julilili42/papers huggingface dataset:
Nitric oxide modulates contrast suppression in a subset of mouse retinal ganglion cells
2024-12-13

Neuromodulators have major influences on the regulation of neural circuit activity across the nervous system. Nitric oxide (NO) has been shown to be a prominent neuromodulator in many circuits and has been extensively studied in the retina. Here, it has been associated with the regulation of light adaptation, gain control, and gap junctional coupling, but its effect on the retinal output, specifically on the different types of retinal ganglion cells (RGCs), is still poorly understood. In this study, we used two-photon Ca2+imaging and multi-electrode array (MEA) recordings to measure light-evoked activity of RGCs in the ganglion cell layer in the ex vivo mouse retina. This approach allowed us to investigate the neuromodulatory effects of NO on a cell type-level. Our findings reveal that NO selectively modulates the suppression of temporal responses in a distinct subset of contrast-suppressed RGC types, increasing their activity without altering the spatial properties of their receptive fields. Given that under photopic conditions, NO release is triggered by quick changes in light levels, we propose that these RGC types signal fast contrast changes to higher visual regions. Remarkably, we found that about one-third of the RGC types, recorded using two-photon Ca2+imaging, exhibited consistent, cell type-specific adaptational response changes throughout an experiment, independent of NO. By employing a sequential-recording paradigm, we could disentangle those additional adaptational response changes from drug-induced modulations. Taken together, our research highlights the selective neuromodulatory effects of NO on RGCs and emphasizes the need of considering non-pharmacological activity changes, like adaptation, in such study designs.
Sexual dimorphism in molecular profiles of resting human skeletal muscle and the response to acute exercise and endurance training
2024-12-13

Abstract Biological sex has a strong impact on skeletal muscle metabolism and performance. By a comprehensive investigation of epigenetic, transcriptomic and proteomic differences between female and male skeletal muscle of untrained subjects we provide a molecular basis for the sexual dimorphism of glucose and lipid metabolism. The sex-specific multi-OMICs profiles indicate higher degree of glucose turnover and higher abundance of fast-twitch fibers in males and high degree of lipid handling in females. Eight-week endurance training equalized initial differences toward an endurance-trained proteomic profile in both sexes. The untrained muscle of females was more resistant to an acute exercise challenge since stress-responsive transcripts were predominantly upregulated in males. In myotubes from the same donors, transcriptomic differences were hardly conserved, but could be partially restored by treatment with sex hormones. In conclusion, after only 8 weeks training mitigates deeply rooted sex-specific molecular profiles in skeletal muscle toward a common metabolically beneficial response.
Oscar Fraas – Pionier der urgeschichtlichen Forschung Zentral-europas und neue Erkenntnisse zu den Funden der Ausgrabung 1870/71 im Hohle Fels bei Schelklingen
2024-12-13

Oscar Fraas was one of the first natural scientists to establish the existence of Ice Age humans. From November 1854 until 1894, he held various positions in the Royal Natural History Cabinet in Stuttgart. As early as the 1860s, he conducted a series of experiments to explain and understand how traces and scratches on Ice Age bone fragments were made. His work is among the first attempts in the world to use Stone Age tools. These were often spontaneous field experiments whose results he did not verify or whose variables are no longer evident today. At the time, however, Fraas’ work was far ahead of most of his colleagues. Overall, Fraas described several attempts to fragment bones and dissect animals using bear mandibles. The following article provides an overview of the experiments carried out by Fraas. In addition, we will present for the first time the perforated horse teeth and bone retouchers from the first archaeological excavation in Hohle Fels in 1870/71 directed by Fraas, which are curated in the collection of the State Museum of Natural History Stuttgart. A new radiocarbon date establishes that Fraas reached at least as deep as the Gravettian layers during his excavation at Hohle Fels.
Mobility and the Importance of Bone and Bulb Retouchers in the Middle Palaeolithic of the Swabian Jura
2024-12-13

Modifying the form of lithic artifacts through retouch represents a central technological feature of the Middle Palaeolithic, and retouchers made of a variety of materials appear frequently in the archaeological record. Bone and bulb retouchers are the most common types. The first, are often described as ad hoc tools with short use-lives, while researchers have tentatively iden-tified the second as curated artifacts included in the mobile toolkit. Here we present two bulb retouchers from the Middle Palaeolithic layers VIII/VII of Sirgenstein Cave in the Ach Valley of the Swabian Jura, and discuss their general characteristics together with bone retouchers re-covered from the same archaeological layers. The data on bone and bulb retouchers from Sir-genstein support the proposed complementary uses of the two types of retouchers. We suggest that the intrinsic properties of bone and flint, together with other aspects specific to the chaînes operatoires of these two materials, played a major role in determining the retouchers’ suitability within toolkits, and can help to explain the high variability in retouching techniques encountered in the Middle Palaeolithic record. Based on these considerations, our study highlights the im-portance of the organization of technology and the potential of retouchers for reconstructing past mobility and settlement dynamics.
Exploring Myth and Reality at Paleolithic Sites in the Romanian Banat
2024-12-13

The early prehistory of the European subcontinent is marked by significant events, among which the immigration of anatomically modern humans (AMH) during the Marine Isotope Stage 3 (MIS 3, ~60,000 to 30,000 cal BP) stands out. Understanding the dynamics of this migration requires tracing the routes taken by AMH and documenting their spread across different regions, such as the Danube corridor. The Upper Pleniglacial period (MIS 2), encompassing the Last Glacial Maximum (LGM), presents another pivotal time in European prehistory. Recent research suggests the existence of a refuge in the Carpathian Basin during the LGM. However, our understanding of population dynamics and cultural evolution during this period in this region remains limited. To address these gaps, sites with well-preserved stratigraphic sequences are crucial.
Improving Clinical Management of Diabetic Macular Edema: Insights from a Global Survey of Patients, Healthcare Providers, and Clinic Staff
2024-12-14

The wealth of systematic data generated by this global survey highlights the breadth and scale of challenges associated with the clinical management of patients with diabetic macular edema. Addressing the opportunities for improvement raised by patients, providers, and clinic staff could increase patient adherence to treatment, reduce appointment burden, and improve clinic capacity.
A power law solution for FLRW universe with observational constraints
2024-12-14

This work analyzes a power law solution under [Formula: see text] gravity for an isotropic and homogeneous universe. To construct [Formula: see text] gravity model, we consider the functional form of [Formula: see text] as the sum of two independent functions of the Ricci scalar R and the trace of the energy–momentum tensor T, i.e. [Formula: see text], with [Formula: see text] being a positive constant where we study the cosmological model under the following two cases: (i) [Formula: see text] and (ii) [Formula: see text]. In the framework of [Formula: see text] gravity with homogeneous and isotropic spacetime, the constructed model yields several features on application of the scale factor [Formula: see text]. We employed the Markov Chain Monte Carlo (MCMC) approach to get model parameters [Formula: see text], [Formula: see text] and [Formula: see text] over a redshift range of [Formula: see text]. The model parameter’s restricted values are listed below: [Formula: see text] km [Formula: see text][Formula: see text]Mpc[Formula: see text], [Formula: see text][Formula: see text]km[Formula: see text] Mpc[Formula: see text], [Formula: see text][Formula: see text]km[Formula: see text]s[Formula: see text] Mpc[Formula: see text], [Formula: see text][Formula: see text]km[Formula: see text]s[Formula: see text][Formula: see text]Mpc[Formula: see text], [Formula: see text][Formula: see text]km[Formula: see text]s[Formula: see text][Formula: see text]Mpc[Formula: see text]. The model was constrained using the Hubble parameter ([Formula: see text]) dataset, Baryon Acoustic Oscillations (BAO) dataset, Pantheon dataset, joint [Formula: see text] + Pantheon dataset and collective [Formula: see text] + BAO + Pantheon dataset. The results from the Planck collaboration group are consistent with these calculated Ho observed values. In order to study and analyze the model, we first look at how the energy circumstances affected our power law assumption. The validity of the model has also been evaluated using the [Formula: see text] diagnostic and the jerk parameter, which are state finding diagnostic tools. We find that the model under investigation agrees with the observed fingerprints within a certain range of constraints.
Dissecting origins of wiring specificity in dense reconstructions of neural tissue
2024-12-15

Abstract What are the origins of the highly specific wiring patterns that are formed by the neurons in the brain? To address this question, we introduce a method to predict the empirically observed wiring diagram – the connectome – at synaptic resolution based on dense electron-microscopic reconstructions of neural tissue. Our method generates the connectome based on the morphological properties of the neurons in combination with synaptic specificity models, whose parameters capture how neurons wire conditional on their subcellular, cellular and cell type properties. We employ simulation-based Bayesian inference to identify all values for these parameters that can generate the observed connectome. Finally, for each synapse in a dense reconstruction, our method provides quantitative measures to reveal which synaptic specificity models are necessary, sufficient and best-suited to generate it. The output of our method are experimentally testable predictions of wiring preferences from subcellular to cell type levels that could account for each synapse in dense reconstructions. We demonstrate our method on dense datasets from mouse primary visual and human temporal cortex. Strikingly, this demonstration shows that just three assumptions, with nearly the same synaptic specificity values, predict the connectivity in both datasets. Our method is openly accessible as a computational framework that includes a comprehensive workflow for the analysis of wiring specificity, and which provides users with full flexibility to define and test their hypotheses. Our method sets the stage to uncover the principles by which neural networks are organized, and to compare these principles across brain areas, species and time points.
Nanostructured Ag‐MoS2 for Surface‐Enhanced Raman Scattering
2024-12-15

This study discusses the influence of the morphological characteristics of molybdenum disulfide (MoS 2 ) substrates on the detection efficiency of Rhodamine B (RhB) via surface‐enhanced Raman scattering (SERS). Commercially available MoS 2 powder and vertically aligned (VA‐MoS 2 ) synthesized using a chemical vapor deposition (CVD) technique are compared. The MoS 2 substrates are functionalized with silver nanoparticles Ag(NPs) through DC‐magnetron sputtering employing nitrogen as reactive gas. Scanning electron microscopy is employed to probe the morphology of the Ag‐ functionalized MoS 2 powder and VA‐MoS 2 samples. Raman spectroscopy demonstrates a significant enhancement in the SERS signal that can be attributed 1) to the MoS 2 valence band alteration reinforcing the chemical mechanism and 2) to the enhanced electric field generated by the Ag(NPs). The VA‐MoS 2 substrate decorated with Ag(NPs) exhibited a high enhancement factor of 3.5 × 10 8 and a low limit of detection of 10 −12 m . The abundance of platelet edges, enhanced by the vertically aligned shape, offers a higher amount of strong and localized electromagnetic field formed between nanoparticle dimers located on the edges, leading to a pronounced enhancement of the SERS signal.
Design, Synthesis, and Biochemical Evaluation of Novel MLK3 Inhibitors: A Target Hopping Example
2024-12-16

The human kinome has tremendous medical potential. In the past decade, mixed-lineage protein kinase 3 (MLK3) has emerged as an interesting and druggable target in oncogenic signaling. The important role of MLK3 has been demonstrated in several types of cancer. In a target hopping example we started with the focal adhesion kinase (FAK) inhibitor PF-431396 (<b>10</b>), which shows off-target activity toward MLK3. We were able to develop highly active compounds in the single digit nanomolar range for MLK3. Furthermore, we achieved a dramatic shift in selectivity from FAK to MLK3. Here we present a new chemical class of MLK3 inhibitors, including our lead compound <b>37</b> with an outstanding IC<sub>50</sub> value of <1 nM in a biochemical MLK3 assay while simultaneously exhibiting kinome-wide selectivity.
Dietary fiber pectin alters the gut microbiota and diminishes the inflammatory immune responses in an experimental peach allergy mouse model
2024-12-16

Abstract Since therapeutic options are limited the utilization of prebiotics is suggested to prevent food allergies (FAs). Using an experimental peach allergy model we explored the effect of dietary fiber pectin, a high-methoxyl heteropolysaccharide, on the manifestation of FA. CBA/J mice were sensitized, subsequently orally boosted and provoked with peach peel extract. For dietary intervention, mice were fed a pectin containing diet before (primary-preventive) or after (secondary-preventive) sensitization. Non-treated allergic and sham-treated mice were fed a diet containing 20% cellulose. Fecal microbiota, humoral and intestinal immune cell responses were analyzed. Pectin remarkably affected the gut microbiota composition and diversity, promoting mainly the growth of Bacteroides . The frequency of mast cells, macrophages, and CD3 + T cells in the lamina propria of the small intestine was reduced, whereas the frequency of B cells and CD4 + T cell subpopulation was enhanced. Pectin intervention in the primary-preventive stetting significantly triggered serum IgA levels, whereas production of IgE and mMCPT-1 was reduced. Remarkably, in both settings peach allergen-specific IgG1/IgG2a ratio and specific IgE were significantly reduced to baseline. The data suggest, that dietary supplementation of pectin in both intervention approaches can diminish inflammatory responses and signs of allergic immune responses, accompanied by alteration of the gut microbiota composition.
Nerve ultrasound helps to distinguish CIDP patients with diabetes from patients with diabetic polyneuropathy
2024-12-16

Abstract Diabetic polyneuropathy (DPN) shares overlapping clinical and electrodiagnostic features with chronic inflammatory demyelinating polyneuropathy (CIDP), which complicates the differential diagnosis of CIDP in diabetic patients. 32 patients with diabetes mellitus and CIDP, 68 patients with CIDP without diabetes, 83 patients with DPN, and 28 diabetic patients without polyneuropathy were examined using clinical scores (Overall Neuropathy Limitation Scale (ONLS), Neuropathy Symptom Score, Neuropathy Deficit Score), nerve conduction studies, and nerve ultrasound (Ultrasound Pattern Sum Score (UPSS)). The ONLS was significantly higher in the CIDP patients with diabetes than in DPN (median [interquartile range]: 4.0 [3.0] vs. 0 [1.0], p &lt; 0.001) as well as the UPSS (4.0 [6.0] vs. 0 [2.9], p &lt; 0.001). Multiple binary logistic regression revealed UPSS and ONLS as statistically significant predictors to differentiate between CIDP with diabetes and DPN. Receiver operating characteristic curve analysis showed the ONLS with an area under the curve (AUC) of 0.918 (95% CI: 0.868-0.0.967, p &lt; 0.001). The UPSS total score had an AUC of 0.826 (95% CI: 0.743–0.909, p &lt; 0.001). An UPSS ≥ 2.5 had a sensitivity of 77.4% and a specificity of 68.7% to detect CIDP. An ONLS ≥ 1.5 had a sensitivity of 87.1% and a specificity of 81.9% to detect CIDP. ROC curve analysis of a composite score of ONLS and UPSS revealed an AUC of 0.959 (95% CI: 0.928–0.991, p &lt; 0.001). CIDP is an important differential diagnosis in people with diabetes mellitus. This study reports that the UPSS is well suited to differentiate between DPN and CIDP.
Differential item functioning between English, German, and Spanish PROMIS® physical function ceiling items
2024-12-16

Abstract Purpose We investigated the validity of the German and Spanish translations of 35 new high functioning items added to the Patient Reported Outcomes Measurement Information System (PROMIS®) Physical Function item bank 2.0. We assessed differential item functioning (DIF) between three general population samples from Argentina, Germany, and the United States. Methods PROMIS Physical Function data was collected in online panels from 3601 individuals (mean age, 41.6 years old; range, 18–88 years; 53.7% female). Of these, 1001 participants completed the Spanish version, 1000 completed the German version, and 1600 completed the English version. DIF was assessed by a multiverse analysis that systematically varied analytic choices across the entire range of plausible options within the logistic ordinal regression framework. Results Translated items generally met the assumptions of unidimensionality, monotonicity, and local independence. The 272 different analyses suggest consistent DIF between languages in four items. Test characteristic curves suggested that the magnitude and impact of DIF on the test scores were negligible for all items at the test level. After correcting for potential DIF, we observed greater scoring for physical functioning in Argentina compared to the US, Cohen’s d = 0.25, [0.17, 0.33], and Argentina compared to Germany, Cohen’s d = 0.23, [0.15, 0.32]. Conclusions Our findings support the universal applicability of PROMIS Physical Function items across general populations in Argentina, Germany, and the U.S. The sensitivity analyses indicate that the identification of DIF items was robust for different data analytic decisions. Multiverse analysis is a promising approach to address lack of clear cutoffs in DIF identification.
Resource-aware research on Universe and Matter: call-to-action in digital transformation
2024-12-16

Abstract Given the urgency to reduce fossil fuel energy production to make climate tipping points less likely, we call for resource-aware knowledge gain in the research areas on Universe and Matter with emphasis on the digital transformation. A portfolio of measures is described in detail and then summarized according to the timescales required for their implementation. The measures will both contribute to sustainable research and accelerate scientific progress through increased awareness of resource usage.
COVID-19 and social distancing: pandemic has altered social relationships and contacts in older adults over 4 years
2024-12-16

Introduction Social isolation is a main risk factor for loneliness, health issues and psychological diseases. With its restriction measures, the coronavirus pandemic has led to an objective reduction in meaningful interactions, communication, and social contacts in general (social isolation). However, it has been shown that older adults cope differently with social isolation. Therefore, the aim of the present study was to investigate the changes of social contacts of older adults over the pandemic period of 4 years. Methods For this purpose, N = 175 older adults ( M age = 72.60, SD age = 6.12 years, Mdn age = 72, Range: 60–87 years) were asked at 3 time points (2019, 2021, 2023) with how many people they had contact in the reference month (May, November). In addition to the number of contacts, participants were also asked about the type of the relationship (e.g., family, friends, neighbors), the type of contact (e.g., telephone, video conference and/or by written messages) and the emotional closeness (close, medium, low). We used an ego-centered “social network” circle to measure social contacts of older adults before, during and after the pandemic. The data collection was limited by the changing corona restrictions. Results Results indicate that behavior in social contacts essentially depends on age, gender, and level of depression. We found a clear temporal drop in social contacts independently of age and gender during the pandemic. After the pandemic close contacts did not recover to prepandemic level. Especially, Young-Old (&amp;lt;72 years) recovered less in terms of the number of social contacts than the Old-Old (≥72 years). Discussion Our study, thus, provides longitudinal insights into the course of social contacts and suggests that social isolation may have more negative and long-term impact on close contacts, which need further clarification and temporal extension.
Self‐Regulation in Preschool: Are Executive Function and Effortful Control Overlapping Constructs?
2024-12-16

ABSTRACT The concepts of executive function (EF) and effortful control (EC) are strikingly similar. EF originates from neurocognitive research and is described as an accumulation of cognitive processes that serve the goal‐oriented self‐regulation of an individual. EC originates from temperament research and is defined as the efficiency of executive attention, including the ability to inhibit a dominant response, activate a subdominant response, proceed in a planned manner, and recognize conflicts or errors. The aim of this article was to examine the association between the constructs of EF and EC at the preschool age. Eighty‐eight children (49 female; M ‐age = 3.93 years, SD = 0.78) were tested with a computerized battery designed to assess EF at 3–6 years of age (EF Touch). Children's parents completed questionnaires assessing EF impairments (BRIEF‐P) and EC (children's behavior questionnaire [CBQ]). Associations between the constructs and their conceptual overlap were analyzed using correlations and confirmatory factor analyses. We found significant correlations between EF and EC measures. A two‐factor confirmatory model fitted the data better than a one‐factor model of self‐regulation. Therefore, our results show that measures of EC and EF have substantial overlap but are separable.