bluuebunny/crossref_metadata_2025 huggingface dataset:
Caenorhabditis elegans ADAR editing and the ERI-6/7/MOV10 RNAi pathway silence endogenous viral elements and LTR retrotransposons
Authors: Fischer Sylvia E. J. , Ruvkun Gary
Published: October 2019

Endogenous retroviruses and LTR retrotransposons are mobile genetic elements that are closely related to retroviruses. Desilenced endogenous retroviruses are associated with human autoimmune disorders and neurodegenerative diseases. C. elegans and related Caenorhabdites contain LTR retrotransposons and, as described here, numerous integrated viral genes including viral envelope genes that are part of LTR retrotransposons. We found that both LTR retrotransposons and endogenous viral elements are silenced by ADARs (adenosine deaminases acting on double-stranded RNA (dsRNA)) together with the endogenous RNAi factor ERI-6/7, a homolog of Mov10 helicase, a retrotransposon and retrovirus restriction factor in human. siRNAs corresponding to integrated viral genes and LTR retrotransposons, but not to DNA transposons, are dependent on the ADARs and ERI-6/7; on the contrary, siRNAs corresponding to palindromic repeats are increased in adar-eri mutants because of an antiviral RNAi response to dsRNA. Silencing of LTR retrotransposons is dependent on downstream RNAi factors and P granule components but is independent of the viral sensor DRH-1/RIG-I and the nuclear Argonaute NRDE-3. The activation of retrotransposons in the ADAR- and ERI-6/7/MOV10-defective mutant is associated with the induction of the Unfolded Protein Response (UPR), a common response to viral infection. The overlap between genes induced upon viral infection and infection with intracellular pathogens, and genes co-expressed with retrotransposons, suggests that there is a common response to different types of foreign elements that includes a response to proteotoxicity presumably caused by the burden of replicating pathogens and expressed retrotransposons.

SIGNIFICANCE

Silencing of transposable elements and viruses is critical for the maintenance of genome integrity, cellular homeostasis and organismal health. Here we describe multiple factors that control different types of transposable elements, providing insight into how they are regulated. We also identify stress response pathways that are triggered upon mis-regulation of these transposable elements. The conservation of these factors and pathways in human suggests that our studies in C. elegans can provide general insight into the regulation of and response to transposable elements and viruses.
Genome-wide diversity of coconut from northern South America uncovers genotypes present in Colombia and strong population structure
Authors: Muñoz-Pérez Jorge Mario , Cañas Gloria Patricia , López Lorena , Arias Tatiana
Published: October 2019

Coconut palms (Cocos nucifera) are a combination of wild admixed populations and perennial crops with a worldwide distribution. Here we develop single nucleotide polymorphisms (SNPs) along the coconut genome based on Genotyping by Sequencing (GBS) for at least four different commercially important and widely cultivated coconut varieties and hybrids growing in northern South America. We present a comprehensive catalog of approximately 27K SNPs to conduct genetic diversity, population structure and linkage disequilibrium analysis. A relatively fast LD decay for the Atlantic accessions within ~250Kb was observed in comparison to the Pacific accessions ~ 1500 Kb.

The complete SNPs sampling showed a strong population structure at K = 2, separating accessions from the Pacific and Atlantic coasts as it has been found in previous studies. At higher K values, one non-admixed group was observed for the Atlantic while further substructures emerged for the Pacific accessions, where three non-admixed groups were found. Population structure analysis also showed a great degree of admixture between the Atlantic and Pacific populations, and SNPs of the Pacific non-admixed genetic groups were mostly introgressed into the Atlantic individuals but the contrary was rarely observed. The results of principal component analysis and Neighbor-Joining Hierarchical Clustering were consistent with the results from Structure and provided a measure of genetic relationships among individual genotypes. The Pacific group has a lower genetic diversity and a higher rate of inbreeding than the Atlantic group. These results suggest that the Pacific coconuts of Colombia belong to the pre-Columbian population found on the Pacific coast of Panama and Peru. If it had been introduced after Columbus (as in Mexico), genetic diversity would have been higher than on the Atlantic coast.
Prediction of druggable proteins using machine learning and functional enrichment analysis: a focus on cancer-related proteins and RNA-binding proteins
Authors: López-Cortés Andrés , Cabrera-Andrade Alejandro , Cruz-Segundo Carlos M. , Dorado Julian , Pazos Alejandro , Gonzáles-Díaz Humberto , Paz-y-Miño César , Pérez-Castillo Yunierkis , Tejera Eduardo , Munteanu Cristian R.
Published: October 2019

Background

Druggable proteins are a trending topic in drug design. The druggable proteome can be defined as the percentage of proteins that have the capacity to bind an antibody or small molecule with adequate chemical properties and affinity. The screening and in silico modeling are critical activities for the reduction of experimental costs.

Methods

The current work proposes a unique prediction model for druggable proteins using amino acid composition descriptors of protein sequences and 13 machine learning linear and non-linear classifiers. After feature selection, the best classifier was obtained using the support vector machine method and 200 tri-amino acid composition descriptors.

Results

The high performance of the model is determined by an area under the receiver operating characteristics (AUROC) of 0.975 ± 0.003 and accuracy of 0.929 ± 0.006 (3-fold cross-validation). Regarding the prediction of cancer-associated proteins using this model, the best ranked druggable predicted proteins in the breast cancer protein set were CDK4, AP1S1, POLE, HMMR, RPL5, PALB2, TIMP1, RPL22, NFKB1 and TOP2A; in the cancer-driving protein set were TLL2, FAM47C, SAGE1, HTR1E, MACC1, ZFR2, VMA21, DUSP9, CTNNA3 and GABRG1; and in the RNA-binding protein set were PLA2G1B, CPEB2, NOL6, LRRC47, CTTN, CORO1A, SCAF11, KCTD12, DDX43 and TMPO.

Conclusions

This powerful model predicts several druggable proteins which should be deeply studied to find better therapeutic targets and thus improve clinical trials. The scripts are freely available at https://github.com/muntisa/machine-learning-for-druggable-proteins.
Inline Liquid Chromatography-Fast Photochemical Oxidation of Proteins Allows for Targeted Structural Analysis of Conformationally Heterogeneous Mixtures
Authors: Tadi Surendar , Misra Sandeep K. , Sharp Joshua S.
Published: October 2019

Structural analysis of proteins in a conformationally heterogeneous mixture has long been a difficult problem in structural biology. In structural analysis by covalent labeling mass spectrometry, conformational heterogeneity results in data reflecting a weighted average of all conformers, complicating data analysis and potentially causing misinterpretation of results. Here, we describe a method coupling size exclusion chromatography (SEC) with hydroxyl radical protein footprinting using inline fast photochemical oxidation of proteins (FPOP). Using a controlled synthetic mixture of holomyoglobin and apomyoglobin, we demonstrate that we can achieve accurate footprints of each conformer using LC-FPOP when compared to off-line FPOP of each pure conformer. We then applied LC-FPOP to analyze the adalimumab heat-shock aggregation process. We found that the LC-FPOP footprint of unaggregated adalimumab was consistent with a previously published footprint of the native IgG. The LC-FPOP footprint of the aggregation product indicated that heat shock aggregation primarily protected the hinge region, suggesting this region is involved with the heat shock aggregation process of this molecule. LC-FPOP offers a new method to probe dynamic conformationally heterogeneous mixtures such as biopharmaceutical aggregates, and obtain accurate information on the topography of each conformer.
Phosphorylation on PstP regulates cell wall metabolism and antibiotic tolerance in Mycobacterium smegmatis
Authors: Shamma Farah , Papavinasasundaram Kadamba , Quintanilla Samantha Y. , Bandekar Aditya , Sassetti Christopher , Boutte Cara C.
Published: October 2019

Mycobacterium tuberculosis and its relatives, like many bacteria, have dynamic cell walls that respond to environmental stresses. Modulation of cell wall metabolism in stress is thought to be responsible for decreased permeability and increased tolerance to antibiotics. The signaling systems that control cell wall metabolism under stress, however, are poorly understood. Here, we examine the cell wall regulatory function of a key cell wall regulator, the Serine Threonine Phosphatase PstP, in the model organism Mycobacterium smegmatis. We show that the peptidoglycan regulator CwlM is a substrate of PstP. We find that a phospho-mimetic mutation, pstP T171E, slows growth, mis-regulates both mycolic acid and peptidoglycan metabolism in different conditions, and interferes with antibiotic tolerance. These data suggest that phosphorylation on PstP affects its activity against various substrates and is important in the transition between growth and stasis.

Importance

Regulation of cell wall assembly is essential for bacterial survival and contributes to pathogenesis and antibiotic tolerance in mycobacteria, including pathogens such as Mycobacterium tuberculosis. However, little is known about how the cell wall is regulated in stress. We describe a pathway of cell wall modulation in Mycobacterium smegmatis through the only essential Ser/Thr phosphatase, PstP. We showed that phosphorylation on PstP is important in regulating peptidoglycan metabolism in the transition to stasis and mycolic acid metabolism in growth. This regulation also affects antibiotic tolerance in growth and stasis. This work helps us to better understand the phosphorylation-mediated cell wall regulation circuitry in Mycobacteria.
Cortical morphology predicts placebo response in multiple sclerosis
Authors: Cherkasova Mariya V. , Fu Jessie F. , Jarrett Michael , Johnson Poljanka , Abel Shawna , Tam Roger , Rauscher Alexander , Sossi Vesna , Kolind Shannon , Li David , Sadovnick A. Dessa , Machan Lindsay , Girard J. Marc , Emond Francois , Vosoughi Reza , Traboulsee Anthony , Stoessl A. Jon
Published: October 2019

Although significant insights have been gained into the neural mechanisms of acute placebo responses, less is known about the mechanisms of longer-term placebo responses, such as those seen in clinical trials, or the interactions between these mechanisms and brain disease. We examined neuropathological and morphological brain correlates of placebo responses in a randomized clinical trial of a controversial endovascular treatment (“liberation therapy”) for multiple sclerosis. Patients were randomized to receive either balloon or sham extracranial venoplasty and followed for 48 weeks. The trial did not support therapeutic efficacy of venoplasty, but a subset of both venoplasty- and sham-treated patients reported an improvement in health-related quality of life that peaked at 12 weeks following treatment, suggesting a placebo response. Placebo responders had higher lesion activity than placebo non-responders. Although placebo responders did not differ from non-responders in terms of total normalized brain volume, regional grey or white matter volume or cortical thickness, graph theoretical analysis of cortical thickness covariance showed that placebo non-responders had a more homogenous cortical thickness topology with a more small-world-like architecture. In placebo non-responders, lesion load inversely predicted cortical thickness in primary somatosensory and motor areas, association areas, precuneus and insula, primarily in the right hemisphere. In placebo responders, lesion load was unrelated to cortical thickness. The neuropathological process in MS may result in a cortical configuration that is less suited to functional integration and less capable of generating a sustained placebo response.
Functional architecture of motion direction in the mouse superior colliculus
Authors: Li Ya-tang , Turan Zeynep , Meister Markus
Published: October 2019

Motion vision is important in guiding animal behavior. Both the retina and the visual cortex process object motion in largely unbiased fashion: all directions are represented at all locations in the visual field. We investigate motion processing in the superior colliculus of the awake mouse, by optically recording neural responses across both hemispheres. Within the retinotopic map, one finds large regions of ∼500 μm size where neurons prefer the same direction of motion. This preference is maintained in depth to ∼350 μm. The scale of these patches, ∼30 deg of visual angle, is much coarser than the animal’s visual resolution. A global map of motion direction shows approximate symmetry between the left and right hemispheres and a net bias for upward-nasal motion in the upper visual field. Unlike other parts of the early visual system, the superior colliculus develops a locally biased representation of object motion.
A peptide inhibitor of Tau-SH3 interactions ameliorates amyloid-β toxicity
Authors: Rush Travis , Roth Jonathan R. , Thompson Samantha J. , Aldaher Adam R. , Cochran J. Nicholas , Roberson Erik D.
Published: October 2019

The microtubule-associated protein Tau is strongly implicated in Alzheimer’s disease (AD) and aggregates into neurofibrillary tangles in AD. Genetic reduction of Tau is protective in several animal models of AD and cell culture models of amyloid-β (Aβ) toxicity, making it an exciting therapeutic target for treating AD. A variety of evidence indicates that Tau’s interactions with Fyn kinase and other SH3 domain–containing proteins, which bind to PxxP motifs in Tau’s proline-rich domain, may contribute to AD deficits and Aβ toxicity. Thus, we sought to determine if inhibiting Tau-SH3 interactions ameliorates Aβ toxicity. We developed a peptide inhibitor of Tau-SH3 interactions and a proximity ligation assay (PLA)-based target engagement assay. Then, we used membrane trafficking and neurite degeneration assays to determine if inhibiting Tau-SH3 interactions ameliorated Aβ oligomer (Aβo)-induced toxicity in primary hippocampal neurons from rats. We verified that Tau reduction ameliorated Aβo toxicity in neurons. Using PLA, we identified a peptide inhibitor that reduced Tau-SH3 interactions in HEK-293 cells and primary neurons. This peptide reduced Tau phosphorylation by Fyn without affecting Fyn’s kinase activity state. In primary neurons, endogenous Tau-Fyn interaction was present primarily in neurites and was reduced by the peptide inhibitor, from which we inferred target engagement. Reducing Tau-SH3 interactions in neurons ameliorated Aβo toxicity by multiple outcome measures, namely Aβo-induced membrane trafficking abnormalities and neurite degeneration. Our results indicate that Tau-SH3 interactions are critical for Aβo toxicity and that inhibiting them is a promising therapeutic target for AD.
Robustness of bidirectional microtubule network self-organization
Authors: Płochocka Aleksandra Z. , Davie Alexander M. , Bulgakova Natalia. A. , Chumakova Lyubov
Published: October 2019

Robustness of biological systems is crucial for their survival, however, for many systems its origin is an open question. Here we analyze one sub-cellular level system, the microtubule cytoskeleton. Microtubules self-organize into a network, along which cellular components are delivered to their biologically relevant locations. While individual microtubule are highly dynamic with their dynamics depends on the organism environment and genetics, network sensitivity to this dynamics would result in pathologies. Combining mathematical modelling with genetic manipulations inDrosophila, we show that the microtubule self-organization indeed does not depend on dynamics of individual microtubules, and thus is robust on the tissue level. We demonstrate the origin of this robustness via a mathematical model, suggesting this being a generic mechanism.
Distinct roles for motor cortical and thalamic inputs to striatum during motor learning and execution
Authors: Wolff Steffen B. E. , Ko Raymond , Ölveczky Bence P.
Published: October 2019

The acquisition and execution of learned motor sequences are mediated by a distributed motor network, spanning cortical and subcortical brain areas. The sensorimotor striatum is an important cog in this network, yet how its two main inputs, from motor cortex and thalamus respectively, contribute to its role in motor learning and execution remains largely unknown. To address this, we trained rats in a task that produces highly stereotyped and idiosyncratic motor sequences. We found that motor cortical input to the sensorimotor striatum is critical for the learning process, but after the behaviors were consolidated, this corticostriatal pathway became dispensable. Functional silencing of striatal-projecting thalamic neurons, however, disrupted the execution of the learned motor sequences, causing rats to revert to behaviors produced early in learning and preventing them from re-learning the task. These results show that the sensorimotor striatum is a conduit through which motor cortical inputs can drive experience-dependent changes in subcortical motor circuits, likely at thalamostriatal synapses.
Obesity Potentiates TH2 Immunopathology via Dysregulation of PPARγ
Authors: Bapat Sagar P. , Liang Yuqiong , Liu Sihao , Zhang Ling-juan , Vogel Ian , Mar Darryl J. , Zhou Carmen , Choi Eun Jung , Chang Christina , He Nanhai , Lee In-kyu , Suh Jae Myoung , Crotty Alexander Laura E. , Liddle Christopher , Atkins Annette R. , Yu Ruth T. , Downes Michael , Ansel K. Mark , Marson Alexander , Gallo Richard L. , Evans Ronald M. , Zheng Ye
Published: October 2019

How obesity affects immune function is not well understood. Clinically, obesity is strongly associated with severe TH2 immunopathology1-3, though the physiological, cellular, and molecular underpinnings of this association remain obscure. Here, we demonstrate that obese mice are susceptible to severe atopic dermatitis (AD), a major manifestation of TH2 immunopathology and disease burden in humans4,5. Mechanistically, we show that dysregulation of the nuclear hormone receptor (NHR) PPARγ (peroxisome proliferator-activated receptor gamma) in T cells is a causal link between obesity and the increased TH2 immunopathology. We find that PPARγ oversees a cellular metabolic transcriptional program that restrains nuclear gene expression of the chief TH2 priming and effector cytokine interleukin-4 (IL-4). Accordingly, thiazolidinediones (TZDs), potent PPARγ agonists, robustly protect obese mice from TH2 immunopathology. Collectively, these findings establish PPARγ as a molecular link between obesity and TH2 immune homeostasis and identify TZDs as novel therapeutic candidates for TH2 immunopathology. Fundamentally, these findings demonstrate that shifting physiologic metabolic states can shape the tone of adaptive immune responses to modulate differential disease susceptibility.
Distinct medial-temporal lobe mechanisms of encoding and amygdala-mediated memory reinstatement for disgust and fear
Authors: Riegel Monika , Wierzba Małgorzata , Wypych Marek , Ritchey Maureen , Jednoróg Katarzyna , Grabowska Anna , Vuilleumier Patrik , Marchewka Artur
Published: October 2019

Remembering events that evoke emotions such as disgust or fear is critical to our survival. However, previous studies investigating the interplay between emotion and memory disregarded the effects of specific emotions, leading to inconsistent results. Also, the role of amygdala throughout memory stages has been poorly understood. Here, we show that after 3 weeks delay, word pairs evoking disgust were remembered better than pairs evoking fear. These two emotions distinctly modulated neural mechanisms of memory. Successful encoding of disgust-evoking information was mediated by univariate activation in amygdala and perirhinal cortex, in contrast to fear-evoking memories that engaged hippocampus and parahippocampal gyrus. Critically, univariate activation in the amygdala during encoding was correlated with memory reinstatement of individual word pairs, and more so for disgust than for fear. Together, these findings shed a new light on the role of the amygdala and medial temporal lobe regions in encoding and reinstatement of specific emotional memories.
Developmental plasticity of hearing sensitivity in red-eared sliderTrachemys scripta elegans
Authors: Wang Jichao , Li Handong , Wang Tongliang , Chen Bo , Cui Jianguo , Shi Haitao
Published: October 2019

Developmental plasticity of hearing sensitivity (DPHS) has been verified in some groups of vertebrates. Turtles face a trade-off between terrestrial and aquatic hearing in different acoustic environments throughout ontogeny. However, how chelonian hearing sensitivity changes throughout ontogeny is still unclear. To verify DPHS in turtles, auditory brainstem responses (ABR) were compared using hearing thresholds and latencies in female red-eared slider (Trachemys scripta elegans) aged 1 week, 1 month, 1 year, and 5 years, and the results showed hearing sensitivity bandwidths of approximately 200–1100, 200–1100, 200–1300, and 200–1400 Hz, respectively. The lowest threshold sensitivity was approximately 600□Hz. Below 600 Hz, ABR threshold decreased rapidly with increasing age (1 week to 1 year), with significant differences between age groups, but no significant difference between the 1- and 5-year age groups (stimulus frequency, 200–600 Hz). Above 600 Hz, ABR threshold was the lowest in the 5-year age group. These findings show that aging was accompanied by hearing sensitivity changes, suggesting rapid, frequency-segmented development during ontogeny. This variability in hearing sensitivity differs from that reported in other vertebrates, and allows adaptation to acoustically distinct environments throughout ontogeny. Our findings further elucidate the developmental patterns of the vertebrate auditory system.
Presynaptic α2δ subunits are key organizers of glutamatergic synapses
Authors: Schöpf Clemens L. , Geisler Stefanie , Stanika Ruslan I. , Campiglio Marta , Kaufmann Walter A. , Nimmervoll Benedikt , Schlick Bettina , Shigemoto Ryuichi , Obermair Gerald J.
Published: October 2019

In nerve cells the genes encoding for α2δ subunits of voltage-gated calcium channels (VGCCs) have been linked to synaptic functions and neurological disease. Here we show that α2δ subunits are essential for the formation and organization of glutamatergic synapses. Using a cellular α2δ subunit triple loss-of-function model, we demonstrate a failure in presynaptic differentiation associated with the downscaling of postsynaptic AMPA receptors and the postsynaptic density. The role of α2δ isoforms as synaptic organizers is highly redundant, as each individual α2δ isoform can rescue presynaptic calcium channel trafficking and expression of synaptic proteins. Mutating the MIDAS site in α2δ-2 dissociates rescuing presynaptic synapsin expression from calcium channel trafficking, suggesting that the regulatory role of α2δ subunits is independent from its role as a calcium channel subunit. Our findings influence the current view on excitatory synapse formation. Firstly, our study suggests that postsynaptic differentiation is secondary to presynaptic differentiation. Secondly, the dependence of presynaptic differentiation on α2δ implicates α2δ subunits as potential nucleation points for the organization of synapses. Finally, our results suggest that α2δ subunits act as trans-synaptic organizers of glutamatergic synapses, thereby aligning the synaptic active zone with the postsynaptic density.
Data-driven modelling of mutational hotspots and in-silico predictors in hypertrophic cardiomyopathy
Authors: Waring A.J. , Harper A.R. , Salatino S. , Kramer C.M. , Neubauer S , Thomson K.L. , Watkins H. , Farrall M.
Published: October 2019

Background

Although rare-missense variants in Mendelian disease-genes have been noted to cluster in specific regions of proteins, it is not clear how to consider this information when evaluating the pathogenicity of a gene or variant. Here we introduce methods for gene-association and variant-interpretation that utilise this powerful signal.

Methods

We present a case-control rare-variant association test, ClusterBurden, that combines information on both variant-burden and variant-clustering. We then introduce a data-driven modelling framework to estimate mutational hotspots in genes with missense variant-clustering and integrate further in-silico predictors into the models.

Results

We show that ClusterBurden can increase statistical power to scan for putative disease-genes, driven by missense variants, in simulated data and a 34-gene panel dataset of 5,338 cases of hypertrophic cardiomyopathy. We demonstrate that data-driven models can allow quantitative application of the ACMG criteria PM1 and PP3, to resolve a wide range of pathogenicity potential amongst variants of uncertain significance. A web application (Pathogenicity_by_Position) is accessible for missense variant risk prediction of six sarcomeric genes and an R package is available for association testing using ClusterBurden.

Conclusion

The inclusion of missense residue position enhances the power of disease-gene association and improves rare-variant pathogenicity interpretation.
CrysX: crystallographic tools for the Android platform
Authors: Sharma Manas , Mishra Debabrata
Published: October 2019

A set of crystallographic tools for computational modelling and manipulation of molecular structures as well as resolving problems related to crystal structure determination, amongst many other tools for performing multidisciplinary research work, have been developed for the Android platform. Superior graphics quality and ergonomics are the trademarks of this nascent software package, CrysX. The tools are packaged as Android applications (apps) that offer an easy-to-use graphical user interface to perform a lot of complex tasks that were once limited to desktop applications. Various tasks including modelling of structures for density functional theory calculations, diffraction pattern simulation and analysis, structure analysis, and calculation of equilibrium energy, bulk modulus, volume etc., can be performed with ease by using smartphones or tablets. The apps aim to increase the productivity of computational condensed matter physicists, chemists and material scientists. The apps can be downloaded and used for free from the Google Play Store or via the link https://bragitoff.com/crysx.
Crystal structure, Hirshfeld surface analysis and PIXEL calculations of a 1:1 epimeric mixture of 3-[(4-nitrobenzylidene)amino]-2(R,S)-(4-nitrophenyl)-5(S)-(propan-2-yl)imidazolidin-4-one
Authors: Gomes Ligia R. , Low John Nicolson , Wardell James L. , Souza Marcus V. N. de , Costa Cristiane F. da
Published: October 2019

A 1:1 epimeric mixture of 3-[(4-nitrobenzylidene)amino]-2(R,S)-(4-nitrophenyl)-5(S)-(propan-2-yl)imidazolidin-4-one, C19H19N5O5, was isolated from a reaction mixture of 2(S)-amino-3-methyl-1-oxobutanehydrazine and 4-nitrobenzaldehyde in ethanol. The product was derived from an initial reaction of 2(S)-amino-3-methyl-1-oxobutanehydrazine at its hydrazine group to provide a 4-nitrobenzylidene derivative, followed by a cyclization reaction with another molecule of 4-nitrobenzaldehyde to form the chiral five-membered imidazolidin-4-one ring. The formation of the five-membered imidazolidin-4-one ring occurred with retention of the configuration at the 5-position, but with racemization at the 2-position. In the crystal, N—H...O(nitro) hydrogen bonds, weak C—H...O(carbonyl) and C—H...O(nitro) hydrogen bonds, as well as C—H...π, N—H...π and π–π interactions, are present. These combine to generate a three-dimensional array. Hirshfeld surface analysis and PIXEL calculations are also reported.
Crystal structure of a two-dimensional coordination polymer of formula [Zn(NDC)(DEF)] (H2NDC is naphthalene-2,6-dicarboxylic acid and DEF is N,N-diethylformamide)
Authors: Saffon-Merceron Nathalie , Vigroux Alain , Hoffmann Pascal
Published: October 2019

A zinc metal–organic framework, namely poly[bis(N,N-diethylformamide)(μ4-naphthalene-2,6-dicarboxylato)(μ2-naphthalene-2,6-dicarboxylato)dizinc(II)], [Zn(C12H6O4)(C15H11NO)]
n
, built from windmill-type secondary building units and forming zigzag shaped two-dimensional stacked layers, has been solvothermally synthesized from naphthalene-2,6-dicarboxylic acid and zinc(II) acetate as the metal source in N,N-diethylformamide containing small amounts of formic acid.
Antibody fragments structurally enable a drug-discovery campaign on the cancer target Mcl-1
Authors: Luptak Jakub , Bista Michal , Fisher David , Flavell Liz , Gao Ning , Wickson Kate , Kazmirski Steven L. , Howard Tina , Rawlins Philip B. , Hargreaves David
Published: October 2019

Apoptosis is a crucial process by which multicellular organisms control tissue growth, removal and inflammation. Disruption of the normal apoptotic function is often observed in cancer, where cell death is avoided by the overexpression of anti-apoptotic proteins of the Bcl-2 (B-cell lymphoma 2) family, including Mcl-1 (myeloid cell leukaemia 1). This makes Mcl-1 a potential target for drug therapy, through which normal apoptosis may be restored by inhibiting the protective function of Mcl-1. Here, the discovery and biophysical properties of an anti-Mcl-1 antibody fragment are described and the utility of both the scFv and Fab are demonstrated in generating an Mcl-1 crystal system amenable to iterative structure-guided drug design.
Bis[2-(dimethylamino-κN)-α,α-diphenylbenzenemethanolato-κO](tetrahydrofuran-κO)magnesium(II)
Authors: Al-Masri Harbi Tomah
Published: October 2019

The title magnesium complex, [Mg(C21H20NO2)2(C4H8O)]
n
, exhibits two N,O-bidentate 2-(dimethylamino)-α,α-diphenylbenzenemethanolate ligands, forming two six-membered chelate rings. The distorted square-pyramidal coordination sphere of the MgII atom is completed by the O atom of a tetrahydrofuran ligand, with its O atom in the apical position. The O and N atoms are in a mutual trans arrangement. Except for two C—H...π interactions, no significant intermolecular interactions are observed in the crystal.
Impact of IoT on social innovation in Japan
Authors: Shenkoya Temitayo , Dae-Woo Cho
Published: October 2019

Purpose

Recently, the discussion on the impact of the Internet of Things (IoT) in theory and in practice is increasing. While some proponent envisage that the IoT will bring about positive radical change in the modern society, others argue that the IoT will introduce more disadvantages in the long run (mainly in terms of job losses) than advantages. The purpose of this paper is to arbitrate this controversy by examining the impact of IoT on the Japanese society.

Design/methodology/approach

While previous studies have largely been qualitative in nature, in this study, a quantitative approach was used. A multi-dimensional analysis was carried out and the statistical method known as the one-way analysis of variance was used to process the data obtained during this study.

Findings

The results show that indeed the IoT has a positive impact on the daily lives of the Japanese people, however the change it brings are mainly incremental change and not radical. Furthermore, rather than reducing job opportunities, it has created more opportunities and simplified operation processes.

Research limitations/implications

However, a limitation of this study is in its narrow scope. It is important to note that further studies on an international level or perhaps multi-national level is needed. Furthermore, there may be other underlining factors, such as culture, social, economic, geographical location, technology capacity, that may contribute to the impact of the IoT on daily life. Therefore, future research needs to verify if indeed this is the case.

Originality/value

This research successful arbitrates the argument about the impact of the IoT on the society by specifically showing that the advantages brought by the IoT out-ways its disadvantages. Furthermore, the uncertainty (fear of job losses) expressed by some experts was addressed in this study. The results obtained showed that the diffusion of the IoT has no correlation with job loss but rather supports improved working environment and creation of jobs.
Habitat structure drives the evolution of aerial displays in birds
Authors: Menezes João C. T. , Santos Eduardo S. A.
Published: October 2019

John Endler's sensory drive hypothesis posits that physical properties of the environment may shape signalling traits by determining how effective they are in communicating. Evidence abounds of signalling environment driving selection on colours and vocalizations, yet little is known about its influence on visual signals produced via body movements (i.e., gestural displays).

Here, we aimed to perform the most taxonomically comprehensive assessment of sensory drive by testing the hypothesis that habitat structure drives the evolution of aerial sexual displays in passerine birds (order Passeriformes). We base this hypothesis on physical properties of habitats that should allow aerial displays to transmit more broadly in open habitats.

To test the hypothesis, we performed Bayesian phylogenetic comparative analyses using species‐level phylogenetic trees and a dataset of 469 species from across the Americas.

We found that evolutionary gain of aerial displays is on average six times more frequent in open‐habitat passerines than in forest ones.

The influence of habitat structure on the evolution of aerial sexual displays attests to the importance of sensory drive as a deterministic evolutionary force within sexual selection, as opposed to models that assume a purely arbitrary direction of sexual trait evolution.
Variation in selective regimes drives intraspecific variation in life‐history traits and migratory behaviour along an elevational gradient
Authors: Lundblad Carl G. , Conway Courtney J.
Published: October 2019

Comparative studies, across and within taxa, have made important contributions to our understanding of the evolutionary processes that promote phenotypic diversity. Trait variation along geographic gradients provides a convenient heuristic for understanding what drives and maintains diversity. Intraspecific trait variation along latitudinal gradients is well‐known, but elevational variation in the same traits is rarely documented. Trait variation along continuous elevational gradients, however, provides compelling evidence that individuals within a breeding population may experience different selective pressures.

Our objectives were to quantify variation in a suite of traits along a continuous elevational gradient, evaluate whether individuals in the population experience different selective pressures along that gradient and quantify variation in migratory tendency along that gradient.

We examined variation in a suite of 14 life‐history, morphological and behavioural traits, including migratory tendency, of yellow‐eyed juncos along a continuous 1000‐m elevational gradient in the Santa Catalina Mountains of Arizona.

Many traits we examined varied along the elevational gradient. Nest survival and nestling growth rates increased, while breeding season length, renesting propensity and adult survival declined, with increasing elevation. We documented the migratory phenotype of juncos (partial altitudinal migrants) and show that individual migratory tendency is higher among females than males and increases with breeding elevation.

Our data support the paradigm that variation in breeding season length is a major selective pressure driving life‐history variation along elevational gradients and that individuals breeding at high elevation pursue strategies that favour offspring quality over offspring quantity. Furthermore, a negative association between adult survival and breeding elevation and a positive association between nest survival and breeding elevation help explain both the downslope and reciprocal upslope seasonal migratory movements that characterize altitudinal migration in many birds. Our results demonstrate how detailed studies of intraspecific variation in suites of traits along environmental gradients can lend new insights into the evolutionary processes that promote diversification and speciation, the causes of migratory behaviour, and how animal populations will likely respond to climate change.
Intraspecific variation in body size of bumblebee workers influences anti‐predator behaviour
Authors: Gavini Sabrina S. , Quintero Carolina , Tadey Mariana
Published: October 2019

Flower‐dwelling predators make flowers dangerous foraging sites for pollinators, potentially affecting their anti‐predator behaviour. Moreover, predation vulnerability often varies among pollinators' body sizes with interspecific comparisons showing that smaller species are more vulnerable than larger ones. However, how intraspecific body size variation influences pollinator behaviour under predation risk is still unknown, especially under natural conditions.

We hypothesized that bumblebee workers of different sizes will exhibit different foraging strategies under predation risk. We predict that (a) small workers should more often exhibit anti‐predator behaviours than larger workers. We also hypothesized that the anti‐predator behaviour should be influenced by predator size and reward availability; therefore, we expect (b) higher avoidance behaviour towards larger predator sizes and (c) more and longer visits to inflorescences with high nectar availability. Finally, we expect that (d) nectar availability should overcome the anti‐predator behaviour in less vulnerable, large, workers.

We recorded flower visitation, time spent and rejection behaviours of different sizes of Bombus terrestris (Apidae) workers (large, medium and small) to inflorescences of Alstroemeria aurea (Alstroemeriaceae) with different treatments of artificial spiders (small and large) and nectar availability (with, without).

Anti‐predator and foraging behaviour of bumblebees was affected by the size of the worker, the presence of artificial spiders and nectar availability. Large and medium size bumblebees strongly reduced flower visitation and time spent in the presence of artificial spiders, consistently avoiding flowers with spiders, regardless of spider size or nectar availability. Instead, small bumblebees seldom modified their behaviour when facing artificial spiders, only increasing their avoidance or decreasing their foraging time in nectarless flowers hosting large artificial spiders.

This pattern of larger workers being more sensitive to predation risk than smaller ones at the intraspecific level in B. terrestris is contrary to the expected and acknowledged trend based on previous interspecific comparisons, but partially consistent with predictions of models of optimal foraging theory. Intraspecific behavioural variability was uncovered only when nectar was available, whereas artificial predator size rarely modified bumblebee anti‐predator and foraging behaviour. Therefore, our findings suggest that the trade‐off between maximizing resource intake and minimizing predation risk strongly varies across bumblebee worker body sizes.
Plastic leaf morphology in three species of Quercus: The more exposed leaves are smaller, more lobated and denser
Authors: Kusi Joseph , Karsai Istvan
Published: October 2019

Phenotypic plasticity and developmental instability in leaf traits are common in oak species but the role of environmental factors is not well understood. To decipher possible correlations between different leaf traits and effects of the position of leaves within the tree canopy, we quantified the plasticity of three leaf traits of 30 trees of Quercus alba L., Quercus palustris Muench and Quercus velutina Lam. We hypothesized that trees could modify the shape of their leaves for better adaptation to the variable microclimate within the canopy. Our results demonstrated that the south and north outer leaves were significantly smaller, more lobed and denser than those situated in the inner canopy. The order of leaves on the branch accounted for the plasticity of leaf traits in Q. alba only. Plasticity of lobing in Q. alba and Q. velutina depended on the height of the trees. We detected fluctuating asymmetry (FA) in all three species, but the source of variation depended on branch position in Q. velutina only. FA was more pronounced in north‐facing leaves. Plasticity of the leaf traits ranged from small to medium. Plasticity of leaf area and leaf mass per area (LMA) depended on the branch position. However, the plasticity of lobation was not affected by the location of a branch within the tree canopy. Quercus alba and Q. palustris had similar plastic responses but the plasticity of Q. velutina was significantly smaller. We concluded that individual plants detect and cope with environmental stress through vegetative organ modification.
An Analysis of Hounsfield Unit Values and Volumetrics from Computerized Tomography of the Proximal Femur for Sex and Age Estimation
Authors: Ford Jonathan M. , Kumm Todd R. , Decker Summer J.
Published: October 2019

Sex and age are two elements in the establishment of a biological profile for forensic identification. While the pelvic bones are the most ideal structures for sex estimation, the condition of a body is not always ideal due to the nature of death, such as in mass disasters, or postmortem processes. This study utilized CT scans and resultant 3D models of 100 male and 100 female adults of known ages ranging from 18 to 98 years old to collect volumetric and Hounsfield unit measurements of the proximal femur. Equations were created to establish logistic regression models for sex estimation and linear regression models for age estimation. The resultant sex estimation method had an accuracy of 93.5% and utilized the volume of the proximal femur. This study provides three linear regression models for age with an accuracy range of 86%–92% ±12 years. As imaging technologies are increasingly adopted for forensic purposes, the power of 3D data will provide the opportunity for more quantitative and reproducible analyses. The proposed method for sex and age estimation provides a reliable tool that can be utilized in both day‐to‐day casework and disaster victim identification.
Ultrasound versus magnetic resonance imaging in the evaluation of shoulder joint pathologies in a cohort of rheumatoid arthritis patients
Authors: Abdelzaher Mohamed Gamal , Tharwat Samar , AbdElkhalek Ahmed , Abdelsalam Adel
Published: October 2019

Background

Rheumatoid arthritis (RA) is a systemic autoimmune disease that has a great impact on different joints, may result in their destruction and loss of function. Although the shoulder is affected in a large portion of patients with RA, it does not receive much attention during the follow up of RA. The precise diagnosis of shoulder pain in RA is a clinical challenge and benefits from a reliable imaging modality to detect its exact origin.

Aim

To determine the diagnostic accuracy of ultrasound (US) in detecting shoulder joint pathologies in RA, considering magnetic resonance imaging (MRI) as the gold standard.

Materials and Methods

This cross‐sectional, observational study was carried out on 30 RA patients complaining of unilateral or bilateral shoulder pain. Patients were subjected to history taking, clinical shoulder examination, plain X‐ray, US examination following a standardized protocol, and MRI. The results were correlated with each other.

Results

In comparison with the MRI findings, US showed high accuracy in terms of sensitivity (Sn) and specificity (Sp) in supraspinatus tendinopathy (Sn 96.6%; Sp 93.3%), biceps tenosynovitis (Sn 87.5%; Sp 97.6%), subacromial‐subdeltoid bursitis (Sn 72.7%; Sp 95.7%), humeral erosions (Sn 90.5%; Sp 97.3%), and acromioclavicular osteoarthritis (Sn 85.7%; Sp 95.7%). In terms of reliability, the agreement between US and MRI was almost perfect (κ = .9, P < .001).

Conclusion

US may have a role as the initial imaging modality in RA patients with shoulder pain, as it is highly sensitive and specific in detecting different pathological abnormalities of the shoulder.
Association of IL‐17A‐197G/A and IL‐17F‐7488T/C polymorphisms and osteoarthritis susceptibility: A meta‐analysis
Authors: Gao Shutao , Mao Chao , Cheng Jie , Deng Qiang , Sheng Weibin
Published: October 2019

Aim

This meta‐analysis was conducted with the aim of collecting and synthesizing the existing evidence on the association of interleukin‐17A (IL‐17A)‐197G/A and IL‐17F‐7488T/C gene polymorphisms and osteoarthritis (OA) susceptibility.

Methods

Six electronic databases including PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, and Wanfang were systematically searched for potentially relevant studies previous to June 2019. The strengths of association were estimated by summary odds ratios (ORs) and 95% confidence intervals (95%CIs) in a model‐free approach. Heterogeneity test and sensitivity analysis were also conducted to guarantee the reliability of this study.

Results

Six eligible case‐control studies comprising 1989 OA patients and 2116 healthy controls were obtained for the meta‐analysis. Dominant model was confirmed to be the optimal genetic model (MM + Mm vs mm). The pooled estimate supported that IL‐17A‐197G/A and IL‐17F‐7488T/C polymorphisms were significantly associated with OA susceptibility in the overall population (IL‐17A‐197G/A: GG + GA vs AA, OR = 0.69, 95%CI 0.57‐0.80; P < .001; IL‐17F‐7488T/C, TT + TC vs CC, OR = 0.46, 95%CI 0.29‐0.71, P < .001). However, subgroup analyses suggested the association only existed in Asians and knee OA.

Conclusion

The findings of the present study indicate that IL‐17A‐197G/A and IL‐17F‐7488T/C polymorphisms are positively associated to reduced risk of knee OA, especially in Asian populations.
Spatially balanced designs for transect‐based surveys
Authors: Foster Scott D. , Hosack Geoffrey R. , Monk Jacquomo , Lawrence Emma , Barrett Neville S. , Williams Alan , Przeslawski Rachel
Published: October 2019

Many sampling techniques rely on taking measurements along a transect; an example is underwater imagery from towed platforms used for marine ecological studies. Despite transect‐based sampling being commonly used, methods to generate randomized survey designs have not hitherto been developed.

We develop methods to generate random transect designs, which respect the user‐defined probability of sampling each grid cell (thecell inclusion probabilities). We show how to: (a) definetransect inclusion probabilitiesfrom user‐specified cell inclusion probabilities, which allows particular environments to be sampled more often; (b) alter the cell and transect inclusion probabilities so that when transects are sampled the frequencies of sampling cells approximate the cell inclusion probabilities, and; (c) draw a spatially balanced probability sample of transects.

The spatially balanced transect designs approximately maintain the cell inclusion probabilities. The greatest of the small departures occur near the extreme corners of our convex study region, which are difficult to place transects into. The proposed designs also exhibit superior spatial balance compared to the non‐balanced counterparts. We illustrate the successful application of the method to a towed‐camera survey of deep‐sea (500–2,000 m depths) seamounts off Tasmania, Australia. This was a challenging application due to the complex topology of the setting, and uneven inclusion probabilities for the property of interest – the presence of a stony coral.

Our approach develops the randomization approach to transect‐based surveys, thereby ensuring that transect‐based surveys can enjoy the same benefits as random point‐based surveys. The method approximates the cell inclusion probabilities, and does so while spatially balancing the transects throughout the study area. Practitioners can access the methods through theR‐packageMBHdesign, which is available from CRAN. We anticipate that it will act as a cornerstone for transect‐based ecological monitoring programmes.