bluuebunny/crossref_metadata_2025 huggingface dataset:
Fgf-driven Tbx protein activities directly inducemyf5andmyodto initiate zebrafish myogenesis
Authors: Osborn Daniel P.S. , Li Kuoyu , Cutty Stephen J. , Nelson Andrew C. , Wardle Fiona C. , Hinits Yaniv , Hughes Simon M.
Published: September 2019

Skeletal muscle derives from dorsal mesoderm that is formed during vertebrate gastrulation. Fibroblast growth factor (Fgf) signalling is known to cooperate with transcription factors of the Tbx family to promote dorsal mesoderm formation, but the role of these proteins in skeletal myogenesis has been unclear. Using the zebrafish, we show that dorsally-derived Fgf signals act through Tbx16 and Tbxta to induce two populations of slow and fast trunk muscle precursors at distinct dorsoventral positions. Tbx16 binds to and directly activates themyf5andmyodgenes that are required for commitment to skeletal myogenesis. Tbx16 activity depends on Fgf signalling from the organiser. In contrast, Tbxta is not required formyf5expression. However, Tbxta binds to a specific site upstream ofmyodnot bound by Tbx16, drivingmyodexpression in the adaxial slow precursors dependent upon Fgf signals, thereby initiating muscle differentiation in the trunk. After gastrulation, when similar muscle cell populations in the post-anal tail are generated from the tailbud, declining Fgf signalling is less effective at initiating adaxial myogenesis, which is instead initiated by Hedgehog signalling from the notochord. Our findings provide insight into the ancestral vertebrate trunk myogenic pattern and how it was co-opted during tail evolution to generate similar muscle by new mechanisms.
A 3D structural affinity model for multi-epitope in silico germinal center simulations
Authors: Robert Philippe A. , Meyer-Hermann Michael
Published: September 2019

Vaccine development for mutating pathogens is challenged by their fast evolution, the complexity of immunodominance, and the heterogeneous immune history of individuals. Mathematical models are critical for predicting successful vaccine conditions or designing potent antibodies. Existing models are limited by their abstract and poorly structural representations of antigen epitopes. Here, we propose a structural lattice-based model for antibody–antigen affinity. An efficient algorithm is given that predicts the best binding structure of an antibody’s amino acid sequence around an antigen with shortened computational time. This structural representation contains key physiological properties, such as affinity jumps and cross-reactivity, and successfully reflects the topology of antigen epitopes, such as pockets and shielded residues. It is suitable for large simulations of affinity maturation. We perform in silico immunizations via germinal center simulations and show that our model can explain complex phenomena like recognition of the same epitope by unrelated clones. We show that the use of cocktails of similar epitopes promotes the development of cross-reactive antibodies. This model opens a new avenue for optimizing multivalent vaccines with combined antigen cocktails or sequential immunizations, and to reveal reasons for vaccine success or failure on a structural basis.
Physiology-forward identification of bile acid sensitive vomeronasal receptors
Authors: Wong Wen Mai , Cao Jie , Zhang Xingjian , Doyle Wayne I. , Mercado Luis L. , Gautron Laurent , Meeks Julian P.
Published: September 2019

Abstract/Summary

The mouse accessory olfactory system (AOS) supports social and reproductive behavior through the sensation of environmental chemosignals. A growing number of excreted steroids have been shown to be potent AOS cues, including bile acids (BAs) found in feces. As is still the case with most AOS ligands, the specific receptors used by vomeronasal sensory neurons (VSNs) to detect BAs remain unknown. To identify VSN BA receptors, we first performed a deep analysis of VSN BA tuning using volumetric GCaMP6f/s Ca2+ imaging. These experiments revealed both broadly and narrowly tuned populations of BA-receptive VSNs with sub-micromolar sensitivities. We then developed a new physiology-forward approach for identifying AOS ligand-receptor interactions, which we call Fluorescence Live Imaging for Cell Capture and RNA-seq, or FLICCR-seq. FLICCR-seq analysis revealed 5 specific V1R-family receptors enriched in BA-sensitive VSNs. These studies introduce a powerful new approach for ligand-receptor matching and reveal biological mechanisms underlying mammalian BA chemosensation.
Diversity of Archaea Domain in Cuatro Cienegas Basin: Archaean Domes
Authors: Medina-Chávez Nahui Olin , Viladomat-Jasso Mariette , Olmedo-Álvarez Gabriela , Eguiarte Luis E , Souza Valeria , De la Torre-Zavala Susana
Published: September 2019

Herein we describe the Archaea diversity in a shallow pond in the Cuatro Ciénegas Basin (CCB), Northeast Mexico, with fluctuating hypersaline conditions containing elastic microbial mats that can form small domes where their anoxic inside reminds us of the characteristics of the Archaean Eon, rich in methane and sulfur gases; thus, we named this site the Archaean Domes (AD). These domes only form after heavy rains that are rare in the Chihuahuan desert. CCB is a unique oasis with hundreds of ponds, containing endemic species of animals, plants and highly diverse and unique microbial communities, despite its very biased stoichiometry, due mostly to extreme low phosphorus content (soils, water columns and sediments). This extreme oligotrophy has favored survival of ancestral microorganisms. Whole metagenome sequencing approach was performed for this unusual site in three different seasons to assess the extent of the Archaea biodiversity, with a focus on extremophiles, since members of the Archaea had been underrepresented in different study sites within the oasis. We found a highly diverse Archaea community compassing ∼5% of the metagenomes. The archaeal portion in all three metagenomes maintained its abundance and most of the strains showed to form a resilient core during three seasonal samplings (2016-2017), despite environmental fluctuations. However, relative abundances of all 230 archaeal OTUs (defined using a 97% cutoff) were low enough (<0.1%) to be considered part of the rare biosphere. AD finding and their description within CCB confirms that this particular pond is the most diverse for Archaea that we are aware of and opens new paths for understanding the forces that once drove and keep shaping microbial community assemblage.
Salmonella grows massively and aerobically in fecal matter
Authors: Guerrero Teresa , Zapata Sonia , Trueba Gabriel
Published: September 2019

The use of wastewater for irrigation and animal manure as fertilizer can cause transmission of intestinal pathogens, conditions frequently observed in Low- and Middle-Income Countries (LMICs). Here we tested the ability of Salmonella to grow in the fecal matter; we inoculated freshly isolated Salmonella strains (from chickens) in chicken fecal matter and incubated for 24, 48 and 72 hrs under aerobic and anaerobic conditions. We found that both Salmonella and E. coli multiplied massively in fecal matter outside a host for 72 hrs, being their growth higher in aerobic conditions. Our results have critical implications in waste management, as we demonstrate that aerobic treatments may not be the best to reduce the number of Salmonella in the environment.
Comparing serial X-ray crystallography and microcrystal electron diffraction (MicroED) as methods for routine structure determination from small macromolecular crystals
Authors: Wolff Alexander M , Young Iris D , Sierra Raymond G , Brewster Aaron S , Martynowycz Michael W , Nango Eriko , Sugahara Michihiro , Nakane Takanori , Ito Kazutaka , Aquila Andrew , Bhowmick Asmit , Biel Justin T , Carbajo Sergio , Cohen Aina E , Cortez Saul , Gonzalez Ana , Hino Tomoya , Im Dohyun , Koralek Jake D , Kubo Minoru , Lazarou Tomas S , Nomura Takashi , Owada Shigeki , Samelson Avi , Tanaka Rie , Tanaka Tomoyuki , Thompson Erin M , van den Bedem Henry , Woldeyes Rahel A , Yumoto Fumiaki , Zhao Wei , Tono Kensuke , Boutet Sébastien , Iwata So , Gonen Tamir , Sauter Nicholas K , Fraser James S , Thompson Michael C
Published: September 2019

Innovative new crystallographic methods are facilitating structural studies from ever smaller crystals of biological macromolecules. In particular, serial X-ray crystallography and microcrystal electron diffraction (MicroED) have emerged as useful methods for obtaining structural information from crystals on the nanometer to micron scale. Despite the utility of these methods, their implementation can often be difficult, as they present many challenges not encountered in traditional macromolecular crystallography experiments. Here, we describe XFEL serial crystallography experiments and MicroED experiments using batch-grown microcrystals of the enzyme cyclophilin A (CypA). Our results provide a roadmap for researchers hoping to design macromolecular microcrystallography experiments, and they highlight the strengths and weaknesses of the two methods. Specifically, we focus on how the different physical conditions imposed by the sample preparation and delivery methods required for each type of experiment effect the crystal structure of the enzyme.
Effects of predictive and incentive value manipulation on sign- and goal-tracking behavior
Authors: Maria-Rios Cristina E. , Fitzpatrick Christopher J. , Morrow Jonathan D.
Published: September 2019

When a neutral stimulus is repeatedly paired with an appetitive reward, two different types of conditioned approach responses may develop: a sign-tracking response directed toward the neutral cue, or a goal-tracking response directed toward the location of impending reward delivery. Sign-tracking responses have been postulated to result from attribution of incentive value to conditioned cues, while goal-tracking reflects the assignment of only predictive value to the cue. We therefore hypothesized that sign-tracking would be more sensitive to manipulations of incentive value, while goal-tracking would be more responsive to changes in the predictive value of the cue. We tested sign- and goal-tracking before and after devaluation of a food reward using lithium chloride, and tested whether either response could be learned under negative contingency conditions that precluded any serendipitous reinforcement of the behavior that might support instrumental learning. We also tested the effects on sign- and goal-tracking of blocking the predictive value of a cue using simultaneous presentation of a pre-conditioned cue. We found that sign-tracking was sensitive to outcome devaluation, while goal-tracking was not. We also confirmed that both responses are Pavlovian because they can be learned under negative contingency conditions. Goal-tracking was completely blocked by a pre-conditioned cue, while sign-tracking was only partially reduced. These results indicate that sign- and goal-tracking follow different rules of reinforcement learning and suggest a need to revise current models of associative learning to account for these differences.
Effects of the cannabinoid receptor agonist CP-55,940 on incentive salience attribution
Authors: Gheidi Ali , Cope Lora M. , Fitzpatrick Christopher J. , Froehlich Benjamin N. , Atkinson Rachel , Groves Coltrane K. , Barcelo Clair N. , Morrow Jonathan D.
Published: September 2019

Pavlovian conditioned approach paradigms are used to characterize the nature of motivational behaviors in response to stimuli as either directed toward the cue (i.e., sign-tracking) or the site of reward delivery (i.e., goal-tracking). Recent evidence has shown that activity of the endocannabinoid system increases dopaminergic activity in the mesocorticolimbic system, and other studies have shown that sign-tracking behaviors are dependent on dopamine. Therefore, we hypothesized that administration of a cannabinoid agonist would increase sign-tracking and decrease goal-tracking behaviors. Forty-seven adult male Sprague Dawley rats were given a low, medium, or high dose of the cannabinoid agonist CP-55,940 (N=12 per group) or saline (N=11) before Pavlovian conditioned approach training. A separate group of rats (N=32) were sacrificed after PCA training for measurement of cannabinoid receptor type 1 (CB1) and fatty acid amide hydrolase (FAAH) using in situ hybridization. Contrary to our initial hypothesis, CP-55,940 dose-dependently decreased sign-tracking and increased goal-tracking behavior. CB1 expression was higher in sign-trackers compared to goal-trackers in the prelimbic cortex, but there were no significant differences in CB1 or FAAH expression in the infralimbic cortex, dCA1, dCA3, dorsal dentate gyrus, or amygdala. These results demonstrate that cannabinoid signaling can specifically influence behavioral biases toward sign- or goal-tracking. Pre-existing differences in CB1 expression patterns, particularly in the prelimbic cortex, could contribute to individual differences in the tendency to attribute incentive salience to reward cues.
Genomics to aid species delimitation and effective conservation of the Sharpnose Guitarfish (Glaucostegus granulatus)
Authors: Johri Shaili , Fellows Sam , Solanki Jitesh , Busch Anissa , Livingston Isabella , Mora Maria Fernanda , Tiwari Anjani , Goodman Asha , Cantu Adrian , Doane Michael P. , Morris Megan , Edwards Robert A. , Dinsdale Elizabeth A.
Published: September 2019

The Sharpnose Guitarfish (Glaucostegus granulatus) is one of fifteen critically endangered Rhino Rays which has been exploited as incidental catch, leading to severe population depletions and localized disappearances. Like many chondrichthyan species, there are no species-specific time-series data available for the Sharpnose Guitarfish that can be used to calculate population reduction, partly due to a lack of species-specific reporting as well as limitations in accurate taxonomic identification. We here present the first complete mitochondrial genome and partial nuclear genome of the species and the first detail phylogenetic assessment of the species. We expect that data presented in the current manuscript will aid in accurate species-specific landing and population assessments of the species in the future and will enable conservation efforts to protect and recover remaining populations.
Establishing two principal dimensions of cognitive variation in Logopenic Progressive Aphasia
Authors: Ramanan Siddharth , Roquet Daniel , Goldberg Zoë-lee , Hodges John. R. , Piguet Olivier , Irish Muireann , Lambon Ralph Matthew A.
Published: September 2019

Logopenic Progressive Aphasia (LPA) is a neurodegenerative syndrome characterised by sentence repetition and naming difficulties arising from left-lateralised temporoparietal atrophy. Clinical descriptions of LPA largely concentrate on profiling language deficits, however, accumulating evidence points to the presence of cognitive deficits, even on tasks with minimal language demands. Although non-linguistic cognitive deficits in LPA are thought to scale with disease severity, patients at discrete stages of language dysfunction display overlapping cognitive profiles, suggesting individual-level variation in cognitive performance, independent of primary language dysfunction. To address this issue, we used principal component analysis to decompose individual-level variation in cognitive performance in 43 well-characterised LPA patients who underwent multi-domain neuropsychological assessments and structural neuroimaging. The principal component analysis solution revealed the presence of two, statistically independent factors, providing stable and clinically intuitive explanations for the majority of variance in cognitive performance in the syndrome. Factor 1 reflected ‘speech production and verbal memory’ deficits which typify LPA. Systematic variations were also confirmed on a second, orthogonal factor mainly comprising visuospatial and executive processes. Adopting a case-comparison approach, we further demonstrate that pairs of patients with comparable Factor 1 scores, regardless of their severity, diverge considerably on visuo-executive test performance, underscoring the inter-individual variability in cognitive profiles in comparably ‘logopenic’ patients. Whole-brain voxel-based morphometry analyses revealed that speech production and verbal memory factor scores correlated with left middle frontal gyrus, while visuospatial and executive factor scores were associated with grey matter intensity of right-lateralised temporoparietal, middle frontal regions and their underlying white matter connectivity. Importantly, LPA patients with poorer visuospatial and executive factor scores demonstrated greater right-lateralised temporoparietal and frontal atrophy. Our findings demonstrate the inherent variation in cognitive performance at an individual- and group-level in LPA, suggesting the presence of a genuine co-occurring cognitive impairment that is independent of language function and disease severity.
No effect of monetary reward in a visual working memory task
Authors: van den Berg Ronald , Zou Qijia , Li Yuhang , Ma Wei Ji
Published: September 2019

Previous work has shown that humans distribute their visual working memory (VWM) resources flexibly across items: the higher the importance of an item, the better it is remembered. A related, but much less studied question is whether people also have control over the total amount of VWM resource allocated to a task. Here, we approach this question by testing whether increasing monetary incentives results in better overall VWM performance. In three experiments, subjects performed a delayed-estimation task on the Amazon Turk platform. In the first two experiments, four groups of subjects received a bonus payment based on their performance, with the maximum bonus ranging from $0 to $10 between groups. We found no effect of the amount of bonus on intrinsic motivation or on VWM performance in either experiment. In the third experiment, reward was manipulated on a trial-by-trial basis using a within-subjects design. Again, no evidence was found that VWM performance depended on the magnitude of potential reward. These results suggest that encoding quality in visual working memory is insensitive to monetary reward, which has implications for resource-rational theories of VWM.
Deep-Channel uses deep neural networks to detect single-molecule events from patch-clamp data
Authors: Celik Numan , O’Brien Fiona , Brennan Sean , Rainbow Richard D. , Dart Caroline , Zheng Yalin , Coenen Frans , Barrett-Jolley Richard
Published: September 2019

Single-molecule research such as patch-clamp recording delivers unique biological insight by capturing the movement of individual proteins in real time, unobscured by whole-cell ensemble averaging. The critical first step in analysis is event detection, so called “idealisation”, where noisy raw data are turned into discrete records of protein movement. To date there have been practical limitations in patch-clamp data idealisation; high quality idealisation is typically laborious and becomes infeasible and subjective with complex biological data containing many distinct native single ion channel proteins gating simultaneously. Here we show a deep learning model based on convolutional neural networks and long short-term memory architecture can automatically idealise complex single molecule activity more accurately and faster than traditional methods. There are no parameters to set; baseline, channel amplitude or numbers of channels for example. We believe this approach could revolutionise the unsupervised automatic detection of single-molecule transition events in the future.
SVF-derived extracellular vesicles carry characteristic miRNAs in lipedema
Authors: Priglinger Eleni , Strohmeier Karin , Weigl Moritz , Lindner Carolin , Barsch Martin , Jacak Jaroslaw , Redl Heinz , Grillari Johannes , Sandhofer Matthias , Hackl Matthias , Wolbank Susanne
Published: September 2019

Lipedema is a chronic, progressive disease of adipose tissue with lack of consistent diagnostic criteria. The aim of this study was a thorough comparative characterization of extracellular microRNAs from the stromal vascular fraction (SVF) of healthy and lipedema adipose tissue. For this, we analyzed 187 extracellular microRNAs in concentrated conditioned media (cCM) and specifically in small extracellular vesicles (sEVs) enriched thereof by size exclusion chromatography. No significant difference in median particle size and concentration was observed between sEV fractions in healthy and lipedema. We found the majority of miRNAs located predominantly in cCM compared to sEV enriched fraction. Surprisingly, hierarchical clustering of the most variant miRNAs showed that only sEV miRNA profiles – but not cCM miRNAs – were impacted by lipedema. Seven sEV miRNAs (miR–16-5p, miR-29a-3p, miR-24-3p, miR-454-p, miR–144-5p, miR-130a-3p, let-7c-5p) were differently regulated in lipedema and healthy, whereas only one cCM miRNA (miR-188-5p) was significantly downregulated in lipedema. Comparing SVF from healthy and lipedema patients, we identified sEVs as the lipedema relevant miRNA fraction. This study contributes to identify the potential role of SVF secreted miRNAs in lipedema.
CaMKII oxidation is a performance/disease trade-off in vertebrate evolution
Authors: Wang Qinchuan , Hernández-Ochoa Erick O. , Viswanathan Meera C. , Blum Ian D. , Granger Jonathan M. , Murphy Kevin R. , Wei An-Chi , Aja Susan , Liu Naili , Antonescu Corina M. , Florea Liliana D. , Talbot C. Conover , Mohr David , Wagner Kathryn R. , Regot Sergi , Lovering Richard M. , Wu Mark N. , Cammarato Anthony , Schneider Martin F. , Bever Gabriel S. , Anderson Mark E.
Published: September 2019

Reactive oxygen species (ROS) contribute to health and disease. CaMKII is a widely expressed enzyme whose activation by oxidation of regulatory domain methionines (ox-CaMKII) contributes to cardiovascular disease, asthma, and cancer. Here we integrate comparative genomic and experimental data to show that CaMKII activation by ROS arose more than half-a-billion years ago on the vertebrate stem lineage where it constituted a bridge between ROS and increased intracellular Ca2+ release, exercise responsive gene transcription, and improved performance in skeletal muscle. These enhancements to fight-or-flight physiology were likely key in facilitating a well-evidenced shift in the behavioural ecology of our immediate chordate ancestors, and, in turn, the evolutionary success of vertebrates. Still, the ox-CaMKII innovation for augmenting performance must be considered a critical evolutionary trade-off, as it rendered us more susceptible to common and often fatal diseases linked to excessive ROS.
Altered hypothalamic diffusivity in Parkinsonian autonomic dysfunction
Authors: Rousseau Célia , Sklerov Miriam , Browner Nina , Lee Yueh Z. , Boucaud Adrien , Prieto Juan , Styner Martin A. , Dayan Eran
Published: September 2019

The pathophysiological basis of autonomic symptoms in Parkinson’s disease remains incompletely understood. The hypothalamus plays a key regulatory role in autonomic function and has been shown to be affected in Parkinson’s disease. Here, using diffusion magnetic resonance imaging, we investigated whether microstructural properties of the hypothalamus differ in Parkinson’s disease patients with high compared to low autonomic symptom burden.

Parkinson’s disease patients with low (n=25) and high (n=25) autonomic symptom burden were identified from a larger pool, based on scores from a questionnaire assessing autonomic symptoms in Parkinson’s disease (SCOPA-AUT). In each patient, we first segmented the hypothalamus manually, based on anatomical landmarks. Diffusivity measures were then extracted from the hypothalamus. Diffusivity measures calculated in the brainstem and the putamen were used to assess the specificity of the results.

Relative to patients with low autonomic symptom burden, patients with high burden showed increased mean, axial, and radial diffusivity in the hypothalamus. In contrast, we did not find significant group differences in any of these measures extracted from the brainstem or the putamen.

These results reveal consistent differences in the microstructural properties of the hypothalamus between patients with low and high autonomic symptom burden. Hypothalamic diffusivity properties can thus potentially be used as an imaging marker to assist in the identification of therapeutic targets for autonomic dysfunction in Parkinson’s disease.
Macrocyclization of an all-D linear peptide improves target affinity and imparts cellular activity: A novel stapled α-helical peptide modality
Authors: Kannan Srinivasaraghavan , Aronica Pietro G. A. , Ng Simon , Thean Dawn , Frosi Yuri , Chee Sharon , Shimin Jiang , Yuen Tsz Ying , Sadruddin Ahmad , Kaan Hung Yi Kristal , Chandramohan Arun , Wong Jin Huei , Tan Yaw Sing , Ferrer Fernando J. , Arumugam Prakash , Han Yi , Chen Shiying , Brown Christopher J. , Johannes Charles W. , Henry Brian , Lane David P. , Sawyer Tomi K. , Verma Chandra S. , Partridge Anthony W.
Published: September 2019

Peptide-based inhibitors hold great potential for targeted modulation of intracellular protein-protein interactions (PPIs) by leveraging vast chemical space relative to primary structureviasequence diversity as well as conformationally through varying secondary and tertiary structures. However, the development of peptide therapeutics has been hindered because of their limited conformational stability, proteolytic sensitivity and cell permeability. Several contemporary peptide design strategies address these issues to varying degrees. Strategic macrocyclization through optimally placed chemical braces such as olefinic hydrocarbon crosslinks, commonly referred to as staples, may address these issues by i) restricting conformational freedom to improve target affinities, ii) improving proteolytic resistance, and iii) enhancing cell permeability. Conversely, molecules constructed entirely from D-amino acids are hyper-resistant to proteolytic cleavage, but generally lack conformational stability and membrane permeability. Since neither approach is a complete solution, we have combined these strategies to identify the first examples of all-D α-helical stapled and stitched peptides. As a template, we used a recently reported all D-linear peptide that is a potent inhibitor of the p53-Mdm2 interaction, but is devoid of cellular activity. To design both stapled and stitched all-D-peptide analogues, we used computational modelling to predict optimal staple placement. The resultant novel macrocyclic all D-peptide was determined to exhibit increased α-helicity, improved target binding, complete proteolytic stability and, most notably, cellular activity.
Peritubular macrophages and spermatogonia are sequentially increased in the testis of rats after mono-(2-ethylhexyl) phthalate exposure
Authors: Gillette Ross , Tiwary Richa , Voss Jorine JLP , Hewage Shavini N , Richburg John H
Published: September 2019

Abstract

Peripubertal exposure to the phthalate metabolite mono-(2-ethylhexyl) phthalate (MEHP) in rodents causes testicular inflammation, spermatocyte apoptosis, and disruption of the blood-testis barrier. The MEHP-induced inflammation response includes an infiltration of macrophages and neutrophils to the testes, although the cause and purpose of this response is unknown. Recently, a population of testicular macrophages phenotypically distinct from those resident in the interstitium was described in mice. Testicular peritubular macrophages aggregate near the spermatogonial stem cell niche and are believed to stimulate their differentiation. We hypothesized that if testicular peritubular macrophages do indeed stimulate spermatogonial differentiation, MEHP exposure would result in an increase of peritubular macrophages to stimulate the replacement of lost spermatocytes. Male rats were exposed to 700 mg/kg MEHP or corn oil (vehicle control)viaoral gavage at PND 28 and euthanized at 48 hours, 1 week, or 2 weeks later. Tubules were stained with immunofluorescent markers for macrophages and undifferentiated spermatogonia. Peritubular macrophages were observed in rat testis similar to those previously described in mice: MHC-II+cells on the surface of seminiferous tubules with heterogeneous morphology. Quantification of MHC-II+cells revealed that, unlike in the mouse, their numbers did not increase through puberty. MEHP increased macrophage presence by six-fold 48-hours after exposure and remained elevated by two-fold two weeks after exposure. An increase of differentiating spermatogonia occurred two weeks after MEHP exposure. Taken together, our results suggest that peritubular macrophages play a crucial role in the testis response to acute injury and the subsequent recovery of spermatogenesis.

Summary Sentence

Phthalate-induced testicular injury results in an increase of specialized peritubular macrophages that may assist in the recovery of spermatogenesis.
How brain reacts to targeted attack at a hub region
Authors: Tu Wenyu , Ma Zilu , Ma Yuncong , Zhang Nanyin
Published: September 2019

The architecture of brain networks has been extensively studied in multiple species. However, exactly how the brain network reconfigures when a local region stops functioning remains elusive. By combining chemogenetics and resting-state functional magnetic resonance imaging (rsfMRI) in awake rodents, we investigated the causal impact of acutely inactivating a hub region (i.e. dorsal anterior cingulate cortex) on brain network properties. We found that disrupting hub activity profoundly changed the function the default-mode network (DMN), and this change was associated with altered DMN-related behavior. Suppressing hub activity also impacted the topological architecture of the whole-brain network in network resilience, segregation and small worldness, but not network integration. This study has established a system that allows for mechanistically dissecting the relationship between local regions and brain network properties. Our data provide direct evidence supporting the hypothesis that acute dysfunction of a brain hub can cause large-scale network changes. This study opens an avenue of manipulating brain networks by controlling hub-node activity.
Kinetic profiling of metabolic specialists demonstrates stability and consistency of in vivo enzyme turnover numbers
Authors: Heckmann David , Campeau Anaamika , Lloyd Colton J. , Phaneuf Patrick , Hefner Ying , Carrillo-Terrazas Marvic , Feist Adam M. , Gonzalez David J. , Palsson Bernhard O.
Published: September 2019

Enzyme turnover numbers (kcats) are essential for a quantitative understanding of cells. Because kcats are traditionally measured in low-throughput assays, they are often noisy, non-physiological, inconsistent, and labor-intensive to obtain.

We use a data-driven approach to estimate in vivo kcats using metabolic specialist E. coli strains that resulted from gene knockouts in central metabolism followed by metabolic optimization via laboratory evolution. By combining absolute proteomics with fluxomics data, we find that in vivo kcats are robust against genetic perturbations, suggesting that metabolic adaptation to gene loss is mostly achieved through other mechanisms, like gene-regulatory changes. Combining machine learning and genome-scale metabolic models, we show that the obtained in vivo kcats predict unseen proteomics data with much higher precision than in vitro kcats. The results demonstrate that in vivo kcats can solve the problem of noisy and inconsistent parameterizations of cellular models.
Gene expression profiling of single cells from archival tissue with laser-capture microdissection and Smart-3SEQ
Authors: Foley Joseph W. , Zhu Chunfang , Jolivet Philippe , Zhu Shirley X. , Lu Peipei , Meaney Michael J. , West Robert B.
Published: September 2019

RNA sequencing (RNA-seq) is a sensitive and accurate method for quantifying gene expression. Small samples or those whose RNA is degraded, such as formalin-fixed paraffin-embedded (FFPE) tissue, remain challenging to study with nonspecialized RNA-seq protocols. Here, we present a new method, Smart-3SEQ, that accurately quantifies transcript abundance even with small amounts of total RNA and effectively characterizes small samples extracted by laser-capture microdissection (LCM) from FFPE tissue. We also obtain distinct biological profiles from FFPE single cells, which have been impossible to study with previous RNA-seq protocols, and we use these data to identify possible new macrophage phenotypes associated with the tumor microenvironment. We propose Smart-3SEQ as a highly cost-effective method to enable large gene expression profiling experiments unconstrained by sample size and tissue availability. In particular, Smart-3SEQ's compatibility with FFPE tissue unlocks an enormous number of archived clinical samples; combined with LCM it allows unprecedented studies of small cell populations and single cells isolated by their in situ context.
Generational differences in relationship between prosocial identity fit and affective commitment
Authors: Rani Nitya , Samuel Anand A.
Published: September 2019

Purpose

The purpose of this paper is to examine the generational differences in the relationship between Person–Organization (P-O) fit of prosocial identity and affective commitment.

Design/methodology/approach

A moderated polynomial regression was used to examine the generational differences in the relationship between P-O fit of prosocial identity and affective commitment.

Findings

Organizational prosocial identity was found to be strongly correlated to affective commitment of employees. Generational differences existed among the employees in affective commitment and perception of organizational prosocial identity with Gen Y employees showing lower affective commitment and lower perception of organizational prosocial identity than older employees. P-O fit of prosocial identity had a significant relationship with affective commitment only for Gen Y employees. Gen Y employees had highest affective commitment when both individual and organizational prosocial identity were high vs when both were low.

Research limitations/implications

This study extends the research on P-O fit by examining the fit of a new dimension – prosocial identity. Further, by examining differences in this relationship for members of each generation, this paper also extends the research on generational theory.

Practical implications

The results of this study provide important input to managers who seek to increase the affective commitment of the “job hopping” Gen Y employees. The P-O fit of prosocial identity may present an important way of improving affective commitment for this generation of employees.

Originality/value

This study is one of the first to examine P-O fit of prosocial identity in India. It is also one of the first to examine this relationship in the context of a multigenerational workforce.
Consumer identification and oppositional organizational identities
Authors: Davis Daniel J. , Scheaf David J. , Williams Eleanor B.
Published: September 2019

Purpose

Oppositional organizational identities are fraught with conflict and often evoke powerful social and cultural identities. Such identities may be a divisive force among consumers. The purpose of this paper is to understand how consumers construct frames that facilitate identification with oppositional organizational identities.

Design/methodology/approach

The authors use online reviews from TripAdvisor.com and Yelp.com of the Creation Museum in Kentucky, USA. The Creation Museum is an ideal research context due to its location within American public discourse regarding religion and science. Through a grounded theory approach of the reviews, the authors propose three identity frames.

Findings

The data suggest that consumers primarily construct three frames to identify with the Creation Museum: transformational experiences, interpretive bricolage and oppositional scripts. Together, these frames engender resonance and facilitate consumer identification.

Originality/value

This paper is one of the first to examine how oppositional organizational identities garner consumer support. Given that consumers are increasingly attentive to organizational processes and the ubiquity of information technology, which reduces the costs of information and interaction, the study provides a much more holistic perspective on oppositional organizational identity and offers a multitude of future avenues for further research.
Controlling disturbing tourist behaviour: a perspective article
Authors: Pearce Philip L.
Published: September 2019

Purpose

Over the past 75 years, and even before that time span, some tourists have been identified as behaving destructively, unsafely and unsustainably. Such behaviours disturb other tourists, cost communities, reduce business profitability and impair life across the planet (Gössling, 2018). The attempts to reduce these negative consequences have been varied; they are not always successful and are likely to be creatively modified for the remainder of the twenty-first century. A summary table identifies key actions for limiting the disturbing tourist behaviour.

Design/methodology/approach

A short review is the requested style of this piece.

Findings

Much remains to be done though some successes are the likely basis for further effort.

Originality/value

This is a new summary, integrating much diverse material and built on very recent work and learning on the author's contributions to appear in Tourist Behaviour The Essential Companion Edward Elgar 2019.
Air transport innovations: a perspective article
Authors: Lohmann Gui , Pereira Bruno Alencar
Published: September 2019

Purpose

This paper aims to review some of the main aviation innovations that have taken place in the past 75 years and also provide some insights into the future of the sector until the end of the twenty-first century.

Design/methodology/approach

The paper uses a historical approach by identifying the main regulatory, technological and economic innovations that have allowed aviation to become such a global phenomenon, supporting the tourism industry worldwide. A similar approach is used to identify future innovations to support safe, sustainable and customer-focused advancements in the next 75 years.

Findings

No particular findings, but rather a timeline of remarkable developments (1945-2095) perspectives of air transport innovations.

Originality/value

This paper is a short review of the main innovations that have supported the air transport industry in the past 75 years, while predicting some other innovations to support the sector in the future.
The expression of cell adhesion molecule 1 and its splicing variants in Sézary cells and cell lines from cutaneous T‐cell lymphoma
Authors: Yamaguchi Mari , Morizane Shin , Hamada Toshihisa , Miyake Tomoko , Sugaya Makoto , Iwata Hiroaki , Fujii Kazuyasu , Haramoto‐Shiratsuki Rie , Nakagawa Yuki , Miura Mayumi , Ohshima Koichi , Morishita Kazuhiro , Takahashi Takahide , Imada Masahide , Okada Ken , Uehara Jiro , Sowa‐Osako Junko , Iwatsuki Keiji
Published: September 2019

Cell adhesion molecule 1 (CADM1) is aberrantly expressed by T‐cell neoplasms such as adult T‐cell leukemia/lymphoma (ATLL) and mycosis fungoides (MF). We studied the expression of CADM1 and its splicing variants in Sézary syndrome (SS), MF, other cutaneous T‐cell lymphoma (CTCL), and cell lines derived from T‐ and B‐cell lymphomas. Soluble CADM1 was measured in the patients’ sera. CADM1+ cells in the blood and skin lesions were examined by flow cytometry and immunostaining, respectively. Soluble CADM1 was measured by ELISA, and the splicing variants of CADM1 transcripts were determined by reverse transcriptase‐polymerase chain reaction, followed by sequencing. As a result, circulating CADM1+ cells were significantly increased in seven out of 10 patients with SS, ranging from 7.9% to 74.5% of the CD3+CD4+ fractions (median 33.7%; cut‐off value 6.5%). The percentages of CADM1+ cells were usually less than those of circulating Sézary cells. CADM1 was expressed, to various degrees, in six of nine T‐cell lines derived from SS, MF, ATLL, and anaplastic large cell lymphoma (ALCL), but negative in B‐cell lymphoma‐derived cell lines. CADM1+ cells were present in the skin infiltrates of MF, SS, ATLL and ALCL. Serum levels of soluble CADM1 were not significantly elevated in SS/MF. Three major splicing variants of CADM1 expressed by neoplastic T‐cells contained different combinations of the exons 7, 8, 9 and 11, including a putative oncogenic variant composed of exons 7‐8‐9‐11. In conclusion, CADM1 is frequently expressed in Sézary cells and cell lines from CTCL.
Markov chain Monte Carlo algorithms for target‐oriented and interval‐oriented amplitude versus angle inversions with non‐parametric priors and non‐linear forward modellings
Authors: Aleardi Mattia , Salusti Alessandro
Published: September 2019

In geophysical inverse problems, the posterior model can be analytically assessed only in case of linear forward operators, Gaussian, Gaussian mixture, or generalized Gaussian prior models, continuous model properties, and Gaussian‐distributed noise contaminating the observed data. For this reason, one of the major challenges of seismic inversion is to derive reliable uncertainty appraisals in cases of complex prior models, non‐linear forward operators and mixed discrete‐continuous model parameters. We present two amplitude versus angle inversion strategies for the joint estimation of elastic properties and litho‐fluid facies from pre‐stack seismic data in case of non‐parametric mixture prior distributions and non‐linear forward modellings. The first strategy is a two‐dimensional target‐oriented inversion that inverts the amplitude versus angle responses of the target reflections by adopting the single‐interface full Zoeppritz equations. The second is an interval‐oriented approach that inverts the pre‐stack seismic responses along a given time interval using a one‐dimensional convolutional forward modelling still based on the Zoeppritz equations. In both approaches, the model vector includes the facies sequence and the elastic properties of P‐wave velocity, S‐wave velocity and density. The distribution of the elastic properties at each common‐mid‐point location (for the target‐oriented approach) or at each time‐sample position (for the time‐interval approach) is assumed to be multimodal with as many modes as the number of litho‐fluid facies considered. In this context, an analytical expression of the posterior model is no more available. For this reason, we adopt a Markov chain Monte Carlo algorithm to numerically evaluate the posterior uncertainties. With the aim of speeding up the convergence of the probabilistic sampling, we adopt a specific recipe that includes multiple chains, a parallel tempering strategy, a delayed rejection updating scheme and hybridizes the standard Metropolis–Hasting algorithm with the more advanced differential evolution Markov chain method. For the lack of available field seismic data, we validate the two implemented algorithms by inverting synthetic seismic data derived on the basis of realistic subsurface models and actual well log data. The two approaches are also benchmarked against two analytical inversion approaches that assume Gaussian‐mixture‐distributed elastic parameters. The final predictions and the convergence analysis of the two implemented methods proved that our approaches retrieve reliable estimations and accurate uncertainties quantifications with a reasonable computational effort.
Effects of nitric oxide on apoptosis and voltage‐gated calcium channels in human cardiac myofibroblasts
Authors: Bae Hyemi , Kim Taeho , Lim Inja
Published: September 2019

We characterised the voltage‐gated Ca2+ channels (VGCCs) in human cardiac fibroblasts (HCFs) and myofibroblasts (HCMFs) and investigated the effects of nitric oxide (NO) on apoptosis and on these channels. Western blotting and immunofluorescence analyses show that α‐smooth muscle actin (a myofibroblast marker) was markedly expressed in passage (P) 12‐15 but not in P4 HCF cells, whereas calponin (a fibroblast marker) was expressed only in P4 cells. CaV1.2 (L‐type) and CaV3.3 (T‐type) of VGCCs were highly expressed in P12‐15 cells, but only weak CaV2.3 (R‐type) expression was identified in P4 cells using reverse transcription‐polymerase chain reaction analysis. S‐Nitroso‐N‐acetylpenicillamine (SNAP, an NO donor) decreased cell viability of HCMFs in a dose‐dependent manner and induced apoptotic changes, and nifedipine (an L‐type Ca2+ channel blocker) prevented apoptosis as shown with immunofluorescence staining and flow cytometry. Whole‐cell mode patch‐clamp recordings demonstrate the presence of L‐type Ca2+ (ICa,L) and T‐type Ca2+ (ICa,T) currents in HCMFs. SNAP inhibited ICa,L of HCMFs, but pre‐treatment with ODQ (a guanylate cyclase inhibitor) or KT5823 (a PKG inhibitor) prevented it. Pre‐treating cells with KT5720 (a PKA inhibitor) or SQ22536 (an adenylate cyclase inhibitor) blocked SNAP‐induced inhibition of ICa,L. 8‐Bromo‐cyclic GMP or 8‐bromo‐cyclic AMP also inhibited ICa,L. However, pre‐treatment with N‐ethylmaleimide (a thiol‐alkylating reagent) did not block the SNAP effect, nor did DL‐dithiothreitol (a reducing agent) reverse it. These data suggest that high concentrations of NO injure HCMFs and inhibit ICa,L through the PKG and PKA signalling pathways but not through the S‐nitrosylation pathway.
Intersex, infertility and the future: early diagnoses and the imagined life course
Authors: Jones Charlotte
Published: September 2019

Infertility is often recognised as a status that is medically identified in adulthood after unsuccessful attempts to conceive. This paper develops existing literature by illustrating how current conceptualisations of infertility do not incorporate a full range of experiences. Drawing on detailed, reflective diaries and in‐depth interviews with five participants, I explore how infertility is experienced and understood by women with variations of sex characteristics (VSCs) or intersex traits. I argue that greater consideration needs to be applied to intersex people and the circumstances of an infertility status that may be received in infancy, childhood or adolescence, before or outside of attempts to conceive, and without undergoing fertility treatment. Through discussions of time and futurity, this paper seeks to explore how visions of the future coalesce with an infertile status that is received in combination with an atypical sex status early in life. The paper indicates that early infertility can hinder some intersex children and young people's ambitions. However, infertility is not understood to be pathological or consistently prohibitive throughout the lives of everyone affected. Intersex women's conceptions of a potentially childless future are varied, complex, ambivalent and, in some cases, transitional throughout the life course.
Determination of Transfer Patterns of Pectobacterium carotovorum subsp. carotovorum Planktonic Cells and Biofilms During Mechanical Cutting of Kimchi Cabbage
Authors: Kang Miran , Kim Su‐Ji , Yoon So‐Ra , Lee Hae‐Won , Lee Jae Yong , Ha Ji‐Hyoung
Published: September 2019

Cross‐contamination of Pectobacterium carotovorum subsp. carotovorum (PCC) from a stainless‐steel surface to cabbage (Brassica rapa L. subsp. pekinensis) was evaluated. To investigate the PCC transfer pattern from mechanical knife surfaces to cabbage during 100 cuts, two mathematical models (power and logarithmic model) were fitted to the mean log10 detection data from cabbage. Overall, regression analysis determined that the best‐fitting regression curves of planktonic cells and detached cells from biofilms transferred onto fresh cabbage were Y = 3.7X–0.41, RMSE = 0.371 and Y = 4.6X–0.35, RMSE = 0.254, respectively. For salted cabbage, the best‐fit regression curves of planktonic cells and biofilm were Y = 5.8X–0.38, RMSE = 0.209 and Y = 5.4X–0.23, RMSE = 0.195, respectively. Our data provide a meaningful indication of the level of PCC cross‐contamination.