bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulating human sleep spindle MEG and EEG from ion channel and circuit level dynamics
Authors: Rosen B.Q. , Krishnan G.P. , Sanda P. , Komarov M. , Sejnowski T. , Rulkov N. , Ulbert I. , Eross L. , Madsen J. , Devinsky O. , Doyle W. , Fabo D. , Cash S. , Bazhenov M. , Halgren E.
Published: October 2017

Background

Although they form a unitary phenomenon, the relationship between extracranial M/EEG and transmembrane ion flows is understood only as a general principle rather than as a well-articulated and quantified causal chain.

Method

We present an integrated multiscale model, consisting of a neural simulation of thalamus and cortex during stage N2 sleep and a biophysical model projecting cortical current densities to M/EEG fields. Sleep spindles were generated through the interactions of local and distant network connections and intrinsic currents within thalamocortical circuits. 32,652 cortical neurons were mapped onto the cortical surface reconstructed from subjects’ MRI, interconnected based on geodesic distances, and scaled-up to current dipole densities based on laminar recordings in humans. MRIs were used to generate a quasi-static electromagnetic model enabling simulated cortical activity to be projected to the M/EEG sensors.

Results

The simulated M/EEG spindles were similar in amplitude and topography to empirical examples in the same subjects. Simulated spindles with more core-dominant activity were more MEG weighted.

Comparison with Existing Methods

Previous models lacked either spindle-generating thalamic neural dynamics or whole head biophysical modeling; the framework presented here is the first to simultaneously capture these disparate scales simultaneously.

Conclusions

This multiscale model provides a platform for the principled quantitative integration of existing information relevant to the generation of sleep spindles, and allows the implications of future findings to be explored. It provides a proof of principle for a methodological framework allowing large-scale integrative brain oscillations to be understood in terms of their underlying channels and synapses.
A novel core promoter element induces bidirectional transcription in CpG island
Authors: Mahpour Amin , Smiraglia Dominic , Scruggs Benjamin S. , Gelman Irwin H. , Ouchi Toru
Published: October 2017

How TATA-less promoters such as those within CpG islands (CGI) control gene expression is still a subject of active research. Here, we have identified the “CGCG element”, a ten-base pair motif with a consensus sequence of TCTCGCGAGA present in a group of promoter-associated CGIs of ribosomal protein and housekeeping genes. This element is evolutionarily conserved in vertebrates, found in DNase-accessible regions and employs RNA polymerase 2 to activate gene expression. Through extensive analysis of several endogenous promoters, we demonstrate that this element activates bidirectional transcription through divergent start sites. Methylation of this element abrogates the associated promoter activity. When coincident with a TATA-box directional transcription remains CGCG-dependent. Because the CGCG element is sufficient to drive transcription, we propose that its unmethylated form functions as a core promoter of TATA-less CGI-associated promoters.
Unsupervised detection of cell-assembly sequences with edit similarity score
Authors: Watanabe Keita , Haga Tatsuya , Euston David R , Tatsuno Masami , Fukai Tomoki
Published: October 2017

Cell assembly is a hypothetical functional unit of information processing in the brain. While technologies for recording large-scale neural activity have been advanced, mathematical methods to analyze sequential activity patterns of cell-assembly are severely limited. Here, we propose a method to extract cell-assembly sequences repeated at multiple time scales and various precisions from irregular neural population activity. The key technology is to combine “edit similarity” in computer science with machine-learning clustering algorithms, where the former defines a “distance” between two strings as the minimal number of operations required to transform one string to the other. Our method requires no external references for pattern detection, and is tolerant of spike timing jitters and length irregularity in assembly sequences. These virtues enabled simultaneous automatic detections of hippocampal place-cell sequences during locomotion and their time-compressed replays during resting states. Furthermore, our method revealed previously undetected cell-assembly structure in the rat prefrontal cortex during goal-directed behavior. Thus, our method expands the horizon of cell-assembly analysis.
Induction of autophagy by trehalose limits opportunistic mycobacterial infections in HIV-infected macrophages
Authors: Sharma Vartika , Makhdoomi Muzamil , Kumar Purnima , Khan Nabab , Singh Sarman , Verma H N , Luthra Kalpana , Sarkar Sovan , Kumar Dhiraj
Published: October 2017

Opportunistic bacterial infections amongst HIV-infected individuals pose serious health challenge. While immediate control of bacterial pathogens is typically attributed to innate defense mechanisms, whether HIV-mediated modulation of innate mechanisms like autophagy promote opportunistic infections, remains obscure. Using U1.1 and U937 macrophages, we show, HIV activation or infection inhibits autophagy and helps survival of pathogenicMycobacterium tuberculosisand non-pathogenic non-tuberculous mycobacterial strains (NTMs) likeMycobacterium aviumcomplex andMycobacterium fortuitum. HIV achieves this by blocking xenophagy flux, which could be reversed by the autophagy inducer trehalose that kills intracellularMtband NTMs. We found trehalose acts as a PI (3,5) P2agonist and activates TRPML1 to induce autophagy. Remarkably, trehalose treatment significantly reduced p24 levels in PBMCs infected with clinical HIV strains and in PBMCs derived from treatment-naive HIV patients. Taken together, our study highlights the immense potential of autophagy modulators in the therapeutic intervention of HIV and associated opportunistic infection.
Females recruit faster alpha motor neurons than males during the patellar stretch reflex: evidence for neurophysiological sexual dimorphism
Authors: Tindell Georgina , Smith Paul A.
Published: October 2017

Objective

Human neurophysiology is sexually dimorphic where the pre-motor latency of the patella stretch reflex (PR) in females occurs earlier than males; an effect unaccounted for by stature difference. Using surface electromyography we investigated whether this difference is due to dimorphism in the conduction velocity (MNCV) of the associated alpha-motor neurons.

Methods

Extracellular linear electrode arrays measured vastus lateralis (VL) motor unit action potential activity (MUAP). MNCV was determined from the relationship between the latency of MUAP initiation and VL distance during a PR.

Results

In females, the PR premotor latency occurred 2.1±0.3 ms earlier than in males and recruited alpha-motor neurons with a MNCV 5 ms−1faster (p<0.02) than males: 52.4±1.5 5 m s−1(n=40) compared to 47.6±1.3 5 m s−1(n=41) respectively.

Conclusions

In males the longer PR premotor latency was accounted for by their slower MNCV. Our finding is contrary to the observations of larger diameter alpha-motor axons and somas seen in males. Since the PR yields MNCVs values at the lower end of published values supports the “size-principle” of motor unit recruitment with a physiological stimulus.

Significance

Our findings evidence gender dimorphism in a routine neurophysiologic test which suggest androgen modulation of skeletal muscle innervation.
What’s in the box? Authentication ofEchinaceaherbal products using DNA metabarcoding and HPTLC
Authors: Raclariu Ancuta Cristina , Ţebrencu Carmen Elena , Ichim Mihael Cristi , Ciupercǎ Oana Teodora , Brysting Anne Krag , de Boer Hugo
Published: October 2017

Background

Differences in regulatory policies between countries as well as a lack of appropriate standardized methods for authentication and quality control of herbal products lead to concerns over quality and safety.Echinaceaproducts are among the top selling herbal products in Europe and the United States with indications for broad range of ailments.

Purpose

This study approached the need for a novel analytical strategy in authentication of herbal products.

Methods

A combination of high performance thin layer chromatography (HPTLC) and DNA metabarcoding was employed. Fifty-threeEchinaceaherbal products marketed across Europe were tested to evaluate the accuracy of these methods in plant identification and their potential in detecting substitutes, adulterants and other unreported plant constituents.

Results

HPTLC provides a high resolution in detectingEchinaceaphytochemical target compounds, but does not offer information on the other species within the product. Alternatively, we showed that the limitation of HPTLC to detect non-targeted species can be overcome through the complementary use of DNA metabarcoding. Using DNA metabarcoding,Echinaceaspecies were detected in 34 out of the 38 retained products (89 %), but with a lack of discriminatory resolution at the species level due to the low level of molecular divergence within theEchinaceagenus. All herbal products showed considerable discrepancies between ingredients listed on the label and the ones detected using DNA metabarcoding registering an overall ingredient fidelity of 43 %.

Conclusion

The results confirm that DNA metabarcoding can be used to test for the presence ofEchinaceaand simultaneously to detect other species present in even highly processed and multi-ingredient herbal products.

Abbreviations

EMA

European Medicines Agency

BLAST

basic local alignment search tool

FTIR

Fourier-transformed infrared spectroscopy

IR

infrared spectrometry

HPTLC

high performance thin layer chromatography

matK

maturase K

MS

mass spectrometry

MOTU

molecular taxonomic unit

nrITS

nuclear ribosomal internal transcribed spacer

Ph.Eur.

European Pharmacopoeia

rbcL

ribulose bisphosphate carboxylase

TLC

thin-layer chromatography

UV-VIS

ultraviolet-visible
Thermal proteome profiling of breast cancer cells reveals proteasomal activation by CDK4/6 inhibitor palbociclib
Authors: Miettinen Teemu P. , Peltier Julien , Härtlova Anetta , Gierliński Marek , Jansen Valerie M. , Trost Matthias , Björklund Mikael
Published: October 2017

Palbociclib is a CDK4/6 inhibitor approved for metastatic estrogen receptor positive breast cancer. In addition to G1 cell cycle arrest, palbociclib treatment results in cell senescence, a phenotype that are not readily explained by CDK4/6 inhibition. In order to identify a molecular mechanism responsible for palbociclib-induced senescence, we performed thermal proteome profiling of MCF7 breast cancer cells. In addition to affecting known CDK4/6 targets, palbociclib induces a thermal stabilization of the 20S proteasome, despite not directly binding to it. We further show that palbociclib treatment increases proteasome activity independently of the ubiquitin pathway. This leads to cellular senescence which can be counteracted by proteasome inhibitors. Palbociclib-induced proteasome activation and senescence is mediated by reduced proteasomal association of ECM29. Loss of ECM29 activates the proteasome, blocks cell proliferation and induces senescence. Finally, we find that ECM29 mRNA levels are predictive of relapse-free survival in breast cancer patients treated with endocrine therapy. In conclusion, thermal proteome profiling identifies the proteasome and ECM29 protein as mediators of palbociclib activity in breast cancer cells.
Modified hCFTRmRNA restores normal lung function in a mouse model of cystic fibrosis
Authors: Haque AKM Ashiqul , Dewerth Alexander , Antony Justin S. , Riethmüller Joachim , Latifi Ngadhnjim , Yasar Hanzey , Weinmann Petra , Pedemonte Nicoletta , Sondo Elvira , Laval Julie , Schlegel Patrick , Seitz Christian , Loretz Brigitta , Lehr Claus-Michael , Handgretinger Rupert , Kormann Michael S. D.
Published: October 2017

Being a classic monogenic disease, gene therapy has always been a promising therapeutic approach for Cystic Fibrosis (CF). However, numerous trials using DNA or viral vectors encoding the correct protein resulted in a general low efficacy. In the last years, chemically modified messenger RNA (cmRNA) has been proven to be a highly potent, pulmonary effective drug. We thus explored the expression of human (h)CFTR encoded by hCFTRcmRNAin vitro, analyzed by flow cytometry and Western Blot and its function with a YFP assay. Very similar effects could be observedin vivowhen hCFTRcmRNA was assembled with Chitosan-coated PLGA to nanoparticles (NPs) and intratracheally (i.t.) or intravenously (i.v) injected, the latter one as an alternative administration route to circumvent the clogged airways of CF patients. This significantly improved lung function, which suggests that hCFTRcmRNA-NPs are a promising therapeutic option for CF patients independent of theirCFTRgenotype.
Modernized Tools for Streamlined Genetic Manipulation of Wild and Diverse Symbiotic Bacteria
Authors: Wiles Travis J. , Wall Elena S. , Schlomann Brandon H. , Hay Edouard A. , Parthasarathy Raghuveer , Guillemin Karen
Published: October 2017

The capacity to associate symbiotic bacteria with vital aspects of plant and animal biology is outpacing our understanding of the mechanisms shaping these interactions. A major barrier to mechanistic studies is the paucity of tools for genetically manipulating wild and diverse bacterial isolates. Solving this problem is crucial to elucidating the cellular and molecular rules that govern symbiotic relationships and ultimately harnessing them for agricultural and biomedical applications. Therefore, we constructed a series of vectors that expedite genetic knock-in and knock-out procedures across a range of bacterial lineages. This was accomplished by developing strategies for domestication-free bacterial conjugation, designing plasmids with customizable features, and streamlining allelic exchange using visual markers of homologous recombination. These tools enabled a comparative study based on live imaging of diverse bacterial symbionts native to the zebrafish intestine, with which we discovered heterogeneous colonization patterns and a striking correlation between bacterial population biogeography and cellular behavior.
The Genetic Chain Rule for Probabilistic Kinship Estimation
Authors: Helfer Brian S. , Fremont-Smith Philip , Ricke Darrell O.
Published: October 2017

Accurate kinship predictions using DNA forensic samples has utility for investigative leads, remains identification, identifying relationships between individuals of interest, etc. High throughput sequencing (HTS) of STRs and single nucleotide polymorphisms (SNPs) is enabling the characterization of larger numbers of loci. Large panels of SNP loci have been proposed for improved mixture analysis of forensic samples. While multiple kinship prediction approaches have been established, we present an approach focusing on these large HTS SNP panels for predicting degree of kinship predictions. Formulas for first degree relatives can be multiplied (chained) together to model extended kinship relationships. Predictions are made using these formulations by calculating log likelihood ratios and selecting the maximum likelihood across the possible relationships. With a panel of 30,000 SNPs evaluated on an in silico dataset, this method can resolve parents from siblings and distinguish 1st, 2nd, and 3rd degree relatives from each other and unrelated individuals.
Genomic Locus Modulating IOP in the BXD RI Mouse Strains
Authors: King Rebecca , Li Ying , Wang Jiaxing , Struebing Felix L. , Geisert Eldon E.
Published: October 2017

Purpose

Intraocular pressure (IOP) is the primary risk factor for developing glaucoma. The present study examines genomic contribution to the normal regulation of IOP in the mouse.

Methods

The BXD recombinant inbred (RI) strain set was used to identify genomic loci modulating IOP. We measured the IOP from 532 eyes from 33 different strains. The IOP data will be subjected to conventional quantitative trait analysis using simple and composite interval mapping along with epistatic interactions to define genomic loci modulating normal IOP.

Results

The analysis defined one significant quantitative trait locus (QTL) on Chr.8 (100 to 106 Mb). The significant locus was further examined to define candidate genes that modulate normal IOP. There are only two good candidate genes within the 6 Mb over the peak, Cdh8 (Cadherin 8) and Cdh11 (Cadherin 11). Expression analysis on gene expression and immunohistochemistry indicate that Cdh11 is the best candidate for modulating the normal levels of IOP.

Conclusions

We have examined the genomic regulation of IOP in the BXD RI strain set and found one significant QTL on Chr. 8. Within this QTL that are two potential candidates for modulating IOP with the most likely gene being Cdh11.
Bird songs on the shelf: assessing vocal activity and output using data hidden in sound archives
Authors: Laverde-R. Oscar , Caycedo-Rosales Paula , Pulgarín-R. Paulo-C. , Cadena Carlos Daniel
Published: October 2017

Understanding how often do animals emit communication signals is of critical importance to address a variety of research questions in behavioral ecology and sexual selection. However, information on vocal output, a central component of investment in signaling, is lacking for most species employing acoustic communication. Because this lack of information is partly due to logistical and methodological difficulties in monitoring animal signaling over time, developing new approaches to quantify vocal output is of special importance. We asked whether the number of recordings of avian vocalizations in sound archives and the times when such recordings were obtained reflect estimates of vocal output and temporal patterns of vocal activity obtained through systematic monitoring of wild bird populations in tropical forest sites. Based on a sample of 43 montane forest species, we found significant relationships between the number of recordings of species detected through continuous monitoring over several months and the number of recordings archived in sound collections, especially when accounting for the area of distribution of each species. In addition, daily activity patterns based on data collected through continuous monitoring over several days did not differ from those based on recordings archived in sound collections in 12 of 15 species of lowland forest birds. Annual patterns in vocal activity of two species estimated based on recordings in collections closely resembled previously published patterns. We conclude that recordings in sound collections contain valuable yet previously unappreciated information about the vocal output and temporal patterns in vocal activity of birds. This opens the possibility of using sound collections to assess vocal output and to consider it as a variable of interest in studies on the ecology and evolution of birds and other animals that use acoustic signals for communication. We encourage field workers to keep the ears wide open, and the recorders wide ready to record.
Cardio- and neurometabolic effects of lower-body pressure-supported exercise in obese non-diabetic women: Resetting autonomic imbalance?
Authors: Godwin Ellen M. , Uglialoro Anthony D. , Ali Andaleeb , Yearwood Leah , Banerji Mary Ann , Kral John G.
Published: October 2017

Background:

Overnutrition and underactivity cause most chronic disease via inflammation and stress. Life-style changes such as diet is largely unsuccessful and exercise is painful, uncomfortable and difficult for people with diabesity, cardiorespiratory and joint diseases and cognitive decline affecting their ability to ambulate and adhere to exercise guidelines. Diets or exercise causing weight loss are stressful and trigger numerous redundant counter regulatory mechanisms defending lean body mass, explaining failures to sustain these behaviors. In this hypothesis-generating pilot study we used a NASA-developed weight supporting lower-body positive pressure (LBPP) treadmill providing comfortable low-amount, low intensity walking, challenging current exercise guidelines.

Methods:

Sixteen nondiabetic, untrained, Black volunteer women (BMI 28-50), age 18-56 years were studied by anthropometry, analyses of energy expenditure and blood chemistry: oral glucose tolerance tests (OGTT) with insulin, C-peptide, GLP-1 and FFA and fasting lipids, cytokines, adipokines and appetitive peptides, before and after 10 weeks of twice weekly 30-minute weight supported LBPP treadmill sessions.

Results:

We found novel baseline associations between gluco- and neuro-regulatory peptides and plasma lipids, inflammatory cytokines and appetitive hormones related to neurogenesis, mood and energy balance. Post-study, independent of body weight or energy expended there were significant decreases in OGTT plasma insulin (p=0.002) and GLP-1 (p=0.060) and fasting triglycerides (p=0.029), ghrelin (p=0.008) and changes in most molecules including increased leptin and beta-endorphin. Correlations between changes among different classes of peptides were highly significant, notably leptin - adiponectin, and beta-endorphin - oxytocin and orexin A. We propose synergy between low-amount, low-intensity exercise at levels below thresholds of increased sympathetic tone, and baro-physiological effects of LBPP normalizing parasympathetic tone.

Conclusion:

Brief, low-dose, lower-body positive-pressure weight-supported treadmill exercise improved cardiometabolic fitness and exhibited favorable changes in neuro-regulatory peptides without weight loss in inner-city obese Black women.
The Antiviral and Cancer Genomic DNA Deaminase APOBEC3H Is Regulated by a RNA-Mediated Dimerization Mechanism
Authors: Shaban Nadine M. , Shi Ke , Lauer Kate V. , Carpenter Michael A. , Richards Christopher M. , Lopresti Michael W. , Salamango Daniel , Wang Jiayi , Banerjee Surajit , Brown William L. , Aihara Hideki , Harris Reuben S.
Published: October 2017

Human APOBEC3H and homologous single-stranded DNA cytosine deaminases are unique to mammals. These DNA editing enzymes function in innate immunity by restricting the replication of viruses and transposons. Misregulated APOBEC3H also contributes to cancer mutagenesis. Here we address the role of RNA in APOBEC3H regulation. APOBEC3H co-purifies with RNA as an inactive protein, and RNase A treatment yields enzyme preparations with stronger DNA deaminase activity. RNA binding-defective mutants are DNA hypermutators. Chromatography profiles and crystallographic data demonstrate a mechanism in which double-stranded RNA mediates enzyme dimerization. RNA binding is required for APOBEC3H cytoplasmic localization and for packaging into HIV-1 particles and antiviral activity. Related DNA deaminases including other APOBEC3 family members and the antibody gene diversification enzyme AID also bind RNA and are predicted to have a similar RNA binding motif suggesting mechanistic conservation and relevance to innate and adaptive immunity and to multiple diseases.

HIGHLIGHTS

RNA inhibits human APOBEC3H DNA cytosine deaminase activity

RNA binding mutants are DNA hypermutators

X-ray structure demonstrates an RNA duplex-mediated APOBEC3H dimerization mechanism

RNA binding is required for packaging into HIV-1 particles and antiviral activity
Paleo-Eskimo genetic legacy across North America
Authors: Flegontov Pavel , Altinişik N. Ezgi , Changmai Piya , Rohland Nadin , Mallick Swapan , Bolnick Deborah A. , Candilio Francesca , Flegontova Olga , Jeong Choongwon , Harper Thomas K. , Keating Denise , Kennett Douglas J. , Kim Alexander M. , Lamnidis Thiseas C. , Olalde Iñigo , Raff Jennifer , Sattler Robert A. , Skoglund Pontus , Vajda Edward J. , Vasilyev Sergey , Veselovskaya Elizaveta , Hayes M. Geoffrey , O’Rourke Dennis H. , Pinhasi Ron , Krause Johannes , Reich David , Schiffels Stephan
Published: October 2017

Paleo-Eskimos were the first people to settle vast regions of the American Arctic around 5,000 years ago, and were subsequently joined and largely displaced around 1,000 years ago by ancestors of the present-day Inuit and Yupik. The genetic relationship between Paleo-Eskimos and Native American populations remains uncertain. We analyze ancient and present-day genome-wide data from the Americas and Siberia, including new data from Alaskan Iñupiat and West Siberian populations, and the first genome-wide DNA from ancient Aleutian Islanders, ancient northern Athabaskans, and a 4,250-year-old individual of the Chukotkan Ust'-Belaya culture. Employing new methods based on rare allele and haplotype sharing as well as established methods based on allele frequency correlations, we show that Paleo-Eskimo ancestry is widespread among populations who speak Na-Dene and Eskimo-Aleut languages. Using phylogenetic modelling with allele frequency correlations and rare variation, we present a comprehensive model for the complex peopling of North America.
Action boosts episodic memory encoding in humans via engagement of a noradrenergic system
Authors: Yebra Mar , Galarza-Vallejo Ana , Soto-Leon Vanesa , Gonzalez-Rosa Javier J , de Berker Archy O , Bestmann Sven , Oliviero Antonio , Kroes Marijn CW , Strange Bryan A
Published: October 2017

We are constantly interacting with our environment whilst we encode memories. However, how actions influence memory formation remains poorly understood. Goal-directed movement engages the locus coeruleus (LC), the main source of noradrenaline in the brain. Noradrenaline is also known to enhance episodic encoding, suggesting that action could improve memory via LC engagement. Here we demonstrate, across seven experiments, that action (Go-response) enhances episodic encoding for stimuli unrelated to the action itself, compared to action inhibition (NoGo). Supporting a noradrenergic mechanism underlying this enhancement, functional magnetic resonance imaging, and pupil diameter as a proxy measure for LC-noradrenaline transmission, indicate increased encoding-related LC activity during action. A final experiment confirmed a novel prediction derived from these data that emotionally aversive stimuli, which recruit the noradrenergic system, modulate the mnemonic advantage conferred by Go-responses relative to neutral stimuli. We therefore provide converging evidence that action boosts episodic memory encoding via a noradrenergic mechanism.
Heterogeneity in local density allows a positive evolutionary relationship between self-fertilisation and dispersal
Authors: Rodger James , Landi Pietro , Hui Cang
Published: October 2017

Theoretical work predicts that dispersal and self-fertilisation (selfing) should always be negatively correlated and the Good Coloniser Syndrome (GCS) of high dispersal and selfing should not occur when both traits are free to evolve. This contradicts positive relationships between selfing and dispersal in empirical data. Critically, previous work assumes density of adults is spatially and temporally homogeneous, so selfing results in homogeneity in propagule production and competition, which eliminates the benefit of dispersal for escaping from local resource competition. We investigate the joint evolution of dispersal and selfing in a demographically structured metapopulation model where local density varies due to stochastic extinction-recolonisation dynamics. Increasing local extinction rate reduces local density across the metapopulation, which favours high selfing to mitigate mate limitation, but increases heterogeneity in density, which favours high dispersal for escape from competition. Together, these effects produce a positive relationship between selfing and dispersal, and evolution of the GCS. Nevertheless, the relationship between selfing and dispersal is context-dependent, as varying dispersal cost yields a negative relationship. Our results imply that if spatiotemporal heterogeneity in environmental suitability increases towards the range edge, the GCS may evolve there, favouring further range expansion (Cf. Baker’s Law).
Comprehensive single cell RNAseq analysis of the kidney reveals novel cell types and unexpected cell plasticity
Authors: Park Jihwan , Shrestha Rojesh , Qiu Chengxiang , Kondo Ayano , Huang Shizheng , Werth Max , Li Mingyao , Barasch Jonathan , Suszták Katalin
Published: October 2017

A key limitations to understand kidney function and disease development has been that specific cell types responsible for specific homeostatic kidney function or disease phenotypes have not been defined at the molecular level.

To fill this gap, we characterized 57,979 cells from healthy mouse kidneys using unbiased single-cell RNA sequencing. We show that genetic mutations that present with similar phenotypes mostly affect genes that are expressed in a single unique differentiated cell type. On the other hand, we found unexpected cell plasticity of epithelial cells in the final segment of the kidney (collecting duct) that is responsible for final composition of the urine. Using computational cell trajectory analysis and in vivo linage tracing, we found that, intercalated cells (that secrete protons) and principal cells (that maintain salt, water and potassium balance) undergo a Notch mediated interconversion via a newly identified transitional cell type. In disease states this transition is shifted towards the principal cell fate. Loss of intercalated cells likely contributes to metabolic acidosis observed in kidney disease.

In summary, single cell analysis advanced a mechanistic description of kidney diseases by identifying a defective homeostatic cell lineage.

One Sentence Summary

A comprehensive single cell atlas of the kidney reveals a transitional cell type and cell plasticity determined by Notch signaling which is defective in chronic kidney disease.
Autism awareness training for youth offending team staff members
Authors: Ashworth Sarah , Tully Ruth J.
Published: October 2017

Purpose

Many in contact with the criminal justice system (CJS) have complex needs, including autism. The purpose of this paper is to present the development, design and evaluation of a training package designed to increase awareness that Youth Offending Team (YOT) staff members in the UK have of autism in the CJS (Talbot, 2010). Training quality and effectiveness was assessed. This paper aims to highlight the need for organisations/individuals providing training services relating to autism to be transparent, evidence based and open to sharing best practice. By evaluating practice, disseminating findings and hopefully providing mutual support, trainers can create networks to enhance the value of training provision, ultimately increasing the quality of support offered to individuals with autism.

Design/methodology/approach

A training package relating to autism in forensic systems was developed and delivered to staff working within a UK YOT. Levels of self-reported knowledge and confidence in working with individuals with autism are measured by evaluation questionnaires completed pre- and post-training.

Findings

Results demonstrate a significant increase in self-reported knowledge and confidence in working with individuals with autism within the CJS following training.

Originality/value

This highlights the potential for evidence-based staff training to enhance individuals’ practice working with individuals with autism within the CJS.
Does “mentoring” offer effective support to autistic adults? A mixed-methods pilot study
Authors: Martin Nicola , Milton Damian Elgin Maclean , Sims Tara , Dawkins Gemma , Baron-Cohen Simon , Mills Richard
Published: October 2017

Purpose

The Research Autism Cygnet Mentoring project was a two-year pilot study, completed in 2016, which aimed to develop, trial and evaluate a mentoring scheme designed with input from autistic people, their families and supporters. The paper aims to discuss these issues.

Design/methodology/approach

The mentoring scheme involved 12 matched pairs (mentor/mentee) meeting once per week for one hour, over a six-month period. All mentors attended a training day, led by the principles of personal construct theory and an emancipatory research ethos. The project and training involved significant involvement of autistic people in both its design and delivery.

Findings

Participants on the autism spectrum found their mentoring experience very helpful in enabling them to progress towards self-identified goals, and mentees felt empowered by the person-centred ethos and the methods employed on the project. However, a number of aspects of the mentoring project have been identified that require further investigation, including: caution over offering mentoring without formal structures, boundary setting, supervision, flexibility and the matching of mentees with mentors.

Originality/value

The project has highlighted the potential benefits of time-limited goal-orientated mentoring and the negligible evidence base underpinning current mentoring practice with adults on the autism spectrum. In order for the project to realise its emancipatory aim, there is a need for a large-scale quantitative study and a health-economics analysis to provide the necessary evidence base for mentoring to be recommended as a cost-effective intervention with clear benefits for individual wellbeing.
Healthcare experiences of young adults with autism spectrum disorder
Authors: Hillier Ashleigh , Galizzi Monica , Ferrante Kianna
Published: October 2017

Purpose

Characteristic challenges that define autism spectrum disorder (ASD), coupled with comorbid conditions and poor communication with providers, can lead to inadequate healthcare. The majority of previous work has focused on children. The purpose of this paper is to examine the healthcare experiences of young adults with ASD within the US healthcare system.

Design/methodology/approach

An online questionnaire was utilized to examine: the accessibility of healthcare for those with ASD: do they make their own appointments, fill out paperwork independently, go in the examination room on their own; the quality of care they receive: what are their medical needs, how effectively can they communicate their needs, do providers understand their disability; and the outcomes of care: do they understand their recommended care, can they follow healthcare instructions accurately, are they satisfied with the care received. The authors compared responses of those with ASD (n=16) with those of parents of adults with ASD (n=50), as well as a matched comparison group of young adults without ASD (n=42) for statistical differences using the Fisher Exact test. The authors also asked parents about their time costs of assisting their adult children through the healthcare process.

Findings

The results suggest that those with ASD overestimated their ability to manage their healthcare needs, felt more positively about the healthcare they received than was warranted, and were significantly less independent in managing their healthcare than their peers. Parents experienced losses and costs in terms of lost productivity, household work, and personal time.

Originality/value

This study furthers the understanding of the healthcare experiences of young adults with ASD which is crucial to dissecting problems which hamper access to quality care.
Defendants with autism spectrum disorders: what is the role of court liaison and diversion?
Authors: Chaplin Eddie , McCarthy Jane , Forrester Andrew
Published: October 2017

Purpose

The purpose of this paper is to examine the role of liaison and diversion services working in the lower courts (also known as Magistrates’ courts) with regard to autism spectrum disorders (ASDs) and their assessment, in particular, the role of pre-sentence and psychiatric reports and interviews.

Design/methodology/approach

Current practice is described in the lower courts in the context of current legislation and procedures.

Findings

When writing reports, there is a need for expertise to offer an opinion on future risk, disposal and what needs to be in place to support people with ASDs. No assumptions should be made when reporting on the basis of an ASD diagnosis alone and each case must be assessed on its individual merits while ensuring that individual human rights are protected.

Originality/value

There is currently a sparse literature examining ASD in court settings. This paper seeks to clarify the current practice.
Benchmarking wine tourism destinations – the case of Bulgaria
Authors: Terziyska Ilinka
Published: October 2017

Purpose

The purpose of this paper is twofold – on the one hand, to introduce a framework for benchmarking of wine regions and on the other, to analyze the activities of wineries in Bulgaria with a clear focus on tourism.

Design/methodology/approach

The research design includes secondary data and content analysis, which are complemented by a survey among wine cellar owners and managers in the country, including respondents from all five wine regions.

Findings

The paper has identified several problems that impede wine tourism development in Bulgaria, including: small number of wineries, small share of Protected Designation of Origin wines, ineffective business hours structure and small share of wineries offering additional services beyond tasting or cellar-door sales. On the other hand, wineries in Bulgaria conform to international trends in terms of providing accommodation, restaurant and SPA treatments. The survey revealed that tourism-hosting wineries consider wine tourism an important part of their activity but do not succeed in attracting a sufficient number of visitors, and the share of tourism-related revenues to their total incomes is small.

Research limitations/implications

The survey included all the wineries in the country; in one of the regions (the Black Sea region), however, the response rate was very low, which means that while results and conclusions are representative for the country as a whole, they might not be applicable to this specific region.

Originality/value

The research results refer to an emerging wine destination, which has not been the object of a comprehensive study yet. In addition, the proposed update of an existing benchmarking model reflects recent changes and trends in the wine tourism industry.
Wine tourist valuation of information sources: the role of prior travel
Authors: Byrd Erick T. , Canziani Bonnie , Boles James S. , Williamson Nicholas Carlton , Sonmez Sevil
Published: October 2017

Purpose

The purpose of this study is to examine winery visitors’ use of information sources in making decisions regarding the choice of wineries to visit. Enrichment theory is used as a framework for determining how previous experience influences the decision on how much and what type of information individuals will use when planning a trip using wine tourism as the context for the research.

Design/methodology/approach

A visitor study was conducted at 23 wineries in the US Southeast. Data were collected from winery visitors using a structured self-administered questionnaire.

Findings

Results from 832 consumers indicate that an individual’s previous travel systematically influences the number and type of information sources that they will seek out when making future consumer decisions. Findings confirmed the hypothesized expectations about wine tourist information search behavior and help to partially explain the nature of bounded rationality in the case of tourists’ winery visit decisions.

Research limitations/implications

Because the study focused only on winery visitors in the US Southeast, the research results may lack generalizability.

Practical implications

These findings can assist winery owners and destinations with wineries in their promotional efforts. Of major importance is the finding that increases in experiential knowledge from prior travel are monotonically associated with increases in the number of information sources marked to be valuable in selecting a winery. The influence of experience is particularly dramatic in that the mean number of information sources marked to be valuable moves from a low of 2.5 to a high of 10.0 out of 16 as travel experience increases.

Originality/value

The study contributed significant and useful findings that advance the application of enrichment theory to wine tourism. Enrichment theory does not currently differentiate between types of knowledge that enrich a consumer’s ability to more easily encode and use new information. The current study confirms that experiential knowledge is an important knowledge construct in models of bounded rationality.
Wine tourism signage programs in the USA
Authors: Byrd Erick T. , Bhadury Joyendu , Troy Samuel P.
Published: October 2017

Purpose

Highway signage programs are important to the success of winery tourism industry. The purpose of this paper is to investigate the regulatory environment US wineries operate under in regards to highway signage programs. The goal then is to compare wine tourism-related highway signage programs in the USA and identify best practices for the programs.

Design/methodology/approach

Twenty-six programs from 13 US states are included in this study. Research collected both primary data (through interviews with 30 officials and representatives) and secondary data (from websites, government publications) to identify the costs, regulations and rules of each program.

Findings

A review of these programs shows that while there are many common elements in these programs, all are managed differently, have different operational and facility requirements for participation and vary in cost.

Practical implications

Highway signage programs related to winery tourism are best administered by a single state-wide governmental agency or foundations/trusts. Second, highway signage program should link with a separate certification program for the wineries which guarantees a certain minimum amount of local content. Winery owners and officials interviewed also emphasized the need for synergy among neighboring wineries to facilitate winery tourism.

Originality/value

Limited research has been conducted about the regulatory environment of signage programs that are specific to the wine industry in the USA. This study begins to address this gap in the literature by presenting an overview and best practices of 26 wine tourism-related highway signage programs from 13 different states across the USA.
Wine prestige and experience in enhancing relationship quality and outcomes
Authors: Loureiro Sandra Maria Correia , Cunha Namércio Pereira da
Published: October 2017

Purpose

The purpose of this study is twofold: conduct a systematic literature review on relationship quality; and analyse the effect of wine brand prestige and wine consumer experience on consumer satisfaction, as well as the wine brand image and word of mouth as outcomes.

Design/methodology/approach

The authors employed a systematic approach to develop the literature review and a survey was designed and used to collect responses from 479 wine consumers and tourists. Partial Least Squares approach was used to test the proposed model and analyse the findings.

Findings

The systematic approach allows to determine the core constructs of relationship quality, main antecedents and outcomes, which help in the conceptualisation of the proposed model. The findings of the survey suggest that wine brand prestige is more effective in enhancing consumer satisfaction than wine consumer experience. Consumer satisfaction acts as a mediator between wine brand prestige and wine consumer experience and the outcomes, that is, wine.

Originality/value

This research sheds light on a strategic and communicational development of prestigious wine brands to enhance wine image and keep wine tourists captivated.
Role of women entrepreneurs and NGOs in promoting entrepreneurship: case studies from Uttarakhand, India
Authors: Lenka Usha , Agarwal Sucheta
Published: October 2017

Purpose

Women establish their enterprise for economic independence and empowerment. This study aims to identify the factors that promote women entrepreneurship in Uttarakhand, a state in India. Although, women have the potential to become entrepreneurs, they do not have the right opportunities to explore it. Therefore, the role of non-government organizations (NGOs) is imminent in supporting women's entrepreneurial cause.

Design/methodology/approach

The problems of women entrepreneurs during venture creation have been explored. Case studies of women entrepreneurs and NGOs operating in Uttarakhand have been developed through an in-depth interview method.

Findings

Entrepreneurial learning occurs because of certain personal, social and environmentally driven motivational factors. Entrepreneurial learning helps in the development of personal, social, managerial and entrepreneurial competencies. These competencies are essential for the performance of an enterprise.

Practical implications

This study provides directions to policymakers and researchers to focus on developmental programmes for women entrepreneurs.

Originality/value

This study explores a conceptual framework for the promotion of women entrepreneurship.
New product announcements effect on stock prices in India
Authors: Mann Bikram Jit Singh , Babbar Sonia
Published: October 2017

Purpose

The purpose of this study is to study the impact of new product announcements on the shareholder value in India since; there is lack of perceptive results regarding the impact. Also, an attempt has been made to analyse the determinants of value creation, by industry type, which has so far escaped the attention of researchers.

Design/methodology/approach

First, standard event study methodology has been used to measure the abnormal gains/losses of the announcing firms for the new product introductions. Second, regression analysis has been conducted to find out the relationship between the shareholder value and the firm and industry characteristic variables.

Findings

The results of the study show that the announcing companies in India have got significant positive returns during the announcement of the new product. The value stands at 0.00455 for the event day. In the second part, the application of the regression test has found that firm size, R&D intensity, free cash flow, debt ratio and market size are significant variables in the determination of the shareholder value.

Originality/value

The present study goes a step further in establishing the reasons for value creation when new product announcements are made by the Indian firms. The analysis has been carried out industry wise to identify the determinants of shareholder value in different industries. This would guide the decision makers at the strategic level and players of the stock market at large in taking much more informed decisions.
When does it make sense to focus business portfolios? A study of business group responses to institutional change in India
Authors: Ramaswamy Kannan , Purkayastha Saptarshi
Published: October 2017

Purpose

This paper aims to report the findings from a longitudinal study of Indian business groups responding to the pro-market reforms that the government had initiated. It explores their diversification choices at the group level and the group performance consequences of these choices during a period of institutional changes (1990-2008).

Design/methodology/approach

Ordinary least squares regressions were used to analyze data spanning the 1988-2008 study period for 98 Indian business groups.

Findings

Results show that business groups that focused their portfolios in the early stages of institutional reforms tended to perform worse than their counterparts that did not do so. However, as market reforms became more established, business groups that made the transition from an unfocused to a more focused portfolio experienced superior performance consequences.

Originality/value

The findings underscore the temporal dimension of focusing and suggest that both changing strategy by refocusing business portfolio too early or waiting too long to refocus can hurt performance outcomes.