bluuebunny/crossref_metadata_2025_split huggingface dataset:
Axial skeleton anterior-posterior patterning is regulated through feedback regulation between Meis transcription factors and retinoic acid
Authors: López-Delgado Alejandra C. , Delgado Irene , Cadenas Vanessa , Sánchez-Cabo Fátima , Torres Miguel 
Published: March 2020

ABSTRACTVertebrate axial skeletal patterning is controlled by coordinated collinear expression ofHoxgenes and axial level-dependent activity of Hox protein combinations. Transcription factors of the Meis family act as cofactors of Hox proteins and profusely bind to Hox complex DNA, however their roles in mammalian axial patterning have not been established. Similarly, retinoic acid (RA) is known to regulate axial skeletal element identity through the transcriptional activity of its receptors, however, whether this role is related to Meis/Hox activity in axial patterning remains unknown. Here we study the role of Meis in axial skeleton formation and its relationship to the RA pathway by characterizingMeis1,Meis2andRaldh2mutant mice. Meis elimination produces axial skeleton defects without affecting Hox gene transcription, including vertebral homeotic transformations and rib mis-patterning associated to defects in the hypaxial myotome. While Raldh2 and Meis positively regulate each other,Raldh2elimination largely recapitulates the defects associated to Meis-deficiency and Meis overexpression rescues the axial skeletal defects inRaldh2mutants. We propose a Meis-RA positive feedback loop whose output is Meis levels and is essential to establish anterior-posterior identities and pattern of the vertebrate axial skeleton.
Transcriptomic characterization of tuberculous sputum reveals a host Warburg effect and microbial cholesterol catabolism
Authors: Lai Rachel PJ , Cortes Teresa , Marais Suzaan , Rockwood Neesha , Burke Melissa L , Garza-Garcia Acely , Horswell Stuart , O’Garra Anne , Young Douglas B , Wilkinson Robert J 
Published: March 2020

AbstractThe crucial transmission phase of tuberculosis (TB) relies on infectious sputum yet cannot easily be modeled. We applied one-step RNA-Sequencing to sputum from infectious TB patients to investigate the host and microbial environments underlying transmission ofMycobacterium tuberculosis(Mtb). In such TB sputa, compared to non-TB controls, transcriptional upregulation of inflammatory responses and a metabolic shift towards glycolysis was observed in the host. Amongst all bacterial sequences in the sputum, only less than 1.5% originated fromMtband its abundance is associated with HIV-1 coinfection status. The transcriptome of sputumMtbmore closely resembled aerobic replication and was characterized by evidence of cholesterol utilization, zinc deprivation and reduced expression of the virulence-associated PhoP regulon. Our study provides a comprehensive analysis of the transcriptional landscape associated with infectious sputum and demonstrates the feasibility of applying advanced sequencing technology to readily accessible pathological specimens in the study of host-pathogen adaptation.
Oculomotor-related measures but not distance visual acuity are predictive of reading ability in first graders
Authors: Portnoy Avi , Gilaie-Dotan Sharon 
Published: March 2020

AbstractVision screening in junior schools around the globe are often limited to distance visual acuity (dVA). Oculomotor dysfunction (OMD) is an umbrella term that includes abnormalities in comfortable and accurate control of the oculomotor system (fixation, pursuits and saccades) and can exist despite normal dVA. Since we assumed that a basic prerequisite for successful reading is that the ocular sensory-motor functions perform in flawless harmony with effortless automaticity, we hypothesized that OMD but not dVA would have profound effect on comfortable and efficient acquisition of effective reading skills. Consequently, we retrospectively compared independently obtained (double blind) reading evaluations and extensive optometric screening examinations of a class of 28 first graders. We found, as we hypothesized, that performance on optometric oculomotor tests, but not dVA, were predictive of reading test performance (both speed and accuracy) according to the standardized national reading norms. Our results suggest reevaluating the effectiveness of dVA as a marker of visual readiness for scholastic achievements. We propose including OMD related assessments as part of a paradigm shift in both vision screening in early readers as well as potential treatment protocols for those pupils struggling to acquire efficient reading skills.
Host species determine symbiotic community composition in Antarctic sponges (Porifera: Demospongiae)
Authors: Sacristán-Soriano Oriol , Criado Natalia Pérez , Avila Conxita 
Published: March 2020

AbstractThe microbiota of four Antarctic sponges,Dendrilla antarctica, Sphaerotylus antarcticus, Mycale acerata, andHemigellius pilosus, collected at two South Shetland Islands and at two locations in the Antarctic Peninsula separated by ca. 670 km, were analyzed together with surrounding seawater. We used high throughput sequencing of the V4 region of the 16S rRNA gene common to Bacteria and Archaea to investigate the microbial diversity and community composition. Our study reveals that sponge-associated prokaryote communities are consistently detected within a particular sponge species regardless of the collection site. Their community structure and composition are typical of low microbial abundance (LMA) sponges. We conclude that prokaryote communities from Antarctic sponges are less diverse and differ in their composition compared to those in the water column. Microbiome analysis indicates that Antarctic sponges harbor a strict core consisting of seven OTUs, and a small variable community comprising several tens of OTUs. Two abundant prokaryotes from the variable microbiota that are affiliated to the archaeal and bacterial phyla Thaumarchaeota and Nitrospirae may be involved in the sponge nitrification process and might be relevant components of the nitrogen cycling in Antarctica. The likely generalist nature of dominant microbes and the host-specific structure of symbiont communities suggest that these Antarctic sponges represent different ecological niches for particular microbial enrichments.
Resistance to Ceftazidime/Avibactam Plus Meropenem/Vaborbactam When Both are Used Together Achieved in Four Steps From Metallo-β-Lactamase NegativeKlebsiella pneumoniae
Authors: Dulyayangkul Punyawee , Douglas Edward J. A. , Lastovka Filip , Avison Matthew B. 
Published: March 2020

AbstractSerine cephalosporinases and carbapenemases are dominant causes of critically important β-lactam resistance inKlebsiella pneumoniae. This has led to the recent clinical deployment of new serine β-lactamase inhibitors used in combination with β-lactams. Starting with clinicalK. pneumoniaeisolates and adding plasmids carrying the OXA-48-like class D carbapenemase, OXA-232, the class A carbapenemase KPC-3, the class A cephalosporinase CTX-M-14 and mutant derivatives of these enzymes, we set out to identify the steps required to give resistance to the recently approved β-lactam/β-lactamase inhibitor pairs ceftazidime/avibactam and meropenem/vaborbactam when both are used together. We show that four steps:ompK36andramRloss-of-function plus carriage of OXA-232 and KPC-3-D178Y, all of which have been observed in clinical isolates, allowK. pneumoniaeto resist the combined use of both β-lactam/β-lactamase inhibitor pairs. These findings have implications for decision making about sequential and combinatorial use of β-lactam/β-lactamase inhibitor pairs to treatK. pneumoniaeinfections, and suggest simple surveillance activities that might identify intermediate stages in resistance acquisition and therefore guide therapy to reduce the emergence of dual resistant strains.
Episodic evolution of coadapted sets of amino acid sites in mitochondrial proteins
Authors: Neverov A.D. , Fedonin G.G. , Cheremukhin E.A. , Klink G.V. , Popova A.V. , Bazykin G.A. 
Published: March 2020

AbstractThe rate of evolution differs between protein sites and changes with time. However, the link between these two phenomena remains poorly understood. Here, we design a phylogenetic approach for distinguishing pairs of amino acid sites that undergo coordinated evolution, i.e., such that substitutions at one site trigger subsequent substitutions at the other; and also pairs of sites that undergo discordant evolution, so that substitutions at one site impede subsequent substitutions at the other. We distinguish groups of amino acid sites that undergo coordinated evolution and evolve discordantly from other such groups. In mitochondrially encoded proteins of metazoans and fungi, we show that concordantly evolving sites are clustered in protein structures. Moreover, the substitution rates within individual concordant groups themselves change in the course of evolution, and phylogenetic positions of these changes are consistent between proteins, suggesting common selective forces underlying them.Author summaryEvolution in most protein sites is constrained by alleles in other sites, this phenomena is called epistasis. Generally, newly arisen allele, if it would not be lost, increases its fitness with time due to adaptive mutations occurred in other sites in the process called the entrenchment. Thus, we expect that the evolution of sites would be coordinated, such that mutations in sites rapidly follow each other on phylogenetic lineages. Indeed, we have observed such coordinated evolution of sites in five proteins encoded in the mitochondria genomes of metazoan and fungi. Unexpectedly, coordinated evolution is observed only for nearby sites on protein structures, such that each protein could be partitioned into several groups of concordantly evolving sites. Evolution of sites from different groups is discordant, i.e. their mutations repel each other into different phylogenetic lineages or clades. Thus, the proteins encoded in mitochondrial genome consist of the sort of structural blocks like elements of the LEGO kit. Some of them have functional specialization, e.g. some blocks are associated with interfaces between proteins composing respiratory complexes.
Unravelling the effects of methylphenidate on the dopaminergic and noradrenergic functional circuits
Authors: Dipasquale Ottavia , Martins Daniel , Sethi Arjun , Veronese Mattia , Hesse Swen , Rullmann Michael , Sabri Osama , Turkheimer Federico , Harrison Neil A , Mehta Mitul A , Cercignani Mara 
Published: March 2020

ABSTRACTFunctional magnetic resonance imaging (fMRI) can be combined with drugs to investigate the system-level functional responses in the brain to such challenges. However, most psychoactive agents act on multiple neurotransmitters, limiting the ability of fMRI to identify functional effects related to actions on discrete pharmacological targets. We recently introduced a multimodal approach, REACT (Receptor-Enriched Analysis of functional Connectivity by Targets), which offers the opportunity to disentangle effects of drugs on different neurotransmitters and clarify the biological mechanisms driving clinical efficacy and side effects of a compound. Here, we focus on methylphenidate (MPH), which binds to the dopamine transporter (DAT) and the norepinephrine transporter (NET), to unravel its effects on dopaminergic and noradrenergic functional circuits in the healthy brain at rest. We then explored the relationship between these target-enriched resting state functional connectivity (FC) maps and inter-individual variability in behavioural responses to a reinforcement-learning task encompassing a novelty manipulation to disentangle the molecular systems underlying specific cognitive/behavioural effects.Results showed a significant MPH-induced FC increase in sensorimotor areas in the functional circuit associated with DAT. We also found that MPH-induced variations in DAT-and NET-enriched FC were significantly correlated with inter-individual differences in effects of MPH on key behavioural responses associated with the reinforcement-learning task.Our findings show that MPH-related FC changes are specifically associated with DAT and provide evidence that when compounds have mixed pharmacological profiles, REACT may be able to capture regional functional effects that are underpinned by the same cognitive mechanism but are related to distinct molecular targets.
Quantifying temperature compensation of Bicoid gradients with a fast T-tunable microfluidic device
Authors: Zhu H. , Cui Y. , Luo C. , Liu F. 
Published: March 2020

ABSTRACTAs a reaction-diffusion system strongly affected by temperature, the early fly embryos surprisingly show highly reproducible and accurate developmental patterns during embryogenesis under temperature perturbations. To reveal the underlying temperature compensation mechanism, it is important to overcome the challenge in quantitative imaging on fly embryos under temperature perturbations. Inspired by a microfluidics generating temperature steps on fly embryos, here we design a microfluidic device capable of ensuring the normal development of multiple fly embryos as well as achieving real-time temperature control and fast temperature jumps for quantitative live imaging with a home-built two-photon microscope. We apply this system to quantify the temperature compensation of the morphogen Bicoid (Bcd) gradient in fly embryos. The length constant of the exponential Bcd gradient reaches the maximum at 25 °C within the measured temperatures of 18-29 °C and gradually adapts to the corresponding value at new temperatures upon a fast temperature switch. Such an adaption decreases to a less degree if temperature is switched in a later developmental stage. This age-dependent temperature compensation could not be explained with the traditional synthesis-diffusion-degradation (SDD) model assuming the static parameters but an extended SDD model incorporating the dynamic change of the parameters controlling the formation of Bcd gradients.SIGNIFICANCEThermal robustness is important for biological systems experiencing temperature fluctuations. To reveal the temperature compensation mechanism, the fruit fly embryo is an ideal model system. It is intriguing how the early fly embryo achieves highly reproducible and accurate patterning despite it is a reaction-diffusion system strongly affected by temperature. However, it has been challenging to quantitatively measure the developmental patterns in fly embryos under temperature perturbations. To overcome this problem, we construct a fast temperature tunable microfluidic device for fly embryos. Combining quantitative imaging with this device and mathematical modeling, we successfully quantify the temperature response of the morphogen Bicoid (Bcd) gradient and reveal that the temperature compensation for the Bcd gradient is stronger in the later developmental stage.
Stigma Receptivity is controlled by Functionally Redundant MAPK Pathway Components in Arabidopsis
Authors: Jamshed Muhammad , Sankaranarayanan Subramanian , Abhinandan Kumar , Samuel Marcus A. 
Published: March 2020

SummaryIn angiosperms, the process of pollination relies on species-specific interaction and signaling between the male (pollen) and female (pistil) counterparts where the interplay between several pollen and stigma proteins decides the fate of the pollen. In Brassicaceae, the dry stigmatic papillary cells control pollen germination by releasing resources only to compatible pollen thereby allowing pollen to hydrate and germinate. Despite the identification of a number of stigmatic proteins that facilitate pollination responses, the signaling mechanisms that regulate functions of these proteins have remained unknown. Here we show that, in Arabidopsis, an extremely functionally redundant mitogen-activated protein kinase (MAPK) cascade is required for maintaining stigma receptivity to accept compatible pollen. Our genetic analyses demonstrate that in stigmas, five MAPK kinases (MKKs), MKK1/2/3/7/9 are required to transmit upstream signals to two MPKs, MPK3/4, to mediate compatible pollination. Compromised functions of these fiveMKKsin the quintuple mutant (mkk1/2/3RNAi/mkk7/9) phenocopied pollination defects observed in thempk4RNAi/mpk3double mutant. We further show that this MAPK nexus converges on Exo70A1, a previously identified stigmatic compatibility factor essential for pollination. Given that pollination is the crucial initial step during plant reproduction, understanding the mechanisms that govern successful pollination could lead to development of strategies to improve crop yield.
Comparative characterisation ofPlasmodium falciparumHsp70-1 relative toE. coliDnaK reveals functional specificity of the parasite chaperone
Authors: Lebepe Charity Mekgwa , Matambanadzo Pearl Rutendo , Makhoba Xolani Henry , Achilonu Ikechukwu , Zininga Tawanda , Shonhai Addmore 
Published: March 2020

ABSTRACTHsp70 is one of the most prominent molecular chaperones. Although Hsp70s from various organisms are generally conserved, they exhibit specialised cellular functions. It remains to be fully understood how these highly conserved molecules exhibit specialised functional features.Plasmodium falciparumHsp70-1 (PfHsp70-1) is a cytosol localised molecular chaperone that is implicated in the cyto-protection and pathogenicity of the malaria parasite. In the current study, we investigated the comparative structure-function features of PfHsp70-1 relative to its homologue,E. coliHsp70 (DnaK) and a chimeric protein, KPf, that was constituted by the ATPase domain of DnaK and the substrate binding domain (SBD) of PfHsp70-1. Recombinant forms of all the three Hsp70s exhibited similar secondary and tertiary structural fold. We further established that compared to DnaK, both KPf and PfHsp70-1 were more stable to heat stress and exhibited higher basal ATPase activity. A recombinantP. falciparumHsp40 (PfHsp40) stimulated the ATPase activities of all the three Hsp70s. In addition, both PfHsp70-1 and KPf exhibited preference for asparagine rich peptides as opposed to DnaK. Furthermore, all the three proteins exhibited self-association capabilities in vitro. RecombinantP. falciparumadenosylmethionine decarboxylase (PfAdoMetDC) co-expressed inE. coliwith either KPf or PfHsp70-1 was produced as a fully folded product. On the other hand, co-expression of PfAdoMetDC with heterologous DnaK inE. colidid not promote folding of the former. These findings demonstrated that the SBD of PfHsp70-1 regulates several functional features of the protein and that this molecular chaperone is tailored to facilitate folding of plasmodial proteins.
Comparing the measures of consumer knowledge calibration
Authors: Pillai Kishore Gopalakrishna , Hofacker Charles F. 
Published: March 2020

Purpose
Studies on consumer knowledge calibration have used different measures of calibration. The purpose of this paper is to undertake a comparative assessment of important measures. In addition, it seeks to identify the best performing measure.

Design/methodology/approach
The paper reports on three studies. The first study uses eight survey data sets. The second and third studies use experiments.

Findings
The study found that the Brier score component measure is most responsive to feedback and is the most suitable measure of knowledge calibration. The results also indicate that researchers should use measures that use item-level confidence judgements, as against an overall confidence judgement.

Research limitations/implications
By documenting the relationship between the different measures of knowledge calibration, the study enables proper interpretation and accumulation of results of various studies that have used different measures. The study also provides guidance to researchers in psychology and education where this issue has been noted.

Practical implications
The study provides guidance to managers in knowledge intensive industries, such as finance and insurance, interested in understanding their consumers’ knowledge calibration.

Originality/value
This is the first study in consumer research that examines this issue.
Asymmetric information linkages across select futures and spot indices
Authors: Siddiqui Saif , Roy Preeti 
Published: March 2020

PurposeThe study investigates the amplitude and direction of the movement of information between spot and futures indices. The study progresses to account for the investor's heterogeneity and compare the evolving structure of investors in emerging and developed economies. Further, the structural linkages in terms of returns and variance have been explored for the futures indices to contribute to meteor shower literature as explained by Engle et al. (1990); Yarovaya et al. (2017).Design/methodology/approachTo facilitate the purpose, the Indian and Chinese markets were selected to represent emerging economies and the United States for developed one. The bivariate wavelet cum BEKK-GARCH (1,1) model was estimated.FindingsFor the developed markets, like the United States, the spot market improves its information transmission role with time horizon while exactly opposite holds for the Chinese market. A bidirectional overnight information spillover was found for all three pairs. The Indian futures market was vulnerable to bad news from the other two markets. Evidence suggesting the dominance of institutional investors in the Chinese futures market and retail investors in the Indian futures market is found.Originality/valueThe spot–futures relation has been studied on both the time and frequency domains considering different investment horizons. Due consideration has been taken to account for the overlapping trading hours.
Determinants of the result of new rural development program in Vietnam
Authors: Hoang Quang Vu 
Published: March 2020

PurposeThe purpose of this paper is to identify the determinants of the proportion of communes that met all national new rural criteria (hereafter NRD communes).Design/methodology/approachFirst, the method of propensity score (PS) stratification is used to classify 63 provinces into the subgroups. Second, the ordinary least squares (OLS) model is used with the subgroups classified from the PS stratification method as one of explicative variables. The dependent variable in the OLS model is the proportion of NRD communes.FindingsWith the sample of 63 provinces of Vietnam, the author found that per capita income growth rate, high growth of gross regional domestic product (GRDP) and effort of the provincial authority have positive impact on the proportion of NRD communes.Practical implicationsThis research suggests that the provincial authority should actively participate in the NRD program, and the economic development is key factor for success implementation of the NRD program.Originality/valueThis research contributes to understand the factors impacting the result of the NRD program and then help to identify the measures to support this program.