bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractCeliac 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

AbstractEndophytic 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

AbstractAtomic 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

AbstractDifferential 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

AbstractSynapse 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

Abstract
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

AbstractHuman 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, 40<age≤50, and >50 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

AbstractIncreasingly, 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

AbstractGlycosphingolipids (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 &quot;omics&quot;, 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

AbstractThe 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

Abstract
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

AbstractCortical 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]&lt;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]&gt;&gt;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

AbstractThe 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~ &gt; 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

AbstractDiseases 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

AbstractIn 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.