Miracle-dz/UniFAR-FTUs huggingface dataset:
Gaussian curvature dilutes the nuclear lamina, favoring nuclear rupture, especially at high strain rate

Nuclear rupture has long been associated with deficits or defects in lamins, with recent results also indicating a role for actomyosin stress, but key physical determinants of rupture remain unclear. Here, lamin-B stably interacts with the nuclear membrane at sites of low Gaussian curvature yet dilutes at high-curvature to favor rupture, whereas lamin-A depletes similarly but only at high strain-rates. Live cell imaging of lamin-B1 gene-edited cancer cells is complemented by fixed-cell imaging of ruptured nuclei in: iPS-derived cells from progeria patients, cells within beating chick embryo hearts, and cancer cells that develop multiple ruptures in migrating through small pores. Dilution and curvature-dependent rupture fit a parsimonious model of a stiff filament that detaches from a curved surface, suggesting an elastic-type response of lamin-B, but rupture is also modestly suppressed by inhibiting myosin-II and by hypotonic stress, which slow the strain rates. Lamin-A dilution and nuclear rupture likelihood indeed increase above a threshold rate of pulling into small pipettes, suggesting a viscoplastic coupling to the envelope for protection against nuclear rupture. Summary statement High nuclear curvature drives lamina dilution and nuclear envelope rupture even when myosin stress is inhibited. Stiff filaments generally dilute from sites of high Gaussian curvature, providing mathematical fits of experiments.
Quantifying the scale of genetic diversity extinction in the Anthropocene

1Department of Plant Biology, Carnegie Institution for Science, Stanford, CA 94305, USA. 2Department of Biology, Stanford University, Stanford, CA 94305, USA. 3Department of Global Ecology, Carnegie Institution for Science, Stanford, CA 94305, USA. 4Department of Zoology, University of British Columbia, Vancouver, Canada. 5Biodiversity Research Centre, University of British Columbia, Vancouver, Canada. 6Department of Genetics, Stanford University, Stanford, CA 94305, USA. 7Department of Computer Science, Stanford University, Stanford, CA 94305, USA. 8Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA 90095, USA. 9Center for Macroecology, Evolution and Climate, GLOBE Inst. , Univ. of Copenhagen, Copenhagen, Denmark. *To whom correspondence should be addressed: moisesexpositoalonso@gmail.com &Authors are listed alphabetically
Extremely reduced supergroup F Wolbachia: transition to obligate insect symbionts

Wolbachia are widely distributed symbionts among invertebrates that manifest by a broad spectrum of lifestyles from parasitism to mutualism. Wolbachia Supergroup F is considered a particularly interesting group which gave rise to symbionts of both arthropods and nematodes, and some of its members are obligate mutualists. Further investigations on evolutionary transitions in symbiosis have been hampered by a lack of genomic data for Supergroup F members. In this study, we present genomic data for five new supergroup F Wolbachia strains associated with four chewing lice species. These new strains in different evolutionary stages show genomic characteristics well-illustrating the evolutionary trajectory which symbiotic bacteria experience during their transition to mutualism. Three of the strains have not yet progressed with the transition, the other two show typical signs of ongoing gene deactivation and removal (genome size, coding density, low number of pseudogenes). Particularly, wMeur1, a symbiont fixed in all Menacanthus eurysternus populations across four continents, possesses a highly reduced genome of 733,850 bp with a horizontally acquired capacity for pantothenate synthesis. Comparing with other strains showed wMeur1 genome as the smallest currently known among all Wolbachia and the first example of Wolbachia which has completed genomic streamlining known from the gammaproteobacterial obligate symbionts.
A High-Resolution Method for the Systematic Detection of EMS-Induced Mutations in a Sequenced Population

The precise detection of causal DNA mutations is very crucial for forward genetic studies. Several sources of errors contribute to false-positive detections by current variant-calling algorithms, and these impact associating phenotypes with genotypes. To improve the accuracy of mutation detection we propose and implemented a high-resolution binning method for the accurate detection of likely EMS-induced mutations in a sequenced mutant population. The approach also incorporates a novel clustering algorithm for detecting likely false negatives with high accuracy. Sorghum bicolor is a very valuable crop species with tremendous potential for uncovering novel gene functions associated with highly desirable agronomical traits. We demonstrate the precision of the proposed method in the detection of likely EMS-induced mutations in the publicly available low-cost sequencing of the M3 generation from 600 sorghum BTx623 mutants. The method detected 3,274,606 single nucleotide polymorphisms (SNPs) of which 96% (3,141,908) were G/C to A/T DNA substitutions, as expected by EMS-mutagenesis action. We demonstrated the general applicability of the method, and showed a high concordance, 94% (3,074,759) SNPs overlap between SAMtools-based and GATK-based variant-calling algorithms. We also implemented a novel clustering algorithm which uncovered evidence for an additional 223,048 likely false-negative shared EMS-induced mutations. The final 3,497,654 SNPs represents an 87% increase in SNPs detected in the previous analysis of the sorghum mutant population. Annotation of the final SNPs revealed 10,263 high impact and 136,639 moderate impact SNPs, including 7,217 stop-gained mutations, and an average of 12 stop-gained mutations per mutant. We have implemented a public search database for this new genetic resource of 30,285 distinct sorghum genes containing medium or high impact EMS-induced mutations. Seedstock for a select 486 of the 600 described mutants are publicly available in the Germplasm Resources Information Network (GRIN) database.
Palaeogenomics reveal a hybrid origin of the world’s largest Camelus species

The extinct Camelus knoblochi is known as the largest camel in genus Camelus, but its relationship to modern Camelus species remains unclear. In this study, we reported the first mitochondrial and nuclear analyses of seven Late Pleistocene C. knoblochi samples from Northeastern China. We found that they are inseparable to wild Bactrian camel on the matrilineal side, but belong to a distinct cluster on the biparental nuclear side. Further admixture proportion analyses suggested hybrid ancestry between both the ancestors of the modern wild and domesticated Bactrian camels, with ~65% contribution from the former and ~35% from the later. By calculating the coalescence time for three Camelus species above, we estimated the hybridization event occurred between approximately 0.8 and 0.33 Ma. We also used Bayesian skyline to reconstruct the maternal demographic trajectories for different Camelus to better compare their evolutionary histories. Our results provide molecular insights into C. knoblochi and fill in a vital piece in understanding the genus Camelus.
Integrated analysis of single-cell and transcriptome based RNA-seq multilayer network and WGCNA for construction and validation of an immune cell-related prognostic model in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer (RCC). The increasing incidence and poor prognosis of ccRCC after tumour metastasis makes the study of its pathogenesis extremely important. Traditional studies mostly focus on the regulation of ccRCC by single gene, while ignoring the impact of tumour heterogeneity on disease progression. The purpose of this study is to construct a prognostic risk model for ccRCC by analysing the differential marker genes related to immune cells in the single-cell database for providing help in clinical diagnosis and targeted therapy. Single-cell data and ligand-receptor relationship pair data were downloaded from related publications, and ccRCC phenotype and expression profile data were downloaded from TCGA and CPTAC. The DEGs and marker genes of the immune cell were combined and then intersected with the ligand-receptor gene data, and the 981 ligand-receptor relationship pairs obtained were intersected with the target gene of the transcription factor afterwards; 7,987 immune cell multilayer network relationship pairs were finally observed. Then, the genes in the network and the genes in TCGA were intersected to obtain 966 genes for constructing a co-expression network. Subsequently, 53 genes in black and magenta modules related to prognosis were screened by WGCNA for subsequent analysis. Whereafter, using the data of TCGA, 28 genes with significant prognostic differences were screened out through univariate Cox regression analysis. After that, LASSO regression analysis of these genes was performed to obtain a prognostic risk scoring model containing 16 genes, and CPTAC data showed that the effectiveness of this model was good. The results of correlation analysis between the risk score and other clinical factors showed that age, grade, M, T, stage and risk score were all significantly different (p < 0.05), and the results of prognostic accuracy also reached the threshold of qualification. Combined with clinical information, univariate and multivariate Cox regression analyses verified that risk score was an independent prognostic factor (p < 0.05). A nomogram constructed based on a predictive model for predicting the overall survival was established, and internal validation performed well. Our findings suggest that the predictive model built based on the immune cells scRNA-seq will enable us to judge the prognosis of patients with ccRCC and provide more accurate directions for basic relevant research and clinical practice.
Composite receptive fields in the mouse auditory cortex

A central question in sensory neuroscience is how neurons represent complex natural stimuli. This process involves multiple steps of feature extraction to obtain a condensed, categorical representation useful for classification and behavior. It has previously been shown that central auditory neurons in the starling have composite receptive fields composed of multiple features when probed with conspecific songs. Whether this property is an idiosyncratic characteristic of songbirds, a group of highly specialized vocal learners, or a generic characteristic of central auditory systems in different animals is, however, unknown. To address this question, we have recorded responses from auditory cortical neurons in mice, and characterized their receptive fields using mouse ultrasonic vocalizations (USVs) as a natural and ethologically relevant stimulus and pitch-shifted starling songs as a natural but ethologically irrelevant control stimulus. We have found that auditory cortical neurons in the mouse display composite receptive fields with multiple excitatory and inhibitory subunits. Moreover, this was the case with either the conspecific or the heterospecific vocalizations. We then trained the sparse filtering algorithm on both classes of natural stimuli to obtain statistically optimal features, and compared the natural and artificial features using UMAP, a dimensionality-reduction algorithm previously used to analyze mouse USVs and birdsongs. We have found that the receptive-field features obtained with the mouse USVs and those obtained with the pitch-shifted starling songs clustered together, as did the sparse-filtering features. However, the natural and artificial receptive-field features clustered mostly separately. These results indicate that composite receptive fields are likely a generic property of central auditory systems in different classes of animals. They further suggest that the quadratic receptive-field features of the mouse auditory cortical neurons are natural-stimulus invariant.
Troponin Variants as Markers of Skeletal Muscle Health and Diseases

Ca2+-regulated contractility is a key determinant of the quality of muscles. The sarcomeric myofilament proteins are essential players in the contraction of striated muscles. The troponin complex in the actin thin filaments plays a central role in the Ca2+-regulation of muscle contraction and relaxation. Among the three subunits of troponin, the Ca2+-binding subunit troponin C (TnC) is a member of the calmodulin super family whereas troponin I (TnI, the inhibitory subunit) and troponin T (TnT, the tropomyosin-binding and thin filament anchoring subunit) are striated muscle-specific regulatory proteins. Muscle type-specific isoforms of troponin subunits are expressed in fast and slow twitch fibers and are regulated during development and aging, and in adaptation to exercise or disuse. TnT also evolved with various alternative splice forms as an added capacity of muscle functional diversity. Mutations of troponin subunits cause myopathies. Owing to their physiological and pathological importance, troponin variants can be used as specific markers to define muscle quality. In this focused review, we will explore the use of troponin variants as markers for the fiber contents, developmental and differentiation states, contractile functions, and physiological or pathophysiological adaptations of skeletal muscle. As protein structure defines function, profile of troponin variants illustrates how changes at the myofilament level confer functional qualities at the fiber level. Moreover, understanding of the role of troponin modifications and mutants in determining muscle contractility in age-related decline of muscle function and in myopathies informs an approach to improve human health.
Preparation and Characterization of Reduced Graphene Oxide /TiO2 Blended Polyphenylene sulfone Antifouling Composite Membrane With Improved Photocatalytic Degradation Performance

Nanosized titanium oxide (TiO2)-based photocatalysts have exhibited great potential for the degradation of organic contaminants, while their weak absorption of visible light limits the photocatalytic efficiency. Herein, a novel reduced graphene oxide/TiO2-polyphenylenesulfone (rGO/TiO2-PPSU) hybrid ultrafiltration membrane has been successfully prepared via a non-solvent induced phase-separation method, in which the synergistic coupling between the rGO and TiO2 could endowed the fabricated membranes with visible-light-driven efficient photocatalytically degradation of organic pollutants and outstanding photocatalytic and antifouling properties. Compared with the PPSU membranes prepared with Graphene oxide and TiO2, respectively, the rGO/TiO2-PPSU membrane demonstrated significant photodegradation towards phenazopyridine hydrochloride (PhP) solution under ultraviolet light (improved about 71 and 43%) and visible light (improved about 153 and 103%). The permeability and flux recovery rates of the membrane indicated that the high flux of the rGO/TiO2-PPSU membrane can be greatly restored after fouling, due to the improved self-cleaning properties under visible light static irradiation. With the properties of high performance of photocatalytic degradation and good self-cleaning ability, the rGO/TiO2-PPSU membrane would have great potential in water treatment.
Lifetime Study of Organic Solar Cells with O-IDTBR as Non-Fullerene Acceptor

Organic solar cells (OSCs) have increased their power conversion efficiency above 18% thanks to the use of non-fullerene acceptors in binary or ternary blends or in tandem configurations. In this article, a study on the lifetime of P3HT:O-IDTBR bulk heterojunction OSCs on ITO-free flexible substrates is presented. A direct comparison of glass–glass and plastic–plastic encapsulation performance, with a special focus on its effect on the lifetime of the devices after degradation procedures, has been carried out complying with the ISOS protocols for organic photovoltaic devices. The manufactured OSCs with 1 cm2 active layer have power conversion efficiencies ranging from 1.9 to 3.4% depending on the encapsulant material, encapsulation process, and substrate. An exponential degradation rate has been found, with a similar functional behavior for glass and plastic differing in the degradation constants, which ranges from k = 0.01 to 0.002 h−1. Only in one case, the ISOS-T3 essay for plastic encapsulation, a double exponential process, was observed with degradation rates of k1 = 0.03 h−1 and a second slower process with k2 = 0.001 h−1. The longest achieved T80 lifetime is 86 h for glass-encapsulated devices under an accelerated ISOS-T3 protocol.
Is Weekly Frequency of Yoga Practice Sufficient? Physiological Effects of Hatha Yoga Among Healthy Novice Women

Beneficial physical and physiological health outcomes of yoga practice are well-supported by empirical data. However, whether weekly frequency of training is sufficient to evoke positive changes, is still an open question. The present intervention study investigated the effects of 10 weekly sessions of beginner level hatha yoga with respect to indicators of physical fitness and physiological markers. 82 young women (mean age of 22.0 ± 3.83 years) participated in the study. The yoga group (N = 49) attended a yoga course consisting of 10 sessions (1.5 h each) on a weekly basis. The control group (N = 33) did not receive any intervention. BMI, body fat percentage, balance (one-leg-stand test with open and closed eyes, functional reach test), flexibility (side bend test, modified sit and reach test) core muscle strength (plank test) as well as resting heart rate (HR), and heart rate variability (HRV) were assessed 1 week before and after the course. Both frequentist and Bayesian analysis showed an improvement in flexibility and balance in the yoga group compared to the control group. The yoga group showed also increased core muscle strength. No changes with respect to BMI, body fat percentage, resting HR and HRV were found. Ninety minute beginner level hatha yoga classes were characterized by 93.39 HR and 195 kcal energy consumption on average. The present findings suggest that weekly setting of a 10-session long hatha yoga training leads to improvements in balance, flexibility and core muscle strength among healthy young women. However, for changes in BMI, body fat percentage, resting HR and HRV longer, and/or more intense interventions are needed.
GH Deficiency and Replacement Therapy in Hypopituitarism: Insight Into the Relationships With Other Hypothalamic-Pituitary Axes

GH deficiency (GHD) in adult patients is a complex condition, mainly due to organic lesion of hypothalamic-pituitary region and often associated with multiple pituitary hormone deficiencies (MPHD). The relationships between the GH/IGF-I system and other hypothalamic-pituitary axes are complicated and not yet fully clarified. Many reports have shown a bidirectional interplay both at a central and at a peripheral level. Signs and symptoms of other pituitary deficiencies often overlap and confuse with those due to GH deficiency. Furthermore, a condition of untreated GHD may mask concomitant pituitary deficiencies, mainly central hypothyroidism and hypoadrenalism. In this setting, the diagnosis could be delayed and possible only after recombinant human Growth Hormone (rhGH) replacement. Since inappropriate replacement of other pituitary hormones may exacerbate many manifestations of GHD, a correct diagnosis is crucial. This paper will focus on the main studies aimed to clarify the effects of GHD and rhGH replacement on other pituitary axes. Elucidating the possible contexts in which GHD may develop and examining the proposed mechanisms at the basis of interactions between the GH/IGF-I system and other axes, we will focus on the importance of a correct diagnosis to avoid possible pitfalls.
Assessing Effects of Reduced Vision on Spatial Orientation Ability Using Virtual Reality

How vision loss affects spatial orientation is relatively unknown. We investigated how simulated reductions in central vision and visual field influence spatial orientation in Virtual Reality. Participants were assigned to three groups: control (typical vision), reduced central vision (low acuity and contrast sensitivity) and reduced field (restricted peripheral vision). Participants were disoriented within a virtual room, and reoriented themselves towards a remembered target. In Experiment 1, we manipulated the shape and features of the room. In Experiment 2, we manipulated the lighting of the room. We measured response times and re-orientation precision. In Experiment 1, the reduced field group was slower and less precise to reorient; all groups were slower when presented with conflicting cues. In Experiment 2, the reduced field group was again slower than the other groups, but we did not observe a difference in precision. When environment lighting was dynamic, all groups were slower to reorient.
Complications for Computational Experiments from Modern Processors

In this paper, we revisit the approach to empirical experiments for combinatorial solvers. We provide a brief survey on tools that can help to make empirical work easier. We illustrate origins of uncertainty in modern hardware and show how strong the influence of certain aspects of modern hardware and its experimental setup can be in an actual experimental evaluation. More specifically, there can be situations where (i) two different researchers run a reasonable-looking experiment comparing the same solvers and come to different conclusions and (ii) one researcher runs the same experiment twice on the same hardware and reaches different conclusions based upon how the hardware is configured and used. We investigate these situations from a hardware perspective. Furthermore, we provide an overview on standard measures, detailed explanations on effects, potential errors
Cardiovascular outcomes in systemic sclerosis with abnormal cardiovascular MRI and serum cardiac biomarkers

Objectives To explore the prognostic value of subclinical cardiovascular (CV) imaging measures and serum cardiac biomarkers in systemic sclerosis (SSc) for the development of CV outcomes of primary heart involvement (pHI). Methods Patients with SSc with no clinical SSc-pHI and no history of heart disease underwent cardiovascular magnetic resonance (CMR) imaging, and measurement of serum high-sensitivity-troponin I (hs-TnI) and N-terminal-pro-brain natriuretic peptide (NT-proBNP). Follow-up clinical and CV outcome data were recorded. CV outcomes were defined as myocarditis, arrhythmia and/or echocardiographic functional impairment including systolic dysfunction and/or diastolic dysfunction. Results Seventy-four patients with a median (IQR) age of 57 (49, 63) years, 32% diffuse cutaneous SSc, 39% interstitial lung disease, 30% Scl70+ were followed up for median (IQR) 22 (15, 54) months. Ten patients developed CV outcomes, comprising one patient with myocarditis and systolic dysfunction and nine arrhythmias: three non-sustained ventricular tachycardia and six supraventricular arrhythmias. The probability of CV outcomes was considerably higher in those with NT-proBNP >125 pg/mL versus normal NT-proBNP (X2=4.47, p=0.035). Trend for poorer time-to-event was noted in those with higher extracellular volume (ECV; indicating diffuse fibrosis) and hs-TnI levels versus those with normal values (X2=2.659, p=0.103; X2=2.530, p=0.112, respectively). In a predictive model, NT-proBNP >125 pg/mL associated with CV outcomes (OR=5.335, p=0.040), with a trend observed for ECV >29% (OR=4.347, p=0.073). Conclusion These data indicate standard serum cardiac biomarkers (notably NT-proBNP) and CMR indices of myocardial fibrosis associate with adverse CV outcomes in SSc. This forms the basis to develop a prognostic model in larger, longitudinal studies.