bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduction of leucocyte cell surface disulfide bonds during immune activation is dynamic as revealed by a quantitative proteomics workflow (SH-IQ)
Authors: Stegmann Monika , Barclay A. Neil , Metcalfe Clive
Published: September 2018

Communication through cell surface receptors is crucial for maintaining immune homeostasis, coordinating the immune response and pathogen clearance. This is dependent on the interaction of cell surface receptors with their ligands and requires functionally active conformational states. Thus, immune cell function can be controlled by modulating the structure of either the receptor or the ligand. Reductive cleavage of labile disulfide bonds can mediate such an allosteric change, resulting in modulation of the immune system by a hitherto little studied mechanism. Identifying proteins with labile disulfide bonds and determining the extent of reduction is crucial in elucidating the functional result of reduction. We describe a mass spectrometry-based method—thiol identification and quantitation (SH-IQ)—to identify, quantify and monitor such reduction of labile disulfide bonds in primary cells during immune activation. These results provide the first insight into the extent and dynamics of labile disulfide bond reduction in leucocyte cell surface proteins upon immune activation. We show that this process is thiol oxidoreductase-dependent and mainly affects activatory (e.g. CD132, SLAMF1) and adhesion (CD44, ICAM1) molecules, suggesting a mechanism to prevent over-activation of the immune system and excessive accumulation of leucocytes at sites of inflammation.
Dual tree complex wavelet transform-based signal denoising method exploiting neighbourhood dependencies and goodness-of-fit test
Authors: Naveed Khuram , Shaukat Bisma , ur Rehman Naveed
Published: September 2018

A novel signal denoising method is proposed whereby goodness-of-fit (GOF) test in combination with a majority classifications-based neighbourhood filtering is employed on complex wavelet coefficients obtained by applying dual tree complex wavelet transform (DT-CWT) on a noisy signal. The DT-CWT has proven to be a better tool for signal denoising as compared to the conventional discrete wavelet transform (DWT) owing to its approximate translation invariance. The proposed framework exploits statistical neighbourhood dependencies by performing the GOF test locally on the DT-CWT coefficients for their preliminary classification/detection as signal or noise. Next, a deterministic neighbourhood filtering approach based on majority noise classifications is employed to detect false classification of signal coefficients as noise (via the GOF test) which are subsequently restored. The proposed method shows competitive performance against the state of the art in signal denoising.
Life in the cystic fibrosis upper respiratory tract influences competitive ability of the opportunistic pathogen
Pseudomonas aeruginosa
Authors: Bara Jeffrey J. , Matson Zachary , Remold Susanna K.
Published: September 2018

Understanding characteristic differences between host-associated and free-living opportunistic pathogens can provide insight into the fundamental requirements for success after dispersal to the host environment, and more generally into the ecological and evolutionary processes by which populations respond to simultaneous selection on complex interacting traits. We examined how cystic fibrosis (CF)-associated and environmental isolates of the opportunistic pathogen
Pseudomonas aeruginosa
differ in the production of an ecologically important class of proteinaceous toxins known as bacteriocins, and how overall competitive ability depends on the production of and resistance to these bacteriocins. We determined bacteriocin gene content in a diverse collection of environmental and CF isolates and measured bacteriocin-mediated inhibition, resistance and the outcome of competition in a shared environment between all possible pairs of these isolates at 25°C and 37°C. Although CF isolates encoded significantly more bacteriocin genes, our phenotypic assays suggest that they have diminished bacteriocin-mediated killing and resistance capabilities relative to environmental isolates, regardless of incubation temperature. Notably, however, although bacteriocin killing and resistance profiles significantly predicted head-to-head competitive outcomes, CF and environmental isolates did not differ significantly in their competitive ability. This suggests that the contribution of bacteriocins to competitive ability involves selection on other traits that may be pleiotropically linked to interference competition mediated by bacteriocins.
Preparation of nanoporous BiVO
4
/TiO
2
/Ti film through electrodeposition for photoelectrochemical water splitting
Authors: Hongxing Dong , Qiuping Liu , Yuehui He
Published: September 2018

A nanoporous BiVO
4
/TiO
2
/Ti film was successfully fabricated by electrodepositing a nanoporous BiOI film on nanoporous TiO
2
arrays followed by annealing at 450°C for 2 h. The electrodeposition of BiOI film was carried out at different times (10, 30, 100, 500 and 1000 s) in Bi(NO
3
)
3
and KI solution. The morphological, crystallographic and photoelectrochemical properties of the prepared BiVO
4
/TiO
2
/Ti heterojunction film were examined by using different characterization techniques. UV–vis spectrum absorption studies confirmed an increase in absorption intensities with increasing electrodeposition time, and the band gap of BiVO
4
/TiO
2
/Ti film is lower than that of TiO
2
/Ti. The photocatalytic efficiency of BiVO
4
/TiO
2
/Ti heterojunction film was higher compared to that of the TiO
2
/Ti film owing to the longer transient decay time for BiVO
4
/TiO
2
/Ti film (3.2 s) than that of TiO
2
/Ti film (0.95 s) in our experiment. The BiVO
4
/TiO
2
/Ti heterojunction film prepared by electrodeposition for 1000 s followed by annealing showed a high photocurrent density of 0.3363 mA cm
−2
at 0.6 V versus saturated calomel electrode. Furthermore, the lowest charge transfer resistance from electrochemical impedance spectroscopy was recorded for the BiVO
4
/TiO
2
/Ti film (1000 s) under irradiation.
Spatial scale changes the relationship between beta diversity, species richness and latitude
Authors: Sreekar Rachakonda , Katabuchi Masatoshi , Nakamura Akihiro , Corlett Richard T. , Slik J. W. Ferry , Fletcher Christine , He Fangliang , Weiblen George D. , Shen Guochun , Xu Han , Sun I-Fang , Cao Ke , Ma Keping , Chang Li-Wan , Cao Min , Jiang Mingxi , Gunatilleke I. A. U. Nimal , Ong Perry , Yap Sandra , Gunatilleke C. V. Savitri , Novotny Vojtech , Brockelman Warren Y. , Xiang Wusheng , Mi Xiangcheng , Li Xiankun , Wang Xihua , Qiao Xiujuan , Li Yide , Tan Sylvester , Condit Richard , Harrison Rhett D. , Koh Lian Pin
Published: September 2018

The relationship between β-diversity and latitude still remains to be a core question in ecology because of the lack of consensus between studies. One hypothesis for the lack of consensus between studies is that spatial scale changes the relationship between latitude and β-diversity. Here, we test this hypothesis using tree data from 15 large-scale forest plots (greater than or equal to 15 ha, diameter at breast height ≥ 1 cm) across a latitudinal gradient (3–30
o
) in the Asia-Pacific region. We found that the observed β-diversity decreased with increasing latitude when sampling local tree communities at small spatial scale (grain size ≤0.1 ha), but the observed β-diversity did not change with latitude when sampling at large spatial scales (greater than or equal to 0.25 ha). Differences in latitudinal β-diversity gradients across spatial scales were caused by pooled species richness (γ-diversity), which influenced observed β-diversity values at small spatial scales, but not at large spatial scales. Therefore, spatial scale changes the relationship between β-diversity, γ-diversity and latitude, and improving sample representativeness avoids the γ-dependence of β-diversity.
Turbulence generation from a stochastic wavelet model
Authors: Du Y. , Lin G.
Published: September 2018

This research presents a new turbulence generation method based on stochastic wavelets and tests various properties of the generated turbulence field in both the homogeneous and inhomogeneous cases. Numerical results indicate that turbulence fields can be generated with much smaller bases in comparison to synthetic Fourier methods while maintaining comparable accuracy. Adaptive generation of inhomogeneous turbulence is achieved by a scale reduction algorithm, which greatly reduces the computation cost and practically introduces no error. The generating formula issued in this research could be adjusted to generate fully inhomogeneous and anisotropic turbulence with given RANS data under divergence-free constraint, which was not achieved previously in similar research. Numerical examples shows that the generated homogeneous and inhomogeneous turbulence are in good agreement with the input data and theoretical results.
Sexual selection on multiple female ornaments in dance flies
Authors: Murray Rosalind L. , Wheeler Jill , Gwynne Darryl T. , Bussière Luc F.
Published: September 2018

Sex-specific ornaments typically occur in males, but they can also develop in females. While there are several models concerning the evolution of male-specific ornaments, it is not clear how, or under what circumstances, those models apply to female-specific ornament evolution. Here, we present a manipulative field experiment that explores the theoretical ‘trait space’ of multiple female-specific ornaments to study how these unusual traits evolved. We measured the attractiveness of two female-specific ornaments (pinnate leg scales and inflatable abdominal sacs) in the dance fly
Rhamphomyia longicauda
in a wild mating swarm. We found significant directional preferences for larger ornaments of both types; however, variation in one of the ornaments (abdominal sacs) was almost three times more effective at improving attractiveness. The abdominal ornament was consistently effective in increasing attractiveness to males regardless of leg ornament expression, while leg ornament size was only effective if abdominal ornaments were very small. These results are consistent with predictions from a sexual conflict model of ornament expression in supporting the probable role of deception in the evolution of female-specific ornaments among dance flies. Sexual conflict can be an important force in generating elaborate sex-specific ornaments in females as well as males.
Single mechanosensory neurons encode lateral displacements using precise spike timing and thresholds
Authors: Yarger Alexandra M. , Fox Jessica L.
Published: September 2018

During locomotion, animals rely on multiple sensory modalities to maintain stability. External cues may guide behaviour, but they must be interpreted in the context of the animal's own body movements. Mechanosensory cues that can resolve dynamic internal and environmental conditions, like those from vertebrate vestibular systems or other proprioceptors, are essential for guided movement. How do afferent proprioceptor neurons transform movement into a neural code? In flies, modified hindwings known as halteres detect forces produced by body rotations and are essential for flight. However, the mechanisms by which haltere neurons transform forces resulting from three-dimensional body rotations into patterns of neural spikes are unknown. We use intracellular electrodes to record from haltere primary afferent neurons during a range of haltere motions. We find that spike timing activity of individual neurons changes with displacement and propose a mechanism by which single neurons can encode three-dimensional haltere movements during flight.
Prostaglandin F2α-induced TGFβ-PMEPA1 pathway is a critical mediator of epithelial plasticity and ovarian carcinoma progression
Authors: Jiménez-Segovia Alba , Mota Alba , Rojo-Sebastián Alejandro , Barrocal Beatriz , Rynne-Vidal Angela , García-Bermejo María-Laura , Gómez-Bris Raquel , Hawinkels Lukas J.A.C. , Sandoval Pilar , Garcia-Escudero Ramon , López-Cabrera Manuel , Moreno-Bueno Gema , Fresno Manuel , Stamatakis Konstantinos
Published: September 2018

Prostaglandin (PG) F2αhas been scarcely studied in cancer. We have identified a new role for PGF2αin ovarian cancer, stimulating the production of TGFβ and the consequent induction of PMEPA1. We show that this induction increases cell plasticity and proliferation, enhancing tumor growth through PMEPA1. Thus, PMEPA1 overexpression in ovarian carcinoma cells, significantly increased cell proliferation rates, whereas PMEPA1 silencing decreased proliferation. In addition, PMEPA1 overexpression buffered TGFβ signaling, via reduction of SMAD-dependent signaling. PMEPA1 overexpressing cells acquired an epithelial morphology, associated to higher E-cadherin expression levels while β-catenin nuclear translocation was inhibited. Interestingly, in mouse xenografts, PMEPA1 overexpressing ovarian cells had a clear survival and proliferative advantage, resulting in higher metastatic capacity, while PMEPA1 silencing had the opposite effect. Furthermore, high PMEPA1 expression in a cohort of advanced ovarian cancer patients was observed, correlating with E-cadherin expression. Most importantly, high PMEPA1 mRNA levels were associated with lower patient survival.

Significance

This work identifies Prostaglandin F2αas an inducer, through NFAT, of TGFβ and together with this up-regulate PMEPA1, which is identified both as a drug target and as a prognostic biomarker in ovarian tumors, potentially useful in clinical practice.
Computationally designing antimicrobial peptides forAcinectobacter Baumannii
Authors: Majumder Ayan , Biswal Malay Ranjan , Prakash Meher K.
Published: September 2018

Acinetobacter Baumannii,which is mostly contracted in hospital stays, has been developing resistance to all available antibiotics, including the last line of drugs, such as carbapenem. Because of its quick adaptation there is an immediate need to design new antibiotics, possibly antimicrobial peptides (AMPs) to which bacteria do not develop resistance easily. Our threefold goal was to curate the available activity of AMPs on the same strain ofA. Baumannii, build a neural network model for predicting their activity and use it to rationally pre-screen for lead generation from the thousands of naturally occurring AMPs. By curating and analyzing the recent activity data from 81 AMPs on ATCC 19606 strain, we develop a quantitative AMP activity prediction model. We selected three other models with comparable performance against a test set with known activities. With the goal of inspiring further studies on AMP drug candidates and their rational shortlisting, we made activity predictions for the entire database of AMPs using all the models. To handle the uncertainty of training with a small data set, highlighted peptides which had consistent results from all models.
Impact of recreational fisheries management on fish biodiversity in gravel pit lakes with contrasts to unmanaged lakes
Authors: Matern S. , Emmrich M. , Klefoth T. , Wolter C. , Wegener N. , Arlinghaus R.
Published: September 2018

Gravel pit lakes constitute novel ecosystems that can be colonized by fishes through natural or anthropogenic pathways. Many of these man-made lakes are used by recreational anglers and experience regular fish stocking. Recreationally unmanaged gravel pits may also be affected by fish introductions, e.g., through illegal fish releases, thereby contributing to the formation of site-specific communities. Our objective was to compare the fish biodiversity in gravel pit lakes with and without the recent influence of recreational fisheries management. We sampled 23 small (< 20 ha) gravel pit lakes (16 managed and 7 unmanaged) in north-western Germany and compared fish community and diversity metrics obtained using littoral electrofishing and multimesh gillnet catch per unit effort data. Given the size of the lakes we sampled we expected species poor communities and elevated fish diversity in the managed systems due to stocking. The two lake types were primarily mesotrophic and did not differ in key abiotic and biotic environmental characteristics. Both lakes types hosted similar fish abundance and biomass, but were substantially different in terms of the fish community structure and species richness. Fish were present in all lakes with at least three species. We discovered a higher α-diversity and a lower β-diversity in managed gravel pit lakes compared to unmanaged lakes. Thus, recreational fisheries management appeared to foster homogenization of fish communities, likely because fisheries managers stock these lakes with desired fish species (e.g., piscivorous fishes and large bodied cyprinids). However, we also detected anthropogenic pathways in the colonization of unmanaged gravel pit lakes, presumably from illegal releases by private people. Importantly, hardly any non-native species were detected in the gravel pits we studied, suggesting that recreational fisheries management not necessarily promotes the spread of exotic species.

Significance Statement

Little is known about fish communities in artificially created gravel pit lakes. We compared those managed by recreational fishers with those lacking fisheries management in north-western Germany. We found fishes in all gravel pit lakes and demonstrated a higher α-diversity but more homogenized fish communities in managed gravel pit lakes compared to unmanaged lakes. We did not detect the establishment of relevant abundances of non-natives fishes despite intensive fisheries management.
PolyA tracks and poly-lysine repeats are the Achilles heel ofPlasmodium falciparum
Authors: Djuranovic Slavica Pavlovic , Erath Jessey , Andrews Ryan J , Bayguinov Peter O , Chung Joyce J , Chalker Douglas L , Fitzpatrick James AJ , Moss Walter N , Szczesny Pawel , Djuranovic Sergej
Published: September 2018

Plasmodium falciparum, the causative agent of human malaria, is an apicomplexan parasite with a complex, multi-host life cycle. Sixty percent of transcripts from its extreme AT-rich (81%) genome possess coding polyadenosine (polyA) runs, distinguishing the parasite from its hosts and other sequenced organisms. Recent studies indicate that transcripts with polyA runs encoding poly-lysine are hot spots for ribosome stalling and frameshifting, eliciting mRNA surveillance pathways and attenuating protein synthesis in the majority of prokaryotic and eukaryotic organisms. Here, we show that theP. falciparumtranslational machinery is paradigm-breaking. Using bioinformatic and biochemical approaches, we demonstrate that both endogenous genes and reporter sequences containing long polyA runs are efficiently and accurately transcribed and translated inP. falciparumcells. Translation of polyA tracks in the parasite does not elicit any response from mRNA surveillance pathways usually seen in host human cells or organisms with similar AT content. The translation efficiency and accuracy of the parasite protein synthesis machinery reveals a unique role of ribosomes in the evolution and adaptation ofP. falciparumto an AU-rich transcriptome and polybasic amino sequences. Finally, we show that the ability ofP. falciparumto synthesize long poly-lysine repeats has given this parasite a unique protein exportome and an advantage in infectivity that can be suppressed by addition of exogenous poly-basic polymers.
Logarithmic molecular sampling for next-generation sequencing
Authors: Horn Caroline , Salzman Julia
Published: September 2018

Next-generation sequencing enables measurement of chemical and biological signals at high throughput and falling cost. Conventional sequencing requires increasing sampling depth to improve signal to noise discrimination, a costly procedure that is also impossible when biological material is limiting. We introduce a new general sampling theory, Molecular Entropy encodinG (MEG), which uses biophysical principles to functionally encode molecular abundance before sampling. SeQUential DepletIon and enriCHment (SQUICH) is a specific example of MEG that, in theory and simulation, enables sampling at a logarithmic or better rate to achieve the same precision as attained with conventional sequencing. In proof-of-principle experiments, SQUICH reduces sequencing depth by a factor of 10. MEG is a general solution to a fundamental problem in molecular sampling and enables a new generation of efficient, precise molecular measurement at logarithmic or better sampling depth.
Generation of four iPSC lines from peripheral blood mononuclear cells (PBMCs) of an Attention Deficit Hyperactivity Disorder (ADHD) individual and a healthy sibling in an Australia-Caucasian family
Authors: Tong Janette , Lee Kyung Min , Liu Xiaodong , Nefzger Christian M , Vijayakumar Prasidhee , Hawi Ziarih , Pang Ken C , Parish Clare L , Polo Jose M , Bellgrove Mark A
Published: September 2018

Peripheral blood mononuclear cells were donated by a male teenager with clinically diagnosed Attention Deficit Hyperactivity Disorder under the Diagnostic and Statistical Manual of Mental Disorders IV criteria and his unaffected male sibling. Induced pluripotent stem cells were developed using integration-free Sendai Reprogramming factors containing OCT, SOX2, KLF4, and c-MYC. All four iPSC lines displayed pluripotent cell morphology, pluripotency-associated factors at protein level, alkaline phosphatase enzymatic activity, male karyotype of 46, XY, and in vitro differentiation capacity into all the three germ layers and negative for Mycoplasma.
lncDIFF: a novel distribution-free method for differential expression analysis of long non-coding RNA
Authors: Li Qian , Yu Xiaoqing , Chaudhary Ritu , Slebos Robbert JC , Chung Christine H. , Wang Xuefeng
Published: September 2018

Motivation

Long non-coding RNA expression data has been increasingly used in finding diagnostic and prognostic biomarkers in cancer studies. Existing differential analysis tools for RNA sequencing does not effectively accommodate low abundant genes, as commonly observed in lncRNA. We propose a novel and robust statistical method lncDIFF to detect differential expressed (DE) genes without assuming the true density on normalized counts.

Results

lncDIFF adopts the generalized linear model with zero-inflated exponential quasi likelihood to estimate group effect on normalized counts, and employs the likelihood ratio test to detect differential expressed genes. The proposed method and tool is suitable for data processed with standard RNA-Seq preprocessing and normalization pipelines. Simulation results illustrate that lncDIFF detects DE genes with more power and lower false discovery rate regardless of the data pattern. The analysis on a head and neck squamous cell carcinomas study also confirms that lncDIFF has better sensitivity in identifying novel lncRNA genes with relatively large fold change and prognostic value.

Availability and Implementation

lncDIFF is an R package available athttps://github.com/qianli10000/lncDIFF.

Supplementary Information

Supplementary Data are available at Bioinformatics online.
A simple, robust, and low-cost method to produce the PURE cell - free system
Authors: Lavickova Barbora , Maerkl Sebastian J.
Published: September 2018

We demonstrate a simple, robust, and low-cost method for producing the PURE cell-free transcription-translation system. Our OnePot PURE system achieved a protein synthesis yield of 156 µg/mL at a cost of 0.09 USD/µL, leading to a 14-fold improvement in cost normalized protein synthesis yield over existing PURE systems. The OnePot method makes the PURE system easy to generate and allows it to be readily optimized and modified.
The phage L capsid decoration protein has a novel OB-fold and an unusual capsid binding strategy
Authors: Newcomer Rebecca L. , Schrad Jason R. , Gilcrease Eddie B. , Casjens Sherwood R. , Feig Michael , Teschke Carolyn M. , Alexandrescu Andrei T. , Parent Kristin N.
Published: September 2018

The major coat proteins of dsDNA tailed phages and herpesviruses form capsids by a mechanism that includes active packaging of the dsDNA genome into a precursor procapsid, followed by expansion and stabilization of the capsid. These viruses have evolved diverse strategies to fortify their capsids, such as non-covalent binding of auxiliary “decoration” (Dec) proteins. The Dec protein from the P22-like phage L has a highly unusual binding strategy that precisely distinguishes between nearly identical three-fold and quasi-three-fold sites of the icosahedral capsid. Cryo-electron microscopy and three-dimensional image reconstruction were employed to determine the structure of native phage L particles. NMR was used to determine the structure/dynamics of Dec in solution. Lastly, the NMR structure and the cryo-EM density envelope were combined to build a model of the capsid-bound Dec trimer. Key regions that modulate the binding interface were verified by site-directed mutagenesis.
Incentive salience attribution, “sensation-seeking” and “novelty-seeking” are independent traits in a large sample of male and female heterogeneous stock rats
Authors: Hughson Alesa R. , Horvath Aidan P. , Holl Katie , Palmer Abraham A. , Woods Leah C. Solberg , Robinson Terry E. , Flagel Shelly B.
Published: September 2018

There are a number of traits that are thought to increase susceptibility to addiction, and some of these are modeled in preclinical studies. For example, “sensation-seeking” is predictive of the initial propensity to take drugs; whereas “novelty-seeking” predicts compulsive drug-seeking behavior. In addition, the propensity to attribute incentive salience to reward cues can predict the propensity to approach drug cues, and reinstatement or relapse, even after relatively brief periods of drug exposure. The question addressed here is the extent to which these three ‘vulnerability factors’ are related; that is, predictive of one another. Some relationships have been reported in small samples, but here a large sample of 1,598 outbred male and female heterogeneous stock rats were screened for Pavlovian conditioned approach behavior (to obtain an index of incentive salience attribution; ‘sign-tracking’), and subsequently tested for sensation-seeking and novelty-seeking. Despite the large N there were no significant correlations between these traits, in either males or females. There were, however, novel relationships between multiple measures of incentive salience attribution and, based on these findings, we generated a new metric that captures “incentive value”. Furthermore, there were sex differences on measures of incentive salience attribution and sensation-seeking behavior that were not previously apparent.
Do mechanical strain magnitude and rate drive bone adaptation in adult women? A 12-month prospective randomized trial
Authors: Troy Karen L. , Mancuso Megan E. , Johnson Joshua E. , Wu Zheyang , Schnitzer Thomas J. , Butler Tiffiny A.
Published: September 2018

Although there is strong evidence that certain activities can increase bone density and structure in some individuals, it is unclear what specific mechanical factors govern the response. This is important because understanding the effect of mechanical signals on bone could contribute to more effective osteoporosis prevention methods and efficient clinical trial design. The degree to which strain rate and magnitude govern bone adaptation in humans has never been prospectively tested. Here, we studied the effects of a voluntary upper extremity compressive loading task in healthy adult women during a twelve month prospective period. One hundred and two women age 21-40 participated in one of two experiments. (1): low (n=21) and high (n=24) strain magnitude. (2): low (n=21) and high (n=20) strain rate. Control: (n=16): no intervention. Strains were assigned using subject-specific finite element models. Load cycles were recorded digitally. The primary outcome was change in ultradistal integral bone mineral content (iBMC), assessed with QCT. Interim timepoints and secondary outcomes were assessed with high resolution pQCT (HRpQCT). Sixty-six subjects completed the intervention, and interim data were analyzed for 77 subjects. Both the low and high strain rate groups had significant 12-month increases to ultradistal iBMC (change in control: -1.3±2.7%, low strain rate: 2.7±2.1%, high strain rate: 3.4±2.2%), total iBMC, and other measures. “Loading dose” was positively related to 12-month change in ultradistal iBMC, and interim changes to total BMD, cortical thickness and inner trabecular BMD. Subjects who gained the most bone completed, on average, 130 loading bouts of (mean strain) 550 με at 1805 με/s. Those with the greatest gains had the highest loading dose. We conclude that signals related to strain magnitude, rate, and number of loading bouts contribute to bone adaptation in healthy adult women, but only explain a small amount of variance in bone changes.
Effects of dietary replacement of broiler litter withMucuna pruriens utilisforage and seed meal on performance, carcass characteristics, blood biochemical and physiological parameters in indigenous goats
Authors: Mthiyane Doctor M.N. , Gamedze Nozipho P. , Dlamini Abednego M. , Hugo Arno , Nsahlai Ignatius V.
Published: September 2018

The productivity of indigenous goats in Africa is constrained by shortage of protein-rich feed especially in winter. This study investigated the nutritional value of mucuna forage (MF) and seed meal (MSM) as alternative protein sources for indigenous goats. Mucuna was planted in 3 parallel and adjacent fields and its foliage nutritional composition determined at 4, 8, 12 and 16 weeks after planting (WAP). MF was harvested at 14 WAP whilst mucuna pods were harvested at 28 – 30 WAP, shelled and the MSM chemically analysed. In a completely randomised design (CRD), 20 indigenous goats were randomly offered 5 treatment diets with, respectively, 0%, 25%, 50% and 100% MF and 100% MSM replacing broiler litter (BL), each with 4 replicates, for 82 days. Both mucuna foliage DM and CF contents increased (P < 0.001) whilst foliage CP, EE and ash contents decreased (P<0.001) with maturity. On the other hand, MSM contained high DM (90.7%), EE (3.7% DM) and CP (26.0% DM) but low CF (9.7% DM) and ash (5.5% DM) contents. Both body weight gain (BWG) and feed conversion efficiency (FCE) were not influenced by dietary mucuna incorporation (P > 0.05). However, dietary MF, particularly at the 100% level, decreased goat feed intake (FI) (P < 0.001) whilst 100% MSM increased (P < 0.001) this parameter. Mucuna had no effect on all carcass characteristics (P > 0.05) but increased (P < 0.05), particularly at the 100% MSM level, hot carcass weight and dressing percentage. There were no effects of mucuna on all biochemical and haematological indices (P > 0.05), except for the increase in serum glucose (P < 0.05). In conclusion, the optimal stage for harvesting and utilisation of MF is between 12 and 16 WAP and both MF and MSM, particularly the latter, are rich alternative protein sources for indigenous goats.
Engineered variants provide new insight into the structural properties important for activity of the highly dynamic, trimeric protein disulfide isomerase, PmScsC
Authors: Furlong Emily J. , Kurth Fabian , Premkumar Lakshmanane , Whitten Andrew E. , Martin Jennifer L.
Published: September 2018

Suppressor of copper sensitivity protein C from Proteus mirabilis (PmScsC) is a homotrimeric disulfide isomerase that plays a role in copper tolerance – a key virulence trait of the uropathogen. Each protomer of the enzyme has an N-terminal trimerisation stem (59 residues) containing a flexible linker (11 residues) connected to a thioredoxin-fold-containing catalytic domain (163 residues). Here, we characterise two PmScsC variants, PmScsCΔN and PmScsCΔLinker. PmScsCΔN, is an N-terminally truncated form of the protomer with two helices of the trimerisation stem removed, generating a protein with dithiol oxidase rather than disulfide isomerase activity. The crystal structure of PmScsCΔN reported here reveals – as expected – a monomer that is structurally similar to the catalytic domain of native PmScsC. The second variant PmScsCΔLinker was designed to remove the 11 amino acid linker and we show that it generates a protein that has neither disulfide isomerase nor dithiol oxidase activity. The crystal structure of PmScsCΔLinker reveals a trimeric arrangement, with the catalytic domains packed together very closely. Small angle X-ray scattering analysis found that native PmScsC is predominantly trimeric in solution even at low concentration, whereas PmScsCΔLinker exists as an equilibrium between monomeric, dimeric and trimeric states, with the monomeric form dominating at low concentrations. These findings increase our understanding of disulfide isomerase activity, showing how (i) oligomerisation, (ii) spacing between, and (iii) dynamic motion of, catalytic domains in PmScsC all contribute to its native function.
Identification of traits and functional connectivity-based neuropsychotypes of chronic pain
Authors: Vachon-Presseau Etienne , Berger Sara E. , Abdullah Taha B. , Griffith James W. , Schnitzer Thomas J. , Apkarian A. Vania
Published: September 2018

Psychological and personality factors, socioeconomic status, and brain properties all contribute to chronic pain but have essentially been studied independently. Here, we administered a broad battery of questionnaires to patients with chronic back pain (CBP). Clustering and network analyses revealed four orthogonal dimensions accounting for 60% of the variance, and defining chronic pain traits. Two of these traits – Pain-trait and Emote-trait - were related to back pain characteristics and could be predicted from distinct distributed functional networks in a cross-validation procedure, identifying neurotraits. These neurotraits were relatively stable in time and segregated CBP patients into subtypes showing distinct traits, pain affect, pain qualities, and socioeconomic status (neuropsychotypes). The results unravel the trait space of chronic pain leading to reliable categorization of patients into distinct types. The approach provides metrics aiming at unifying the psychology and the neurophysiology of chronic pain across diverse clinical conditions, and promotes prognostics and individualized therapeutics.
Integrin-mediated attachment of the blastoderm to the vitelline envelope impacts gastrulation of insects
Authors: Münster Stefan , Jain Akanksha , Mietke Alexander , Pavlopoulos Anastasios , Grill Stephan W. , Tomancak Pavel
Published: September 2018

During gastrulation, physical forces reshape the simple embryonic tissue to form a complex body plan of multicellular organisms1. These forces often cause large-scale asymmetric movements of the embryonic tissue2,3. In many embryos, the tissue undergoing gastrulation movements is surrounded by a rigid protective shell4,5. While it is well recognized that gastrulation movements depend on forces generated by tissue-intrinsic contractility6,7, it is not known if interactions between the tissue and the protective shell provide additional forces that impact gastrulation. Here we show that a particular part of the blastoderm tissue of the red flour beetleTribolium castaneumtightly adheres in a temporally coordinated manner to the vitelline envelope surrounding the embryo. This attachment generates an additional force that counteracts the tissue-intrinsic contractile forces to create asymmetric tissue movements. Furthermore, this localized attachment is mediated by a specific integrin, and its knock-down leads to a gastrulation phenotype consistent with complete loss of attachment. Moreover, analysis of another integrin in the fruit flyDrosophila melanogastersuggests that gastrulation in this organism also relies on adhesion between the blastoderm and the vitelline. Together, our findings reveal a conserved mechanism whereby the spatiotemporal pattern of tissue adhesion to the vitelline envelope provides controllable counter-forces that shape gastrulation movements in insects.
The effect of stimulus choice on an EEG-based objective measure of speech intelligibility
Authors: Verschueren Eline , Vanthornhout Jonas , Francart Tom
Published: September 2018

Objectives

Recently an objective measure of speech intelligibility, based on brain responses derived from the electroencephalogram (EEG), has been developed using isolated Matrix sentences as a stimulus. We investigated whether this objective measure of speech intelligibility can also be used with natural speech as a stimulus, as this would be beneficial for clinical applications.

Design

We recorded the EEG in 19 normal-hearing participants while they listened to two types of stimuli: Matrix sentences and a natural story. Each stimulus was presented at different levels of speech intelligibility by adding speech weighted noise. Speech intelligibility was assessed in two ways for both stimuli: (1) behaviorally and (2) objectively by reconstructing the speech envelope from the EEG using a linear decoder and correlating it with the acoustic envelope. We also calculated temporal response functions (TRFs) to investigate the temporal characteristics of the brain responses in the EEG channels covering different brain areas.

Results

For both stimulus types the correlation between the speech envelope and the reconstructed envelope increased with increasing speech intelligibility. In addition, correlations were higher for the natural story than for the Matrix sentences. Similar to the linear decoder analysis, TRF amplitudes increased with increasing speech intelligibility for both stimuli. Remarkable is that although speech intelligibility remained unchanged in the no noise and +2.5 dB SNR condition, neural speech processing was affected by the addition of this small amount of noise: TRF amplitudes across the entire scalp decreased between 0 to 150 ms, while amplitudes between 150 to 200 ms increased in the presence of noise. TRF latency changes in function of speech intelligibility appeared to be stimulus specific: The latency of the prominent negative peak in the early responses (50-300 ms) increased with increasing speech intelligibility for the Matrix sentences, but remained unchanged for the natural story.

Conclusions

These results show (1) the feasibility of natural speech as a stimulus for the objective measure of speech intelligibility, (2) that neural tracking of speech is enhanced using a natural story compared to Matrix sentences and (3) that noise and the stimulus type can change the temporal characteristics of the brain responses. These results might reflect the integration of incoming acoustic features and top-down information, suggesting that the choice of the stimulus has to be considered based on the intended purpose of the measurement.
Evaluation of endothelial nitric oxide synthase gene expression in mice genetically heterozygous in Cx43 (Cx43 + / - mice)
Authors: Obaalologhi Wilfred
Published: September 2018

Gap junctions are proteins made of connexins which are involved in the regulation of vascular function. Deletion of connexins 43 (Cx43) modifies expression of genes known to be involved in the regulation of the vasculature, differentiation and function of vascular cells. Interestingly, mutant mice lacking endothelial nitric oxide synthase (eNOS) gene have been shown to be hypertensive, suggesting that nitric oxide (NO) plays a role in the physiological control of blood pressure. It was therefore hypothesised that the endothelial deletion of Cx43 in the pulmonary vasculature induces endothelial dysfunction and causes eNOS impairment thereby reducing NO biosynthesis, thus leading to vasoconstriction and vascular remodelling which subsequently leads to the development of pulmonary arterial hypertension (PAH). This project was aimed at evaluating eNOS gene expression in mice genetically heterozygous (HET) in Cx43 (Cx43 +/- mice). This was achieved by using lung tissues from four groups of wild type (W/T) and Cx43 +/- (male and female) mice. Ribonucleic acid (RNA) was isolated from the lung tissues using RNA II isolation system and was reverse transcribed to complementary deoxyribonucleic acid (cDNA). End – point polymerase chain reaction (PCR) and real time PCR were used to measure the expression of eNOS gene. eNOS gene expression levels were found to be the same in all four groups of mice tested, with no significant difference. The result therefore suggests that eNOS gene is expressed in mice genetically heterozygous in Cx43 (Cx43 + / -).
Adopting Literature-based Discovery on Rehabilitation Therapy Repositioning for Stroke
Authors: Meng Guilin , Huang Yong , Yu Qi , Ding Ying , Wild David , Zhao Yanxin , Liu Xueyuan , Song Min
Published: September 2018

Stroke is a common disabling disease severely affecting the daily life of the patients. There is evidence that rehabilitation therapy can improve the movement function. However, there are no clear guidelines that identify specific, effective rehabilitation therapy schemes, and the development of new rehabilitation techniques has been fairly slow. One informatics translational approach, called ABC model in Literature-based Discovery, was used to mine an existing rehabilitation candidate which is most likely to be repositioned for stroke. As in the classic ABC model originated from Don Swanson, we built the internal links of stroke (A), assessment scales (B), rehabilitation therapies (C) in PubMed relating to upper limb function measurements for stroke patients. In the first step, with E-utility we retrieved both stroke related assessment scales and rehabilitation therapies records, and complied two datasets called Stroke_Scales and Stroke_Therapies, respectively. In the next step, we crawled all rehabilitation therapies co-occurred with the Stroke_Theapies, named as All_Therapies. Therapies that were already included in Stroke_Therapies were deleted from All_Therapies, so that the remaining therapies were the potential rehabilitation therapies, which could be repositioned for stroke after subsequent filtration by manual check. We identified the top ranked repositioning rehabilitation therapy following by subsequent clinical validation. Hand-arm bimanual intensive training (HABIT) ranked the first in our repositioning rehabilitation therapies list, with the most interaction links with Stroke_Scales. HABIT showed a significant improvement in clinical scores on assessment scales of Fugl-Meyer Assessment and Action Research Arm Test in the clinical validation on upper limb function for acute stroke patients. Based on the ABC model and clinical validation of the results, we put forward that HABIT as a promising rehabilitation therapy for stroke, which shows that the ABC model is an effective text mining approach for rehabilitation therapy repositioning. The results seem to be promoted in clinical knowledge discovery.

Author Summary

In the present study, we proposed a text mining approach to mining terms related to disease, rehabilitation therapy, and assessment scale from literature, with a subsequent ABC inference analysis to identify relationships of these terms across publications. The clinical validation demonstrated that our approach can be used to identify potential repositioning rehabilitation therapy strategies for stroke. Specifically, we identified a promising rehabilitation method called HABIT previously used in pediatric congenital hemiplegia. A subsequent clinical trial confirmed this as a highly promising rehabilitation therapy for stroke.
Systematic identification and characterization of Aedes aegypti long noncoding RNAs
Authors: Azlan Azali , Obeidat Sattam M. , Yunus Muhammad Amir , Azzam Ghows
Published: September 2018

Long noncoding RNAs (lncRNAs) play diverse roles in biological process including developmental regulation and host-pathogen interactions. Aedes aegypti (Ae. aegypti), a blood-sucking mosquito, is the principal vector responsible for replication and transmission of arboviruses including dengue, zika, and chikungunya virus. Systematic identification and developmental characterisation of Ae. aegypti lncRNAs are still limited. We performed genome-wide identification of lncRNAs followed by developmental profiling of lncRNA expression in Ae. aegypti. We identified a total of 4,689 novel lncRNA transcripts, of which 2,064, 2,076, and 549 were intergenic, intronic, and antisense respectively. Ae. aegypti lncRNAs shared many of the characteristics with other species including low expression, low GC content, short in length, low conservation, and their expression tended to be correlated with neighbouring and antisense protein-coding genes. Subsets of lncRNAs showed evidence that they were maternally inherited, suggesting potential roles in early-stage embryos. Additionally, lncRNAs showed higher tendency to be expressed in developmental and temporal specific manner. Upon infection of Ae. aegypti cells with dengue virus serotype 1, we identified 2,335 differentially expressed transcripts, 957 of which were lncRNA transcripts. The systematic annotation, developmental profiling, and transcriptional response upon virus infection provide foundation for future investigation on the function of Ae. aegypti lncRNAs.
Crosstalk between alternative polyadenylation and miRNAs in the regulation of protein translational efficiency
Authors: Fu Yonggui , Chen Liutao , Chen Chengyong , Ge Yutong , Kang Mingjing , Song Zili , Li Jingwen , Feng Yuchao , Huo Zhanfeng , He Guopei , Hou Mengmeng , Chen Shangwu , Xu Anlong
Published: September 2018

3′ UTRs play important roles in the gene regulation network via their influence on mRNA stability, translational efficiency, and subcellular localization. For a given gene, 3′ UTRs of different lengths generated by alternative polyadenylation (APA) may result in functional differences in regulation. The mechanistic details of how length changes of 3′ UTRs alter gene function remain unclear. By combining APA sequencing and polysome profiling, we observed that mRNA isoforms with shorter 3′ UTRs were bound with more polysomes in six cell lines but not in NIH3T3 cells, suggesting that changing 3′ UTRs to shorter isoforms may lead to a higher gene translational efficiency. By interfering with the expression of TNRC6A and analyzing AGO2-PAR-CLIP data, we revealed that the APA effect on translational efficiency was mainly regulated by miRNAs, and this regulation was cell cycle dependent. The discrepancy between NIH3T3 and other cell lines was due to contact inhibition of NIH3T3. Thus, the crosstalk between APA and miRNAs may be needed for the regulation of protein translational efficiency.
The novel metallo-β-lactamase PNGM-1 from a deep-sea sediment metagenome: crystallization and X-ray crystallographic analysis
Authors: Park Kwang Seung , Hong Myoung-Ki , Jeon Jin Wan , Kim Ji Hwan , Jeon Jeong Ho , Lee Jung Hun , Kim Tae Yeong , Karim Asad Mustafa , Malik Sumera Kausar , Kang Lin-Woo , Lee Sang Hee
Published: September 2018

Metallo-β-lactamases (MBLs) are present in major Gram-negative pathogens and environmental species, and pose great health risks because of their ability to hydrolyze the β-lactam rings of antibiotics such as carbapenems. PNGM-1 was the first reported case of a subclass B3 MBL protein that was identified from a metagenomic library from deep-sea sediments that predate the antibiotic era. In this study, PNGM-1 was overexpressed, purified and crystallized. Crystals of native and selenomethionine-substituted PNGM-1 diffracted to 2.10 and 2.30 Å resolution, respectively. Both the native and the selenomethionine-labelled PNGM-1 crystals belonged to the monoclinic space groupP21, with unit-cell parametersa= 122,b= 83,c= 163 Å, β = 110°. Matthews coefficient (VM) calculations suggested the presence of 6–10 molecules in the asymmetric unit, corresponding to a solvent content of ∼31–58%. Structure determination is currently in progress.