bluuebunny/crossref_metadata_2025 huggingface dataset:
Enforced expression of PPP1R13L increases tumorigenesis and invasion through p53-dependent and p53-independent mechanisms.
Authors: Laska Magdalena , Lowe Scott , Zender Lars , Hearn Stephen , Vogel Ulla , Jensen Uffe Birk , Bric Anka , Nexø Bjørn
Published: July 2019

PPP1R13L was initially identified as a protein that binds to the NF-[kappa]B subunit p65/RelA and inhibits its transcriptional activity. It also binds p53 and inhibits its action. One set of experimental findings based on over-expression of PPP1R13L indicates that PPP1R13L blocks apoptosis. Another set of experiments, based on endogenous production of PPP1R13L, suggests that the protein may sometimes be pro-apoptotic. We have used primary mouse embryonic fibroblasts (MEFs), dually transformed by H-ras and Adenovirus E1A and differing in their p53 status, to explore the effects of PPP1R13L over-expression, thus examining the ability of PPP1R13L to act as an oncoprotein. We found that over-expression of PPP1R13L strongly accelerated tumor formation by ras/E1A and also resulted in an increased metastatic potential of the tumors. PPP1R13L over-expressing cells were depleted for both p53 and active p65/RelA and we found that both p53 dependent and independent apoptosis pathways were regulated by PPP1R13L. Finally, studies with the proteasome inhibitor MG132 revealed that over-expression of PPP1R13L causes faster p53 degradation, a likely explanation for the depletion of p53. Taken together, our results show that increased levels of PPP1R13L can increase tumorigenesis and furthermore pinpoint PPP1R13L as a gene that influences metastasis.
Dendritic spike induction of postsynaptic cerebellar LTP
Authors: Canepari Marco , Vogt Kaspar
Published: July 2019

The architecture of parallel fiber (PF) axons contacting cerebellar Purkinje neurons (PNs) retains spatial information over long distances. PF synapses can trigger local dendritic calcium spikes, but whether and how this calcium signal leads to plastic changes that decode the PF input organization is unknown. By combining voltage and calcium imaging, we show that PF-elicited calcium signals, mediated by voltage-gated calcium channels, increase non-linearly during high-frequency bursts of electrically constant calcium spikes because they locally and transiently saturate the endogenous buffer. We demonstrate that these non-linear calcium signals, independently of NMDA or metabotropic glutamate receptor activation, can induce PF long-term potentiation (LTP). Two-photon imaging in coronal slices revealed that calcium signals inducing LTP can be observed by stimulating either the PF or the ascending fiber pathway. We propose that local dendritic calcium spikes, evoked by synaptic potentials, provide a unique mechanism to spatially decode PF signals into cerebellar circuitry changes.
Guided Tissue Remineralization of Resin-Bonded Acid-Etched Dentin
Authors: Tay Franklin , Pashley David
Published: July 2019

Contemporary biomineralization strategies incorporate non-classical crystallization pathways of fluidic amorphous nanoprecursors and mesoscopic transformation. Using two functional biomimetic molecules, we previously regenerated mineralized dentin from acid-etched dentin using the Guided Tissue Remineralization (GTR) approach, with definitive intrafibrillar remineralization of type-I collagen. Degradation of denuded collagen within dentin adhesive resin-infiltrated dentin is a pertinent problem in dentin bonding. Here, we show that GTR provides a means of salvaging these degrading bonds by remineralizing resin-dentin interfaces. The GTR medium consists of a Portland cement/simulated body fluid that includes polyacrylic acid and polyvinylphosphonic acid biomimetic analogs for amorphous calcium phosphate dimension regulation and collagen targeting. Both interfibrillar and intrafibrillar apatites became readily discernible within the adhesive-bonded dentin after 2-4 months. Amorphous nanoprecursors created by GTR also penetrated the adhesive resin matrix to create nanocomposites. We anticipate GTR to be the starting point for more sophisticated strategies in extending the longevity of resin-dentin bonds.
Towards a model of non-equilibrium binding of a metal ion in a biological system
Authors: Beardmore James , Exley Christopher
Published: July 2019

We have used a systems biology approach to address the hitherto insoluble problem of the quantitative analysis of non-equilibrium binding of aqueous metal ions by competitive ligands in heterogeneous media. To-date, the relative proportions of different metal complexes in aqueous media have only been modelled at chemical equilibrium and there are no quantitative analyses of the approach to equilibrium1. While these models have improved our understanding of how metals are used in biological systems they cannot account for the influence of kinetic factors in metal binding, transport and fate2. Here we have modelled the binding of aluminium in blood serum by the iron transport protein transferrin (Tf) as it is widely accepted that the biological fate of this non-essential metal is not adequately described by experiments, in vitro and in silico, which have consistently demonstrated that at equilibrium 90% of serum Al(III) is bound by Tf3-5. We have coined this paradox 'the blood-aluminium problem'6 and herein applied a systems biology approach which utilised well-found assumptions to pare away the complexities of the problem such that it was defined by a comparatively simple set of computational rules and, importantly, its solution assumed significant predictive capabilities. Here we show that our novel computational model successfully described the binding of Al(III) by Tf both at equilibrium and as equilibrium for AlTf was approached. The model provided an explanation of why the distribution of Al(III) in the body cannot be adequately described by its binding and transport by Tf and it highlighted the significance of kinetic in addition to thermodynamic constraints in defining the fate of metal ions in biological systems. This is the first model of non-equilibrium metal binding in a biological system and it should prove to be a valuable predictive tool in furthering our understanding of the bioinorganic chemistry of metals.
Community dynamics generates complex epidemiology through self-induced amplification and suppression
Authors: Zhao Zhenyuan , Calderon Juan Pablo , Xu Chen , Hui Pak Ming , Johnson Neil
Published: July 2019

The development of quantitative models of outbreaks is key to their eventual control, from human and computer viruses through to social (and antisocial) activities. Standard epidemiological models can reproduce many general features of outbreaks. Unfortunately, the large temporal fluctuations which often dominate real-world data are thought to require more complicated, system-specific models involving super-spreaders, specific social network topologies and rewirings, and birth-death processes. However we show here that these large fluctuations have a generic explanation in terms of underlying community dynamics. Communities increasing (or decreasing) in size, act as instantaneous amplifiers (or suppressors) yielding a complex temporal evolution whose features vary dramatically according to the relative timescales of the community dynamics. We uncover, and provide an analytic theory for, a novel epidemiological phase transition driven by the population's response to an outbreak. An imminent epidemic will be suppressed if individual communities start to break up more frequently or join together less frequently, but will be amplified if the reverse is true.
Molecular implications of prolonged aggression experience: Th, Dat1, Snca and Bdnf gene expression in the ventral tegmental area of the victorious male mice
Authors: Bondar Natalia P. , Boyarskikh Ul’yana A. , Kovalenko Irina L. , Filipenko Maxim L. , Kudryavtseva Natalia
Published: July 2019

Th, Dat1, Snca and Bdnf were the genes whose mRNA levels in the ventral tegmental area of the midbrain were measured in male mice that were victorious in 20 daily agonistic interactions and in a group of such victorious mice that had later not been allowed to fight for 14 days. This experiment demonstrated increased Th, Dat1 and Snca but not Bdnf mRNA levels in the former group as compared to the controls. In the latter group, the expression of the Th and Dat1 genes was still enhanced, while the level of Snca mRNA did not differ from that in the controls. These findings suggest that positive fighting experience enhances the expression of the genes concerned with dopaminergic systems and this enhanced expression is preserved for a long time afterwards. Significant positive correlations were found between the level of aggression and Th and Snca mRNA levels in the winners.
Molecular implications of prolonged aggression experience: Th, Dat1, Snca and Bdnf gene expression in the ventral tegmental area of the victorious male mice
Authors: Bondar N. , Boyarskikh U. , Kovalenko I. , Filipenko M. , Kudryavtseva N.
Published: July 2019

Th, Dat1, Snca and Bdnf were the genes whose mRNA levels in the ventral tegmental area of the midbrain were measured in male mice that were victorious in 20 daily agonistic interactions and in a group of such victorious mice that had later not been allowed to fight for 14 days. This experiment demonstrated increased Th, Dat1 and Snca but not Bdnf mRNA levels in the former group as compared to the controls. In the latter group, the expression of the Th and Dat1 genes was still enhanced, while the level of Snca mRNA did not differ from that in the controls. These findings suggest that positive fighting experience enhances the expression of the genes concerned with dopaminergic systems and this enhanced expression is preserved for a long time afterwards. Significant positive correlations were found between the level of aggression and Th and Snca mRNA levels in the winners.
Feeding preferences of Microcerotermes championi (snyder) on different timbers dried at different temperatures under choice and no choice trials
Authors: Rasib Khalid Zamir
Published: July 2019

Ten species of wood were tested for their natural resistance and to reveal feeding preferences of M. championi. In "no choice" laboratory experiments, Abies pindrow was found highly resistant and Populus euramericana highly palatable. The impact of drying temperature (60°C, 70°C, 80°C, 90°C and 100°C) was studied. The amount of wood consumed in general, increased with increase in drying temperature indicating that heat contributed to the loss of natural resistance components of the woods. When M. championi was given a choice and the woods were offered in combination of two, this termite species repeated its instinct, easily identified the more preferred wood and consumed more of it. Consequently, M. championi showed maximum feeding on P. euramericana and the minimum on A. pindrow and the mean feeding propensity was significantly different (P < 0.0028). Based on the feeding propensity, the woods are arranged in descending order of preference: Populus euramericana > Azadirachta indica > Cedrus deodara > Pinus roxburghii > Morus alba > Tectona grandis > Mangifera indica > Acacia arabica > Thuja occidentalis > Abies pindrow. Although M. championi fed aggressively on P. roxburghii, the wooden blocks had undesirable effect on the survival of the species, manifesting toxic nature of the wood.
Mechanisms linking plant diversity to large herbivore performance
Authors: Wang Ling , Wang Deli , He Zhengbiao , Liu Guofang , Hodgkinson Ken
Published: July 2019

There is established concern that loss of biodiversity will affect ecosystem productivity, nutrient cycling, carbon storage, stability and other properties^1,2^. Interactions between trophic levels are thought to link changes to biodiversity and ecosystem processes^3-6^. However, there is a lack of empirical studies linking plant diversity with altered trophic levels^7,8^, especially for large herbivores, the important but often neglected, controlling trophic level in terrestrial systems. Here we examine responses in performance of the large generalist herbivore to changes in plant diversity, using an indoor cafeteria trial and a field experiment. Our results show that increased plant diversity improves herbivore performance but it is depressed at highest plant diversity levels. We propose the Disturbance Selection Hypothesis for explaining plant diversity effects on primary consumers. Increasing the number of plant species in grassland, increases consumption and enhances nutrient intake (presumably improving animal fitness) by modifying nutrient balance, toxin dilution and taste modulation. High plant diversity simultaneously intensifies animal diet switching frequency, and weakens the herbivore's ability to select food, thereby increasing foraging cost and disturbing the herbivore's selection of forage. Thus, the consequence of plant diversity for large herbivore performance depends on the trade-off between the positive and negative effects. At highest plant diversity the positive effects weaken and negative effects strengthen. We suggest knowledge of the mechanisms is the means for understanding relationships between biodiversity and ecosystem functioning, and the management of large herbivores on rangelands used for conservation and grazing.
Cortical responses reflecting inhibition of return (IOR): a magnetoencephalographic study
Authors: Hashimoto Akiko , Takeshima Yasuyuki , Inui Koji , Kakigi Ryusuke
Published: July 2019

Inhibition of return (IOR) is a phenomenon whereby the reaction time (RT) to detect a second stimulus (target) presented at the same location as the first stimulus (cue) is longer than when the target is presented at an un-cued location. In the present study, we investigated cortical activities under a standard IOR paradigm by recording visual evoked magnetic fields (VEFs). In Experiment 1, subjects directed their attention to the target at the periphery of the screen and the RT was measured. In Experiment 2, they paid attention to the center of the screen and the RT was not measured. In both experiments, the peak latency of the major deflection of VEFs in the occipito-temporal area was greater for the cued target than un-cued target. This is the first study to report the IOR response of the visual cortex, and our results support the pre-attentive nature of the IOR phenomenon.
Reservoir of Bacterial Exotoxin Genes in the Environment
Authors: Casas Veronica , Magbanua Joseph , Sobrepeña Gerico , Maloy Stanley
Published: July 2019

This is the first report of an environmental reservoir of a bacterial exotoxin gene harbored in an atypical host in the environment. Screening bacterial isolates from the environment via sea-specific PCR identified an isolate with a DNA sequence >95% identical to the Staphylococcus aureus enterotoxin A gene (sea). 16S DNA sequence comparisons identified the environmental isolate as a Pseusodomonad. Laboratory studies confirmed that this Pseudomonad is psychrophilic. The results indicate that the sea gene is present in an alternative bacterial host, providing the first evidence for an environmental reservoir of exotoxin genes in bacteria. Transfer of these genes between phage and alternative bacterial hosts may promote the evolution of novel human diseases.
Oilseed Rape straw for Cultivation of Oyster Mushroom
Authors: Peyvast Gholamali , Nowroozi Ahmad , Olfati Jamal-Ali
Published: July 2019

Oyster mushroom [Pleurotus ostreatus var. sajor caju (Fr.) Singer] cultivation can play an important role in managing organic waste. It can be cultivated on a wide rang of substrates containing lignin and cellulose. Oyster mushroom was grown on five substrates: Rise straw (Oryza sativa L. var. Alikazemi), Rise straw + Oilseed Rape straw (Brassica napus var. Hyola 401) (75:25 dw /dw), Rise straw + Oilseed Rape straw (50:50 dw /dw), Rise straw + Oilseed Rape straw (25:75 dw /dw) and Oilseed Rape straw alone. Oilseed Rape straw alone and Rise straw + Oilseed Rape straw (25:75 dw /dw) were best for fruit body production of P. ostreatus. Time to fruiting for P. ostreatus was also shorter on Oilseed Rape straw. Protein content of the fruit bodies obtained from Oilseed Rape straw was higher than those from other substrates. Using Oilseed Rape straw as a substrate appears to be suitable for oyster mushroom production.
Caloric restriction causes symmetric cell division and delays aging in Escherichia coli
Authors: Watve Milind , Watve Samit , Belsare Prajakta , Lele Uttara , Bari Snehal , Karande Sarika
Published: July 2019

Aging is one of the most intriguing processes of biology and despite decades of research, many aspects of aging are poorly understood. Aging is known to occur in bacteria and yeast that divide with morphological asymmetry. Morphologically symmetrically dividing bacteria such as Escherichia coli were assumed not to age until they were shown to divide with functional asymmetry leading to aging and death of some of the cells even in exponentially growing cultures. In asymmetrically dividing E. coli the newly synthesized components are presumed to occupy one pole so that after division one of the daughter cells receives newly synthesized components whereas the other retains the older components. Mathematical models predicted that at the population level, asymmetric growth should result in higher growth rate and symmetric growth in higher growth yield. Therefore, arguably symmetric cell division should be selected in low nutrient environments and asymmetric division in nutrient rich environments. A further prediction was that lower substrate concentrations should strengthen repair mechanisms and suppress aging whereas higher substrate concentrations suppress repair and enhance aging. We show here that E. coli divides more symmetrically under caloric restriction, that both genetic selection and phenotypic plasticity are important determinants of cell division symmetry and also that the proportion of cells that stop dividing and therefore are presumably dead is significantly lower in symmetrically dividing cultures. However, contrary to the prediction, symmetry was not always accompanied by reduced growth rate. These results demonstrate that asymmetry of division in E. coli is not hardwired but responsive to the nutritional environment. This provides a new perspective on why caloric restriction increases lifespan in organisms ranging from microbes to mammals. Symmetry of division may be a mechanism spanning across the width of life forms but regulating aging in different ways in different forms.
Body Fat is Associated with Decreased Endocrine and Cognitive Resilience to Acute Emotional Stress
Authors: Mujica-Parodi Lilianne , Renelique Rudolph , Taylor Marcus
Published: July 2019

*Objective:*

Cortisol is elevated both in individuals with increased emotional stress as well as with higher percentages of body fat. Cortisol is also known to affect cognitive performance, particularly spatial processing, selective attention, and working memory. We hypothesized that increased body fat might therefore be associated with decreased performance on a spatial processing task, in response to an acute real-world stressor. *Design:* We tested two separate samples of subjects undergoing their first (tandem) skydive. In the first sample (N=78), subjects were tested for salivary cortisol and state-anxiety (Spielberger State Anxiety Scale) during the plane's fifteen-minute ascent to altitude in immediate anticipation of the jump. In a second sample (N=20), subjects were tested for salivary cortisol, as well as cardiac variables (heart rate, autonomic regulation via heart rate variability) and performance on a cognitive task of spatial processing, selective attention, and working memory.

*Results:*

In response to the skydive, individuals with greater body fat percentages showed significantly increased reactivity for both cortisol (on both samples) and cognition, including decreased accuracy of our task of spatial processing, selective attention, and working memory. These cognitive effects were restricted to the stress response and were not found under baseline conditions. There were no body fat interactions with cardiac changes in response to the stressor, suggesting that the cognitive effects were specifically hormone-mediated rather than secondary to general activation of the autonomic nervous system.

*Conclusions:*

Our results indicate that, under real-world stress, increased body fat may be associated with endocrine stress-vulnerability, with consequences for deleterious cognitive performance.
Genome-wide analysis to predict protein sequence variations that change phosphorylation sites or their corresponding kinases
Authors: Ryu Gil-Mi , Song Pamela , Kim Kyu-Won , Oh Kyung-Soo , Kim Jong Hun
Published: July 2019

We define phosphovariants as genetic variations that change phosphorylation sites or their interacting kinases. Considering the essential role of phosphorylation in protein functions, it is highly likely that phosphovariants change protein functions and may constitute a proportion of the mechanisms by which genetic variations cause individual differences or diseases. We categorized phosphovariants into three subtypes and developed a system that predicts them. Our method can be used to screen important polymorphisms and help to identify the mechanisms of genetic diseases.
Fossil evidence for the origin of spider spinnerets
Authors: Selden Paul , Shear William
Published: July 2019

Silk production from opisthosomal glands is a defining characteristic of spiders (Araneae). Silk emerges from spigots (modified setae) borne on spinnerets (modified appendages). Spigots from Attercopus fimbriunguis (Shear, Selden & Rolfe, 1987^1^), from Middle Devonian (386 Ma) strata of Gilboa, New York were described in 1989^2^ as evidence for the oldest spider and the first use of silk by animals. Slightly younger (374 Ma) material from South Mountain, New York, conspecific with A. fimbriunguis, includes spigots and other evidence which elucidate the evolution of early Araneae and the origin of spider silk. No known Attercopus spigots, including the original specimen^2^, occur on true spinnerets but are arranged along the edges of plates. Spinnerets originated from biramous appendages of opisthosomal somites 4 and 5; while present in Limulus, no other arachnids have opisthosomal appendage homologues on these segments. The spigot arrangement in Attercopus shows a primitive state prior to the re-expression of the dormant genetic mechanism which gave rise to spinnerets in later spiders. The inability of Attercopus precisely to control silk weaving suggests its original use as a wrapping, lining or homing material.
How do you choose your literature search tool(s)?
Authors: Acharya Kshitish , Kasliwal Greta , Haridas Haritha
Published: July 2019

With increasing number of bio-literature search engines, scientists and health professionals either make a subjective choice of tool(s) or face a challenge of analyzing multiple features of a plethora of bibliographic software. There is an urgent need for a thorough comparative analysis of the available literature scanning tools, from the user’s perspective. We report results of the first time semi-quantitative comparison of 21 search programs, which can search published (partial or full text) documents in life science areas. The observations can assist life science researchers and medical professionals to make an informed selection among the programs, depending on their search objectives. Some of the important findings are: 1. Most of the hits obtained from Scopus, ReleMed, EBImed, CiteXplore, and HighWire Press were usually relevant (i.e., these tools showed a better precision than other tools). 2. But a very high number of relevant citations were retrieved by HighWire Press, Google Scholar, CiteXplore and Pubmed Central (they had better recall). 3. HWP and CiteXplore seemed to have a good balance of precision and recall efficiencies. 4. PubMed Central, PubMed and Scopus provided the most useful query systems. 5. GoPubMed, BioAsk, EBIMed, ClusterMed could be more useful among the tools that can automatically process the retrieved citations for further scanning of bio-entities such as proteins, diseases, tissues, molecular interactions etc). The authors suggest the use of PubMed, Scopus, Google Scholar and HighWire Press - for better coverage, and GoPubMed - to view the hits categorized based on the MeSH and gene ontology terms.
Threshold Decline in Mesoamerican Coral Growth and Resiliency
Authors: Carilli Jessica , Norris Richard
Published: July 2019

Caribbean coral reefs have been massively altered in recent decades due to human impacts, resulting in a dramatic reduction of live coral cover but quantitative data before the 1970s have not been available to assess how these changes came about1,2,3. We produced master chronologies of growth rates in massive Montastrea faveolata corals from the Mesoamerican reef tract that provide a method for extending records of coral health further back into the past. Our records reveal a unique reduction in growth rate associated with the 1998 coral bleaching event that has no parallel in the past 75 to 150 years. Of 92 cores collected from live coral heads in 2006-2007, 94% have severely reduced growth rates and 14% exhibit partial mortality scars in 1998-1999 whereas only 3 stress bands are found in single cores prior to 1998, and none of these cores exhibited earlier partial mortality. Some corals returned to pre-1998 extension rates by 2001, although corals in areas affected by sediment-laden runoff or high human population density still had not fully recovered by the time of sample collection eight years later. Previous episodic stresses like hurricane strikes and a warming event in 1983 more severe than 1998 had little to no effect on M. faveolata growth rates. The 1998 event apparently surpassed a threshold in coral tolerance precipitating a catastrophic shutdown in growth that had lasting effects throughout the Mesoamerican reef system but was particularly prolonged in areas exposed to other stressors. These findings suggest that projected increases in global temperatures over the next century are likely to result in drastic reductions in growth rather than a gradual decline in coral health, but that corals with fewer local stresses will be better able to survive bleaching events, underscoring the need for local conservation measures.
Binge and Emotional Eating in obese subjects seeking weight loss treatment
Authors: Ricca Valdo , Castellini Giovanni , Lo Sauro Carolina , Ravaldi Claudia , Lapi Francesco , Mannucci Edoardo , Rotella Carlo Maria , Faravelli Carlo
Published: July 2019

Objective:

Binge Eating Disorder (BED) is highly prevalent among individuals seeking weight loss treatment. Considering the possible trigger factors for BED, different studies focused on the role of emotional eating. The present study compared threshold, subthreshold BED, and subjects without BED in a population of overweight/obese individuals seeking weight loss treatment, considering the anamnesis, the eating disorder specific and general psychopathology, the organic and psychiatric comorbidity, the emotional eating as a trigger factor for binge eating, and the quality of life. Design: cross-sectional survey.

Subjects:

Four hundred thirty eight overweight subjects seeking weight loss treatment have been enrolled in the study. Measurements: Subjects have been evaluated by means of a clinical interview (SCID I) and different self-reported questionnaires (Eating Disorder Examination Questionnaire, Binge Eating Scale, Beck Depression Inventory, Spielberg's State-Trait Anxiety Inventory, Symptom Checklist 90, Emotional Eating Scale, and Obesity Related Well-Being questionnaire).

Results:

One hundred and five subjects (24% of the sample) fulfilled the DSM-IV criteria of lifetime BED, 146 (33.3%) fulfilled the criteria of lifetime subthreshold BED, and 187 (42.7%) subjects were diagnosed overweight non-BED. No correlations between the binges frequencies and the overweight levels were found. All the three groups showed high psychiatric comorbidities, and the three groups significantly differed in terms of emotional eating, which was positively correlated to the binge eating frequencies.

Conclusions:

Threshold and subthreshold BED deserve a careful psychopathological investigation and emotional eating seems to play a key role as trigger factor for binge eating. Obesity is associated with a high psychiatric comorbidity and a low quality of life, independently from the specific and general eating disorder psychopathology.
Technological Solutions for Energy Security and Sustainability
Authors: Werbos Paul
Published: July 2019

This paper addresses the question: how can we minimize the expected time between now and the time when we achieve three measures of sustainability and security together — independence from oil in cars and trucks, very deep reductions in greenhouse gas emissions and deep reductions in natural gas for electricity? Specific new technologies and metrics for progress are discussed, in context, linked to new information from IEEE, NSF, the State of the Future project and other sources.
Decoding the Design Principles of Amino Acids and the Chemical Logic of Protein Sequences
Authors: Jayaram B.
Published: July 2019

That only 20 amino acids occur naturally accounting for the structural and functional diversity of proteins remains a mystery. We show here that this is a consequence of the action of a symmetry group, identify the presence of hydrogen bond donor groups, presence of sp3 hybridized [gamma] carbons, absence of [delta] carbons and linearity as properties central to side chain design and quantify the chemical logic of protein sequences.
PocketMatch: A new algorithm to compare binding sites in protein structures
Authors: Kalidas Yeturu , Chandra Nagasuma
Published: July 2019

Background:

Recognizing similarities and deriving relationships among protein molecules is a fundamentalrequirement in present-day biology. Similarities can be present at various levels which can be detected through comparison of protein sequences or their structural folds. In some cases similarities obscure at these levels could be present merely in the substructures at their binding sites. Inferring functional similarities between protein molecules by comparing their binding sites is still largely exploratory and not as yet a routine protocol. One ofthe main reasons for this is the limitation in the choice of appropriate analytical tools that can compare binding sites with high sensitivity. To benefit from the enormous amount of structural data that is being rapidly accumulated, it is essential to have high throughput tools that enable large scale binding site comparison.

Results:

Here we present a new algorithm PocketMatch for comparison of binding sites in a frame invariantmanner. Each binding site is represented by 90 lists of sorted distances capturing shape and chemical nature of the site. The sorted arrays are then aligned using an incremental alignment method and scored to obtain PMScores for pairs of sites. A comprehensive sensitivity analysis and an extensive validation of the algorithm have been carried out. Perturbation studies where the geometry of a given site was retained but the residue types were changed randomly, indicated that chance similarities were virtually non-existent. Our analysis also demonstrates that shape information alone is insufficient to discriminate between diverse binding sites, unlesscombined with chemical nature of amino acids.

Conclusions:

A new algorithm has been developed to compare binding sites in accurate, efficient andhigh-throughput manner. Though the representation used is conceptually simplistic, we demonstrate that alongwith the new alignment strategy used, it is sufficient to enable binding comparison with high sensitivity. Novel methodology has also been presented for validating the algorithm for accuracy and sensitivity with respect to geometry and chemical nature of the site. The method is also fast and takes about 1/250th second for one comparison on a single processor. A parallel version on BlueGene has also been implemented.
Pegs and Ropes: Geometry at Stonehenge
Authors: Johnson Anthony , Pimpinelli Alberto
Published: July 2019

A recent computer-aided-design investigation of the Neolithic 56 Aubrey Hole circuit at Stonehenge has led to the discovery of an astonishingly simple geometrical construction for drawing an approximately regular 56-sided polygon, feasible with a compass and straightedge. In the present work, we prove analytically that the aforementioned construction yields as a byproduct, an extremely accurate method for approximating a regular heptagon, and we quantify the accuracy that prehistoric surveyors may have ideally attained using simple pegs and ropes. We compare this method with previous approximations, and argue that it is likely to be at the same time the simplest and most accurate. Implications of our findings are discussed.
Courtship plasticity reveals the evolution of dialects in allopatric fish populations
Authors: Gonzalez Zuarth Cesar , Vallarino Adriana , Macias Garcia Constantino
Published: July 2019

Traditionally, reproductive isolation between disjoint populations has been thought to emerge as a result of the accumulation of different mutations, genetic drift, or through the effects of natural and sexual selection^1^. Alternatively, the ability of an organism to express different phenotypes depending on the environment (i.e. phenotypic plasticity) could produce reproductive isolation^2,3^. Sexually selected traits are expected to be phenotypically plastic and can result in modifications of the species recognition system and thus originate new species^4^. Here we show that the population-characteristic male courtship behaviour of a fish (Girardinichthys multiradiatus) is modified in the presence of females from other populations, that this is due to the males responding to subtle cues from females, and that they fail to emulate the female's population-characteristic behaviour. We conclude that plasticity has led to the creation of local dialects in the courtship pattern that hampers communication between heterogametic individuals and promotes pre-mating isolation.
Successful use of axonal transport for drug delivery by synthetic molecular vehicles
Authors: Filler Aaron , Whiteside Garth , Bacon Mark , Frederickson Martyn , Howe Franklyn , Rabinowitz Miri , Sokoloff Alan , Deacon Terrence , Abell Chris , Munglani Raj , Griffiths John , Bell B. Anthony , Lever Andrew
Published: July 2019

We report the use of axonal transport to achieve intraneural drug delivery. We constructed a novel tripartite complex of an axonal transport facilitator conjugated to a linker molecule bearing up to a hundred reversibly attached drug molecules. The complex efficiently enters nerve terminals after intramuscular or intradermal administration and travels within axonal processes to neuron cell bodies. The tripartite agent provided 100-fold amplification of saturable neural uptake events, delivering multiple drug molecules per complex. in vivo, analgesic drug delivery to systemic and to non-targeted neural tissues was greatly reduced compared to existing routes of administration, thus exemplifying the possibility of specific nerve root targeting and effectively increasing the potency of the candidate drug gabapentin 300-fold relative to oral administration.
Exaptation and emergence as mechanisms to cross fitness valleys during evolution: an example using simulated homing behaviour
Authors: Stafford Richard
Published: July 2019

Evolution is often considered a gradual hill climbing process, slowly increasing the fitness of organisms. I investigate the evolution of homing behaviour in simulated intertidal limpets. In order to evolve path integration as a homing mechanism, a temporary reduction in an organism’s fitness is required – since high developmental costs occur before a successful homing strategy evolves. Simple hill-climbing algorithms, therefore, only rarely result in the evolution of a functional homing behaviour. The inclusion of a second behaviour (trail-following) greatly increases the frequency of success of evolution of a path integration strategy. Initially an emergent homing behaviour is formed combining path integration with trail following. This also demonstrates evolution through exaptation, since the original role of trail following is likely to be unrelated to homing. Analysis of the fitness landscapes of homing in the presence of trail-following behaviour shows a high variability of fitness, which results in the formation of ‘stepping-stones’ of high fitness across fitness valleys. By using these stepping-stones, simple hill-climbing algorithms can reach the global maximum fitness value.
Stress responsive miR-23a attenuates skeletal muscle atrophy by targeting MAFbx /atrogin-1
Authors: Wada Shogo , Kato Yoshio , Okutsu Mitsuharu , Miyaki Shigeru , Suzuki Katsuhiko , Yan Zhen , Asahara Hiroshi , Ushida Takashi , Akimoto Takayuki
Published: July 2019

Muscle atrophy occurs in many pathological states and results primarily from accelerated protein degradation by the ubiquitin-proteasome pathway. We used dexamethasone to induce muscle wasting and investigated the role of a microRNA (miRNA) in the control of muscle-specific E3 ubiquitin ligase MAFbx/atrogin-1. Here we show that miR-23a suppresses MAFbx/atrogin-1 translation by binding to 3'UTR of the mRNA. Furthermore, ectopic expression of miR-23a is sufficient to protect myocytes from atrophy in vitro and in vivo in response to dexamethasone treatment, and heat stress-induced miR-23a protects muscle from dexamethasone-induced muscle atrophy. Our surprising discovery of the physiological role of miR-23a in preventing the atrophy program should lay the basis not only for further understanding of the mechanisms of muscle wasting in diverse diseases, but also for developing novel therapies for these debilitating conditions.
Building Block and Building Rule: Dual Descriptor Method for Biological Sequence Analysis
Authors: Ma Bin-Guang
Published: July 2019

The emergence of “Systems Biology” in recent years highlights the systematic viewpoint of bio-system modeling. Building on such a background, Dual Descriptor Method, a generic methodology for biological sequence analysis is proposed. From a systematic perspective, Dual Descriptor is defined as a two element set of Composition Weight Map and Position Weight Function which aim at reflecting the composition and permutation information of a sequence. An alternate training algorithm is provided to get an optimum description of the building patterns of the sequences. In this paper, dual descriptor method has been applied to the analysis of two typical problems of molecular biology: gene identification and the prediction of protein function. Satisfactory and insightful results are achieved. Owing to the generality of this methodology, dual descriptor method has wide application perspective for many problems of pattern recognition, especially those involved in “Systems Biology”.
Logic motif of combinatorial control in transcriptional networks
Authors: Wu Xuebing , Sun Zhirong , Jiang Rui
Published: July 2019

Combinatorial control is prevalent in transcriptional regulatory networks. However, whether there are specific logic patterns over- or under-represented in real networks remains uninvestigated. Using a theoretic model and in-silico simulations, we systematically study how the relative abundance of distinct regulatory logic patterns influences the network’s global dynamics. We find that global dynamic characteristics are sensitive to several specific logic patterns regardless of the detailed network topology. We show it is possible to infer logic motifs based on the sensitivity profile and the biological interpretations of these global characteristics.
Testing a new intervention to enhance road safety
Authors: Spiegel Rainer , Kalla Roger , Spiegel Frank , Strupp Michael
Published: July 2019

By 2020, it is estimated that road accidents will have moved from ninth to third in the worldwide ranking of burden of disease, as assessed in the disability adjusted life years (DALY)^1,2^. Therefore, it is vital to find effective methods to enhance road safety. Speed limits and traffic calming have the potential to reduce injuries due to road accidents^3,4^. Many drivers, however, do not adhere to speed limits^1-7^. Several studies have shown that adherence to speed limits can be explained by the theory of planned behaviour ^5-7^ and that it is possible to focus on drivers' intentions via self-report questionnaires. It is often difficult, however, to reach the majority of drivers on accident-prone locations with self-report questionnaires. This paper demonstrates an intervention that can be interpreted in the light of two of the theory's key variables^8^. It also has the potential to reach a large number of drivers on such locations. It is a speed-displaying device mounted next to the road (especially in villages). It tells drivers their actual speed (which is publicly visible). The measurement takes place continuously, giving the driver the chance to adjust speed and see the new speed shortly thereafter. The results show that the feedback about the current speed is associated with a significant speed reduction relative to a Control condition.
Low Cardiorespiratory Fitness is an Independent Predictor of Metabolic Syndrome in Young Korean Adults
Authors: Kang Hyun-Sik , Park Soo-Hyun , Kim Shinuk
Published: July 2019

Objective:

To investigate the relationship between cardio/respiratory fitness (CRF) and metabolic syndrome (MS) in young Korean men. Design: In a cross-sectional study, we examined 909 young Korean men (mean&177;SD age, 24.0&177;2 years) who were healthy and not taking any medications affecting blood pressure, glucose, or lipids concentrations. Body fatness, resting blood pressures, and fasting blood levels of lipids, glucose, and insulin were measured with our standardized laboratory protocols. CRF was quantified as the maximum volume of minute oxygen consumption measured during a graded treadmill test. Metabolic syndrome was defined with the National Cholesterol Education Program Adult Treatment Panel III criteria and a modified cut-off value of waist circumference from the Asia-Pacific Perspective: Redefining Obesity and its Treatment.

Results:

Group analyses showed significant and inverse dose-response trends between the metabolic syndrome markers and CRF levels such that men with high and moderate CRF levels had more favorable profiles in body fatness, resting blood pressures, mean values in fasting lipids, glucose, and insulin, and homeostasis model of assessment-insulin resistance than men with low CRF level. After adjusting for several potential confounders such as age, smoking, and body fatness variables, the low and moderate CRF groups had odds of 4.64 (95% CI, 2.00 to 10.79) and 2.57 (95% CI, 1.04 to 6.34) for having metabolic syndrome than the high CRF group. Conclusion: These findings suggest that low CRF is a significant and independent risk factor for metabolic syndrome in young Korean men.
Seeing the invisible: The scope and limits of unconscious processing in binocular rivalry
Authors: Lin Zhicheng , He Sheng
Published: July 2019

When an image is presented to one eye and a very different image is presented to the corresponding location of the other eye, they compete for conscious representation, such that only one image is visible at a time while the other is suppressed. Called binocular rivalry, this phenomenon and its deviants have been extensively exploited to study the mechanism and neural correlates of consciousness. In this paper, we propose a framework, the unconscious binding hypothesis, to distinguish unconscious processing from conscious processing. According to this framework, the unconscious mind not only encodes individual features but also temporally binds distributed features to give rise to cortical representation, but unlike conscious binding, such unconscious binding is fragile. Under this framework, we review evidence from psychophysical and neuroimaging studies, which suggests that: (1) for invisible low level features, prolonged exposure to visual pattern and simple translational motion can alter the appearance of subsequent visible features (i.e. adaptation); for invisible high level features, although complex spiral motion cannot produce adaptation, nor can objects/words enhance subsequent processing of related stimuli (i.e. priming), images of tools can nevertheless activate the dorsal pathway; and (2) although invisible central cues cannot orient attention, invisible erotic pictures in the periphery can nevertheless guide attention, likely through emotional arousal; reciprocally, the processing of invisible information can be modulated by attention at perceptual and neural levels.
Phonology is Fundamental in Skilled Reading
Authors: Ashby Jane
Published: July 2019

There is controversy about the importance of phonology in skilled reading. Event-related potential (ERP) evidence from the initial moments of visual word recognition indicates that processing sub-lexical phonology is fundamental to skilled reading. The early timecourse of this phonological activation explains the predictive power of phonological awareness for early reading development, affirms the importance of phonological processing in learning to read, and illuminates the persistent challenges of dyslexia.
Experiment study on Ma-Xing-Shi-Gan-Tang (MXSGT) and its decomposed recipes on anti-influenza virus A
Authors: Gao Wen , Li Jiyang , Tang Ying , Zhuang Changlong , Li Bo , Wang Shuguang , Huang Hai
Published: July 2019

Ancient China was an East Asian country with large population. As we review the history of China, large scale epidemic like Black Death in Europe rarely occurs. It can be seen that the Traditional Chinese Medicine (TCM) make great effort to antivirus and anti-infection treatment. When the SARS broke out in China in 2003, all medical drugs cannot to prevent or treat it. Preventive with TCM and strict disinfection help control the extension of SARS in short time.The using of TCM in clinical must abide by a most important principle that called principal, assistant, complement and guide. We investigate a famous complex recipe Ma Xing Shi Gan Tang (MXSGT) which is record by well-known clinical textbook "Treatise on Cold-induced Febride Diseases". In order to exploring prescription principle of MXSGT, We examined its decomposed recipes on anti-influenza virus A in vitro. MXSGT was disassembled into 15 recipes according to the design of composing prescriptions. Cell culture technique and MTT test were used to determine the effects of MXSGT and its decomposed recipes on MDCK cells infected by influenza virus A.
Optimization-Based Peptide Mass Fingerprinting for Protein Mixture Identification
Authors: He Zengyou , Yang Chao , Yang Can , Qi Robert Z , Tam Jason Po-Ming , Yu Weichuan
Published: July 2019

*Motivation:* In current proteome research, peptide sequencing is probably the most widely used method for protein mixture identification. However, this peptide-centric method has its own disadvantages such as the immense volume of tandem Mass Spectrometry (MS) data for sequencing peptides. With the fast development of technology, it is possible to investigate other alternative techniques. Peptide Mass Fingerprinting (PMF) has been widely used to identify single purified proteins for more than 15 years. Unfortunately, this technique is less accurate than peptide sequencing method and cannot handle protein mixtures, which hampers the widespread use of PMF technique. If we can remove these limitations, PMF will become a useful tool in protein mixture identification.

*Results:*

We first formulate the problem of PMF protein mixture identification as an optimization problem. Then, we show that the use of some simple heuristics enables us to find good solutions. As a result, we obtain much better identification results than previous methods. Moreover, the result on real MS data can be comparable with that of the peptide sequencing method. Through a comprehensive simulation study, we identify a set of limiting factors that hinder the performance of PMF method in protein mixtures. We argue that it is feasible to remove these limitations and PMF can be a powerful tool in the analysis of protein mixtures.