Miracle-dz/UniFAR-FTUs huggingface dataset:
Aberrant Expression of FGFRL1 in Esophageal Cancer and Its Regulation by miR-107

Background: Fibroblast growth factor receptors are growth factor receptor tyrosine kinases, exerting their roles in embryogenesis, tissue homeostasis, and development of cancer. However, little is known about the expression and function of FGFRL1 in esophageal cancer (EC). Methods: We systematically evaluated the expression of FGFRL1 in TCGA and GETex datasets followed by expression analysis in EC cell lines and clinical specimens using immunofluorescence (IF) and immunohistochemistry (IHC) respectively. Results: GEPIA analysis on TCGA and GETex datasets identified significant upregulation of FGFRL1 in EC patients (n=182) compared to normal controls (n=286, p<0.05). IHC analysis showed significantly higher FGFRL1 expression in EC tissues as compared to the distant matched non-malignant tissues (p<0.001). Immunoflourescence in EC cells suggested increased expression of FGFRL1 from WDSCC (KYSE30) to MDSCC (KYSE140) and finally to PDSCC (KYSE410). In-silico tools predicted miR-107 as most significant miRNA regulating FGFRL1 expression. qRT-PCR revealed miR-107 expression to be significantly and inversely correlated with FGFRL1 expression in 73% (22/30) EC tissues (p=0.015) and over-expression of miR-107 resulted in significantly decreased expression of FGFRL1 at mRNA (fold change=0.11, p=0.0016) as well as protein level in miR-107 versus NC treated cells. Luciferase reporter assay using FGFRL1-3’UTR further confirmed it to be a direct target of miR-107. Conclusion: Our results herein document clinical as well as functional relevance of FGFRL1 in EC and its regulation by miR-107.
An Examination of the Non-linear Relationship Between Cognition and Total Hemoglobin Among the Cognitively Normal Older Adults by Gender

Objectives: This exploratory study aimed to identify the potential non-linear relationship between hemoglobin (Hgb) and cognition among cognitively normal older adults and how this relationship differs in terms of gender in generalized additive models (GAM). Methods: This is a secondary data analysis using Wave II (2010–2011) data from the National Social Life, Health, and Aging Project. A generalized additive model was used to understand the non-linear relationship between Hgb and cognition, and to identify critical Hgb point related to cognition. Results: While both genders had a non-linear association between Hgb and cognition, the degree of non-linearity was more pronounced in male older adults with EDF value close to 2. The inflection point of 15.10 g/dL for male older adults and inflection point of 11.72 g/dL for female older adults were obtained. Conclusion: Further studies are needed to validate these results and develop precision medicine approaches to integrate these results into clinical practice.
Experimental studies of partial photodetachment cross sections in K − below the K(7 2 P ) threshold

A collinear beams apparatus has been used to determine photodetachment cross sections for K − in the photon energy range 4.250–4.360 eV. State selective detection, utilizing a resonance ionization scheme, was applied to measure partial cross sections for those channels which leave the residual K atoms in the excited 7 2 S , 5 2 F and 5 2 G states. The energy region studied encompassed the openings of the aforementioned channels, as well as the channel that leaves the K atom in the 7 2 P state. Two previously unobserved resonances were seen in all three partial cross sections between the K(5 2 G ) and K(7 2 P ) thresholds. It is shown that a more reliable determination of resonance parameters can be made if the same resonances are observed in several channels. In the region below the K(5 2 F ) threshold, three previously observed resonances were investigated [Kiyan et al. Phys. Rev. Lett. 84 , 5979 (2000)]. A greatly increased modulation of the signal was obtained by detecting in the K(7 2 S ) channel, instead of the K(5 2 S ) channel used in the previous study. Furthermore, the shapes of the cross sections in the threshold regions are discussed. A detailed description of the apparatus and the experimental procedure employed is presented in the paper.
Simulating the effects of long‐distance dispersal and landscape heterogeneity on the eco‐evolutionary outcomes of range expansion in an invasive riverine fish, Tench (Tinca tinca)

Predicting how quickly populations expand their range and whether they will retain genetic diversity when they are introduced to new regions or track environmental conditions suited to their survival is an important applied and theoretical challenge. The literature suggests that long‐distance dispersal, landscape heterogeneity and the evolution of dispersal influence populations' expansion rates and genetic diversity. We used individual‐based spatially explicit simulations to examine these relationships for Tench (Tinca tinca), an invasive fish expanding its geographical range in eastern North America since the 1990s. Simulated populations varied greatly in expansion rates (1.1–28.6 patches year−1) and genetic diversity metrics, including changes in observed heterozygosity (−19 to +0.8%) and effective number of alleles (−0.32 to −0.01). Populations with greater dispersal distances expanded faster than those with smaller dispersal distances but exhibited considerable variation in expansion rate among local populations, implying less predictable expansions. However, they tended to retain genetic diversity as they expanded, suggesting more predictable evolutionary trajectories. In contrast, populations with smaller dispersal distances spread predictably more slowly but exhibited more variability among local populations in genetic diversity losses. Consistent with empirical data, populations spreading in a longer, narrower dispersal corridor lost more neutral genetic variation to the stochastic fixation of alleles. Given the unprecedented pace of anthropogenic environmental change and the increasing need to manage range‐expanding populations, our results have conservation ramifications as they imply that the evolutionary trajectories of populations characterised by shorter dispersal distances spreading in narrower landscapes are more variable and, therefore, less predictable.
Direct Numerical Simulations of Aggregation of Monosized Spherical Particles in Homogeneous Isotropic Turbulence

Direct numerical simulations of turbulent solid–liquid suspensions have been performed. The liquid is Newtonian, and the particles are identical spheres. The spheres have a tendency to aggregate since they are attracted to one another as a result of a square-well potential. The size of the particles is typically larger than the Kolmogorov scale, albeit of the same order of magnitude. In such situations, the particle dynamics (including the aggregation process), and turbulence strongly interact which explains the need for direct simulations. The lattice-Boltzmann method combined with an immersed boundary method for representing the no-slip conditions at the spherical solid–liquid interfaces was used. The results show that the aggregate size distributions depend on both the strength of particle–particle interactions and the intensity of the turbulence. V
Carotid body contribution to the physio‐pathological consequences of intermittent hypoxia: role of nitro‐oxidative stress and inflammation

Obstructive sleep apnoea (OSA), characterized by chronic intermittent hypoxia (CIH), is considered to be an independent risk for hypertension. The pathological cardiorespiratory consequences of OSA have been attributed to systemic oxidative stress, inflammation and sympathetic overflow induced by CIH, but an emerging body of evidence indicates that a nitro‐oxidative and pro‐inflammatory milieu within the carotid body (CB) is involved in the potentiation of CB chemosensory responses to hypoxia, which contribute to enhance the sympathetic activity. Accordingly, autonomic and cardiovascular alterations induced by CIH are critically dependent on an abnormally heightened CB chemosensory input to the nucleus of tractus solitarius (NTS), where second‐order neurons project onto the rostral ventrolateral medulla (RVLM), activating pre‐sympathetic neurons that control pre‐ganglionic sympathetic neurons. CIH produces oxidative stress and neuroinflammation in the NTS and RVLM, which may contribute to the long‐term irreversibility of the CIH‐induced alterations. This brief review is mainly focused on the contribution of nitro‐oxidative stress and pro‐inflammatory molecules on the hyperactivation of the hypoxic chemoreflex pathway including the CB and the brainstem centres, and whether the persistence of autonomic and cardiorespiratory alterations may depend on the glial‐related neuroinflammation induced by the enhanced CB chemosensory afferent input.
Using the ear photoplethysmographic waveform as an early indicator of central hypovolemia in healthy volunteers utilizing LBNP induced hypovolemia model

Objective. To study the photoplethysmographic (PPG) waveforms of different locations (ear and finger) during lower body negative pressure (LBNP) induced hypovolemia. Then, to determine whether the PPG waveform can be used to detect hypovolemia during the early stage of LBNP. Approach. 36 healthy volunteers were recruited for progressive LBNP induced hypovolemia, with an endpoint of −60 mmHg or development of hypoperfusion symptoms, whichever comes first. Subjects tolerating the entire protocol without symptoms were designated as high tolerance (HT), while symptomatic subjects were designated as low tolerance (LT). Subjects were monitored with an electrocardiogram, continuous noninvasive blood pressure monitor, and two pulse oximetry probes, one on the ear (Xhale) and one the finger (Nellcor). Stroke volume was measured non-invasively utilizing Non-Invasive Cardiac Output Monitor (NICOM, Cheetah Medical). The waveform morphology was analyzed using novel PPG waveforms indices, including phase hemodynamic index (PHI) and amplitude hemodyamaic index and were evaluated from the ear PPG and finger PPG at different LBNP stages. Main results. The PHI, particularly the phase relationship between the second harmonic and the fundamental component of the ear PPG denoted as ∇φ2, during the early stage of LBNP (−15 mmHg) in the HT and LT groups is statistically significantly different (p value = 0.0033) with the area under curve 0.81 (CI: 0.616–0.926). The other indices are not significantly different. The 5 fold cross validation shows that ∇φ2 during the early stage of LBNP (−15 mmHg) as the single index could predict the tolerance of the subject with the sensitivity, specificity, accuracy and F1 as 0.771 ± 0.192, 0.71 ± 0.107, 0.7 ± 0.1 and 0.771 ± 0.192 respectively. Significance. The ear’s PPG PHI which compares the phases of the fundamental and second harmonic has the potential to be used as an early predictor of central hypovolemia.
Age‐related changes in sensory and motor components of the Hoffmann‐reflex pathway of the flexor carpi radialis

Ageing is accompanied by numerous changes within the sensory and motor components of the muscle spindle pathway. To further document these age‐related changes, this study compared the characteristics of the Hoffmann (H) reflex and M wave, evoked with several pulse durations, between young and old adults. The H‐reflex and M‐wave recruitment curves were recorded at rest in the flexor carpi radialis of 12 young (21–36 years) and 12 older adults (62–80 years). For each pulse duration (0.05, 0.2 and 1 ms), the maximal M‐wave (MMAX) and H‐reflex (HMAX) amplitude, the M‐wave amplitude associated with HMAX (MHmax) and the H‐reflex amplitude for a stimulus intensity evoking an M‐wave of 5% MMAX (HM5%) were measured. The strength‐duration time constant and response threshold were estimated from the charge/stimulus‐duration relation for the H reflex and M wave. Results indicate that varying pulse duration mainly induces a similar effect on H‐reflex and M‐wave recruitment curves between young and older adults. Regardless of pulse duration, old adults had lesser HMAX (p = 0.029) and HM5% (p < 0.001) but greater MHmax (p < 0.001). The H‐reflex and M‐wave response thresholds were greater in old than young adults (p = 0.003), but the strength‐duration time constant was lesser in old than young adults for the H reflex (p = 0.048) but not the M wave (p = 0.21). These results suggest greater age‐related changes in the sensory than the motor component of the H‐reflex pathway, which may be indicative of a greater loss of sensory than motor axons or alterations of synapses between Ia afferents and motor neurones.
Understanding Instabilities of Tropical Cyclones and Their Evolution with a Moist Convective Rotating Shallow-Water Model

AbstractInstabilities of hurricane-like vortices are studied with the help of a rotating shallow-water model, including the effects of moist convection. Linear stability analysis demonstrates that dominant unstable modes are mixed Rossby–inertia–gravity waves. It is shown that, depending on fine details of the vorticity profile, a wavenumber selection of the instability may operate or not, leading in some cases to an unstable mode with a distinctively maximal growth rate and in other cases to an ensemble of unstable modes with close growth rates. Numerical simulations are performed in order to investigate nonlinear saturation of the instability and to understand the dynamical role of moisture. In agreement with previous studies, the authors confirm axisymmetrization of vorticity in the course of the development of the instability, which induces changes of intensity of the hurricane. In “dry” simulations, winds are intensified only inside the radius of maximum wind, while the maximum value of the wind decr.
Atmospheric and Oceanic Excitations to LOD Change on Quasi-biennial Time Scales

We use wavelet transform to study the time series of the Earth's rotation rate (length-of-day, LOD), the axial components of atmospheric angular momentum (AAM) and oceanic angular momentum (OAM) in the period 1962–2005, and discuss the quasi-biennial oscillations (QBO) of LOD change. The results show that the QBO of LOD change varies remarkably in amplitude and phase. It was weak before 1978, then became much stronger and reached maximum values during the strong El Nino events in around 1983 and 1997. Results from analyzing the axial AAM indicate that the QBO signals in axial AAM are extremely consistent with the QBOs of LOD change. During 1963–2003, the QBO variance in the axial AAM can explain about 99.0% of that of the LOD, in other words, all QBO signals of LOD change are almost excited by the axial AAM, while the weak QBO signals of the axial OAM are quite different from those of the LOD and the axial AAM in both time-dependent characteristics and magnitudes. The combined effects of the axial AAM and OAM can explain about 99.1% of the variance of QBO in LOD change during this period.
Role of HR in Driving CSR: An In-depth Study of (Comparison Between) Tata Steel and ITC

The purpose of this study is to find out the role of human resource management (HRM) in driving socially responsible and sustainable initiatives in organisations. The annual reports of two major Indian companies, Tata Steel and ITC were studied with specific focus on their HR policies and practices, business responsibility and sustainability activities and analysed by the authors. The findings show the role that HRM plays in implementing following SDG goals. The paper is an interdisciplinary study viewing the role of HRM in CSR and sustainability and extends and broadens the area of research by an in-depth study of two established companies in India.
MYPT1 is a non-canonical AKAP that tethers PKA to the MLCP signaling node

The activity of myosin light chain phosphatase (MLCP) is fine-tuned by the phosphorylation status of the MLCP target subunit 1 (MYPT1), which is determined by the antagonistic effects of Rho kinase (ROCK) and cAMP/cGMP-dependent protein kinases (PKA and PKG). PKA is composed of two regulatory (PKA-R, of which four variants exist) and two catalytic (PKAcat) subunits. PKA is targeted to the vicinity of its substrates by binding to A kinase anchoring proteins (AKAPs). MYPT1 is part of a complex signaling node that includes kinases and other enzymes involved in signal transduction. We hypothesized that MYPT1 might function as an AKAP to target PKA to the MLCP signaling node. Using a combination of immunoprecipitation, affinity pulldown and in situ proximity ligation assay (PLA) in human platelets and endothelial cells, we show that MYPT1 directly interacts with all four PKA-R variants and mapped the interaction to a 200 residues long central region of MYPT1. The interaction does not involve the docking and dimerization domain of PKA-R typically required for binding to AKAPs. Using peptide array overlay we identified K595, E676 and the PKA/ROCK kinase substrate motif R693/R694/S695/T696 as critical for the interaction. Substitution of S695, T696 or both by aspartic acid or the corresponding phosphorylated residue abolished binding. Our findings reveal that MYPT1 functions as a non-canonical AKAP to anchor PKA to the vicinity of non-phosphorylated S695/T696, where PKA-R would prevent PKAcat, and potentially also ROCK, from interacting with and phosphorylating MYPT1.
Preparation of physiologically active inside-out vesicles from plant inner mitochondrial membranes

For many metabolites, the major barrier between cytosol and mitochondrial matrix is the inner envelope membrane of mitochondria, the site of the respiratory electron transport chain. In consequence, it houses numerous transporters which facilitate the controlled exchange of metabolites, ions, and even proteins between these cellular compartments. While their import into the organelle can be studied with isolated mitochondria or mitoplasts, the analysis of their export from the matrix into the intermembrane space or even the cytosol demands for more sophisticated approaches. Among those, inside-out inner membrane vesicles are particularly useful, since they allow the direct presentation of the potential export substrates to the membrane without prior import into the organelle. Here we present a protocol for the isolation of such inside-out vesicles of the inner envelope membrane of plant mitochondria based on repeated freeze/thaw-cycles of freshly prepared mitoplasts. Electron microscopy and Western analysis could show that the majority of the vesicles have single envelope membranes in an inside-out topology. The vesicles are furthermore physiologically active, as demonstrated by assays measuring the enzymatic activities of Complex I (NADH dehydrogenase), Complex V (ATP synthase) and the mitochondrial processing peptidase (MPP) associated with Complex III. Hence, the method presented here provides a good basis for further studies of the inner mitochondrial envelope membrane and mitochondrial export processes.
Transcriptomic analysis of the ocular posterior segment completes a cell atlas of the human eye

Although the visual system extends through the brain, most vision loss originates from defects in the eye. Its central element is the neural retina, which senses light, processes visual signals, and transmits them to the rest of the brain through the optic nerve (ON). Surrounding the retina are numerous other structures, conventionally divided into anterior and posterior segments. Here we used high-throughput single nucleus RNA sequencing (snRNA-seq) to classify and characterize cells in the extraretinal components of the posterior segment: ON, optic nerve head (ONH), peripheral sclera, peripapillary sclera (PPS), choroid, and retinal pigment epithelium (RPE). Defects in each of these tissues are associated with blinding diseases – for example, glaucoma (ONH and PPS), optic neuritis (ON), retinitis pigmentosa (RPE), and age-related macular degeneration (RPE and choroid). From ∼151,000 single nuclei, we identified 37 transcriptomically distinct cell types, including multiple types of astrocytes, oligodendrocytes, fibroblasts, and vascular endothelial cells. Our analyses revealed a differential distribution of many cell types among distinct structures. Together with our previous analyses of the anterior segment and retina, the new data complete a “Version 1” cell atlas of the human eye. We used this atlas to map the expression of >180 genes associated with the risk of developing glaucoma, which is known to involve ocular tissues in both anterior and posterior segments as well as neural retina. Similar methods can be used to investigate numerous additional ocular diseases, many of which are currently untreatable.
Dynamic Adaptation of Default Mode Network in Resting state and Autobiographical Episodic Memory Retrieval State

The default mode network is a brain network processing mental states featuring an internal representation of subjective experiences like autobiographical episodic memory retrieval and a resting state. If the default mode network is the common spatial domain processing such mental states, then the temporal domain might present the differences in the mental states. To detect adaptations in dynamics of a single brain network dependent on the mental states it processes, we suggested a novel analysis method called one-to-many dynamic functional connectivity analysis for fMRI. The analysis method assesses the variance in the partial correlations of a center that are time-windowed functional correlations of a brain region (a center) to the rest of the regions in a brain network, then compares the similarities in the directions of their major variance from the same or distinct mental states. We applied one-to-many dynamic functional connectivity analysis to the default mode network and measured the similarity between the major variances of the partial correlations from three autobiographical episodic memory retrieval states and a resting state. If the major direction of the variance is a configuration presenting the mental states of the brain network, we expect to see the high similarity for the same mental states and less similarity for the distinct mental states. To test our hypothesis with the new analysis method, we chose a single subject who is a late blind with advanced mental imagery ability. The results showed that the dynamic adaption in the default mode network in the two mental states could be well depicted when the posterior cingulate cortex is the center in this single case. Furthermore, we could observe that the weight of the correlation between the posterior cingulate cortex and the right parahippocampal cortex varied mostly and therefore its contribution to the dynamic adaptation was relatively higher than the other correlations.
Characterization of factors that underlie transcriptional silencing in C. elegans oocytes

While it has been appreciated for decades that prophase-arrested oocytes are transcriptionally silenced on a global level, the molecular pathways that promote silencing have remained elusive. Previous work in C. elegans has shown that both topoisomerase II (TOP-2) and condensin II collaborate with the H3K9me heterochromatin pathway to silence gene expression in the germline during L1 starvation, and that the PIE-1 protein silences the genome in the P-lineage of early embryos. Here, we show that all three of these silencing systems, TOP-2/condensin II, H3K9me, and PIE-1, are required for transcriptional repression in oocytes. We find that H3K9me3 marks increase dramatically on chromatin during silencing, and that silencing is under cell cycle control. We also find that PIE-1 localizes to the nucleolus just prior to silencing, and that nucleolar dissolution during silencing is dependent on TOP-2/condensin II. Our data identify both the molecular components and the trigger for genome silencing in oocytes and establish a link between PIE-1 nucleolar residency and its ability to repress transcription.