bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanoconfinement of spider silk fibrils begets superior strength, extensibility and toughness
Authors: Giesa Tristan , Arslan Melis , Pugno Nicola , Buehler Markus 
Published: July 2019

AbstractSilk is an exceptionally strong, extensible and tough material made from simple protein building blocks. The molecular structure of dragline spider silk repeat units consists of semi-amorphous and nanocrystalline beta-sheet protein domains. Here we show by a series of computational experiments how the nanoscale properties of silk repeat units are scaled up to create macroscopic silk fibers with outstanding mechanical properties despite the presence of cavities, tears and cracks. We demonstrate that the geometric confinement of silk fibrils to diameters of 50±30 nm width is critical to facilitate a powerful mechanism by which hundreds of thousands of protein domains synergistically resist deformation and failure to provide enhanced strength, extensibility and toughness at the macroscale, closely matching experimentally measured mechanical properties. Through this mechanism silk fibers exploit the full potential of the nanoscale building blocks, regardless of the details of microscopic loading conditions and despite the presence of large defects. Experimental results confirm that silk fibers are composed of silk fibril bundles with diameters in the range of 20-150 nm, in agreement with our predicted length-scale. Our study reveals a general mechanism to map nanoscale properties to the macroscale and provides a potent design strategy towards novel fiber and bulk nanomaterials.
Neem leaf glucosamine stimulates Interleukin-2 (IL-2) in swiss albino mice
Authors: Venugopalan Santhosh Kumar , Viswesharan Navaratnam , Aiyalu Rajasekaran , N K Nair 
Published: July 2019

AbstractNeem leaf glucosamine-mediated immune stimulation was studied in male swiss albino mice. Mice were treated with three doses of Neem leaf glucosamine (266, 400 and 800 µg/30gm mouse, intraperitoneal injection) one dose per week for four weeks. At doses of 266, 400 and 800 µg/30gm mouse a significant increase in Interleukin-2 in mice serum was observed when compared to the control group and also an increase in relative organ weight of the thymus was observed but there was a mild increase in liver and kidney weights. The immune stimulatory response of Neem leaf glucosamine was also observed in T-lymphocyte proliferation. Overall, Neem leaf glucosamine showed a stimulatory effect on immune functions in mice. The immunostimulatory effect of Neem leaf glucosamine as reported in this study will have special relevance for the prophylactic and potential therapeutic treatment of various infectious diseases and antitumor activity.
Cancer invasion associated gene expression signature is present in differentially expressed genes in the reprogramming of fibroblasts into stem cells
Authors: Cheng Wei-yi , Kim Hoon , Kandel Jessica , Anastassiou Dimitris 
Published: July 2019

AbstractTumors become invasive by penetrating adjacent connective tissue, but the underlying biological mechanisms remain obscure. We recently identified a precise gene expression signature of fibroblastic origin associated with cancer invasion, the first step of the metastatic cascade. The signature contains many coordinately overexpressed genes, prominent among which are COL11A1, THBS2 and INHBA. Here we show that there is a striking similarity between the set of expressed genes in this metastasis-associated fibroblastic (MAF) signature and the set of genes that are downregulated when fibroblasts are reprogrammed to induced pluripotent stem cells (iPSCs). Because it is known that fibroblast reprogramming involves a mesenchymal epithelial transition (MET), the above facts suggest that, conversely, the metastasis-associated fibroblasts responsible for the signature may result from stem-like cells undergoing some type of epithelial-mesenchymal transition (EMT). Therefore, we speculate that cancer stem cells (CSCs) undergoing some type of EMT become fibroblastic to obtain motility and invasiveness, reactivating early embryonic developmental pathways, and that these fibroblast-like cells are the main source of the MAF signature that we previously identified.
Genetic Analysis of ABO and Rh Blood Groups in Brahmin Population of Uttar Pradesh, India”
Authors: Rai Vandana 
Published: July 2019

AbstractA series of glycoprotein and glycolipids on the red blood cell surface constitute blood group antigens. These are A, B, AB and O in ABO blood group system and Rh in rhesus blood group system. These antigens are genetically controlled. Certain diseases have been shown to be associated with certain blood groups. In the present study an attempt is made to study the distribution of ABO and Rh. (D) blood group systems among the Brahmin caste population of Uttar Pradesh State. A total of 200 unrelated Brahmin individuals from Uttar Pradesh were studied for the phenotype and allele frequency distribution of ABO and Rh (D) blood groups. The order of occurrence of ABO phenotypes is B>O>A>AB. The corresponding allele frequencies of O, A, and B alleles are found to be 0.5790, 0.1510 and 0.2697 respectively. The allele frequency of D (0.735) is more than d (0.265). The present study was compared with the other studies reported to understand the affinity between them.
Tuning and regulating the repertoire of glycan determinants
Authors: Wallace Rodrick , Wallace Deborah 
Published: July 2019

AbstractWe apply Tlusty's information-theoretic index theorem analysis of the genetic code to the glycome, using a cognitive paradigm by which external information sources constrain and tune the glycan code error network, in the context of available metabolic energy. The model suggests spontaneous symmetry breaking of the glycan code as a function of metabolic energy intensity, an effect that may be currently present, or embedded in evolutionary trajectory, recording large-scale ecosystem resilience shifts in energy availability such as the aerobic transition. Once focused on a subset of the glycan error code network however, the glycan production machinery must then be regulated by an elaborate cognitive process to ensure that what is produced matches what has been chosen for production. Index theorem methods emerge in a highly natural manner for this composite system whose failures will be represented by a spectrum of glycan disorders.
Information homeostasis as a fundamental principle governing the cell division and death
Authors: Kumar Arvind , Singh Harinder 
Published: July 2019

AbstractTo express genetic information with minimal error is one of the key functions of a cell. Here we propose an information theory based phenomenological model for the expression of genetic information. Based on the model we propose, the concept of "information homeostasis" ensures that genetic information is expressed with minimal error. We suggest that together with energy homeostasis, information homeostasis is a fundamental working principle of a biological cell. This model proposes a novel explanation of why a cell divides and why it stops to divide and thus provides novel insight into oncogenesis and various neuro-degenerative diseases. Moreover, the model suggests a theoretical framework to understand cell division and death, beyond specific biochemical pathways.
Consciousness and subjective time: a plausible auditory approach
Authors: Ehsani Sepehr 
Published: July 2019

AbstractThe perception of time is an indispensable facet of human consciousness, and may in fact be dynamically present in primates and other species, albeit with different manifestations. Moreover, contrary to the physical measures of time, cognitive temporal perception may be subjectively affected by both internal and environmental cues. Here we review the evidence for the potential role of the auditory system in shaping the cortical measures of time, and propose possible auditory methods for studying this aspect of consciousness.
Molecular evolution of RRM-containing proteins and glycine-rich RNA-binding proteins in plants
Authors: Gomez-Porras Judith , Lewinski Martin , Riaño-Pachón Diego Mauricio , Staiger Dorothee 
Published: July 2019

Abstract
Background:
In angiosperms, RNA-binding proteins with an RNA recognition motif (RRM)-type RNA interaction domain play an important role in developmental and environmental responses. Despite their pivotal role, a comprehensive analysis of their number and diversity has only been performed in Arabidopsis so far.

Results:
Here we present a detailed phylogenetic analysis of RRM-containing proteins in plants, the red algae Cyanidioschyzon merolae and cyanobacteria. We identified two major events during the diversification of the RRM in plants, one at the emergence of green plants, and the other at the water-to-land transition. We focused on proteins that combine a single RRM with a glycine-rich stretch, known as glycine-rich RNA-binding proteins (GRPs). We found that GRPs are present in cyanobacteria, however plant and cyanobacterial GRPs are not of monophyletic origin. We provide evidence that plant GRPs form a polyphyletic group.*Conclusion:*Our work provides insights into the origin of GRPs in plants. We determined that the RRM from plants and cyanobacteria do not have a common origin. We could also determine that the acquisition of the glycine-rich stretch has happened at least on three separate occasions during the evolution of GRPs. One event led to the emergence of cyanobacterial GRPs, while later acquisition events led to the emergence of GRPs in the green lineage. No GRPs were found in red or marine green algae. We found a subgroup of GRPs exclusive to land plants, and its appearance may be linked to challenges related to the water-to-land transition.
On the social induction of Alzheimer's disease: An index theorem aging model for amyloid formation
Authors: Wallace Rodrick , Wallace Deborah 
Published: July 2019

AbstractThe central 'risk factor' for Alzheimer's disease (AD) is age. From first principles, we construct a mathematical model of protein folding and its in vivo regulation that gives this result in a natural manner. We extend the basic approach using topological information theory methods, and examine a case history of socially-induced premature aging in the United States.
Efficient Replication of Over 180 Genetic Associations with Self‐Reported Medical Data
Authors: Francke Uta , Naughton Brian , Naughton Joanna , Wojcicki Anne , Tung Joyce , Do Chuong , Hinds David , Kiefer Amy , Macpherson J. Michael , Eriksson Nicholas , Chowdry Arnab 
Published: July 2019

AbstractWhile the cost and speed of generating genomic data have come down dramatically in recent years, the slow pace of collecting medical data for large cohorts continues to hamper genetic research. Here we evaluate a novel online framework for amassing large amounts of medical information in a recontactable cohort by assessing our ability to replicate genetic associations using these data. Using web‐based questionnaires, we gathered self-reported data on 50 medical phenotypes from a generally unselected cohort of over 20,000 genotyped individuals. Of a list of genetic associations curated by NHGRI, we successfully replicated about 75% of the associations that we expected to (based on the number of cases in our cohort and reported odds ratios, and excluding a set of associations with contradictory published evidence). Altogether we replicated over 180 previously reported associations, including many for type 2 diabetes, prostate cancer, cholesterol levels, and multiple sclerosis. We found significant variation across categories of conditions in the percentage of expected associations that we were able to replicate, which may reflect systematic inflation of the effects in some initial reports, or differences across diseases in the likelihood of misdiagnosis or misreport. We also demonstrated that we could improve replication success by taking advantage of our recontactable cohort, offering more in‐depth questions to refine self‐reported diagnoses. Our data suggests that online collection of self‐reported data in a recontactable cohort may be a viable method for both broad and deep phenotyping in large populations.
Protein Regge Trajectories, Phase Coexistence and Loop Aetiology in Alzheimers Disease
Authors: Niemi Antti , Krokhotin Andrey 
Published: July 2019

AbstractAlzheimer's disease has a devastating impact on its victims by causing severe neurodegeneration in the brain that leads to a certain death. Only in a small number of cases can the origin be traced to a variety of genetic mutations, for the greater part the reasons for its onset are unclear.The defining factor is the formation of extracellular senile amyloid plaques in the brain, but therapeutic approaches to remove them remain to be shown effective in humans. Here we investigate physical processes that are involved in the release of the extracellular amyloid, by scrutinizing the intracellular domain of its precursor protein. We identify a phenomenon that has never before been discussed in the context of protein research: Like ice and water together, the intracellular domain of the amyloid precursor protein can form a complex of phase coexistence with another protein. This leads to an inherent instability that could well be among the missing pieces in the puzzle of Alzheimer's disease.
Openness as Infrastructure
Authors: Wilbanks John 
Published: July 2019

AbstractOpenness at the layer of cultural works and data is the key to the data infrastructure we need to accelerate science. This article lays out three key elements of data infrastructure - collaboration, classification, and openness - which draw us inevitably towards the long-claimed, but rarely-achieved, goal of the scientific method: to make claims that are reproducible under similar circumstances by someone other than the claimant, to be reproducible.
A decline in pollinator dependent vegetable crop productivity in India indicates pollination limitation and consequent agro-economic crises.
Authors: Basu Parthiba , Bhattacharya Ritam , Ianetta Pietro 
Published: July 2019

AbstractApproximately 70% of the tropical crop species depend on pollinators for optimum yields (Roubik, 1995, Klein 2007). The economic value of such pollinated crops to India is $726 million and India is the world's second largest vegetable producer (Sidhu, 2005). This status has been underpinned by large-scale changes in land-use and pesticide dependency (Fazal, 2000; Shaw & Satish, 2007). A method (c.f. Aizen et al. 2008) that partitions crops into categories depending on their relative pollinator dependence (Index of pollinator dependence, DI) was applied to analysis of vegetable yields for India over 45 years (1963-2008) using FAO data. This has revealed that since 1993, relative yields of crop production has either flattened or declined, while pollinator non dependent crops show no similar decline. This pattern of yield limitation may be due to several factors, among which pollinator limitation would be a major factor (Kearns et al. 1998) and this risk is discussed. Pollinator decline will have serious socio-economic consequences for countries like India, which host a large population of small and marginal farms for whom falling yield level would be critical for subsistence (Kearns et al. 1998; Kremen et al., 2002; Klein et al., 2007; Potts et al., 2010). We show here for the first time any indication of pollination limitation in India, an emerging economy that is still predominantly agrarian. Detailed land use and ecological surveys are urgently required to assess the ecology of pollinating insects within and around agricultural systems in India.
Genetic Normalization of Differentiating Aneuploid Human Embryos
Authors: Brezina Paul , Barker Andrew , Benner Andrew , Ross Ric , Nguyen Khanh-Ha , Anchan Raymond , Richter Kevin , Cutting Garry , Kearns William 
Published: July 2019

AbstractEarly embryogenesis involves a series of dynamic processes, many of which are currently not well described or understood. Aneuploidy and aneuploid mosaicism, a mixture of aneuploid and euploid cells within one embryo, in early embryonic development are principal causes of developmental failure.^1,2^ Here we show that human embryos demonstrate a significant rate of genetic correction of aneuploidy, or "genetic normalization" when cultured from the cleavage stage on day 3 (Cleavage) to the blastocyst stage on day 5 (Blastocyst) using routine in vitro fertilization (IVF) laboratory conditions. One hundred and twenty-six human Cleavage stage embryos were evaluated for clinically indicated preimplantation genetic screening (PGS). Sixty-four of these embryos were found to be aneuploid following Cleavage stage embryo biopsy and single nucleotide polymorphism (SNP) 23 chromosome molecular karyotype (microarray). Of these, 25 survived to the Blastocyst stage of development and repeat microarray evaluation was performed. The inner cell mass (ICM), containing cells destined to form the fetus, and the trophectoderm (TE), containing cells destined to form the placenta were evaluated. Sixteen of 25 embryos (64%) [95% CI: 44-80%] possessed diploid karyotypes in both the ICM and TE cell populations. An additional three Blastocyst stage embryos showed genetic correction of the TE but not the ICM and one Blastocyst stage embryo showed the reverse. Mosaicism (exceeding 5%), was not detected in any of the ICM and TE samples analyzed. Recognizing that genetic normalization may occur in developing human embryos has important implications for stem cell biology, preimplantation and developmental genetics, embryology, and reproductive medicine.1)Hassold, T. et al. A cytogenetic study of 1000 spontaneous abortions. Ann Hum Genet. 44, 151-78 (1980).2)Menasha, J., Levy, B., Hirschhorn, K., & Kardon, N.B. Incidence and spectrum of chromosome abnormalities in spontaneous abortions: new insights from a 12-year study. Genet Med. 7, 251-63 (2005).
A novel therapeutic strategy for pancreatic neoplasia using a novel RNAi platform targeting PDX-1
Authors: Wang Zhaohui , Stehling Kelly , Gibbs Richard , Fisher William , Norman Michael , Brunicardi Charles , Templeton Nancy , Liu Shi-He , Rao Donald , Nemunaitis John , Senzer Neil , Dawson David , DeMayo Francesco , Gingras Marie-Claude 
Published: July 2019

AbstractBi-functional shRNA (bi-shRNA), a novel RNA interference (RNAi) effector platform targeting PDX-1 utilizing a systemic DOTAP-Cholesterol delivery vehicle, was studied in three mouse models of progressive pancreatic neoplasia. Species-specific bi-functional PDX-1 shRNA (bi-shRNAPDX-1) lipoplexes inhibited insulin expression and secretion while also substantially inhibiting proliferation of mouse and human cell lines via disruption of cell cycle proteins in vitro. Three cycles of either bi-shRNA&lt;sup&gt;mousePDX-1&lt;/sup&gt; or shRNA&lt;sup&gt;mousePDX-1&lt;/sup&gt; lipoplexes administered intravenously prevented death from hyperinsulinemia and hypoglycemia in a lethal insulinoma mouse model. Three cycles of shRNA&lt;sup&gt;mousePDX-1&lt;/sup&gt; lipoplexes reversed hyperinsulinemia and hypoglycemia in an immune-competent mouse model of pancreatic neoplasia. Moreover, three cycles of the bi-shRNA&lt;sup&gt;humanPDX-1&lt;/sup&gt; lipoplexes resulted in near complete ablation of tumor volume and considerably improved survival in a human PANC-1 implanted SCID-mouse model. Human pancreatic neoplasia specimens also stained strongly for PDX-1 expression. Together, these data support the clinical development of a novel therapeutic strategy using systemic bi-shRNA&lt;sup&gt;PDX-1&lt;/sup&gt; lipoplexes against pancreatic neoplasia.
Gulf War Syndrome: A role for organophosphate induced plasticity of locus coeruleus neurons
Authors: Cao Jun-li , Varnell Andrew , Cooper Donald 
Published: July 2019

AbstractGulf War syndrome is a chronic multi-symptom illness that has affected about a quarter of the deployed veterans of the 1991 Gulf War. Exposure to prolonged low-level organophosphate insecticides and other toxic chemicals is now thought to be responsible. Chlorpyrifos was one commonly used insecticide. The metabolite of chlorpyrifos, chlorpyrifos oxon, is a potent irreversible inhibitor of acetylcholinesterase, much like the nerve agent Sarin. To date, the target brain region(s) most susceptible to the neuroactive effects of chlorpyrifos oxon have yet to be identified. To address this we tested ability of chlorpyrifos oxon to influence neuronal excitability and induce lasting changes in the locus coeruleus, a brain region implicated in anxiety, substance use, attention and emotional response to stress. Here we used an ex vivo rodent model to identify a dramatic effect of chlorpyrifos oxon on locus coeruleus noradrenergic neuronal activity. Prolonged exposure to chlorpyrifos oxon caused acute inhibition and a lasting rebound excitatory state expressed after days of exposure and subsequent withdrawal. Our findings indicate that the locus coeruleus is a brain region vulnerable to chlorpyrifos oxon-induced neuroplastic changes possibly leading to the neurological symptoms affecting veterans of the Gulf War.
Structures at the Atomic Level of Cobalt, Zinc and Lead Niobates
Authors: Heyrovska Raji 
Published: July 2019

AbstractThe author has found in recent years that bond lengths are exact sums of the radii of adjacent atoms and or ions, where the ions have Golden ratio based radii. This work was prompted by the exciting observation last year of the Golden ratio in the magnetic properties of cobalt niobate. It is shown here that in cobalt and zinc niobates, cobalt, zinc and oxygen ions have Golden ratio based ionic radii, whereas in lead niobate, all atoms have covalent radii. Also, the angles at the single bond oxygen anion and atom are close to 1080, as in a pentagon.
Structures at the Atomic Level of Cobalt, Zinc and Lead Niobates (with an Appendix: Atomic structure of cobalt niobate crystal)
Authors: Heyrovska Raji 
Published: July 2019

AbstractThe author has found in recent years that bond lengths are exact sums of the radii of adjacent atoms and or ions, where the ions have Golden ratio based radii. This work was prompted by the exciting observation last year of the Golden ratio in the magnetic properties of cobalt niobate. It is shown here that in cobalt and zinc niobates, cobalt, zinc and oxygen ions have Golden ratio based ionic radii, whereas in lead niobate, all atoms have covalent radii. Also, the angles at the single bond oxygen anion and atom are close to 1080, as in a pentagon.
Formation of an SIR-Nucleosome Filament in vitro and Its Modulation by O-Acetyl-ADP-Ribose
Authors: Wu Yu-Yi , Hong Jia-Yang , Lee Sue-Ping , Shen Hsiao-Hsuian , Tsai Shu-Ping , Liou Gunn-Guang 
Published: July 2019

AbstractIt is not possible to clearly visualize how chromatin condenses to heterochromatin in vivo. However, in an in vitro system for Saccharomyces cerevisiae, the requirements for heterochromatin filament formation mirror those found in vivo. Here we report that the nucleosomes and the Sir2, Sir3 and Sir4 proteins, which are required for in vitro filament assembly, are also components of these filaments, confirming that the filaments are SIR-nucleosome filaments. We show the individual localization patterns of the Sir proteins on this SIR-nucleosome filament, and demonstrate that the metabolite, AAR, plays a specific and essential role in promoting the formation of this SIR-nucleosome filament.