julilili42/papers huggingface dataset:
Electron‐Deficient Imidazolium Substituted Cp Ligands and their Ru Complexes
2020-09-30

Abstract The synthesis of electron‐poor mono‐, di‐ and tri(imidazolium)‐substituted Cp‐ylides is presented and their electronic properties are discussed based on NMR spectroscopy, X‐ray structure analyses, electrochemical investigations and DFT calculations as well as by their reactivity toward [Ru(CH 3 CN) 3 Cp*](PF 6 ). With mono‐ and di(imidazolium)‐substituted cyclopentadienides the respective monocationic and dicationic ruthenocences are formed (X‐ray), whereas tri(imidazolium) cyclopentadienides are too electron‐poor to form the ruthenocenes. Cyclic voltammetric analysis of the ruthenocenes shows reversible oxidation at a potential that increases with every additional electron‐withdrawing imidazolium substituent at the Cp ligand by 0.53–0.55 V in an electrolyte based on a weakly coordinating anion. A reversible oxidation can be observed for the free 1,3‐disubstituted ligand as well.
Higher-order linearly implicit full discretization of the Landau–Lifshitz–Gilbert equation
2020-09-30

For the Landau--Lifshitz--Gilbert (LLG) equation of micromagnetics we study linearly implicit backward difference formula (BDF) time discretizations up to order combined with higher-order non-conforming finite element space discretizations, which are based on the weak formulation due to Alouges but use approximate tangent spaces that are defined by -averaged instead of nodal orthogonality constraints. We prove stability and optimal-order error bounds in the situation of a sufficiently regular solution. For the BDF methods of orders to~ , this requires %a mild time step restriction and that the damping parameter in the LLG equations be above a positive threshold; this condition is not needed for the A-stable methods of orders and , for which furthermore a discrete energy inequality irrespective of solution regularity is proved.
Investigation of the Autoregulator-Receptor System in the Pristinamycin Producer Streptomyces pristinaespiralis
2020-09-30

Pristinamycin biosynthesis in <i>Streptomyces pristinaespiralis</i> is governed by a complex hierarchical signaling cascade involving seven different transcriptional regulators (SpbR, PapR1, PapR2, PapR3, PapR4, PapR5, and PapR6). The signaling cascade is triggered by γ-butyrolactone (GBL)-like effector molecules, whereby the chemical structure of the effector, as well as its biosynthetic origin is unknown so far. Three of the pristinamycin transcriptional regulators (SpbR, PapR3, and PapR5) belong to the type of γ-butyrolactone receptor (GBLR). GBLRs are known to either act as "real" GBLRs, which bind GBLs as ligands or as "pseudo" GBLRs binding antibiotics or intermediates thereof as effector molecules. In this study, we performed electromobility shift assays (EMSAs) with SpbR, PapR3, and PapR5, respectively, in the presence of potential ligand samples. Thereby we could show that all three GBLRs bind synthetic 1,4-butyrolactone but not pristinamycin as ligand, suggesting that SpbR, PapR3, and PapR5 act as "real" GBLRs in <i>S. pristinaespiralis</i>. Furthermore, we identified a cytochrome P450 monooxygenase encoding gene <i>snbU</i> as potential biosynthesis gene for the GBLR-interacting ligand. Inactivation of <i>snbU</i> resulted in an increased pristinamycin production, which indicated that SnbU has a regulatory influence on pristinamycin production. EMSAs with culture extract samples from the <i>snbU</i> mutant did not influence the target binding ability of SpbR, PapR3, and PapR5 anymore, in contrast to culture supernatant samples from the <i>S. pristinaespiralis</i> wild-type or the pristinamycin deficient mutant <i>papR2::apra</i>, which demonstrates that SnbU is involved in the synthesis of the GBLR-interacting ligand.
Malaria parasites differentially sense environmental elasticity during transmission
2020-09-30

Abstract Transmission of malaria-causing parasites to and by the mosquito rely on active parasite migration and constitute bottlenecks in the Plasmodium life cycle. Parasite adaption to the biochemically and physically different environments must hence be a key evolutionary driver for transmission efficiency. To probe how subtle but physiologically relevant changes in environmental elasticity impact parasite migration, we introduce 2D and 3D polyacrylamide gels to study ookinetes, the parasite forms emigrating from the mosquito blood meal and sporozoites, the forms transmitted to the vertebrate host. We show that ookinetes adapt their migratory path but not their speed to environmental elasticity and are motile for over 24 hours on soft substrates. In contrast, sporozoites evolved more short-lived rapid gliding motility for rapidly crossing the skin. Strikingly, sporozoites are highly sensitive to substrate elasticity possibly to avoid adhesion on soft endothelial cells on their long way to the liver. Hence the two migratory stages of Plasmodium evolved different strategies to overcome the physical challenges posed by the respective environments and barriers they encounter. Highlights Plasmodium ookinetes can move for over 24 hours on very soft substrates mimicking the blood meal Plasmodium ookinetes change their migration path according to substrate stiffness Plasmodium sporozoites are highly sensitive to subtle changes in substrate elasticity Sporozoite may have evolved to not attach to the soft endothelium to help reach the liver
Improving echo-planar imaging-based diffusion weighted imaging of the head and neck using local shim coils
2020-09-30

Purpose: To evaluate the performance of additional local shim coils within the head/neck surface coil for diffusion-weighted imaging (DWI) MRI of the head/neck region using a 3-Tesla scanner. Material and Methods: Ten healthy volunteers underwent single-shot echo-planar DWI and T1 gradient echo acquisition of the head/neck region, without (sEPI; sGRE) and with (cEPI; cGRE) the use of additional shim coils integrated into the head/neck coil. Additionally, B 0 field maps with and without additional shim coils were acquired using a dual-echo T1w GRE sequence. Acquisitions were performed on a clinical 3T scanner. In the DWI images, visual evaluation was performed for overall image quality (OAIQ), signal loss, distortions and ghosting. Failure of fat saturation was visually assessed for all sequences. Assessments were quantified using a 4-point scale by two radiologists in consensus. The effects on static field homogeneities were evaluated visually in the acquired field maps. Apparent diffusion coefficients (ADCs) were quantified in the spinal cord, spinal fluid and trapezius muscle for sEPI and cEPI. Results: Compared to sEPI, cEPI significantly improved OAIQ, distortion and ghosting and decreased signal loss (p≤0.008). Additionally, cEPI resulted in significantly improved fat saturation compared to sEPI, sGRE and cGRE (p<0.001). Regarding the static magnetic field, additional local shim coils resulted in marked homogenisation, especially in the lower/posterior neck. ADC values did not differ significantly (p≥0.08). Conclusions: Additional local shim coils integrated into the head/neck surface coil improve homogenisation of the static magnetic field and providing improved DWI quality compared to standard sEPI. For T1-weighted sGRE, additional coils have no significant effect on fat saturation.
Faculty Opinions recommendation of Cross-reactivity between tumor MHC class I-restricted antigens and an enterococcal bacteriophage.
2020-09-30

Intestinal microbiota have been proposed to induce commensal-specific memory T cells that cross-react with tumor-associated antigens. We identified major histocompatibility complex (MHC) class I-binding epitopes in the tail length tape measure protein (TMP) of a prophage found in the genome of the bacteriophage Enterococcus hirae Mice bearing E. hirae harboring this prophage mounted a TMP-specific H-2Kb-restricted CD8+ T lymphocyte response upon immunotherapy with cyclophosphamide or anti-PD-1 antibodies. Administration of bacterial strains engineered to express the TMP epitope improved immunotherapy in mice. In renal and lung cancer patients, the presence of the enterococcal prophage in stools and expression of a TMP-cross-reactive antigen by tumors correlated with long-term benefit of PD-1 blockade therapy. In melanoma patients, T cell clones recognizing naturally processed cancer antigens that are cross-reactive with microbial peptides were detected.Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. PMID: 32820119
Interoception and Its Role for Eating, Obesity, and Eating Disorders
2020-10-01

Abstract. The importance of the sense of ourselves from within for understanding adaptive behavior and psychopathology has been increasingly recognized during the last decades. Interoception builds the foundation of our embodied self and dysfunctional interoception lies at the core of many psychosomatic disorders. Eating is fundamental for survival with consequences for health and well-being. It is deeply grounded in homoeostatic and allostatic psychophysiological needs and is driven by interoceptive signals of the body. This narrative review summarizes a selection of empirical findings and draws conclusions on the role of interoception in eating behavior, body weight, and eating disorders. Beyond disordered eating behavior, eating disorders are characterized by impairment of the sense of self, with dysfunctional interoception at its core. Predictive coding accounts are addressed to integrate conclusions and to underline the relevance of interventions to modify interoception.
Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C
2020-10-01

Abstract Context 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. Objective To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. Design An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. Setting This was a multicenter retrospective study using information collected from 3 predominant centers. Patients A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. Main Outcome Measures Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. Results The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. Conclusions Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder.
High resolution parameter study of the vertical shear instability
2020-10-01

ABSTRACT Theoretical models of protoplanetary discs have shown the vertical shear instability (VSI) to be a prime candidate to explain turbulence in the dead zone of the disc. However, simulations of the VSI have yet to show consistent levels of key disc turbulence parameters like the stress-to-pressure ratio α. We aim to reconcile these different values by performing a parameter study on the VSI with focus on the disc density gradient p and aspect ratio h = H/R. We use full 2π 3D simulations of the disc for chosen set of both parameters. All simulations are evolved for 1000 reference orbits, at a resolution of 18 cells per h. We find that the saturated stress-to-pressure ratio in our simulations is dependent on the disc aspect ratio with a strong scaling of α∝h2.6, in contrast to the traditional α model, where viscosity scales as ν∝αh2 with a constant α. We also observe consistent formation of large scale vortices across all investigated parameters. The vortices show uniformly aspect ratios of χ ≈ 10 and radial widths of approximately 1.5H. With our findings we can reconcile the different values reported for the stress-to-pressure ratio from both isothermal and full radiation hydrodynamics models, and show long-term evolution effects of the VSI that could aide in the formation of planetesimals.
The noise and impedance of microelectrodes
2020-10-01

Abstract Objective. While the positive correlation between impedance and noise of microelectrodes is well known, their quantitative relationship is too rarely described. Knowledge of this relationship provides useful information for both microsystems engineers and electrophysiologists. Approach. We discuss the physical basis of noise in recordings with microelectrodes, and compare measurements of impedance spectra to noise of microelectrodes. Main results. Microelectrode recordings intrinsically include thermal noise, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:msub> <mml:mi>v</mml:mi> <mml:mrow> <mml:mtext>t</mml:mtext> </mml:mrow> </mml:msub> <mml:mo>=</mml:mo> <mml:msup> <mml:mfenced close="]" open="["> <mml:mrow> <mml:mn>4</mml:mn> <mml:msub> <mml:mi>k</mml:mi> <mml:mrow> <mml:mtext>B</mml:mtext> </mml:mrow> </mml:msub> <mml:mi>T</mml:mi> <mml:mo>∫</mml:mo> <mml:mrow> <mml:mtext>Re</mml:mtext> </mml:mrow> <mml:mo stretchy="false">(</mml:mo> <mml:mi>Z</mml:mi> <mml:mo stretchy="false">)</mml:mo> <mml:mi>d</mml:mi> <mml:mi>f</mml:mi> </mml:mrow> </mml:mfenced> <mml:mrow> <mml:mn>1</mml:mn> <mml:mrow> <mml:mo>/</mml:mo> </mml:mrow> <mml:mn>2</mml:mn> </mml:mrow> </mml:msup> </mml:math> , with the real component of impedance integrated over the recording frequency band. Impedance spectroscopy allows the quantitative prediction of thermal noise. Optimization of microelectrode noise should also consider the contribution of amplifier noise. These measures enable a quantitative evaluation of microelectrodes’ recording quality which is more informative than common but limited comparisons based on the impedance magnitude at 1 kHz. Significance. Improved understanding of the origin of microelectrode noise will support efforts to produce smaller yet low noise microelectrodes, capable of recording from higher numbers of neurons. This tutorial is relevant for single microelectrodes, tetrodes, neural probes and microelectrode arrays, whether used in vitro or in vivo .
Pallidal Connectivity Profiling of Stimulation‐Induced Dyskinesia in Parkinson's Disease
2020-10-01

ABSTRACT Objectives The aim of this study is to identify anatomical regions related to stimulation‐induced dyskinesia (SID) after pallidal deep brain stimulation (DBS) in Parkinson's disease (PD) patients and to analyze connectivity associated with SID. Methods This retrospective study analyzed the clinical and imaging data of PD patients who experienced SID during the monopolar review after pallidal DBS. We analyzed structural and functional connectivity using normative connectivity data with the volume of tissue activated (VTA) modeling. Each contact was assigned to either that producing SID (SID VTA) or that without SID (non‐SID VTA). Structural and functional connectivity was compared between SID and non‐SID VTAs. “Optimized VTAs” were also estimated using the DBS settings at 6 months after implantation. Results Of the 68 consecutive PD patients who underwent pallidal implantation, 20 patients (29%) experienced SID. SID VTAs were located more dorsally and anteriorly compared with non‐SID and optimized VTAs and were primarily in the dorsal globus pallidus internus (GPi) and dorsal globus pallidus externus (GPe). SID VTAs showed significantly higher structural connectivity than non‐SID VTAs to the associative cortex and supplementary motor area/premotor cortex ( P &lt; 0.0001). Simultaneously, non‐SID VTAs showed greater connectivity to the primary sensory cortex, cerebellum, subthalamic nucleus, and motor thalamus (all P &lt; 0.0004). Functional connectivity analysis showed significant differences between SID and non‐SID VTAs in multiple regions, including the primary motor, premotor, and prefrontal cortices and cerebellum. Conclusion SID VTAs were primarily in the dorsal GPi/GPe. The connectivity difference between the motor‐related cortices and subcortical regions may explain the presence and absence of SID. © 2020 International Parkinson and Movement Disorder Society
DamageProfiler: Fast damage pattern calculation for ancient DNA
2020-10-01

Abstract In ancient DNA research, the authentication of ancient samples based on specific features remains a crucial step in data analysis. Because of this central importance, researchers lacking deeper programming knowledge should be able to run a basic damage authentication analysis. Such software should be user-friendly and easy to integrate into an analysis pipeline. Here, we present DamageProfiler, a Java based, stand-alone software to determine damage patterns in ancient DNA. The results are provided in various file formats and plots for further processing. DamageProfiler has an intuitive graphical as well as command line interface that allows the tool to be easily embedded into an analysis pipeline.
Plasma proteome profiles treatment efficacy of incretin dual agonism in diet‐induced obese female and male mice
2020-10-01

Abstract Aims Unimolecular peptides targeting the receptors for glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) (GLP‐1/GIP co‐agonist) have been shown to outperform each single peptide in the treatment of obesity and cardiometabolic disease in preclinical and clinical trials. By combining physiological treatment endpoints with plasma proteomic profiling (PPP), we aimed to identify biomarkers to advance non‐invasive metabolic monitoring of compound treatment success and exploration of ulterior treatment effects on an individual basis. Materials and methods We performed metabolic phenotyping along with PPP in body weight‐matched male and female diet‐induced obese (DIO) mice treated for 21 days with phosphate‐buffered saline, single GIP and GLP‐1 mono‐agonists, or a GLP‐1/GIP co‐agonist. Results GLP‐1R/GIPR co‐agonism improved obesity, glucose intolerance, non‐alcoholic fatty liver disease (NAFLD) and dyslipidaemia with superior efficacy in both male and female mice compared with mono‐agonist treatments. PPP revealed broader changes of plasma proteins after GLP‐1/GIP co‐agonist compared with mono‐agonist treatments in both sexes, including established and potential novel biomarkers for systemic inflammation, NAFLD and atherosclerosis. Subtle sex‐specific differences have been observed in metabolic phenotyping and PPP. Conclusions We herein show that a recently developed unimolecular GLP‐1/GIP co‐agonist is more efficient in improving metabolic disease than either mono‐agonist in both sexes. PPP led to the identification of a sex‐independent protein panel with the potential to monitor non‐invasively the treatment efficacies on metabolic function of this clinically advancing GLP‐1/GIP co‐agonist.
The structure of autocatalytic networks, with application to early biochemistry
2020-10-01

Metabolism across all known living systems combines two key features. First, all of the molecules that are required are either available in the environment or can be built up from available resources via other reactions within the system. Second, the reactions proceed in a fast and synchronized fashion via catalysts that are also produced within the system. Building on early work by Stuart Kauffman, a precise mathematical model for describing such self-sustaining autocatalytic systems (RAF theory) has been developed to explore the origins and organization of living systems within a general formal framework. In this paper, we develop this theory further by establishing new relationships between classes of RAFs and related classes of networks, and developing new algorithms to investigate and visualize RAF structures in detail. We illustrate our results by showing how it reveals further details into the structure of archaeal and bacterial metabolism near the origin of life, and provide techniques to study and visualize the core aspects of primitive biochemistry.
Skeletal muscle effects of two different 10‐week exercise regimens, voluntary wheel running, and forced treadmill running, in mice: A pilot study
2020-10-01

Physical activity and exercise induce a complex pattern of adaptation reactions in a broad variety of tissues and organs, particularly the cardiovascular and the musculoskeletal systems. The underlying mechanisms, however, specifically the molecular changes that occur in response to training, are still incompletely understood. Animal models help to systematically elucidate the mechanisms of exercise adaptation. With regard to endurance-based running exercise in mice, two basic regimens have been established: forced treadmill running (FTR), usually consisting of several sessions per week, and voluntary wheel running (VWR). However, the effects of these two programs on skeletal muscle molecular adaptation patterns have never been directly compared. To address this issue, in a pilot study, we analyzed the effects of two ten-week training regimens in juvenile, male, C57BL/6 mice: moderate-intensity forced treadmill running three-times-a-week, employing a protocol that has been widely used in similar studies before, and voluntary wheel running. Our data suggest that there are similarities, but also characteristic differences in the molecular responses of different skeletal muscle species to the two training regimens. In particular, we found that VWR induces a significant fiber type shift toward more type IIX fibers in the slow, oxidative soleus muscle (p = .0053), but not in the other three muscles analyzed. In addition, while training-induced expression patterns of the two metabolic markers Ppargc1a, encoding Pgc-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) and Nr4a3 (nuclear receptor subfamily 4 group A member 3) were roughly similar, downregulation of the Mstn (myostatin) gene and the "atrogene" Fbox32 could only be observed in response to VWR in specific muscles, such as in the gastrocnemius (p = .0015 for Mstn) and in the tibialis anterior (p = .0053 for Fbox32) muscles, suggesting that molecular adaptation reactions to the two training regimens show distinct characteristics.