bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapamycin administration during an acute heat stress challenge in growing pigs
Authors: Mayorga Edith J , Horst Erin A , Goetz Brady M , Rodríguez-Jiménez Sonia , Abeyta Megan A , Al-Qaisi Mohmmad , Lei Samantha , Rhoads Robert P , Selsby Joshua T , Baumgard Lance H
Published: May 2021

Study objectives were to determine the effects of rapamycin (Rapa) on biomarkers of metabolism and inflammation during acute heat stress (HS) in growing pigs. Crossbred barrows (n = 32; 63.5 ± 7.2 kg body weight [BW]) were blocked by initial BW and randomly assigned to 1 of 4 environmental-therapeutic treatments: 1) thermoneutral (TN) control (n = 8; TNCon), 2) TN and Rapa (n = 8; TNRapa), 3) HS control (n = 8; HSCon), or 4) HS and Rapa (n = 8; HSRapa). Following 6 d of acclimation to individual pens, pigs were enrolled in two experimental periods (P). During P1 (10 d), pigs were fed ad libitum and housed in TN conditions (21.3 ± 0.2°C). During P2 (24 h), HSCon and HSRapa pigs were exposed to constant HS (35.5 ± 0.4°C), while TNCon and TNRapa pigs remained in TN conditions. Rapamycin (0.15 mg/kg BW) was orally administered twice daily (0700 and 1800 hours) during both P1 and P2. HS increased rectal temperature and respiration rate compared to TN treatments (1.3°C and 87 breaths/min, respectively; P < 0.01). Feed intake (FI) markedly decreased in HS relative to TN treatments (64%; P < 0.01). Additionally, pigs exposed to HS lost BW (4 kg; P < 0.01), while TN pigs gained BW (0.7 kg; P < 0.01). Despite marked changes in phenotypic parameters caused by HS, circulating glucose and blood urea nitrogen did not differ among treatments (P > 0.10). However, the insulin:FI increased in HS relative to TN treatments (P = 0.04). Plasma nonesterified fatty acids (NEFA) increased in HS relative to TN treatments; although this difference was driven by increased NEFA in HSCon compared to TN and HSRapa pigs (P < 0.01). Overall, circulating white blood cells, lymphocytes, and monocytes decreased in HS compared to TN pigs (19%, 23%, and 33%, respectively; P ≤ 0.05). However, circulating neutrophils were similar across treatments (P > 0.31). The neutrophil-to-lymphocyte ratio (NLR) was increased in HS relative to TN pigs (P = 0.02); however, a tendency for reduced NLR was observed in HSRapa compared to HSCon pigs (21%; P = 0.06). Plasma C-reactive protein tended to differ across treatments (P = 0.06) and was increased in HSRapa relative to HSCon pigs (46%; P = 0.03). Circulating haptoglobin was similar between groups. In summary, pigs exposed to HS had altered phenotypic, metabolic, and leukocyte responses; however, Rapa administration had limited impact on outcomes measured herein.
Retinoic acid stimulates transcription of the rat SHARP-2 gene via multiple pathways
Authors: Hayashi Momoko , Misaki Toshinori , Yoshida Sena , Tokutake Hiroshi , Aruga Tomoki , Yoda Kazuya , Kenmochi Eri , Saito Kaho , Togashi Momo , Nakano Mai , Maejima Misato , Amemiya Riho , Sakuma Airi , Nakazawa Yuuri , Takagi Katsuhiro , Tsukada Akiko , Yamada Kazuya
Published: May 2021

Members of the enhancer of split- and hairy-related protein (SHARP) family, SHARP-1 and SHARP-2, are basic helix−loop−helix transcriptional repressors and belong to the clock genes. In this study, an effect of retinoic acid (RA) on the SHARP family gene expression in the differentiated cells was examined. RA rapidly and temporarily induced the SHARP-2 mRNA expression in hepatic H4IIE cells. Then, whether the SHARP-2 mRNA expression is altered by dexamethasone (Dex), insulin, and the combination of RA and Dex or RA and insulin was examined. Dex had different effects on the expression of SHARP-2 mRNA in the presence or absence of RA. Then, the molecular mechanisms were investigated using inhibitors of various signaling molecules. The RA-induction of SHARP-2 mRNA level was mainly inhibited by LY294002, staurosporine, and actinomycin D, respectively. Finally, whether RA acts on the transcriptional regulatory region of the SHARP-2 gene was analysed using luciferase reporter gene assay. At least two RA-responsive regions were mapped at the nucleotide sequences between −3,700 and −1,600 of the SHARP-2 gene. In addition, this effect was dependent on the RA receptor and retinoid X receptor. Thus, we conclude that RA stimulated transcription of the SHARP-2 gene via multiple pathways.
Cissus quadrangularis extract attenuates diabetic nephropathy by altering SIRT1/DNMT1 axis
Authors: Syed Anees Ahmed , Reza Mohammad Irshad , Garg Richa , Goand Umesh K , Gayen Jiaur R
Published: May 2021

Objectives

Hyperglycemia-induced SIRT1, DNMT1, SODs, as well as oxidative stress, play a pivotal role in the progression of diabetic nephropathy. Cissus quadrangularis, holds antioxidant and hypoglycemic activity; however, a direct link between its activity and prevention of diabetic nephropathy has not been ascertained yet. Accordingly, we aimed to delineate the protective effect of ethanolic extract of Cissus quadrangularis (EECQ) against high-fat diet/streptozotocin (HFD/STZ) induced diabetic nephropathy rats.

Methods

The control group was fed with a normal chow diet. Rats kept on an HFD for 12 weeks with a single low dose of STZ manifested the features of diabetic nephropathy. The treatment was done by the oral administration of EECQ (200 mg/kg) for six weeks (six rats in each group).

Key findings

Treatment with EECQ demonstrated substantial attenuation of elevated insulin resistance, lipid profile and creatinine level. Additionally, EECQ restored albuminuria, glomerular filtration rate and creatinine clearance in diabetic nephropathy rats. Furthermore, HFD consumption in rats culminated in reduced SIRT1 and enhanced DNMT1 expression, nonetheless, rescued by EECQ. Moreover, EECQ augmented the SOD 1 and 3 levels, thereby safeguarded from oxidative damage and renal inflammation. Besides, treatment protected from renal fibrosis by downregulating TGFβ, Smad2/3 and col1/3 expression in diseased rats.

Conclusions

Thus, based on the above findings, we conclude that EECQ shows a protective effect against diabetic nephropathy.
Tick borne relapsing fever after travelling to a Greek island
Authors: Billiet Antoon , Vanderschueren Steven , Lagrou Katrien , Pilate Thomas , Fournier Pierre-Edouard , Luciani Lea , Henckaerts Liesbet
Published: May 2021

A 23-year-old man presented to the emergency department with recurrent fever after returning from a camping trip on the Greek island of Tilos in the Aegean sea. In the last 2 months, four distinct episodes of fever, chills and myalgia occurred. A peripheral-blood smear revealed an unexpected guest.
SmKFB5 protein regulates phenolic acid biosynthesis by controlling the degradation of phenylalanine ammonia-lyase inSalvia miltiorrhiza
Authors: Yu Haizheng , Li Dongyue , Yang Dongfeng , Xue Zheyong , Li Jie , Xing Bingcong , Yan Kaijing , Han Ruilian , Liang Zongsuo
Published: May 2021

Phenolic acids are the major secondary metabolites and significant bioactive constituents of the medicinal plant Salvia miltiorrhiza. Many enzyme-encoding genes and transcription factors involved in the biosynthesis of phenolic acids have been identified, but the underlying post-translational regulatory mechanisms are poorly understood. Here, we demonstrate that the S. miltiorrhiza Kelch repeat F-box protein SmKFB5 physically interacts with three phenylalanine ammonia-lyase (PAL) isozymes and mediates their proteolytic turnover via the ubiquitin-26S proteasome pathway. Disturbing the expression of SmKFB5 reciprocally affected the abundance of SmPAL protein and the accumulation of phenolic acids, suggesting that SmKFB5 is a post-translational regulator responsible for the turnover of PAL and negatively controlling phenolic acids. Furthermore, we discovered that treatment of the hairy root of S. miltiorrhiza with methyl jasmonate suppressed the expression of SmKFB5 while inducing the transcription of SmPAL1 and SmPAL3. These data suggested that methyl jasmonate consolidated both transcriptional and post-translational regulation mechanisms to enhance phenolic acid biosynthesis. Taken together, our results provide insights into the molecular mechanisms by which SmKFB5 mediates the regulation of phenolic acid biosynthesis by jasmonic acid, and suggest valuable targets for plant breeders in tailoring new cultivars.
In da club: the cytoplasmic kinase MAZZA joins CLAVATA signaling and dances with CLV1-like receptors
Authors: Müller-Xing Ralf , Xing Qian
Published: May 2021

This article comments on:

Blümke P, Schlegel J, Gonzalez-Ferrer C, Becher S, Pinto K, Monaghan J, Simon R. 2021. Receptor-like cytoplasmickinase MAZZA mediates developmental processes with CLAVATA1 family receptors in Arabidopsis. Journal of Experimental Botany 72, 4853–4870.
Association of Plasma Fibrinogen Levels on Postoperative Day 1 with 2-Year Survival of Orthotopic Liver Transplantation for HBV-Related HCC
Authors: Liu Xia , Guo Renyong , Tian Jie
Published: May 2021

Objective

To clarify the prognostic values of hemostatic parameters to predict the survival of patients undergoing orthotopic liver transplantation (OLT) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).

Methods

The data of 182 consecutive adult patients who underwent OLT for HBV-related HCC were subjected to univariate and multivariate analyses.

Results

Ascites and fibrinogen levels on postoperative day (POD) 1 were independent predictors of postoperative 2-year mortality (both P <.05). Kaplan-Meier survival analysis showed that the higher the fibrinogen level on POD 1, the better the 1- and 2-year survival of patients with ascites (P <.05), whereas the fibrinogen level on POD 1 was associated with 1-year (P <.05) but not 2-year survival of patients without ascites.

Conclusion

Fibrinogen on POD 1 is a predictor of 2-year post-OLT survival of patients with HBV-related HCC with ascites.
Mode identification and seismic study of δ Scuti, the prototype of a class of pulsating stars
Authors: Daszyńska-Daszkiewicz J , Pamyatnykh A A , Walczak P , Handler G , Pigulski A , Szewczuk W
Published: May 2021

We present a seismic study of δ Scuti based on a mode identification from multicoulor photometry. The dominant frequency can be associated only with a radial mode and the second frequency is, most probably, a dipole mode. The other six frequencies have more ambiguous identifications. The photometric mode identification provided also some constraints on the atmospheric metallicity [m/H] ≈ +0.5 and microturbulent velocity ξt ≈ 4 km s−1. For models reproducing the dominant frequency, we show that only the fundamental mode is possible and the first overtone is excluded. However, the location of δ Scuti near the terminal age main sequence requires the consideration of three stages of stellar evolution. For the star to be on the main sequence, it is necessary to include overshooting from the convective core with a parameter of at least αov = 0.25 at the metallicity greater than Z = 0.019. It turned out that the value of the relative amplitude of the bolometric flux variations (the non-adiabatic parameter f) is mainly determined by the position of the star in the HR diagram, i.e. by its effective temperature and luminosity, whereas the effect of the evolutionary stage is minor. On the other hand, the convective efficiency in the subphotospheric layers has a dominant effect on the value of the parameter f. Comparing the theoretical and empirical values of f for the radial dominant mode, we obtain constraints on the mixing length parameter αMLT which is less than about 1.0, independently of the adopted opacity data and chemical mixture. This value of αMLT is substantially smaller than for a calibrated solar model indicating rather low to moderately efficient convection in the envelope of δ Scuti.
Deep Extragalactic VIsible Legacy Survey (DEVILS): SED fitting in the D10-COSMOS field and the evolution of the stellar mass function and SFR–M⋆ relation
Authors: Thorne Jessica E , Robotham Aaron S G , Davies Luke J M , Bellstedt Sabine , Driver Simon P , Bravo Matías , Bremer Malcolm N , Holwerda Benne W , Hopkins Andrew M , Lagos Claudia del P , Phillipps Steven , Siudek Malgorzata , Taylor Edward N , Wright Angus H
Published: May 2021

We present catalogues of stellar masses, star formation rates (SFRs), and ancillary stellar population parameters for galaxies spanning 0 < z < 9 from the Deep Extragalactic VIsible Legacy Survey (DEVILS). DEVILS is a deep spectroscopic redshift survey with very high completeness, covering several premier deep fields including COSMOS (D10). Our stellar mass and SFR estimates are self-consistently derived using the spectral energy distribution (SED) modelling code ProSpect, using well-motivated parametrizations for dust attenuation, star formation histories, and metallicity evolution. We show how these improvements, and especially our physically motivated assumptions about metallicity evolution, have an appreciable systematic effect on the inferred stellar masses, at the level of ∼0.2 dex. To illustrate the scientific value of these data, we map the evolving galaxy stellar mass function (SMF) and the SFR–M⋆ relation for 0 < z < 4.25. In agreement with past studies, we find that most of the evolution in the SMF is driven by the characteristic density parameter, with little evolution in the characteristic mass and low-mass slopes. Where the SFR–M⋆ relation is indistinguishable from a power law at z > 2.6, we see evidence of a bend in the relation at low redshifts (z < 0.45). This suggests evolution in both the normalization and shape of the SFR–M⋆ relation since cosmic noon. It is significant that we only clearly see this bend when combining our new DEVILS measurements with consistently derived values for lower redshift galaxies from the Galaxy And Mass Assembly (GAMA) survey: this shows the power of having consistent treatment for galaxies at all redshifts.
A lander radio science experiment for the estimation of the gravity field and rotation of comet 133P/Elst-Pizarro
Authors: Gao Wutong , Yan Jianguo , Wang Bo , Xi Guo , Ye Mao , Jin Weitong , Barriot Jean-Pierre
Published: May 2021

The main belt comet 133P/Elst-Pizarro is one of the targets of the proposed Chinese small body exploration mission. The rotation and gravity of this comet will be modelled at the end of the mission phase. To prepare this mission, we performed a radio science simulation based on the current knowledge of the characteristics of 133P/Elst-Pizarro. Simulated two-way Earth–orbiter and orbiter–lander range rate tracking data with a lander positioned at the comet equator were used to determine the gravity field coefficients and the rotational parameters. Our simulation results show that the introduction of the orbiter–lander range rate data can significantly decrease the uncertainty in the initial state vector of the orbiter as well as the uncertainty in the rotation and gravity parameters.
A highly accreting low-mass black hole hidden in the dust: Suzaku and NuSTAR observations of the NLS1 Mrk 1239
Authors: Jiang Jiachen , Baloković Mislav , Brightman Murray , Liu Honghui , Harrison Fiona A , Lansbury George B
Published: May 2021

We present torus modelling for the X-ray spectra of a nearby narrow-line Seyfert 1 galaxy Mrk 1239 (z = 0.0199), based on archival Suzaku, NuSTAR, and Swift observations. Our model suggests very soft intrinsic power-law continuum emission of Γ ≈ 2.57 in 2019 and Γ ≈ 2.98 in 2007. By applying a correction factor to the unabsorbed X-ray luminosity, we find that Mrk 1239 is accreting near or around the Eddington limit. Our best-fitting spectral model also suggests a torus with a column density of log (NH,ave/ cm−2) = 25.0 ± 0.2 and a high covering factor of 0.90 in Mrk 1239, indicating that this source is most likely to be viewed almost face-on with i ≈ 26°. Our line of sight might cross the edge of the torus with NH,los = 2–5 × 1023 cm−2. The high Eddington ratio and the high line-of-sight column density makes Mrk 1239 one of the active galactic nuclei that are close to the limit where wind may form near the edge of the torus due to high radiation pressure.
Broad-band spectral and timing properties of MAXI J1348–630 using AstroSat and NICER observations
Authors: Jithesh V , Misra Ranjeev , Maqbool Bari , Mall Gitika
Published: May 2021

We present broad-band X-ray spectral-timing analysis of the new Galactic X-ray transient MAXI J1348–630 using five simultaneous AstroSat and NICER observations. Spectral analysis using AstroSat data identify the source to be in the soft state for the first three observations and in a faint and bright hard state for the next two. Quasi-periodic oscillations at ∼0.9 and ∼6.9 Hz, belonging to the type-C and type-A class are detected. In the soft state, the power density spectra are substantially lower (by a factor >5) for the NICER (0.5–12 keV) band compared to the AstroSat/LAXPC (3–80 keV) one, confirming that the disc is significantly less variable than the Comptonization component. For the first time, energy-dependent fractional rms and time lag in the 0.5–80 keV energy band was measured at different Fourier frequencies, using the bright hard state observation. Hard time lag is detected for the bright hard state, while the faint one shows evidence for soft lag. A single-zone propagation model fits the LAXPC results in the energy band 3–80 keV with parameters similar to those obtained for Cygnus X–1 and MAXI J1820+070. Extending the model to lower energies, reveals qualitative similarities but having quantitative differences with the NICER results. These discrepancies could be because the NICER and AstroSat data are not strictly simultaneous and because the simple propagation model does not take into account disc emission. The results highlight the need for more joint coordinated observations of such systems by NICER and AstroSat.
Pulsar candidate identification using semi-supervised generative adversarial networks
Authors: Balakrishnan Vishnu , Champion David , Barr Ewan , Kramer Michael , Sengar Rahul , Bailes Matthew
Published: May 2021

Machine learning methods are increasingly helping astronomers identify new radio pulsars. However, they require a large amount of labelled data, which is time consuming to produce and biased. Here, we describe a Semi-supervised generative adversarial network, which achieves better classification performance than the standard supervised algorithms using majority unlabelled data sets. We achieved an accuracy and mean F-Score of 94.9 per cent trained on only 100 labelled candidates and 5000 unlabelled candidates compared to our standard supervised baseline which scored at 81.1 per cent and 82.7 per cent, respectively. Our final model trained on a much larger labelled data set achieved an accuracy and mean F-score value of 99.2 per cent and a recall rate of 99.7 per cent. This technique allows for high-quality classification during the early stages of pulsar surveys on new instruments when limited labelled data are available. We open-source our work along with a new pulsar-candidate data set produced from the High Time Resolution Universe – South Low Latitude Survey. This data set has the largest number of pulsar detections of any public data set and we hope it will be a valuable tool for benchmarking future machine learning models.
Zinc stable isotope analysis reveals Zn dyshomeostasis in benign tumours, breast cancer, and adjacent histologically normal tissue
Authors: Sullivan Kaj V , Moore Rebekah E T , Capper Miles S , Schilling Kathrin , Goddard Kate , Ion Charlotte , Layton-Matthews Daniel , Leybourne Matthew I , Coles Barry , Kreissig Katharina , Antsygina Olga , Coombes R Charles , Larner Fiona , Rehkämper Mark
Published: May 2021

The disruption of Zn homeostasis has been linked with breast cancer development and progression. To enhance our understanding of changes in Zn homeostasis both inside and around the tumour microenvironment, Zn concentrations and isotopic compositions (δ66Zn) were determined in benign (BT) and malignant (MT) tumours, healthy tissue from reduction mammoplasty (HT), and histologically normal tissue adjacent to benign (NAT(BT)) and malignant tumours (NAT(MT)). Mean Zn concentrations in NAT(BT) are 5.5 µg g−1 greater than in NAT(MT) (p = 0.00056) and 5.1 µg g−1 greater than in HT (p = 0.0026). Zinc concentrations in MT are 12.9 µg g−1 greater than in HT (p = 0.00012) and 13.3 µg g−1 greater than in NAT(MT) (p < 0.0001), whereas δ66Zn is 0.17‰ lower in MT than HT (p = 0.017). Benign tumour Zn concentrations are also elevated compared to HT (p = 0.00013), but are not significantly elevated compared to NAT(BT) (p = 0.32). The δ66Zn of BT is 0.15‰ lower than in NAT(BT) (p = 0.045). The similar light δ66Zn of BT and MT compared to HT and NAT may be related to the isotopic compensation of increased metallothionein (64Zn-rich) expression by activated matrix metalloproteinase (66Zn-rich) in MT, and indicates a resultant 66Zn-rich reservoir may exist in patients with breast tumours. Zinc isotopic compositions thus show promise as a potential diagnostic tool for the detection of breast tumours. The revealed differences of Zn accumulation in healthy and tumour-adjacent tissues require additional investigation.
YbeY is required for ribosome small subunit assembly and tRNA processing in human mitochondria
Authors: D’Souza Aaron R , Van Haute Lindsey , Powell Christopher A , Mutti Christian D , Páleníková Petra , Rebelo-Guiomar Pedro , Rorbach Joanna , Minczuk Michal
Published: May 2021

Mitochondria contain their own translation apparatus which enables them to produce the polypeptides encoded in their genome. The mitochondrially-encoded RNA components of the mitochondrial ribosome require various post-transcriptional processing steps. Additional protein factors are required to facilitate the biogenesis of the functional mitoribosome. We have characterized a mitochondrially-localized protein, YbeY, which interacts with the assembling mitoribosome through the small subunit. Loss of YbeY leads to a severe reduction in mitochondrial translation and a loss of cell viability, associated with less accurate mitochondrial tRNASer(AGY) processing from the primary transcript and a defect in the maturation of the mitoribosomal small subunit. Our results suggest that YbeY performs a dual, likely independent, function in mitochondria being involved in precursor RNA processing and mitoribosome biogenesis. Issue Section: Nucleic Acid Enzymes.
noisyR: enhancing biological signal in sequencing datasets by characterizing random technical noise
Authors: Moutsopoulos Ilias , Maischak Lukas , Lauzikaite Elze , Vasquez Urbina Sergio A , Williams Eleanor C , Drost Hajk-Georg , Mohorianu Irina I
Published: May 2021

High-throughput sequencing enables an unprecedented resolution in transcript quantification, at the cost of magnifying the impact of technical noise. The consistent reduction of random background noise to capture functionally meaningful biological signals is still challenging. Intrinsic sequencing variability introducing low-level expression variations can obscure patterns in downstream analyses. We introduce noisyR, a comprehensive noise filter to assess the variation in signal distribution and achieve an optimal information-consistency across replicates and samples; this selection also facilitates meaningful pattern recognition outside the background-noise range. noisyR is applicable to count matrices and sequencing data; it outputs sample-specific signal/noise thresholds and filtered expression matrices. We exemplify the effects of minimizing technical noise on several datasets, across various sequencing assays: coding, non-coding RNAs and interactions, at bulk and single-cell level. An immediate consequence of filtering out noise is the convergence of predictions (differential-expression calls, enrichment analyses and inference of gene regulatory networks) across different approaches.
HP1021 is a redox switch protein identified in Helicobacter pylori
Authors: Szczepanowski Piotr , Noszka Mateusz , Żyła-Uklejewicz Dorota , Pikuła Fabian , Nowaczyk-Cieszewska Malgorzata , Krężel Artur , Stingl Kerstin , Zawilak-Pawlik Anna
Published: May 2021

Helicobacter pylori is a gram-negative, microaerophilic, pathogenic bacterium and a widespread colonizer of humans. H. pylori has developed mechanisms that enable it to overcome the harsh environment of the human stomach, including reactive oxygen species (ROS). Interestingly, up to now no typical regulator dedicated to the oxidative-stress response has been discovered. In this work, we reveal that the inhibitor of replication initiation HP1021 functions as a redox switch protein in H. pylori and plays an important role in response to oxidative stress of the gastric pathogen. Each of the two predicted HP1021 domains contains three cysteine residues. We show that the cysteine residues of HP1021 are sensitive to oxidation both in vitro and in vivo, and we demonstrate that HP1021 DNA-binding activity to oriC depends on the redox state of the protein. Moreover, Zn2+ modulates HP1021 affinity towards oriC template DNA. Transcription analysis of selected H. pylori genes by RT-qPCR indicated that HP1021 is directly involved in the oxygen-dependent control of H. pylori fecA3 and gluP genes, which are implicated in response to oxidative stress. In conclusion, HP1021 is a redox switch protein and could be a target for H. pylori control strategies.
Identification of an RNA sponge that controls the RoxS riboregulator of central metabolism in Bacillus subtilis
Authors: Durand Sylvain , Callan-Sidat Adam , McKeown Josie , Li Stephen , Kostova Gergana , Hernandez-Fernaud Juan R , Alam Mohammad Tauqeer , Millard Andrew , Allouche Delphine , Constantinidou Chrystala , Condon Ciarán , Denham Emma L
Published: May 2021

sRNAs are a taxonomically-restricted but transcriptomically-abundant class of post-transcriptional regulators. While of major importance for adaption to the environment, we currently lack global-scale methodology enabling target identification, especially in species without known RNA hub proteins (e.g. Hfq). Using psoralen RNA cross-linking and Illumina-sequencing we identify RNA–RNA interacting pairs in vivo in Bacillus subtilis, resolving previously well-described interactants. Although sRNA–sRNA pairings are rare (compared with sRNA–mRNA), we identify a robust example involving the conserved sRNA RoxS and an unstudied sRNA RosA (Regulator of sRNA A). We show RosA to be the first confirmed RNA sponge described in a Gram-positive bacterium. RosA interacts with at least two sRNAs, RoxS and FsrA. The RosA/RoxS interaction not only affects the levels of RoxS but also its processing and regulatory activity. We also found that the transcription of RosA is repressed by CcpA, the key regulator of carbon-metabolism in B. subtilis. Since RoxS is already known to be transcriptionally controlled by malate via the transcriptional repressor Rex, its post-transcriptional regulation by CcpA via RosA places RoxS in a key position to control central metabolism in response to varying carbon sources.
Genome-Wide Association Study Identifies Genetic Risk Factors for Spastic Cerebral Palsy
Authors: Hale Andrew T , Akinnusotu Oluwatoyin , He Jing , Wang Janey , Hibshman Natalie , Shannon Chevis N , Naftel Robert P
Published: May 2021

BACKGROUND

Although many clinical risk factors of spastic cerebral palsy (CP) have been identified, the genetic basis of spastic CP is largely unknown. Here, using whole-genome genetic information linked to a deidentified electronic health record (BioVU) with replication in the UK Biobank and FinnGen, we perform the first genome-wide association study (GWAS) for spastic CP.

OBJECTIVE

To define the genetic basis of spastic CP.

METHODS

Whole-genome data were obtained using the multi-ethnic genotyping array (MEGA) genotyping array capturing single-nucleotide polymorphisms (SNPs), minor allele frequency (MAF) > 0.01, and imputation quality score (r2) > 0.3, imputed based on the 1000 genomes phase 3 reference panel. Threshold for genome-wide significance was defined after Bonferroni correction for the total number of SNPs tested (P < 5.0 × 10–8). Replication analysis (defined as P < .05) was performed in the UK Biobank and FinnGen.

RESULTS

We identify 1 SNP (rs78686911) reaching genome-wide significance with spastic CP. Expression quantitative trait loci (eQTL) analysis suggests that rs78686911 decreases expression of GRIK4, a gene that encodes a high-affinity kainate glutamatergic receptor of largely unknown function. Replication analysis in the UK Biobank and FinnGen reveals additional SNPs in the GRIK4 loci associated with CP.

CONCLUSION

To our knowledge, we perform the first GWAS of spastic CP. Our study indicates that genetic variation contributes to CP risk.
Understanding Nonadherence to Tuberculosis Medications in India Using Urine Drug Metabolite Testing: A Cohort Study
Authors: Subbaraman Ramnath , Thomas Beena E , Kumar J Vignesh , Thiruvengadam Kannan , Khandewale Amit , Kokila S , Lubeck-Schricker Maya , Ranjith Kumar M , Gaurkhede Gunjan Rahul , Walgude Apurva Shashikant , Hephzibah Mercy J , Kumbhar Jagannath Dattatraya , Eliasziw Misha , Mayer Kenneth H , Haberer Jessica E
Published: May 2021

Background

Poor adherence to tuberculosis (TB) treatment is associated with disease recurrence and death. Little research has been conducted in India to understand TB medication nonadherence.

Methods

We enrolled adult drug-susceptible TB patients, approximately half of whom were people with human immunodeficiency virus (PWH), in Chennai, Vellore, and Mumbai. We conducted a single unannounced home visit to administer a survey assessing reasons for nonadherence and collect a urine sample that was tested for isoniazid content. We described patient-reported reasons for nonadherence and identified factors associated with nonadherence (ie, negative urine test) using multivariable logistic regression. We also assessed the association between nonadherence and treatment outcomes.

Results

Of 650 participants in the cohort, 77 (11.8%) had a negative urine test. Nonadherence was independently associated with daily wage labor (adjusted odds ratio [aOR], 2.7; confidence interval [CI], 1.1–6.5; P = .03), the late continuation treatment phase (aOR, 2.0; CI, 1.1–3.9; P = .03), smear-positive pulmonary disease (aOR, 2.1; CI, 1.1–3.9; P = .03), alcohol use (aOR, 2.5; CI, 1.2–5.2; P = .01), and spending ≥30 minutes collecting medication refills (aOR, 6.6; CI, 1.5–29.5; P = .01). People with HIV reported greater barriers to collecting medications than non-PWH. Among 167 patients reporting missing doses, reported reasons included traveling from home, forgetting, feeling depressed, and running out of pills. The odds of unfavorable treatment outcomes were 4.0 (CI, 2.1–7.6) times higher among patients with nonadherence (P < .0001).

Conclusion

Addressing structural and psychosocial barriers will be critical to improve TB treatment adherence in India. Urine isoniazid testing may help identify nonadherent patients to facilitate early intervention during treatment.
Characterization of Bacterial and Fungal Infections in Hospitalized Patients With Coronavirus Disease 2019 and Factors Associated With Health Care-Associated Infections
Authors: Kubin Christine J , McConville Thomas H , Dietz Donald , Zucker Jason , May Michael , Nelson Brian , Istorico Elizabeth , Bartram Logan , Small-Saunders Jennifer , Sobieszczyk Magdalena E , Gomez-Simmonds Angela , Uhlemann Anne-Catrin
Published: May 2021

Background

Patients hospitalized with coronavirus disease 2019 (COVID-19) are at increased risk of health care–associated infections (HAIs), especially with prolonged hospital stays. We sought to identify incidence, antimicrobial susceptibilities, and outcomes associated with bacterial/fungal secondary infections in a large cohort of patients with COVID-19.

Methods

We evaluated adult patients diagnosed with COVID-19 between 2 March and 31 May 2020 and hospitalized >24 hours. Data extracted from medical records included diagnoses, vital signs, laboratory results, microbiological data, and antibiotic use. Microbiologically confirmed bacterial and fungal pathogens from clinical cultures were evaluated to characterize community- and health care–associated infections, including describing temporal changes in predominant organisms on presentation and throughout hospitalization. Univariable and multivariable logistic regression analyses were performed to investigate risk factors for HAIs.

Results

A total of 3028 patients were included and accounted for 899 positive clinical cultures. Overall, 516 (17%) patients with positive cultures met criteria for infection. Community-associated coinfections were identified in 183 (6%) patients, whereas HAIs occurred in 350 (12%) patients. Fifty-seven percent of HAIs were caused by gram-negative bacteria and 19% by fungi. Antibiotic resistance increased with longer hospital stays, with incremental increases in the proportion of vancomycin resistance among enterococci and ceftriaxone and carbapenem resistance among Enterobacterales. Intensive care unit stay, invasive mechanical ventilation, and steroids were associated with HAIs.

Conclusions

HAIs occur in a small proportion of patients hospitalized with COVID-19 and are most often caused by gram-negative and fungal pathogens. Antibiotic resistance is more prevalent with prolonged hospital stays. Antimicrobial stewardship is imperative in this population to minimize unnecessary broad-spectrum antibiotic use.
The genomic revolution and species delimitation in birds (and other organisms): Why phenotypes should not be overlooked
Authors: Cadena Carlos Daniel , Zapata Felipe
Published: May 2021

Given the availability of genomic data to identify separately evolving groups of organisms, many researchers establish species limits based on assessments of the extent of gene flow among populations and often use analytical approaches to identify species in which gene flow is explicitly disallowed. Strictly considering lack of—or limited—gene flow as the main or only criterion to delimit species involves two main complications in practice. First, approaches often used to analyze genome-wide data cannot by themselves distinguish species limits from within-species population structure, particularly in allopatric organisms. Second, recognizing as species only those lineages one can identify using such approaches fails to embrace the role of other evolutionary forces (i.e. various forms of selection) in defining evolutionary lineages. Using examples from various groups of birds, we call for the importance of considering evolutionary forces additional to gene flow in species delimitation and explain why genomic approaches commonly used in taxonomic studies may be insufficient by themselves to properly uncover species limits. By considering the processes that structure genotypic and phenotypic variation during speciation, we argue that rigorous analyses of phenotypic variation remain crucial for species delimitation in the genomics era because phenotypes uniquely inform us about the role of selection maintaining the cohesion of evolutionary lineages. Evolutionary theory describing the roles of gene flow, genetic drift and natural and sexual selection in the origin and maintenance of species calls for an integration of genomics with phenomics in avian species delimitation.
Synthesis and structural characterizations of HAp–NaOH–Al2O3 composites for liquid petroleum gas sensing applications
Authors: Avinashi Sarvesh Kumar , Hussain Ajaz , Kumar Kuldeep , Yadav Bal Chandra , Gautam Chandkiram
Published: May 2021

The main objective of present work was to synthesize sodium doped polycrystalline hydroxyapatite NaHAp (NaOH-HAp) powder by employing wet chemical precipitation method and its composites with alumina (Al2O3; 0, 10, 40, 70 wt%) using a scalable solid-state reaction method. Detailed investigations of NaHAp and its composites using X-ray powder diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy, UV–visible spectroscopy, scanning electron microscopy followed by energy-dispersive X-ray spectroscopy and sensing behaviour is carefully described. XRD results exhibited major and minor phase of HAp, Ca2P2O7 and NaOH for NaHAp sample while for all fabricated composites of HAp–NaOH–Al2O3 and revealed the major phase of hibonite CaO(Al2O3)6 along with secondary phases of Ca2P2O7, Na4[Al(PO4)2(OH)], Na3Al(OH)(HPO4)(PO4), NaAl3(PO4)2(OH)4 and NaOH. The crystallite size of NaHAp-based composites was also determined and lies in the range of 200–2800 nm, which is larger than that of Al2O3. FTIR and Raman spectroscopic studies reveal the bonding formation of P–O, O–P–O and Al–O due to intramolecular interaction of Na4(Al(PO4)2(OH)), Na3Al(OH)(HPO4)(PO4) and NaAl3(PO4)2(OH)4 in the HAp–NaOH–Al2O3 composite, while bonding formation of Al–O–H recognized to intermolecular interaction in between Al with H atoms of Na4(Al(PO4)2(OH)), Na3Al(OH)(HPO4)(PO4) and NaAl3(PO4)2(OH)4. The SEM and energy dispersive spectroscopy analysis revealed the presence of all constituent elements of used chemicals which also validate the purity of used materials. It is concluded that the fabricated sensor (60 NaHAp–40 Al2O3) shows lowest response and recovery time, 4 and 3 s for the 0.5 vol.% concentration of the LPG. Therefore, among all composites, this fabricated composite can be used for LPG gas sensing applications.
Structural and biochemical analyses of concanavalin A circular permutation by jack bean asparaginyl endopeptidase
Authors: Nonis Samuel G. , Haywood Joel , Schmidberger Jason W. , Mackie Emily R. R. , Soares da Costa Tatiana P. , Bond Charles S. , Mylne Joshua S.
Published: May 2021

Over 30 years ago, an intriguing posttranslational modification was found responsible for creating concanavalin A (conA), a carbohydrate-binding protein from jack bean (Canavalia ensiformis) seeds and a common carbohydrate chromatography reagent. ConA biosynthesis involves what was then an unprecedented rearrangement in amino-acid sequence, whereby the N-terminal half of the gene-encoded conA precursor (pro-conA) is swapped to become the C-terminal half of conA. Asparaginyl endopeptidase (AEP) was shown to be involved, but its mechanism was not fully elucidated. To understand the structural basis and consequences of circular permutation, we generated recombinant jack bean pro-conA plus jack bean AEP (CeAEP1) and solved crystal structures for each to 2.1 and 2.7 Å, respectively. By reconstituting conA biosynthesis in vitro, we prove CeAEP1 alone can perform both cleavage and cleavage-coupled transpeptidation to form conA. CeAEP1 structural analysis reveals how it is capable of carrying out both reactions. Biophysical assays illustrated that pro-conA is less stable than conA. This observation was explained by fewer intermolecular interactions between subunits in the pro-conA crystal structure and consistent with a difference in the prevalence for tetramerization in solution. These findings elucidate the consequences of circular permutation in the only posttranslation example known to occur in nature.
Role of the unitary correlation operator on high-momentum antisymmetrized molecular dynamics using the bare NN interaction for 3H and 4He
Authors: Zhao Qing , Isaka Masahiro , Myo Takayuki , Lyu Mengjiao , Toki Hiroshi , Horiuchi Hisashi , Takemoto Hiroki , Wan Niu
Published: May 2021

We extend high-momentum antisymmetrized molecular dynamics (HMAMD) by incorporating the short-range part of the unitary correlation operator method (UCOM) as the variational method of finite nuclei. In this HMAMD+UCOM calculation of light nuclei, HMAMD is mainly in charge of the tensor correlation with up to four-body correlation, while the short-range correlation is further improved by using UCOM. The binding energies of the $^3$H and $^4$He nuclei are calculated with HMAMD+UCOM using the AV8$'$ bare nucleon–nucleon ($NN$) interaction. The different roles of the short-range and tensor correlations from HMAMD and UCOM are analyzed in the numerical results. Compared with previous calculations based on different variational methods, this newly extended HMAMD+UCOM method can almost provide consistent results with ab initio results.
A review of health-related quality of life associated with pneumococcal disease: pooled estimates by age and type of disease
Authors: Tang Zhaoli , Matanock Almea , Jeon Seonghye , Leidner Andrew J
Published: May 2021

Background

Estimates in the research literature on the health-related quality of life (QOL) associated with pneumococcal disease exhibit variation. It complicates the selection of estimates in modeling projects that evaluate the health impact and economic value of the prevention and treatment. This study reviewed the literature and developed pooled QOL estimates associated with pneumococcal disease states.

Methods

We searched peer-reviewed literature for studies that reported pneumococcal disease-related QOL estimates. For each study, we extracted QOL estimates and categorized by age group and disease state. QOL estimates were converted to quality-adjusted life-years (QALYs). Pooled QALY estimates were calculated using simple average, sample-size weighting and inverse-variance weighting.

Results

From 18 studies, we organized QOL estimates into 20 groups based on age and disease state. We observed the largest within-disease state variations of QALY estimates in meningitis-related disease states compared to other disease states. Across all age–disease state categories, the pooled QALY estimates ranged from 0.39 for meningitis with long-term sequelae among 0- to 18-year-olds, to 1.00 for non-inpatient pneumonia among 0- to 18-year-olds.

Conclusions

Our results indicated disparities in QOL estimates associated with pneumococcal disease from the literature. Pooled estimates provided a source of consistency that can be used in future modeling efforts.
Health research in the Syrian conflict: opportunities for equitable and multidisciplinary collaboration
Authors: Ekzayez Abdulkarim , Olabi Amina , Douedari Yazan , Meagher Kristen , Bowsher Gemma , Farhat Bashar , Patel Preeti
Published: May 2021

There is considerable global momentum from Syrian researchers, policy makers and diaspora to address health, security and development challenges posed by almost a decade of armed conflict and complex geopolitics that has resulted in different areas of political control. However, research funders have been so far reluctant to invest in large-scale research programmes in severely conflict-affected areas such as northern Syria. This paper presents examples of collaborations and programmes that could change this through equitable partnerships between academic and operational humanitarian organizations involving local Syrian researchers—a tremendous way forward to capitalize and accelerate this global momentum.

Several academic and humanitarian organizations have initiated collaborations to build new networks and partnerships for better research and policy engagement in Syria. The networks conducted two consecutive annual conferences in 2019 and 2020. Key messages from these conference include: (1) equitable partnerships between organizations and individual researchers must form the basis of conducting better research; (2) ensuring the inclusion of local Syrian researchers is crucial in the development of any viable partnership; (3) capacity strengthening in health research is urgently needed in Syria’s current phase of active conflict to inform, develop and implement strengthened and sustainable health systems in the post-conflict phase.
Geophilosophical exemption to mandatory vaccination
Authors: Kahambing Jan Gresil S
Published: May 2021

This correspondence introduces the ethics behind a specific exemption to mandatory vaccination. Public health acknowledges medical and non-medical reasons for vaccination exemption. Geophilosophical ones, which the author coined, can provide an option to remote populations with low density and are seeking more choices in confronting the dilemma of being vaccinated.
Mental health and legal education in the time of pandemic
Authors: Macaraan Maryrose C
Published: May 2021

In response to an article published in this journal where the authors systematically reviewed the impact of shifted norms and practices due to the COVID-19 pandemic on the mental health of people, this paper explores this aspect within a more specific set of the population—the law students. It addresses the impact of transition from physical face-to-face classes to a virtual online platform on their psychological wellness and coping mechanism. In the end, the paper mentions strategies that the law students may adopt amid the lack or absence of physical interaction with professors, classmates and friends.
Building vaccine confidence through public participation
Authors: Corpuz Jeff Clyde G
Published: May 2021

A recently published correspondence proposed the involvement of private-owned companies in Coronavirus Disease 2019 (COVID-19) vaccination program. This article raises awareness that vaccine hesitancy could undermine the effectiveness of COVID-19 vaccination programs. This article proposes the idea of public participation: dialog-based approach, incentive-based (non-financial) approach and reminder-recall approach based on the World Health Organization guidelines.
Can the ECG be used to estimate age-related survival?
Authors: Kellett J , Bogh S B , Ekelund U , Brabrand M
Published: May 2021

Background

There are few reports of the relationship between electrocardiogram (ECG) findings and the age-related survival of acutely ill patients.

Aim

This study compared the 1-year survival curves of patients attending two Danish emergency departments (EDs) with normal and abnormal ECGs. Patients were divided into age groups from 20 to 90 years of age, and an abnormal ECG was defined as low QRS voltage (i.e. lead I + II <1.4 mV) or QTc interval prolongation >434 ms.

Methods

A retrospective register-based observational study on 35 496 patients attending two Danish EDs, with 100% follow-up for 1 year.

Results

ECG abnormality increases linearly with age, and between 30 and 70 years of age. Patients aged 20–29 years with ECG abnormalities are more than four times more likely to die within a year than patients of the same age with a normal ECG. An individual with an abnormal ECG has the same risk of dying within a year as an individual with a normal ECG who is 10 years older. After 70 years of age this tight relationship ends, but for younger individuals with an abnormal ECG the increase in mortality is even higher.

Conclusion

An ECG may be a simple practical estimate of age-related survival. For a patient under 70 years, an abnormal QRS voltage or a prolonged QTc interval may increase 1-year mortality to that of a patient ∼10 years older.