bluuebunny/crossref_metadata_2025 huggingface dataset:
Cx26 keratitis ichthyosis deafness syndrome mutations trigger alternative splicing of Cx26 to prevent expression and cause toxicityin vitro
Authors: Cook Jonathan , de Wolf Elizabeth , Dale Nicholas
Published: August 2019

The Cx26 mRNA has not been reported to undergo alternative splicing. In expressing a series of human keratitis ichthyosis deafness (KID) syndrome mutations of Cx26 (A88V, N14K and A40V), we found the production of a truncated mRNA product. These mutations, although not creating a cryptic splice site, appeared to activate a pre-existing cryptic splice site. The alternative splicing of the mutant Cx26 mRNA could be prevented by mutating the predicted 3′, 5′ splice sites and the branch point. The presence of a C-terminal fluorescent protein tag (mCherry or Clover) was necessary for this alternative splicing to occur. Strangely, Cx26A88Vcould cause the alternative splicing of co-expressed WT Cx26—suggesting a trans effect. The alternative splicing of Cx26A88Vcaused cell death, and this could be prevented by the 3′, 5′ and branch point mutations. Expression of the KID syndrome mutants could be rescued by combining them with removal of the 5′ splice site. We used this strategy to enable expression of Cx26A40V-5′and demonstrate that this KID syndrome mutation removed CO2sensitivity from the Cx26 hemichannel. This is the fourth KID syndrome mutation found to abolish the CO2-sensitivity of the Cx26 hemichannel, and suggests that the altered CO­2-sensitivity could contribute to the pathology of this mutation. Future research on KID syndrome mutations should take care to avoid using a C-terminal tag to track cellular localization and expression or if this is unavoidable, combine this mutation with removal of the 5′ splice site.
Why are some personalities less plastic?
Authors: Dubois Frédérique
Published: August 2019

Individuals from the same population typically show consistent differences in behavioural traits that are frequently associated with differences in contextual plasticity. Yet such a correlation might arise either because some individuals are better able than others to detect environmental changes or because the benefits of being plastic are condition-dependent. To discriminate between these two competing hypotheses, I developed an individual-based model that simulates a population in which individuals of varying fighting ability compete by pairwise interactions using either the fixed hawk (aggressive) or dove (peaceful) strategies or a conditional assessment strategy. As anticipated, the model predicts that only individuals with low (and/or intermediate) fighting ability should use the assessment strategy, giving rise to a negative (or dome-shaped) relationship between aggressiveness and plasticity. The proportion of plastic individuals, however, should be affected not only by the environmental conditions in which individuals live but also by the mechanism that would maintain variation in the traits that determine the benefits of plasticity. In particular, if individual differences in fighting ability may be eroded by natural selection, it predicts that ecological conditions that cause assortative interactions (e.g. high predation risks) would contribute in maintaining variation among individuals in their fighting ability, thereby favouring greater plasticity.
Enhanced mindfulness based stress reduction (MBSR+) in episodic migraine: a randomized clinical trial with MRI outcomes
Authors: Seminowicz David A. , Burrowes Shana AB , Kearson Alexandra , Zhang Jing , Krimmel Samuel R , Samawi Luma , Furman Andrew J , Keaser Michael L , Gould Neda F. , Magyari Trish , White Linda , Goloubeva Olga , Goyal Madhav , Peterlin B. Lee , Haythornthwaite Jennifer A.
Published: August 2019

We aimed to evaluate the efficacy of an enhanced mindfulness based stress reduction (MBSR+) versus stress management for headache (SMH). We performed a randomized, assessor-blind, clinical trial of 98 adults with episodic migraine recruited at a single academic center comparing MBSR+ (n=50) to SMH (n=48). MBSR+ and SMH were delivered weekly by group for 8 weeks, then bi-weekly for another 8 weeks. The primary clinical outcome was reduction in headache days from baseline to 20 weeks. MRI outcomes included activity of left dorsolateral prefrontal cortex (DLPFC) and cognitive task network during cognitive challenge, resting state connectivity of right dorsal anterior insula (daINS) to DLPFC and cognitive task network, and gray matter volume of DLPFC, daINS, and anterior midcingulate. Secondary outcomes were headache-related disability, pain severity, response to treatment, migraine days, and MRI whole-brain analyses. Reduction in headache days from baseline to 20 weeks was greater for MBSR+ (7.8 [95%CI, 6.9-8.8] to 4.6 [95%CI, 3.7-5.6]) than for SMH (7.7 [95%CI 6.7-8.7] to 6.0 [95%CI, 4.9-7.0]) (P=0.04). 52% of the MBSR+ group showed a response to treatment (50% reduction in headache days) compared with 23% in the SMH group (P=0.004). Reduction in headache-related disability was greater for MBSR+ (59.6 [95%CI, 57.9-61.3] to 54.6 [95%CI, 52.9-56.4]) than SMH (59.6 [95%CI, 57.7-61.5] to 57.5 [95%CI, 55.5-59.4])(P=0.02). There were no differences in clinical outcomes at 52 weeks or MRI outcomes at 20 weeks, although changes related to cognitive networks with MBSR+ were observed. MBSR+ is an effective treatment option for episodic migraine.
Map3k2-Regulated Intestinal Stromal Cells (MRISC) Define a Distinct Sub-cryptic Stem Cell Niche for Damage Induced Wnt Agonist R-spondin1 Production
Authors: Wu Ningbo , Sun Hongxiang , Zhao Xiaoyun , Chen Lei , Qi Yuanyuan , Han Yuheng , Liu Xianan , Gao Caixia , Wang Qun , He Lingjuan , Niu Xiaoyin , Liu Zhiduo , Li Hua-Bing , Zeng Yi Arial , Roulis Manolis , Liu Dou , Yang Zhengfeng , Zhou Bin , Flavell Richard A. , Su Bing
Published: August 2019

Intestinal stem cell propagation and differentiation are essential for rapid repair of tissue damage in the gut. While intestinal stromal cells were recently identified as key mediators of this process, the cellular and molecular mechanisms by which this diverse population induces tissue repair remains poorly understood. Here we show that Map3k2 has a colon stromal cell specific function critically required for maintenance of Lgr5+ intestinal stem cells and protection against acute intestinal damage. This Map3k2-specific function is mediated by enhancing Wnt agonist R-spondin1 production. We further reveal a unique novel cell population, named Map3k2-regulated intestinal stromal cells (MRISC), as the primary cellular source of R-spondin1 following intestinal injury. Together, our data identify a novel intestinal stem cell niche organized by MRISC, which specifically dependent on the Map3k2-signaling pathway to augment the production of Wnt agonist R-spondin1 and promote regeneration of the acutely damaged intestine.

Highlights

Map3k2 protects mice from DSS-induced colitis by promoting intestinal stem cell regeneration.

Map3k2-MAPK pathway cross-talks with Wnt signaling pathway via upregulation of R-spondin1.

Map3k2-Regulated Intestinal Stromal Cells (MRISC) marked by co-expression of CD90, CD34 and CD81 defines a novel colonic stem cell niche.
The interaction between elapsed time and decision accuracy differs between humans and rats
Authors: Shevinsky Carly A , Reinagel Pamela
Published: August 2019

A stochastic visual motion discrimination task is widely used to study rapid decision-making in humans and animals. Among trials of the same sensory difficulty within a block of fixed decision strategy, humans and monkeys are widely reported to make more errors in the individual trials with longer reaction times. This finding has posed a challenge for the drift-diffusion model of sensory decision-making, which in its basic form predicts that errors and correct responses should have the same reaction time distributions. We previously reported that rats also violate this model prediction, but in the opposite direction: for rats, motion discrimination accuracy was highest in the trials with the longest reaction times. To rule out task differences as the cause of our divergent finding in rats, the present study tested humans and rats using the same task and analyzed their data identically. We confirmed that rats’ accuracy increased with reaction time, whereas humans’ accuracy decreased with reaction time in the same task. These results were further verified using a new temporally-local analysis method, ruling out that the observed trend was an artifact of non-stationarity in the data of either species. The main effect was found whether the signal strength (motion coherence) was varied in randomly interleaved trials or held constant within a block. The magnitude of the effects increased with motion coherence. These results provide new constraints useful for refining and discriminating among the many alternative mathematical theories of decision-making.
Mutation of Ebola virus VP35 Ser129 uncouples interferon antagonist and replication functions
Authors: Morwitzer MJ , Corona A , Zinzula L , Fanunza E , Nigri C , Distinto S , Vornholt C , Kumar V , Tramontano E , Reid SP
Published: August 2019

Ebolaviruses are non-segmented, negative-sense RNA viruses (NNSVs) within the orderMononegaviralesthat possess the multifunctional virion protein 35 (VP35), a major determinant of virulence and pathogenesis that is indispensable for viral replication and host innate immune evasion. VP35 is functionally equivalent to the phosphoprotein (P) of other mononegaviruses such as rhabdoviruses and paramyxoviruses. Phosphorylation of the P protein is universally regarded as functionally important however, a regulatory role(s) of phosphorylation on VP35 function remains unexplored. Here, we identified a highly conserved Ser129 residue near the homo-oligomerization coiled coil motif, which is essential for VP35 functions. Affinity-purification MS followed by post-translational modification (PTM) analysis predicted phosphorylation of Ser129. Co-immunoprecipitation, cross-linking, and biochemical characterization studies revealed a moderately decreased capacity of VP35-S129A to oligomerize. Functional analysis showed that Ser-to-Ala substitution of Ebola virus (EBOV) VP35 did not affect IFN inhibitory activity but nearly abolished EBOV minigenome activity. Further coimmunoprecipitation studies demonstrated a lost interaction between VP35-S129A and the amino terminus of the viral polymerase but not between viral nucleoprotein (NP) or VP35-WT. Taken together, our findings provide evidence that phosphorylation modulates VP35 function, supporting VP35 as a NNSV P protein and providing a potentially valuable therapeutic target.

Importance

Ebola virus (EBOV) can cause severe disease in humans. The 2013-2016 West African epidemic and the two recent outbreaks in the Democratic Republic of the Congo underscore the urgent need for effective countermeasures, which remain lacking. A better understanding of EBOV biology and the modulation of multifunctional viral proteins is desperately needed to develop improved therapeutics. We provide evidence here that function of virion protein 35 (VP35) is modulated by phosphorylation of Ser129, a conserved residue among other ebolavirus species. These findings shed light on EBOV biology and present a potential target for broad acting anti-ebolavirus therapeutics.
SMART: An open source extension of WholeBrain for iDISCO+ LSFM intact mouse brain registration and segmentation
Authors: Jin Michelle , Nguyen Joseph D. , Weber Sophia J. , Mejias-Aponte Carlos A. , Madangopal Rajtarun , Golden Sam A.
Published: August 2019

Mapping immediate early gene (IEG) expression across intact brains is becoming a popular approach for identifying the brain-wide activity patterns underlying behavior. Registering whole brains to an anatomical atlas presents a technical challenge that has predominantly been tackled using automated voxel-based registration methods; however, these methods may fail when brains are damaged or only partially imaged, can be challenging to correct, and require substantial computational power. Here we present an open source package in R called SMART (semi-manual alignment to reference templates) as an extension to the WholeBrain framework for automated segmentation and semi-automated registration of experimental images to vectorized atlas plates from the Allen Brain Institute Mouse Common Coordinate Framework (CCF).

The SMART package was created with the novice programmer in mind and introduces a streamlined pipeline for aligning, registering, and segmenting large LSFM volumetric datasets with the CCF across the anterior-posterior axis, using a simple ‘choice game’ and interactive user-friendly menus. SMART further provides the flexibility to register partial brains or discrete user-chosen experimental images across the CCF, making it compatible with analysis of traditionally sectioned coronal brain slices. In addition to SMART, we introduce a modified tissue clearing protocol based on the iDISCO+ procedure that is optimized for uniform Fos antibody labeling and tissue clearing across whole intact mouse brains. Here we demonstrate the utility of the SMART-WholeBrain pipeline, in conjunction with the modified iDISCO+ Fos procedure, by providing example datasets alongside a full user tutorial. Finally, we present a subset of these data online in an interactive web applet. The complete SMART package is available for download on GitHub.
A Dual-sensing DNA Nanostructure with an Ultra-broad Detection Range
Authors: Kang Byunghwa , Park Soyeon V. , Soh H. Tom , Oh Seung Soo
Published: August 2019

Despite considerable interest in the development of biosensors that can measure analyte concentrations with a dynamic range spanning many orders of magnitude, this goal has proven difficult to achieve. We describe here a modular biosensor architecture that integrates two different readout mechanisms into a single-molecule construct that can achieve target detection across an extraordinarily broad dynamic range. Our dual-mode readout DNA biosensor (DMRD) combines an aptamer and a DNAzyme to quantify ATP with two different mechanisms, which respond to low (micromolar) and high (millimolar) concentrations by generating distinct readouts based on changes in fluorescence and absorbance, respectively. Importantly, we have also devised regulatory strategies to finely tune the target detection range of each sensor module by controlling the target-sensitivity of each readout mechanism. Using this strategy, we report the detection of ATP at a dynamic range spanning 1–500,000 μM—more than five orders of magnitude, representing the largest dynamic range reported to date with a single biosensor construct.
Drp1-mediated mitochondrial fission regulates calcium and F-actin dynamics during wound healing
Authors: Ponte Susana , Carvalho Lara , Gagliardi Maria , Campos Isabel , Oliveira Paulo J. , Jacinto António
Published: August 2019

Mitochondria adapt to cellular needs by changes in morphology through fusion and fission events, referred to as mitochondrial dynamics. Mitochondrial function and morphology are intimately connected and the dysregulation of mitochondrial dynamics is linked to several human diseases. In this work, we investigated the role of mitochondrial dynamics in wound healing in theDrosophilaembryonic epidermis. Mutants for mitochondrial fusion and fission proteins fail to close their wounds, indicating that the regulation of mitochondrial dynamics is required for wound healing. By live-imaging, we found that loss of function of the mitochondrial fission protein Dynamin-related protein 1 (Drp1) compromises the increase of cytosolic and mitochondrial calcium upon wounding and leads to F-actin defects at the wound edge, culminating in wound healing impairment. Our results highlight a new role for mitochondrial dynamics in the regulation of calcium and F-actin during epithelial repair.

We show that mitochondrial dynamics proteins are required for epithelial repair. In particular, Drp1 loss-of-function leads to defects in the dynamics of cytosolic and mitochondrial calcium and F-actin upon wounding.
Markov modelling of run length and velocity for molecular motors
Authors: Buchanan James L , Gilbert Robert P
Published: August 2019

Molecular motors are nanometer scale proteins involved in various in-tracellular processes such as cargo transport, muscle contraction and cell division. The steps in the chemo-mechanical cycle that use ATP hydrolysis to generate motion along the cytoskeletal tracks can be characterized by stepping rates depending only on the current state, permitting modeling of the cycle as a Markov process. To learn more about the nature of motor mo-tion, cell researchers have conducted in vitro experiments in which molecular motors pull beads along filaments attached to glass slides and their veloc-ity and run length until detachment from the microtubule are recorded. In this article a formula is derived for distance traveled until detachment. Combining this with a standard result for time to absorption for Markov processes gives a formula for velocity. Two kinesins, and two variants of myosin VI, for which there are run length and velocity measurements in the literature are considered. In each case the derived formulas for run length and velocity have a generalized Michaelis-Menten form as functions of ATP concentration. The degrees of the numerator and denominator polynomials increase with the complexity of chemo-mechanical cycle. The degrees of the Michaelis-Menten form determine the maximum number of of reaction rates that can be determined from experimental data on run length and velocity, however consistency conditions may reduce this number and restrict which rates can be determined.
Twister3: a simple and fast microwire twister
Authors: Newman Jonathan P. , Voigts Jakob , Borius Maxim , Karlsson Mattias , Harnett Mark T. , Wilson Matthew A.
Published: August 2019

We present Twister3, a microwire twisting machine. This device greatly increases the speed and repeatability of constructing twisted microwire neural probes (e.g. stereotrodes and tetrodes) compared to existing options. It is cheap, well documented, and all associated designs and source code are open-source. Twister3 is of interest to any lab performing twisted microwire neural recordings, for example, using tetrode drives.
On the evolution of sexual receptivity in female primates
Authors: Rooker Kelly , Gavrilets Sergey
Published: August 2019

There has been much interest in the evolutionary forces responsible for, and underlying the diversity in, female primate reproductive cycles. Some primate species are like humans, sexually receptive to mating throughout their entire estrus cycle, while other species are the opposite, receptive for mere hours out of their several-week cycles. Why is there such prominent variation in sexual receptivity length among primate species? Here we examine the evolutionary trade-offs associated with sexual receptivity length using mathematical modeling. We investigate how various factors, including having ovulation signs present vs. concealed ovulation, female physiological costs, and group size, each influence the length of females’ receptive periods. We find that both continuous receptivity and very short lengths of receptivity are able to evolve. Our model predicts that increasing the impacts of infanticide will increase the length of the female receptive period, emphasizing the possible importance of paternity confusion. Similar effects can also be achieved by increasing the non-genetic benefits provided by males. Overall, our work offers a theoretical framework for understanding the evolution and diversity of mating traits in female primates.
Genomic predictive ability for foliar nutritive traits in perennial ryegrass
Authors: Arojju Sai Krishna , Cao Mingshu , Jahufer M. Z. Zulfi , Barrett Brent A , Faville Marty J
Published: August 2019

Forage nutritive value impacts animal nutrition, which underpins livestock productivity, reproduction and health. Genetic improvement for nutritive traits has been limited, as they are typically expensive and time-consuming to measure through conventional methods. Genomic selection is appropriate for such complex and expensive traits, enabling cost-effective prediction of breeding values using genome-wide markers. The aims of the present study were to assess the potential of genomic selection for a range of nutritive traits in a multi-population training set, and to quantify contributions of genotypic, environmental and genotype-by-environment (G × E) variance components to trait variation and heritability for nutritive traits. The training set consisted of a total of 517 half-sibling (half-sib) families, from five advanced breeding populations, evaluated in two distinct New Zealand grazing environments. Autumn-harvested samples were analyzed for 18 nutritive traits and maternal parents of the half-sib families were genotyped using genotyping-by-sequencing. Significant (P<0.05) genotypic variation was detected for all nutritive traits and genomic heritability (h2g) was moderate to high (0.20 to 0.74). G × E interactions were significant and particularly large for water soluble carbohydrate (WSC), crude fat, phosphorus (P) and crude protein. GBLUP, KGD-GBLUP and BayesC genomic prediction models displayed similar predictive ability, estimated by 10-fold cross validation, for all nutritive traits with values ranging fromr= 0.16 to 0.45 using phenotypes from across two environments. High predictive ability was observed for the mineral traits sulphur (0.44), sodium (0.45) and magnesium (0.45) and the lowest values were observed for P (0.16), digestibility (0.22) and high molecular weight WSC (0.23). Predictive ability estimates for most nutritive traits were retained when marker number was reduced from 1 million to as few as 50,000. The moderate to high predictive abilities observed suggests implementation of genomic selection is feasible for most of the nutritive traits examined. For traits with lower predictive ability, multi-trait genomic prediction approaches that exploit the strong genetic correlations observed amongst some nutritive traits may be useful. This appears to be particularly important for WSC, considered one of the primary constituent of nutritive value for forages.
24-hour multi-omics analysis of residential sewage reflects human activity and informs public health
Authors: Matus Mariana , Duvallet Claire , Soule Melissa Kido , Kearney Sean M. , Endo Noriko , Ghaeli Newsha , Brito Ilana , Ratti Carlo , Kujawinski Elizabeth B. , Alm Eric J.
Published: August 2019

High-throughput molecular analysis of sewage is a promising tool for precision public health. Here, we combine sewer network and demographic data to identify a residential catchment for sampling, and explore the potential of applying untargeted genomics and metabolomics to sewage to collect actionable public health data. We find that wastewater sampled upstream in a residential catchment is representative of the human microbiome and metabolome, and we are able to identify glucuronidated compounds indicative of direct human excretion, which are typically degraded too quickly to be detected at treatment plants. We show that diurnal variations during 24-hour sampling can be leveraged to discriminate between biomarkers in sewage that are associated with human activity from those related to the environmental background. Finally, we putatively annotate a suite of human-associated metabolites, including pharmaceuticals, food metabolites, and biomarkers of human health and activity, suggesting that mining untargeted data derived from residential sewage can expand currently-used biomarkers with direct public health or policy relevance.
bioPROTACs as versatile modulators of intracellular therapeutic targets: Application to proliferating cell nuclear antigen (PCNA)
Authors: Lim Shuhui , Khoo Regina , Peh Khong Ming , Teo Jinkai , Chang Shih Chieh , Ng Simon , Beilhartz Greg L. , Melnyk Roman A. , Johannes Charles W. , Brown Christopher J. , Lane David P. , Henry Brian , Partridge Anthony W.
Published: August 2019

Targeted degradation approaches have recently generated much excitement as a paradigm shift to address human disease in unprecedented ways. Amongst these, small molecule based approaches such as Proteolysis targeting chimeras (PROTACs) have attracted the lion’s share of attention due to their potential to tackle historically intractable targets and achieve greater potency, efficacy, and specificity over traditional small molecule inhibitors. Despite their promise, the identification of high-affinity ligands that can serve as starting points for PROTAC strategies remains challenging. As a complementary approach, we describe herein a class of intracellular biologics termed bioPROTACs. The substrate binding component of these fusion proteins consists of a peptide or an antibody-mimetic which allows for an unprecedented diversity of protein targets that can be addressed. The high-affinity binder is linked directly to an E3 ubiquitin ligase to harness the power of targeted degradation. Using GFP-tagged proteins as model substrates, we show that there is considerable flexibility in both the choice of substrate binders (binding positions, scaffold-class) and the E3 ligases. Indeed, 9 out of 16 binder-E3 combinations tested resulted in greater than 70% target clearance. Through a systematic approach, we then identified a highly effective bioPROTAC against an oncology target, proliferating cell nuclear antigen (PCNA), a sliding DNA clamp with critical roles in DNA replication and repair. The bioPROTAC, termed Con1-SPOP, elicited rapid and robust PCNA degradation and associated effects on DNA synthesis and cell cycle progression. Compared to RNAi-based approaches which typically take days to manifest, PCNA knockdown using Con1-SPOP was evident within 4 h. The advantage of degradation versus stoichiometric inhibition was also clearly demonstrated with bioPROTAC strategies. Combining superior pharmacological inhibition and relative ease of development, bioPROTACs are powerful tools for interrogating the degradability of a substrate, for guiding the identification of the fittest E3 ligase, for studying the functional consequences associated with target protein down-regulation, and potentially for making therapeutic impacts.
C. difficile-associated antibiotics prime the host for infection by a microbiome-independent mechanism
Authors: Kester Jemila C. , Brubaker Douglas K. , Velazquez Jason , Wright Charles , Lauffenburger Douglas A. , Griffith Linda G.
Published: August 2019

The most clinically relevant risk factor for Clostridioides difficile-associated disease (CDAD) is recent antibiotic treatment. Though most broad-spectrum antibiotics significantly disrupt the structure of the gut microbiota, only particular ones increase CDAD risk, suggesting additional factors might increase the risk from certain antibiotics. Here we show that commensal-independent effects of antibiotics collectively prime an in vitro germ-free human gut for CDAD. We found a marked loss of mucosal barrier and immune function with CDAD-associated antibiotic pretreatment distinct from pretreatment with an antibiotic unassociated with CDAD, which did not reduce innate immune or mucosal barrier functions. Importantly, pretreatment with CDAD-associated antibiotics sensitized mucosal barriers to C. difficile toxin activity in primary cell-derived enteroid monolayers. These data implicate commensal-independent host changes in the increased risk of CDAD with specific antibiotics. Our findings are contrary to the previously held belief that antibiotics allow for CDAD solely through disruption of the microbiome. We anticipate this work to suggest potential avenues of research for host-directed treatment and preventive therapies for CDAD, and to impact human tissue culturing protocols.
Gamma oscillations during episodic memory processing reveal reversal of information flow between the hippocampus and prefrontal cortex
Authors: Seger Sarah , Rugg Michael D. , Lega Bradley C.
Published: August 2019

A critical and emerging question in human episodic memory is how the hippocampus interacts with the prefrontal cortex during the encoding and retrieval of items and their contexts. In the present study, participants performed an episodic memory task (free recall) while intracranial electrodes were simultaneously inserted into the hippocampus and multiple prefrontal locations, allowing the quantification of relative onset times of gamma band activity in the cortex and the hippocampus in the same individual. We observed that in left anterior ventrolateral prefrontal cortex (aVLPFC) gamma band activity onset was significantly later than in the hippocampus during memory encoding, whereas its activity significantly preceded that in the hippocampus during memory retrieval. These findings provide direct evidence to support models of prefrontal-hippocampal interactions derived from studies of rodents, but suggest that in humans, it is the aVLPFC rather than medial prefrontal cortex that demonstrate these reciprocal interactions.
Modulation of articulation muscles during listening and reading: a matter of intention to speak out loud
Authors: Zur Naama , Eviatar Zohar , Karni Avi
Published: August 2019

The articulation of speech sounds is often contingent on the intention to subsequently produce other sounds (co-articulation). Thus, intended acts affect the way current acts are executed. We show that the intention to subsequently repeat a short sentence, overtly or covertly, significantly modulated articulatory muscle activity already during speech perception or reading (input interval) and when delaying response (i.e., prior to production). Young adults were instructed to read (whole sentences or word-by-word) or listen to recordings of sentences to be repeated afterwards, either covertly or overtly. Surface electromyography (sEMG) recordings showed different patterns of articulatory muscle modulation in the two articulatory muscles measured – orbicularis oris inferior (OOI) and sternohyoid (STH). In the OOI, activity increased relative to baseline during speech perception or reading in both intended output conditions (overt and covert); in the STH, articulatory muscle activity decreased, during the input intervals, in both intended output conditions. However, the modulations in EMG activity were contingent on the intention to subsequently repeat the input overtly or covertly, so that activation in the OOI, and inhibition in the STH, were significantly more pronounced when overt responses were intended. Input modality was also a factor; immediately before overt responses, activity in the OOI muscle increased for listening and word-by-word reading, but not in reading whole sentences. The current results suggest that speech perception and articulation interact already during the input phase, listening or reading, reflecting the intended responses. However, this interaction may differentially affect facial-articulatory and laryngeal control mechanisms of speech production.
Comprehensive Analysis of Human Subtelomeres by Whole Genome Mapping
Authors: Young Eleanor , Abid Heba Z. , Kwok Pui-Yan , Riethman Harold , Xiao Ming
Published: August 2019

Detailed comprehensive knowledge of the structures of individual long-range telomere-terminal haplotypes are needed to understand their impact on telomere function, and to delineate the population structure and evolution of subtelomere regions. However, the abundance of large evolutionarily recent segmental duplications and high levels of large structural variations have complicated both the mapping and sequence characterization of human subtelomere regions. Here, we use high throughput optical mapping of large single DNA molecules in nanochannel arrays for 154 human genomes from 26 populations to present a comprehensive look at human subtelomere structure and variation. The results catalog many novel long-range subtelomere haplotypes and determine the frequencies and contexts of specific subtelomeric duplicons on each chromosome arm, helping to clarify the currently ambiguous nature of many specific subtelomere structures as represented in the current reference sequence (HG38). The organization and content of some duplicons in subtelomeres appear to show both chromosome arm and population-specific trends. Based upon these trends we estimate a timeline for the spread of these duplication blocks.

Author Summary

The ends of human chromosomes have caps called telomeres that are essential. These telomeres are influenced by the portions of DNA next to them, a region known as the subtelomere. We need to better understand the subtelomeric region to understand how it impacts the telomeres. This subtelomeric region is not well described in the current references. This is due to large variations in this region and portions that are repeated many times, making current sequencing technologies struggle to capture these regions. Many of these variations are evolutionary recent. Here we use 154 different samples from the 26 geographic regions of the world to gain a better understanding of the variation in these regions. We found many new haplotypes and clarified the haplotypes existing in the current reference. We then examined population and chromosome specific trends.
Growth behavior and glyphosate resistance level in 10 biotypes ofEchinochloa colonain Australia
Authors: Mahajan Gulshan , Kaur Vishavdeep , Thompson Michael , Chauhan Bhagirath S.
Published: August 2019

Recently, poor control ofEchinochloa colonawith glyphosate has been reported in no-till agriculture systems of the northern grain region (NGR) of Australia. Two experiments were conducted using 10 biotypes ofE. colonaselected from the NGR of Australia to understand differences in their growth behavior and resistance pattern. Growth studies revealed that these biotypes differed in plant height (53-70 cm plant−1), tiller production (30-52 tillers plant−1), leaf production (124-186 leaves plant−1) and seed head production (37-65 seed heads plant−1). Days taken to seed heads and shoot biomass in these biotypes ranged between 40-48 d and 21-27 g plant−1, respectively. Seed production in these biotypes ranged between 5380 and 10244 seeds plant−1; lowest for biotype B17/25 and highest for biotype B17/13. Correlation studies revealed that seed number plant−1had a positive correlation with plant height (r= 0.67), tiller number plant−1(r= 0.89), leaf number plant−1(r= 0.73), seed heads plant−1(r= 0.78), seed head weight (r= 0.79), shoot biomass (r= 0.77) and root biomass (r= 0.46). The glyphosate dose-response study showed a wide range of responses in these biotypes and the glyphosate dose required to reduce 50% biomass (GR50values) was estimated between 217 to 2159 g a.e. glyphosate ha−1. GR50values of biotypes B17/16, B 17/34 and B17/35 were 719, 2159 and 884 g ha−1, respectively, making them 3, 10 and 4-fold resistant to glyphosate compared with the susceptible biotype B17/37. Growth behavior and seed production potential in these biotypes had no correlation with the resistance index. These results suggest that some biotypes ofE. colonaare highly problematic; for example, biotype B17/34 was not only highly glyphosate-resistant, but also produced a high seed number (9300 seeds plant−1). This study demonstrated that there is a possibility of great risk with the increased use of glyphosate for managingE. colonain the NGR of Australia. The results warrant integrated weed management strategies and improved stewardship guidelines are required for managing glyphosate-resistant biotypes ofE. colonaand to restrict further movement of resistant biotypes to other regions of Australia.
N-Tosyl-L-proline benzene hemisolvate: a rare example of a hydrogen-bonded carboxylic acid dimer with symmetrically disordered H atoms
Authors: Wojnarska Joanna , Ostrowska Katarzyna , Gryl Marlena , Stadnicka Katarzyna Marta
Published: August 2019

The carboxylic acid group is an example of a functional group which possess a good hydrogen-bond donor (–OH) and acceptor (C=O). For this reason, carboxylic acids have a tendency to self-assembly by the formation of hydrogen bonds between the donor and acceptor sites. We present here the crystal structure of N-tosyl-L-proline (TPOH) benzene hemisolvate {systematic name: (2S)-1-[(4-methylbenzene)sulfonyl]pyrrolidine-2-carboxylic acid benzene hemisolvate}, C12H15NO4S·0.5C6H6, (I), in which a cyclic R
2
2(8) hydrogen-bonded carboxylic acid dimer with a strong O—(1 \over 2H)...(1 \over 2H)—O hydrogen bond is observed. The compound was characterized by single-crystal X-ray diffraction and NMR spectroscopy, and crystallizes in the space group I2 with half a benzene molecule and one TPOH molecule in the asymmetric unit. The H atom of the carboxyl OH group is disordered over a twofold axis. An analysis of the intermolecular interactions using the noncovalent interaction (NCI) index showed that the TPOH molecules form dimers due to the strong O—(1 \over 2H)...(1 \over 2H)—O hydrogen bond, while the packing of the benzene solvent molecules is governed by weak dispersive interactions. A search of the Cambridge Structural Database revealed that the disordered dimeric motif observed in (I) was found previously only in six crystal structures.
Futures of new post-truth: new research frontiers on disturbingly fascinating pathologies affecting information dissemination and knowledge production
Authors: Ahen Frederick
Published: August 2019

Purpose

The purpose of this study is to explore in depth the anatomy of post-truth in the quest to set a new research agenda. The author interrogates knowledge production/dissemination and the political positions of those behind them. This study diagnoses and challenges existing claims of supremacy of certain hegemonic epistemological and ontological orthodoxies that have been weaponized.

Design/methodology/approach

This study philosophically engages with different worlds of credible ‘pluriversal’ knowledge(s) and leads to the exposure of historically ‘taken-for-granted’ definitions of the nature and composition of acceptable truth and how it is deeply entrenched in interest group politics.

Findings

Each generation in different contexts has had to battle with specific troubling forces of deception and organized hypocrisy. Here, both new social actors and incumbents influence the disgruntled, deceive the gullible or connect with the enlightened masses at the emotional level whilst strongly undermining the rules-of-logic and fact-based discourses using disruptive social media technologies. The author specifies how the five P’s: political power, profits, populism, politics and the private visions of technologists and scientists will continue to play very influential roles in how knowledge production will affect future policies and global governance.

Social implications

Based on historicized explanations, the author argues that deception and mass ignorance as weaponized features of global governance and its capitalist order are typical Machiavellian strategies for gaining control over knowledge production/information dissemination. Massive changes are not expected in the future unless society and academia introduce novel science, technology and political platforms for engaging society and policy-makers.

Originality/value

The author provides ample historical illustrations to support the claims made in this study that public insights into the postulated structures of post-truth remain extremely superficial, making people insufficiently informed to engage in crucial discourses about knowledge production and dissemination that affect their futures. This study provides several ingredients for stimulating further debate.
Thermal analysis and post construction verification
Authors: Flood Cormac , Scott Lloyd
Published: August 2019

Purpose

The residential sector in Ireland accounted for 25 per cent of energy related CO2 emissions in 2016 through burning fossil fuels, a major contributor to climate change. In support of Ireland’s CO2 reduction targets, the existing housing stock could contribute greatly to the reduction of space-heating energy demand through retrofit. Approximately 50 per cent of Ireland’s 2m dwellings pre-date building regulations and are predominantly of cavity and solid wall construction, the performance of which has not been extensively investigated at present. Although commitment to thermal upgrade/retrofit of existing buildings may increase under future government policies, the poor characterisation of actual thermal performance of external walls may hinder the realisation of these targets. Thermal transmittance (U-values) of exterior walls represents a source of uncertainty when estimating the energy performance of dwellings. It has been noted in research that the standard calculation methodology for thermal transmittance should be improved. Implementing current U-value calculation methods may result in misguided retrofit strategies due to the considerable discrepancies between in situ measurements and calculated wall U-values as documented in the case studies carried out in this research. If the method of hygrothermal analysis were to be employed as a replacement for the current standard calculation, it could have significant implications for policy and retrofit decision making. The paper aims to discuss this issue.

Design/methodology/approach

This research project analysed a case study situated in Dublin, Ireland. The case studies offer an account of the in situ thermal transmittance of exterior walls and link these to hygrothermally simulated comparisons along with more traditional design U-values.

Findings

The findings of this research identify discrepancies between in situ and design U-values, using measurement, hygrothermal simulation and standard method U-value calculations. The outcomes of the research serve as an introduction to issues emanating from a larger research project in order to encourage researchers to understand and further explore the topic.

Originality/value

It has previously been highlighted that moisture content is linked to the increase in thermal conductivity of building materials, thus reducing the thermal effectiveness and increasing the elemental U-value. Therefore, it is vital to implement reliable prediction tools to assess potential thermal performance values. This paper presents the findings of a critical instance case study in Dublin, Ireland in which an existing west facing external wall in a semi-detached dwelling was analysed, simulated and measured to verify the elemental wall assembly and quantify thermal transmittance (U-value) incorporating the major criteria required for building performance simulation.
Barriers to low-carbon warehousing and the link to carbon abatement
Authors: Goh Shao Hung
Published: August 2019

Purpose

Warehouses are large emitters of greenhouse gases and their impact on climate change is under increasing focus. The purpose of this paper is to investigate the barriers that inhibit the adoption of low-carbon warehousing in Asia-Pacific and their links to carbon abatement performance.

Design/methodology/approach

An exploratory conceptual model was first developed from a literature review of the general barriers to sustainable supply chain practices and hence potentially in low-carbon warehousing. A large contract logistics services provider in the Asia-Pacific served as the subject of a case study. The perceived barriers to low-carbon warehousing were derived from an internal survey of respondents from the case company and regressed against carbon abatement outcomes at that organization’s operations across the region.

Findings

Results show that the case company reduced carbon emissions by 36 percent on a revenue-normalized basis between 2008 and 2014, but with relatively lower success in emerging markets vs mature markets. An Elastic Net regression analysis confirms that technology and government-related factors are the most important barriers in the case company’s efforts to “decarbonize” its local warehousing operations. However, results suggest that the customer-related barrier, which is highly correlated with the government barrier, is in part driven by the latter.

Research limitations/implications

This case study is based on a single multinational company in Asia-Pacific, but nonetheless serves as an impetus for more cross-sectional studies to form an industry-wide view.

Originality/value

An extended stewardship framework based on the natural resource-based view has been proposed, in which logistics services providers take on a proactive boundary-spanning role to lower the external barriers to low-carbon warehousing.
Self-neglect and safeguarding adult reviews: towards a model of understanding facilitators and barriers to best practice
Authors: Preston-Shoot Michael
Published: August 2019

Purpose

The purpose of this paper is twofold: first, to update the core data set of self-neglect safeguarding adult reviews (SARs) and accompanying thematic analysis; second, to draw together the learning available from this data set of reviews to propose a model of good practice that can be used as the basis for subsequent SARs.

Design/methodology/approach

Further published reviews are added to the core data set from the websites of Safeguarding Adults Boards (SABs). Thematic analysis is updated using the four domains employed previously. A sufficient number of reviews have been performed from which to construct an evidence-based model of good practice. A framework is presented with the proposition that this can be used as a proportional methodology for further SARs where self-neglect is in focus.

Findings

Familiar findings emerge from the thematic analysis. This level of analysis, constructed over time and across reviews, enables a framework to be developed that pulls together the findings into a model of good practice with individuals who self-neglect and for policies and procedures with which to support those practitioners involved in such cases. This framework can then be used as an evidence-based model with which to review new cases where SARs are commissioned.

Research limitations/implications

The national database of reviews commissioned by SABs is incomplete and does not contain many of the SARs reported in this evolving data set. The Care Act 2014 does not require publication of reports but only a summary of findings and recommendations in SAB annual reports. It is possible, therefore, that this data set is also incomplete. Drawing together the findings from the reviews nonetheless enables conclusions to be proposed about the components of effective practice, and effective policy and organisational arrangements for practice. Future reviews can then explore what enables such effective to be achieved and what barriers obstruct the realisation of effective practice.

Practical implications

Answering the question “why” is a significant challenge for SARs. A framework is presented here, drawn from research on SARs featuring self-neglect, that enables those involved in reviews to explore the enablers and barriers with respect to an evidence-based model of effective practice. The framework introduces explicitly research and review evidence into the review process.

Originality/value

The paper extends the thematic analysis of available reviews that focus on work with adults who self-neglect, further building on the evidence base for practice. The paper also proposes a new approach to SARs by using the findings and recommendations systematically within a framework designed to answer “why” questions – what promotes and what obstructs effective practice.