julilili42/papers huggingface dataset:
The inflammatory spectrum of cardiomyopathies
2024-02-23

Infiltration of the myocardium with various cell types, cytokines and chemokines plays a crucial role in the pathogenesis of cardiomyopathies including inflammatory cardiomyopathies and myocarditis. A more comprehensive understanding of the precise immune mechanisms involved in acute and chronic myocarditis is essential to develop novel therapeutic approaches. This review offers a comprehensive overview of the current knowledge of the immune landscape in cardiomyopathies based on etiology. It identifies gaps in our knowledge about cardiac inflammation and emphasizes the need for new translational approaches to improve our understanding thus enabling development of novel early detection methods and more effective treatments.
Identification and quantification of projectile impact marks on bone: new experimental insights using osseous points
2024-02-23

Abstract Shifts in projectile technology potentially document human evolutionary milestones, such as adaptations for different environments and settlement dynamics. A relatively direct proxy for projectile technology is projectile impact marks (PIM) on archaeological bones. Increasing awareness and publication of experimental data sets have recently led to more identifications of PIM in various contexts, but diagnosing PIM from other types of bone-surface modifications, quantifying them, and inferring point size and material from the bone lesions need more substantiation. Here, we focus on PIM created by osseous projectiles, asking whether these could be effectively identified and separated from lithic-tipped weapons. We further discuss the basic question raised by recent PIM research in zooarchaeology: why PIM evidence is so rare in archaeofaunal assemblages (compared to other human-induced marks), even when they are explicitly sought. We present the experimental results of shooting two ungulate carcasses with bone and antler points, replicating those used in the early Upper Paleolithic of western Eurasia. Half of our hits resulted in PIM, confirming that this modification may have been originally abundant. However, we found that the probability of a skeletal element to be modified with PIM negatively correlates with its preservation potential, and that much of the produced bone damage would not be identifiable in a typical Paleolithic faunal assemblage. This quantification problem still leaves room for an insightful qualitative study of PIM. We complement previous research in presenting several diagnostic marks that retain preservation potential and may be used to suggest osseous, rather than lithic, projectile technology.
Redundancy and Complementarity in Language and the Environment: How Intermodal Information Is Combined to Constrain Learning
2024-02-23

Abstract To acquire language, learners have to map the language onto the environment, but languages vary as to how much information they include to constrain how a sentence relates to the world. We investigated the conditions under which information within the language and the environment is combined for learning. In a cross‐situational artificial language learning study, participants listened to transitive sentences and viewed two scenes, and selected which scene was described by the sentence. There were three conditions, involving different language variants. All variants had free word order but varied as to whether or not they contained morphosyntactic information that defined the subject and object roles of nouns in the sentence. We found that participants were able to learn information about word order and vocabulary from each variant, demonstrating that learners are not reliant on information within a language only, but can combine constraints from language and environment to support acquisition. Data and analyses are available at: https://osf.io/hxqzc/?view_only=ea6ba6fff6bb468e8de2e8596f029dca
Power-to-Vitamins: Producing Folate (Vitamin B9) from Renewable Electric Power and CO2with a Microbial Protein System
2024-02-23

Abstract Meeting a surging demand for superior micronutrient-rich protein sources and finding production practices that are less detrimental to the climate will be critical challenges of the 21 st century. New technologies are needed to decouple food production from land use. Our group previously proposed a two-stage Power-to-Protein technology to produce microbial protein from renewable electric power and CO2. Two stages were operated in series : (1) Clostridium ljungdahlii in Stage A to utilize H2 to reduce CO2 into acetate; and (2) Saccharomyces cerevisiae in Stage B to utilize O2 and produce microbial protein from acetate. Renewable energy would power water electrolysis to produce H2 and O2. A disadvantage of C. ljungdahlii in Stage A is the need to continuously feed vitamins to sustain growth and acid production. Changing to the more robust thermophilic acetogen Thermoanaerobacter kivui avoids providing any vitamins. Additionally, S. cerevisiae produces folate when grown with acetate as a sole carbon source under aerobic conditions. A total folate concentration of 6.7 mg per 100 g biomass with an average biomass concentration of 3 g L -1 in Stage B is achieved. The developed Power-to-Vitamin system enables folate production from renewable power and CO2 with zero or negative net-carbon emissions.
Ferritinophagy: Assessing the Selective Degradation of Iron by Autophagy in Human Fibroblasts
2024-02-23

Mutations in the autophagy gene WDR45/WIPI4 are the cause of beta-propeller-associated neurodegeneration (BPAN), a subtype of human diseases known as neurodegeneration with brain iron accumulation (NBIA) due to the presence of iron deposits in the brains of patients. Intracellular iron levels are tightly regulated by a number of cellular mechanisms, including the critical mechanism of ferritinophagy. This paper describes how ferritinophagy can be assessed in primary, skin-derived human fibroblasts. In this protocol, we use iron-modulating conditions for inducing or inhibiting ferritinophagy at the cellular level, such as the administration of bafilomycin A1 to inhibit lysosome function and ferric ammonium citrate (FAC) or deferasiox (DFX) treatments to overload or deplete iron, respectively. Such treated fibroblasts are then subjected to high-throughput imaging and CellProfiler-based quantitative localization analysis of endogenous ferritin and autophagosomal/lysosomal markers, here LAMP2. Based on the level of autophagosomal/lysosomal ferritin, conclusions can be drawn regarding the level of ferritinophagy. This protocol can be used to assess ferritinophagy in BPAN patient-derived primary fibroblasts or other types of mammalian cells.
Physical activity improves stress load, recovery, and academic performance-related parameters among university students: a longitudinal study on daily level
2024-02-24

Abstract Background Physical activity has been proven to be beneficial for physical and psychological health as well as for academic achievement. However, especially university students are insufficiently physically active because of difficulties in time management regarding study, work, and social demands. As they are at a crucial life stage, it is of interest how physical activity affects university students' stress load and recovery as well as their academic performance. Methods Student ́s behavior during home studying in times of COVID-19 was examined longitudinally on a daily basis during a ten-day study period ( N = 57, aged M = 23.5 years, SD = 2.8, studying between the 1st to 13th semester ( M = 5.8, SD = 4.1)). Two-level regression models were conducted to predict daily variations in stress load, recovery and perceived academic performance depending on leisure-time physical activity and short physical activity breaks during studying periods. Parameters of the individual home studying behavior were also taken into account as covariates. Results While physical activity breaks only positively affect stress load (functional stress b = 0.032, p &lt; 0.01) and perceived academic performance (b = 0.121, p &lt; 0.001), leisure-time physical activity affects parameters of stress load (functional stress: b = 0.003, p &lt; 0.001, dysfunctional stress: b = -0.002, p &lt; 0.01), recovery experience (b = -0.003, p &lt; 0.001) and perceived academic performance (b = 0.012, p &lt; 0.001). Home study behavior regarding the number of breaks and longest stretch of time also shows associations with recovery experience and perceived academic performance. Conclusions Study results confirm the importance of different physical activities for university students` stress load, recovery experience and perceived academic performance in home studying periods. Universities should promote physical activity to keep their students healthy and capable of performing well in academic study: On the one hand, they can offer opportunities to be physically active in leisure time. On the other hand, they can support physical activity breaks during the learning process and in the immediate location of study.
Defining benchmark outcomes for mesial temporal lobe epilepsy surgery: A global multicenter analysis of 1119 cases
2024-02-24

Abstract Objective Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug‐resistant mesial temporal lobe epilepsy (MTLE). Methods This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow‐up. Patients were risk‐stratified by applying outcome‐relevant comorbidities, and benchmarks were calculated for low‐risk (“benchmark”) cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. Results A total of 1119 patients with a mean age (range) of 36.7 (1–74) years and a male‐to‐female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in‐hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%–72.9% of cases per center and leaving 742 patients in the high‐risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow‐up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1‐year follow‐up) and ≥69.5% (mean follow‐up of 39.0 months). Significance This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques.
Synaptic vesicle characterization of iPSC-derived dopaminergic neurons provides insight into distinct secretory vesicle pools
2024-02-24

ABSTRACT The impairment of dopaminergic (DA) neurons plays a central role in the development of Parkinson’s disease. Evidence for distinct populations of synaptic vesicles (SVs) differing in neurotransmitter content (glutamate versus dopamine) has been attributed to differences in trafficking pathways and their exocytosis kinetics. However, the molecular and ultrastructural organization of the two types of vesicles remains poorly understood. Here we examined the development of axonal varicosities in human iPSC-derived DA neurons and glutamatergic neurons (i 3 Neurons). While i 3 Neurons are comprised of 40-50 nm small clear SVs, DA neurons are predominantly comprised of large pleiomorphic vesicles including empty and dense core vesicles, in addition to the classical SVs. The large vesicles were positive for VMAT2, the monoamine vesicular transporter responsible for loading dopamine, and are distinctly larger in size and spatially segregated from the VGLUT1/2-positive vesicles when expressed in an ectopic SV-like organelle reconstitution system. Moreover, these VMAT2-positive vesicles were also colocalized to known SV markers such as Rab3, SCAMP5, VAMP2, SV2C and can be clustered by the matrix protein synapsin. Our results show that DA neurons display inherent differences in their populations of neurotransmitter-containing secretory vesicles, and iPSC-derived neurons are powerful models for the study of presynaptic structures.
Sweeping the dirt under the rug: measuring spillovers of an anti-corruption measure
2024-02-24

Abstract This article studies the spillover effects of an Italian anti-corruption measure targeting municipalities colluding with organized crime. We assess its impact on neighboring municipalities’ procurement practices. Our findings reveal that neighboring municipalities increase contracts falling below the 40,000 Euro threshold, which bear lighter evidentiary requirements, and are consequently harder to monitor. The neighboring municipalities strategically evade stricter regulations by fragmenting major projects into different sub-threshold contracts. Our analysis presents three evidence that this response stems from greater law enforcement monitoring. First, the number of arrests increases in the area after the implementation of the measure. Then, we demonstrate that the spillovers are more pronounced in areas with greater prior law enforcement activity. Lastly, we illustrate how neighboring municipalities react to the dissolution by reducing their engagement in activities that are more susceptible to monitoring. This is evident in their decreased participation in renegotiating public works contracts (JEL D730, H570, K420).
BTK and MMP9 regulate NLRP3 inflammasome-dependent cytokine and NET responses in primary neutrophils
2024-02-24

Abstract Background Inflammation is a double-edged state of immune activation that is required to resolve threats harmful to the host but can also cause severe collateral damage. Polymorphonuclear neutrophils (PMN,) the primary leukocyte population in humans, mediate inflammation through the release of cytokines and neutrophil extracellular traps (NETs). Whilst the pathophysiological importance of NETs is unequivocal, the multiple molecular pathways driving NET release are not fully defined. Recently, NET release was linked to the NLRP3 inflammasome which is regulated by Bruton’s tyrosine kinase (BTK) in macrophages. Objective As NLRP3 inflammasome regulation by BTK has not been studied in neutrophils, we here explored a potential regulatory role of BTK in primary murine and human neutrophils and matched monocytes or macrophages from Btk-deficient vs WT mice or healthy donors (HD) vs BTK deficient X-linked agammaglobulinemia (XLA) patients, respectively. Methods Cytokine, MPO and MMP-9 release were quantified by ELISA, NET release and inflammasome formation by immunofluorescence. Results Surprisingly, in both mouse and human primary neutrophils, we observed a significant increase in NLRP3 inflammasome-dependent IL-1β and NETs when BTK was absent or inhibited, whereas IL-1β release was decreased in corresponding primary mouse macrophages or human PBMC, respectively. This suggests a negative regulatory role of BTK in neutrophil NLRP3 activation. Both IL-1β and NET release in mouse and human primary neutrophils were strictly dependent on NLRP3, caspase-1 and, surprisingly, MMP-9. Conclusion This highlights BTK and MMP-9 as novel and versatile inflammasome regulators and may have implications for the clinical use of BTK inhibitors. Key messages Neutrophils contribute to inflammation by release of interleukin-1β and Neutrophil Extracellular Traps (NETs) via the NLRP3 inflammasome Bruton’s tyrosine kinase (BTK) is a negative regulator of NLRP3-mediated primary human neutrophil functions, whereas it positively regulates NLRP3 in monocytes MMP-9 is both effector and regulator of the neutrophil NLRP3 inflammasome Capsule summary Here we report that interleukin-1β and Neutrophil Extracellular Traps (NETs) release via the NLRP3 inflammasome is negatively regulated by Bruton’s tyrosine kinase (BTK) in primary neutrophils. Thus, targeting BTK using FDA-approved inhibitors might increase neutrophil functions.
An iPSC model for POLR3A-associated spastic ataxia: Generation of three unrelated patient cell lines
2024-02-25

Spastic Ataxias (SA) are a group of neurodegenerative disorders with combined pyramidal and cerebellar system affection, leading to an overlap phenotype between Hereditary Spastic Paraplegias (HSP) and Cerebellar Ataxias (CA). Here we describe the generation of iPSCs from three unrelated patients with an ultra-rare subtype of SA caused by compound heterozygous mutations in POLR3A, that encodes the largest subunit of RNA polymerase III. iPSCs were reprogrammed from normal human dermal fibroblasts (NHDFs) using episomal reprogramming with integration-free plasmid vectors: HIHRSi004-A, derived from a 44 year-old male carrying the mutations c.1909 + 22G > A/c.3944_3945delTG, HIHRSi005-A obtained from a 66 year-old male carrying the mutations c.1909 + 22G > A/c.1531C > T, and HIHRSi006-A from a 27 year-old male carrying the mutations c.1909 + 22G > A/c.2472_2472delC (ENST00000372371.8).
Modern anthropogenic drought in Central Brazil unprecedented during last 700 years
2024-02-26

Abstract A better understanding of the relative roles of internal climate variability and external contributions, from both natural (solar, volcanic) and anthropogenic greenhouse gas forcing, is important to better project future hydrologic changes. Changes in the evaporative demand play a central role in this context, particularly in tropical areas characterized by high precipitation seasonality, such as the tropical savannah and semi-desertic biomes. Here we present a set of geochemical proxies in speleothems from a well-ventilated cave located in central-eastern Brazil which shows that the evaporative demand is no longer being met by precipitation, leading to a hydrological deficit. A marked change in the hydrologic balance in central-eastern Brazil, caused by a severe warming trend, can be identified, starting in the 1970s. Our findings show that the current aridity has no analog over the last 720 years. A detection and attribution study indicates that this trend is mostly driven by anthropogenic forcing and cannot be explained by natural factors alone. These results reinforce the premise of a severe long-term drought in the subtropics of eastern South America that will likely be further exacerbated in the future given its apparent connection to increased greenhouse gas emissions.
The driving force behind tool-stone selection in the African Middle Stone Age
2024-02-26

In the Stone Age, the collection of specific rocks was the first step in tool making. Very little is known about the choices made during tool-stone acquisition. Were choices governed by the knowledge of, and need for, specific properties of stones? Or were the collected raw materials a mere by-product of the way people moved through the landscape? We investigate these questions in the Middle Stone Age (MSA) of southern Africa, analyzing the mechanical properties of tool-stones used at the site Diepkloof Rock Shelter. To understand knapping quality, we measure flaking predictability and introduce a physical model that allows calculating the relative force necessary to produce flakes from different rocks. To evaluate their quality as finished tools, we investigate their resistance during repeated use activities (scraping or cutting) and their strength during projectile impacts. Our findings explain tool-stone selection in two emblematic periods of the MSA, the Still Bay and Howiesons Poort, as being the result of a deep understanding of these mechanical properties. In both cases, people chose those rocks, among many others, that allowed the most advantageous trade-off between anticipated properties of finished tools and the ease of acquiring rocks and producing tools. The implications are an understanding of African MSA toolmakers as engineers who carefully weighed their choices taking into account workability and the quality of the tools they made.
Multidisciplinary approach and treatment of acral and mucosal melanoma
2024-02-26

Acral and mucosal melanoma are uncommon variants of melanoma. Acral melanoma has an age-adjusted incidence of approximately 1.8 cases per million individuals per year, accounting for about 2% to 3% of all melanoma cases. On the other hand, mucosal melanoma, with an incidence of 2.2 cases per million per year, makes up around 1.3% of all melanoma cases. These melanomas, in addition to being biologically and clinically distinct from cutaneous melanoma, share certain clinical and pathologic characteristics. These include a more aggressive nature and a less favorable prognosis. Furthermore, they exhibit a different mutational pattern, with KIT mutations being more prevalent in acral and mucosal melanomas. This divergence in mutational patterns may partially account for the relatively poorer prognosis, particularly to immune checkpoint inhibitors. This review explores various aspects of acral and mucosal melanoma, including their clinical presentation, pathologic features, mutational profiles, current therapeutic approaches, outcomes associated with systemic therapy, and potential strategies to address resistance to existing treatments.
Rare-Earth-Metal Methyl and Methylidene Complexes Stabilized by TpR,R′-Scorpionato Ligands─Size Matters
2024-02-26

Homoleptic tetramethylaluminates Ln(AlMe<sub>4</sub>)<sub>3</sub> react with KTp<sup><i>t</i>Bu,Me</sup> (Tp<sup><i>t</i>Bu,Me</sup> = tris(3-<i>t</i>Bu-5-Me-pyrazolyl)borato) to yield rare-earth-metal methylidene complexes (Tp<sup><i>t</i>Bu,Me</sup>)Ln(μ<sub>3</sub>-CH<sub>2</sub>)[(μ-Me)AlMe<sub>2</sub>]<sub>2</sub> (Ln = La, Ce, Nd). The lanthanum reaction is prone to additional C-H- and B-N-bond activation, affording coproducts La[HB(pz<sup>Me,<i>t</i>Bu</sup>)(pz<sup>CMe2,Me</sup>)<sub>2</sub>][(μ-CH<sub>2</sub>)(μ-Me)AlMe<sub>2</sub>]<sub>2</sub> and [La(μ-pz<sup><i>t</i>Bu,Me</sup>)(AlMe<sub>4</sub>)<sub>2</sub>]<sub>2</sub> (pz<sup><i>t</i>Bu,Me</sup> = 3-<i>t</i>Bu-5-Me-pyrazolato). The protonolysis reaction of Ln(AlMe<sub>4</sub>)<sub>3</sub> and Hpz<sup><i>t</i>Bu,Me</sup> provides more efficient access to [Ln(μ-pz<sup><i>t</i>Bu,Me</sup>)(AlMe<sub>4</sub>)<sub>2</sub>]<sub>2</sub> (Ln = La, Nd). Treatment of Ln(AlMe<sub>4</sub>)<sub>3</sub> with KTp<sup>Me,Me</sup> led to methylidene complexes (Tp<sup>Me,Me</sup>)Ln(μ<sub>3</sub>-CH<sub>2</sub>)[(μ-Me)AlMe<sub>2</sub>]<sub>2</sub> (Ln = Nd, Sm) or bis(tetramethylaluminate) complexes (Tp<sup>Me,Me</sup>)Ln(AlMe<sub>4</sub>)<sub>2</sub> (Ln = Y, Lu). The neodymium reaction generated methine derivative (Tp<sup>Me,Me</sup>)Nd[(μ<sub>4</sub>-CH)(AlMe<sub>2</sub>)<sub>2</sub>(μ-pz<sup>,Me,Me</sup>)][(μ-Me)AlMe<sub>2</sub>] as a minor coproduct. The reaction of Ln(GaMe<sub>4</sub>)<sub>3</sub> (Ln = Y, La, Ce, Nd, Sm, Ho) with HTp<sup><i>t</i>Bu,Me</sup> gave methylidene complexes (Tp<sup><i>t</i>Bu,Me</sup>)Ln(μ<sub>3</sub>-CH<sub>2</sub>)[(μ-Me)GaMe<sub>2</sub>]<sub>2</sub> (Ln = La, Ce, Nd, Sm) and alkyl complexes (Tp<sup><i>t</i>Bu,Me</sup>)LnMe[(μ-Me)GaMe<sub>3</sub>] (Ln = Y, Ho), while competing B-N bond activation reactions produced GaMe<sub>2</sub>[BH(Me)(μ-pz<sup><i>t</i>Bu,Me</sup>)<sub>2</sub>] and (Tp<sup><i>t</i>Bu,Me</sup>)Ln(η<sup>2</sup>-pz<sup><i>t</i>Bu,Me</sup>)[(μ-Me)GaMe<sub>3</sub>] (Ln = Y, Ho). The steric impact of the Tp<sup>R,Me</sup> ligands was examined by cone angle calculations. Rare-earth-metal methylidene complexes (Tp<sup><i>t</i>Bu,Me</sup>)Ln(μ<sub>3</sub>-CH<sub>2</sub>)[(μ-Me)EMe<sub>2</sub>]<sub>2</sub> (E = Al, Ga) successfully promote carbonyl methylenation reactions upon addition of ketone.