bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbially induced calcite precipitation usingBacillus velezensiswith guar gum
Authors: Dikshit Rashmi , Jain Animesh , Dey Arjun , Kamilya Sujit , Mondal Abhishake , Kumar Aloke
Published: May 2019

The present study was performed to explore the efficiency of microbially induced calcite precipitation (MICP) via locally isolated bacterial strains. Strains were isolated from soil and were screened for urease activity as well as microbial precipitation. Among all screened isolates, a carbonate precipitating soil bacterium was subjected for 16S rRNA gene sequencing. This strain was identified asBacillus velezensis. The MICP characteristics of this strain were explored under three different media compositions and significant amount of precipitation in all cases was observed. Highest amount of precipitation was seen with guar as a biopolymer additive medium under experimented conditions. Activity of isolated strain with reference to pH profile, and ammonia concentration and total reducing sugar was further explored under media supplemented with four concentrations of guar (0.25%, 0.5%, 0.75% and 1% w/v). Microstructural analysis of microbial precipitation was performed with the help of scanning electron microscopy (SEM) and X-ray powder diffraction (XRD) analysis, which confirmed the presence of calcium carbonate in different phases. The strain was subjected to bio-cementation and locally available sand was successfully consolidated. XRD results confirmed the presence of calcium carbonate on consolidated samples.
Immediate inhibition of sucrose uptake inCorynebacterium glutamicumin response to intracellular glucose-6-phosphate accumulation requires theptsGencoded EII-permease
Authors: Petrov Dimitar P. , Goldbeck Oliver , Krämer Reinhard , Seibold Gerd M.
Published: May 2019

Corynebacterium glutamicumco-metabolizes most carbon sources, such as glucose and sucrose. Uptake of those sugars by the PTS involves a glucose- and a sucrose-specific permease EIIGlc(ptsG) and EIISuc(ptsS), respectively. Block of glycolysis by deletion ofpgi(encodes phosphoglucoisomerase) redirects glucose-driven carbon flux towards pentose phosphate pathway.C. glutamicumΔpgigrows poorly with glucose but has unaffected, good growth with sucrose. However, addition of glucose to sucrose-cultivatedC. glutamicumΔpgiimmediately arrested growth via inhibition of the EIISuc–mediated sucrose uptake and reduction ofptsS-mRNA amounts. Kinetic analyses revealed that sucrose uptake inhibition inC. glutamicumΔpgitook place within 15 s after glucose addition. We show that inhibition of PTS-mediated sucrose uptake occurs as direct response to glucose-6-P accumulation. Moreover, addition of non-PTS substrates, which are metabolized to glucose-6-P such as maltose or glucose-6-P itself (uptake was enabled by heterologously produced UhpT), led to similar growth and sucrose uptake inhibition as glucose addition. Despite EIIGlcnot being involved in uptake of these substrates, negative effects on sucrose uptake after addition of maltose and glucose-6-P were absent in the EIIGlc–deficient strainC. glutamicumΔpgiΔptsG. These results show that theptsG-encoded EIIGlcis part of a novel mechanism for perception of intracellular glucose-6-P accumulation and instantaneous inhibition of EIISuc-mediated sucrose uptake inC. glutamicum. This novel mode of control of PTS activity by an early glycolytic metabolite probably allows efficient adaptation of sugar uptake to the capacity of the central metabolism during co-metabolization, which is characteristic forC. glutamicum.

IMPORTANCE

Coordination of substrate uptake and metabolism are a prerequisite for efficient co-utilization of substrates, a trait typical for the Gram-positiveC. glutamicum. Sucrose uptake via the PTS permease EIISucin this organism immediately was inhibited in response to intracellular accumulation of the glycolysis intermediate glucose-6-phosphate. This inhibition depends exclusively on the presence but not activity of the PTS permease EIIGluc. Thus,C. glutamicumpossesses a novel, immediate, and PTS-dependent way to control and coordinate both uptake and metabolization of multiple substrates by monitoring of their metabolic levels in the cell. This offers new insights and interesting concepts for a further rational engineering of this industrially important production organism and exemplifies a putative general strategy of bacteria for the coordination of sugar uptake and central metabolism.
Stability and dynamics interrelations in a Lipase: Mutational and MD simulations based investigations
Authors: Moharana Tushar Ranjan , Kumar Virendra , Rao N. Madhusudhana
Published: May 2019

Dynamics plays crucial role in the function and stability of proteins. Earlier studies have provided ambivalent nature of these interrelations. Epistatic effects of amino acid substitutions on dynamics are an interesting strategy to investigate such relations. In this study we investigated the interrelation between dynamics with that of stability and activity ofBacillus subtilislipase (BSL) using experimental and molecular dynamics simulation (MDS) approaches. Earlier we have identified many stabilising mutations in BSL using directed evolution. In this study these stabilizing mutations were clustered based on their proximity in the sequence into four groups (CM1 to 4). Activity, thermal stability, protease stability and aggregations studies were performed on these four mutants, along with the wild type BSL, to conclude that the mutations in each region contributed additively to the overall stability of the enzyme without suppressing the activity. Root mean square fluctuation and amide bond squared order parameter analysis from MDS revealed that dynamics has increased for CM1, CM2 and CM3 compared to the wild type in the amino acid region 105 to 112 and for CM4 in the amino acid region 22 to 30. In all the mutants core regions dynamics remained unaltered, while the dynamics in the rigid outer region (RMSF <0.05 nm) has increased. Alteration in dynamics, took place both in the vicinity (CM2, 0.41 nm) as well as far away from the mutations (CM1, 2.6 nm; CM3 1.5 nm; CM4 1.7 nm). Our data suggests that enhanced dynamics in certain regions in a protein may actually improve stability.

Statement of Significance

How does a protein readjust its dynamics upon incorporation of an amino acid that improved its stability? Are the stabilizing effects of a substitution being local or non-local in nature? While there is an excellent documentation (from x-ray studies) of both local and non-local adjustments in interactions upon incorporation of a stabilizing mutations, the effect of these on the protein dynamics is less investigated. The stability and MD data presented here on four mutants, stabilized around four loop regions of a lipase, suggests that stabilizing effects of these mutations influence two specific regions leaving rest of the protein unperturbed. In addition, our data supports, observations by others, wherein enhancement in stability in a protein need not result in dampening of dynamics of a protein.
Evidence of transcription at polyT short tandem repeats
Authors: Bessière Chloé , Saraswat Manu , Grapotte Mathys , Menichelli Christophe , Ramilowski Jordan A. , Severin Jessica , Hayashizaki Yoshihide , Itoh Masayoshi , Hasegawa Akira , Suzuki Harukazu ,   FANTOM consortium, Carninci Piero , Hoon Michiel J.L. de , Wasserman Wyeth W. , Bréhélin Laurent , Lecellier Charles-Henri
Published: May 2019

Background

Using the Cap Analysis of Gene Expression technology, the FANTOM5 consortium provided one of the most comprehensive maps of Transcription Start Sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers.

Results

Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at short tandem repeats (STRs) corresponding to homopolymers of thymidines (T). Additional analyse confirm that these CAGEs are truly associated with transcriptionally active chromatin marks. Furthermore, we train a sequence-based deep learning model able to predict CAGE signal at T STRs with high accuracy (~81%) Extracting features learned by this model reveals that transcription at T STRs is mostly directed by STR length but also instructions lying in the downstream sequence. Excitingly, our model also predicts that genetic variants linked to human diseases affect this STR-associated transcription.

Conclusions

Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism. We also provide a new metric that can be considered in future studies of STR-related complex traits.
Emergence of consistent intra-individual locomotor patterns during zebrafish development
Authors: Fitzgerald Jennifer A. , Kirla Krishna T. , Zinner Carl P. , vom Berg Colette M.
Published: May 2019

The analysis of larval zebrafish locomotor behavior has emerged as a powerful indicator of perturbations in the nervous system and is used in many fields of research, such as neuroscience, toxicology or drug discovery. The behavior of larval zebrafish, however, is highly variable, resulting in the use of high numbers of animals and the inability to detect small effects. In this study, we analyzed whether individual locomotor behavior is stable over development and whether behavioral parameters correlate with physiological and morphological features of the larvae, with the aim to better understand variability and predictability of larval locomotor behavior. We found that locomotor activity of individuals is consistent within the same day and becomes predictable during development especially during dark phases, when larvae are performing exploratory light-searching behavior and display increased activity. Stimulus induced startle responses were less predictable for an individual, and response strength did not correlate with inherent locomotor activity. Moreover, locomotor activity was not associated with physiological and morphological features of the larva (resting heart rate, body length, size of the swim bladder). These findings highlight the areas of intra-individual consistency, which could be used to improve the sensitivity of assays using zebrafish locomotor activity as an endpoint.
A cytochrome P450 from juvenile mustard leaf beetles hydroxylates geraniol, a key step in iridoid biosynthesis
Authors: Fu Nanxia , Yang Zhi-ling , Pauchet Yannick , Paetz Christian , Brandt Wolfgang , Boland Wilhelm , Burse Antje
Published: May 2019

Juveniles of the leaf beetle Phaedon cochleariae synthesize iridoid via the mevalonate pathway to repel predators. The normal terpenoid biosynthesis is integrated into the dedicated defensive pathway by the ω-hydroxylation of geraniol to 8-hydroxygeraniol. Here we identify and characterize the geraniol 8-hydroxylase as a P450 monooxygenase using integrated transcriptomic and proteomic analyses. In the fat body, 73 individual cytochrome P450s were identified. The double stranded RNA (dsRNA)-mediated knock down of CYP6BH5 led to a significant reduction of 8-hydroxygeraniol-glucoside in the hemolymph and, later, of the chrysomelidial in the defensive secretion. Heterologously expressed CYP6BH5 converted geraniol to 8-hydroxygeraniol. In addition to geraniol, CYP6BH5 also catalyzes other monoterpenols, such as nerol and citronellol, into the corresponding α, ω-dihydroxy compounds.

Highlights

The geraniol 8-hydroxylase in Phaedon cochleariae was identified as a cytochrome P450 CYP6BH5.

RNA interference emphasized the importance of CYP6BH5 in iridoid biosynthesis.

In vitro enzyme assays showed that recombinant CYP6BH5 is a substrate promiscuous enzyme, converting the ω-hydroxylation of geraniol, nerol, citronellol but not linalool.

Homology modeling suggested the -OH group of the substrate plays an important role in coordinating the substrates with the enzyme’s catalytic cavity.
MCC950/CRID3 potently targets the NACHT domain of wildtype NLRP3 but not disease-associated mutants for inflammasome inhibition
Authors: Vande Walle Lieselotte , Stowe Irma B. , Šácha Pavel , Lee Bettina L. , Demon Dieter , Fossoul Amelie , Van Hauwermeiren Filip , Saavedra Pedro H. V. , Šimon Petr , Šubrt Vladimír , Kostka Libor , Stivala Craig E. , Pham Victoria C. , Staben Steven T. , Yamazoe Sayumi , Konvalinka Jan , Kayagaki Nobuhiko , Lamkanfi Mohamed
Published: May 2019

The NLRP3 inflammasome drives pathological inflammation in a suite of autoimmune, metabolic, malignant and neurodegenerative diseases. Additionally,NLRP3gain-of-function point mutations cause systemic periodic fever syndromes that are collectively known as cryopyrin-associated periodic syndromes (CAPS). There is significant interest in the discovery and development of diarylsulfonylurea Cytokine Release Inhibitory Drugs (CRIDs) such as MCC950/CRID3, a potent and selective inhibitor of the NLRP3 inflammasome, for the treatment of CAPS and other diseases. However, drug discovery efforts have been constrained by the lack of insight in the molecular target and mechanism by which these CRIDs inhibit the NLRP3 inflammasome. Here, we show that the NACHT domain of NLRP3 is the molecular target of diarylsulfonylurea inhibitors. Interestingly, we find photoaffinity labelling of the NACHT domain requires an intact (d)ATP-binding pocket and is substantially reduced for most CAPS-associated NLRP3 mutants. In concordance, MCC950/CRID3 failed to inhibit NLRP3- driven inflammatory pathology in two mouse models of CAPS. Moreover, it abolished circulating levels of interleukin (IL)-1β and IL-18 in LPS-challenged wildtype mice but not inNlrp3L351Pknock-in mice and ex vivo-stimulated mutant macrophages. These results identify wildtype NLRP3 as the molecular target of MCC950/CRID3, and show that CAPS-related NLRP3 mutants escape efficient MCC950/CRID3 inhibition. Collectively, this work suggests that MCC950/CRID3-based therapies may effectively treat inflammation driven by wildtype NLRP3, but not CAPS-associated mutants.
Infection-driven activation of transglutaminase 2 boosts glucose uptake and hexosamine biosynthesis
Authors: Maffei Benoit , Laverrière Marc , Wu Yongzheng , Triboulet Sébastien , Perrinet Stéphanie , Duchateau Magalie , Matondo Mariette , Hollis Robert L. , Gourley Charlie , Rupp Jan , Keillor Jeffrey W. , Subtil Agathe
Published: May 2019

Transglutaminase 2 (TG2) is a ubiquitous enzyme with transamidating activity. We report here that the expression and activity of TG2 are enhanced in cells infected with the obligate intracellular bacteriaChlamydia trachomatis. Genetic or pharmacological inhibition of TG2 activity impair bacterial development. We show that TG2 increases glucose import by up-regulating the transcription of the glucose transporter genesGLUT-1andGLUT-3. Furthermore, TG2 activation drives one specific glucose-dependent pathway in the host, i.e. hexosamine biosynthesis. Mechanistically, we identify the glucosamine:fructose-6-phosphate amidotransferase (GFPT) among the substrates of TG2. GFPT modification by TG2 increases its enzymatic activity, resulting in higher levels of UDP-N-acetylglucosamine biosynthesis. As a consequence, TG2 activation results in increased proteinO-GlcNAcylation. The correlation between TG2 transamidating activity andO-GlcNAcylation is disrupted in infected cells because host hexosamine biosynthesis is being exploited by the bacteria, in particular to assist their division. In conclusion, our work establishes TG2 as a key player in controlling glucose-derived metabolic pathways in mammalian cells, themselves hijacked byC. trachomatisto sustain their own metabolic needs.
BIOTIN ATTACHMENT DOMAIN-CONTAINING proteins, inhibitors of ACCase, are regulated by WRINKLED1
Authors: Liu Hui , Zhai Zhiyang , Kuczynski Kate , Keereetaweep Jantana , Schwender Jorg , Shanklin John
Published: May 2019

WRINKLED1 (WRI1) is a transcriptional activator that binds to AW boxes in the promoters of many genes from central metabolism and FA synthesis, resulting in their transcription. BIOTIN ATTACHMENT DOMAIN-CONTAINING (BADC) proteins are homologs of BIOTIN CARBOXYL CARRIER PROTEIN (BCCP) that lack a biotin-attachment domain and are therefore inactive. In the presence of excess FA, BADC1 and BADC3 are primarily responsible for the observed long-term irreversible inhibition of ACETYL-COA CARBOXYLASE (ACCase), and consequently FA synthesis. Purified WRI1 bound with high affinity (Kds in the low nanomolar range) to canonical AW-boxes from the promoters of all three BADC genes. Consistent with this observation, the expression of BADC1, BADC2 and BADC3 genes and BADC1 protein levels were reduced in wri1-1 relative to wild type (WT), and BADCs gene expression and BADC1 protein levels also were elevated upon WRI1 overexpression. The double mutant badc1badc2 phenocopied wri1-1 with respect to both reduction in root length, and elevation of indole-3-acetic acid-Asp (IAA-Asp) levels relative to WT. Overexpression of BADC1 in wri1-1 decreased its IAA-Asp and partially rescued its short-root phenotype demonstrating a role for BADCs in seedling establishment. That WRI1 positively regulates genes encoding both FA synthesis and BADCs i.e., conditional inhibitors of FA synthesis, represents a coordinated mechanism to achieve lipid homeostasis in which plants couple the transcription their FA synthetic capacity with their capacity to biochemically downregulate it.

One sentence summary

WRI1 regulates genes encoding both fatty acid synthesis and inhibitors of FA synthesis (BADCs), creating a lipid homeostatic mechanism in which the transcription of FA synthetic capacity is coordinated with the capacity to biochemically downregulate FA synthesis.
Probing RNA conformational equilibria within the functional cellular context
Authors: Ganser Laura R. , Chu Chia-Chieh , Bogerd Hal P. , Kelly Megan L. , Cullen Bryan R. , Al-Hashimi Hashim M.
Published: May 2019

Many regulatory RNAs undergo changes in their structure from the dominant ground-state (GS) toward short-lived low-abundance ‘excited-states’ (ES) that reorganize local elements of secondary structure. ESs are increasingly observedin vitroand implicated in the folding and biological activities of regulatory RNAs and as targets for developing therapeutics. However, whether these ESs also form with comparable abundance within the complex cellular environment remains unknown. Here, we developed an approach for assessing the relative stability and abundance of RNA ESs within the functional cellular context. The approach uses point substitution mutations to increase the population of an inactive ES relative to the active GS. The cellular activity of such ES-stabilizing mutants then provides an indirect measure of any residual population of the active GS within the functional cellular context. Compensatory rescue mutations that restore the GS are used to control for changes in cellular activity arising due to changes in sequence. The approach is applied to probe ESs in two highly conserved and functionally important regulatory RNAs from HIV-1: the transactivation response element (TAR) and the Rev response element (RRE). For both RNAs, ES-stabilizing mutations inhibited cellular activity to a degree that correlates with the extent to which they stabilize the ES relative to the GSin vitro. These results indicate that the non-native ESs of TAR and RRE likely form in cells with abundances comparable to those measuredin vitroand their targeted stabilization provides a new avenue for developing anti-HIV therapeutics.
VE-PTP participates in vasculogenic mimicry by preventing autophagic degradation of VE-cadherin
Authors: Delgado-Bellido Daniel , Bueno-Galera Concepción , Garcia-Diaz Angel , Oliver F. Javier
Published: May 2019

Aberrant extra-vascular expression of VE-cadherin has been observed in metastasis associated with Vasculogenic Mimicry (VM); we have recently shown that in VM prone (VM+) tumor cells VE-cadherin is mainly in the form of pVE-cadherin in Y658 allowing an increased plasticity that potentiates VM development. As excessive VE-cadherin phosphorylation is regulated by the phosphatase VEPTP in endothelial cells in the current study we analysed its role in this aberrant phenotype in malignant tumor cells. We show that human malignant melanoma cells VM+, also express VE-PTP although at lower levels than endothelial cells. The complex VE-PTP/VE-Cadherin/p120-catenin act as a safeguard to prevent VE-cadherin degradation by autophagy. Indeed, silencing of VE-PTP results in complete degradation of VE-cadherin with the features of autophagy and increases the global p120 tyrosine phosphorylation status. In summary, we show that VE-PTP is involved in VM formation and disruption of VE-PTP/VE-Cadherin/p120 complex results in enhanced autophagy in aggressive VM+ cells.
Frontal theta and beta oscillations during lower-limb movement in Parkinson’s disease
Authors: Singh Arun , Cole Rachel C. , Espinoza Arturo I. , Brown Darin , Cavanagh James F. , Narayanan Nandakumar
Published: May 2019

Background

Motor and cognitive dysfunction has been linked in patients with Parkinson’s disease (PD). EEG theta and beta rhythms are reliably associated with cognitive and motor functions, respectively. We tested the hypothesis that PD patients with lower-limb abnormalities would exhibit abnormal beta and theta rhythms in the mid-frontal region during action initiation.

Methods

We recruited thirty-nine subjects, including PD patients with FOG (PDFOG+; n=13) and without FOG (PDFOG−; n=13), and demographically-matched healthy subjects (n=13). Scalp electroencephalogram (EEG) signals were collected during a lower-limb pedaling motor task, which required intentional initiation and stopping of a motor movement.

Results

FOG scores were correlated with disease severity and cognition. PDFOG+ patients pedaled with reduced speed and decreased acceleration compared to PDFOG− patients and to controls. PDFOG+ patients exhibited attenuated theta-band (4-8 Hz) power and increased beta-band (13-30 Hz) power at mid-frontal electrode Cz during pedaling. Frontal theta- and beta-band oscillations also correlated with lower-limb movement in PD patients.

Conclusions

Frontal theta and beta oscillations are predictors of lower-limb motor symptoms in PD. These data provide insight into the mechanism of lower-limb dysfunction in PD, and could be used to design neuromodulation for PD-related lower-limb abnormalities.
Mixed support for the idea that lower elevation animals are better competitors than their upper elevation relatives
Authors: Freeman Benjamin G.
Published: May 2019

What factors set species’ range edges? One general hypothesis, often attributed to Darwin and MacArthur, is that interspecific competition prevents species from inhabiting the warmest portions along geographic gradients (i.e., low latitudes or low elevations). A prediction arising from the Darwin-MacArthur hypothesis is that lower elevation species are better competitors than are related upper elevation species. I tested this prediction by conducting a meta-analysis of studies that have measured behavioral competition between related species along elevational gradients. I found that (1) interspecific aggression appears to be a reliable indicator of interspecific competition; (2) as predicted, lower elevation species showed stronger interspecific aggression, but only for tropical species-pairs tested with playback experiments (nearly all songbirds); (3) for a broader range of taxa where authors directly observed behavioral interactions, upper elevation species showed stronger interspecific aggression; and (4) in general, larger species showed greater interspecific aggression. One potential explanation for why upper elevation species often show more interspecific aggression is that they tend to be larger (Bergmann’s rule; larger body sizes in colder environments). Supporting this possibility, tropical species tested with playback experiments, which do not follow Bergmann’s rule, were the only group that matched predictions arising from the Darwin-MacArthur hypothesis. Hence, available evidence does not consistently support the longstanding hypothesis that relative range position predicts the outcome of interspecific competition. Instead, body size is a better predictor of behavioral competition. Last, I consider these results in the context of the hypothesis that behavioral interactions may impact rates of upslope range shifts associated with recent warming.
Impact of maternal malnutrition on gut barrier defence: implications for pregnancy health and fetal development.
Authors: Srugo Sebastian A. , Bloise Enrrico , Nguyen Tina Tu-Thu Ngoc , Connor Kristin L.
Published: May 2019

Small intestinal Paneth cells, enteric glial cells (EGC), and goblet cells maintain gut mucosal integrity, homeostasis, and influence host physiology locally and through the gut-brain axis. Little is known about their roles during pregnancy, or how maternal malnutrition impacts these cells and their development. Pregnant mice were fed a control diet (CON), undernourished by 30% vs. control (UN), or fed a high-fat diet (HF). At day 18.5 (term=19), gut integrity and function were assessed by immunohistochemistry and qPCR. UN mothers displayed reduced mRNA expression of Paneth cell antimicrobial peptides (AMP; Lyz2, Reg3g) and an accumulation of villi goblet cells, while HF had reduced Reg3g and mucin (Muc2) mRNA and increased lysozyme protein. UN fetuses had increased mRNA expression of gut transcription factor Sox9, associated with reduced expression of maturation markers (Cdx2, Muc2), and increased expression of tight junctions (TJ; Cldn-7). HF fetuses had increased mRNA expression of EGC markers (S100b, Bfabp, Plp1), AMP (Lyz1, Defa1, Reg3g), and TJ (Cldn-3, Cldn-7), and reduced expression of an AMP-activator (Tlr4). Maternal malnutrition altered expression of genes that maintain maternal gut homeostasis, and altered fetal gut permeability, function, and development. This may have long-term implications for host-microbe interactions, immunity, and offspring gut-brain axis function.
Efficient strategies to detect genome editing and integrity in CRISPR-Cas9 engineered ESCs
Authors: Gehre Maja , Buccitelli Christopher , Diaz Nichole , Korbel Jan , Noh Kyung-Min
Published: May 2019

CRISPR-mediated genome engineering provides a powerful tool to study the function of genes and proteins. In the past decades, the advances in genome and transcriptome sequencing techniques have shed light on the genetic causes underlying many human diseases, such as neurodevelopmental disabilities or cancer. Sometimes, a single point-mutation in a protein coding gene has been identified as the primary cause of the disease. CRISPR-Cas offers the possibility to introduce or remove such a mutation of interest to understand disease mechanisms and even bears therapeutic potential. We describe the adaptation of an experimental strategy that allows the mutation of protein residues in mouse embryonic stem cells (ESCs) and propose a new screening method, Mismatch-qPCR, to reliably detect editing events in clonal cell lines as an alternative to restriction digest or Sanger sequencing. Finally, we show that RNA-Sequencing (RNA-Seq) data or low-coverage genomic sequencing data can be used to detect large chromosomal deletions and rearrangements that frequently occur at the CRISPR-targeting site.
A method for non-invasive prenatal diagnosis of monogenic autosomal recessive disorders
Authors: Cutts Anthony , Vavoulis Dimitrios V. , Petrou Mary , Smith Frances , Clark Barnaby , Henderson Shirley , Schuh Anna
Published: May 2019

Non-invasive prenatal testing (NIPT) to date is used in the clinic primarily to detect foetal aneuploidy. Few studies so far have focused on the detection of monogenic autosomal recessive disorders where mother and foetus carry the same mutation. In particular, NIPT is currently not available for the detection of Sickle Cell Anaemia (SCA), the most common monogenic disorder world-wide and the most common indication for invasive prenatal testing in high-income countries. Here, we report the clinical validation of a novel diagnostic approach that combines ultra-sensitive amplicon-based sequencing of cell-free DNA (cfDNA) with internal controls and bias factor correction to calculate the probability for the presence of allelic imbalance from maternal plasma without prior knowledge of the paternal genotype. Identification of the foetal genotype was determined using a hierarchical probabilistic model based on the relative number of reads from the sequencing, along with the foetal fraction. NIPT was performed on a cohort of 57 patients, all of whom had previously undergone invasive prenatal testing so that the foetal genotype was known. Overall, NIPT demonstrated 100% sensitivity and negative predictive value for foetal fractions higher than 0.5%, and 100% specificity and positive predictive value for foetal fractions higher than or equal to 4%. Our methodology can be used as a safe, non-invasive screening tool in any clinical scenarios where early prenatal diagnosis of SCA or other recessive disorders is important.
Phenotype‐by‐environment interactions influence dispersal
Authors: Baines Celina B. , Ferzoco Ilia Maria C. , McCauley Shannon J.
Published: May 2019

Numerous studies have demonstrated that dispersal is dependent on both disperser phenotype and the local environment. However, there is substantial variability in the observed strength and direction of phenotype‐ and environment‐dependent dispersal. This has been hypothesized to be the result of interactive effects among the multiple phenotypic and environmental factors that influence dispersal.

Here, our goal was to test the hypothesis that these interactions are responsible for generating variation in dispersal behaviour.

We achieved these goals by conducting a large, 2‐year, mark–release–recapture study of the backswimmerNotonecta undulatain an array of 36 semi‐natural ponds. We measured the effects of multiple phenotypic (sex and body size) and environmental (population density and sex ratio) factors, on both dispersal probability and dispersal distance.

We found support for the hypothesis that interactive effects influence dispersal and produce variability in phenotype‐ and environment‐dependent dispersal: dispersal probability was dependent on the three‐way interaction between sex, body mass and population density. Small males displayed strong, positive density dependence in their dispersal behaviour, while large males and females overall did not respond strongly to density. Small notonectids, regardless of sex, were more likely to disperse, but this effect was strongest at high population densities. Finally, the distance dispersed by backswimmers was a negative function of population density, a pattern which we hypothesize could be related to: (a) individuals from high and low density patches having different dispersal strategies, or (b) the effect of density on dispersal capacity.

These results suggest that phenotype‐by‐environment interactions strongly influence dispersal. Since phenotype‐ and environment‐dependent dispersal has different consequences for ecological and evolutionary dynamics (e.g. metapopulation persistence and local adaptation) than random dispersal, interactive effects may have wide‐reaching impacts on populations and communities. We therefore argue that more investment should be made into estimating the effects of multiple, interacting factors on dispersal and determining whether similar interactive effects are acting across systems.
A chromosome‐level genome of black rockfish, Sebastes schlegelii, provides insights into the evolution of live birth
Authors: He Yan , Chang Yue , Bao Lisui , Yu Mengjun , Li Rui , Niu Jingjing , Fan Guangyi , Song Weihao , Seim Inge , Qin Yating , Li Xuemei , Liu Jinxiang , Kong Xiangfu , Peng Meiting , Sun Minmin , Wang Mengya , Qu Jiangbo , Wang Xuangang , Liu Xiaobing , Wu Xiaolong , Zhao Xi , Wang Xuliang , Zhang Yaolei , Guo Jiao , Liu Yang , Liu Kaiqiang , Wang Yilin , Zhang He , Liu Longqi , Wang Mingyue , Yu Haiyang , Wang Xubo , Cheng Jie , Wang Zhigang , Xu Xun , Wang Jian , Yang Huanming , Lee Simon Ming‐Yuen , Liu Xin , Zhang Quanqi , Qi Jie
Published: May 2019

The black rockfish (Sebastes schlegelii) is a teleost in which eggs are fertilized internally and retained in the maternal reproductive system, where they undergo development until live birth (viviparity). In the present study, we report a chromosome‐level black rockfish genome assembly. High‐throughput transcriptome analysis (RNA‐seq and ATAC‐seq) coupled with in situ hybridization (ISH) and immunofluorescence reveal several candidate genes for maternal preparation, sperm storage and release, and hatching. We propose that zona pellucida (ZP) proteins retain sperm at the oocyte envelope, while genes in two distinct astacin metalloproteinase subfamilies serve to release sperm from the ZP and free the embryo from chorion at prehatching stage. We present a model of black rockfish reproduction, and propose that the rockfish ovarian wall has a similar function to the uterus of mammals. Together, these genomic data reveal unprecedented insights into the evolution of an unusual teleost life history strategy, and provide a sound foundation for studying viviparity in nonmammalian vertebrates and an invaluable resource for rockfish ecological and evolutionary research.
Ex Post Settling Up in Cash Compensation: New Evidence
Authors: Albuquerque Ana , Chen Bingyi , Dong Qi (Flora) , Riedl Edward J.
Published: May 2019

This paper provides new evidence on whether and how boards solve costly ex post settling up to recover CEO cash compensation for unrealized gains that fail to materialize. Our analyses are motivated by the likely expanding role for ex post settling up as the risk of compensating executives for unrealized gains that may never materialize increases in a more intangibles‐based economy, as well as by the conflicting evidence of prior research. We provide evidence consistent with ex post settling up by (i) using alternative truncation methods to derive observations most likely to fall within the theoretically motivated incentive zone; (ii) replicating and reconciling the conflicting results of prior research that supports (Leone et al. 2006) and fails to support (Shaw and Zhang 2010) ex post settling up; (iii) using Incentive Lab data with contract‐specific information, allowing strong identification of observations in the incentive zone; and (iv) documenting predictable cross‐sectional variation, with ex post settling up being more pronounced for firms with stronger corporate governance, less conservative accounting earnings, and a larger proportion of total pay in the form of cash compensation. Overall, we conclude that evidence is strong in support of the ex post settling up hypothesis.
A meta‐analysis of the efficacy of gabapentin for treating alcohol use disorder
Authors: Kranzler Henry R. , Feinn Richard , Morris Paige , Hartwell Emily E.
Published: May 2019

Background and Aims

Studies of the efficacy of gabapentin for treating alcohol use disorder (AUD) have yielded mixed findings. The aims of our study were to estimate gabapentin's effects on six alcohol‐related outcomes, test potential moderators, examine publication bias and evaluate the quality of the studies.

Methods

Meta‐analysis of placebo‐controlled randomized controlled trials (RCTs). Using PubMed and ClinicalTrials.gov, we selected RCTs of gabapentin's effects on alcohol consumption or a biochemical correlate of it, excluding studies limited to other primary outcomes or that combined gabapentin with other medications. We assessed study quality and used a random‐effects model to analyze each outcome measure and the Egger regression test and funnel plots to assess publication bias.

Results

We identified seven RCTs of gabapentin that met study criteria. The quality of the studies overall was good, and there was no evidence of publication bias. Four to seven studies contributed to the analysis of the six outcome measures. For all outcome measures the effect estimates were in a direction that favored gabapentin over placebo. However, only for percentage of heavy drinking days was there good evidence of a benefit (g = −0.64, 95% confidence interval = −1.22 to −0.06).

Conclusions

Although gabapentin appears to be more efficacious than placebo in treating AUD, the only measure on which the analysis clearly favors the active medication is percentage of heavy drinking days. Additional studies are needed to define more clearly the role of gabapentin in AUD treatment.
Information and communication technology among early and late middle‐aged adults in urban China: Daily use and anticipated support in old age
Authors: Song Yajun , Chen Yan‐Yan
Published: May 2019

Objectives

Guided by the unified theory of acceptance and use of technology (UTAUT), the study explored information and communications technology (ICT) use and anticipation among middle‐aged adults in urban China.

Methods

Path analysis was performed on data from 401 participants aged 45‐65 to examine the associations between anticipated ICT support and the acceptance and adoption process of ICT.

Results

For the late middle‐aged adults, those who had greater belief in ICT usefulness and received more social support for ICT use were more likely to anticipate greater ICT support in old age. These associations were not found in the early middle‐aged group.

Discussion

The frequency of ICT use may be the key explanation for different ICT predictors and patterns. The constructs of UTAUT are sequential steps. Middle‐aged adults may believe in ICT usefulness even though they have not witnessed it in person.
Oxygenation of adipose tissue: A human perspective
Authors: Lempesis Ioannis G. , van Meijel Rens L. J. , Manolopoulos Konstantinos N. , Goossens Gijs H.
Published: May 2019

Obesity is a complex disorder of excessive adiposity, and is associated with adverse health effects such as cardiometabolic complications, which are to a large extent attributable to dysfunctional white adipose tissue. Adipose tissue dysfunction is characterized by adipocyte hypertrophy, impaired adipokine secretion, a chronic low‐grade inflammatory status, hormonal resistance and altered metabolic responses, together contributing to insulin resistance and related chronic diseases. Adipose tissue hypoxia, defined as a relative oxygen deficit, in obesity has been proposed as a potential contributor to adipose tissue dysfunction, but studies in humans have yielded conflicting results. Here, we will review the role of adipose tissue oxygenation in the pathophysiology of obesity‐related complications, with a specific focus on human studies. We will provide an overview of the determinants of adipose tissue oxygenation, as well as the role of adipose tissue oxygenation in glucose homeostasis, lipid metabolism and inflammation. Finally, we will discuss the putative effects of physiological and experimental hypoxia on adipose tissue biology and whole‐body metabolism in humans. We conclude that several lines of evidence suggest that alteration of adipose tissue oxygenation may impact metabolic homeostasis, thereby providing a novel strategy to combat chronic metabolic diseases in obese humans.
A systematic review of patient‐reported outcomes associated with the use of direct‐acting oral anticoagulants
Authors: Afzal Saima Kishvar , Hasan Syed Shahzad , Babar Zaheer Ud‐Din
Published: May 2019

Aims

Patient‐reported outcomes (PROs) are a distinctive method of evaluating patient response to health care or treatment. This systematic review aimed to analyse the impact of PROs in patients on direct oral anticoagulant (DOAC) treatment, prescribed for any indication (e.g. venous thromboembolism treatment or atrial fibrillation) using controlled trials (CT) and real‐world observational studies (OS).

Methods

A systematic search of articles was conducted according to PRISMA guidelines using databases, with the last update in November 2018. The Cochrane Collaboration tool for assessing bias in randomized CTs and the Newcastle‐Ottawa Scale adapted for cross‐sectional studies were used. Outcomes evaluated were related to health‐related quality of life (HRQoL), satisfaction, adherence and compliance.

Results

Twenty‐one original studies (6 CT, 15 OS) were included. HRQoL was assessed by 6 (1 CT, 5 OS) studies and reported that HRQoL scores were similar in patients on DOACs and warfarin. Patients prescribed DOACs presented higher HRQoL scores which were attributed to lack of intense monitoring required compared with warfarin but this was not statistically significant. The majority of studies (5 CT, 9 OS) investigated patient‐reported satisfaction, indicating greater satisfaction with DOACs with significantly lower burden and increased benefit scores for patients on DOACs. Patient‐reported expectations, compliance and adherence were similar for patients on DOACs and warfarin.

Conclusion

Patients appear to prefer treatment with DOACs vs warfarin. This is shown by the higher quality of life, satisfaction and adherence described in the studies. However, heterogeneity in the analysed studies does not allow firm conclusions.
Factors related to skin health in hairdressing apprentices from two Croatian regions
Authors: Franić Zrinka , Babić Željka , Bjelajac Adrijana , Macan Jelena
Published: May 2019

Background

Hairdressing apprentices are at high risk for developing occupational contact dermatitis.

Objectives

The objective of this study was to analyse whether there are differences in skin health, skin protection and health‐related quality of life between apprentices from two Croatian regions (Zagreb and Dalmatia).

Materials and methods

Final‐year hairdressing apprentices from Zagreb (n = 101) and Dalmatia (n = 77) were enrolled in the study. Clinical examination of hands was performed by use of the Osnabrück Hand Eczema Severity Index. Transepidermal water loss (TEWL) was measured on forearm and hand. A history of self‐reported skin symptoms, work‐related exposure to skin hazards and health‐related quality of life were assessed with validated questionnaires.

Results

Apprentices from Zagreb reported having been engaged in practical work more days per month than Dalmatian apprentices (median 12 days vs 8 days, respectively, P < 0.001), and washing their hands >20 times per day more frequently (28% vs 10%, respectively, P = 0.004), and consequently more frequently having dry hands (37% vs 16%, respectively, P = 0.002), and significantly higher TEWL values on the hand and forearm, which was confirmed by the results obtained with multiple linear regression models.

Conclusions

A higher extent of exposure to skin hazards was related to poorer skin barrier function, which confirms the need for improvement of appropriate safety practices in hairdressing schools.
Outcomes, complications, and economic impact of ABO‐incompatible living kidney transplantation: A single‐center Japanese cohort study
Authors: Kakuta Yoichi , Okumi Masayoshi , Unagami Kohei , Iizuka Junpei , Takagi Toshio , Ishida Hideki , Tanabe Kazunari
Published: May 2019

ABO‐incompatible kidney transplantation (ABO‐ILKT) has been reported to have a higher rate of early complications and higher medical costs than ABO‐compatible kidney transplantation (ABO‐CLKT). We aimed to compare the clinical outcomes, complications, and medical costs between ABO‐ILKTs and ABO‐CLKTs at 2 years post‐transplantation. We included 65 ABO‐ILKTs and 94 ABO‐CLKTs in this retrospective analysis. The patient survival, graft survival, rejection incidence, and graft function were similar between ABO‐CLKT and ABO‐ILKT. The hospitalization costs for ABO‐CLKT and ABO‐ILKT were 26 544 ± 4168 USD and 34 906 ± 18 732 USD, respectively (P = 0.0001). Total 2‐year medical costs were 77 117 ± 15 609 USD and 85 325 ± 33 997 USD for ABO‐CLKT and ABO‐ILKT, respectively, indicating that the medical costs of ABO‐ILKT recipients were non‐significantly higher than those of ABO‐CLKT recipients at 2 years post‐transplantation (P = 0.0866). ABO‐ILKT and ABO‐CLKT recipients showed similar infectious adverse events and complications. In conclusion, medical cost at 2 years post‐transplantation, including transplant hospitalization cost, and the frequency of early complications were not significantly higher in the ABO‐ILKT group than in the ABO‐CLKT group. ABO‐ILKT is an acceptable treatment for patients with ESRD and is comparable to ABO‐CLKT not only in terms of outcomes but also in terms of medical cost.
Challenging socioeconomic status: A cross‐cultural comparison of early executive function
Authors: Howard Steven J. , Cook Caylee J. , Everts Lizl , Melhuish Edward , Scerif Gaia , Norris Shane , Twine Rhian , Kahn Kathleen , Draper Catherine E.
Published: May 2019

The widely and internationally replicated socioeconomic status (SES) gradient of executive function (EF) implies that intervention approaches may do well to extrapolate conditions and practices from contexts that generate better child outcomes (in this case, higher SES circumstances) and translate these to contexts with comparatively poorer outcomes (often low‐SES populations). Yet, can the reverse also be true? Using data from equivalent assessments of 1,092 pre‐schoolers’ EFs in South Africa and Australia, we evaluated: the SES gradient of EF within each sample; and whether this SES gradient extended cross‐culturally. The oft‐found EF‐SES gradients were replicated in both samples. However, contrary to the inferences of EF‐SES associations found nationally, the most highly disadvantaged South African subsample outperformed middle‐ and high‐SES Australian pre‐schoolers on two of three EFs. This suggests the possibility of EF‐protective and ‐promotive practices within low‐ and middle‐income countries that may aid understandings of the nature and promotion of EFs.
Chaos, danger, and maternal parenting in families: Links with adolescent adjustment in low‐ and middle‐income countries
Authors: Deater‐Deckard Kirby , Godwin Jennifer , Lansford Jennifer E. , Tirado Liliana Maria Uribe , Yotanyamaneewong Saengduean , Alampay Liane Peña , Al‐Hassan Suha M. , Bacchini Dario , Bornstein Marc H. , Chang Lei , Di Giunta Laura , Dodge Kenneth A. , Oburu Paul , Pastorelli Concetta , Skinner Ann T. , Sorbring Emma , Steinberg Laurence , Tapanya Sombat
Published: May 2019

The current longitudinal study is the first comparative investigation across low‐ and middle‐income countries (LMICs) to test the hypothesis that harsher and less affectionate maternal parenting (child age 14 years, on average) statistically mediates the prediction from prior household chaos and neighborhood danger (at 13 years) to subsequent adolescent maladjustment (externalizing, internalizing, and school performance problems at 15 years). The sample included 511 urban families in six LMICs: China, Colombia, Jordan, Kenya, the Philippines, and Thailand. Multigroup structural equation modeling showed consistent associations between chaos, danger, affectionate and harsh parenting, and adolescent adjustment problems. There was some support for the hypothesis, with nearly all countries showing a modest indirect effect of maternal hostility (but not affection) for adolescent externalizing, internalizing, and scholastic problems. Results provide further evidence that chaotic home and dangerous neighborhood environments increase risk for adolescent maladjustment in LMIC contexts, via harsher maternal parenting.