bluuebunny/crossref_metadata_2025 huggingface dataset:
Biofilm formation by Mycobacterium avium ssp. paratuberculosis in aqueous extract of schmutzdecke for clarifying untreated water in water treatment operations
Authors: Aboagye G. , Rowe M.T.
Published: June 2018

AIMS

To determine the effect of aqueous extract of schmutzdecke on adhesion and biofilm formation by three isolates of Mycobacterium avium ssp. paratuberculosis (Map) under laboratory conditions.

METHODS AND RESULTS

Strains of Mycobacterium avium ssp. paratuberculosis in aqueous extract of schmutzdecke were subjected to adhesion tests on two topologically different substrata i.e. aluminium and stainless steel coupons. Biofilm formation was then monitored in polyvinyl chloride (PVC) plates. All the three strains adhered onto both coupons, howbeit greatly on aluminium than stainless steel. In the PVC plates, however, all strains developed biofilms which were observed by spectrophotometric analysis.

CONCLUSIONS

The environmental isolates of Map attained higher cell proliferation in both filtered and unfiltered aqueous extracts of schmutzdecke (FAES and UAES respectively) compared with the human isolate. Furthermore, the results showed that irrespective of the media used, Map might have developed biofilm by its genetic competence to do so under favourable conditions that the immediate environment might have provided.

Significance and impact of the study

Composites of the schmutzdecke which is the dirty layer formed within 10 to 20 days of operation of a slow sand filter bed had a proliferative effect on Map. Therefore when entrapped, Map could form a biofilm and access human populations through potable water. Therefore, schmutzdecke should be monitored and scraped periodically to curtail its support for environmentally persistent pathogens that can pose health risks to humans.

Highlights

Schmutzdecke; a reservoir of nutrient composites atop slow sand filter bed

Adhesion by Map on aluminium and stainless steel coupons was achieved

Map strains from water sources developed biofilms better than the human strain

In distilled water, biofilm formation by all strains was evident

Protracted build-up of schmutzdecke may proliferate waterborne pathogens
Identification of pathogens in culture-negative infective endocarditis cases by metagenomic analysis
Authors: Cheng Jun , Hu Huan , Kang Yue , Chen Weizhi , Fang Wei , Wang Kaijuan , Zhang Qian , Fu Aisi , Zhou Shuilian , Cheng Chen , Cao Qingqing , Wang FeiYan , Lee Shela , Zhou Zhou
Published: June 2018

Pathogens identification is critical for the proper diagnosis and precise treatment of infective endocarditis. Although blood and valve cultures are the gold standard for IE pathogens detection, many cases are culture-negative, especially in patients who had received long-term antibiotic treatment, and precise diagnosis has therefore become a major challenge in the clinic. Metagenomic sequencing can provide both information on the pathogenic strain and the antibiotic susceptibility profile of patient samples without culturing, offering a powerful method to deal with culture-negative cases. In this work, we assessed the feasibility of a metagenomic approach to detect the causative pathogens in resected valves from IE patients.

Using our in-house developed bioinformatics pipeline, we analyzed the sequencing results generated from both next-generation sequencing and Oxford Nanopore Technologies MinION nanopore sequencing for the direct identification of pathogens from the resected valves of seven clinically culture-negative IE patients according to the modified Duke criteria. Moreover, we were able to simultaneously characterize respective antimicrobial resistance features. This provides clinicians with valuable information to diagnose and treat IE patients after valve replacement surgery.
Novel Staphylococcal Cassette Chromosome composite island (SCC-CI) with a new subtype ofSCCmecVI cassette found in ST5 MRSA in France
Authors: Barraud Olivier , Laurent Frédéric , Dyon-Tafani Virginie , Dupieux-Chabert Céline , Bes Michèle , Ploy Marie-Cécile , Garnier Fabien , Simões Patricia Martins
Published: June 2018

An emergent kanamycin-susceptible ST5-MRSA lineage has been identified in France. Whole genome sequencing revealed a 40 kb SCC composite island with a mosaic structure including 3 SCC elements: a ΨSCCcop/ars, a SCCLim88Awith accrC recombinase, and a novel subtype of SCCmectype VI (VIb). This mosaic structure suggests a high recombination rate of SCC elements from distinct staphylococci species.
Species tree-aware simultaneous reconstruction of gene and domain evolution
Authors: Muhammad Sayyed Auwn , Sennblad Bengt , Lagergren Jens
Published: June 2018

Most genes are composed of multiple domains, with a common evolutionary history, that typically perform a specific function in the resulting protein. As witnessed by many studies of key gene families, it is important to understand how domains have been duplicated, lost, transferred between genes, and rearranged. Analogously to the case of evolutionary events affecting entire genes, these domain events have large consequences for phylogenetic reconstruction and, in addition, they create considerable obstacles for gene sequence alignment algorithms, a prerequisite for phylogenetic reconstruction.

We introduce the DomainDLRS model, a hierarchical, generative probabilistic model containing three levels corresponding to species, genes, and domains, respectively. From a dated species tree, a gene tree is generated according to the DL model, which is a birth-death model generalized to occur in a dated tree. Then, from the dated gene tree, a pre-specified number of dated domain trees are generated using the DL model and the molecular clock is relaxed, effectively converting edge times to edge lengths. Finally, for each domain tree and its lengths, domain sequences are generated for the leaves based on a selected model of sequence evolution.

For this model, we present a MCMC-based inference framework called DomainDLRS that takes a dated species tree together with a multiple sequence alignment for each domain family as input and outputs an estimated posterior distribution over reconciled gene and domain trees. By requiring aligned domains rather than genes, our framework evades the problem of aligning full-length genes that have been exposed to domain duplications, in particular non-tandem domain duplications. We show that DomainDLRS performs better than MrBayes on synthetic data and that it outperforms MrBayes on biological data. We analyse several zincfinger genes and show that most domain duplications have been tandem duplications, some involving two or more domains, but non-tandem duplications have also been common.
Membrane-mediated interactions induce spontaneous filament bundling
Authors: Vahid Afshin , Dadunashvili George , Idema Timon
Published: June 2018

The plasma membrane and cytoskeleton of living cells are closely coupled dynamical systems. Internal cytoskeletal elements such as actin filaments and microtubules continually exert forces on the membrane, resulting in the formation of membrane protrusions. In this paper we investigate the interplay between the shape of a cell distorted by pushing and pulling forces generated by microtubules and the resulting rearrangement of the microtubule network. From analytical calculations, we find that two microtubules that deform the vesicle can both attract or repel each other, depending on their angular separations and the direction of the imposed forces. We also show how the existence of attractive interactions between multiple microtubules can be deduced analytically, and further explore general interactions through Monte Carlo simulations. Our results suggest that the commonly reported parallel structures of microtubules in both biological and artificial systems can be a natural consequence of membrane mediated interactions.
Comparative transcriptomics of albino and warningly coloured caterpillars
Authors: Galarza Juan A.
Published: June 2018

Colouration is perhaps one of the most prominent adaptations for survival and reproduction of most taxa. Colouration is of particular importance for aposematic species, which rely on their colouring and patterning to act as a warning signal against predators. Most research has focused on the evolution of warning colouration by natural selection. However, little information is available for colour mutants of aposematic species, particularly at the genomic level. Here I compare the transcriptomes of albino mutant caterpillars of the wood tiger moth (Arctia plantaginis) to those of their full-sibs having their distinctive orange-black warning colouration. The results showed >300 differentially expressed genes transcriptome-wide. Genes involved in the immune system, structural constituents of cuticle, and peptidase activity were mostly down-regulated in the albino larvae. Surprisingly, higher expression was observed in core melanin genes from albino larvae, suggesting that melanin synthesis may be disrupted in terminal ends of the pathway during its final conversion. I further identified 25 novel genes uniquely expressed in the albino larvae. Functional annotation showed that these genes are involved in nucleotide biosynthesis, copper ion transmembrane transport, and nucleic acid binding. Taken together, these results suggest that caterpillar albinism may not be due to a depletion of melanin precursor genes. In contrast, the albino condition may result from the combination of faulty melanin conversion late in its synthesis and structural deficiencies in the cuticle preventing its deposition.
High throughput screen identifies IFN-γ-dependent inhibitors of Toxoplasma gondii growth
Authors: Radke Joshua B. , Carey Kimberly L. , Shaw Subrata , Metkar Shailesh R. , Mulrooney Carol , Gale Jennifer P. , Bittker Joshua A. , Hilgraf Robert , Comer Eamon , Schreiber Stuart L. , Virgin Herbert W. , Perez Jose R. , Sibley L. David
Published: June 2018

Toxoplasma gondii is an obligate intracellular parasite capable of causing severe disease due to congenital infection and in patients with compromised immune systems. Control of infection is dependent on a robust Th1 type immune response including production of interferon gamma (IFN-γ), which is essential for control. IFN-γ activates a variety of anti-microbial mechanisms in host cells, which are then able to control intracellular parasites such as T. gondii. Despite the effectiveness of these pathways in controlling acute infection, the immune system is unable to eradicate chronic infections that can persist for life. Similarly, while antibiotic treatment can control acute infection, it is unable to eliminate chronic infection. To identify compounds that would act synergistically with IFN-γ, we performed a high-throughput screen of diverse small molecule libraries to identify inhibitors of T. gondii. We identified a number of compounds that inhibited parasite growth in vitro at low μM concentrations and that demonstrated enhanced potency in the presence of low level of IFN-γ. A subset of these compounds act by enhancing the recruitment of LC3 to the parasite-containing vacuole, suggesting they work by an autophagy-related process, while others were independent of this pathway. The pattern of IFN-γ-dependence was shared among the majority of analogs from 6 priority scaffolds and analysis of structure activity relationships for one such class revealed specific stereochemistry associated with this feature. Identification of these IFN-γ-dependent leads may lead to development of improved therapeutics due to their synergistic interactions with immune responses.
Proteomic Analysis of Urine from California Sea Lions (Zalophus californianus): a Resource for Urinary Biomarker Discovery
Authors: Neely Benjamin A. , Prager Katherine C. , Bland Alison M. , Fontaine Christine , Gulland Frances M. , Janech Michael G.
Published: June 2018

Urinary markers for the assessment of kidney diseases in wild animals are limited, in part, due to the lack of urinary proteome data, especially for marine mammals. One of the most prevalent kidney diseases in marine mammals is caused byLeptospira interrogans, which is the second most common etiology linked to stranding of California sea lions (Zalophus californianus). Urine proteins from eleven sea lions with leptospirosis kidney disease and eight sea lions without leptospirosis or kidney disease were analyzed using shotgun proteomics. In total, 2694 protein groups were identified and 316 were differentially abundant between groups. Major urine proteins in sea lions were similar to major urine proteins in dogs and humans except for the preponderance of resistin, lysozyme C, and PDZ domain containing 1, which appear to be over-represented. Previously reported urine protein markers of kidney injury in humans and animals were also identified. Notably, neutrophil gelatinase-associated lipocalin, osteopontin, and epidermal fatty acid binding protein were elevated over 20-fold in the leptospirosis-infected sea lions. Consistent with leptospirosis infection in rodents, urinary proteins associated with the renin-angiotensin system were depressed, including neprilysin. This study represents a foundation from which to explore the clinical use of urinary protein markers in California sea lions.

Abbreviations

RAS

renin-angiotensin system

lepto

leptospirosis

SCr

serum creatinine

BUN

blood urea nitrogen
Astroglial biophysics probed with a realistic cell model
Authors: Savtchenko Leonid P. , Bard Lucie , Jensen Thomas P. , Reynolds James P. , Kraev Igor , Medvedev Mikola , Stewart Michael G. , Henneberger Christian , Rusakov Dmitri A.
Published: June 2018

Electrically non-excitable astroglia take up neurotransmitters, buffer extracellular K+ and generate Ca2+ signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the nanoscopic, sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we have systematically evaluated the multi-scale morphology of protoplasmic astroglia to construct a realistic multi-compartmental cell model that can be biophysically interrogated in NEURON computational environment. This approach has been implemented as an astrocyte-model builder ASTRO. As a proof of concept, we explored a hippocampal astrocyte reconstructed in silico against a battery of physiological and imaging experiments. This exploration has unveiled some basic features of astroglial physiology inaccessible empirically, such as the characteristic length of membrane voltage propagation, membrane effects of local glutamate transport, spatiotemporal dynamics of intracellular K+ redistribution, key Ca2+ buffering properties, and some basic relationships between free Ca2+ dynamics and experimental readout of fluorescent Ca2+ indicators.
Toward machine-guided design of proteins
Authors: Biswas Surojit , Kuznetsov Gleb , Ogden Pierce J. , Conway Nicholas J. , Adams Ryan P. , Church George M.
Published: June 2018

Proteins—molecular machines that underpin all biological life—are of significant therapeutic and industrial value. Directed evolution is a high-throughput experimental approach for improving protein function, but has difficulty escaping local maxima in the fitness landscape. Here, we investigate how supervised learning in a closed loop with DNA synthesis and high-throughput screening can be used to improve protein design. Using the green fluorescent protein (GFP) as an illustrative example, we demonstrate the opportunities and challenges of generating training datasets conducive to selecting strongly generalizing models. With prospectively designed wet lab experiments, we then validate that these models can generalize to unseen regions of the fitness landscape, even when constrained to explore combinations of non-trivial mutations. Taken together, this suggests a hybrid optimization strategy for protein design in which a predictive model is used to explore difficult-to-access but promising regions of the fitness landscape that directed evolution can then exploit at scale.
Closed-loop coupling of a muscle to a robotic device for dynamic assessment of muscle function
Authors: Sundar Kartik , Ting Lena H. , DeWeerth Stephen P.
Published: June 2018

The contributions of individual muscles to the performance of functional tasks are difficult to evaluate using traditional isolated muscle protocols. During movements, skeletal muscles work against a variety of environmental loads that influence their energetics and function. In turn, these changes in muscle length and muscle velocity alter the forces that the muscle can generate. Classic single-muscle experiments clamp at least one muscle state (length, velocity, force) such that it is independent of the other states, interrupting the dynamic interactions between the muscle and its environment. The purpose of this study was to design and build a real-time feedback system to virtually couple an isolated muscle to a robotic device. Using this approach, the muscle length is not prescribed, but results from the dynamic interactions between the muscle and a physical environment. Therefore our device facilitates the study of how physical interactions between a muscle, limb, and environments alter the force and motion produced by the muscle during controlled muscle activation. To demonstrate the utility of our system, we replicated some salient features of frog swimming, we coupled a frog plantaris longus muscle to a one-degree of freedom “limb” that drove a frog foot through water. We demonstrate that under identical muscle stimulation parameters, changes to muscle moment arm, environmental viscosity, and muscle fatigue can significantly alter the resulting muscle force, length, and work.
Genetic diversity and distribution of indigenous soybean-nodulating bradyrhizobia in the Philippines
Authors: Tabing Mason Maria Luisa , Cortez Tabing Baby Lyn , Yamamoto Akihiro , Saeki Yuichi
Published: June 2018

The diversity of indigenous bradyrhizobia from soils collected at 11 locations in the Philippines was investigated using PSB-SY2 local soybean cultivar as the host plant. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) treatment for 16S rRNA, 16S-23S rRNA internal transcribed spacer (ITS) region and rpoB housekeeping gene was performed primarily to detect the genetic variation among the 424 isolates collected. Then, sequence analysis of 16S rRNA, ITS region and rpoB gene was performed for the representative isolates. Majority of the isolates were classified under Bradyrhizobium elkanii, B. diazoefficiens, B. japonicum, Bradyrhizobium sp., and few isolates were related to B. yuanmingense. Genetic variations observed through PCR-RFLP and sequence analyses of the ITS region and rpoB gene generally occurred in B. elkanii, suggesting an occurrence of gene transfer. Shannon’s diversity index showed varied results with a lowest score of 0.00 and highest at 0.98 indicating a very diverse population of bradyrhizobia across the country. Among all the factors considered in this work, soil management such as period of flooding and some soil properties provided major influence on the distribution and diversity of soybean bradyrhizobia in the country. Thus, it is proposed that the major micro-symbiont of soybean in the Philippines are B. elkanii for non-flooded soils, then B. diazoefficiens and B. japonicum for flooded soils.

Importance

Agriculture production in the Philippines has been and is currently heavily dependent on chemical inputs with mainly rice or corn mono-cropping that it rendered the soil acidic and unproductive. Legume research in the country are mainly focused on plant varietal improvements and very few are aimed at understanding the ecological niche of rhizobia present in the soil. Since soybean has mutual relationship with rhizobia, this legume is a good fallow crop or a rotation crop after rice and corn to help build up the nitrogen stock in the soil. The significance of this research is the better understanding of the ecological niche of indigenous soybean bradyrhizobia, particularly in a tropical archipelago like the Philippines. This work was conceptualized with the utmost goal to increase soybean yield by harnessing and evaluating the indigenous rhizobia in the soil to make production more sustainable and human-friendly.
Synergistic Activity of Silver Nanoparticles and Vancomycin Against a Spectrum ofStaphylococcus aureusBiofilm Types
Authors: Hair Bryan B. , Conley Matthew E. , Wienclaw Trevor M. , Conley Mark J. , Berges Bradford K.
Published: June 2018

Staphylococcus aureus(SA) is an important human pathogen, causing potentially lethal infections of the blood, skin, and lungs. SA is becoming increasingly difficult to treat due to high levels of antibiotic resistance, and new treatments are needed. SA is able to evade antibiotics and immune surveillance through biofilm development. Biofilms are communities of microorganisms that are able to prevent the entry of antimicrobials and immune cells. Biofilms are also involved in SA transmission because biofilms can form on medical devices. In this study, we tested silver nanoparticles and vancomycin for their anti-biofilm effects on SA. We used 10 different SA isolates, representing a spectrum of biofilm-forming ability, and a crystal violet assay to measure biofilm mass. 2μg/mL vancomycin treatment resulted in a significant reduction in established SA biofilms in 7/10 isolates, including 4/5 methicillin susceptible SA (MSSA) and 3/5 methicillin-resistant (MRSA) isolates (mean reduction in crystal violet stain of 13.0%; high of 26.5% and low of 0%). Silver nanoparticle treatment of SA biofilms resulted in a significant reduction in 6/10 isolates, including 4/5 MSSA and 2/5 MRSA (mean reduction of 8.7%; high of 21.2% and low of 0%). A combinatorial treatment with silver nanoparticles and vancomycin resulted in significant reductions in 9/10 isolates (mean reduction of 20.8%; high of 39.3% and low of 0%). We conclude that both vancomycin and silver nanoparticle treatment of established tissue culture-based SA biofilms result in significant reductions in biofilm mass, with a combinatorial treatment even more effective than either treatment alone.
In vivovirulence characterization of pregnancy-associatedListeria monocytogenesinfections
Authors: Morrison Holly A. , Lowe David , Robbins Jennifer R. , Bakardjiev Anna I.
Published: June 2018

Listeria monocytogenesis a foodborne pathogen that infects the placenta and can cause pregnancy complications. Listeriosis infections usually occur as sporadic infections, but large outbreaks are also reported. Virulence from clinical isolates is rarely analyzed due to the large number of animals required, but this knowledge could help guide the response to an outbreak. We implemented a DNA barcode system using signature tags that allowed us to efficiently assay variations in virulence across a large number of isolates. We tested 77 signature-tagged clones of clinicalL. monocytogenesstrains from 72 infected human placentas and five immunocompromised patients, all isolated since 2000. These strains were tested for virulence in a modified competition assay in comparison to the laboratory strain 10403S. We used twoin vivomodels of listeriosis: the non-pregnant mouse and the pregnant guinea pig. Strains that were frequently found at high abundance within infected organs were considered “hypervirulent,” while strains frequently found at low abundance were considered “hypovirulent.” Virulence split relatively evenly among hypovirulent, hypervirulent, and strains equally virulent to 10403S. The laboratory strain was found to have an intermediate virulence phenotype, supporting its suitability for pathogenesis studies. Further, we found that splenic and placental virulence are closely linked in both guinea pig and mouse models. This suggests that outbreak and sporadic pregnancy-associatedL. monocytogenesare not generally more virulent than lab reference strains. However, some strains did show consistent and reproducible virulence differences, suggesting that their further study may reveal deeper insights into the biological underpinnings of listeriosis.
Specialized mechanoreceptor systems in rodent glabrous skin
Authors: Walcher Jan , Ojeda-Alonso Julia , Haseleu Julia , Oosthuizen Maria K. , Rowe Ashlee H. , Bennett Nigel C. , Lewin Gary R.
Published: June 2018

Rodents use their forepaws to actively interact with their tactile environment. Studies on the physiology and anatomy of glabrous skin that makes up the majority of the forepaw are almost non-existent in the mouse. Here we developed a preparation to record from single sensory fibers of the forepaw and compared anatomical and physiological receptor properties to those of the hind paw glabrous and hairy skin. We found that the mouse forepaw skin is equipped with a very high density of mechanoreceptors; >3 fold more than hind paw glabrous skin. In addition, rapidly adapting mechanoreceptors that innervate Meissner’s corpuscles of the forepaw were several-fold more sensitive to slowly moving mechanical stimuli compared to their counterparts in the hind paw glabrous skin. All other mechanoreceptors types as well as myelinated nociceptors had physiological properties that were invariant regardless of which skin area they occupied. We discovered a novel D-hair receptor innervating a small group of hairs in the middle of the hind paw glabrous skin in mice. Glabrous D-hair receptors were direction sensitive albeit with an orientation sensitivity opposite to that described for hairy skin D-hair receptors. Glabrous D-hair receptors do not occur in all rodents, but are present in North American and African rodent species that diverged more than 65 million years ago. The function of these specialized hairs is unknown, but they are nevertheless evolutionarily very ancient. Our study reveals novel physiological specializations of mechanoreceptors in the glabrous skin that likely evolved to facilitate tactile exploration.
The genetic basis of mutation rate variation in yeast
Authors: Gou Liangke , Bloom Joshua S. , Kruglyak Leonid
Published: June 2018

Mutations are the root source of genetic variation and underlie the process of evolution. Although the rates at which mutations occur vary considerably between species, little is known about differences within species, or the genetic and molecular basis of these differences. Here we leveraged the power of the yeastSaccharomyces cerevisiaeas a model system to uncover natural genetic variants that underlie variation in mutation rate. We developed a high-throughput fluctuation assay and used it to quantify mutation rates in natural yeast isolates and in 1040 segregant progeny from a cross between BY, a lab strain, and RM, a wine strain. We observed that mutation rate varies among yeast strains and is highly heritable (H2=0.46). We performed linkage mapping in the segregants and identified four quantitative trait loci (QTLs) underlying mutation rate variation in the cross. We fine-mapped two QTLs to the underlying causal genes,RAD5andMKT1, that contribute to mutation rate variation. These genes also underlie sensitivity to the DNA damaging agents 4NQO and MMS, suggesting a connection between spontaneous mutation rate and mutagen sensitivity.
Genome-scale oscillations in DNA methylation during exit from pluripotency
Authors: Rulands Steffen , Lee Heather J , Clark Stephen J , Angermueller Christof , Smallwood Sébastien A , Krueger Felix , Mohammed Hisham , Dean Wendy , Nichols Jennifer , Rugg-Gunn Peter , Kelsey Gavin , Stegle Oliver , Simons Benjamin D , Reik Wolf
Published: June 2018

Pluripotency is accompanied by the erasure of parental epigenetic memory with naïve pluripotent cells exhibiting global DNA hypomethylation bothin vitroandin vivo. Exit from pluripotency and priming for differentiation into somatic lineages is associated with genome-widede novoDNA methylation. We show that during this phase, coexpression of enzymes required for DNA methylation turnover, DNMT3s and TETs, promotes cell-to-cell variability in this epigenetic mark. Using a combination of single-cell sequencing and quantitative biophysical modelling, we show that this variability is associated with coherent, genome-scale, oscillations in DNA methylation with an amplitude dependent on CpG density. Analysis of parallel single-cell transcriptional and epigenetic profiling provides evidence for oscillatory dynamics bothin vitroandin vivo. These observations provide fresh insights into the emergence of epigenetic heterogeneity during early embryo development, indicating that dynamic changes in DNA methylation might influence early cell fate decisions.

Highlights

Co-expression of DNMT3s and TETs drive genome-scale oscillations of DNA methylation

Oscillation amplitude is greatest at a CpG density characteristic of enhancers

Cell synchronisation reveals oscillation period and link with primary transcripts

Multiomic single-cell profiling provides evidence for oscillatory dynamicsin vivo
Stiffness as a control factor for object manipulation
Authors: Kennedy Scott D. , Schwartz Andrew B.
Published: June 2018

We act on the world by producing forces that move objects. During manipulation, force is exerted with the expectation that an object will move in an intended manner. This prediction is a learned coordination between force and displacement. Mechanically, impedance is a way to describe this coordination. As an efficient control strategy, object interaction could be anticipated by setting impedance before the hand moves the object. We examined this possibility with a paradigm in which subjects moved a handle to a specific target position along a track. The handle was locked in place until the subject exerted enough force to cross a specific threshold; then the handle was abruptly released and could move along the track. We hypothesized that this ballistic-release task would encourage subjects to modify their arm impedance in anticipation of the upcoming movement. If we consider the handle as an object, this paradigm loosely approximates the uncertainty encountered at the end of a reach when contacting a fixed object. We found that one component of arm impedance, stiffness, varied in a way that matched the behavioral demands of the task and we were able to dissociate stiffness from changes in force and displacement. We also found separate components of muscle activity that corresponded to stiffness and to changes in force. Our results show that subjects used a robust and efficient strategy to coordinate force and displacement by modulating muscle activity in a way that was behaviorally relevant in the task.

New & Noteworthy

The arm can behave like a spring, suggesting the concept of exerting force to move an object by selecting a spring of a certain length and stiffness that, respectively, depend on the movement and force requirements of the task. We show that these spring-like characteristics describe the strategy used to arrest a pre-loaded handle. These results extend our understanding of the arm’s spring-like behavior to include force and movement constraints, important factors for object interaction.
Yeast PAF1 complex restricts the accumulation of RNA polymerase III and counters the replication stress on the transcribed genes
Authors: Bhalla Pratibha , Vernekar Dipti , Shukla Ashutosh , Gilquin Benoit , Couté Yohann , Bhargava Purnima
Published: June 2018

Many regulatory proteins and complexes influence transcription by RNA polymerase (pol) II. In comparison, only a few regulatory proteins are known for pol III, which transcribes mostly house-keeping and non-coding genes. Yet, pol III transcription is precisely regulated under various stress conditions like starvation. We used pol III transcription complex components TFIIIC (Tfc6), pol III (Rpc128) and TFIIIB (Brf1) as baits to identify potential interactors through mass spectrometry-based proteomics. A large interactome constituting known chromatin modifiers, factors and regulators of transcription by pol I and pol II revealed the possibility of a large number of signaling cues for pol III transcription against adverse conditions. We found one of the pol II-associated factors, Paf1 complex (PAF1C) interacts with the three baits. Its occupancy on the pol III-transcribed genes is low and not correlated with pol III occupancy. Paf1 deletion leads to higher occupancy of pol III, γ-H2A and DNA pol2 but no change in nucleosome positions. Genotoxins exposure causes pol III but not Paf1 loss from the genes. PAF1C promotes the pol III pausing and restricts its accumulation on the genes, which reduces the replication stress caused by the pol III barrier and transcription-replication conflict on these highly transcribed genes.
Critical role of post-transcriptional regulation for IFN-γ in tumor-infiltrating T cells
Authors: Salerno Fiamma , Guislain Aurelie , Freen-van Heeren Julian J. , Nicolet Benoit P. , Young Howard A. , Wolkers Monika C.
Published: June 2018

Protective T cell responses against tumors require the production of Interferon gamma (IFN-γ). However, tumor-infiltrating T cells (TILs) gradually lose their capacity to produce IFN-γ and therefore fail to clear malignant cells. Dissecting the underlying mechanisms that block cytokine production is thus key for improving T cell products. Here we show that although TILs express substantial levels of Ifng mRNA, post-transcriptional mechanisms impede the production of IFN-γ protein due to loss of mRNA stability. CD28 triggering, but not PD1 blocking antibodies, effectively restores the stability of Ifng mRNA. Intriguingly, TILs devoid of AU-rich elements within the 3’untranslated region maintain stabilized Ifng mRNA and produce more IFN-γ protein than wild-type TILs. This sustained IFN-γ production translates into effective suppression of tumor outgrowth, which is almost exclusively mediated by direct effects on the tumor cells. We therefore conclude that post-transcriptional mechanisms could be modulated to potentiate effective T cell therapies in cancer.
Weakly supervised classification of aortic valve malformations using unlabeled cardiac MRI sequences
Authors: Fries Jason A. , Varma Paroma , Chen Vincent S. , Xiao Ke , Tejeda Heliodoro , Saha Priyanka , Dunnmon Jared , Chubb Henry , Maskatia Shiraz , Fiterau Madalina , Delp Scott , Ashley Euan , Ré Christopher , Priest James R.
Published: June 2018

Biomedical repositories such as the UK Biobank provide increasing access to prospectively collected cardiac imaging, however these data are unlabeled which creates barriers to their use in supervised machine learning. We develop a weakly supervised deep learning model for classification of aortic valve malformations using up to 4,000 unlabeled cardiac MRI sequences. Instead of requiring highly curated training data, weak supervision relies on noisy heuristics defined by domain experts to programmatically generate large-scale, imperfect training labels. For aortic valve classification, models trained with imperfect labels substantially outperform a supervised model trained on hand-labeled MRIs. In an orthogonal validation experiment using health outcomes data, our model identifies individuals with a 1.8-fold increase in risk of a major adverse cardiac event. This work formalizes a learning baseline for aortic valve classification and outlines a general strategy for using weak supervision to train machine learning models using unlabeled medical images at scale.
Detection of task-relevant and task-irrelevant motion sequences: application to motor adaptation in goal-directed and whole-body movements
Authors: Furuki Daisuke , Takiyama Ken
Published: June 2018

Motor variability is inevitable in our body movements and is discussed from several various perspectives in motor neuroscience and biomechanics; it can originate from the variability of neural activities, it can reflect a large degree of freedom inherent in our body movements, it can decrease muscle fatigue, or it can facilitate motor learning. How to evaluate motor variability is thus a fundamental question in motor neuroscience and biomechanics. Previous methods have quantified (at least) two striking features of motor variability; the smaller variability in the task-relevant dimension than in the task-irrelevant dimension and the low-dimensional structure that is often referred to as synergy or principal component. However, those previous methods were not only unsuitable for quantifying those features simultaneously but also applicable in some limited conditions (e.g., a method cannot consider motion sequence, and another method cannot consider how each motion is relevant to performance). Here, we propose a flexible and straightforward machine learning technique that can quantify task-relevant variability, task-irrelevant variability, and the relevance of each principal component to task performance while considering the motion sequence and the relevance of each motion sequence to task performance in a data-driven manner. We validate our method by constructing a novel experimental setting to investigate goal-directed and whole-body movements. Furthermore, our setting enables the induction of motor adaptation by using perturbation and evaluating the modulation of task-relevant and task-irrelevant variabilities through motor adaptation. Our method enables the identification of a novel property of motor variability; the modulation of those variabilities differs depending on the perturbation schedule. Although a gradually imposed perturbation does not increase both task-relevant and task-irrelevant variabilities, a constant perturbation increases task-relevant variability.
Proteomic Analysis of Rat Serum Revealed the Effects of Chronic Sleep Deprivation on Metabolic, Cardiovascular and Nervous System
Authors: Ma Bo , Chen Jincheng , Mu Yongying , Xue Bingjie , Zhao Aimei , Wang Daoping , Chang Dennis , Pan Yinghong , Liu Jianxun
Published: June 2018

Sleep is an essential and fundamental physiological process that plays crucial roles in the balance of psychological and physical health. Sleep disorder may lead to adverse health outcomes. The effects of sleep deprivation were extensively studied, but its mechanism is still not fully understood. The present study aimed to identify the alterations of serum proteins associated with chronic sleep deprivation, and to seek for potential biomarkers of sleep disorder mediated diseases. A label-free quantitative proteomics technology was used to survey the global changes of serum proteins between normal rats and chronic sleep deprivation rats. A total of 309 proteins were detected in the serum samples and among them, 117 proteins showed more than 1.8-folds abundance alterations between the two groups. Functional enrichment and network analyses of the differential proteins revealed a close relationship between chronic sleep deprivation and several biological processes including energy metabolism, cardiovascular function and nervous function. And four proteins including pyruvate kinase M1, clusterin, kininogen1 and profilin-1were identified as potential biomarkers for chronic sleep deprivation. The four candidates were validated via parallel reaction monitoring (PRM) based targeted proteomics. In addition, protein expression alteration of the four proteins was confirmed in myocardium and brain of rat model. In summary, the comprehensive proteomic study revealed the biological impacts of chronic sleep deprivation and discovered several potential biomarkers. This study provides further insight into the pathological and molecular mechanisms underlying sleep disorders at protein level.
Racemic mefloquinium chlorodifluoroacetate: crystal structure and Hirshfeld surface analysis
Authors: Wardell James L. , Wardell Solange M. S. V. , Jotani Mukesh M. , Tiekink Edward R. T.
Published: June 2018

In the racemic title molecular salt, C17H17F6N2O+·C2ClF2O3
− (systematic name: 2-{[2,8-bis(trifluoromethyl)quinolin-4-yl](hydroxy)methyl}piperidin-1-ium chlorodifluoroacetate), the cation, which is protonated at the piperidine N atom, has the shape of the letter, L, with the piperidin-1-ium group being approximately orthogonal to the quinolinyl residue [the Cq—Cm—Cm–Na (q = quinolinyl; m = methine; a = ammonium) torsion angle is 177.79 (18)°]. An intramolecular, charge-assisted ammonium-N—H...O(hydroxyl) hydrogen bond ensures the hydroxy-O and ammonium-N atoms lie to the same side of the molecule [Oh—Cm—Cm—Na (h = hydroxyl) = −59.7 (2)°]. In the crystal, charge-assisted hydroxyl-O—H...O−(carboxylate) and ammonium-N+—H...O−(carboxylate) hydrogen bonds generate a supramolecular chain along [010]; the chain is consolidated by C—H...O interactions. Links between chains to form supramolecular layers are of the type C—Cl...π(quinolinyl-C6) and the layers thus formed stack along the a-axis direction without directional interactions between them. The analysis of the calculated Hirshfeld surface points to the dominance of F...H contacts to the surface (40.8%) with significant contributions from F...F (10.5%) and C...F (7.0%) contacts.
Impact of enterprise mobile system implementation on organizational ambidexterity mediated through BPM customizability
Authors: Choudhary Praveen , Mital Monika , Pani Ashis Kumar , Papa Armando , Vicentini Francesca
Published: June 2018

Purpose

The purpose of this paper is to examine how organizational workers improve their perceived mobile user experience (UX) locus of control affected through organizational ambidexterity when using enterprise mobile systems (EMS). This study investigates the mediation role of business process customizability in the relationship between habitual use of EMS by individuals and organizational ambidexterity.

Design/methodology/approach

Over 150 possible respondent mobile phone users across 40 organizations in metropolitan National Capital Region (NCR) of Delhi with approximately were given the questionnaire. The data of a total of 121 NCR valid respondents aged between 22 and 49, after scrutinizing all collected questionnaires and removing those that had too many missing values or had the same answer to all questions, were used for analysis. The respondents were sampled from a research panel directory of a set of firms of the research firm hired for this survey.

Findings

The study finds complete mediation between the habitual use of EMS and organizational ambidexterity. Importantly, the empirical findings provide the research community with a deeper understanding of how EMS usage impacts organizational ambidexterity and individual’s UX locus of control.

Originality/value

It draws some newer areas of research with respect to interactions between enterprise mobile systems, business process customization due to enterprise mobile systems and organizational ambidexterity, which were hitherto unexplored.
Labor congestion in the automotive cluster: the role of wages
Authors: Mendoza-Velazquez Alfonso , Santillana José Antonio , Zárate-Mirón Viviana Elizabeth , Cabanas Martha
Published: June 2018

Purpose

The purpose of this study is to investigate labor congestion in the automotive industry in Mexico.

Design/methodology/approach

By using the cluster and subcluster definitions by Delgado et al. (2016) and relying on an efficiency and production function perspective, this study estimates a standard production function and measures marginal returns of labor at the regional cluster and subclusters levels. To assess whether wages affect the finding of congestion and productivity, the model also measures the individual impact of wages on both total productivity and marginal returns of labor.

Findings

Among other results, this paper finds evidence of labor congestion in the automotive cluster in Mexico. This congestion deepens with wages and it is specific to some regions and some subclusters.

Research limitations/implications

The methods used are based on panel data techniques but are fundamentally cross-section in nature. The time period available may condition these findings.

Originality/value

To the authors’ knowledge, this is the first study reporting congestion in the automotive cluster in Mexico.
Forecasting the next likely purchase events of insurance customers
Authors: Mau Stefan , Pletikosa Irena , Wagner Joël
Published: June 2018

Purpose

The purpose of this paper is to demonstrate the value of enriched customer data for analytical customer relationship management (CRM) in the insurance sector. In this study, online quotes from an insurer’s website are evaluated in terms of serving as a trigger event to predict churn, retention, and cross-selling.

Design/methodology/approach

For this purpose, the records of online quotes from a Swiss insurer are linked to records of existing customers from 2012 to 2015. Based on the data from automobile and home insurance policyholders, random forest prediction models for classification are fitted.

Findings

Enhancing traditional customer data with such additional information substantially boosts the accuracy for predicting future purchases. The models identify customers who have a high probability of adjusting their insurance coverage.

Research limitations/implications

The findings of the study imply that enriching traditional customer data with online quotes yields a valuable approach to predicting purchase behavior. Moreover, the quote data provide supplementary features that contribute to improving prediction performance.

Practical implications

This study highlights the importance of selecting the relevant data sources to target the right customers at the right time and to thus benefit from analytical CRM practices.

Originality/value

This paper is one of the first to investigate the potential value of data-rich environments for insurers and their customers. It provides insights on how to identify relevant customers for ensuing marketing activities efficiently and thus avoiding irrelevant offers. Hence, the study creates value for insurers as well as customers.
Farmer knowledge and willingness to pay for soil testing in Haiti
Authors: Kokoye Senakpon , Molnar Joseph , Jolly Curtis , Shannon Dennis , Huluka Gobena
Published: June 2018

Purpose

The purpose of this paper is to investigate factors affecting farmers’ perceptions and knowledge of soil testing benefits and fertilizers use in Northern Haiti.

Design/methodology/approach

Data were collected from 452 farmers within 17 localities in Northern Haiti. The findings reveal that farmers currently have little or no knowledge of soil testing benefits and but know better about fertilizer use. The soil testing benefits and knowledge on fertilizers use were collected using Likert scale. Analyses were done using structural equations model and choice model.

Findings

Factors such as farm size, participation in project, rice, banana and cocoa growers, affect farmers’ perceptions and knowledge of soil testing benefits. Factors affecting willingness to pay include group membership, type of crops grown, whether farmer’ land is on the slope, his farm size and whether he participates in the US Agency for International Development (USAID) project. Knowledge on fertilizer use is influenced by rice and banana growers, fertilizer use, participation in soil testing program and AVANSE/USAID. The effects of both latent variables are found to be positive but non-significant.

Practical implications

As policy implication; farmers need training module to be better informed on soil testing benefits.

Originality/value

Soil testing is a novel agricultural input that is being popularized in developing countries. For sustainability of the laboratory to be installed, this study is needed to fill the gap in research on farmers’ behaviors toward and demand of soil testing in Northern Haiti.