bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractObjectiveHuman 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.MethodsExtracellular 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.ResultsIn 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.ConclusionsIn 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.SignificanceOur 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

AbstractBackgroundDifferences 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.PurposeThis study approached the need for a novel analytical strategy in authentication of herbal products.MethodsA 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.ResultsHPTLC 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 %.ConclusionThe 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.AbbreviationsEMAEuropean Medicines AgencyBLASTbasic local alignment search toolFTIRFourier-transformed infrared spectroscopyIRinfrared spectrometryHPTLChigh performance thin layer chromatographymatKmaturase KMSmass spectrometryMOTUmolecular taxonomic unitnrITSnuclear ribosomal internal transcribed spacerPh.Eur.European PharmacopoeiarbcLribulose bisphosphate carboxylaseTLCthin-layer chromatographyUV-VISultraviolet-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

AbstractPalbociclib 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

AbstractBeing 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

ABSTRACTThe 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

ABSTRACTAccurate 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

AbstractPurposeIntraocular 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.MethodsThe 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.ResultsThe 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.ConclusionsWe 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

AbstractUnderstanding 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

AbstractBackground: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

SUMMARYHuman 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.HIGHLIGHTSRNA inhibits human APOBEC3H DNA cytosine deaminase activityRNA binding mutants are DNA hypermutatorsX-ray structure demonstrates an RNA duplex-mediated APOBEC3H dimerization mechanismRNA 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

AbstractPaleo-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

SUMMARYWe 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

AbstractTheoretical 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

AbstractA 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 SummaryA 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.