Miracle-dz/UniFAR-FTUs huggingface dataset:
PPP1R12C Promotes Atrial Hypocontractility in Atrial Fibrillation

BACKGROUND: Atrial fibrillation (AF)—the most common sustained cardiac arrhythmia—increases thromboembolic stroke risk 5-fold. Although atrial hypocontractility contributes to stroke risk in AF, the molecular mechanisms reducing myofilament contractile function remain unknown. We tested the hypothesis that increased expression of PPP1R12C (protein phosphatase 1 regulatory subunit 12C)—the PP1 (protein phosphatase 1) regulatory subunit targeting MLC2a (atrial myosin light chain 2)—causes hypophosphorylation of MLC2a and results in atrial hypocontractility. METHODS: Right atrial appendage tissues were isolated from human patients with AF versus sinus rhythm controls. Western blots, coimmunoprecipitation, and phosphorylation studies were performed to examine how the PP1c (PP1 catalytic subunit)-PPP1R12C interaction causes MLC2a dephosphorylation. In vitro studies of pharmacological MRCK (myotonic dystrophy kinase-related Cdc42-binding kinase) inhibitor (BDP5290) in atrial HL-1 cells were performed to evaluate PP1 holoenzyme activity on MLC2a. Cardiac-specific lentiviral PPP1R12C overexpression was performed in mice to evaluate atrial remodeling with atrial cell shortening assays, echocardiography, and AF inducibility with electrophysiology studies. RESULTS: In human patients with AF, PPP1R12C expression was increased 2-fold versus sinus rhythm controls (P=2.0×10−2; n=12 and 12 in each group) with >40% reduction in MLC2a phosphorylation (P=1.4×10−6; n=12 and 12 in each group). PPP1R12C-PP1c binding and PPP1R12C-MLC2a binding were significantly increased in AF (P=2.9×10−2 and 6.7×10−3, respectively; n=8 and 8 in each group). In vitro studies utilizing drug BDP5290, which inhibits T560-PPP1R12C phosphorylation, demonstrated increased PPP1R12C binding with both PP1c and MLC2a and dephosphorylation of MLC2a. Mice treated with lentiviral PPP1R12C vector demonstrated a 150% increase in left atrial size versus controls (P=5.0×10−6; n=12, 8, and 12), with reduced atrial strain and atrial ejection fraction. Pacing-induced AF in mice treated with lentiviral PPP1R12C vector was significantly higher than in controls (P=1.8×10−2 and 4.1×10−2, respectively; n=6, 6, and 5). CONCLUSIONS: Patients with AF exhibit increased levels of PPP1R12C protein compared with controls. PPP1R12C overexpression in mice increases PP1c targeting to MLC2a and causes MLC2a dephosphorylation, which reduces atrial contractility and increases AF inducibility. These findings suggest that PP1 regulation of sarcomere function at MLC2a is a key determinant of atrial contractility in AF.
A composite recruitment index to describe interannual changes in the population structure of Antarctic krill at South Georgia

A composite recruitment index based on density data derived from acoustic surveys and on length-frequency data obtained from either target or station net hauls is described. This composite index is compared with an index where density and length data are derived from standard station net hauls only. Comparison of these indices showed substantial differences, due in part to bias arising from a large number of krill in just one of the station net hauls. Therefore, when the number of station net hauls is limited, bias is likely to be reduced if target net haul data can be included by using the composite recruitment index. This index is used to describe the population structure of krill around South Georgia during seven cruises between 1989 and 1998. Before 1994 the number of 1+ krill found around South Georgia was very low (proportion of 1+ krill <7%), while between 1994 and 1998 the number of 1+ krill found in the population increased with a very successful recruitment year due to krill spawned in 1994/95.
Soils Stones and Symbols Cultural Perceptions of the Mineral World

Transforming the Earth: from veneration to exploitation Ochre, Clay, Stone and Art: the symbolic importance of minerals Striking Stones: the significance of stone in the monuments of Neolithic Britain A Phenomenology of the Buried Landscape The Role of Clay in Shaping the Neolithic World Geoarchaeology and the Goddess Laksmi The Cosmic Earth: materiality and mineralogy in the Americas Geology, Colour and Intentionality in the Megalithic Monuments of Western Europe Tools of the Ancestors Reading the Earth.
Lidocaine ameliorates intestinal barrier dysfunction in irritable bowel syndrome by modulating corticotropin‐releasing hormone receptor 2

Intestinal barrier dysfunction is a prevalent pathogenic factor underlying various disorders. Currently there is no effective resolution. Previous studies have reported the potential anti‐inflammatory properties of lidocaine and its ability to alleviate visceral hypersensitivity in individuals with irritable bowel syndrome (IBS). Therefore, our study will further verify the effect of lidocaine on intestinal barrier dysfunction in IBS and investigate the underlying mechanisms.
Minimally Invasive Surgery for Managing Grade IV and V Spondylolisthesis

Abstract Surgical treatment of high-grade spondylolisthesis is controversial and aims at restoring the spinopelvic sagittal balance through complete or partial reduction of the listhesis. Nerve decompression and interbody fusion are necessary for patients presenting with neurological deficit, severe pain, lower limb asymmetry, or deformities. We present the case and the results of a patient with high-grade spondylolisthesis, in whom minimally invasive management was performed. A narrative review in this topic is also provided. We performed a literature review of high-grade spondylolisthesis to compare our technique to current surgical alternatives. We included articles from PubMed, Embase, Scopus, Ovid, and Science Direct published between 1963 and 2022 that were written in English, German, and Spanish. The terms used were the following: “high grade spondylolisthesis,” “spondyloptosis,” “surgical management,” “interbody fusion,” and “arthrodesis. ” In all, 485 articles were displayed, from which we filtered 112 by title and abstract. At the end, 75 references were selected for the review. Different interbody fusion techniques can be used to correct the lumbosacral kyphosis and restore the spinopelvic parameters. A complete reduction of the listhesis is not always required. The surgical procedure carried out in our patient corresponds to the first known case of minimally invasive circumferential arthrodesis with iliac screws and sacral fixation in a high-grade dysplastic spondylolisthesis. This approach guarantees the correction of the lumbosacral kyphosis and a complete reduction of the listhesis. Further studies are required to determine whether the results of this case can be extrapolated to other patients with high-grade spondylolisthesis.
Well-trained Endurance Runners’ Foot Contact Patterns: Barefoot vs. Shod Condition

Abstract We aimed to investigate the initial foot contact and contact time in experienced endurance runners at individualized speeds, in running shoes and barefoot. Forty-eight participants (33.71±7.49 y, 70.94±8.65 kg, 175.07±7.03 cm, maximum aerobic speed 18.41±1.54 km . h -1 ) were distributed into three groups according to athletic performance: highly-trained runners, middle-trained runners, and control group. An incremental running test until exhaustion was performed for assessing maximum aerobic speed. After≥24 h of recovery participants randomly walked and ran, barefoot and in running shoes, over a pressure plate at ~4.7 km . h -1 and 85% of the maximum aerobic speed, respectively. They wore the same model of running shoes with homogeneous lacing pattern. A rearfoot strike was performed by 68.8% and 77.1% of participants when running barefoot and in running shoes, respectively. Considering the tendency to develop a rearfoot strike was lower in the barefoot condition, runners with higher performance may benefit from training in minimalist running shoes because their foot contact pattern could tend towards a non-rearfoot strike. Our results suggest that initial foot contact and contact time are related to running performance and may also be influenced by running shoes.
Characterization of Chlorinated Ethene Degradation in a Vertical Flow Constructed Wetland

Abstract : Chlorinated solvents, including perchloroethene (PCE) and trichlorethene (TCE), are among the most common groundwater contaminants found in the United States. The use of constructed wetlands has shown promise as an effective and less costly alternative for the treatment of chlorinated solvent contaminated groundwater. This study characterized and evaluated the concentration of chlorinated ethenes within a vertical flow constructed wetland, fed with PCE contaminated groundwater, at Wright-Patterson Air Force Base (WPAFB), Ohio. Chlorinated ethene concentrations were characterized within three distinct layers of the wetland cell, as well as within the influent, and effluent. In addition, a pore-water sampler prototype was designed and developed for this research effort in order to obtain a more detailed contaminant profile. PCE concentrations declined from an average of 46.5 mug/L in the influent to an average of 0.5 mug/L in the upper layer, a 98.9% decrease. The chlorinated ethene concentration profiles indicate that the lower half of the wetland provides favorable conditions for the complete anaerobic reductive dechlorination of the PCE. Within the upper half of the wetland, contaminant profiles indicate dominant degradation processes other than anaerobic reductive dechlorination, possibly including aerobic or anaerobic oxidation or direct volatization.
Towards Efficient Interaction for Personal Health Data Queries on Smartwatches

The smartwatch is rapidly becoming a go-to personal health tracking device, allowing for the collection of a broad range of personal health data. Yet, access to this data is often limited to discrete glanceable visualizations. This in part is due to a lack in our understanding of the queries desired to access such data. Thus, as practitioners and application designers, our ability to enable efficient exploratory interactions is limited. In this work, through analysis of a public dataset, we characterize personal health data queries desired for exploration on the smartwatch across multiple dimensions: (i) data requested and attributes of this data, (ii) aggregation methods, (iii) mechanisms for filtering, and (iv) interrogatives used. We conclude with discussion around our findings that can be utilized in future works aimed toward enabling efficient interaction with personal health data on the smartwatch.
Subcortical volumes, frontal cortical thickness, and pro-inflammatory cytokines in schizophrenia versus methamphetamine-induced psychosis

Background Clinical features of schizophrenia and methamphetamine-induced psychosis (MAP) have significant overlap. Schizophrenia is associated with alterations in subcortical volumes, cortical thickness and pro-inflammatory cytokines that may correlate with clinical features. However, analogous work on MAP is lacking. This study compared subcortical volumes, cortical thickness and pro-inflammatory cytokines in individuals with schizophrenia, MAP, and healthy controls. It also assessed associations of neuroimaging measures and cytokine levels with each other, with illness duration and symptom severity in schizophrenia and MAP, and with duration of substance use in MAP. Methods Participants included 36 individuals with schizophrenia, 27 with MAP, and 32 healthy controls matched for age and sex. Diagnosis was determined using the Structured Clinical Interview for Axis I Disorders and symptom severity was assessed using the Positive and Negative Syndrome Scale. Structural T1-weighted images were acquired using a 3 Tesla magnetic resonance imaging scanner. Serum peripheral cytokine concentrations levels were measured using a multiplex bead array. Analysis of covariance was used to compare measures across groups. Results Individuals with schizophrenia and with MAP had decreased left amygdala volumes and frontal cortical thickness compared to healthy controls. Individuals with schizophrenia had increased volumes in bilateral caudate, putamen, and nucleus accumbens compared to healthy controls, and increased right globus pallidus and NAcc volumes compared to MAP. Individuals with MAP had increased right orbitofrontal cortical thickness compared to healthy controls. Decreased left amygdala volumes and frontal cortical thickness were significantly associated with longer illness duration in schizophrenia, and with longer duration of methamphetamine use in MAP. There was no significant difference across groups in cytokine levels, and no significant associations of cytokine levels with neuroimaging or clinical measures. Conclusion This study found overlaps and differences in the neurobiology of schizophrenia and MAP, a finding that is consistent with previous research. Further studies with larger sample sizes and more robust measures are needed to understand immune mechanisms underlying these conditions.
Uncovering Invariant Representations in Functional Neuroimaging with Deep Metric Learning

With the increasing ability to record neuroimaging with higher spatial and temporal resolution, there is a growing need for methods that reduce these high-dimensional representations into latent low-dimensional structures that are discriminative and/or predictive of behavior, disease, or in general experimental context. We propose a metric learning framework to extract meaningful latent structures from high-dimensional fMRI data. This method learns the latent embeddings that reduce the intra-group variability while maximizing the inter-group variability. In addition, our method leverages advances in few-shot learning approaches to adapt to small sample-size fMRI datasets, allowing one to learn the latent structure from just a few samples per context. We evaluate our work on two publicly available fMRI datasets and report superior results compared to popular alternative approaches such as Principal Component Analysis (84.7% vs. 60%; 21.8% vs. 8.3%). We provide the Python code as open-source at Github.
PURA Syndrome-causing mutations impair PUR-domain integrity and affect P-body association

Mutations in the human PURA gene cause the neuro-developmental PURA syndrome. In contrast to several other mono-genetic disorders, almost all reported mutations in this nucleic acid binding protein result in the full disease penetrance. In this study, we observed that patient mutations across PURA impair its previously reported co-localization with processing bodies. These mutations either destroyed the folding integrity, RNA binding or dimerization of PURA. We also solved the crystal structures of the N- and C-terminal PUR domains of human PURA and combined them with molecular dynamics simulations and NMR measurements. The observed unusually high dynamics and structural promiscuity of PURA indicated that this protein is particularly susceptible to mutations impairing its structural integrity. It offers an explanation why even conservative mutations across PURA result in the full penetrance of symptoms in patients with PURA syndrome.
Cohesin mediated loop extrusion from active enhancers form chromatin jets in C. elegans

In mammals, cohesin and CTCF organize the 3D genome into topologically associated domains (TADs) to regulate communication between cis-regulatory elements. However, many organisms, including S. cerevisiae, C. elegans, and A. thaliana lack CTCF. Here, we use C. elegans as a model to investigate the function of cohesin in 3D genome organization in an animal without CTCF. We use auxin-inducible degradation to acutely deplete SMC-3 or its negative regulator WAPL-1 from somatic cells. Using Hi-C data, we identify a cohesin-dependent 3D genome organization feature called chromatin jets (aka fountains). These are population average reflections of DNA loops that are ∼20-40 kb in scale and often cover a few transcribed genes. The jets emerge from NIPBL occupied segments, and the trajectory of the jets coincides with cohesin binding. Cohesin translocation from jet origins depends on a fully intact complex and is extended upon WAPL-1 depletion. Hi-C results support the idea that cohesin is preferentially loaded at NIPBL occupied sites and loop extrudes in an effectively two-sided manner. The location of putative loading sites coincide with active enhancers and the strength of chromatin jet pattern correlates with transcription. Hi-C analyses upon WAPL-1 depletion reveal unequal loop extrusion processivity on each side and stalling due to cohesin molecules colliding. Compared to mammalian systems, average processivity of C. elegans cohesin is ∼10-fold shorter and NIPBL binding does not depend on cohesin. We conclude that the processivity of cohesin scales with genome size; and regardless of CTCF presence, preferential loading of cohesin at enhancers is a conserved mechanism of genome organization that regulates the interaction of gene regulatory elements in 3D.
A new dataset and empirical relationships between magnitude/intensity and epicentral distance for liquefaction in central-eastern Sicily

Strong earthquakes can trigger several phenomena inducing soil deformation, such as liquefaction, ground fracturing and landslides, which can often cause more damage than the seismic shaking itself. A research performed on numerous historical accounts reporting descriptions of seismogeological effects in central-eastern Sicily, allowed the authors to update the previous liquefaction datasets. 75 liquefaction-induced phenomena observed in 26 sites, triggered by 14 earthquakes, have been used to define relationships between intensity/magnitude values and epicentral distance from the liquefied sites. The proposed upper bound-curves, at regional scale for central- eastern Sicily, are realized by using the updating liquefaction dataset and also the new CPTI04 Italian earthquake parametric catalogue. These relationships can be useful in hazard assessment to evaluate the minimum energy of an earthquake inducing liquefactions.
Prediction of body weight from body volume of Savanna goats in Limpopo province, South Africa

Savanna goats is one of the South African commercial meat breeds. This study was conducted to predict body weight from body volume (BV), heart girth (HG) and body length (BL). A total of 139 savanna goats of the age between 1 and 5 years old of different sex (male and female) were used in the study for collection of body weight, body length and heart girth. The animals were kept under semi-intensive production system, where they were supplemented in the afternoon. Body volume was derived using cylinder volume formula from body length and heart girth as the components of model. R-studio software was employed for Pearson correlation matrix to assess the association between body weight, body length, heart girth and body volume. Simple linear regression was used to establish model to predict body weight. Pearson correlation results indicated that BW had a highly statistical significant (p<0.01) correlation with HG (r = 0.90), BV (r = 0.84) and BL (r = 0.66), respectively. Regression model findings indicated that HG had highest coefficient of determination (R2 = 0.81) and lowest mean square error (MSE = 24.85), and BV indicated highest coefficient of determination (R2 = 0.76) and low mean square error of (MSE = 35.07) while BL indicated lowest coefficient determination of (R2 = 0.45) and high mean square error (MSE = 70.80). In conclusion, correlation result suggests that by improving HG, BV and BL will result in improving BW of Savanna goats. Simple linear regression suggest that HG and BV can be used to estimate BW of Savanna goats.
Early morning run-training results in enhanced endurance performance adaptations in mice

Time-of-day differences in acute exercise performance in mice are well established with late active phase (afternoon) runners exhibiting significantly greater endurance performance compared to early active phase (morning) runners. In this study, we asked if performance adaptations would be different when training for 6 weeks at two different times of day, and if this corresponds to steady state changes in the phase of peripheral tissue clocks. To address these questions, we endurance trained female PER2::Luciferase mice, at the same relative workload, either in the morning, at ZT13, or in the afternoon, at ZT22. Then, after training, we recorded luminescence from tissues of PER2::Luciferase mice to report timing of tissue clocks in several peripheral tissues. After 6 weeks, we found that both groups exhibited significant improvements in maximal endurance capacity (total treadmill work)(p < 0.0001), but the morning runners exhibited an enhanced rate of adaptation as there was no detectable difference in maximal endurance capacity (p = 0.2182) between the morning and afternoon runners. In addition, morning and afternoon runners exhibited divergent clock phase shifts with a significant 5-hour phase advance in the EDL (p < 0.0001) and soleus (p < 0.0001) of morning runners, but a phase delay in the EDL (p < 0.0001) and Soleus (p < 0.0001) of afternoon runners. Therefore, our data demonstrate that morning training enhances endurance adaptations compared to afternoon training in mice, and we suggest this is due to phase advancement of muscle clocks to better align metabolism with exercise performance. Key points summary Time-of-day differences in exercise performance are well established in the literature. We observe that after 6 weeks of endurance exercise training there is no longer a time-of-day specific difference in endurance performance. Consistent endurance training performed in morning (ZT13) results in a greater performance increase compared to exercise training during the afternoon (ZT22). Removal of time-of-day differences in performance through exercise training is strongly associated with significant phase shifts (~5 hour advance) of the muscle clock.
Intra-ocular Predation of Fluoroquinolone-Resistant Pseudomonas aeruginosa and Serratia marcescens by Predatory Bacteria

Endogenous endophthalmitis caused by Gram-negative bacteria is an intra-ocular infection that can rapidly progress to irreversible loss of vision. While most endophthalmitis isolates are susceptible to antibiotic therapy, the emergence of resistant bacteria necessitates alternative approaches to combat intraocular bacterial proliferation. In this study the ability of predatory bacteria to limit intraocular growth of Pseudomonas aeruginosa, Serratia marcescens, and Staphylococcus aureus was evaluated in a New Zealand White rabbit endophthalmitis prevention model. Predatory bacteria Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus were able to reduce proliferation of keratitis isolates of P. aeruginosa and S. marcescens. However, it was not able to significantly reduce S. aureus, which is not a productive prey for these predatory bacteria, suggesting that the inhibitory effect on P. aeruginosa requires active predation rather than an antimicrobial immune response. Similarly, UV-inactivated B. bacteriovorus were unable to prevent proliferation of P. aeruginosa. Together, these data suggest in vivo predation of Gram-negative bacteria within the intra-ocular environment.