bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissecting the transcriptional program of phosphomannomutase 2-deficient cells: Lymphoblastoide B cell lines as a valuable model for congenital disorders of glycosylation studies
Authors: Parrado Antonio , Rubio Gonzalo , Serrano Mercedes , De la Morena-Barrio María Eugenia , Ibáñez-Micó Salvador , Ruiz-Lafuente Natalia , Schwartz-Albiez Reinhard , Esteve-Solé Ana , Alsina Laia , Corral Javier , Hernández-Caselles Trinidad
Published: August 2021

Congenital disorders of glycosylation (CDG) include 150 genetically and clinically heterogeneous diseases, showing significant glycoprotein hypoglycosylation that leads to pathological consequences in multiple organs and systems whose underlying mechanisms are not yet understood. A few cellular and animal models have been used to study specific CDG characteristics, although they have given limited information due to the few CDG mutations tested and the still missing comprehensive molecular and cellular basic research. Here, we provide specific gene expression profiles, based on ribonucleic acid (RNA) microarray analysis, together with some biochemical and cellular characteristics of a total of nine control Epstein–Barr virus-transformed lymphoblastoid B cell lines (B-LCL) and 13 CDG B-LCL from patients carrying severe mutations in the phosphomannomutase 2 (PMM2) gene, strong serum protein hypoglycosylation and neurological symptoms. Significantly dysregulated genes in PMM2-CDG cells included those regulating stress responses, transcription factors, glycosylation, motility, cell junction and, importantly, those related to development and neuronal differentiation and synapse, such as carbonic anhydrase 2 (CA2) and ADAM23. PMM2-CDG-associated biological consequences involved the unfolded protein response, RNA metabolism and the endoplasmic reticulum, Golgi apparatus and mitochondria components. Changes in the transcriptional and CA2 protein levels are consistent with the CDG physiopathology. These results demonstrate the global transcriptional impact in phosphomannomutase 2-deficient cells, reveal CA2 as a potential cellular biomarker and confirm B-LCL as an advantageous model for CDG studies.
Evaluation of the MYCOPLASMA IST3 urogenital mycoplasma assay in an international multicentre trial
Authors: Boostrom Ian , Bala Yohan , Vasic Jelena Minic , Gluvakov Jelena , Chanard Emmanuel , Barratt Andrew H , Sands Kirsty , Portal Edward , Devigne Laurence , Jones Lucy C , Spiller Owen B
Published: August 2021

Objectives

To evaluate the accuracy, susceptibility and specificity of MYCOPLASMA IST3, the next generation of the most popular culture-based in vitro diagnostic device designed to detect, identify and test the susceptibility of urogenital mycoplasma infections.

Methods

MYCOPLASMA IST3 was evaluated against culture- and molecular-based gold standard methodologies to detect, identify, enumerate and determine antimicrobial resistance for Mycoplasma hominis and Ureaplasma species in 516 clinical samples collected across France, Serbia and the UK. Sample types included vulvovaginal/endocervical or urethral swabs (dry swab or eSwab®), semen and urine samples, which included blinded analysis following addition of a panel of 80 characterized control strains.

Results

Overall species identification was excellent for both Ureaplasma spp. (98.4% sensitivity, 99.7% specificity) and M. hominis (95.7% sensitivity, 100% specificity) relative to combined colony morphology on agar and quantitative PCR standards. Non-dilution-based bacterial load estimation by the assay was accurate between 83.7% (M. hominis) and 86.3% (Ureaplasma spp.) of the time (increased to 94.2% and 100%, respectively, if ±10-fold variance was allowed) relative to colonies counted on agar. Resistance accuracy for Ureaplasma spp. varied from gold standards for only 11/605 of individual tests (major error rate = 1.8%) and for 14/917 individual tests for M. hominis (major error rate = 1.5%).

Conclusions

The redesigned MYCOPLASMA IST3 assay eliminated previous shortcomings by providing independent accurate resistance screening of M. hominis and Ureaplasma species, even in mixed infections, with CLSI-compliant thresholds. Specificity, sensitivity and enumeration estimates correlated closely with the confirmatory methods.
Intrathoracic lipoma in the horizontal fissure of the right lung: a case report
Authors: Nakajima Eiji , Takahashi Hidenobu , Kajiwara Naohiro , Furukawa Kinya , Ishizumi Taichiro , Kataba Hiroaki , Okubo Mitsuru , Hirano Hiroshi , Ikeda Norihiko
Published: August 2021

Lipomas are benign tumors that originate from mesenchymal tissue, such as subcutaneous tissue. Intrathoracic lipomas are rare, and they can occur in the chest wall, mediastinum and bronchi. In the present case, the patient had an intrathoracic lipoma that was located in the horizontal fissure of the right lung. Retrospective review of chest radiographs taken at a previous health checkup confirmed that the tumor was growing. The patient had no symptoms, and computed tomography and magnetic resonance imaging suggested that the tumor was a hamartoma. The tumor was resected by video-assisted thoracic surgery, and was diagnosed by pathological analysis as an intrathoracic lipoma consisting of no atypical fats.
Three classes of hemoglobins are required for optimal vegetative and reproductive growth of Lotus japonicus: genetic and biochemical characterization of LjGlb2-1
Authors: Villar Irene , Rubio Maria C , Calvo-Begueria Laura , Pérez-Rontomé Carmen , Larrainzar Estibaliz , Wilson Michael T , Sandal Niels , Mur Luis A , Wang Longlong , Reeder Brandon , Duanmu Deqiang , Uchiumi Toshiki , Stougaard Jens , Becana Manuel
Published: August 2021

Legumes express two major types of hemoglobins, namely symbiotic (leghemoglobins) and non-symbiotic (phytoglobins), with the latter being categorized into three classes according to phylogeny and biochemistry. Using knockout mutants, we show that all three phytoglobin classes are required for optimal vegetative and reproductive development of Lotus japonicus. The mutants of two class 1 phytoglobins showed different phenotypes: Ljglb1-1 plants were smaller and had relatively more pods, whereas Ljglb1-2 plants had no distinctive vegetative phenotype and produced relatively fewer pods. Non-nodulated plants lacking LjGlb2-1 showed delayed growth and alterations in the leaf metabolome linked to amino acid processing, fermentative and respiratory pathways, and hormonal balance. The leaves of mutant plants accumulated salicylic acid and contained relatively less methyl jasmonic acid, suggesting crosstalk between LjGlb2-1 and the signaling pathways of both hormones. Based on the expression of LjGlb2-1 in leaves, the alterations of flowering and fruiting of nodulated Ljglb2-1 plants, the developmental and biochemical phenotypes of the mutant fed on ammonium nitrate, and the heme coordination and reactivity of the protein toward nitric oxide, we conclude that LjGlb2-1 is not a leghemoglobin but an unusual class 2 phytoglobin. For comparison, we have also characterized a close relative of LjGlb2-1 in Medicago truncatula, MtLb3, and conclude that this is an atypical leghemoglobin.
Family Involvement in the End-of-Life Decision-Making Process: Legal and Bioethical Analysis of Empirical Findings
Authors: Karako-Eyal Nili , Gilbar Roy
Published: August 2021

End-of-life decision making involves clinicians, patients, and relatives; yet, the law in Israel hardly recognises the role of relatives. This raises the question of the law’s impact in practice and, hence, whether it should be amended. This issue is examined on the basis of findings from a qualitative, interview-based study conducted in Israel among relatives of dying patients. The findings indicate that there are areas in which clinicians and relatives do not adhere to the law in the end-of-life decision-making process. For example, they do not always ascertain the patient's end-of-life preferences, which ignores a patient's right to autonomy and their right to make informed decisions. The apparent gaps between the actual conduct of clinicians and relatives on the one hand and the directives of the Israeli Dying Patient Act 2005 on the other, lead us to propose several changes to the Act.
Axisymmetric simulations of the convective overstability in protoplanetary discs
Authors: Teed Robert J , Latter Henrik N
Published: August 2021

Protoplanetary discs at certain radii exhibit adverse radial entropy gradients that can drive oscillatory convection (‘convective overstability’; COS). The ensuing hydrodynamical activity may reshape the radial thermal structure of the disc while mixing solid material radially and vertically or, alternatively, concentrating it in vortical structures. We perform local axisymmetric simulations of the COS using the code snoopy, showing first how parasites halt the instability’s exponential growth, and secondly, the different saturation routes it takes subsequently. As the Reynolds and (pseudo-) Richardson numbers increase, the system moves successively from (i) a weakly non-linear state characterized by relatively ordered non-linear waves, to (ii) wave turbulence, and finally to (iii) the formation of intermittent and then persistent zonal flows. In three dimensions, we expect the latter flows to spawn vortices in the orbital plane. Given the very high Reynolds numbers in protoplanetary discs, the third regime should be the most prevalent. As a consequence, we argue that the COS is an important dynamical process in planet formation, especially near features such as dead zone edges, ice lines, gaps, and dust rings.
Signatures of hierarchical mergers in black hole spin and mass distribution
Authors: Tagawa Hiromichi , Haiman Zoltán , Bartos Imre , Kocsis Bence , Omukai Kazuyuki
Published: August 2021

Recent gravitational wave (GW) observations by LIGO/Virgo show evidence for hierarchical mergers, where the merging BHs are the remnants of previous BH merger events. These events may carry important clues about the astrophysical host environments of the GW sources. In this paper, we present the distributions of the effective spin parameter (χeff), the precession spin parameter (χp), and the chirp mass (mchirp) expected in hierarchical mergers. Under a wide range of assumptions, hierarchical mergers produce (i) a monotonic increase of the average of the typical total spin for merging binaries, which we characterize with $\scriptstyle{{\bar{\chi }}_\mathrm{typ}\equiv \overline{(\chi _\mathrm{eff}^2+\chi _\mathrm{p}^2)^{1/2}}}$, up to roughly the maximum mchirp among first-generation (1g) BHs, and (ii) a plateau at ${\bar{\chi }}_\mathrm{typ}\sim 0.6$ at higher mchirp. We suggest that the maximum mass and typical spin magnitudes for 1g BHs can be estimated from ${\bar{\chi }}_\mathrm{typ}$ as a function of mchirp. The GW data observed in LIGO/Virgo O1–O3a prefers an increase in ${\bar{\chi }}_\mathrm{typ}$ at low mchirp, which is consistent with the growth of the BH spin magnitude by hierarchical mergers at ∼2σ confidence. A Bayesian analysis using the χeff, χp, and mchirp distributions suggests that 1g BHs have the maximum mass of ∼15–$30\, {\rm M}_\odot$ if the majority of mergers are of high-generation BHs (not among 1g–1g BHs), which is consistent with mergers in active galactic nucleus discs and/or nuclear star clusters, while if mergers mainly originate from globular clusters, 1g BHs are favoured to have non-zero spin magnitudes of ∼0.3. We also forecast that signatures for hierarchical mergers in the ${\bar{\chi }}_\mathrm{typ}$ distribution can be confidently recovered once the number of GW events increases to ≳ O(100).
Baryonic dense matter in view of gravitational-wave observations
Authors: Thapa Vivek Baruah , Kumar Anil , Sinha Monika
Published: August 2021

The detection of gravitational waves (GWs) from the merger of binary neutron star (NS) events (GW170817 and GW190425) and subsequent estimations of tidal deformability play a key role in constraining the behaviour of dense matter. In addition, massive NS candidates (∼2 M⊙) along with NICER mass–radius measurements also set sturdy constraints on the dense matter equation of state. Strict bounds from GWs and massive NS observations constrain the theoretical models of nuclear matter comportment at large density regimes. On the other hand, model parameters providing the highly dense matter response are bounded by nuclear saturation properties. This work analyses coupling parametrizations from two classes based on covariant density functional models: non-linear and density-dependent schemes. Considering these constraints together, we study possible models and parametrization schemes with the feasibility of exotic degrees of freedom in dense matter which go well with the astrophysical observations as well as the terrestrial laboratory experiments. We show that most parametrizations with non-linear schemes do not support the observations and experiments while density-dependent scheme goes well with both. Astrophysical observations are well explained if the inclusion of heavier non-strange baryons is considered as one fraction of the dense matter particle spectrum.
Surface brightness fluctuations to constrain secondary stellar populations: revealing very low-metallicity stars in massive galaxies
Authors: Rodríguez-Beltrán P , Vazdekis A , Cerviño M , Beasley M A
Published: August 2021

The aim of this work is to explore the potential of surface brightness fluctuations (SBF) for studying composite stellar populations (CSP). To do so, we have computed the standard (mean) and SBF spectra with E-MILES stellar population synthesis code. We have created a set of models composed by different mass fractions of two single stellar populations, as a first approximation of a CSP scenario. With these models we present an ensemble of SBF colour–colour diagnostic diagrams that reveal different secondary populations depending on the bands used. For this work we focus on those colours capable of unveiling small fractions of metal-poor components in elliptical galaxies, which are dominated by old metal-rich stellar populations. We fit a set of synthetic models and a selection of nearby elliptical galaxies to our CSP models using both mean and SBF colours. We find that the results are highly improved and return small secondary components when mean and SBF values are applied simultaneously, instead of employing them separately or as a constraint. Finally, we explore the possibility of tracking chemical enrichment histories by including in the analysis a variety of SBF colours. For this purpose we present an example where, with two different SBF colour–colour diagrams, we untangle a small contribution of a young solar population and an old metal-poor component from an old solar principal population. The results we have found are promising, but limited by the available data. We highlight the urgent need for new, better, and more consistent SBF observations.
Constraints on warm dark matter from UV luminosity functions of high-z galaxies with Bayesian model comparison
Authors: Rudakovskyi Anton , Mesinger Andrei , Savchenko Denys , Gillet Nicolas
Published: August 2021

The number density of small dark matter (DM) haloes hosting faint high-redshift galaxies is sensitive to the DM free-streaming properties. However, constraining these DM properties is complicated by degeneracies with the uncertain baryonic physics governing star formation. In this work, we use a flexible astrophysical model and a Bayesian inference framework to analyse ultraviolet (UV) luminosity functions (LFs) at z = 6–8. We vary the complexity of the astrophysical galaxy model (single versus double power law for the stellar – halo mass relation) as well as the matter power spectrum [cold DM versus thermal relic warm DM (WDM)], comparing their Bayesian evidences. Adopting a conservatively wide prior range for the WDM particle mass, we show that the UV LFs at z = 6–8 only weakly favour cold DM over WDM. We find that particle masses of ≲ 2 keV are rejected at a 95 per cent credible level in all models that have a WDM-like power spectrum cutoff. This bound should increase to ∼2.5 keV with the James Webb Space Telescope (JWST).
Conversions between gas-phase metallicities in MaNGA
Authors: Scudder Jillian M , Ellison Sara L , El Meddah El Idrissi Loubna , Poetrodjojo Henry
Published: August 2021

We present polynomial conversions between each of 11 different strong line gas-phase metallicity calibrations, each based on ∼1.1 million star-forming spaxels in the public Sloan Digital Sky Survey (SDSS) Data Release 15 (DR15) Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey. For this sample, which is ∼20 times larger than previous works, we present fifth-order polynomial fits for each of 110 possible calibration conversions, for both Small Magellanic Cloud-type and Milky Way-type dust corrections. The typical 2σ scatter around our polynomial fits is 0.1 dex; we present the range over which the metallicities are valid. Conversions between metallicities which rely on the same set of line ratios, or a heavily shared set of emission lines, have reduced scatter in their conversions relative to those conversions with little overlap in required emission lines. Calibration conversions with less consistent sets of emission lines also have increased galaxy-to-galaxy variability, and this variability can account for up to 35 per cent of the total scatter. We also compare our conversions to previous work with the single fibre SDSS DR7 spectra along with higher spatial resolution data from the TYPHOON Integral Field Spectroscopy survey, resulting in comparison samples with spatial resolutions from several kpc down to ∼100 pc. Our metallicity conversions, obtained with the large sample of MaNGA, are robust against the influence of diffuse ionized gas, redshift, effective radius, and spatial blurring, and are therefore consistent across both integrated spectra and the high-resolution integral field spectroscopy data.
Characterization of the hidden break in giant clam 28S ribosomal RNA
Authors: Tan Keana , Conaco Cecilia
Published: August 2021

The molluscan 28S ribosomal RNA (rRNA) naturally cleaves into two fragments of similar size as 18S rRNA. This phenomenon, known as the hidden break, has been described in many other protostome species. Here, we characterize the 28S rRNA hidden break region in seven giant clam species, Tridacna gigas, T. derasa, T. maxima, T. noae, T. crocea, Hippopus hippopus and H. porcellanus. We confirm that the break consistently occurs in giant clams and is observed in all tissues and developmental stages. The region of the giant clam 28S rRNA break is located at a position homologous to the well-characterized 28S rRNA break in insects. High AU content and a stem–loop secondary structure in the region may contribute to fragmentation of the 28S rRNA molecule. An awareness of the existence of the hidden break in molluscs, such as the giant clams, which are emerging systems for understanding how environmental change affects life in the ocean, will facilitate progress of RNA sequencing-based analyses that currently rely on standard RNA profiles as a measure of sample integrity.
The Polycomb protein RING1B enables estrogen-mediated gene expression by promoting enhancer–promoter interaction and R-loop formation
Authors: Zhang Yusheng , Liu Tong , Yuan Fenghua , Garcia-Martinez Liliana , Lee Kyutae D , Stransky Stephanie , Sidoli Simone , Verdun Ramiro E , Zhang Yanbin , Wang Zheng , Morey Lluis
Published: August 2021

Polycomb complexes have traditionally been prescribed roles as transcriptional repressors, though increasing evidence demonstrate they can also activate gene expression. However, the mechanisms underlying positive gene regulation mediated by Polycomb proteins are poorly understood. Here, we show that RING1B, a core component of Polycomb Repressive Complex 1, regulates enhancer–promoter interaction of the bona fide estrogen-activated GREB1 gene. Systematic characterization of RNA:DNA hybrid formation (R-loops), nascent transcription and RNA Pol II activity upon estrogen administration revealed a key role of RING1B in gene activation by regulating R-loop formation and RNA Pol II elongation. We also found that the estrogen receptor alpha (ERα) and RNA are both necessary for full RING1B recruitment to estrogen-activated genes. Notably, RING1B recruitment was mostly unaffected upon RNA Pol II depletion. Our findings delineate the functional interplay between RING1B, RNA and ERα to safeguard chromatin architecture perturbations required for estrogen-mediated gene regulation and highlight the crosstalk between steroid hormones and Polycomb proteins to regulate oncogenic programs.
Charcot–Marie–Tooth mutation in glycyl-tRNA synthetase stalls ribosomes in a pre-accommodation state and activates integrated stress response
Authors: Mendonsa Samantha , von Kuegelgen Nicolai , Bujanic Lucija , Chekulaeva Marina
Published: August 2021

Toxic gain-of-function mutations in aminoacyl-tRNA synthetases cause a degeneration of peripheral motor and sensory axons, known as Charcot–Marie–Tooth (CMT) disease. While these mutations do not disrupt overall aminoacylation activity, they interfere with translation via an unknown mechanism. Here, we dissect the mechanism of function of CMT mutant glycyl-tRNA synthetase (CMT-GARS), using high-resolution ribosome profiling and reporter assays. We find that CMT-GARS mutants deplete the pool of glycyl-tRNAGly available for translation and inhibit the first stage of elongation, the accommodation of glycyl-tRNA into the ribosomal A-site, which causes ribosomes to pause at glycine codons. Moreover, ribosome pausing activates a secondary repression mechanism at the level of translation initiation, by inducing the phosphorylation of the alpha subunit of eIF2 and the integrated stress response. Thus, CMT-GARS mutant triggers translational repression via two interconnected mechanisms, affecting both elongation and initiation of translation.
HbA1c and beyond
Authors: Rossing Peter
Published: August 2021

The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on Diabetes Management in Chronic Kidney Disease from 2020 comes at an opportune time when progress in diabetes technology and therapeutics offers new options to manage the large population of patients with diabetes and chronic kidney disease (CKD) at high risk of poor health outcomes. Management of haemoglobin A1c is important in diabetes, but an enlarging base of evidence from large clinical trials has demonstrated important new treatments offering organ protection and not just glucose management, such as sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists. It is the ambition that the guideline can help to optimize the clinical care of people with diabetes and CKD by integrating new options with existing management strategies based on high-quality evidence. Here, the focus has been on comprehensive care of patients with diabetes and CKD, glycaemic monitoring and targets, antihyperglycaemic therapies in patients with diabetes and CKD, and new developments since the guideline was published offering new opportunities and a wider target population for the new interventions.
Use of Electronic Cigarettes as a Predictor of Cannabis Experimentation: A Longitudinal Study Among German Youth
Authors: Seidel Ann-Kathrin , Morgenstern Matthis , Galimov Artur , Pedersen Anya , Isensee Barbara , Goecke Michaela , Hanewinkel Reiner
Published: August 2021

Introduction

Experimentation with e-cigarettes is rising among youth, and there are concerns that e-cigarettes could be a new risk factor for initiating substance use. This study aimed to investigate whether e-cigarette use longitudinally predicts experimentation with cannabis.

Aims and Methods

During 2017–2019, a prospective cohort study with an observation period of 18 months was conducted with 3040 students from Germany who had never used cannabis (mean age = 14.8, range: 13–18 years). A multiple Poisson regression was used to investigate whether e-cigarette use was an independent predictor of future cannabis use.

Results

Lifetime e-cigarette use was reported by 29.4% of the survey population (n = 894) at baseline, and 17.4% (n = 529) initiated cannabis use during the observation period. Among e-cigarette ever users, the initiation rate was 34.5% compared with 10.4% of never users. Results were robust to adjustment for age, sex, migrant status, type of school, sensation seeking, peer cannabis use, the use of alcohol and conventional cigarettes (ARR = 1.83; 95% CI: 1.48–2.25). Further analyses revealed that the association between e-cigarette use and cannabis experimentation was stronger among youth with low sensation-seeking scores (ARR = .77, CI: .61–.97) and no conventional cigarette use (ARR = .48, CI: .37–.64) at baseline.

Conclusions

E-cigarette use is associated with a subsequent initiation of cannabis use. This association seems to be stronger for youth who have a lower risk for substance use in general. Future studies need to investigate whether this is only true for experimental or also more frequent cannabis use.

Implications

The study indicates a prospective association between e-cigarette use and initiation of cannabis experimentation independent of other risk factors. It suggests that e-cigarette use is more strongly associated with cannabis initiation for youth with a lower propensity to use substances (low sensation-seekers and non-smokers).
bHLH transcription factors LP1 and LP2 regulate longitudinal cell elongation
Authors: Lu Rui , Zhang Jiao , Wu Yu-Wei , Wang Yao , Zhang Jie , Zheng Yong , Li Yang , Li Xue-Bao
Published: August 2021

Basic helix–loop–helix/helix–loop–helix (bHLH/HLH) transcription factors play substantial roles in plant cell elongation. In this study, two bHLH/HLH homologous proteins leaf related protein 1 and leaf-related protein 2 (AtLP1 and AtLP2) were identified in Arabidopsis thaliana. LP1 and LP2 play similar positive roles in longitudinal cell elongation. Both LP1 and LP2 overexpression plants exhibited long hypocotyls, elongated cotyledons, and particularly long leaf blades. The elongated leaves resulted from increased longitudinal cell elongation. lp1 and lp2 loss-of-function single mutants did not display distinct phenotypes, but the lp1lp2 double mutant showed decreased leaf length associated with less longitudinal polar cell elongation. Furthermore, the phenotype of lp1lp2 could be rescued by the expression of LP1 or LP2. Expression of genes related to cell elongation was upregulated in LP1 and LP2 overexpression plants but downregulated in lp1lp2 double mutant plants compared with that of wild type. LP1 and LP2 proteins could directly bind to the promoters of Longifolia1 (LNG1) and LNG2 to activate the expression of these cell elongation related genes. Both LP1 and LP2 could interact with two other bHLH/HLH proteins, IBH1 (ILI1 binding BHLH Protein1) and IBL1 (IBH1-like1), thereby suppressing the transcriptional activation of LP1 and LP2 to the target genes LNG1 and LNG2. Thus, our data suggested that LP1 and LP2 act as positive regulators to promote longitudinal cell elongation by activating the expression of LNG1 and LNG2 genes in Arabidopsis. Moreover, homodimerization of LP1 and LP2 may be essential for their function, and interaction between LP1/LP2 and other bHLH/HLH proteins may obstruct transcriptional regulation of target genes by LP1 and LP2.
Cortical thinning and sleep slow wave activity reductions mediate age-related improvements in cognition during mid-late adolescence
Authors: Ong Ju Lynn , Jamaluddin S Azrin , Tandi Jesisca , Chee Nicholas I Y N , Leong Ruth L F , Huber Reto , Lo June C , Chee Michael W L
Published: August 2021

Study Objectives

Gains in cognitive test performance that occur during adolescence are associated with brain maturation. Cortical thinning and reduced sleep slow wave activity (SWA) are markers of such developmental changes. Here we investigate whether they mediate age-related improvements in cognition.

Methods

109 adolescents aged 15–19 years (49 males) underwent magnetic resonance imaging, polysomnography (PSG), and a battery of cognitive tasks within a 2-month time window. Cognitive tasks assessed nonverbal intelligence, sustained attention, speed of processing and working memory and executive function. To minimize the effect of sleep history on SWA and cognitive performance, PSG and test batteries were administered only after at least 8 nights of 9-h time-in-bed (TIB) sleep opportunity.

Results

Age-related improvements in speed of processing (r = 0.33, p = 0.001) and nonverbal intelligence (r = 0.24, p = 0.01) domains were observed. These cognitive changes were associated with reduced cortical thickness, particularly in bilateral temporoparietal regions (rs = −0.21 to −0.45, ps < 0.05), as well as SWA (r = −0.35, p < 0.001). Serial mediation models found that ROIs in the middle/superior temporal cortices, together with SWA mediated the age-related improvement observed on cognition.

Conclusions

During adolescence, age-related improvements in cognition are mediated by reductions in cortical thickness and sleep SWA.
Aberrant expression of SNHG12 contributes to N, N-dimethylformamide-induced hepatic apoptosis both in short-term and long-term DMF exposure
Authors: Liu Ye , Wen Cuiju , Zhang Yangchun , Liu Ziqi , He Qianmei , Cui Mengxing , Peng Honghao , Wang Yuqing , Zhang Xueying , Li Xudong , Wang Qing
Published: August 2021

N, N-Dimethylformamide (DMF) can cause liver damage in occupationally exposed workers, but the molecular mechanism of DMF-induced liver damage has not been fully elucidated. Researches have proved that lncRNA plays a major function in chemical-induced liver toxicity and can be used as a biomarker and therapeutic target for liver injury. In order to verify that lncRNA also participates in DMF-induced liver damage, we treated HL-7702 cells with 75 or 150 mM DMF, and obtained lncRNA expression profiles through high-throughput sequencing. Among the differentially expressed lncRNAs, lncRNA SNHG12 was proved to be significantly downregulated in DMF-treated HL-7702 cells and participate in DMF-mediated apoptosis, even under long-term low-dose DMF exposure (5–10 mM, 8 weeks). In addition, according to bioinformatics analysis, miR-218-5p is expected to be a potential target of SNHG12, which was verified by the dual luciferase reporter assay in HEK293FT cells. MiR-218-5p mimic can induce apoptosis in HL-7702 cells. Among the predicted targets of miR-218-5p, protein kinase C epsilon (PRKCE) was reported to be involved in apoptosis, and was indeed downregulated by miR-218-5p mimic in our study. Further experiments showed that changes of the expression of SNHG12 can affect the expression of PRKCE. In the epidemiological study of occupational population, we also found that SNHG12 was downregulated in the serum exosomes of workers exposed to DMF. These results indicated that SNHG12 can mediate DMF-induced apoptosis of HL-7702 cells through miR-218-5p/PRKCE pathway.
A novel epidemiological scoring system for the prediction of mortality in COVID-19 patients
Authors: Mishra Prabhaker , Singh Ratender Kumar , Nath Alok , Pande Shantanu , Agarwal Anil , Sanjeev Om Prakash , Gupta Devendra , Singh Prateek , Ghatak Tanmoy , Hashim Zia , Khare Vansh , Khuba Sandeep , Rastogi Amit , Dhiman Radha K
Published: August 2021

Background

Most of the reported risk score models for coronavirus disease 2019 (COVID-19) mortality are based on the levels of inflammatory markers, comorbidities or various treatment modalities, and there is a paucity of risk score models based on clinical symptoms and comorbidities.

Methods

To address this need, age, clinical symptoms and comorbidities were used to develop a COVID-19 scoring system (CSS) for early prediction of mortality in severe COVID-19 patients. The CSS was developed with scores ranging from 0 to 9. A higher score indicates higher risk with good discrimination quality presented by Mann Whitney U test and area under receiver operating characteristic curve (AUROC).

Results

Patient age of ≥60 y, cough, breathlessness, diabetes and any other comorbidity (with or without diabetes) are significant and independent risk factors for non-survival among COVID-19 patients. The CSS showed good sensitivity and specificity (i.e. 74.1% and 78.5% at CSS≥5, respectively), with an overall diagnostic accuracy of 82.8%, which was close to the diagnostic accuracy detected in the validation cohort (81.9%). In the validation cohort, high (8–9), medium (5–7) and low (0–4) CSS groups had 54.80%, 28.60% and 6.5% observed mortality, respectively, which was very close to the predicted mortality (62.40%, 27.60% and 5.2%, respectively, by scoring cohort).

Conclusions

The CSS shows a positive relationship between a higher score and proportion of mortality and, as its validation showed, it is useful for the prediction of risk of mortality in COVID-19 patients at an early stage, so that referral for triage and admission can be predetermined even before admission to hospital.
The role of soils on pollination and seed dispersal
Authors: Carvalheiro Luísa G. , Bartomeus Ignasi , Rollin Orianne , Timóteo Sérgio , Tinoco Carla Faleiro
Published: August 2021

Ongoing environmental changes are affecting physical, chemical and biological soil components. Evidence of impacts of soil changes on pollinators' and seed dispersers' behaviour, fitness and density is scarce, but growing. Here, we reviewed information on such impacts and on a number of mechanisms that may explain its propagation, taking into account the full range of resources required by the large and diverse number of species of these two important functional groups. We show that while there is substantial evidence on the effects of soil nitrogen enrichment and changes in soil water content on the quality and quantity of floral and fruit resources, little is known on the effects of changes of other soil properties (e.g. soil pH, soil structure, other nutrients). Also, the few studies showing correlations between soil changes and pollinator and seed disperser foraging behaviour or fitness do not clearly identify the mechanisms that explain such correlation. Finally, most studies (including those with nitrogen and water) are local and limited to a small number of species, and it remains unclear how variable such effects are across time and geographical regions, and the strength of interactive effects between soil properties. Increasing research on this topic, taking into consideration how impacts propagate through species interaction networks, will provide essential information to predict impacts of ongoing environmental changes and help guide conservation plans that aim to minimize impacts on ecosystem functioning.

This article is part of the theme issue ‘The role of soils in delivering Nature's Contributions to People’.
The role of soils in the regulation of ocean acidification
Authors: Renforth P. , Campbell J. S.
Published: August 2021

Soils play an important role in mediating chemical weathering reactions and carbon transfer from the land to the ocean. Proposals to increase the contribution of alkalinity to the oceans through ‘enhanced weathering’ as a means to help prevent climate change are gaining increasing attention. This would augment the existing connection between the biogeochemical function of soils and alkalinity levels in the ocean. The feasibility of enhanced weathering depends on the combined influence of what minerals are added to soils, the formation of secondary minerals in soils and the drainage regime, and the partial pressure of respired CO2around the dissolving mineral. Increasing the alkalinity levels in the ocean through enhanced weathering could help to ameliorate the effects of ocean acidification in two ways. First, enhanced weathering would slightly elevate the pH of drainage waters, and the receiving coastal waters. The elevated pH would result in an increase in carbonate mineral saturation states, and a partial reversal in the effects of elevated CO2. Second, the increase in alkalinity would help to replenish the ocean's buffering capacity by maintaining the ‘Revelle Factor’, making the oceans more resilient to further CO2emissions. However, there is limited research on the downstream and oceanic impacts of enhanced weathering on which to base deployment decisions.

This article is part of the theme issue ‘The role of soils in delivering Nature's Contributions to People’.
The role of soils in the regulation of hazards and extreme events
Authors: Saco P. M. , McDonough K. R. , Rodriguez J. F. , Rivera-Zayas J. , Sandi S. G.
Published: August 2021

The frequency and intensity of natural hazards and extreme events has increased throughout the last century, resulting in adverse socioeconomic and ecological impacts worldwide. Key factors driving this increase include climate change, the growing world population, anthropogenic activities and ecosystem degradation. One ecologically focused approach that has shown potential towards the mitigation of these hazard events is the concept of nature's contributions to people (or NCP), which focuses on enhancing the material and non-material benefits of an ecosystem to reduce hazard vulnerability and enhance overall human well-being. Soils, in particular, have been identified as a key ecosystem component that may offer critical hazard regulating functionality. Thus, this review investigates the modulating role of soils in the regulation of natural hazards and extreme events, with a focus on floods, droughts, landslides and sand/dust storms, within the context of NCP.

This article is part of the theme issue ‘The role of soils in delivering Nature's Contributions to People’.
Identification of a developmental switch in information transfer between whisker S1 and S2 cortex in mice
Authors: Cai Linbi , Yang Jenq-Wei , Chou Shen-Ju , Wang Chia-Fang , Luhmann Heiko , Karayannis Theofanis
Published: August 2021

The whiskers of rodents are a key sensory organ that provides critical tactile information for animal navigation and object exploration throughout life. Previous work has explored the developmental sensory-driven activation of the primary sensory cortex processing whisker information (wS1), also called barrel cortex. This body of work has shown that the barrel cortex is already activated by sensory stimuli during the first post-natal week. However, it is currently unknown when over the course of development these stimuli begin being processed by higher order cortical areas, such as secondary whisker somatosensory area (wS2). Here we investigate for the first time the developmental engagement of wS2 by sensory stimuli and the emergence of cortico-cortical communication from wS1 to wS2. Using in vivo wide-field imaging and electrophysiological recordings in control and conditional knock-out mice we find that wS1 and wS2 are able to process bottom-up information coming from the thalamus already right after birth. We identify that it is only at the end of the first post-natal week that wS1 begins to provide excitation into wS2, a connection which begins to acquire feed-forward inhibition characteristics after the second post-natal week. Therefore, we have uncovered a developmental window during which excitatory versus inhibitory functional connectivity between wS1 and wS2 takes place.
Task space exploration improves adaptation after incompatible virtual surgeries
Authors: Berger Denise J. , Borzelli Daniele , d’Avella Andrea
Published: August 2021

Humans have a remarkable capacity to learn new motor skills, a process that requires novel muscle activity patterns. Muscle synergies may simplify the generation of muscle patterns through the selection of a small number of synergy combinations. Learning new motor skills may then be achieved by acquiring novel muscle synergies. In a previous study, we used myoelectric control to construct virtual surgeries that altered the mapping from muscle activity to cursor movements. After compatible virtual surgeries, which could be compensated by recombining subject-specific muscle synergies, participants adapted quickly. In contrast, after incompatible virtual surgeries, which could not be compensated by recombining existing synergies, participants explored new muscle patterns, but failed to adapt. Here, we tested whether task space exploration can promote learning of novel muscle synergies, required to overcome an incompatible surgery. Participants performed the same reaching task as in our previous study, but with more time to complete each trial, thus allowing for exploration. We found an improvement in trial success after incompatible virtual surgeries. Remarkably, improvements in movement direction accuracy after incompatible surgeries occurred faster for corrective movements than for the initial movement, suggesting that learning of new synergies is more effective when used for feedback control. Moreover, reaction time was significantly higher after incompatible than after compatible virtual surgeries, suggesting an increased use of an explicit adaptive strategy to overcome incompatible surgeries. Taken together, these results indicate that exploration is important for skill learning and suggest that human participants, with sufficient time can learn new muscle synergies.

NEW & NOTEWORTHY

Motor skill learning requires the acquisition of novel muscle patterns, a slow adaptive process. Here we show that learning to control a cursor after an incompatible virtual surgery, a complex skill requiring new muscle synergies, is possible when enough time for task space exploration is provided. Our results suggest that learning new synergies is related to the exceptional human capacity to acquire a wide variety of novel motor skills with practice.
Columnar processing of border ownership in primate visual cortex
Authors: Franken Tom P. , Reynolds John H.
Published: August 2021

To understand a visual scene, the brain segregates figures from background by assigning borders to foreground objects. Neurons in primate visual cortex encode which object owns a border (border ownership), but the underlying circuitry is not understood. Here we used multielectrode probes to record from border ownership selective units in different layers in macaque visual area V4 to study the laminar organization and timing of border ownership selectivity.

We find that border ownership selectivity occurs first in deep layer units, in contrast to spike latency for small stimuli in the classical receptive field. Units on the same penetration typically share the preferred side of border ownership, also across layers, similar to orientation preference. Units are often border ownership selective for a range of border orientations, where the preferred sides of border ownership are systematically organized in visual space.

Together our data reveal a columnar organization of border ownership in V4 where the earliest border ownership signals are not simply inherited from upstream areas, but computed by neurons in deep layers, and may thus be part of signals fed back to upstream cortical areas or the oculomotor system early after stimulus onset. The finding that preferred border ownership is clustered and can cover a wide range of spatially contiguous locations, suggests that the asymmetric context integrated by these neurons is provided in a systematically clustered manner, possibly through corticocortical feedback and horizontal connections.
Ladostigil attenuates the oxidative and ER stress in human neuroblast-like SH-SY5Y cells
Authors: Zohar Keren , Lezmi Elyad , Eliyahu Tsiona , Linial Michal
Published: August 2021

A hallmark of the aging brain is the robust inflammation mediated by microglial activation. Neuroinflammation resulting from the induction of oxidative stress in neurodegenerative diseases and following brain injury. Chronic treatment of aging rats by ladostigil, a compound with antioxidant and anti-inflammatory function, prevented microglial activation and learning deficits. In this study, we investigate the effect of ladostigil on neuronal-like SH-SY5Y cells. We show that SH-SY5Y cells exposed to acute (by H2O2) or chronic oxidative stress (by Sin1, 3-morpholinosydnonimine) induced apoptotic cell death. However, in the presence of ladostigil, the decline in cell viability and the oxidative levels were partially reversed. RNA-seq analysis showed that chronic oxidation by Sin1 resulted in coordinated suppression of endoplasmic reticulum (ER) quality control and ER stress response gene sets. Chronic oxidative stress impacted ER proteostasis and induced the expression of numerous lncRNAs. Pre-incubation with ladostigil before exposing SH-SY5Y cells to Sin1 induced Clk1 (Cdc2-like kinase 1) which was implicated in psychophysiological stress in mice and Alzheimer disease. Ladostigil also suppressed the expression of Ccpg1 (Cell cycle progression 1) and Synj1 (Synaptojanin 1) that function in ER-autophagy and endocytic pathways. We postulate that ladostigil alleviated cell damage by oxidation and ER stress. Therefore, it may attenuate neurotoxicity and cell death that accompany chronic stress conditions in the aging brain.
Emigration Effects on Estimates of Age- and Sex-specific Survival of Small Mammals
Authors: Weldy Matthew J. , Lesmeister Damon B. , Epps Clinton W.
Published: August 2021

Age- and sex-specific survival estimates are crucial to understanding important life-history characteristics and variation in these estimates can be a key driver of population dynamics. When estimating survival using Cormack–Jolly–Seber (CJS) models and capture–recapture data, emigration is typically assumed to have a negligible effect on estimates such that apparent survival is indistinguishable from true survival. Consequently, especially for populations or age classes with high dispersal rates, apparent survival estimates are often biased low and temporal patterns in survival might be masked when site fidelity varies temporally.

We used 9 years of annual mark-recapture data to estimate age-, sex-, and time-specific apparent survival of Humboldt’s flying squirrels (Glaucomys oregonensis) and Townsend’s chipmunks (Neotamias townsendii). For Humboldt’s flying squirrels, these estimates support a small body of research investigating potential variation of survival among age and sex classes, but age- and sex-specific survival has not been evaluated for Townsend’s chipmunks. We also quantified the effects of age- and sex-specific emigration on confounded estimates of apparent survival.

Our estimates of juvenile flying squirrel survival were high relative to other small mammal species and estimates for both species were variable among years. We found survival differed moderately among age and sex classes for Humboldt’s flying squirrels, but little among age and sex classes for Townsend’s chipmunks, and that the degree to which emigration confounded apparent survival estimates varied substantially among years. Without correcting for emigration, apparent survival estimates were lower and temporal variation was obscured, particularly for male Humboldt’s flying squirrels and female Townsend’s chipmunks.

Our results demonstrate that emigration can influence commonly used estimates of apparent survival. Unadjusted estimates confounded the interpretation of differences in survival between age and sex classes and masked potential temporal patterns in survival because the magnitude of adjustment varied among years. We conclude that apparent survival estimators are robust during some time periods; however, when emigration rates vary in time the effects of emigration should be carefully considered and accounted for, especially in comparative studies and those with policy and conservation implications.