bluuebunny/crossref_metadata_2025 huggingface dataset:
Biodiversity informatics: the challenge of linking data and the role of shared identifiers
Authors: Page Roderic
Published: July 2019

A major challenge facing biodiversity informatics is integrating data stored in widely distributed databases. Initial efforts have relied on taxonomic names as the shared identifier linking records in different databases. However, taxonomic names have limitations as identifiers, being neither stable nor globally unique, and the pace of molecular taxonomic and phylogenetic research means that a lot of information in public sequence databases is not linked to formal taxonomic names. This review explores the use of other identifiers, such as specimen codes and GenBank accession numbers, to link otherwise disconnected facts in different databases. The structure of these links can also be exploited using the PageRank algorithm to rank the results of searches on biodiversity databases. The key to rich integration is a commitment to deploy and reuse globally unique, shared identifiers (such as DOIs and LSIDs), and the implementation of services that link those identifiers.
A PI3K-mediated negative feedback regulates Drosophila motor neuron excitability
Authors: Howlett Eric , Lin Curtis , Lavery William , Stern Michael
Published: July 2019

Negative feedback can act as a homeostatic mechanism to maintain neuronal activity at a particular specified value. At the Drosophila neuromuscular junction, a mutation in the type II metabotropic glutamate receptor gene (mGluRA) increased motor neuron excitability by disrupting an autocrine, glutamate-mediated negative feedback. We show that mGluRA mutations increase neuronal excitability by preventing PI3 kinase (PI3K) activation and consequently hyperactivating the transcription factor Foxo. Furthermore, glutamate application increases levels of phospho-Akt, a product of PI3K signaling, within motor nerve terminals in an mGluRA-dependent manner. In humans, PI3K and type II mGluRs are implicated in epilepsy, neurofibromatosis, autism, schizophrenia and other neurological disorders; however, neither the link between type II mGluRs and PI3K, nor the role of Foxo in the control of neuronal excitability, had been previously reported. Our work suggests that some of the deficits in these neurological disorders might result from disruption of glutamate-mediated homeostasis of neuronal excitability.
Immunity to self co-generates regulatory T cells
Authors: Dromey James , Lee Bo Han , Young Helen , Mannering Stuart , Jensen Kent , Thearle Daniel , Fourlanos Spiros , Belov Larissa , Harrison Leonard
Published: July 2019

Immune responses to self are kept in check by tolerance mechanisms, including suppression by regulatory T cells (Tregs). The defective generation of Tregs specific for self-antigens may lead to autoimmune disease. We identified a novel population of human CD4^+^ Tregs, characterized by high surface expression of CD52, which is co-generated in response to autoantigen. Blood CD4^+^CD52^hi^ T cells were generated preferentially in response to low-dose autoantigen and suppressed proliferation and interferon-[gamma] production by other T cells. Depletion of resting CD4^+^CD52^hi^ T cells enhanced the T-cell response to autoantigen. CD4^+^CD52^hi^ Tregs were neither derived from nor distinguished by markers of conventional resting CD4^+^CD25^+^ Tregs. In response to the pancreatic islet autoantigens glutamic acid decarboxylase, the generation of CD4^+^CD52^hi^ Tregs was impaired in individuals with and at-risk for type 1 diabetes, compared to healthy controls and individuals with type 2 diabetes. CD4^+^CD52^hi^ Tregs co-generated to self-antigen may therefore contribute to immune homeostasis and protect against autoimmune disease.
Suggested actions from the Melbourne HVP Information Seminar
Authors: Cotton Richard , Axton Myles , Bankier Agnes , Brais Bernard , Cavedon Lawrence , du Sart Desirée , George Peter , Goldgar David , Harrison Terence , Hibbert Marienne , Hopper John , Macrae Finlay , O’Keefe Christine , Ravine David , Savarirayan Ravi , Sheffield Les , Smith Tim , Stokes Nicola , Sundararajan Vijaya , Thorburn David , Winship Ingrid
Published: July 2019

The Human Variome Project (HVP; www.humanvariomeproject.org) was initiated at a meeting in June 2006 and addressed the problems of collecting genetic information and generated 96 recommendations (http://www.nature.com/ng/journal/v39/n4/full/ng0407-423.html) to overcome these, with the focus on Mendelian disease. A considerable number of projects have been added, to those that have been ongoing for a number of years, since that meeting. Also, a planning meeting is to be held May 25-29, 2008 in Spain (http://www.humanvariomeproject.org/HVP2008/).A dramatic boost has been given to the HVP by the preparedness and action of the International Society for Gastrointestinal Hereditary Tumours (InSiGHT; www.insight-group.org), to, in order to improve their own informatics systems for dealing with inherited colon cancer, set up a pilot system for collection and databasing mutation and phenotype information, i.e. to act as pilot for the HVP. This is then intended to be transferred to other genes and countries. Much relevant activity in this project is being led from and is based in Melbourne.This meeting in Melbourne has been conceived to review the current local situation and plans for the future. We are privileged that Myles Axton, Editor of Nature Genetics, a strong supporter of the HVP (see April 2007 Nature Genetics Editorial) and who has some ideas in the area (see August 2007 Nature Genetics Editorial) agreed to be keynote speaker.We proposed that the output of this meeting be published and, with permission, the abstracts and presentations placed on the website (www.humanvariomeproject.org/?p=Melbourne_Meeting). We also hope it will inform the May HVP Planning Meeting.
Backup machinery of yeast transcriptional regulatory network
Authors: Sengupta Dhriti , Kundu Sudip
Published: July 2019

Several studies have suggested the existence of backup machinery of transcriptional regulatory networks (TRNs). Here, we have quantified the backup machinery of yeast gene's TRNs under five different conditions in terms of alternate paths and have revealed that a statistically significant (p<0.0001) stronger backup is maintained for endogenous processes (ENPs) than exogenous processes (EXPs). A number of biologically important genes (SUC2, MF(ALPHA)2, CLN2 etc) are observed that maintain a higher backup. Hub and random transcription factor (TF) knockouts in TRNs have showed ENPs are more robust to deletion than EXPs. While higher average connectivity of TFs in EXPs than ENPs can't explain the higher robustness in ENPs, we have found that the later have a densely interconnectedness explaining their specialized architecture that may have evolved due to evolutionary pressure. Some non-hub TFs identified here are more likely to be essential, and if not essential, have a larger impact on fitness.
Experimental and theoretical study of DNA oxidation
Authors: Song Yuanzhi
Published: July 2019

The electrochemical oxidation of DNA and bases at a glassy carbon electrode were investigated using cyclic and square-wave voltammetry analysis. The predicted oxidative potentials for DNA and bases using DFT method (B3LYP) are in agreement with the experimental ones.The DNA oxidation ascribes to N-protonated guanine and adenine. The calculated oxidative peaks indicate that the initial potential of DNA oxidation is around 0.432V for N-protonated guanine and 0.368V (vs.hydrogen standard electrode) at pH 7.00, and DNA as well as bases in acidity solution are more stable than those in alkalescent solution.
Biogeographic relationships among deep-sea hydrothermal vent faunas at global scale
Authors: Bachraty Charleyne , Legendre Pierre , Desbruyères Daniel
Published: July 2019

The discovery of deep-sea hydrothermal vent fauna, kilometers deep in the oceans, is a great achievement of 20th-century marine biology. The deep-sea hydrothermal food web does not directly depend on the sun energy. Vent communities rely primarily on trophic associations between chemoautotrophic bacteria and consumers. A small number of endemic taxa are adapted to this highly toxic environment distributed along ridge crests. Where they appeared and how they dispersed is among the important questions ecologists must answer. Here, by statistical analysis of the most comprehensive data base ever assembled about deep-sea hydrothermal fauna, we delineate six major hydrothermal provinces in the World Ocean, then we identify five significant dispersal flows between adjacent provinces and derive a hypothesis about the center from which that fauna has dispersed to the oceanic ridges of the world. Our data-driven conclusion can be tested by phylogenetic studies and completed by surveys of less explored fields.
Seeing faces: evidence suggesting cortical disinhibition in the genesis of visual hallucinations.
Authors: Iaria Giuseppe , Fox Christopher , Barton Jason
Published: July 2019

The neural mechanisms responsible for triggering visual hallucinations are poorly understood. Here, we report a unique patient whose hallucinations consist exclusively of faces, and which could be reliably precipitated by looking at trees. Using functional Magnetic Resonance Imaging (fMRI), we found that, while face hallucinations was associated with increased neural activity in a number of cortical regions, including low-level visual areas, there was significant decreased activity in the right fusiform face area, a region that is empirically defined by increase activity during veridical perception of faces. These findings indicate key differences in how hallucinatory and veridical perceptions lead to the same phenomenological experience of seeing faces, and are consistent with the hypothesis that hallucinations may be generated by decreased inhibitory inputs to key cortical regions, in contrast to the excitatory synaptic inputs underlying veridical perception.
Integrated disease management using environmental control in tea fields
Authors: Tomihama Tsuyoshi , Toshiyuki Nonaka , Yatsuka Nishi , Kei Arai
Published: July 2019

The occurrence of plant disease depends on interactions between the host plant, a pathogen, and the environment in a dynamic called "the disease triangle". Bacterial shoot blight (BSB) disease, caused by Pseudomonas syringae pv. theae (Pst), is a major bacterial disease of tea plants in Japan and substantially reduces tea productivity. BSB mainly occurs in the low-temperature season, and lesion formation by Pst is enhanced by both low temperature and the presence of ice nucleation-active Xanthomonas campestris (INAX), which catalyses ice formation at -2 to -4^o^C and is frequently co-isolated with Pst from tea plants^5^. Low temperature is thus the most important environmental factor to influence the incident; however, the effects of environmental controls in fields on the occurrence of the disease are poorly understood. Here we show that the natural incidence of BSB in the field is closely related to low temperatures in late autumn. Frost protection in late autumn, which protected tea plants against extremely low temperatures, significantly decreased the incidence of BSB, and frost protection combined with bactericide application held the incident under the economic threshold level. Our data indicate that environmental control in the field based on microbial interactions in the host offers a new strategy for plant disease control using integrated plant disease management based on the disease triangle concept.
Systems biology of energetic and atomic costs in the yeast transcriptome, proteome, and metabolome
Authors: Barton Michael , Papp Balazs , Delneri Daniela , Oliver Stephen , Rattray Magnus , Bergman Casey
Published: July 2019

Background:

Every protein has a variable atomic and energetic cost to the cell based on the synthesis of its constituent amino acids. Quantifying the cost of amino acid synthesis is challenging, however natural selection is expected to favour the use of proteins whose constituents are cheaper to produce in terms of energetic and atomic cost.

Results:

We develop a systems biology approach to estimate the cost of amino acid synthesis based on genome-scale metabolic models, and directly investigate the effects of the cost of amino acid synthesis on transcriptomic, proteomic and metabolomic data in Saccharomyces cerevisiae. We used our two new and six previously reported measures of amino acid cost in conjunction with codon usage bias, tRNA gene number and atomic composition to identify the factors that predict transcript, protein and free amino acid levels in the yeast cell. While most previously reported cost measures are highly correlated, we find that our systems approach to formulating the cost of amino acid synthesis produces a novel measure of cost, which explains similar levels of variation in gene expression. Regardless of the measure used, the cost of amino acid synthesis is weakly associated with transcript and protein levels, independent of codon usage bias. In contrast, energetic costs explain a large proportion of variation in levels of free amino acids.

Conclusions:

In the economy of the yeast cell, the cost of amino acid synthesis correlates with transcript and protein levels to a lesser degree than translational optimisation, whereas atomic and energetic cost plays a much larger role in explaining levels in free amino acids. However, as there appears to be no single currency to compute the cost of amino acid synthesis, a systems approach is necessary to uncover the full effects of amino acid biosynthetic cost in complex biological systems that vary with cellular and environmental conditions.
Tautomeric Equilibria Studies by Mass Spectrometry
Authors: Allegretti Patricia , Schiavonni Mercedes , Castro Eduardo , Furlong Jorge
Published: July 2019

Tautomerism in organic chemistry has been extensively studied in condensed phase by spectrometric methods, mainly by IR and NMR techniques. Mass spectrometry studies start 40 years ago but just recently it has been recognized the importance of the mass spectral data for the study of tautomerism in the gas phase.Mass spectrometry can provide valuable information in regard to tautomeric equilibria when studying mass spectra among the members of different families of organic compounds.The relevance of the mass spectral data resides on several facts but there are two that are of key importance:1- Mass spectral fragmentation assignments should be tautomer specific since the corresponding abundances ratios are supposed to be correlated to the keto/enol contents.2- Ionization in the ion source is supposed to have no effect on the position of the equilibrium so that the results reflect the tautomers content in the gas phase previous to ionization.Some of the carbonylic compounds do not exhibit noticeable tautomerism so the fragment abundances assigned to the enol form is very low or not measurable. Since enolization is more noticeable in the case of thio-derivatives (which correlates adequately with the oxygenated analogues), the study of their mass spectra is an interesting choice to reach some degree of generalization. In addition, experimental findings are supported by semiempirical theoretical calculations, which probed to be adequate not only for supporting tendency correlations among the members of a compound family but also to calculate heats of tautomerization in gas phase.Reports using mass spectrometry for tautomerism are becoming less common. One of the reasons is that now it would appear that the interpretation of MS results is not as straightforward as it was once believed, even though in a recent review it was written that: “Mass spectrometry is the most informative and practical method for studying and identifying tautomers in the gas phase” [1]. In fact, mass spectrometry seems to be very informative for studying and identifying tautomers, because in this case external factors like solvents, intermolecular interactions, etc., can be excluded by transferring the tautomeric system into gas phase, where the process becomes truly unimolecular [1].This review covers the study of Tautomerism by Mass Spectrometry in the last four decades.
IL-1 regulates the IL-23 response to wheat gliadin, the etiologic agent of Celiac Disease
Authors: Harris Kristina , Fasano Alessio , Mann Dean
Published: July 2019

Celiac disease (CD) is an autoimmune disease prevalent in ~1% of the general population. CD is unique because both the major genetic (Human Leukocyte Antigen-DQ2/DQ8 alleles) and etiologic factors (dietary glutens) for susceptibility are known. While these alleles are responsible for the inappropriate T cell response that characterizes CD, they are not sufficient since most HLA-DQ2+/DQ8+ individuals exposed to glutens never develop disease. The reasons for this have not been explained; however our novel findings strongly advocate a role for interleukin-23 (IL-23) in the immunopathogenesis of CD. We demonstrate that wheat gliadin stimulates monocytes to produce significantly higher amounts of inflammatory cytokines IL-1b, IL-23, and tumor necrosis factor-a (TNFa) in CD patients compared to HLA-DQ2+ healthy individuals. Furthermore, we determine that IL-1 signalling is obligatory for production of IL-23, since IL-1b triggers IL-23 secretion in a dose-dependent manner and IL-1 receptor antagonist (IL-1ra) blocks IL-23 responses to gliadin. Our results suggest that gliadin activation of monocytes and the subsequent robust secretion of IL-1b and IL-23 initiate the immune response cascade that is manifest as CD, and reveal for the first time that the IL-1 system regulates production of IL-23. The discovery of IL-23 has highlighted the critical role of the innate immune response in autoimmunity and other inflammatory conditions. We anticipate that our novel findings will lead to the discovery of therapeutic targets for this disease and other inflammatory diseases mediated by IL-23.
Light converts endosymbiotic fungus to pathogen, influencing seedling survival and host tree recruitment
Authors: Alvarez Patricia , White Jr James , Gil Nataly , Svenning Jens-Christian , Balslev Henrik , Kristiansen Thea
Published: July 2019

Endophytic fungi that asymptomatically colonize plants^1^ are diverse and abundant in tropical ecosystems^2^. These organisms can be weakly pathogenic^3^ and/or mutualistic, frequently enabling plants to adapt to extreme environments, alter competitive abilities of host individuals and improve host fitness under abiotic or biotic stresses^4,5,6^. Diplodia mutila is a symbiotic endophyte/plant pathogenic fungus infecting the palm Iriartea deltoidea^7^, which dominates many wet lowland Neotropical forests. The fungus is an asymptomatic endophyte in mature plants, and disease and mortality are expressed in some seedlings, while others remain disease free. Here we show that seedlings bearing the endophyte show enhanced resistance to insect herbivory. However, high light availability triggers pathogenicity of the fungus, while low light favors endosymbiotic development, constraining recruitment of endophyte-infested seedlings to the shaded understory by limiting survival of seedlings in direct light. These results provide evidence that patterns of plant abundance and the mechanisms maintaining tropical forest biodiversity are the result of a more complex interplay between abiotic and biotic environments than previously thought.
Valid and efficient formula for free energy difference from nonequilibrium work
Authors: Chen Liao
Published: July 2019

Atomic force microscopes and optical tweezers afford direct probe into the inner working of single biomolecules by mechanically unfolding them.^1-15^ Critical to the success of this type of probe is to correctly extract the free energy differences between the various conformations of a protein/nucleic acid along its forced unfolding pathways. Current studies rely on the Jarzynski equality^16^ (JE) or its undergirding Crooks fluctuation theorem^17^ (CFT), even though questions remain on its validity^17-19^ and on its accuracy.^13,20-21^ The validity of JE relies on the assumption of microscopic reversibility.^17,18^ The dynamics of biomolecules, however, is Langevin stochastic in nature. The frictional force in the Langevin equation breaks the time reversal symmetry and renders the dynamics microscopically irreversible even though detailed balance holds true. The inaccuracy of JE has largely been attributed to the fact that one cannot sample a large enough number of unfolding paths in a given study, experimental or computational.^13,15^ Here I show that both of these questions can be answered with a new equation relating the nonequilibrium work to the equilibrium free energy difference. The validity of this new equation requires detailed balance but not microscopic reversibility. Taking into the new equation equal number of unfolding and refolding paths, the accuracy is enhanced ten folds in comparison to a JE study based on a similar but larger number of unfolding paths.
Trichoscopy criteria for diagnosing female androgenic alopecia.
Authors: Rakowska Adriana , Slowinska Monika , Kowalska-Oledzka Elzbieta , Olszewska Malgorzata , Rudnicka Lidia
Published: July 2019

Differential diagnosis of chronic hair loss remains a challenge in dermatology. The aim of the study was to evaluate the value of a new scalp visualization technique, trichoscopy, in differential diagnosis of hair loss. Trichoscopy was performed in 131 females (59 with androgenic alopecia, 33 with chronic telogen effluvium, 39 healthy controls). Based study results, a standardized trichoscopy report was developed and diagnostic criteria for female androgenic alopecia were established. Major criteria: increased number of yellow dots and thin hairs, as well as decreased average hair thickness in frontal area. Minor criteria: increased frontal area to occiput ratio of single-hair units (>2:1), vellus hairs (>1.5:1) and follicles with perifollicular discoloration (>3:1) Fulfillments of 2 major criteria or 1 major and 2 minor is diagnostic for female androgenic alopecia with a 92% specificity. In conclusion, trichoscopy is the first method which allows differential diagnosis of hair loss and establishing the diagnosis of female androgenic alopecia.
Synaptic modification and entrained phase are phase dependent in STDP
Authors: Zhao Gang
Published: July 2019

Synapse strength can be modified in an activity dependent manner, in which the temporal relationship between pre- and post-synaptic spikes plays a major role. This spike timing dependent plasticity (STDP) has profound implications in neural coding, computation and functionality, and this line of research is booming in recent years. Many functional roles of STDP have been put forward. Because the STDP learning curve is strongly nonlinear, initial state may have great impacts on the eventual state of the system. However, this feature has not been explored before. This paper proposes two possible functional roles of STDP by considering the influence of initial state in modeling studies. First, STDP could lead to phase-dependent synaptic modification that have been reported in experiments. Second, rather than leading to a fixed phase relation between pre- and post-synaptic neurons, STDP that includes suppression between the effects of spike pairs lead to a distributed entrained phase which also depend on the initial relative phase. This simple mechanism is proposed here to have the ability to organize temporal firing pattern into dynamic cell assemblies in a probabilistic manner and cause cell assemblies to update in a deterministic manner. It has been demonstrated that olfactory system in locust, and even other sensory systems, adopts the strategy of combining probabilistic cell assemblies with their deterministic update to encode information. These results suggest that STDP rule is a potentially powerful mechanism by which higher network functions emerge.
Overweight, Obesity and Socio-economic Change among Tangkhul Naga Tribal Women of Manipur, North East India
Authors: Mungreiphy N.K. , Kapoor Satwanti
Published: July 2019

Background:

The prevalence of overweight and obesity is increasing worldwide at an alarming rate. Although in countries like India, which is multi-ethnic having multi socio-economic levels, is typically known for high prevalence of under nutrition, significant proportions of overweight and obese now coexist with the undernourished.

Objectives:

The study aims to find the prevalence of overweight and obesity, and its association with socio-economic change among Tangkhul Naga women of Manipur, North East India and also to compare with other female populations of India.

Methods:

A cross-sectional study was carried out among 346 Tangkhul Naga tribal women of Manipur, age ranging from 20 to 70 years, divided into five different age groups with ten years interval each.

Results and conclusions:

Mean BMI was found to be lowest among the youngest age group and it increased with age till fifty nine years and then declined. BMI was assessed using recommended cut-off points for Asians and the prevalence of overweight and obesity among the Tangkhul Naga women was found to be 27.1%. When BMI was assessed using the WHO International Classification of adult overweight and obesity, the prevalence percentage was 9.8. Though the prevalence of obesity among Tangkhul females (2.0%) was low when compared to Indian non-tribal female populations the prevalence of overweight (25.1%) was not far behind. Tangkhul Naga is a population where majority of them were believed to be thin traditionally owing to difficult hilly terrain habitation and physically active lifestyle. With urbanization and economic development, a nutritional transition characterized by improved dietary habits, improvement in socio-economic status and increasingly sedentary lifestyle has been observed which has contributed to the increasing prevalence of overweight and obesity among the Tangkhul Naga tribal women.
Is the innate bio-protection power against human virus the same between males and females? A conclusion based on blood donor data of HTLV-I infection
Authors: Eshima Nobuoki , Tabata Minoru , Higuchi Yasunori , Karukaya Shigeru
Published: July 2019

Human T-cell leukemia virus type I (HTLV-I) is a retrovirus that causes adult T-cell leukemia. The male-to-female transmission is stronger than the reverse, so the carrier proportion of women is greater than that of men. On the other hand, since the mother-to-child transmission route via the breast-feeding is common for baby boys and girls, it has been thought the HTLV-I proportions of boys and girls are the same until now. A question arises as to whether the "innate protection powers against human virus" are the same between baby boys and girls. We utilize Blood donors in 1995-1998, which were provided by Japan Red Cross Society of Oita, Japan. The data are summarized into the frequency table with respect to gender and age. The age groups are <20, 20<age≤30, 30<age≤40, 4050 years old. The comparison of carrier proportions of males and females under 20 years old is made with a two-sided statistical test and for the other groups one-sided tests are carried out. The preset statistical analysis shows that the carrier proportion of girls is less than that that of boys. It implies that in HTLV-I the mother-to-child transmission probability of females is less than that of males. According to the present findings, it follows that the female's innate protection power against HTLV-I is stronger than that of males, and the conclusion may become a valid proposition for general human virus.
Ontology (Science)
Authors: Smith Barry
Published: July 2019

Increasingly, in data-intensive areas of the life sciences, experimental results are being described in algorithmically useful ways with the help of ontologies. Such ontologies are authored and maintained by scientists to support the retrieval, integration and analysis of their data. The proposition to be defended here is that ontologies of this type – the Gene Ontology (GO) being the most conspicuous example – are a part of science. Initial evidence for the truth of this proposition (which some will find self-evident) is the increasing recognition of the importance of empirically-based methods of evaluation to the ontology develop¬ment work being undertaken in support of scientific research. Ontologies created by scientists must, of course, be associated with implementations satisfying the requirements of software engineering. But the ontologies are not themselves engineering artifacts, and to conceive them as such brings grievous consequences. Rather, ontologies such as the GO are in different respects comparable to scientific theories, to scientific databases, and to scientific journal publications. Such a view implies a new conception of what is involved in the author¬ing, maintenance and application of ontologies in scientific contexts, and therewith also a new approach to the evaluation of ontologies and to the training of ontologists.
Structural and functional glycosphingolipidomics by glycoblotting with aminooxy-functionalized gold nanoparticle
Authors: Nagahori Noriko , Abe Midori , Nishimura Shin-Ichiro
Published: July 2019

Glycosphingolipids (GSLs) synthesized in Golgi apparatus by sequential transfer of sugar residues to a ceramide lipid anchor are ubiquitously distributing on vertebrate plasma membranes. Standardized method allowing for high throughput structural profiling and functional characterization of living cell surface GSLs is of growing importance because they function as crucial signal transduction molecules in various processes of dynamic cellular recognitions. However, methods are not available for amplification of GSLs, while the genomic scale PCR amplification permits large-scale mammalian proteomic analysis.&x3000;Here we communicate such an approach to a novel "omics", namely glycosphingolipidomics based on the glycoblotting method. The method, which involves selective ozonolysis of the C-C double bond in ceramide moiety and subsequent enrichment of generated GSL-aldehydes by chemical ligation using aminooxy-functionalized gold nanoparticle (aoGNP) should be of widespread utility for identifying and characterizing whole GSLs present in the living cell surfaces. The present protocol using glycoblotting permitted MALDI-TOFMS-based high throughput structural profiling of mouse brain gangliosides such as GM1, GD1a/GD1b, and GT1b for adult or GD3 in case for embryonic mouse. When mouse melanoma B16 cells were subjected to this protocol, it was demonstrated that gangliosides enriched from the plasma membranes are only GM3 bearing microheteogeneity in the structure of N-acyl chain. Surface plasmon resonance analysis revealed that aoGNP displaying whole GSLs blotted from mouse B16 melanoma cell surfaces can be used directly for monitoring specific interaction with self-assembled monolayer (SAM) of Gg3Cer (gangliotriaosylceramide). Our results indicate that GSL-selective enrichment onto aoGNP from living cell surfaces allows for rapid reconstruction of plasma membrane models mimicking intact GSL-microdomain feasible for further structural and functional characterization.
Dynamic hydration valve controlled ion permeability and stability of NaK channel
Authors: Shen Rong , Guo Wanlin , Zhong Wenyu
Published: July 2019

The K^+^, Na^+^, Ca^2+^ channels are essential to neural signalling, but our current knowledge at atomic level is mainly limited to that of K^+^ channels. Unlike a K^+^ channel having four equivalent K^+^-binding sites in its selectivity filter, a NaK channel conducting both Na^+^ and K^+^ ions has a vestibule in the middle part of its selectivity filter, in which ions can diffuse but not bind specifically. However, how the NaK channel conducts ions remains elusive. Here we find four water grottos connecting with the vestibule of the NaK selectivity filter. Molecular dynamics and free energy calculations show that water molecules moving in the vestibule-grotto complex hydrate and stabilize ions in the filter and serve as a valve in conveying ions through the vestibule for controllable ion permeating. During ion conducting, the water molecules are confined within the valve to guarantee structure stability. The efficient exquisite hydration valve should exist and play similar roles in the large family of cyclic nucleotide-gated channels which have similar selectivity filter sequences. The exquisite hydration valve mechanism may shed new light on the importance of water in neural signalling.
Angiogenesis and Vasculogenesis at 7-Day of Reperfused Acute Myocardial Infarction
Authors: Kang Sheng , Yang Yue-jin , Wang Qing-zhi , Li Yue , Tian Yi , Cheng Yu-tong , Shen Wei-feng
Published: July 2019

Objectives

This study is to investigate the angiogenesis and vasculogenesis at the first week of reperfused acute myocardial infarction (AMI).Methods 16 of mini-swines (20 to 30 Kg) were randomly assigned to the sham-operated group and the AMI group. The acute myocardial infarction and reperfusion model was created and the pig tail catheter was performed to monitor hemodynamics before left anterior descending coronary artery (LAD) occlusion, 90 min of LAD occlusion and 120 min of LAD reperfusion. Pathologic myocardial tissue was collected at 7-day of LAD reperfusion and further assessed by immunochemistry, dual immunochemistry, in-situ hybridization, real-time quantitative polymerase chain reaction and western blot. Results The infarcted area had higher FLK1 mRNA expression than sham-operated area and the normal area (all P<0.05), and the infarcted and marginal areas showed higher CD146 protein expression than the sham-operated area (all P<0.05), but the microvessel density (CD31 positive expression of microvessels/HP) was not significantly different between the infarcted area and the sham-operated area (8.92±3.05 vs 6.43±1.54) at 7-day of reperfused acute myocardial infarction (P>0.05).

Conclusions

FLK1 and CD146 expression significantly increase in the infarcted and marginal areas, and the microvessel density is not significantly different between the infarcted area and the sham-operated area, suggesting that angiogenesis and vasculogenesis in the infarcted area appear to high frequency of increase in 7-day of reperfused myocardial infarction.
Migraine aura: retracting particle-like waves in weakly susceptible cortex
Authors: Dahlem Markus , Hadjikhani Nouchine
Published: July 2019

Cortical spreading depression (SD) has been suggested to underlie migraine aura. Despite a precise match in speed, the spatio-temporal patterns of SD and aura symptoms on the cortical surface ordinarily differ in aspects of size and shape. We show that this mismatch is reconciled by utilizing that both pattern types bifurcate from an instability point of generic reaction-diffusion models. To classify these spatio-temporal pattern we suggest a susceptibility scale having the value [sigma]=1 at the instability point. We predict that human cortex is only weakly susceptible to SD ([sigma]<1), and support this prediction by directly matching visual aura symptoms with anatomical landmarks using fMRI retinotopic mapping. We discuss the increased dynamical repertoire of cortical tissue close to [sigma]=1, in particular, the resulting implications on migraine pharmacology that is hitherto tested in the regime ([sigma]>>1), and potentially silent aura occurring below a second bifurcation point at [sigma]=0 on the susceptible scale.
A Hyperstable Miniprotein: Additive Effects of D- and L-Ala Substitutions
Authors: Williams D. , Barua Bipasha , Andersen Niels
Published: July 2019

The effects of alanine substitutions in each helical segment of the structure, and Gly to D-Ala mutations at sites where glycines have positive phi angles in the Trp-cage miniprotein are reported. The effects of the stabilizing mutation were additive, yielding a 20-residue construct (Tm = 83^o^C). Gly to L-Ala substitutions were uniformly destabilizing ([DELTA][DELTA]G~F~ > 11 kJ/mol): the preference for a D-Ala can be as large as 16 kJ/mol. Glycine to D-Ala mutations are validated as a strategy for the design of hyperstable miniprotein scaffolds suitable for stereospecific pharmacophore display.
Recombinant Mitochondrial Transcription Factor A with N-terminal Mitochondrial Transduction Domain Increases Respiration and Mitochondrial Gene Expression in G11778A Leber's Hereditary Optic Neuropathy Cybrid Cells
Authors: Iyer Shilpa , Thomas Ravindar , Portell Francisco , Dunahm Lisa , Quigley Caitlin , Bennett James
Published: July 2019

Diseases involving mitochondrial defects usually manifest themselves in high-energy, post-mitotic tissues such as brain, retina, skeletal and cardiac muscle and frequently cause deficiencies in mitochondrial bioenergetics. We have developed a scalable procedure to produce recombinant human mitochondrial transcription factor A (TFAM) modified with an N-terminal protein transduction domain (PTD) and mitochondrial localization signal (MLS) that allow it to cross membranes and enter mitochondria through its "mitochondrial transduction domain" (MTD,=PTD+MLS). in vitro studies in a classic mitochondrial disease cell model demonstrated that Alexa488-labeled MTD-TFAM rapidly entered the mitochondrial compartment. MTD-TFAM treatment of these cell lines reversibly increased oxygen consumption (respiration) rates 3-fold, levels of respiratory proteins and mitochondrial gene expression. in vivo results demonstrated that respiration increased to lesser degrees in mitochondria from tissues of mice injected with MTD-TFAM. MTD-TFAM can alter mitochondrial bioenergetics and holds promise for treatment of mitochondrial diseases involving deficiencies of energy production.
Activation of Ras-ERK pathway by Fgf8 and its downregulation by Sprouty2 for the isthmus organizing activity
Authors: Suzuki-Hirano Asuka , Sato Tatsuya , Nakamura Harukazu
Published: July 2019

In the previous studies, we showed that strong Fgf8 signaling activates the Ras-ERK pathway to induce cerebellum. Here, we show importance of negative regulation of this pathway. 'Prolonged' activation of ERK by misexpression of Fgf8b and dominant-negative Sprouty2 (dnSprouty2) did not change the fate of the mesencephalic alar plate. Downregulation of ERK activity using a MEK inhibitor, U0126, or by tetracycline dependent Tet-off system after co-expression of Fgf8b and dnSprouty2, forced the mesencephalic alar plate to differentiate into cerebellum. We then paid attention to Mkp3. After misexpression of dnMkp3 and Fgf8b, slight downregulation of ERK activity occurred, which may be due to Sprouty2, and the mesencephalon transformed to the isthmus-like structure. The results indicate that ERK must be once upregulated and then be downregulated for cerebellar differentiation, and that differential ERK activity level established by negative regulators receiving Fgf8 signal may determine regional specificity of mesencephalon and metencephalon.
The effect of personality on reasoning
Authors: Fumero Ascensión , Santamaría Carlos , Johnson-Laird Phil
Published: July 2019

The ability to reason depends on intelligence, but preferences for different sorts of reasoning may depend on an individual’s personality. The possibility is unlikely if reasoning is akin to a formal proof in logic. But, such effects are predicted from the theory that reasoning is a semantic process of envisaging possibilities consistent with the meanings of premises and knowledge. According to the standard ‘big five’ model of personality, individuals differ in their openness to experience and in their conscientiousness. Certain inferential problems are ambiguous, e.g., if a pilot falls from a plane without a parachute then the pilot dies; this pilot didn’t die; how come? A deductive response is: the pilot didn’t fall from a plane without a parachute; an inductive response is: the plane was on the ground. Highly conscientious individuals who are also less open to experience should focus on the possibilities consistent with the premises, and tend to make a deduction, whereas those who are open to experience and not very conscientious should go beyond these possibilities, and tend to make an induction. Here we show that these biases occurred both for stable personality traits and for the same attitudes induced experimentally, either from false feedback about performance in a personality test or from participants’ recall of autobiographical episodes illustrating the required attitudes. Researchers have often assumed that reasoning is a universal akin to the ability to use natural language. They have also assumed that personality traits are stable with constant effects on cognition and behaviour. Our results imply that neither assumption is invariably correct. They also corroborate the semantic view of human reasoning, and may lead to the discovery of other effects of personality traits, such as extraversion and neuroticism, on reasoning.
A comparative analysis of 21 literature search engines
Authors: Acharya Kshitish , Kasliwal Greta , Haridas Haritha
Published: July 2019

With increasing number of bibliographic software, scientists and health professionals either make a subjective choice of tool(s) that could suit their needs or face a challenge of analyzing multiple features of a plethora of search programs. There is an urgent need for a thorough comparative analysis of the available bio-literature scanning tools, from the user’s perspective. We report results of the first time semi-quantitative comparison of 21 programs, which can search published (partial or full text) documents in life science areas. The observations can assist life science researchers and medical professionals to make an informed selection among the programs, depending on their search objectives. Some of the important findings are: 1. Most of the hits obtained from Scopus, ReleMed, EBImed, CiteXplore, and HighWire Press were usually relevant (i.e. these tools show a better precision than other tools). 2. But a very high number of relevant citations were retrieved by HighWire Press, Google Scholar, CiteXplore and Pubmed Central (they had better recall). 3. HWP and CiteXplore seemed to have a good balance of precision and recall efficiencies. 4. PubMed Central, PubMed and Scopus provided the most useful query systems. 5. GoPubMed, BioAsk, EBIMed, ClusterMed could be more useful among the tools that can automatically process the retrieved citations for further scanning of bio-entities such as proteins, diseases, tissues, molecular interactions, etc. The authors suggest the use of PubMed, Scopus, Google Scholar and HighWire Press - for better coverage, and GoPubMed - to view the hits categorized based on the MeSH and gene ontology terms. The article is relavant to all life science subjects.
Smoking-induced long-lasting modifications of human platelet serotonin catabolism through a MAO epigenetic regulation
Authors: Launay Jean-Marie , Del Pino Muriel , Chironi Gilles , Callebert Jacques , Peoc’h Katell , Mégnien Jean-Louis , Mallet Jacques , Simon Alain , Rendu Francine
Published: July 2019

Postulating that serotonin, secreted from smoking-activated platelets, could be involved in smoking-induced vascular modifications, we studied 115 men distributed in smokers (S), former smokers (FS) and never smokers (NS). The platelet serotonin content was similar in S and NS but lower in FS. This was unexpected because the monoamine oxidase (MAO) activity, which catabolizes serotonin, was inhibited during smoking. However, the amount of platelet MAO was higher in S and FS than in NS. The persistent elevated MAO amount in FS prompted us to study the methylation of its gene promoter in an additional series of patients: it was markedly lower for S and FS vs. NS due to cigarette smoke-induced increase of nucleic acid demethylase activity. This smoking-induced demethylation of the MAO gene promoter, resulting in high MAO amount persisting long after quitting smoking, has cardiovascular consequences and could impact fields such as behavior, mental health, and cancer.
Music in the first days of life
Authors: Perani Daniela , Saccuman Maria Cristina , Scifo Paola , Spada Danilo , Andreolli Guido , Rovelli Rosanna , Baldoli Cristina , Koelsch Stefan
Published: July 2019

In adults, specific neural systems with right-hemispheric weighting are necessary to process pitch, melody and harmony, as well as structure and meaning emerging from musical sequences. To which extent does this neural specialization result from exposure to music or from neurobiological predispositions? We used fMRI to measure brain activity in 1 to 3 days old newborns while listening to Western tonal music, and to the same excerpts altered, so as to include tonal violations or dissonance. Music caused predominant right hemisphere activations in primary and higher-order auditory cortex. For altered music, activations were seen in the left inferior frontal cortex and limbic structures. Thus, the newborn's brain is able to plenty receive music and to figure out even small perceptual and structural differences in the music sequences. This neural architecture present at birth provides us the potential to process basic and complex aspects of music, a uniquely human capacity.
Weight Stigma and Educators' Perceptions of Children's Psychological Symptoms
Authors: Pryor John , Reber Laura
Published: July 2019

Objective:

To investigate whether weight stigma influences educators' judgments about psychological symptoms in children.

Design:

Experimental study manipulating the weight status of children with school problems and examining implicit and explicit anti-fat attitudes as potential moderators of stigmatizing judgments.

Subjects:

188 pre-service educators.

Measurements:

Attributions of laziness as primary dependent variable plus measures of implicit and explicit anti-fat attitudes as potential moderators.

Results:

Educators were more likely to attribute laziness to overweight children with school problems. Implicit anti-fat attitudes moderated this effect.

Conclusion:

Spontaneous anti-fat attitudes were importantly related to educators' biases in understanding the psychological problems of obese children at school. Educators with more negative implicit anti-fat attitudes were more likely to attribute the school-relevant psychological symptoms of obese children to laziness. Explicit anti-fat attitudes did not moderate these attributions.
Chronic thoracic hemisection spinal cord injury in adult rats induces a progressive decline in transmission from uninjured fibers to lumbar motoneurons
Authors: Arvanian Victor , Schnell Lisa , Lou Li , Golshani Roobeh , Hunanyan Arsen , Ghosh Arko , Pearse Damien , Robinson John , Schwab Martin , Fawcett James , Mendell Lorne
Published: July 2019

Although most spinal cord injuries are anatomically incomplete, only limited functional recovery has been observed in people and rats with partial lesions. To address why surviving fibers cannot mediate more complete recovery, we evaluated the physiological and anatomical status of spared fibers after unilateral hemisection (HX) of thoracic spinal cord in adult rats. We made intracellular and extracellular recordings at L5 (below HX) in response to electrical stimulation of contralateral white matter above (T6) and below (L1) HX. Responses from T6 displayed reduced amplitude, increased latency and elevated stimulus threshold in the fibers across from HX, beginning 1-2 weeks after HX. Ultrastructural analysis revealed demyelination of intact axons contralateral to the HX, with a time course similar to the conduction changes. Behavioral studies indicated partial recovery which arrested when conduction deficits began. These findings suggest a chronic pathological state in intact fibers and necessity for prompt treatment to minimize it.