bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of gestational and developmental age on human airway epithelial innate immune responses to Respiratory Syncytial Virus (RSV) in early life
Authors: Groves Helen , Broadbent Lindsay , Guo-Parke Hong , Shields Mike , Power Ultan 
Published: April 2019

Background
RSV is a major respiratory pathogen in infants, with preterm and young infants being at increased risk of severe disease. Airway epithelial cell (AEC) innate immune responses represent an important first line of defence. Development of these responses in early life is poorly understood.

Methods
Well differentiated cultures were generated using nasal AECs harvested from term and preterm infants at birth and from the same infants at one-year old. Cultures were infected with RSV and resulting cytopathology and innate immune responses studied.

Results
RSV growth kinetics were similar between preterm and term newborn cohorts at birth and in the one-year-old repeat cohort. Secretion of interferon lambda-1 (IFN-l1), CXCL10 (IP-10), CCL5 (RANTES) and CXCL8 (IL-8) were similar between RSV-infected preterm and term newborn AECs. Following RSV infection, significantly higher secretion of IFN-l1 (P=0.0034), CXCL10 (P<0.05) and CCL5 (P<0.05) was noted in one-year-derived AECs compared to newborn AECs. We also identified differential expression of a novel endogenously expressed anti-RSV protein, pleiotrophin (PTN), which interacts with nucleolin, a cofactor for RSV entry. PTN expression/secretion was significantly decreased in preterm versus term AECs (P=0.014) and in newborn compared to one-year WD-PNECs (P=0.0008).

Conclusion
These exciting findings represent the first description of age- and prematurity-related differences in AEC innate immune responses, demonstrating greater RSV-induced expression of pro-inflammatory chemokines with increasing age and developmental differences in expression of the novel anti-RSV protein PTN. These findings may, in part, explain the increased susceptibility of preterm and very young infants to severe RSV disease.
Do uropathogenic E. coli require changes before it can spread into the bloodstream?
Authors: Goswami Cosmika , Fox Stephen , Leanord Alistair , Evans Thomas 
Published: April 2019

Background
Uropathogenic Eschericha coli are the leading cause of urinary tract infections (UTIs). The microbe can spread from bladder to kidney and finally to blood. We wished to determine whether genetic changes accompany the passage of these infections from urine to blood.

Material/methods
12 paired urine and blood samples were collected from patients in Greater Glasgow and Clyde; the interval between sample collection time between pairs was less than 48 h. Whole genomic sequencing of these paired samples was performed using the Illumina MiSeq platform. De novoassembly of reads was carried out using Shovill assembler; whereas SNPs were identified using SMALT, VarScan and Gubbins tools.

Results
Urine and blood samples in each pair had the same MLST type. Surprisingly, however, there were multiple differences in the presence of plasmid genes, phage elements and insertion sequences within pairs, as well as numerous SNPs. For example, the mercury reductase merAgene and mercuric transport protein merPhave been acquired in a plasmid of a blood isolate compared to the contemporaneous urine sample. We also identified missense mutations in genes involved in several metabolic pathways in bloodstream isolates. Several of the observed gene deletions/insertions and SNPs were found in more than one of the paired blood and urine isolates.

Conclusions
The observed sequence differences between contemporaneous blood and urine isolates suggests that genomic differences accumulate within the urinary bladder prior to blood stream invasion. The observed blood stream variants may thus possess a selective advantage in invasion and/or survival within blood.
Generalized locomotion of brittle stars with a flexible number of arms
Authors: Wakita Daiki , Kagaya Katsushi , Aonuma Hitoshi 
Published: April 2019

AbstractTypical brittle stars have five radially symmetrical arms, which coordinate to move their body in a certain direction. However, some species of them show individual difference in the number of arms. We found this trait unique since intact legged animals each own a fixed number of limbs in general. How does a single species manage such different numbers of motile organs to realize adaptive locomotion? We here described four-, five-, six-, and seven-armed locomotion with the aim to generalize a common rule which is flexible with arm numbers in brittle stars. We mechanically stimulated an arm inOphiactis brachyaspisto analyze escape direction and arm movements. Gathering quantitative indices and employing Bayesian statistical modeling, we figured out an average locomotion: regardless of the total number of arms, a front position emerges at one of the second neighboring arms to a mechanically stimulated arm, while side arms adjacent to the front synchronously work as left and right rowers. We suggest a model where some afferent signal runs either clockwise or anticlockwise along the nerve ring while linearly counting how many arms it passes. This idea would explain how ‘left and right’ emerges in a radially symmetrical body via a decentralized system.
Angiocrine FSTL1 insufficiency leads to atrial and vein wall fibrosis via SMAD3 activation
Authors: Jiang Haijuan , Zhang Luqing , Liu Xuelian , Sun Wei , Kato Katsuhiro , Chen Chuankai , Li Xiao , Han Wencan , Zhang Fujing , Xiao Qi , Yang Zhongzhou , Qin Zhihai , Adams Ralf H. , Gao Xiang , He Yulong 
Published: April 2019

AbstractAngiocrine factors, mediating the endothelial-mural cell interaction in vascular wall construction as well as maintenance, are incompletely characterized. Here we show that loss of follistatin-like protein 1 (FSTL1) in endothelial cells (Fstl1ECKO) led to an increase of pulmonary vascular resistance, resulting in the heart regurgitation especially with tricuspid valves. However, this abnormality was not detected in mutant mice withFstl1deletion in smooth muscle cells or hematopoietic cells. We further showed that there was excessive alpha-smooth muscle actin (αSMA) associated with atrial endocardia, heart valves, veins and microvessels after the endothelial FSTL1 deletion. Consistently, there was an increase of collagen deposition as demonstrated in livers ofFstl1ECKOmutants. The SMAD3 phosphorylation was significantly enhanced and pSMAD3 staining was colocalized with αSMA in vein walls, suggesting the activation of TGFβ signaling in vascular mural cells ofFstl1ECKOmice. The findings imply that endothelial FSTL1 is critical for the homeostasis of atria and veins and its insufficiency may favor cardiovascular fibrosis leading to heart failure.
Human biting Culex pipiens bioform molestus is spread in several areas in south Sweden
Authors: Nafula Luande Verah , Eklöf Disa , Lindström Anders , Nyanjom Steven Ger , Evander Magnus , Lilja Tobias 
Published: April 2019

AbstractThe mosquito species Culex pipiens is a potential vector of several pathogens infecting humans and occurs in two distinct bioforms, pipiens and molestus. Traditional morphological identification fails to separate the bioforms of Cx. pipiens despite their behavioural differences since they are morphologically indistinguishable. However, molecular methods can identify the two bioforms. The bioform molestus thrives in urban environments and bite all kinds of vertebrates, whereas bioform pipiens is more rural and mainly feed on birds.Mosquito samples submitted in a citizen science project from people experiencing mosquito problems in South Sweden were analyzed to determine the geographical distribution of the molestus bioform of Cx. pipiens. Mosquito specimens were identified to species by DNA barcoding of the cytochrome C oxidase subunit I (COI) gene and the bioforms were determined with the CQ11 microsatellite marker. To establish other differences between the bioforms, part of the CPIJ001674 gene was sequenced. Culex pipiens f molestus, was present both within and outside of urban areas in several sites in southern Sweden. In one site, hybrids between the two bioforms were found. Culex pipiens f molestus has previously been found in urban areas in Sweden, but the detection of the bioform in several rural areas was surprising, indicating that it may be more widely spread than previously thought.
Three-dimensional Monolayer Stress Microscopy
Authors: Serrano Ricardo , Aung Aereas , Yeh Yi-Ting , Varghese Shyni , Lasheras Juan C. , del Álamo Juan C. 
Published: April 2019

ABSTRACTMany biological processes involve the collective generation and transmission of mechanical stresses across cell monolayers. In these processes, the monolayer undergoes lateral deformation and bending due to the tangential and normal components of the cell-generated stresses. Monolayer Stress Microscopy (MSM) methods have been developed to measure the intracellular stress distribution in cell monolayers. However, current methods assume plane monolayer geometry and neglect the contribution of bending to the intracellular stresses.This work introduces a three-dimensional (3D) MSM method that calculates monolayer stress from measurements of the 3D traction stresses exerted by the cells on a flexible substrate. The calculation is carried out by imposing equilibrium of forces and moments in the monolayer, subject to external loads given by the 3D traction stresses. The equilibrium equations are solved numerically, and the algorithm is validated for synthetic loads with known analytical solutions.We present 3D-MSM measurements of monolayer stress in micropatterned islands of endothelial cells of different sizes and shapes. These data indicate that intracellular stresses caused by lateral deformation emerge collectively over long distances; they increase with the distance from the island edge until they reach a constant value that is independent of island size. On the other hand, bending-induced intracellular stresses are more concentrated spatially and remain confined to within 1-2 cell lengths of bending sites. The magnitude of these bending stresses is highest at the edges of the cell islands, where they can exceed the intracellular stresses caused by lateral deformations. Our data from non-patterned monolayers suggests that biomechanical perturbations far away from monolayer edges also cause significant localized alterations in bending tension. The localized effect of bending-induced stresses may be important in processes like cellular extravasation, which are accompanied by significant normal deflections of a cell monolayer (i.e. the endothelium), and which require localized changes in monolayer permeability.
The identification of temporal communities through trajectory clustering correlates with single-trial behavioural fluctuations in neuroimaging data
Authors: Thompson William Hedley , Wright Jessey , Shine James M. , Poldrack Russell A. 
Published: April 2019

AbstractInteracting sets of nodes and fluctuations in their interaction are important properties of a dynamic network system. In some cases the edges reflecting these interactions are directly quantifiable from the data collected. However, in many cases (such as functional magnetic resonance imaging (fMRI) data), the edges must be inferred from statistical relations between the nodes. Here we present a new method, Temporal Communities through Trajectory Clustering (TCTC), that derives time-varying communities directly from time-series data collected from the nodes in a network. First, we verify TCTC on resting and task fMRI data by showing that time-averaged results correspond with expected static connectivity results. We then show that the time-varying communities correlate and predict single-trial behaviour. This new perspective on temporal community detection of node-collected data identifies robust communities revealing ongoing spatiotemporal community configurations during task performance.
Molecular mapping of transmembrane mechanotransduction through the β1 integrin-CD98hc-TRPV4 axis
Authors: Potla Ratnakar , Hirano-Kobayashi Mariko , Wu Hao , Chen Hong , Mammoto Akiko , Matthews Benjamin D. , Ingber Donald E. 
Published: April 2019

ABSTRACTOne of the most rapid (< 4 msec) transmembrane cellular mechanotransduction events involves activation of Transient Receptor Potential Vanilloid 4 (TRPV4) ion channels by mechanical forces transmitted across β1 integrin receptors in endothelial cells, and the transmembrane Solute Carrier family 3 member 2 (CD98hc) protein has been implicated in this response. Here, we show that β1 integrin, CD98hc, and TRPV4 all tightly associate and co-localize in focal adhesions where mechanochemical conversion takes place. CD98hc knock down inhibits TRPV4-mediated calcium influx induced by mechanical forces, but not by chemical activators, thus confirming the mechanospecificity of this signaling response. Molecular analysis revealed that forces applied to β1 integrin must be transmitted from its cytoplasmic C-terminus to the CD98hc cytoplasmic tail, and from there to the ankyrin repeat domain of TRPV4 in order to produce ultra-rapid, force-induced, channel activation within the focal adhesion.Abstract FigureGraphical abstractSUMMARYA direct path of mechanical signal transfer between β1 integrin, CD98hc, and TRPV4 channels is identified that mediates ultra-rapid transmembrane mechanochemical conversion within focal adhesions.
A low cost, open source Turbidostat design for in-vivo control experiments in Synthetic Biology
Authors: Guarino Agostino , Shannon Barbara , Marucci Lucia , Grierson Claire , Savery Nigel , Bernardo Mario di 
Published: April 2019

AbstractTo characterise the dynamics of new engineered systems in Synthetic biology, continuous culture platforms are required. In this paper, after a brief review of the existing machines present in literature, we describe the design and the implementation of a new flexible and low cost turbidostat for in-vivo control experiments. Then, the results of a 3 hours long experiment of control of the Optical Density is reported. Since the foundation of our design is flexibility, in this work we also discuss some possible extensions of our design, with particular attention to their application to validate in-vivo multicellular control design.
Efficient use of genomic information for sustainable genetic improvement in small cattle populations
Authors: Obšteter J. , Jenko J. , Hickey J. M. , Gorjanc G. 
Published: April 2019

ABSTRACTThis paper compares genetic gain, genetic variation, and the efficiency of converting variation into gain under different genomic selection scenarios with truncation or optimum contribution selection in a small dairy population by simulation. Breeding programs have to maximize genetic gain but also ensure sustainability by maintaining genetic variation. Numerous studies showed that genomic selection increases genetic gain. Although genomic selection is a well-established method, small populations still struggle with choosing the most sustainable strategy to adopt this type of selection. We developed a simulator of a dairy population and simulated a model after the Slovenian Brown Swiss population with ~10,500 cows. We compared different truncation selection scenarios by varying i) the method of sire selection and their use on cows or bull-dams, and ii) selection intensity and the number of years a sire is in use. Furthermore, we compared different optimum contribution selection scenarios with optimization of sire selection and their usage. We compared the scenarios in terms of genetic gain, selection accuracy, generation interval, genetic and genic variance, the rate of coancestry, effective population size, and the conversion efficiency. The results show that early use of genomically tested sires increased genetic gain compared to progeny testing as expected from changes in selection accuracy and generation interval. A faster turnover of sires from year to year and higher intensity increased the genetic gain even further but increased the loss of genetic variation per year. While maximizing intensity gave the lowest conversion efficiency, a faster turn-over of sires gave an intermediate conversion efficiency. The largest conversion efficiency was achieved with the simultaneous use of genomically and progeny tested sires that were used over several years. Compared to truncation selection optimizing sire selection and their usage increased the conversion efficiency by either achieving comparable genetic gain for a smaller loss of genetic variation or achieving higher genetic gain for a comparable loss of genetic variation. Our results will help breeding organizations to implement sustainable genomic selection.
The knockout of the HMG domain of the porcine SRY gene causes sex reversal in gene-edited pigs
Authors: Kurtz Stefanie , Lucas-Hahn Andrea , Schlegelberger Brigitte , Göhring Gudrun , Niemann Heiner , Mettenleiter Thomas C. , Petersen Björn 
Published: April 2019

1AbstractThe sex-determining region on the Y chromosome (SRY) is thought to be the central genetic element of male sex development. Mutations within the SRY gene are associated with a male-to-female sex reversal syndrome in humans and other mammalian species such as mice and rabbits. However, the underlying mechanisms are largely unknown. To understand the biological function of the SRY gene, a site-directed mutational analysis is required to investigate associated phenotypic changes at the molecular, cellular and morphological level. In our study, we successfully generated a knockout of the porcine SRY gene by microinjection of two clustered regularly interspaced short palindromic repeats (CRISPR) – associated protein - 9 nuclease (Cas9) ribonucleoprotein (RNP) complexes targeting the centrally located “high mobility group” (HMG) domain of the SRY gene. Mutations within this region resulted in the development of complete external and internal female genitalia in genetically male pigs. The internal female genitalia including uteri, ovaries, and oviducts, revealed substantial size differences in 9-months old SRY-knockout pigs compared to age-matched female wild type controls. In contrast, a deletion within the 5’ flanking region of the HMG domain was not associated with sex reversal. Results of this study demonstrates for the first time the central role of the HMG domain of the SRY gene in male sex determination in pigs. Moreover, quantitative analysis by digital PCR revealed evidence for a duplication of the porcine SRY locus. Our results pave the way towards the generation of boars exclusively producing phenotypically female offspring to avoid surgical castration without anesthesia in piglets. Moreover, the study establishes a large animal model that is much more similar to humans in regard of physiology and anatomy and pivotal for longitudinal studies.
FOXP2 exhibits projection neuron class specific expression, but is not required for multiple aspects of cortical histogenesis
Authors: Kast Ryan J , Lanjewar Alexandra L , Smith Colton D , Levitt Pat 
Published: April 2019

AbstractThe expression patterns of the transcription factor FOXP2 in the developing mammalian forebrain have been described, and some studies have tested the role of this protein in the development and function of specific forebrain circuits by diverse methods and in multiple species. Clinically, mutations in FOXP2 are associated with severe developmental speech disturbances, and molecular studies indicate that impairment of Foxp2 may lead to dysregulation of genes involved in forebrain histogenesis. Here, anatomical and molecular phenotypes of the cortical neuron populations that express FOXP2 were characterized in mice. Additionally, Foxp2 was removed from the developing mouse cortex at different prenatal ages using two Cre-recombinase driver lines. Detailed molecular and circuit analyses were undertaken to identify potential disruptions of development. Surprisingly, the results demonstrate that Foxp2 function is not required for many functions that it has been proposed to regulate, and therefore plays a more limited role in cortical development than previously thought.
Differences of endogenous polyamines and putative genes associated with paraquat resistance in goosegrass (Eleusine indica L.)
Authors: Luo Qiyu , Wei Jiping , Dong Zhaoxia , Shen Xuefeng , Chen Yong 
Published: April 2019

AbstractBackgroundParaquat is one of the most effective herbicides used to control weeds in agricultural management, while the pernicious weed goosegrass (Eleusine indica) has evolved resistance to herbicides, including paraquat. Polyamines provide high-level paraquat resistance in many plants. In the present study, we selected three polyamines, namely, putrescine, spermidine, and spermine, as putative genes to investigate their correlation with paraquat resistance by using paraquat-resistant (R) and paraquat-susceptible (S) goosegrass populations.ResultsThere was no significant difference in the putrescine nor spermine content between the R and S biotypes. However, 30 and 90 min after paraquat treatment, the spermidine concentration was 346.14-fold and 421.04-fold (P < 0.001) higher in the R biotype than in the S biotype, but the spermidine concentration was drastically reduced to a marginal level after 90 min. Since the transcript level ofPqEwas low while the spermidine concentration showed a transient increase, thePqEgene was likely involved in the synthesis of the paraquat resistance mechanism, regulation of polyamine content, and synthesis of spermidine and spermine.PqTS1,PqTS2,andPqTS3encode transporter proteins involved in the regulation of paraquat concentration but showed different transcription patterns with synchronous changes in polyamine content.ConclusionEndogenous polyamines (especially spermidine) play a vital role in paraquat resistance in goosegrass.PqE, PqTS1, PqTS2, andPqTS3were speculated on the relationship between polyamine metabolism and paraquat resistance. To validate the roles ofPqE, PqTS1, PqTS2, andPqTS3in polyamine transport systems, further research is needed.