depleted osteolectin+ cells and common lymphoid progenitors. These results show that a peri-arteriolar niche for osteogenesis and lymphopoiesis in bone marrow is maintained by mechanical stimulation and depleted during ageing. PMID: 33627868 Funding information This work was supported by: NIDDK NIH HHS, United States Grant ID: R01 DK118745 NHLBI NIH HHS, United States Grant ID: F32 HL139016
Dataset for the lecture "Neural Data Science" at University of Tübingen
2021-04-20

This file is needed for the coding labs for the course "Neural Data Science" tought at the University of Tübingen. Github repository of the coding labs: https://github.com/berenslab/neural_data_science Data sources: Ecker et al.,Decorrelated Neuronal Firing in Cortical Microcircuits, Science, 2010, http://bethgelab.org/datasets/v1gratings/ Ecker et al.,State Dependence of Noise Correlations in Macaque Primary Visual Cortex, Neuron, 2014 Harris et al.,Classes and continua of hippocampal CA1 inhibitory neurons revealed by single-cell transcriptomics, PLOS Biology, https://figshare.com/articles/dataset/Transcriptomic_analysis_of_CA1_inhibitory_interneurons/6198656 Reinhard et al., A projection specific logic to sampling visual inputs in mouse superior colliculus, eLife, 2019, https://osf.io/b4qtr/
Stable Atlantic deep water mass sourcing on glacial-interglacial timescales: Nd isotope data of IODP Site U1313
2021-04-20

This dataset contains neodymium isotope data of IODP Site U1313 covering the time period of the past 100 kyr as published in Pöppelmeier et al. (2021), <em>Geophysical Research Letters</em>. For detailed information on sampling and data processing please see Pöppelmeier et al. (2021).
Stable Atlantic deep water mass sourcing on glacial-interglacial timescales: Nd isotope data of IODP Site U1313
2021-04-20

&lt;p&gt;This dataset contains neodymium isotope data of IODP Site U1313 covering the time period of the past 100 kyr as published in P&ouml;ppelmeier et al. (2021), &lt;em&gt;Geophysical Research Letters&lt;/em&gt;.&lt;/p&gt; &lt;p&gt;For detailed information on sampling and data processing please see P&ouml;ppelmeier et al. (2021).&lt;/p&gt;
Visualising and understanding cGMP signals in the cardiovascular system
2021-04-21

cGMP is an important signalling molecule in humans. Fluorescent cGMP biosensors have emerged as powerful tools for the sensitive analysis of cGMP pathways at the single‐cell level. Here, we briefly outline cGMP's multifaceted role in (patho)physiology and pharmacotherapy. Then we summarise what new insights cGMP imaging has provided into endogenous cGMP signalling and drug action, with a focus on the cardiovascular system. Indeed, the use of cGMP biosensors has led to several conceptual advances, such as the discovery of local, intercellular and mechanosensitive cGMP signals. Importantly, single‐cell imaging can provide valuable information about the heterogeneity of cGMP signals within and between individual cells of an isolated cell population or tissue. We also discuss current challenges and future directions of cGMP imaging, such as the direct visualisation of cGMP microdomains, simultaneous monitoring of cGMP and other signalling molecules and, ultimately, cGMP imaging in tissues and animals under close‐to‐native conditions. LINKED ARTICLES This article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc
Hippocampal and Hippocampal-Subfield Volumes From Early-Onset Major Depression and Bipolar Disorder to Cognitive Decline
2021-04-21

Background: The hippocampus and its subfields (HippSub) are reported to be diminished in patients with Alzheimer's disease (AD), bipolar disorder (BD), and major depressive disorder (MDD). We examined these groups vs healthy controls (HC) to reveal HippSub alterations between diseases. Methods: We segmented 3T-MRI T2-weighted hippocampal images of 67 HC, 58 BD, and MDD patients from the AFFDIS study and 137 patients from the DELCODE study assessing cognitive decline, including subjective cognitive decline (SCD), amnestic mild cognitive impairment (aMCI), and AD, via Free Surfer 6.0 to compare volumes across groups. Results: Groups differed significantly in several HippSub volumes, particularly between patients with AD and mood disorders. In comparison to HC, significant lower volumes appear in aMCI and AD groups in specific subfields. Smaller volumes in the left presubiculum are detected in aMCI and AD patients, differing from the BD group. A significant linear regression is seen between left hippocampus volume and duration since the first depressive episode. Conclusions: HippSub volume alterations were observed in AD, but not in early-onset MDD and BD, reinforcing the notion of different neural mechanisms in hippocampal degeneration. Moreover, duration since the first depressive episode was a relevant factor explaining the lower left hippocampal volumes present in groups.
Impaired executive function exacerbates neural markers of posttraumatic stress disorder
2021-04-21

Abstract Background A major obstacle in understanding and treating posttraumatic stress disorder (PTSD) is its clinical and neurobiological heterogeneity. To address this barrier, the field has become increasingly interested in identifying subtypes of PTSD based on dysfunction in neural networks alongside cognitive impairments that may underlie the development and maintenance of symptoms. The current study aimed to determine if subtypes of PTSD, based on normative-based cognitive dysfunction across multiple domains, have unique neural network signatures. Methods In a sample of 271 veterans (90% male) that completed both neuropsychological testing and resting-state fMRI, two complementary, whole-brain functional connectivity analyses explored the link between brain functioning, PTSD symptoms, and cognition. Results At the network level, PTSD symptom severity was associated with reduced negative coupling between the limbic network (LN) and frontal-parietal control network (FPCN), driven specifically by the dorsolateral prefrontal cortex and amygdala Hubs of Dysfunction. Further, this relationship was uniquely moderated by executive function (EF). Specifically, those with PTSD and impaired EF had the strongest marker of LN-FPCN dysregulation, while those with above-average EF did not exhibit PTSD-related dysregulation of these networks. Conclusion These results suggest that poor executive functioning, alongside LN-FPCN dysregulation, may represent a neurocognitive subtype of PTSD.
A multi-phenotype genome-wide association study of clades causing tuberculosis in a Ghanaian- and South African cohort
2021-04-21

Despite decades of research and advancements in diagnostics and treatment, tuberculosis remains a major public health concern. New computational methods are needed to interrogate the intersection of host- and bacterial genomes. Paired host genotype datum and infecting bacterial isolate information were analysed for associations using a multinomial logistic regression framework implemented in SNPTest. A cohort of 853 admixed South African participants and a Ghanaian cohort of 1359 participants were included. Two directly genotyped variants, namely rs529920 and rs41472447, were identified in the Ghanaian cohort as being statistically significantly associated with risk for infection with strains of different members of the MTBC. Thus, a multinomial logistic regression using paired host-pathogen data may prove valuable for investigating the complex relationships driving infectious disease.
Sequential Analysis of Trace Elements in a Micro Volume Urine Sample Using Inductively Coupled Plasma Mass Spectrometry
2021-04-21

In this work, we describe a simple, fast, cheap, accurate and high-throughput method for the determination of Al; V; Cr; Mn; Fe; Co; Cu; Zn; As; Se; Mo; Cd; Sn; Ba; TI; Pb in a micro volume of urine by using inductively coupled mass spectrometry (ICP-MS) equipped with an octupole-based collision cell. The samples were directly analyzed after a simple acidification with 3% nitric acid. Validation of this method was performed by using certified urine reference material. He and H were used as collision gas for reducing polyatomic interference for most of the measured elements. Finally, we partook in an external quality assurance conducted by ISNTAND e.V. 2. Results show that our high-throughput method is ideal for detecting elements in newborns and infants because of its simplicity, speed, accuracy and low sample volume.
Efficiency and prioritization of inference-based credit assignment
2021-04-21

Organisms adapt to their environments by learning to approach states that predict rewards and avoid states associated with punishments. Knowledge about the affective value of states often relies on credit assignment (CA), whereby state values are updated on the basis of reward feedback. Remarkably, humans assign credit to states that are not observed but are instead inferred based on a cognitive map that represents structural knowledge of an environment. A pertinent example is authors attempting to infer the identity of anonymous reviewers to assign them credit or blame and, on this basis, inform future referee recommendations. Although inference is cognitively costly, it is unknown how it influences CA or how it is apportioned between hidden and observable states (for example, both anonymous and revealed reviewers). We addressed these questions in a task that provided choices between lotteries where each led to a unique pair of occasionally rewarding outcome states. On some trials, both states were observable (rendering inference nugatory), whereas on others, the identity of one of the states was concealed. Importantly, by exploiting knowledge of choice-state associations, subjects could infer the identity of this hidden state. We show that having to perform inference reduces state-value updates. Strikingly, and in violation of normative theories, this reduction in CA was selective for the observed outcome alone. These findings have implications for the operation of putative cognitive maps.
Self-Organization Toward Criticality by Synaptic Plasticity
2021-04-22

Self-organized criticality has been proposed to be a universal mechanism for the emergence of scale-free dynamics in many complex systems, and possibly in the brain. While such scale-free patterns were identified experimentally in many different types of neural recordings, the biological principles behind their emergence remained unknown. Utilizing different network models and motivated by experimental observations, synaptic plasticity was proposed as a possible mechanism to self-organize brain dynamics toward a critical point. In this review, we discuss how various biologically plausible plasticity rules operating across multiple timescales are implemented in the models and how they alter the network’s dynamical state through modification of number and strength of the connections between the neurons. Some of these rules help to stabilize criticality, some need additional mechanisms to prevent divergence from the critical state. We propose that rules that are capable of bringing the network to criticality can be classified by how long the near-critical dynamics persists after their disabling. Finally, we discuss the role of self-organization and criticality in computation. Overall, the concept of criticality helps to shed light on brain function and self-organization, yet the overall dynamics of living neural networks seem to harnesses not only criticality for computation, but also deviations thereof.
Regulatory Immune Cells in Idiopathic Pulmonary Fibrosis: Friends or Foes?
2021-04-22

The immune system is receiving increasing attention for interstitial lung diseases, as knowledge on its role in fibrosis development and response to therapies is expanding. Uncontrolled immune responses and unbalanced injury-inflammation-repair processes drive the initiation and progression of idiopathic pulmonary fibrosis. The regulatory immune system plays important roles in controlling pathogenic immune responses, regulating inflammation and modulating the transition of inflammation to fibrosis. This review aims to summarize and critically discuss the current knowledge on the potential role of regulatory immune cells, including mesenchymal stromal/stem cells, regulatory T cells, regulatory B cells, macrophages, dendritic cells and myeloid-derived suppressor cells in idiopathic pulmonary fibrosis. Furthermore, we review the emerging role of regulatory immune cells in anti-fibrotic therapy and lung transplantation. A comprehensive understanding of immune regulation could pave the way towards new therapeutic or preventive approaches in idiopathic pulmonary fibrosis.