bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel CARM1–HuR axis involved in muscle differentiation and plasticity misregulated in spinal muscular atrophy
Authors: Ravel-Chapuis Aymeric , Haghandish Amir , Daneshvar Nasibeh , Jasmin Bernard J , Côté Jocelyn 
Published: November 2021

Abstract
Spinal muscular atrophy (SMA) is characterized by the loss of alpha motor neurons in the spinal cord and a progressive muscle weakness and atrophy. SMA is caused by loss-of-function mutations and/or deletions in the survival of motor neuron (SMN) gene. The role of SMN in motor neurons has been extensively studied, but its function and the consequences of its loss in muscle have also emerged as a key aspect of SMA pathology. In this study, we explore the molecular mechanisms involved in muscle defects in SMA. First, we show in C2C12 myoblasts, that arginine methylation by CARM1 controls myogenic differentiation. More specifically, the methylation of HuR on K217 regulates HuR levels and subcellular localization during myogenic differentiation, and the formation of myotubes. Furthermore, we demonstrate that SMN and HuR interact in C2C12 myoblasts. Interestingly, the SMA-causing E134K point mutation within the SMN Tudor domain, and CARM1 depletion, modulate the SMN–HuR interaction. In addition, using the Smn2B/− mouse model, we report that CARM1 levels are markedly increased in SMA muscles and that HuR fails to properly respond to muscle denervation, thereby affecting the regulation of its mRNA targets. Altogether, our results show a novel CARM1–HuR axis in the regulation of muscle differentiation and plasticity as well as in the aberrant regulation of this axis caused by the absence of SMN in SMA muscle. With the recent developments of therapeutics targeting motor neurons, this study further indicates the need for more global therapeutic approaches for SMA.
Vorinostat Corrects Cognitive and Non-Cognitive Symptoms in a Mouse Model of Fragile X Syndrome
Authors: Ding Qi , Wu Xueting , Li Xuan , Wang Hongbing 
Published: November 2021

Abstract

Background
Fragile X syndrome (FXS) is caused by mutations in the FMR1 gene. It is a form of heritable intellectual disability and autism. Despite recent advance in elucidating disease mechanisms, there is no efficacious medication. Because de novo drug development is a lengthy process, repurposing the existing FDA-approved drugs offers an opportunity to advance clinical intervention for FXS. Our previous study with transcriptome analysis predicts potential therapeutic effects of vorinostat on FXS.

Methods
We analyzed the vorinostat-induced transcriptome changes and confirmed its similarity to that induced by trifluoperazine, which was previously shown to correct pathological outcomes associated with FXS. To validate the therapeutic efficacy, we examined vorinostat’s effect on correcting the key behavioral and cellular symptoms in a mouse model of FXS.

Results
We found that vorinostat restores object location memory and passive avoidance memory in the Fmr1 knockout mice. For the non-cognitive behavioral symptoms, vorinostat corrected the autism-associated alterations, including repetitive behavior and social interaction deficits. In the open field test, vorinostat dampened hyperactivity in the center area of the arena. Surprisingly, vorinostat did not correct the abnormally elevated protein synthesis in cultured Fmr1 knockout hippocampal neurons, suggesting that different aspects of pathological outcomes may respond differently to a specific therapeutic intervention.

Conclusions
We used the drug-induced transcriptome signature to predict new application of existing drugs. Our data reveal the therapeutic effects of the FDA-approved drug vorinostat in a mouse model of FXS.
Monoclonal Antibody Treatment of Breakthrough COVID-19 in Fully Vaccinated Individuals with High-Risk Comorbidities
Authors: Bierle Dennis M , Ganesh Ravindra , Tulledge-Scheitel Sidna , Hanson Sara N , Arndt Lori L , Wilker Caroline G , Razonable Raymund R 
Published: November 2021

Abstract

Background
Breakthrough coronavirus disease 2019 (COVID-19) may occur in fully vaccinated persons.

Methods
We assessed the clinical outcomes of breakthrough COVID-19 in fully vaccinated individuals.

Results
In this cohort of 1395 persons (mean age, 54.3 years; 60% female; median body mass index, 30.7) who developed breakthrough COVID- 19, there were 107 (7.7%) who required hospitalization by day 28. Hospitalization was significantly associated with the number of medical comorbidities. Antispike monoclonal antibody treatment was significantly associated with a lower risk of hospitalization (odds ratio, 0.227; 95% confidence interval, 0.128–0.403; P &lt; .001). The number needed to treat (NNT) to prevent 1 hospitalization was 225 among the lowest risk patient group compared with NNT of 4 among those with highest numbers of medical comorbidity.

Conclusions
Monoclonal antibody treatment is associated with reduced hospitalization in vaccinated high-risk persons with mild to moderate COVID-19.
Comparison viaeher
Authors: Umbach Carla , Solt Stephanie 
Published: November 2021

AbstractThis paper is about the semantics of the German adverb eher, which has three, or perhaps four, readings: temporal, epistemic, metalinguistic and—depending on whether it is accepted as a genuine reading—preference. In its epistemic reading, eher gained prominence in semantics because it was used by Kratzer (1981) to argue that the notion of possibility is gradable. Eher has also received attention from a diachronic perspective, where it has been compared to the English adverb rather ( Gergel 2009).Our analysis starts from the temporal reading which, first of all, expresses temporal precedence. We argue that temporal eher is indexical (unlike früher/‘earlier’), comparing closeness to a perspectival center, and that the non-temporal readings inherit their basic structure from the temporal one. The analysis of the non-temporal readings will be embedded in a Kratzer-style ordering semantics, deviating from the standard picture in assuming (i), that both the modal base and the ordering source are relativized to a perspective holder and (ii), that in the case of metalinguistic eher, interpretations (in the sense of Barker 2002/ Krifka 2012) are compared instead of worlds. Our analysis is different from that developed by Herburger & Rubinstein (2018), which ignores the temporal as well as the metalinguistic reading and takes recourse to “degrees of belief”.At the end of the paper, we briefly look at expressions related to eher, including English more and its German counterpart mehr as well as English rather, and also at the modal reading of German schon (‘already’).
Novel type of medial meniscus ramp lesion: a case report and surgical technique
Authors: Alomar Abdulaziz Z 
Published: November 2021

Abstract
Meniscal ramp lesions have been reported in 9–24% of patients who underwent anterior cruciate ligament reconstruction (ACLR). We report a rare type of double medial meniscus ramp lesion in in a 26-year-old male soccer player who presented with persistent knee instability and an inability to return to sports after a successful ACLR due to unaddressed and untreated ramp lesions. To the best of our knowledge, this is the first reported case of a double ramp lesion, with tears occurring in two separate locations: one tear at the meniscosynovial junction and associated with meniscotibial ligament disruption; and a second, more posteriorly located at the meniscocapsular junction and associated with meniscocapsular attachment disruption. It was found to be very unstable upon arthroscopic assessment and was clinically associated with persistent knee instability even after ACLR, thus necessitating surgical repair to restore knee kinematics.
“The Greatest Encouragement to Seamen”: Pay, Families, and the State in Britain during the French Wars, 1793–1815
Authors: Bickham Troy , Abbey Ian 
Published: November 2021

Abstract
In 1795, Britain’s Parliament passed the “Seamen’s Families Bill” which enabled sailors to allot half of their monthly pay to either their mothers or wives for the duration of their service. This article examines the significance of the bill from a number of perspectives. First is the unprecedented level of national and local bureaucratic organization needed to implement pay allotments successfully. Second, and most extensively, the article examines the records produced by the bill’s implementation, which include such information as place of residence, number and gender of children, rank, wages, and relationship to the recipient. Drawing from a considerable sample of sailors who served from 1795 to the end of the French wars in 1815, the authors created a database of 7,514 sailors, who volunteered to allot half of their pay, as means to better understand the ordinary men who made up the rank and file of the Royal Navy. Among several findings is a strong challenge to the notion of the independent and irresponsible sailor who enlisted to escape an unhappy home life. Finally, the article considers the significance of the allotments within the British system of poor relief. Highly localized since its inception two centuries earlier, poor relief varied enormously across Britain. Equating annually to roughly one-quarter of poor relief expenditure across Britain, pay allotments to sailors’ families mark an unparalleled intervention by the British central government into social welfare.
Elevated Serum HE4 Concentrations and Risk of Cardiac Complications among Hospitalized Patients with Burns
Authors: Wu Yangyang , Cao Ling , Qi Jun 
Published: November 2021

Abstract

Background
The decrease in effective blood volume after burns is closely related to abnormal heart function.

Objective
To investigate whether serum human epididymis protein 4 (HE4), an indicator of early renal injury, contributes to increased risk of cardiac complications in patients with burns.

Methods
Within 24 hours after hospital admission, clinical condition assessment and biochemical testing in patients with burns were performed. Multivariate analysis was performed by evaluating the relationship between serum HE4 levels and risk of cardiac complications (cardiac insufficiency, arrhythmia, and myocardial infarction) during hospitalization.

Results
The number (percentage) of cardiac complications in all included patients with burns was 80 (15.6%). The results of sensitivity analysis suggest that elevated serum HE4 levels were related to higher risk of cardiac complications in patients with sepsis (OR = 2.1; 95% CI, 1.19–3.17; P &lt;.001) and in patients without sepsis (OR = 2.29; 95% CI, 1.33–4.71l; P = .005), respectively, after adjustments for clinical confounding factors were made. Sepsis did not have a modification effect on the association between serum and cardiac complications among these patients. Also, the results of ROC curve analysis showed that serum HE4 levels have good predictive value for predicting cardiac complications in patients with burns (AUC = 0.708; 95% CI, 0.61–0.81; P &lt;.001).

Conclusions
In the current study, we identified that elevated HE4 levels contributed to increased risk of cardiac complications in the hospital in patients with burns. This novel finding suggests that burn patients with serum HE4 may provide the opportunity to predict cardiac complications before hospital admission.
Characterizing spatial variations of PAH emission in the reflection nebula NGC 1333
Authors: Knight C , Peeters E , Wolfire M , Stock D J 
Published: November 2021

ABSTRACT
Infrared emission features at 3.3, 6.2, 7.7, 8.6, and 11.2 µm, attributed to polycyclic aromatic hydrocarbons (PAHs), show variations in relative intensity, shape, and peak position. These variations depend on the physical conditions of the photodissociation region (PDR) in which strong PAH emission arises but their relationship has yet to be fully quantified. We aim to better calibrate the response of PAH species to their environment using observations with matching apertures and spatial resolution. We present observations from the Field-Imaging Far-Infrared Line Spectrometer onboard the Stratospheric Observatory for Infrared Astronomy of the gas cooling lines [O i] 63, 146 µm and [C ii] 158 µm in the reflection nebula NGC 1333 and use archival dust continuum observations from the Photodetector Array Camera and Spectrometer (PACS) onboard Herschel. We employ PDR modelling to derive the physical conditions and compare these with the characteristics of the PAH emission as observed with the Infrared Spectrometer onboard Spitzer. We find distinct spatial characteristics for the various PAH spectral components. We conclude that the ionic bands (6.2, 7.7, 8.6, and 11.0) and the 7–9 µm emission are due to multiple PAH subpopulations and that the plateaus are distinct from the features perched on top. The 6–9 µm PAH emission exhibits a significant change in behaviour between the irradiated PDR and diffuse outskirts, confirming these bands arise from multiple PAH subpopulations with different underlying molecular properties. We find multiple promising relationships between PAH ratios and the far-ultraviolet radiation field strength but no clear correlations with the PAH ionization parameter.
Modelling cosmic masers in C-type shock waves – the coexistence of Class I CH3OH and 1720 MHz OH masers
Authors: Nesterenok A V 
Published: November 2021

ABSTRACT
The collisional pumping of CH3OH and OH masers in non-dissociative C-type shock waves is studied. The chemical processes responsible for the evolution of molecule abundances in the shock wave are considered in detail. The large velocity gradient approximation is used to model radiative transfer in molecular lines. We present calculations of the optical depth in maser transitions of CH3OH and OH for a grid of C-type shock models that vary in cosmic ray ionization rate, gas density, and shock speed. We show that pre-shock gas densities nH, tot = 2 × 104–2 × 105 cm−3 are optimal for the pumping of methanol maser transitions. A complete collisional dissociation of methanol at the shock front takes place for shock speeds us ≳ 25 km s−1. At high pre-shock gas density nH, tot = 2 × 106 cm−3, the collisional dissociation of methanol takes place at shock speeds just above the threshold speed us ≈ 15–17.5 km s−1, corresponding to sputtering of icy mantles of dust grains. We show that the methanol maser transition E 4−1 → 30 at 36.2 GHz has an optical depth |τ| higher than that of the transition A+ 70 → 61 at 44.1 GHz at high cosmic ray ionization rate $\zeta _\mathrm{H_2} \gtrsim 10^{-15}$ s−1 and pre-shock gas density nH, tot = 2 × 104 cm−3. These results can be applied to the interpretation of observational data on methanol masers near supernova remnants and in molecular clouds of the Central Molecular Zone. At the same time, a necessary condition for the operation of 1720 MHz OH masers is a high ionization rate of molecular gas, $\zeta _\mathrm{H_2} \gtrsim 10^{-15}$ s−1. We find that physical conditions conducive to the operation of both hydroxyl and methanol masers are cosmic ray ionization rate $\zeta _\mathrm{H_2} \approx 10^{-15}$–3 × 10−15 s−1 and a narrow range of shock speeds 15 ≲ us ≲ 20 km s−1. The simultaneous observations of OH and CH3OH masers may provide restrictions on the physical parameters of the interstellar medium in the vicinity of supernova remnants.
Cosmological constraints from H ii starburst galaxy, quasar angular size, and other measurements
Authors: Cao Shulei , Ryan Joseph , Ratra Bharat 
Published: November 2021

ABSTRACT
We compare the constraints from two (2019 and 2021) compilations of H ii starburst galaxy (H iiG) data and test the model independence of quasar (QSO) angular size data using six spatially flat and non-flat cosmological models. We find that the new 2021 compilation of H iiG data generally provides tighter constraints and prefers lower values of cosmological parameters than those from the 2019 H iiG data. QSO data by themselves give relatively model-independent constraints on the characteristic linear size, lm, of the QSOs within the sample. We also use Hubble parameter [H(z)], baryon acoustic oscillation (BAO), Pantheon Type Ia supernova (SN Ia) apparent magnitude (SN-Pantheon), and DES-3 yr binned SN Ia apparent magnitude (SN-DES) measurements to perform joint analyses with H iiG and QSO angular size data, since their constraints are not mutually inconsistent within the six cosmological models we study. A joint analysis of H(z), BAO, SN-Pantheon, SN-DES, QSO, and the newest compilation of H iiG data provides almost model-independent summary estimates of the Hubble constant, $H_0=69.7\pm 1.2\ \rm {km\,s^{-1}\,Mpc^{-1}}$, the non-relativistic matter density parameter, $\Omega _{\rm m_0}=0.293\pm 0.021$, and lm = 10.93 ± 0.25 pc.
Redshift space three-point correlation function of IGM at z &lt; 0.48
Authors: Maitra Soumak , Srianand Raghunathan , Gaikwad Prakash , Khandai Nishikanta 
Published: November 2021

ABSTRACT
Ly α forest decomposed into Voigt profile components allows us to study clustering properties of the intergalactic-medium and its dependence on various physical quantities. Here, we report the first detections of probability excess of low-z (i.e z &lt; 0.48) Ly α absorber triplets over redshift-space scale of r∥ ≤ 8 pMpc (Mpc in physical units) with maximum amplitude of $8.76^{+1.96}_{-1.65}$ at a longitudinal separation of 1–2 pMpc. We measure non-zero three-point correlation ($\zeta = 4.76^{+1.98}_{-1.67}$) only at this scale with reduced three-point correlation Q = $0.95^{+0.39}_{-0.38}$. The measured ζ shows an increasing trend with increasing minimum H i column density (NH i) threshold while Q does not show any NH i dependence. About 88 per cent of the triplets contributing to ζ (at z ≤ 0.2) have nearby galaxies (whose distribution is known to be complete for ∼0.1L* at z &lt; 0.1 and for ∼L* at z ∼ 0.25 within 20 arcsec to the quasar sightlines) within velocity separation of 500 km s−1 and median impact parameter of 405 pkpc. The measured impact parameters are consistent with majority of the identified triplets not originating from individual galaxies but tracing the underlying galaxy distribution. Frequency of occurrence of Broad-Ly α absorbers (b &gt; 40 km s−1) in triplets (∼85 per cent) is factor ∼3 higher than that found among the full sample (∼32 per cent). Using four different cosmological simulations, we quantify the effect of peculiar velocities and feedback and show that most of the observed trends are broadly reproduced. However, ζ at small scales (r∥ &lt; 1 pMpc) and its b-dependence found in simulations are inconsistent with observations. This could either be related to the failure of these simulations to reproduce the observed b and NH i distributions for NH i &gt; 1014 cm−2 self-consistently or to the wide spread of signal-to-noise ratio in the observed data.
Long-term evolution of quantitative traits in theDrosophila melanogasterspecies subgroup
Authors: Yassin Amir , Gidaszewski Nelly , Debat Vincent , David Jean R. 
Published: November 2021

ABSTRACTQuantitative genetics aims at untangling the genetic and environmental effects on phenotypic variation. Trait heritability, which summarizes the relative importance of genetic effects, is estimated at the intraspecific level, but theory predicts that heritability could influence long-term evolution of quantitative traits. The phylogenetic signal concept bears resemblance to heritability and it has often been called species-level heritability. Under certain conditions, such as trait neutrality or contribution to phylogenesis, within-species heritability and between-species phylogenetic signal should be correlated. Here, we investigate the potential relationship between these two concepts by examining the evolution of multiple morphological traits for which heritability has been estimated inDrosophila melanogaster. Specifically, we analysed 42 morphological traits in both sexes on a phylogeny inferred from 22 nuclear genes for nine species of themelanogastersubgroup. We used Pagel’s λ as a measurement of phylogenetic signal because it is the least influenced by the number of analysed taxa. Pigmentation traits showed the strongest concordance with the phylogeny, but no correlation was found between phylogenetic signal and heritability estimates mined from the literature. We obtained data for multiple climatic variables inferred from the geographical distribution of each species. Phylogenetic regression of quantitative traits on climatic variables showed a significantly positive correlation with heritability. Convergent selection, the response to which depends on the trait heritability, may have led to the null association between phylogenetic signal and heritability for morphological traits inDrosophila. We discuss the possible causes of discrepancy between both statistics and caution against their confusion in evolutionary biology.
Expression and novel alternative purification of the recombinant nucleocapsid (N) protein of SARS-CoV-2 in Escherichia coli for the serodiagnosis of COVID-19
Authors: Rosales Jose David , Quintero William , Cruz Jhon , Perdomo Balbino , Quintero Militza , Bastidas Marcos , Lugo Jose Domingo , Rodriguez Keila Rivas , Freites-Perez Juan Carlos , Castillo Annie 
Published: November 2021

AbstractThe SARS-CoV-2 coronavirus causes severe acute respiratory syndrome and has caused a global pandemic by causing the COVID-19 disease. To monitor and control it, diagnostic methods such as molecular and serological tests are necessary. The serological approach uses SARS-CoV-2 antigens to detect the antibodies present in patients using quantitative techniques such as enzyme-linked immunosorbent assay (ELISA) or qualitative rapid tests such as lateral flow chromatography (RDT’s). The main antigens used are the spike protein (S) and the nucleocapsid protein (N). Both proteins are obtained in different expression systems, in eukaryotic cells, their production is expensive, so in this work we chose a simpler and cheaper system such as prokaryotic to express and purify the N protein. Thereore, the nucleotide sequence had to being optimized to be expressed in Escherichia coli. The protein N is sensitive to E.coli proteases and also has the ability to self-proteolyze under native conditions, degrading into different fragments. However, under denaturing conditions, using urea and at pH 5.3 it is stable and efficiently purified using metal exchange chromatography (IMAC). In our purification strategy, we surprisingly found that by not using a sonicator, a homogeneous and time-stable preparation of the recombinant antigen is obtained. An approximate yield of 200 mg / L was obtained. It was then tested with healthy sera and sera from COVID-19 convalescent patients in Wester-blot tests that were able to recognize it. Our work provides a novel strategy to produce the SARS-CoV-2 protein N so that it can be used as an input in the development and innovation of serological tests in the diagnosis of COVID-19.