bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling Resting-State Brain Functional Integration
Authors: Zuo Xi-Nian
Published: July 2019

During the past 15 years, resting state fMRI has rapidly emerged as a powerful and reliable approach to explore the human brain architecture. There are two concepts of human brain working mechanism: functional segregation and integration. In this report, I mainly focused on functional integration. Relevant mathematics and statistics in this field are reviewed including both seed-based and independent component analysis (ICA) resting state functional connectivity. Moreover, ICA was applied to study the abnormalities of a fronto-striatal-insular network in ADHD. First, mathematical methods to investigate the functional integration by using rs-fMRI were reviewed as well as more details on ICA. Two topics have been addressed: ranking components and applying ICA to reveal the dysfunctional fronto-striatal-insular network (FSIN) in ADHD. All methods referred in the report have been implemented by Linux shell scripts.
Formation of Plant Battery from Xerophytic Plants
Authors: Charan R.V.K.
Published: July 2019

Nature has supplied abundant energy to plants in form of electricity and among them the xerophytics and specially the Opuntias have got the maximum due to adaptness of dry condition. Several researchers have already found voltage across their cells but the present endeavour to harness the total electrical energy conserved in plants in form of a Plant Battery, however of low potential, but is a step forward towards non-conventional energy.
New discovery of the oldest maize weevils in the world from Jomon potteries, Japan
Authors: Obata Hiroki , Manabe Aya , Nakamura Naoko , Onishi Tomokazu , Senba Yasuko
Published: July 2019

The maize weevil (Sitophilus zeamais) and rice weevil (Sitophilus oryzae) are two of the most damaging insects for stored grains, and are characteristic species of ancient Japan. Both species and the granary weevil (Sitophilus granarius) are common elsewhere in the world, but the natural distribution of maize and rice weevils is restricted to the Old World^1^. Japanese archaeological records contain a few maize weevil fossils after the Middle Yayoi period (ca. 2000 aBP)^2^. However, since evidence of weevils was discovered as impressions in Jomon potsherds in 2004^3^, many weevil impressions have been found. The oldest is from the Late Jomon (ca. 4000 to 3200 aBP). These findings and other archaeological evidence suggest that the maize weevil invaded Japan from Korea, accompanying the spread of rice cultivation^4^. However, in 2010 we discovered older weevil impressions dating to ca. 9000 aBP. These specimens are the oldest harmful insects discovered from archaeological sites around the world. The new discovery is valuable for future entomological research because such specimens are absent from the fossil record. It is also archaeologically and culturally interesting because this provides evidence of harmful insects living in Jomon villages. However, the new discovery raises the question of what these weevils infested: did cereal cultivation exist 9000 years ago? We have no persuasive answer, but hope one will be provided by future interdisciplinary collaborations among geneticists, entomologists, and archaeologists.
Improved prediction of protein interaction from microarray data using asymmetric correlation
Authors: Yano Kojiro
Published: July 2019

Background:

Detection of correlated gene expression is a fundamental process in the characterization of gene functions using microarray data. Commonly used methods such as the Pearson correlation can detect only a fraction of interactions between genes or their products. However, the performance of correlation analysis can be significantly improved either by providing additional biological information or by combining correlation with other techniques that can extract various mathematical or statistical properties of gene expression from microarray data. In this article, I will test the performance of three correlation methods-the Pearson correlation, the rank (Spearman) correlation, and the Mutual Information approach-in detection of protein-protein interactions, and I will further examine the properties of these techniques when they are used together. I will also develop a new correlation measure which can be used with other measures to improve predictive power. Results:Using data from 5,896 microarray hybridizations, the three measures were obtained for 30,499 known protein-interacting pairs in the Human Protein Reference Database (HPRD). Pearson correlation showed the best sensitivity (0.305) but the three measures showed similar specificity (0.240 - 0.257). When the three measures were compared, it was found that better specificity could be obtained at a high Pearson coefficient combined with a low Spearman coefficient or Mutual Information. Using a toy model of two gene interactions, I found that such measure combinations were most likely to exist at stronger curvature. I therefore introduced a new measure, termed asymmetric correlation (AC), which directly quantifies the degree of curvature in the expression levels of two genes as a degree of asymmetry. I found that AC performed better than the other measures, particularly when high specificity was required. Moreover, a combination of AC with other measures significantly improved specificity and sensitivity, by up to 50%.

Conclusions:

A combination of correlation measures, particularly AC and Pearson correlation, can improve prediction of protein-protein interactions. Further studies are required to assess the biological significance of asymmetry in expression patterns of gene pairs.
The water clock of Proteus mirabilis paces colony periodic and synchronous swarming
Authors: Lahaye Elodie , Jamme Frederic , Sire Olivier
Published: July 2019

For decades, the origin of the concentric ring pattern of bacterial swarming colonies has puzzled microbiologists. Thanks to _in situ_ and real time infrared microspectroscopy and the brilliance of the infrared beam at SOLEIL synchrotron, we demonstrate here that Proteus mirabilis swarming is paced by a periodic variation of the water activity at colony's edge. This periodic variation originates a phase transition within the extracellular matrix water H bond network which switches on and off the exopolysaccharides viscoelasticity and, consequently, the ability of bacterial cells to swarm. A dynamic behaviour emerges from the global properties of the multicellular entity which here relies on the ability of the bacterial cells to tune exoproducts synthesis in order to undergo sharp transitions above/below a given water activity threshold.
Multidrug resistance of non-adherent cancer cells
Authors: Singh Navneet , Chakrabarty Subhas , Liu Guangming
Published: July 2019

Metastases are the cause of 90% of human cancer deaths. Cancer in situ can usually be effectively removed by surgery. Once cancer cells disseminate from the original site and start to circulate in blood, lymph, or other body fluids, the disease becomes almost incurable. Here we show that cancer cells in a non-adherent, 3-dimentional growth pattern are highly drug resistant compared to their adherent counterparts that grow in monolayer, attaching to the wall of tissue culture plates. The non-adherent cancer cells retain the adhering potential and can attach to an appropriate surface to reacquire adherent phenotype. Once the non-adherent cancer cells become attached, they regain drug response, similar to the original adherent cells. A significant increase in the expression of CD133, CD44, Nanog, survivin, and thymidylate synthase was observed in the non-adherent cancer cells compared to their adherent counterparts, which may underlie the mechanisms of multidrug resistance of the cells. Since the non-adherent cancer cells cultured in vitro resemble the circulating metastatic cells in vivo in that both cells exhibit suspended non-adherent phenotype, possess re-attaching potential, and are highly drug resistant, we suggest that circulating metastatic cells can attach to an appropriate surface to gain adherent phenotype and subsequently acquire drug sensitivity. We propose that devices coated with cell attachment materials or small particles of extracellular matrix and collagen that mimic the structural framework of real human tissues to which cells can attach and grow may be able to stabilize the circulating metastatic cells. Once the metastatic cells undergo attachment and become adherent, they gain drug sensitivity and can be killed by anticancer drugs that are either administered to the blood or conjugated to the devices.
Fractal geometry of nature (bone) may inspire medical devices shape
Authors: Longoni Salvatore , Sartori Matteo
Published: July 2019

Medical devices, as orthopaedics prostheses and dental implants, have been designed over years on the strength of mechanical, clinical and biological indications. This sequence is the commonly accepted cognitive and research process: adapting the device to the surrounding environment (host tissue). Inverting this traditional logical approach, we started from bone microarchitecture analysis. Here we show that a unique geometric rule seems to underlie different morphologic and functional aspects of human jaw bone tissue: fractal properties of white trabeculae in low quality bone are similar to fractal properties of black spaces in high quality bone and vice versa. These data inspired the fractal bone quality classification and they were the starting point for reverse engineering to design specific dental implants threads. We introduce a new philosophy: bone decoding and with these data devices encoding. In the future, the method will be implemented for the analysis of other human or animal tissues in order to project medical devices and biomaterials with a microarchitecture driven by nature.
Asynchronous Rhythm of Steroidogenic Factor 1 and Period Homolog 2 mRNA Expression in Mouse Y1 Adrenocorticol Tumor Cells
Authors: Ohe Kenji , Sonoda Kouichirou , Akashi Makoto , Oba Koichi , Nomura Masatoshi , Okabe Taijiro , Node Koichi , Takayanagi Ryoichi , Nawata Hajime , Yanase Toshihiko
Published: July 2019

The relationship between the expression of Steroidogenic factor 1 (Sf1) and the circadian-related gene, period homolog 2 (Per2), in the adrenal cortex is still unknown. We show here that in Y1 adrenocortical tumor cells, expression of steroidogenic-related genes such as P450scc mRNA and Sf1 mRNA were asynchronous with Per2 mRNA. SF1 promoter analyses showed that the E-box element functions in a rhythmic pattern. Rhythmic expression of Upstream factor 1 mRNA, correlated well with Sf1 mRNA expression. We propose that tumorigenesis of adrenocortical lesions cause disruption of synchronous expression of steroidogenic-related and circadian-related genes.
New Equations for Atomic Mass, Mass per Nucleon and Mass defects of Elements in Terms of Rest Mass Based Neutron Numbers
Authors: Heyrovska Raji
Published: July 2019

Conventional neutron numbers are based on the approximations that the mass of the electron is zero and that those of the proton and neutron are each equal to unity. It was shown, by using the exact rest masses, that the neutron numbers are actually one or two less than the conventional ones for atomic masses greater than 108. Presented here are new equations for the atomic mass, mass per nucleon and mass defects for the most abundant stable isotope (or the one with the longest half life) of each of the 118 elements of the Periodic Table.
Effect of Escherichia coli endotoxin on Archachatina marginata haemolymph coagulation system
Authors: Salawu Musa , Oloyede Oyelola , Oladiji Adenike , Muhammad Nasiru , Yakubu Musa
Published: July 2019

The effect of E. coli endotoxin on the heamolymph coagulation response of Archachatina marginata was studied. Heamocyte Lysate(HL), Haemocyte Lysate Supernatant(HLS) and Haemocyte Lysate Debris (HLD) were exposed to Escherichia coli endotoxin. Controls were prepared with endotoxin-free water(<0.025 EU/ml). The differential protein coagulation was estimated in each mixture. Fractions of the haemolymph exposed to endotoxin produced higher protein coagulates than endotoxin-free fractions when incubated at 37 °C for 1 h (p<0.05). The results showed significantly higher (p<0.05) concentrations of protein coagulated when HL/plasma mixture were used than when either fraction was used. At a ratio 1:1 of HL:Plasma, highest protein coagulation was recorded. This study revealed that maximum protein coagulation in response to endotoxin was elicited by a synergy between plasma and haemocyte lysate(HL). From this research haemolymph fractions of Archachatina marginata may provide an alternative test material for endotoxin in medical preparations in the future.
The E3 ubiquitin ligase c-IAP1 regulates PCSK9-mediated LDLR degradation: Linking the TNF-&x03B1; pathway to cholesterol uptake
Authors: Xu Weiming , Liu Lizhi
Published: July 2019

Proprotein convertase subtilisin/kexin type 9 (PCSK9), in addition to LDLR (low-density lipoprotein receptor) and APOB (apolipoprotein B), is one of three loci implicated in autosomal dominant hypercholesterolaemia (ADH)^1^. A number of PCSK9 gain-of-function mutations and loss-of-function mutations have been identified from families afflicted with ADH with hypercholesterolaemia or hypocholesterolaemia, respectively^1-4^. In humans, the main function of PCSK9 appears to be the post-transcriptional regulation of the number of cell-surface LDL receptors^5-7^. To date, only LDLR and its closest family members VLDLR and ApoER2 have been shown to bind with PCSK9^8,9^. To find new binding partners for PCSK9, we used a shotgun proteomic method to analyse the protein complex pulled down by immunoprecipitation against FLAG-tagged PCSK9 protein. Among 22 potential novel binding proteins identified, we found that the cellular inhibitor of apoptosis protein 1 (c-IAP1^10^) and the TNF receptor-associated factor 2 (TRAF2^11^) complex are regulated differently in different dominant PCSK9 mutations that occur naturally. Further immunoprecipitation analysis showed that c-IAP1 is a direct binding partner for PCSK9. One of the "gain-of-function" mutants, PCSK9-S127R, which has impaired autocatalytic activity, is defective in binding to c-IAP1. The other dominant mutation, PCSK9-D374Y^12^, which is 10-fold more potent in degrading the LDLR protein than wild-type PCSK9, can be significantly ubiquitinated by c-IAP1 in vitro. The ubiquitinated PCSK9-D374Y is unable to degrade LDLR, which is its main cause of hypercholesterolaemia in patients. These results indicate that there is a novel cholesterol uptake regulation pathway linking PCSK9/LDLR to the E3 ubiquitin ligase c-IAP1 in a TNF-[alpha] response pathway. This highlights the possibility of developing new treatments for human cardiovascular diseases through ubiquitin ligase-mediated ubiquitination of target proteins in cholesterol metabolism.
Thermal characterization of Plasmodium falciparum species specific proteins in Indian geographical area.
Authors: Bhardwaj Mohit , Bharadwaj Leena , Trigunayat Kritika , Trigunayat Madan Mohan
Published: July 2019

The paper reveals thermal characteristics of P.falciparum species specific proteins. These proteins determine why P. vivex species are dominant over P.falciparum in Indian geographical area. Outside human host plasmodium parasite survives in poikilothermal mosquitoes. Climatic temperature conditions greatly affect native state of P.falciparum species specific proteins in mosquitoes. Study of climatic temperature conditions in Indian geographical area reveals that Pfsd protein for Plasmodium falciparum can remain in native state between &8805;7 degree centigrade and &8804;42.6 degree centigrade temperature conditions. While their best optimum functions (activity) was noted between 25.3 degree centigrade to 33degree centigrade. Pfsd protein were found more heat susceptible for temperature minima and maxima than Pvsd proteins of P. vivex causing all time high population ratio of P.falciparum species.
The Size-Weight Illusion Is Not an Illusion When Picking the Best Objects to Throw
Authors: Zhu Qin , Bingham Geoffrey
Published: July 2019

Heaviness perception involves a misperception of weight known, since the 19th century, as the Size-Weight Illusion ^1^. The larger of two objects of equal mass is reported to be lighter than the smaller when they are lifted. The illusion has been found to be reliable and robust. It persists even when people know that the masses are equal and handle objects properly ^2^. It has been exhibited by children of only 2 years of age ^3,4^. All this suggests that the effect might be intrinsic to humans. Although different hypotheses have been advanced to account for the illusion over the 100+ years it has been studied ^5-11^, its origin remains unknown. More recently, people's perception of optimal objects for long distance throwing was found to exhibit a size-weight relation similar to the illusion ^12,13^, greater weights were picked for larger objects and they were indeed thrown to the greatest distances. Here we show that the perception of heaviness (including the illusion) and perception of optimal objects for long distance throwing are in fact equivalent. Thus, the size-weight illusion has a useful application: optimal objects for throwing are picked by a thrower as having a particular heaviness, which is the best heaviness learned when learning to throw ^14,15^. Long distance throwing is a uniquely human ability that is understood to have enabled our species to survive and even thrive during the ice ages ^16-22^. The fact that the illusion is a functional component of human throwing skill adds credence to the idea that it is intrinsic to the species.
TreeBASE2: Rise of the Machines
Authors: Vos Rutger , Lapp Hilmar , Piel William , Tannen Val
Published: July 2019

TreeBASE is a public repository of peer-reviewed phylogenetic knowledge. Researchers submit their results to TreeBASE when they are writing a manuscript based on them for publication in a suitable journal. The submitted data are assigned permanent, unique identifiers and web addresses that authors can refer to in their article. Anyone can locate and access the data once the study has been published by TreeBASE and by the targeted journal.A prototype of this system has served the phylogenetics community well for a number of years, accumulating the results of thousands of studies. The usage model was that of a silo where data could only be accessed through a web browser, and only be downloaded in representations that omitted important associated metadata. A human with considerable expertise needed to read and interpret the web pages through which everything was served up to make sense out of what was available. This model is not always practical. For example, phyloinformatic research often uses so much data that automation is becoming necessary. Where human intervention is no longer feasible, machines – which are stupid – must be able to do the job instead; and they need to be told what is what. This has spurred more explicit standardization of the syntax and semantics of phylogenetic knowledge. The latest version of TreeBASE facilitates this by adopting a collection of community standards: * PhyloWS for automated searching using a contextual query language and retrieval using a clearly defined URL API. * NeXML for robust data syntax and flexible metadata annotation. * CDAO (and other ontologies) for defining the semantics of the metadata. We will present an overview of how these components work together to make phylogenetic knowledge accessible to machines on the semantic web. Using this new architecture, client side software (including off-the-shelve tools such as RSS readers) can query, transform and download TreeBASE data autonomously.
GMOD for Evolutionary Biology
Authors: Buels Robert , Clements Dave
Published: July 2019

The Generic Model Organism Database (GMOD, "http://gmod.org":http://gmod.org) project provides interoperable, open source software tools for managing, visualizing and annotating biological data. GMOD is also a community of people addressing common challenges with biological data. Some well known software in GMOD includes GBrowse and JBrowse for genome browsing, Apollo for genome annotation, Chado for managing data, CMap for comparative map viewing, Galaxy for workflow creation and persistence, and BioMart for warehousing biological data.This talk will focus on three areas of particular interest to iEvoBio participants. 1) GBrowse_syn comparative genomics viewer2) Natural Diversity Module of the Chado database schema3) GMOD evolutionary biology hackathon The GBrowse_syn comparative genomics viewer displays synteny between a reference and any number of related species. It shows inversions, duplications, and indels, and can show synteny across non-contiguous regions. It is built on the widely used GBrowse genome viewer. The Natural Diversity Module is an extension to GMOD’s Chado database schema to enable Chado to support natural diversity, population genomics, individuals, breeding, phenotypes and geolocation information. This module is the first extension to Chado to be designed by the community, rather than at one institution. We will close by soliciting nominations and ideas for a GMOD Evolutionary Biology Hackathon. This hackathon will be held November 8-12, at NESCent, which is sponsoring the event. There will be an open call for participation in August.
Effective Phylogenetic Compression with TreeZip
Authors: Matthews Suzanne , Sul SeungJin , Williams Tiffani
Published: July 2019

Phylogenetic trees are family trees that represent the relationships between a group of organisms, or taxa. The most popular techniques for reconstructing phylogenetic trees intelligently navigate an exponentially-sized tree space by solving NP-hard optimization problems that that best hypothesize the evolutionary history for a given set of taxa. Instead of reconstructing a single tree, these heuristics often return tens to hundreds of thousands of trees that represent equally-plausible hypotheses for how the taxa of interest evolved from a common ancestor. As biologists attempt to reconstruct increasingly larger phylogenies, these tree collections only continue to grow in size. To combat the cost of storage and to facilitate the transfer of these large tree files, we developed a new compression algorithm called TreeZip that reduces the requirements for storing large collections of evolutionary trees over standard compression methods. TreeZip is distributed under the GPL license and can be accessed at: "http://treezip.googlecode.com":http://treezip.googlecode.com.
Isotope fractionation during impacts
Authors: Huang Hua
Published: July 2019

Evaporation-condensation, a significant process, happens during impact events^1^. Of special interest, this process can lead to significant isotope fractionations e.g. C, O, Mg, Si, S, Fe, and Cr.
From aptamer-based biomarker discovery to diagnostic and clinical applications: an aptamer-based, streamlined multiplex proteomic assay
Authors: Kraemer Stephan , Vaught Jonathon , Bock Christopher , Gold Larry , Katilius Evaldas , Keeney Tracy , Kim Nancy , Saccomano Nicholas , Wilcox Sheri , Zichi Dom , Sanders Glenn
Published: July 2019

Recently, we reported an aptamer-based, highly multiplexed assay for the purpose of biomarker identification. To enable seamless transition from highly multiplexed biomarker discovery assays to a format suitable and convenient for diagnostic and life-science applications, we developed a streamlined, plate-based version of the assay. The plate-based version of the assay is robust, sensitive (sub-picomolar), rapid, can be highly multiplexed (upwards of 60 analytes), and fully automated. We demonstrate that quantification by microarray-based hybridization, Luminex bead-based methods, and qPCR are each compatible with our platform, further expanding the breadth of proteomic applications for a wide user community.
It is better than you think: fluid intelligence across the lifespan
Authors: Alloway Tracy Packiam , Alloway Ross
Published: July 2019

The growth and decline of fluid intelligence is associated with brain structural changes. For example, development of fluid IQ is associated with cortex thickness during the critical period between 6 to 12 years old. On the other end of the lifespan, poor performance in cognitive functioning is attributed to a decrease of frontal gray matter density in elderly populations. In particular, there is a sharp decline in fluid IQ scores after 65 years of age. There is substantial evidence that working memory and fluid intelligence (Gf) share neural substrates, such as the prefrontal and parietal cortices. However, very little research has examined whether the pattern of growth and decline in working memory mirrors that of fluid intelligence. For example, does the decline of working memory skills in elderly populations mirror fluid intelligence? Is the rate of working memory decline similar to the rate of growth?
Validation of a Multivariate Serum Profile for Epithelial Ovarian Cancer Using a Prospective Multi-Site Collection
Authors: Seshaiah Partha , Bertenshaw Greg , Chen Tzong-Hao , Bergstrom Katharine , Zhao Jinghua , Mapes James , Stephen Laurie , Amonkar Suraj , McCollum Michael , Miller Brigitte , Roman Lynda , Karlan Beth , Chalas Eva , DiSilvestro Paul , Barter James , Orr James , Bigsby Glenn , Holloway Robert , Alvarez Ronald , Yip Ping , Mansfield Brian
Published: July 2019

In previous studies we described the use of a retrospective collection of ovarian cancer and benign disease samples, in combination with a large set of multiplexed immunoassays and a multivariate pattern recognition algorithm, to develop an 11-biomarker classification profile that is predictive for the presence of epithelial ovarian cancer. In this study, customized, Luminex-based multiplexed immunoassay kits were GMP-manufactured and the classification profile was refined from 11 to 8 biomarkers (CA-125, epidermal growth factor receptor, CA 19-9, C-reactive protein, tenascin C, apolipoprotein AI, apolipoprotein CIII, and myoglobin). The customized kits and the 8-biomarker profile were then validated in a double-blinded manner using prospective samples collected from women scheduled for surgery, with a gynecologic oncologist, for suspicion of having ovarian cancer. The performance observed in model development held in validation, demonstrating 81.1% sensitivity (95% CI 72.6 – 87.9%) for invasive epithelial ovarian cancer and 85.4% specificity (95% CI 81.1 – 88.9%) for benign ovarian conditions. The specificity for normal healthy women was 95.6% (95% CI 83.6 – 99.2%). These results have encouraged us to undertake a second validation study arm, currently in progress, to examine the performance of the 8-biomarker profile on the population of women not under the surgical care of a gynecologic oncologist.
Origin and diversification of steroids: Co-evolution of enzymes and nuclear receptors
Authors: Baker Michael
Published: July 2019

Recent sequencing of amphioxus and sea urchin genomes has provided important data for understanding the origins of enzymes that synthesize adrenal and sex steroids and the receptors that mediate physiological response to these vertebrate steroids. Phylogenetic analyses reveal that CYP11A and CYP19, which are involved in the synthesis of adrenal and sex steroids, first appear in the common ancestor of amphioxus and vertebrates. This correlates with recent evidence for the first appearance in amphioxus of receptors with close similarity to vertebrate steroid receptors. Other CYP450 enzymes involved in steroid synthesis can be traced back to invertebrates, in which they have at least two functions: detoxifying xenobiotics and catalyzing the synthesis of sterols that activate nuclear receptors. CYP450 metabolism of hydrophobic xenobiotics may have been a key event in the origin of ligand-activated steroid receptors from constitutively active nuclear receptors.
Simple reverse genetics approach to elucidating the biosynthetic pathway of complex thiopeptide nocathiacin
Authors: Wei Maochen , Deng Jing , Wang Shuzhen , Liu Nan , Chen Yijun
Published: July 2019

Biothythetic pathway of the most drugable thiopeptide nocathiacin has been elucidated by applying reverse genetics method based on its structural features. The present study provides an efficient approach for an easy access to the biosynthetic gene clusters of complex bioactive peptides that are ribosomally synthesized with extensive posttranslational modifications.
The Future of the Journal? Integrating research data with scientific discourse
Authors: de Waard Anita
Published: July 2019

To advance the pace of scientific discovery we propose a conceptual format that forms the basis of a truly new way of publishing science. In our proposal, all scientific communication objects (including experimental workflows, direct results, email conversations, and all drafted and published information artifacts) are labeled and stored in a great, big, distributed data store (or many distributed data stores that are all connected). Each item has a set of metadata attached to it, which includes (at least) the person and time it was created, the type of object it is, and the status of the object including intellectual property rights and ownership. Every researcher can (and must) deposit every knowledge item that is produced in the lab into this repository. With this deposition goes an essential metadata component that states who has the rights to see, use, distribute, buy or sell this item. Into this grand (and system-wise distributed, cloud-based) architecture, all items produced by a single lab, or several labs, are stored, labeled and connected.
Detection of MicroRNAs in Dried Serum Blots
Authors: Patnaik Santosh , Mallick Reema , Yendamuri Sai
Published: July 2019

MicroRNAs are short RNAs which can be utilized as biomarkers for a variety of conditions. They are detectable in serum, and changes in the levels of circulating microRNAs have been associated with different diseases. We tested for the presence of microRNAs in serum that is dried on paper and stored unrefrigerated instead of being kept frozen. MicroRNAs were readily detectable in such blots, and their detectability was improved by using paper made of cellulose instead of glass fiber, and by re-hydrating dried blots with Trizol™ instead of water, phosphate-buffered saline, or guanidine hydrochloride before RNA extraction. MicroRNA preservation was not diminished by drying of blots at 37, 45 or 60 ºC instead of room temperature or by storage of blots at 37, 45 or 60 ºC instead of room temperature, but was worse when blots were dried incompletely or exposed to high humidity during storage. Preservation of microRNAs in serum was not adversely affected if instead of being kept frozen at -80 ºC it was stored as dried blots at room temperature or 37 ºC for ten or eight and a half months, respectively. In a group of ten individuals, microRNA quantifications of -80 ºC-frozen or dried sera stored at room temperature correlated well. Dried blots may thus be a convenient and safer way to save, transport, and store serum without refrigeration for microRNA assays.
The Etiology of Depression in Parkinson's Disease
Authors: Sourani Dafhna , Eitan Renana , Oelman Gadi
Published: July 2019

Although a high percentage of Parkinson's disease (PD) patients suffer from depression in addition to their motor disabilities, the etiology of this depression is unknown. Within the framework of the monoamine deficiency hypothesis of depression, we present a neuronal circuitry that accounts for depression in PD. Using behavioral and direct neuronal circuitry measurements we show that the habenula mediates the coupling between the dopaminergic and the serotonergic systems and argue that alterations in basal ganglia activity cause habenula hyperactivity that result with depression in PD. Behavioral results from novelty suppressed feeding and force swim tests, as well as direct circuitry measures with manganese enhanced MRI indicate (i) depressive-like behavior and reduced raphe nuclei connectivity/excitability in unilateral 6-hydroxydopamine injected rats, (ii) partial normalization of behavior and raphe connectivity after apomorphine treatment, and (iii) normalization of behavior after bilateral lesion of the habenula. These findings open up avenues for therapeutic intervention.
Without magic bullets: the biological basis for public health interventions against protein folding disorders
Authors: Wallace Rodrick
Published: July 2019

Protein folding disorders of aging like Alzheimer's and Parkinson's diseases currently present intractable medical challenges. 'Small molecule' interventions - drug treatments - often have, at best, palliative impact, failing to alter disease course. The design of individual or population level interventions will likely require a deeper understanding of protein folding and its regulation than currently provided by contemporary 'physics' or culture-bound medical magic bullet models. Here, a topological rate distortion analysis is applied to the problem of protein folding and regulation that is similar in spirit to Tlusty's (2010a) elegant exploration of the genetic code. The formalism produces large-scale, quasi-equilibrium 'resilience' states representing normal and pathological protein folding regulation under a cellular-level cognitive paradigm similar to that proposed by Atlan and Cohen (1998) for the immune system. Generalization to long times produces diffusion models of protein folding disorders in which epigenetic or life history factors determine the rate of onset of regulatory failure, in essence, a premature aging driven by familiar synergisms between disjunctions of resource allocation and need in the context of socially or physiologically toxic exposures and chronic powerlessness at individual and group scales.
Beautifying Data in the Real World
Authors: Willighagen Egon , Bradley Jean-Claude , Guha Rajarshi , Lang Andrew , Lindenbaum Pierre , Neylon Cameron , Williams Antony
Published: July 2019

This chapter from the O'Reilly book "Beautiful Data" describes the use of Open Notebook Science to crowdsource solubility data. The use of GoogleDocs, wikis, ChemSpider, RDF, the Chemistry Development Kit and Second Life is described.
The association between having a household member with a cancer-related limitation and human papillomavirus vaccine uptake
Authors: Offutt-Powell Tabatha , Ojha Rohit , Tota Joseph , Singh Karan
Published: July 2019

OBJECTIVE: To evaluate the association between having a household member with a cancer-related limitation (physical, mental, or emotional) and human papillomavirus (HPV) vaccine uptake among females aged 9 – 17 years.

METHODS:

We analyzed 2008 National Health Interview Survey for our cross-sectional analysis. All households with females aged 9 – 17 years were eligible for inclusion in our analysis. Our outcomes of interest included HPV vaccine initiation (≥1 dose) and series completion (full 3 doses). A dichotomous variable indicating a cancer-related limitation for a household member was created if at least one adult in the household responded to having a limitation caused by cancer. We used Firth’s bias-reducing penalized likelihood for logistic regression[11] to estimate prevalence odds ratios (ORs) and corresponding 95% profile penalized likelihood confidence intervals (CIs) for HPV vaccine uptake among young females who had a household member with a cancer-related limitation compared to young females who did not have a household member with a cancer-related limitation after adjusting for child’s age, race/ethnicity, and SES.

RESULTS:

HPV vaccine initiation and completion were higher among females aged 9-17 years who had a household member with a cancer-related limitation (Initiation: OR=1.42, 95%CI: 0.26, 5.18); Completion: OR=2.50, 95%CI: 0.26, 11.58).

CONCLUSION:

Our results suggest that females aged 9 – 17 years in the United States who have a household member with a cancer-related limitation (physical, mental, or emotional) may be more likely to initiate and complete the HPV vaccination. However, our point estimates lack precision (evident by wide confidence intervals) because of limited prevalence of the exposure in our study population.
Hierarchical nanomechanics of collagen microfibrils
Authors: Gautieri Alfonso , Vesentini Simone , Redaelli Alberto , Buehler Markus J.
Published: July 2019

Collagen constitutes one third of the human proteome, providing mechanical stability, elasticity and strength to connective tissues. Collagen is also the dominating material in the extracellular matrix (ECM) and is thus crucial for cell differentiation, growth and pathology. However, fundamental questions remain with respect to the origin of the unique mechanical properties of collagenous tissues, and in particular its stiffness, extensibility and nonlinear mechanical response. By using x-ray diffraction data of a collagen fibril reported by Orgel et al. (Proceedings of the National Academy of Sciences USA, 2006) in combination with protein structure identification methods, here we present an experimentally validated model of the nanomechanics of a collagen microfibril that incorporates the full biochemical details of the amino acid sequence of the constituting molecules. We report the analysis of its mechanical properties under different levels of stress and solvent conditions, using a full-atomistic force field including explicit water solvent. Mechanical testing of hydrated collagen microfibrils yields a Young’s modulus of ≈300 MPa at small and ≈1.2 GPa at larger deformation in excess of 10% strain, in excellent agreement with experimental data. Dehydrated, dry collagen microfibrils show a significantly increased Young’s modulus of ≈1.8 to 2.25 GPa (or ≈6.75 times the modulus in the wet state) owing to a much tighter molecular packing, in good agreement with experimental measurements (where an increase of the modulus by ≈9 times was found). Our model demonstrates that the unique mechanical properties of collagen microfibrils can be explained based on their hierarchical structure, where deformation is mediated through mechanisms that operate at different hierarchical levels. Key mechanisms involve straightening of initially disordered and helically twisted molecules at small strains, followed by axial stretching of molecules, and eventual molecular uncoiling at extreme deformation. These mechanisms explain the striking difference of the modulus of collagen fibrils compared with single molecules, which is found in the range of 4.8±2 GPa or ≈10-20 times greater. These findings corroborate the notion that collagen tissue properties are highly scale dependent and nonlinear elastic, an issue that must be considered in the development of models that describe the interaction of cells with collagen in the extracellular matrix. A key impact the atomistic model of collagen microfibril mechanics reported here is that it enables the bottom-up elucidation of structure-property relationships in the broader class of collagen materials such as tendon or bone, including studies in the context of genetic disease where the incorporation of biochemical, genetic details in material models of connective tissue is essential.
Fractal-like Distributions over the Rational Numbers in High-throughput Biological and Clinical Data
Authors: Trifonov Vladimir , Pasqualucci Laura , Dalla-Favera Riccardo , Rabadan Raul
Published: July 2019

Recent developments in extracting and processing biological and clinical data are allowing quantitative approaches to studying living systems. High-throughput sequencing, expression profiles, proteomics, and electronic health records are some examples of such technologies. Extracting meaningful information from those technologies requires careful analysis of the large volumes of data they produce. In this note, we present a set of distributions that commonly appear in the analysis of such data. These distributions present some interesting features: they are discontinuous in the rational numbers, but continuous in the irrational numbers, and possess a certain self-similar (fractal-like) structure. The first set of examples which we present here are drawn from a high-throughput sequencing experiment. Here, the self-similar distributions appear as part of the evaluation of the error rate of the sequencing technology and the identification of tumorogenic genomic alterations. The other examples are obtained from risk factor evaluation and analysis of relative disease prevalence and co-mordbidity as these appear in electronic clinical data. The distributions are also relevant to identification of subclonal populations in tumors and the study of the evolution of infectious diseases, and more precisely the study of quasi-species and intrahost diversity of viral populations.
A Discrete State Model for Kinesin-1 with Rate Constants Modulated by Neck Linker Tension
Authors: Koch Steven , Herskowitz Lawrence
Published: July 2019

Kinesin-1 is a homodimeric molecular motor protein that uses ATP and a hand-over-hand motion to transport cargo along microtubules. How kinesin converts chemical energy into directed motion is a question that has been actively studied since its discovery. Even at the most coarse-grained level of chemical kinetics, understanding is still lacking. Minimal kinetic models are often developed to both explain kinesin’s hand-over-hand forward-stepping behavior and to infer important kinetic rate constants from experimental data. These minimal models are often limited to a handful of two-headed states on a core cycle and have been essential for the current level of understanding. However, it is not always clear how to evolve these core-cycle models to explain more complex behavior such as non-processive motion. We have taken a different approach and have developed a kinetic model without a pre-defined core cycle. Our model includes 80 two-headed states and permits transitions between any two states that differ by a single catalytic or binding event. We constrain the rate constants as much as possible by published experimental data. We define many of the remaining unknown rate constants based on mechanical strain in the kinesin neck linkers and their docking state. We present a one-dimensional model for neck-linker modulation of head binding and unbinding rates and nucleotide binding and unbinding rates. We show that our model reproduces a run length (processivity) and run time in the range of experimental results. The core cycles that emerge are slightly different than those commonly discussed. We also explore how processivity and speed change with neck linker length. Our modeling applications are available as LabVIEW open-source code and compiled executables for PCs, which will allow other research groups to adapt the model and rate constants and may aid in general understanding of molecular motor behavior.
Elevated central serotonin levels inhibit emotional crying
Authors: van der Veen Frederik , Jorritsma Joyce , Krijger Carola , Vingerhoets Ad
Published: July 2019

Previous research has suggested a possible role of serotonin in emotional expressions, such as crying. We have found that a transient increase of central serotonin levels by means of oral administration of paroxetine reduces crying in response to emotional movies in healthy female volunteers. This is the first direct evidence of an important role of serotonin in this uniquely human emotional response.
Auditory cortex mediates the perceptual effects of acoustic temporal expectation
Authors: Jaramillo Santiago , Zador Anthony
Published: July 2019

When events occur at predictable instants, anticipation improves performance. Knowledge of event timing modulates motor circuits, improving response speed. By contrast, the neuronal mechanisms underlying changes in sensory perception due to expectation are not well understood. We have developed a novel behavioral paradigm for rats in which we manipulated expectations about sound timing. Valid expectations improved both the speed and the accuracy of subjects' performance, indicating not only improved motor preparedness but also enhanced perception. Single neuron recordings in primary auditory cortex revealed enhanced representation of sounds during periods of heightened expectation. Furthermore, we found that activity in auditory cortex was causally linked to the performance of the task, and that changes in the neuronal representation of sounds predicted performance on a trial-by-trial basis. Our results indicate that changes in neuronal representation as early as primary sensory cortex mediate the perceptual advantage conferred by temporal expectation.
Lego DNA assembling, a simple in vitro method for constructing DNA molecule
Authors: Xian Mo , Jiang Xinglin , Yang Jianming , Zhang Haibo , Liu Huaiwei , Zheng Yanning , Wang Cong , Su Sizheng
Published: July 2019

Digestion-ligation based and recombination based methods for constructing recombinant DNA are the basic techniques in molecular biology and thus built one of the foundations for the modern life sciences. Here we describe a new strategy that can radically simplify some of the same task. The lego DNA assembling, based on strand annealing, allows in vitro assembly of multi DNA fragments in one step with precise junctions and excludes the need for any enzyme. As a proof of concept, we rapidly constructed plasmids from 4, 6 and 8 fragments with very high efficiencies (100%). And we found this method a powerful tool for synthetic biology, constructing a partial isoprene biosynthesis pathway (consisting of four genes) in 2 days. We also assembled a customized expression vector to show its modularity.
Local field potentials, BOLD and spiking activity – relationships and physiological mechanisms
Authors: Berens Philipp , Logothetis Nikos , Tolias Andreas
Published: July 2019

Extracellular voltage fluctuations (local field potentials, LFPs) reflecting neural mass action are ubiquitous across species and brain regions. Numerous studies have characterized the properties of LFP signals in the cortex to study sensory and motor computations as well as cognitive processes like attention, perception and memory. In addition, its extracranial counterpart – the electroencephalogram – is widely used in clinical applications. However, the link between LFP signals and the underlying activity of local populations of neurons is still largely elusive. For the LFP to aid our understanding of cortical computation, however, we need to know as precisely as possible what aspects of neural mass action it reflects. In this chapter, we examine recent advances and results regarding the origin, the feature selectivity and the spatial resolution of the local field potential and discuss its relationship to local spiking activity as well as the BOLD signal used in fMRI. We place particular focus on the gamma-band of the local field potential since it has long been implicated to play an important role in sensory processing. We conclude that in contrast to spikes, the local field potential does not measure the output of the computation performed by a cortical circuit, but are rather indicative of the synaptic and dendritic processes, as well as the dynamics of cortical computation.