julilili42/papers huggingface dataset:
Organotypic Retinal Explant Cultures from Macaque Monkey
2022-08-24

Hereditary retinal degeneration (RD) is characterized by progressive photoreceptor cell death. Overactivation of the cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) pathway in photoreceptor cells causes photoreceptor cell death, especially in models harboring phosphodiesterase 6b (PDE6b) mutations. Previous studies on RD have used mainly murine models such as rd1 or rd10 mice. Given the genetic and physiological differences between mice and humans, it is important to understand to which extent the retinas of primates and rodents are comparable. Macaques share a high level of genetic similarity with humans. Therefore, wild-type macaques (aged 1-3 years) were selected for the in vitro culture of retinal explants that included the retina-retinal pigment epithelium (RPE)-choroid complex. These explants were treated with different concentrations of the PDE6 inhibitor zaprinast to induce the cGMP-PKG signaling pathway and simulate RD pathogenesis. cGMP accumulation and cell death in primate retinal explants were subsequently verified using immunofluorescence and the TUNEL assay. The primate retinal model established in this study may serve for relevant and effective studies into the mechanisms of cGMP-PKG-dependent RD, as well as for the development of future treatment approaches.
Hydrodynamics of non-equilibrium soil water retention
2022-08-24

Water retention in soil exhibits diverse phenomena, including suction-saturation hysteresis, non-unique air entrapment at zero suction and negative suction under partial saturations. The constancy of suction after a long rest can be broken by relatively minor mechanical or hydraulic agitations such as low-amplitude wetting cycles -- this fact is here being related to metastable states that differ from the true equilibrium. The complete suction-saturation relationships are thus being recovered using non-equilibrium Landau's hydrodynamic theory and Onsager's reciprocity principles. Equilibrium suction does not pertain to hysteresis, yet can be approached through small amplitude agitations over long duration. Conditions for rate independence are being described, while rate-dependency are also accommodated and illustrated. Finally, it is shown that the new non-equilibrium theory retains the rigorously derived equilibrium result of the effective stress of partially saturated soils.
In vivo and In vitro Characterization of the ClpC AAA+ ATPase of Chlamydia trachomatis
2022-08-24

Abstract Bacterial AAA+ unfoldases are crucial for bacterial physiology by recognizing specific substrates and, typically, unfolding them for degradation by a proteolytic component. The c aseinolytic p rotease (Clp) system is one example where a hexameric unfoldase (e.g., ClpC) interacts with the tetradecameric proteolytic core ClpP. Unfoldases can have both ClpP-dependent and ClpP-independent roles in protein homeostasis, development, virulence, and cell differentiation. ClpC is an unfoldase predominantly found in Gram-positive bacteria and mycobacteria. Intriguingly, the obligate intracellular Gram-negative pathogen Chlamydia , an organism with a highly reduced genome, also encodes a ClpC ortholog, implying an important function for ClpC in chlamydial physiology. Here, we used a combination of in vitro and in vivo approaches to gain insight into the function of chlamydial ClpC. ClpC exhibits intrinsic ATPase and chaperone activities, with a primary role for the Walker B motif in the first nucleotide binding domain (NBD1). Furthermore, ClpC binds ClpP1P2 complexes via ClpP2 to form the functional protease ClpCP2P1 in vitro , which degraded arginine-phosphorylated β-casein. In vivo experiments confirmed that higher order complexes of ClpC are present in chlamydial cells. Importantly, the in vivo data further revealed severe negative effects of both overexpression and depletion of ClpC in Chlamydia as revealed by a significant reduction in chlamydial growth. Here again, NBD1 was critical for ClpC function. Hence, we provide the first mechanistic insight into the molecular and cellular function of chlamydial ClpC, which supports its essentiality in Chlamydia . ClpC is, therefore, a potential novel target for the development of anti-chlamydial agents. Significance Chlamydia trachomatis is an obligate intracellular pathogen and the world’s leading cause of preventable infectious blindness and bacterial sexually transmitted infections. Due to the high prevalence of chlamydial infections along with negative effects of current broad-spectrum treatment strategies, new anti-chlamydial agents with novel targets are desperately needed. In this context, bacterial Clp proteases have emerged as promising new antibiotic targets, since they often play central roles in bacterial physiology and, for some bacterial species, are even essential for survival. Here, we report on the chlamydial AAA+ unfoldase ClpC, its functional reconstitution and characterization, individually and as part of the ClpCP2P1 protease, and establish an essential role for ClpC in chlamydial growth and intracellular development, thereby identifying ClpC as a potential target for anti-chlamydial compounds.
Extending the Indications for Direct Transcutaneous Lower Blepharoplasty With an Infraorbital Incision to Tear Trough Deformities, Suborbicularis Oculi Fat, Festoons, and Revision Blepharoplasty
2022-08-24

Introduction: Treatment of high-grade lower eyelid deformities with massive skin laxity and retroseptal fat pads can be challenging. Common techniques such as the transconjunctival approach and transcutaneous technique performed through a subciliary incision are associated with increased complication rates. Direct excision of the lower eyelid through an infraorbital incision is an alternative technique that allows safe treatment of dermatochalasis and pigmentation and correction of tear trough deformities, suborbicularis oculi fat, and festoons. This study aimed to determine whether direct transcutaneous blepharoplasty with an infraorbital incision could be indicated for these conditions instead of the established operative methods. Methods: A retrospective study of 21 patients with Fratila grades 9 or 10, Hirmand grade 3, and Barton grade 3 who underwent direct transcutaneous lower eyelid blepharoplasty via an infraorbital incision under local anesthesia was performed. All patients underwent surgery during a 9-year period from January 2010 to December 2018. The follow-up period was 12 months. Results were rated postoperatively using Barton grading. Results: Of 21 consecutive patients (13 women and 8 men), 18 required retroseptal fat pad removal, 3 had laxity of the skin and orbicularis muscle, and 5 had triangular cheek festoons. Combined lower and upper blepharoplasty was performed for 12 patients. All patients were satisfied with their surgical results and major improvements were observed. Scar quality was considered good by all patients. Conclusion: Direct transcutaneous lower blepharoplasty of the orbital rim can be indicated for different tear trough deformities, suborbicularis oculi fat laxity, and festoons.
Additional file 4 of DNA methylation analysis of normal colon organoids from familial adenomatous polyposis patients reveals novel insight into colon cancer development
2022-08-24

Additional file 4: Table S2. Summary of DMR analysis across all studies used in study that overlapped DMRs identified in FAP study. Positive "meandiff" corresponds to increased beta values (DNA methylation) in FAP (or tumor samples).
Additional file 6 of DNA methylation analysis of normal colon organoids from familial adenomatous polyposis patients reveals novel insight into colon cancer development
2022-08-24

Additional file 6: Table S4. Summary of qPCR and RNA-seq analysis performed on selected gene targets. Positive fold changes and t values indicate increased expression in TCGA-COAD tumor and FAP colon organoids, respectively.
Closing the loop – The human role in artificial intelligence for education
2022-08-25

Recent advancements in artificial intelligence make its use in education more likely. In fact, existing learning systems already utilize it for supporting students’ learning or teachers’ judgments. In this perspective article, we want to elaborate on the role of humans in making decisions in the design and implementation process of artificial intelligence in education. Therefore, we propose that an artificial intelligence-supported system in education can be considered a closed-loop system, which includes the steps of (i) data recording, (ii) pattern detection, and (iii) adaptivity. Besides the design process, we also consider the crucial role of the users in terms of decisions in educational contexts: While some implementations of artificial intelligence might make decisions on their own, we specifically highlight the high potential of striving for hybrid solutions in which different users, namely learners or teachers, are provided with information from artificial intelligence transparently for their own decisions. In light of the non-perfect accuracy of decisions of both artificial intelligence-based systems and users, we argue for balancing the process of human- and AI-driven decisions and mutual monitoring of these decisions. Accordingly, the decision-making process can be improved by taking both sides into account. Further, we emphasize the importance of contextualizing decisions. Potential erroneous decisions by either machines or humans can have very different consequences. In conclusion, humans have a crucial role at many stages in the process of designing and using artificial intelligence for education.
Musical Activity During Life Is Associated With Multi-Domain Cognitive and Brain Benefits in Older Adults
2022-08-25

Regular musical activity as a complex multimodal lifestyle activity is proposed to be protective against age-related cognitive decline and Alzheimer’s disease. This cross-sectional study investigated the association and interplay between musical instrument playing during life, multi-domain cognitive abilities and brain morphology in older adults (OA) from the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study. Participants reporting having played a musical instrument across three life periods ( n = 70) were compared to controls without a history of musical instrument playing ( n = 70), well-matched for reserve proxies of education, intelligence, socioeconomic status and physical activity. Participants with musical activity outperformed controls in global cognition, working memory, executive functions, language, and visuospatial abilities, with no effects seen for learning and memory. The musically active group had greater gray matter volume in the somatosensory area, but did not differ from controls in higher-order frontal, temporal, or hippocampal volumes. However, the association between gray matter volume in distributed frontal-to-temporal regions and cognitive abilities was enhanced in participants with musical activity compared to controls. We show that playing a musical instrument during life relates to better late-life cognitive abilities and greater brain capacities in OA. Musical activity may serve as a multimodal enrichment strategy that could help preserve cognitive and brain health in late life. Longitudinal and interventional studies are needed to support this notion.
Low IGF1 and high IGFBP1 predict diabetes onset in prediabetic patients
2022-08-25

Abstract Objectives Some individuals develop type 2 diabetes mellitus (T2DM) despite significant metabolic improvements through lifestyle intervention. We tested the hypotheses that insulin growth factor 1 (IGF1) and its binding proteins 1 and 2 predict the onset of T2DM in prediabetes patients and determine the capacity for metabolic regeneration. Design We measured fasting serum IGF1, insulin growth factor-binding protein 1 (IGFBP1) and IGFBP2 in three randomized controlled lifestyle intervention trials, covering at least 1 year of intervention period and 1 year of additional follow-up. Methods Within a sample of 414 high-risk prediabetes patients (58% women; 28–80 years), we analyzed fasting serum concentrations of IGF1, IGFBP1 and IGFBP2 in relation to diabetes incidence and metabolic parameters over 2 years. Three hundred and forty-five subjects finished the first year of intervention. Results The interventions significantly improved body weight (BMI: −3.24%, P &amp;lt; 0.001), liver fat (−36.8%, P &amp;lt; 0.001), insulin sensitivity (IS) (homeostatic model assessment-insulin resistance: −6.3%, P &amp;lt; 0.001) and insulin secretion (disposition index: +35%, P &amp;lt; 0.001) in the cohort. Fourteen percent developed T2DM within 2 years. Mean IGFBP1 levels at baseline were lower in prediabetes compared to a healthy population. Also, prediabetes patients with obesity and nonalcoholic fatty liver disease had lower IGFBP1. Those with impaired glucose tolerance had higher IGFBP1 compared to those with only impaired fasting glucose. Baseline IGF1 was lower (122.5 vs 146.6 μg/L) and IGFBP1 was higher (3.32 vs 2.09 μg/L) in subjects who developed T2DM (n = 57), resulting in a significant prediction of diabetes incidence (hazard ratio (HR) IGF1: 0.991 μg/L, P = 0.003; HR IGFBP1: 1.061 μg/L, P = 0.002). This translates into a 20% and 9% difference in T2DM incidence for IGF1 and IGFBP1, respectively. Despite reduced weight, visceral fat and hepatic fat in response to 1 year of lifestyle intervention, those who developed T2DM had not improved insulin sensitivity, glucose tolerance or IGFBP1. Conclusions Lower IGF1 and higher IGFBP1 in prediabetes predicted the incidence of T2DM, indicating an impairment of beta-cell function, which explains the unresponsiveness to lifestyle intervention.
Two New Rhizobiales Species Isolated from Root Nodules of Common Sainfoin (Onobrychis viciifolia) Show Different Plant Colonization Strategies
2022-08-25

The intensive use of chemical fertilizers has a variety of negative effects on the environment. Increased utilization of biological nitrogen fixation (BNF) is one way to mitigate those negative impacts.
Accuracy of Three-Dimensional Soft-Tissue Prediction Considering the Facial Aesthetic Units Using a Virtual Planning System in Orthognathic Surgery
2022-08-25

Virtual surgical planning (VSP) is commonly used in orthognathic surgery. A precise soft-tissue predictability would be a helpful tool, for determining the correct displacement distances of the maxilla and mandible. This study aims to evaluate the soft-tissue predictability of the VSP software IPS CaseDesigner® (KLS Martin Group, Tuttlingen, Germany). Twenty patients were treated with bimaxillary surgery and were included in the study. The soft-tissue simulation, done by the VSP was exported as STL files in the engineering software Geomagic Control XTM (3D systems, RockHill, SC, USA). Four months after surgery, a 3D face scan of every patient was performed and compared to the preoperative simulation. The quality of the soft-tissue simulation was validated with the help of a distance map. This distance map was calculated using the inter-surface distance algorithm between the preoperative simulation of the soft-tissue and the actual scan of the postoperative soft-tissue surface. The prediction of the cranial parts of the face (upper cheek, nose, upper lip) was more precise than the prediction of the lower areas (lower cheek, lower lip, chin). The percentage of correctly predicted soft-tissue for the face in total reached values from 69.4% to 96.0%. The VSP system IPS CaseDesigner® (KLS Martin Group; Tuttlingen, Germany) predicts the patient’s post-surgical soft-tissue accurately. Still, this simulation has to be seen as an approximation, especially for the lower part of the face, and continuous improvement of the underlying algorithm is needed for further development.
A real-time fMRI neurofeedback system for the clinical alleviation of depression with a subject-independent classification of brain states: A proof of principle study
2022-08-25

Most clinical neurofeedback studies based on functional magnetic resonance imaging use the patient's own neural activity as feedback. The objective of this study was to create a subject-independent brain state classifier as part of a real-time fMRI neurofeedback (rt-fMRI NF) system that can guide patients with depression in achieving a healthy brain state, and then to examine subsequent clinical changes. In a first step, a brain classifier based on a support vector machine (SVM) was trained from the neural information of happy autobiographical imagery and motor imagery blocks received from a healthy female participant during an MRI session. In the second step, 7 right-handed female patients with mild or moderate depressive symptoms were trained to match their own neural activity with the neural activity corresponding to the “happiness emotional brain state” of the healthy participant. The training (4 training sessions over 2 weeks) was carried out using the rt-fMRI NF system guided by the brain-state classifier we had created. Thus, the informative voxels previously obtained in the first step, using SVM classification and Effect Mapping, were used to classify the Blood-Oxygen-Level Dependent (BOLD) activity of the patients and converted into real-time visual feedback during the neurofeedback training runs. Improvements in the classifier accuracy toward the end of the training were observed in all the patients [Session 4–1 Median = 6.563%; Range = 4.10–27.34; Wilcoxon Test (0), 2-tailed p = 0.031]. Clinical improvement also was observed in a blind standardized clinical evaluation [HDRS CE2-1 Median = 7; Range 2 to 15; Wilcoxon Test (0), 2-tailed p = 0.016], and in self-report assessments [BDI-II CE2-1 Median = 8; Range 1–15; Wilcoxon Test (0), 2-tailed p = 0.031]. In addition, the clinical improvement was still present 10 days after the intervention [BDI-II CE3-2_Median = 0; Range −1 to 2; Wilcoxon Test (0), 2-tailed p = 0.50/ HDRS CE3-2 Median = 0; Range −1 to 2; Wilcoxon Test (0), 2-tailed p = 0.625]. Although the number of participants needs to be increased and a control group included to confirm these findings, the results suggest a novel option for neural modulation and clinical alleviation in depression using noninvasive stimulation technologies.
Researching Alcohol Consumption During Pregnancy. Opportunities and Challenges With Two Methods of Data Acquisition
2022-08-25

Qualitative research methods, primarily interviews, have become more common in the field of addiction research. Other data sources were often neglected, although sources such as social media can offer insights into the realities of people, since social media also plays a relevant role in today's living environments. This article examines the use of online forums as an underutilized data source in contrast to telephone interviews, to identify methodological opportunities and challenges. We analyzed nine discussion threads and seven interviews about ‘alcohol consumption during pregnancy’. Discursive comparison of the results was performed with a focus on sampling issues, comparability and risks for participants and researchers. Key issues were present in both data sources. People with different opinions were openly hostile in forums, while tolerance was more often expressed in interviews. The interviews showed a rather mild communication style, which could be attributed to social desirability. In the forum discussions, the participants often expressed themselves very directly. To comprehensively grasp the subject matter of the research, it is important to recognize the types of communication promoted by different data sources. These results have implications for research about female substance use. Knowledge of the issues will bestow a valuable contribution to researchers working in the field of substance use to help develop appropriate research approaches, as they engage in research into this highly stigmatized and controversial area.
The kinesin motor KIF1C is a putative transporter of the exon junction complex in neuronal cells
2022-08-25

Abstract Neurons critically depend on regulated RNA localization and tight control of spatio-temporal gene expression to maintain their morphological and functional integrity. Mutations in the kinesin motor protein gene KIF1C cause Hereditary Spastic Paraplegia, an autosomal recessive disease leading to predominant degeneration of the long axons of central motoneurons. In this study we aimed to gain insight into the molecular function of KIF1C and understand how KIF1C dysfunction contributes to motoneuron degeneration. We used affinity proteomics in neuronally differentiated neuroblastoma cells (SH-SY5Y) to identify the protein complex associated with KIF1C in neuronal cells; candidate interactions were then validated by immunoprecipitation and mislocalization of putative KIF1C cargoes was studied by immunostainings. We found KIF1C to interact with all core components of the exon junction complex (EJC); expression of mutant KIF1C in neuronal cells leads to loss of the typical localization distally in neurites. Instead, EJC core components accumulate in the pericentrosomal region, here co-localizing with mutant KIF1C. These findings suggest KIF1C as a neuronal transporter of the EJC. Interestingly, the binding of KIF1C to the EJC is RNA-mediated, as treatment with RNAse prior to immunoprecipitation almost completely abolishes the interaction. Silica-based solid-phase extraction of UV-crosslinked RNA-protein complexes furthermore supports direct interaction of KIF1C with RNA, as recently also demonstrated for kinesin heavy chain. Taken together, our findings are consistent with a model where KIF1C transports mRNA in an EJC-bound and therefore transcriptionally silenced state along neurites, thus providing the missing link between the EJC and mRNA localization in neurons.
Issue linkage versus ringfencing in international agreements*
2022-08-25

Abstract Issue linkage is often regarded as a means to enhance international cooperation in the presence of a sovereignty constraint. This constraint means a country can leave an agreement whenever it likes, if the perceived gains from leaving are larger than the gains from staying in the agreement. We set up a model of international agreements in which future gains from cooperation are uncertain, and it is bad realizations that can lead to exit. In this environment, we show that ringfencing dominates issue linkage, even in the absence of complementarities between separate issues, if the degree of uncertainty is sufficiently large.