julilili42/papers huggingface dataset:
Venomics and Peptidomics of Palearctic Vipers: A Clade-Wide Analysis of Seven Taxa of the Genera Vipera, Montivipera, Macrovipera, and Daboia across Türkiye
2024-07-09

Snake venom variations are a crucial factor to understand the consequences of snakebite envenoming worldwide, and therefore it is important to know about toxin composition alterations between taxa. Palearctic vipers of the genera <i>Vipera</i>, <i>Montivipera</i>, <i>Macrovipera,</i> and <i>Daboia</i> have high medical impacts across the Old World. One hotspot for their occurrence and diversity is Türkiye, located on the border between continents, but many of their venoms remain still understudied. Here, we present the venom compositions of seven Turkish viper taxa. By complementary mass spectrometry-based bottom-up and top-down workflows, the venom profiles were investigated on proteomics and peptidomics level. This study includes the first venom descriptions of <i>Vipera berus barani</i>, <i>Vipera darevskii</i>, <i>Montivipera bulgardaghica albizona,</i> and <i>Montivipera xanthina</i>, as well as the first snake venomics profiles of Turkish <i>Macrovipera lebetinus obtusa</i>, and <i>Daboia palaestinae</i>, including an in-depth reanalysis of <i>M. bulgardaghica bulgardaghica</i> venom. Additionally, we identified the modular consensus sequence pEXW(PZ)<sub>1-2</sub>P(EI)/(KV)PPLE for bradykinin-potentiating peptides in viper venoms. For better insights into variations and potential impacts of medical significance, the venoms were compared against other Palearctic viper proteomes, including the first genus-wide <i>Montivipera</i> venom comparison. This will help the risk assessment of snakebite envenoming by these vipers and aid in predicting the venoms' pathophysiology and clinical treatments.
Sustained innate interferon is an essential inducer of tertiary lymphoid structures
2024-07-09

Abstract Tertiary lymphoid structures (TLS) resemble follicles of secondary lymphoid organs and develop in nonlymphoid tissues during inflammation and cancer. Which cell types and signals drive the development of TLS is largely unknown. To investigate early events of TLS development in the lungs, we repeatedly instilled p(I:C) plus ovalbumin (Ova) intranasally. This induced TLS ranging from lymphocytic aggregates to organized and functional structures containing germinal centers. We found that TLS development is independent of FAP + fibroblasts, alveolar macrophages, or CCL19 but crucially depends on type I interferon (IFN‐I). Mechanistically, IFN‐I initiates two synergistic pathways that culminate in the development of TLS. On the one hand, IFN‐I induces lymphotoxin (LT)α in lymphoid cells, which stimulate stromal cells to produce the B‐cell‐attracting chemokine CXCL13 through LTβR‐signaling. On the other hand, IFN‐I is sensed by stromal cells that produce the T‐cell‐attracting chemokines CXCL9, CXCL10 as well as CCL19 and CCL21 independently of LTβR. Consequently, B‐cell aggregates develop within a week, whereas follicular dendritic cells and germinal centers appear after 3 weeks. Thus, sustained production of IFN‐I together with an antigen is essential for the induction of functional TLS in the lungs.
Modality Matters: Fasted Individuals Inhibit Food Stimuli Better Than Neutral Stimuli for Words, but Not for Pictures
2024-07-09

The current study aimed to evaluate the effect different modalities (pictures and words) of food stimuli have on inhibitory control under different homeostatic states. To this end, the homeostatic state was altered by asking participants to fast for 16 h (n = 67) or eat lunch as usual (n = 76) before completing an online stop-signal task with modal (pictures) and amodal (words) food and valenced-matched non-food stimuli. The inclusion of non-food stimuli allowed us to test the food specificity of the effect. We found a significant Group × Modality × Stimulus Type interaction (F(1,141) = 5.29, p = 0.023, ηp2 = 0.036): fasted individuals had similar inhibitory capacity for modal and amodal food stimuli but better inhibitory capacity for non-food words compared to images, while there were no inhibitory differences in dependence on either modality or stimulus type in satiated individuals. Thus, we were able to show that inhibitory capacities to modal compared to amodal stimuli depend on participants’ current state of fasting. Future studies should focus on how this lowered inhibitory capacity influences food intake, as well as the role of stimulus valence in cognitive processing, to clarify potential implications for dieting and weight loss training.
More cooperation than conflict despite no ‘Third Level’? Understanding the dynamics of paradiplomacy towards the EU in Bavaria and Baden-Württemberg
2024-07-09

This article advances new understandings of paradiplomacy in action, by reconsidering the mobilisation towards the EU of two German Länder, Bavaria and Baden-Württemberg, over a 30-year period (1992–2022). Refining its traditional usage as a catch-all concept, we deploy a novel typology of layers of paradiplomatic activity, in order to unpack the inherent dynamics of substate engagement with the EU and explore the implications of paradiplomacy on intergovernmental relations in Germany. We find little difference between Bavaria and Baden-Württemberg in the dominant mode of interaction with the federal government resulting from paradiplomacy, the cooperative mode, though modes of interaction differ across the layers of paradiplomatic activity, ranging from more active cooperation in the policy space through to benign neglect on cross-border cooperation and on regional identity promotion.
Associations between adrenal gland volume and adipose tissue compartments – a whole body MRI study
2024-07-09

Abstract Background Obesity is associated with alterations in the hypothalamic–pituitary–adrenal (HPA) axis. Effects of glucocorticoids on adipose tissues appear to depend on the specific adipose depot, in which they take place. In this study, we aimed to investigate the role of MRI-based adrenal gland volume as an imaging marker in association with different adipose tissue compartments. Methods The study cohort derives from the population-based research platform KORA ( Cooperative Health Research in the Augsburg Region, Germany) MRI sub-study, a cross-sectional sub-study investigating the interactions between subclinical metabolic changes and cardiovascular disease in a study sample of 400 participants. Originally, eligible subjects underwent a whole-body MRI. MRI-based segmentations were performed manually and semi-automatically for adrenal gland volume, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), epi- and pericardial fat and renal sinus fat. Hepatic and pancreatic lipid content were measured as pancreatic proton density fraction (PDFF) and MR-spectroscopic hepatic fat fraction (HFF). Multivariable linear regression analyses were performed. Results A number of 307 participants (56.2 ± 9.1 years, 60.3% male, 14.3% with type 2 diabetes (T2DM), 30.6% with obesity, 34.2% with hypertension) were included. In multivariable analyses, strong positive associations between adrenal gland volume and VAT, total adipose tissue (TAT) as well as HFF persisted after extensive step-wise adjustment for possible metabolic confounders (VAT: beta = 0.31, 95%-CI [0.71, 0.81], p &lt; 0.001; TAT: beta = 0.14, 95%-CI [0.06, 0.23], p &lt; 0.001; HFF: beta = 1.17, 95%-CI [1.04, 1.31], p = 0.009). In contrast, associations between adrenal gland volume and SAT were attenuated in multivariate analysis after adjusting for BMI. Associations between pancreatic PDFF, epi- and pericardial fat and renal sinus fat were mediated to a great extent by VAT (pancreatic PDFF: 72%, epicardial adipose tissue: 100%, pericardial adipose tissue: 100%, renal sinus fat: 81.5%). Conclusion Our results found MRI-based adrenal gland volume as a possible imaging biomarker of unfavorable adipose tissue distribution, irrespective of metabolic risk factors. Thus, adrenal gland volume may serve as a potential MRI-based biomarker of metabolic changes and contributes to an individual characterization of metabolic states and individual risk stratification. Future studies should elucidate in a longitudinal study design, if and how HPA axis activation may trigger unfavorable adipose tissue distribution and whether and to which extent this is involved in the pathogenesis of manifest metabolic syndrome.
A semi-analytical x-space solution for parton evolution — Application to non-singlet and singlet DGLAP equation
2024-07-09

A bstract We present a novel semi-analytical method for parton evolution. It is based on constructing a family of analytic functions spanning x -space which is closed under the considered evolution equation. Using these functions as a basis, the original integro-differential evolution equation transforms into a system of coupled ordinary differential equations, which can be solved numerically by restriction to a suitably chosen finite subsystem. The evolved distributions are obtained as analytic functions in x with numerically obtained coefficients, providing insight into the analytic behavior of the evolved parton distributions. As a proof-of-principle, we apply our method to the leading order non-singlet and singlet DGLAP equation. Comparing our results to traditional Mellin-space methods, we find good agreement. The method is implemented in the code POMPOM in Mathematica as well as in Python.
Viscous circumbinary protoplanetary discs – I. Structure of the inner cavity
2024-07-10

ABSTRACT Many of the most intriguing features, including spirals and cavities, in the current disc observations are found in binary systems like GG Tau, HD 142527, or HD 100453. Such features are evidence of the dynamic interactions between binary stars and the viscous disc. Understanding these dynamic interactions and how they result in the structure and growth of asymmetric circumbinary discs is a difficult problem, for which there is no complete analytical solution, that predicts the shape of the observed disc accurately. We use numerical simulations to evolve circumbinary discs with varying disc viscosities and investigate the size and shape of the inner cavities in such protoplanetary discs. We have simulated over 140 locally isothermal 2D grid-based disc models for 3 × 104 binary orbits each and mapped out the parameter space relevant for protoplanetary discs. With this, it becomes possible to create parametrized profiles for individual discs to compare to observations and find limits to their binary eccentricity or internal viscosity from the simulation data. In the long-term simulations, larger cavity sizes than previously considered are possible within the parameter space ( 6 binary separations). As an example, we find that the eccentricity of the disc around HD 142527 suggests the impact of the binary dynamics on the disc. However, even considering the larger cavity sizes, the large size of the cavity in HD 142527 remains unexplained by the simulations considering the most recent orbital constraints.
Longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adults
2024-07-10

Abstract Background For over three decades, the concomitance of cortical neurodegeneration and white matter hyperintensities (WMH) has sparked discussions about their coupled temporal dynamics. Longitudinal studies supporting this hypothesis remain nonetheless scarce. Methods In this study, we applied regional and global bivariate latent growth curve modelling (BLGCM) to longitudinal data from 436 cognitively unimpaired participants (DELCODE cohort; median age 69.70 [IQR 65.44, 74.49] years; 52.98% female) to examine the extent to which WMH and cortical thickness were interrelated over a four-year period. Results Our findings were three-fold. First, at baseline, individuals with larger WMH volumes had lower mean cortical thicknesses over the entire brain. Second, individuals who experienced a steeper thinning of their cingulate and temporal cortices over time had larger baseline WMH volumes in the frontal, parietal, and occipital lobes. Third, individuals with thinner cortices at baseline tended to undergo faster WMH progression over four years, particularly in the occipital and parietal lobes. Conclusions Our study suggests that cortical thinning and WMH progression could be mutually reinforcing rather than parallel, unrelated processes, which become entangled before cognitive deficits are detectable. Trial Registration German Clinical Trials Register (DRKS00007966, 04/05/2015)
Proton-pump inhibitors increaseC. difficileinfection risk by altering pH rather than by affecting the gut microbiome based on a bioreactor model
2024-07-10

Abstract Clostridioides difficile infections often occur after antibiotic use, but they have also been linked to proton-pump inhibitor (PPI) therapy. The underlying mechanism—whether infection risk is due to a direct effect of PPIs on the gut microbiome or changes in gastrointestinal pH—has remained unclear. To disentangle both possibilities, we studied the impact of the proton-pump inhibitor omeprazole and pH changes on key members of the human gut microbiome and stool-derived microbial communities from different donors in vitro . We then developed a custom multiple-bioreactor system to grow a model human microbiome community in chemostat mode and tested the effects of omeprazole exposure, pH changes, and their combination on C. difficile growth within this community. Our findings show that changes in pH significantly affect the gut microbial community’s biomass and the abundances of different strains, leading to increased C. difficile growth within the community. However, omeprazole treatment alone did not result in such effects. These findings imply that the higher risk of C. difficile infection following proton-pump inhibitor therapy is probably because of alterations in gastrointestinal pH rather than a direct interaction between the drug and the microbiome. This understanding paves the way for reducing infection risks in proton-pump inhibitor therapy.
A Series of Cyclopentadienyl Lanthanum Complexes with Metalloid Germanium Clusters
2024-07-10

A series of cyclopentadienyllanthanum complexes with the disilylated metalloid germanium cluster [Ge<sub>9</sub>(Hyp)<sub>2</sub>]<sup>2-</sup> [Hyp = Si(SiMe<sub>3</sub>)<sub>3</sub>] has been prepared and fully characterized. The synthetic procedure is based on the salt metathesis reaction of two different cyclopentadienyllanthanum diiodides CpLaI<sub>2</sub> (Cp: Cp*, pentamethylcyclopentadienyl; Cp<sup>ttt</sup>, 1,2,4-tri-<i>tert</i>-butylcyclopentadienyl) with K<sub>2</sub>[Ge<sub>9</sub>(Hyp)<sub>2</sub>] in tetrahydrofuran (THF) with a subsequent extraction with <i>n</i>-hexane. The composition of the obtained compounds and the mode of coordination of the germanium cluster to the rare-earth metal are strongly influenced by the steric demand of the cyclopentadienyl ligands and the crystallization conditions. The centrosymmetric dimeric compounds with the common formula [CpLa(solv)(η<sup>2,3</sup>-Ge<sub>9</sub>(Hyp)<sub>2</sub>)]<sub>2</sub> [<b>1</b>, Cp = Cp*, solv-THF; <b>2</b>, Cp = Cp<sup>ttt</sup>, solv-NCCH<sub>2</sub>C(Me)NSiMe<sub>3</sub>] have been isolated by the slow evaporation of a <i>n</i>-hexane solution, while a mononuclear complex [Cp<sup>ttt</sup>La(THF)<sub>2</sub>(η<sup>3</sup>-Ge<sub>9</sub>(Hyp)<sub>2</sub>)] (<b>4</b>) was found by crystallization from THF. The repeated recrystallization of <b>1</b> from <i>n</i>-hexane afforded the asymmetric dimer [Cp*La(THF)(η<sup>2,3</sup>-Ge<sub>9</sub>(Hyp)<sub>2</sub>)][Cp*La(η<sup>2,3</sup>-Ge<sub>9</sub>(Hyp)<sub>2</sub>)] (<b>3</b>) with only one coordinated THF molecule.
De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome
2024-07-11

Abstract Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes 1 . Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome 2 . We identify an 18 base pair region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 115 individuals with NDD. Most individuals (77.4%) have the same highly recurrent single base insertion (n.64_65insT). In 54 individuals in whom it could be determined, the de novo variants were all on the maternal allele. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to RNU4-1 and other U4 homologues. Using RNA sequencing, we show how 5′ splice-site use is systematically disrupted in individuals with RNU4-2 variants, consistent with the known role of this region during spliceosome activation. Finally, we estimate that variants in this 18 base pair region explain 0.4% of individuals with NDD. This work underscores the importance of non-coding genes in rare disorders and will provide a diagnosis to thousands of individuals with NDD worldwide.
Characterization of zoonotic hepatitis E virus in domestic pigs and wild boar in Vietnam: Implications for public health
2024-07-11

Vietnam's unprecedented demand for meat from livestock, including pigs and farmed wildlife, underscores the importance of understanding zoonotic reservoirs for hepatitis E virus (HEV). This study aimed to identify and characterize circulating zoonotic HEV in domestic pigs and wild boar to understand genotype frequencies, transmission dynamics, and associated human health burdens. Rectal swabs, feces, and liver samples from 415 pigs and 102 wild boars were collected across various farms and slaughterhouses in central and southern Vietnam and screened for HEV RNA using nested PCR. HEV RNA-positive samples underwent sanger sequencing and genotyping. Overall, 10% (n = 54/517) of samples were HEV RNA-positive, with wild boars exhibiting the highest HEV positivity rate at 25%, followed by domestic pigs at 7%. Southern Vietnam showed a higher HEV RNA positivity rate (20%) compared to central Vietnam (7%). Notably, rectal swabs demonstrated the highest positivity rate (15%), followed by feces (8%) and liver (4%). HEV-3a was the predominant genotype at 85%, followed by HEV-4b at 9% and HEV-3f at 6%. While HEV-3a was distributed across both central and southern Vietnam, HEV-3f was exclusively detected in central Vietnam, and HEV-4b was identified in wild boar in southern Vietnam. These findings underscore the substantial prevalence of HEV in wild boars, emphasizing their potential as crucial zoonotic reservoirs alongside domestic pigs. Further investigations involving occupationally exposed individuals in high-prevalence areas are warranted to evaluate the human health impact of zoonotic hepatitis E and inform preventive measures. Regular epidemiological studies are imperative for assessing the prevalence and transmission of zoonotic HEV infections among common reservoirs, thereby aiding in the prevention of spillover events within the community.
China in the era of ‘Top-level design’: hard steering by the central commission for comprehensively deepening reform (CCCDR) in National policymaking
2024-07-11

This article reviews the history and working mode of the Central Commission for Comprehensively Deepening Reform (CCCDR) to shed light on the underpinnings of 'top-level design' in China's policy process. We demonstrate the paradoxical nature of the CCCDR's 'hard steering': on the one hand, agenda-setting and the creation of major reform policies has been centralized and highly formalized; on the other hand, local circumstances are not adequately taken into account, resulting in low resource-efficiency in policy implementation. This article makes an important contribution to our understanding of the Chinese policy process under conditions of 'top-level design'. By showing how political steering is conducted at the central level and by drawing on a case study, we also critically assess the CCP's governing capacity in the Xi Jinping era.
Macrophage Migration Inhibitory Factor Promotes Thromboinflammation and Predicts Fast Progression of Aortic Stenosis
2024-07-11

BACKGROUND: Aortic stenosis (AS) is driven by progressive inflammatory and fibrocalcific processes regulated by circulating inflammatory and valve resident endothelial and interstitial cells. The impact of platelets, platelet-derived mediators, and platelet-monocyte interactions on the acceleration of local valvular inflammation and mineralization is presently unknown. METHODS: We prospectively enrolled 475 consecutive patients with severe symptomatic AS undergoing aortic valve replacement. Clinical workup included repetitive echocardiography, analysis of platelets, monocytes, chemokine profiling, aortic valve tissue samples for immunohistochemistry, and gene expression analysis. RESULTS: The patients were classified as fast-progressive AS by the median ∆Vmax of 0.45 m/s per year determined by echocardiography. Immunohistological aortic valve analysis revealed enhanced cellularity in fast-progressive AS (slow- versus fast-progressive AS; median [interquartile range], 247 [142.3–504] versus 717.5 [360.5–1234]; P &lt;0.001) with less calcification (calcification area, mm 2 : 33.74 [27.82–41.86] versus 20.54 [13.52–33.41]; P &lt;0.001). MIF (macrophage migration inhibitory factor)-associated gene expression was significantly enhanced in fast-progressive AS accompanied by significantly elevated MIF plasma levels (mean±SEM; 6877±379.1 versus 9959±749.1; P &lt;0.001), increased platelet activation, and decreased intracellular MIF expression indicating enhanced MIF release upon platelet activation (CD62P, %: median [interquartile range], 16.8 [11.58–23.8] versus 20.55 [12.48–32.28], P =0.005; MIF, %: 4.85 [1.48–9.75] versus 2.3 [0.78–5.9], P &lt;0.001). Regression analysis confirmed that MIF-associated biomarkers are strongly associated with an accelerated course of AS. CONCLUSIONS: Our findings suggest a key role for platelet-derived MIF and its interplay with circulating and valve resident monocytes/macrophages in local and systemic thromboinflammation during accelerated AS. MIF-based biomarkers predict an accelerated course of AS and represent a novel pharmacological target to attenuate progression of AS.