bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of CD4+ T Cells in HIV Patients Presenting with Malaria at the University of Ilorin Teaching Hospital Nigeria
Authors: Agbede Olajide , Ajiboye Temitope , Kolawole Olatunji , Babatunde Samuel , Odeigha Louis
Published: July 2019

CD4 count is an important immunological marker of disease progression in HIV seropositive patients. This study was carried out to determine the effect of malaria or fever of unknown origin on the population of CD4+ T lymphocytes of HIV seropositive patients attending the highly active antiretroviral therapy (HAART) clinic of the University of Ilorin Teaching Hospital, Ilorin, Nigeria. 36 subjects were selected for this study. Ongoing history of fever was used as a case definition for malaria and malaria was confirmed from microscopic examination of thick and thin film of blood sample obtained from the patients during presentation with fever. The CD4 count was evaluated during presentation of fever and post-fever using flow cytometry. There was significant decrease in CD4 count of the patients. However, upon classifying the patients into 2 groups - those that returned to the clinic after a week and those that returned after a month - a significant increase in CD4 count was noticed in the group that returned after a week, while a significant decrease was noticed in the group that returned after a month (at p value of 95%). Further classification of the patients based on presence of malaria parasite, and body temperature resulted in varying effects on CD4 count post-fever (in the general group, 27 were positive for malaria parasites. Of these 27, there was an increase in CD4 count in 9 (33.3%). However in the group that returned after a week, all 6 (100%) that were positive for malaria parasites showed increase in CD4 count. Five (26.3%) of the 19 patients that had body temperature within the range of 35.5-37.4^o^C showed an increase in CD4 count, while 7 (41.2%) the 17 patients that had body temperature of 37.5^o^C and above showed an increase in CD4 count. The results led to the conclusion that while some components of the immune response to malaria could strengthen the immune system of HIV seropositive patients by increasing their CD4 count, other components will suppress their immunity by decreasing their CD4 count, accelerating the progression to AIDS.
Caveat Emptor: The Meaning of Perception and Integration in Speech Perception
Authors: Massaro Dominic
Published: July 2019

A recent letter^1^ claimed integration of auditory and tactile information in speech perception. Although I have been an advocate of multisensory integration, neither perception nor integration was sufficiently formalized, operationalized, and tested to support this claim.
Quantification of growth hormone in serum by isotope dilution mass spectrometry
Authors: Arsene Cristian , Henrion André , Diekmann Nina , Manolopoulou Jenny , Bidlingmaier Martin
Published: July 2019

Inter-assay variation of antibody based routine tests is hampering comparability of measurement results for growth hormone (GH) between different laboratories and decision making in clinical practice. Here it is demonstrated, that quantification of GH by isotope dilution mass spectrometry (IDMS) constitutes a way to precise and reliable results which can be referred to in evaluation of performance of commercial test kits. With the IDMS method developed, tryptic cleavage products YSFLQNPQTSLCFSESIPTPSNR (T6) and LEDGSPR (T12) of GH are quantified by LC/MS-MS using the isotopically labeled forms of the peptides as internal standards. The GH cleavage fragments are obtained by whole-serum tryptic proteolysis and then extracted from the resulting mixture by semi-preparative reversed phase liquid chromatography followed by strong cation-exchange chromatography. Method validation basing on recovery of recombinant 22 kDa GH spiked to blank serum in defined amounts covering the intended concentration range (3-30 µg/L) would yield mean recoveries of 101.6% (100.7%), standard deviations of 2.5% (2.4%) and combined uncertainties (u~c~) of 3.0% (2.5%) if quantifying T6 (T12) as GH derived fragments, while the LOQ were 1.7 µg/L (2.7 µg/L). Potential to acquisition of reference values is exemplified by application to serum materials used in a recent quality assessment exercise for routine laboratories.
Protein Data Integration through Ontologies
Authors: Sidhu Amandeep
Published: July 2019

In this paper, we consider the challenges of information integration in proteomics from the prospective of researchers using information technology as an integral part of their discovery process. Specifically, data integration, meta-data specification, data provenance and data quality are discussed here. Here we review existing protein data integration methods and propose the use of common vocabulary for protein data integration using ontologies.
Biospheric context of Siberian development
Authors: Alexandrov Georgii , Inoue Gen , Matsunaga Tsuneo
Published: July 2019

Recent publications on human appropriation of Net Primary Production (NPP) raise the question of how much of the biosphere’s productivity we can appropriate in a sustainable way. This article brings the issue into the context of Siberian development. In contrast to many other regions of the world, the population density in Siberia is still very low as compared to the NPP supplied by regional ecosystems. Hence, it is not too late to raise the question on how much of the NPP supplied by Siberian ecosystems we can appropriate in a sustainable way.
We Need A Web For Data
Authors: Wilbanks John
Published: July 2019

The Web has many forums for sharing personal data, but not for scientific data and not in a way that allows the data to be accessed by "machines as users." A Web of data could add tremendous value by integrating disparate disciplines or conduct data-driven queries. Doing this is very complex and requires more robust standards than currently exist. The intended user for most data is not a person; it is a software application that can manipulate the data into something useful for humans. Such software could be "search engines, analytic software, visualization tools, database back ends, and more." This need creates a much different requirement for standards than those that were developed for displaying web data to people. Data software needs a much greater understanding of context and that context has to be supplied alongside the data either through direct integration with the data or linking to a description of it in a persistent and accessible location. Data interoperability must be addressed at the beginning of developing systems because it is significantly harder and costlier to make these connections after both systems have separately implemented non-standardized data collections. Data interoperability must address three levels: legal (intellectual property rights), technical (computer languages and formats), and semantic (meaning of the data). The technical level is the furthest along, with the Semantic Web technologies. Getting scientists to agree on the semantic level could be nearly impossible. The legal level has the greatest opportunity by putting the data into the public domain. There are already precedents for this with genome data and the International Visual Observatory. Putting data into the public domain simplifies the implementation of the technical level. Libraries and publishers in the scholarly publishing community should lead the web of data initiative as they can ensure the connection, curation, and preservation needed. The NSF mandated data sharing could result in funding opportunities to build the web of data. But all involved must be in agreement not to replicate the copyright-controlled model that currently exists with books and journals.
Natural Selection of Paths in Networks
Authors: Fernando Chrisantha , Vasas Vera , Szathmáry Eörs , Husbands Philip
Published: July 2019

We present a novel algorithm that exhibits natural selection of paths in a network. If each node and weighted directed edge has a unique identifier, a path in the network is defined as an ordered list of these unique identifiers. We take a population perspective and view each path as a genotype. If each node has a node phenotype then a path phenotype is defined as the list of node phenotypes in order of traversal. We show that given appropriate path traversal, weight change and structural plasticity rules, a path is a unit of evolution because it can exhibit multiplicative growth (i.e. change it’s probability of being traversed), and have variation and heredity. Thus, a unit of evolution need not be a spatially distinct physical individual. The total set of paths in a network consists of all possible paths from the start node to a finish node. Each path phenotype is associated with a reward that determines whether the edges of that path will be multiplicatively strengthened (or weakened). A pair-wise tournament selection algorithm is implemented which compares the reward obtained by two paths. The directed edges of the winning path are strengthened, whilst the directed edges of the losing path are weakened. Edges shared by both paths are not changed (or weakened if diversity is desired). Each time a node is activated there is a probability that the path will mutate, i.e. find an alternative route that bypasses that node. This generates the potential for a novel but correlated path with a novel but correlated phenotype. By this process the more frequently traversed paths are responsible for most of the exploration. Nodes that are inactive for some period of time are lost (which is equivalent to connections to and from them being broken). This network-based natural selection compares favourably with a standard pair-wise tournament-selection based genetic algorithm on a range of combinatorial optimization problems and continuous parametric optimization problems. The network also exhibits memory of past selective environments and can store previously discovered characters for reuse in later optimization tasks. The pathway evolution algorithm has several possible implementations and permits natural selection with unlimited heredity without template replication.
Plasma amino acid profile is altered by visceral fat accumulation and is a predictor of visceral obesity in humans
Authors: Tanaka Takayuki , Ishizaka Yuko , Mitushima Toru , Tani Mizuki , Toda Akiko , Toda Eiichi , Okada Minoru , Yamamoto Hiroshi , Yamakado Minoru
Published: July 2019

Background:

The plasma amino acid profile can be a useful indicator in clinical settings because it changes in response to various metabolic alternations. However, the association between the plasma amino acid profile and body fat accumulation has not been evaluated in humans.

Objective:

This study aimed to relate plasma amino acids to visceral fat accumulation in humans because excess visceral fat raises the odds ratio of developing metabolic syndrome.

Design:

A total of 1,449 subjects (985 males and 464 females) who had undergone a comprehensive health screening were enrolled in this study. The visceral fat area (VFA) was determined in each subject using CT imaging. Subjects were then divided into two groups according to VFA: high-VFA (&8805;100 cm2, n=867) and low-VFA (<100 cm2, n=582). The plasma amino acid profile was analyzed together with other metabolic valuables and then compared between the two groups using uni- and multivariate analyses.

Results:

As the degree of visceral fat accumulation increased, plasma concentrations of several amino acids changed significantly. Glu, Val, Leu, Ile, Tyr, Ala, Phe, Pro, Lys, Orn, Trp, Met, His and alpha-aminobutyric acid (ABA) levels were significantly higher in the high-VFA group compared to the low-VFA group, whereas the levels of Gly, Ser, Gln and Asn were significantly lower. To evaluate the potential of using amino acids as an indicator of VFA, a discriminant analysis was conducted with the multivariate logistic regression analysis "AminoIndex", and the ROC curve was calculated. The resulting "AminoIndex" exhibited an area under the ROC curve of 0.81 (95% confidence interval; 0.78 to 0.83), with higher sensitivity and specificity by 80% and 65%, respectively.

Conclusions:

The plasma amino acid profile changes depending on visceral fat content and can be used as a marker for diagnosing elevated visceral obesity in humans.
Are men evolutionarily wired to love the "Easy" buttons?
Authors: Trofimova Irina
Published: July 2019

Men's drive for group control and power appears to be an evolutionary inheritance, but it is females, and not males, who developed better abilities for prolonged control and group interaction while males have higher rates of ADHD and autism. This contradictory allocation of sex-related abilities describes the observable behavior, but not the internal meaning attribution leading to the motivation of men and women. Our study in Canada, China and Russia shows that men estimate power- and status-related concepts in significantly more positive terms than women, but give significantly more negative estimations to work-related and reality-related concepts. Men also have a consistent tendency to estimate concepts as less real (even "Reality"), less complex (even "Complexity"), less organized (even "Order"), and more stable (even time-related concepts), than women. These results are interpreted in terms of the evolutionary characteristic of the male sex for irrelevance/redundancy pruning of excessive complexity in human activities.
Higher Efficiency In Prediction Of TIBO Activity By Evolutionary Neural Network
Authors: Seal Abhik
Published: July 2019

The treatment of acquired immunodeficiency syndrome (AIDS) is a challenging medical problem. TIBO is a nonnucleoside reverse transcriptase inhibitor, which binds non-competitively to the hydrophobic pocket on the p66 subunit of RT enzyme. We used a dataset consisting of physicochemical properties and reverse transcriptase inhibitor activities of 88 set of 4,5,6,7-tetrahydro-y-imidazo-[4,5,1-jk][1,4]-x-benzodiazepin-2-(1h)one derivatives that are variously substituted by halogens, alkyl groups. The dataset was taken from the BIOBYTE database at (www.davidhoekman.com). The concentration of the compound leading to 50% effect has been measured and expressed as IC50. The logarithm of the inverse of this parameter has been used as biological end points (log 1/C) in the QSAR studies. The evolutionary neural network (ENN) is a new system for modeling multivariate data. The strengths of ENN’s are that they can extract insignificant predictors, choose the size of the hidden layers and nodes and fine tune the parameters needed in training the network. We have used an ENN to predict the biological activities of Reverse Transcriptase Inhibitors. We have found out that Evolutionary Neural networks are better predictor of activity values than Multiple linear regression and Multilayered Perceptrons. We have calculated the correlation coefficient of each of the methods where we have found ENNs are the best.
Different Approaches For Protein Engineering In Industrial Biotechnology
Authors: Khan Israr , Waheed Akhtar Muhammad
Published: July 2019

Protein engineering is the novel field which has wide applications from pharmaceutics, industry, commercial, laundry and research. It may apply rational design or non rational design or both. Site directed mutagenesis is a classical approach involving the protein folding principles and as such different techniques involving multidisciplinary research and broad knowledge is required involving biocomputing of complex data obtained from various sequencing projects and prediction of the future protein structure either chemically or genetically modified. Non rational mutagenesis or directed evolution involves random mutations in the gene encoding protein or shuffling the genes encoding different domains producing a random set of numerous large libraries of mutant proteins, using advanced technology the desired protein can be selected but the exact structure or changes may remain unnoticed.
Breeding ecology and conservation of Brown booby in Gorgona Island, eastern tropical Pacific Ocean
Authors: Ospina-Alvarez Andres
Published: July 2019

Breeding ecology and reproductive traits of Brown Booby _Sula leucogaster_ etesiaca in Gorgona Natural National Park, Colombia, were studied. Adults morphometrics, eggs dimensions, chicks growth and nesting site characteristics, were examined at three different locations in the park. As with other subspecies, Brown Booby in Gorgona presents inverted sexual dimorphism, with adult females being lengthier, wider and heavier than adult males. Breeding of S. l. etesiaca results in eggs from the first deposition bigger in weight and dimensions than eggs from the second or third deposition. Growth of brown boobies chicks fit to a natural log equation: bodymass(g) = 0.8773 ln(days) + 3.3895. A variety of spawning aggregations was found, and their relationship with the other marine birds nesting in the area is discussed.
Laboratory culture of stem borer, Aeolesthes holosericea F., method developed
Authors: Sinha Ravi Bhushan , Debnath Anil Kumar , Singh Bishwa Mohan Kumar , Prasad Bhagwan Chandra
Published: July 2019

Aeolesthes holosericea, a polyphagous stem borer has been reported to damage up to 40% of tropical tasar silkworm host-plants wherever infestation is high. Known control measures are not very effective as information on its life cycle and susceptible stages against insecticides and bio-agents are insufficient. Laboratory culture of the insect is inevitable for developing control measures as the insect passes most of its life within stem tissues. Culture method of other borer species was not applied to it due to sophistication of process. A convenient laboratory culture method has been developed for the insect. The culture includes complete larval rearing; preservation of pupa; rearing and mating of adults followed by oviposition, incubation and hatching. Other available culture methods are incomplete and hence of little applied value. The present method is simple, economic and easy to be adopted in absence of a sophisticated laboratory having provision for stepwise observation to suit testing of control measures. This method can be utilized by Agriculture and Forest Entomologists and Sericulturists for testing and developing its control measures to save precious forests and to increase production of tasar silk. Anybody can be trained easily.
Inhibition of central insulin-receptor signaling by S961 causes hyperglycemia and glucose intolerance in rats
Authors: Vikram Ajit , Jena Gopabandhu
Published: July 2019

Genetic ablation studies confirmed the role of central insulin-receptor signaling (CIRS) in fuel metabolism. However, the need to examine the role of CIRS in glucose homeostasis under normal physiological condition is indispensable, as insulin affects the neuronal growth, differentiation and synaptic plasticity. Intracerebral administration of S961 induced hyperglycemia and glucose intolerance in normal rats, and provided direct evidence for the involvement of CIRS in the regulation of glucose homeostasis.
Length, Weight, and Yield in Channel Catfish, Lake Diane, MI
Authors: Keenan Elizabeth , Warner Sarah , Crowe Ashley , Courtney Michael
Published: July 2019

Background:

Channel catfish (Ictalurus punctatus) are important to both commercial aquaculture and recreational fisheries. Little published data is available on length-weight relationships of channel catfish in Michigan. Though there is no record of public or private stocking, channel catfish appeared in Lake Diane between 1984 and 1995 and it has developed into an excellent fishery.

Materials and Methods:

Sport angling provided 38 samples which were weighed and measured (fork length). Fillets were also weighed. The best fit estimates of parameters a and b in the model, W(L) = aLb, were obtained by both linear least-squares (LLS) regression (log(W) = log(a) + b log(L)) and non-linear least-squares (NLLS) regression. Best-fit parameters of an improved model, W(L) = (L/L1)^b, were also determined by NLLS regression; the parameter L1 is the typical length of a fish weighing 1 kg. The resulting best-fit parameters, parameter standard errors, and covariances are compared between the two models. The average relative weight for this sample of channel catfish is also determined, along with the typical meat yield obtained by filleting.

Results:

NLLS regression yields parameter estimates of b = 3.2293 and a = 0.00522. The improved model yields the same estimate for the exponent, b, and a length estimate (parameter L1) of 45.23 cm. Estimates of uncertainty and covariance are smaller for the improved model, but the correlation coefficient is r = 0.995 in both cases. LLS regression produced different parameter values, a = 0.01356 and b = 2.9726, and a smaller correlation coefficient, r = 0.980. On average, catfish in the sample weighed 106.0% of the standard weight, (Brown et al.) and the linear regression (no slope) of fillet yield vs. total weight suggests a typical fillet yield of 28.1% with r = 0.989.

Conclusion:

Most of the fish in the sample were above the standard weight, heavier than the 75th percentile for their length. Channel catfish are doing well in Lake Diane and the population is well matched to the food supply. Management should attempt to maintain current population levels. In this case, the improved length-weight model, W(L) = (L/L1)^b, provided lower uncertainties in parameter estimates and smaller covariance than the traditional model.
Integrin-mediated membrane blebbing is dependent on the NHE1 and NCX1 activities.
Authors: Yi Yung-Hsiang , Chang Yu-Sun , Lin Chi-Hung , Lew Tien-Shen , Tang Chih-Yung , Chen Tsung-Yu , Tseng Wei-Lien , Tseng Ching-Ping , Lo Szecheng
Published: July 2019

Integrin-mediated signal transduction and membrane blebbing have been well studied to modulate cell adhesion, spreading and migration^1-6^. However, the relationship between membrane blebbing and integrin signaling has not been explored. Here we show that integrin-ligand interaction induces membrane blebbing and membrane permeability change. We found that sodium-proton exchanger 1 (NHE1) and sodium-calcium exchanger 1 (NCX1) are located in the membrane blebbing sites and inhibition of NHE1 disrupts membrane blebbing and decreases membrane permeability change. However, inhibition of NCX1 enhances cell blebbing to cause cell swelling which is correlated with an intracellular sodium accumulation induced by NHE17. These data suggest that sodium influx induced by NHE1 is a driving force for membrane blebbing growth, while sodium efflux induced by NCX1 in a reverse mode causes membrane blebbing retraction. Together, these data reveal a novel function of NHE1 and NCX1 in membrane permeability change and blebbing and provide the link for integrin signaling and membrane blebbing.
A Tobacco Homolog of DCN1 is Involved in Cellular Reprogramming and in Developmental Transitions
Authors: Hosp Julia , Ribarits Alexandra , Szaszka Katarzyna , Jin Yongfeng , Tashpulatov Alisher , Baumann Marina , Resch Tatiana , Friedmann Christina , Ankele Elisabeth , Voronin Viktor , Palme Klaus , Touraev Alisher , Heberle-Bors Erwin
Published: July 2019

Plant proteomes show remarkable plasticity in reaction to environmental challenges and during developmental transitions. Some of this adaptability comes from ubiquitin-mediated protein destruction regulated by cullin-RING E3 ubiquitin ligases (CRLs). CRLs are activated through modification of the cullin subunit with the ubiquitin-like protein RUB/NEDD8 by an E3 ligase called defective in cullin neddylation 1 (DCN1). Here we show that tobacco DCN1 binds ubiquitin and RUB/NEDD8, and associates with cullin. When knocked down by RNAi, tobacco pollen formation stopped and zygotic embryogenesis was blocked around the globular stage. Additionally, we found that RNAi of DCN1 inhibited the stress-triggered reprogramming of cultured microspores from their intrinsic gametophytic mode of development to an embryogenic state. This stress-induced developmental switch is a known feature in many important crops and leads ultimately to the formation of haploid embryos and plants. Compensating the RNAi effect by re-transformation with a promoter-silencing construct restored pollen development and zygotic embryogenesis, as well as the ability for stress-induced formation of embryogenic microspores. Overexpression of DCN1, however, accelerated pollen tube growth and increased the potential for microspore reprogramming. These results demonstrate that the biochemical function of DCN1 is conserved in plants and that its activity is specifically required for transitions during pollen development and embryogenesis, and for pollen tube tip growth.
A Quantitative Approach to Investigating the Hypothesis of Prokaryotic Intron Loss
Authors: Sinclair Robert
Published: July 2019

Using a novel method, we show that ordered triplets of motifs usually associated with spliceosomal intron recognition are underrepresented in the protein coding sequence of complete Thermotogae, archaeal and bacterial genomes. The underrepresentation observed does not extend to the noncoding strand, suggesting that the cause of the asymmetry is related to mRNA rather than DNA. Our data do not suggest that the underrepresentation is due to gene transfer from eukaryotes. We speculate that one possible explanation for these observations is that the protein coding sequence of Thermotogae, Archaea and Bacteria was at some time in the past subjected to selection against certain motifs appearing in an order which might initiate splicing in environments harboring a functional spliceosome. This is consistent with, but certainly does not prove, a hypothetical scenario in which at least some prokaryote lineages once possessed a functional spliceosome. Thus, we present a new quantitative method, observations obtained using the method, and a speculative discussion of a possible explanation of the observations.
Human Immune Responses to Plasmodium falciparum infection: Molecular Evidence for a Suboptimal THαβ(TH9) and TH17 Bias over Ideal and Effective Traditional TH1 Immunity
Authors: Hu Wan-Chung , Bourgeois August Louis , Wolfe Nathan , Singh Sher , Jedlicka Anne , Scott Alan
Published: July 2019

Using microarray analysis, we showed up-regulation of Toll-like receptors 1,2,4,7,8, NF-[kappa][BETA], TNF-[alpha], p38-MAPK and MHC molecules in human peripheral blood mononuclear cells following infection with Plasmodium falciparum. We report herein further studies based on time-course microarray analysis with a focus on malaria-induced host immunity. Results show that in early malaria; selected immunity-related genes were up-regulated including alpha, beta, and gamma interferon related genes, as well as genes of IL-15, CD36, chemokines (CXCL10, CCL2, S100A8/9, CXCL9, and CXCL11), TRAIL and IgG Fc receptors. During acute febrile malaria, up-regulated genes included alpha, beta, and gamma interferon related genes, IL-8, IL-1[beta], IL-10 downstream genes, TGFB1, oncostatin-M, chemokines, IgG Fc receptors, ADCC signaling, complement-related genes, granzymes, NK cell killer/inhibitory receptors and Fas antigen. During remission, genes for NK receptors, immunoglobins, and granzymes/perforin were up-regulated. When viewed in terms of immunity type, malaria infection appeared to induce a mixed TH1 response, in which α and β interferon driven responses appear to predominate over the more classic IL-12 driven pathway. In addition, TH17 pathway also appears to be playing a significant role in the immunity to Plasmodium falciparum. Gene markers of TH17 (neutrophil-related genes, TGFB1 and IL-6 family (oncostatin-M)) and TH[alpha]/[beta] (IFN-[alpha]/[beta] and NK cytotoxicity and ADCC gene) immunity were up-regulated. Initiation of TH[alpha]/[beta] immune response was associated with an IFN-[alpha]/[beta] response which ultimately resulted in IL-10 and IFN-[gamma] achieved via a different pathway from the more classic IL-12 TH1 pattern. Based on these observations, we speculate that in Plasmodium falciparum infection, TH[alpha]/[beta] and TH17 immunity may predominate over the more traditional TH1 response.
X-ray phase contrast imaging of biological specimens with tabletop synchrotron radiation
Authors: Kneip Stefan , McGuffey Chris , Dollar Franklin , Bloom Michael , Chvykov Vladimir , Kalintchenko Galina , Krushelnick Karl , Maksimchuk Anatoly , Mangles Stuart , Matsuoka Takeshi , Najmudin Zulfikar , Palmer Charlotte , Schreiber Joerg , Schumaker Will , Thomas Alexander , Yanovsky Victor
Published: July 2019

Since their discovery in 1896, x-rays have had a profound impact on science, medicine and technology. Here we show that the x-rays from a novel tabletop source of bright coherent synchrotron radiation can be applied to phase contrast imaging of biological specimens, yielding superior image quality and avoiding the need for scarce or expensive conventional sources.
Consensus virtual screening approaches to predict protein ligands
Authors: Kukol Andreas
Published: July 2019

In order to exploit the advantages of receptor-based virtual screening, namely time/cost saving and specificity, it is important to rely on algorithms that predict a high number of active ligands at the top ranks of a small molecule database. Towards that goal consensus methods combining the results of several docking algorithms were developed and compared against the individual algorithms. Furthermore, a recently proposed rescoring method based on drug efficiency indices was evaluated. Among AutoDock Vina 1.0, AutoDock 4.2 and GemDock, AutoDock Vina was the best performing single method in predicting high affinity ligands from a database of known ligands and decoys. The rescoring of predicted binding energies with the water/butanol partition coeffcient did not lead to an improvement averaged over all receptor targets. Various consensus algorithms were investigated and a simple combination of AutoDock and AutoDock Vina results gave the most consistent performance that showed early enrichment of known ligands for all receptor targets investigated. In case a number ligands is known for a specific target, every method proposed in this study should be evaluated.
Generation of Human Epidermis-Derived Mesenchymal Stem Cell-like Pluripotent Cells and their reprogramming in mouse chimeras
Authors: Huang Bing , Li KaiJing , Yu Jie , Zhang Min , Li YongPing , Xu XiaoPing , Luo Ting , Huang JianFa , Guan LiPing , Li WeiHua , Zhang WenXin , Lin ShaoChun , Huang XinTao , Lin LiPing , Lin YongLiang , Zhang YiChi , Wang WenCong , Wang ZhiChong , Gao QianYing , Chen XiGu , Song XinMing , Ge Jian
Published: July 2019

Stem cells can be derived from the embryo (embryonic stem cells, ESCs), from adult tissues (adult stem cells, ASCs), and by induction of fibroblasts (induced pluripotent stem cells, iPSs). Ethical problems, immunological rejection, and difficulties in obtaining human tissues limit the use of ESCs in clinical medicine. Induced pluripotent stem cells are difficult to maintain in vitro and carry a greater risk of tumor formation. Furthermore, the complexity of maintenance and propagation is especially difficult in the clinic. Adult stem cells can be isolated from several adult tissues and present the possibility of self-transplantation for the clinical treatment of a variety of human diseases. Recently, several ASCs have been successfully isolated and cultured in vitro, including hematopoietic stem cells (HSCs) , mesenchymal stem cells (MSCs), epidermis stem cells, neural stem cells (NSCs), adipose-derived stem cells (ADSCs), islet stem cells, and germ line stem cells. Human mesenchymal stem cells originate mainly from bone marrow, cord blood, and placenta, but epidermis-derived MSCs have not yet been isolated. We isolated small spindle-shaped cells with strong proliferative potential during the culture of human epidermis cells and designed a medium to isolate and propagate these cells. They resembled MSCs morphologically and demonstrated pluripotency in vivo; thus, we defined these cells as human epidermis-derived mesenchymal stem cell-like pluripotent cells (hEMSCPCs). These hEMSCPCs present a possible new cell resource for tissue engineering and regenerative medicine.
Molecular-genetic analysis of Mycobacterium tuberculosis strains spread in different patient groups in St.Petersburg (Russia)
Authors: Chernyaeva Ekaterina , Dobrynin Pavel , Pestova Natalia , Matveeva Natalia , Zhemkov Vladimir , Kozlov Andrei
Published: July 2019

Molecular epidemiological features of M.tuberculosis strains spread among different patient groups in Russia is not studied well. The aim of our study was to compare genotypes of M.tuberculosis strains circulating among TB patients from different groups: homeless, HIV-infected, prisoners and general population of St.Petersburg citizens.One hundred fifty M.tuberculosis complex isolates from different TB patient groups were studied using spoligotyping method.The majority of studied M.tuberculosis isolates in all groups belonged to Beijing family (56% among homeless; 77% among HIV-infected; 60% among general population; 83% among prisoners). There were no significant difference in Beijing family prevalence among homeless patients, HIV/TB co-infected and general population of TB patients. The lowest genetic diversity of the pathogen was detected among imprisoned patients.

Results

of our study demonstrate that M.tuberculosis strains circulating among homeless and HIV-infected people are also spread among general population of St.Petersburg citizens. Thus, we have investigated participation of high-risk groups in the TB infection spread in the city.
Finding the key transition states and intermediates controlling net reaction rates and selectivity
Authors: Stegelmann Carsten , Andreasen Anders
Published: July 2019

In this paper Campbell's degree of rate control is extended to introduce the concepts of degree of kinetic rate control, degree of kinetic selectivity control, degree of thermodynamic rate control and degree of thermodynamic selectivity control. It is demonstrated by applying hypothetical but realistic kinetic models of varying complexity that the new methods offers a rigorous framework to analyze the importance of kinetic and thermodynamic parameters i.e. establishing the critical parameters of the kinetic model. The methods are general and can be applied to complex reaction networks with multiple overall reactions not only in heterogeneous catalysis but for all sorts of chemical kinetic models.
When Spandrels Become Arches: Neural crosstalk and the evolution of consciousness
Authors: Wallace Rodrick
Published: July 2019

Once cognition is recognized as having a 'dual' information source, the information theory chain rule implies that isolating coresident information sources from crosstalk requires more metabolic free energy than permitting correlation. This provides conditions for an evolutionary exaptation leading to the rapid, shifting global neural broadcasts of consciousness. The argument is quite analogous to the well-studied exaptation of noise to trigger stochastic resonance amplification in neurons and neuronal subsystems. Astrobiological implications are obvious.
Translational Oncogenomics and Human Cancer Interactome Networks:
Authors: Baianu I.
Published: July 2019

An overview of translational, human oncogenomics, transcriptomics and cancer interactomic networks is presented together with basic concepts and potential, new applications to Oncology and Integrative Cancer Biology. Novel translational oncogenomics research is rapidly expanding through the application of advanced technology, research findings and computational tools/models to both pharmaceutical and clinical problems. A self-contained presentation is adopted that covers both fundamental concepts and the most recent biomedical, as well as clinical, applications. Sample analyses in recent clinical studies have shown that gene expression data can be employed to distinguish between tumor types as well as to predict outcomes. Potentially important applications of such results are individualized human cancer therapies or, in general, ‘personalized medicine’. Several cancer detection techniques are currently under development both in the direction of improved detection sensitivity and increased time resolution of cellular events, with the limits of single molecule detection and picosecond time resolution already reached. The urgency for the complete mapping of a human cancer interactome with the help of such novel, high-efficiency / low-cost and ultra-sensitive techniques is also pointed out.
Translational Oncogenomics and Human Cancer Interactome Networks
Authors: Baianu I.
Published: July 2019

An overview of translational, human oncogenomics, transcriptomics and cancer interactomic networks is presented together with basic concepts and potential, new applications to Oncology and Integrative Cancer Biology. Novel translational oncogenomics research is rapidly expanding through the application of advanced technology, research findings and computational tools/models to both pharmaceutical and clinical problems. A self-contained presentation is adopted that covers both fundamental concepts and the most recent biomedical, as well as clinical, applications. Sample analyses in recent clinical studies have shown that gene expression data can be employed to distinguish between tumor types as well as to predict outcomes. Potentially important applications of such results are individualized human cancer therapies or, in general, ‘personalized medicine’. Several cancer detection techniques are currently under development both in the direction of improved detection sensitivity and increased time resolution of cellular events, with the limits of single molecule detection and picosecond time resolution already reached. The urgency for the complete mapping of a human cancer interactome with the help of such novel, high-efficiency / low-cost and ultra-sensitive techniques is also pointed out.
Soluble oligomerization provides a beneficial fitness effect on destabilizing mutations.
Authors: Bershtein Shimon , Shakhnovich Eugene
Published: July 2019

Protein stability is widely recognized as a major evolutionary constraint. However, the relation between mutation-induced perturbations of protein stability and biological fitness has remained elusive. Here we explore this relation by introducing a selected set of mostly destabilizing mutations into an essential chromosomal gene of E.coli encoding dihydrofolate reductase (DHFR) to determine how changes in protein stability, activity and abundance affect fitness. Several mutant strains showed no growth while many exhibited fitness higher than wild type. Overexpression of chaperonins (GroEL/ES) buffered the effect of mutations by rescuing the lethal phenotypes and worsening better-fit strains. Changes in stability affect fitness by mediating the abundance of active and soluble proteins; DHFR of lethal strains aggregates, while destabilized DHFR of high fitness strains remains monomeric and soluble at 30oC and forms soluble oligomers at 42oC. These results suggest an evolutionary path where mutational destabilization is counterbalanced by specific oligomerization protecting proteins from aggregation.
Power-law behavior reveals phase transitions in landscape controls of fire regimes
Authors: McKenzie Donald , Kennedy Maureen
Published: July 2019

In low-severity fire regimes of the American West and elsewhere, landscape memory of fire events is registered in fire-scarred trees, with temporal record lengths often exceeding 200 years^1-5^. Understanding the environmental controls on historical wildfires, and how they changed across spatial scales, is difficult because there are no surviving explicit records of either weather or vegetation (fuels). We show how power laws associated with fire-event time series arise in limited domains of parameters that represent critical transitions in the controls on landscape fire. We used stochastic simulations iteratively with Monte Carlo inference to replicate the spatio-temporal structure of historical fire-scar records in forested watersheds of varying topographic complexity. We find that the balance between endogenous and exogenous controls on fire spread shifts with topographic complexity, where in the most complex landscapes the endogenous controls dominate and the pattern exhibits criticality. Comparison to an self-organized criticality (SOC) model^6,7^ shows that the latter mimics historical fire only in a limited domain of criticality, and is not an adequate mechanism to explain landscape fire dynamics, which are shaped by both endogenous and exogenous controls. Our results identify a continuous phase transition in landscape controls, marked by power laws, and provide an ecological analogue to critical behavior in physical and chemical systems^8-11^. This explicitly cross-scale analysis provides a paradigm for identifying critical thresholds in landscape dynamics that may be crossed in a rapidly changing climate.
Human Cancer Cells Express Slug-based Epithelial-Mesenchymal Transition Gene Signature Obtained in Vivo
Authors: Kandel Jessica , Anastassiou Dimitris , Rumjantseva Viktoria , Cheng Wei-yi , Huang Jianzhong , Canoll Peter , Yamashiro Darrell
Published: July 2019

The biological mechanisms underlying cancer cell motility and invasiveness remain unclear, although it has been hypothesized that they involve some type of epithelial-mesenchymal transition (EMT). Here we show that human cancer cells express in vivo a precise multi-cancer invasion-associated gene expression signature characterized by the prominent presence of collagen COL11A1 and thrombospondin THBS2. The signature is present in the expression of all solid tumor datasets that we analyzed and includes numerous EMT markers, among them the transcription factor Slug, fibronectin, and α SMA. Using xenograft models of human cancer cells in immunocompromised mice and profiling the harvested tumors separately with species specific probes, we found that human, but not mouse, cells express most of the genes of the signature and Slug is the only upregulated EMT-inducing transcription factor. Taken together with the presence of the signature in many publicly available datasets, our results suggest that this Slug based EMT signature is produced by the cancer cells themselves in multiple cancer types, including even nonepithelial cancers such as neuroblastoma. Furthermore, we found that the presence of the signature in human xenografted cells was associated with a downregulation of adipocyte markers in the mouse tissue adjacent to the invasive tumor, suggesting contextual microenvironmental interactions when the cancer cells encounter adipocytes, as previously reported. The known and consistent gene composition of this cancer EMT signature, particularly when combined with simultaneous analysis of the adjacent microenvironment, provides unique opportunities for shedding light on the underlying mechanisms of cancer invasiveness as well as identifying potential diagnostic markers and targets for metastasis-inhibiting therapeutics.
Synaptic state matching: a dynamical architecture for predictive internal representation and feature perception
Authors: Tavazoie Saeed
Published: July 2019

Here we consider the possibility that a fundamental function of sensory cortex is the generation of an internal simulation of sensory environment in real-time. A logical elaboration of this idea leads to a dynamical neural architecture that oscillates between two fundamental network states, one driven by external input, and the other by recurrent synaptic drive in the absence of sensory input. Synaptic strength is modified by a proposed synaptic state matching (SSM) process that ensures equivalence of spike statistics between the two network states. Remarkably, SSM, operating locally at individual synapses, generates accurate and stable network-level predictive internal representations, enabling pattern completion and unsupervised feature detection from noisy sensory input. SSM is a biologically plausible substrate for learning and memory because it brings together sequence learning, feature detection, synaptic homeostasis, and network oscillations under a single parsimonious computational framework. Beyond its utility as a potential model of cortical computation, artificial networks based on this principle have remarkable capacity for internalizing dynamical systems, making them useful in a variety of application domains including time-series prediction and machine intelligence.
BioenergyProduction From Plant Biomass: Bioethanol From Concept To Reality
Authors: Khan Israr , Akhtar Muhammad Waheed
Published: July 2019

Natural energy reserves like petrol and diesel etc are depleting. As such, it is of paramount importance to find alternative fuels. Solar energy is trapped as biomass in plants. Biomass provide an excellent reserve for trapping solar energy on field. Complex enzymatic machinery comprising of hydrolytic reactions and consolidated bioprocessing is needed to make viable bioenergy, mostly biofuels like bioethanol for locomotives, industries and general use in the future.
Statistical analysis of protein molecules
Authors: Shah Kushal
Published: July 2019

In this paper, entropy and auto-correlation values of main chain dihedral angles of 22,356 protein molecules are calculated and found to lie within a well-specified range for most proteins. Also, the entropy values obey a Gaussian distribution, which indicates that entropy plays a crucial role in evolution and conservation of protein tertiary structures. A comparison of the auto-correlation values of the dihedral angles of the entire protein molecule with those of the alpha helices and beta sheets indicates that random coils play an important role in determining the tertiary structure of protein molecules.
PrionOme: A database of prions and other sequences relevant to prion phenomena
Authors: Sowdhamini Ramanathan , Harrison Paul , Harbi Djamel , Parthiban Marimuthu , Gendoo Deena , Ehsani Sepehr , Kumar Manish , Schmitt-Ulms Gerold
Published: July 2019

Prions are units of propagation of an altered state of a protein or proteins. Prions can propagate from cell to cell, and from organism to organism, through cooption of other protein copies. Prions contain no necessary nucleic acids, and are important both as both pathogenic agents, and as a potential force in epigenetic phenomena. The original prions were derived from a misfolded form of the mammalian Prion Protein PrP. Infection by these prions causes neurodegenerative diseases. Other prions cause non-Mendelian inheritance in budding yeast, and sometimes act as diseases of yeast. We have compiled a database of >2000 prion-related sequences, called the PrionOme. The database comprises seven PrionOme classification categories: prionogenic sequences (i.e., sequences that can make prions), ‘prionoids’ (i.e., phenomena that have some prion characteristics), orthologs, paralogs, pseudogenes, prion interactors, and prion-like molecules. Database entries list: supporting information for PrionOme classifications, prion-determinant areas (where relevant), and disordered and compositionally-biased regions. Also included are original references for the PrionOme classifications, transcripts and genomic coordinates, and structural data (including comparative models). We provide database usage examples for both vertebrate and fungal prion contexts. As development of this resource is on-going, we will be very happy to receive and act on any constructive comments from peer scientists in the areas of prion biology and protein misfolding, either by email or using the feedback form provided on the PrionOme website. We hope that this database will be a valuable experimental aid and reference resource. It is freely available at: http://libaio.biol.mcgill.ca/prion.
Isoglitter
Authors: Bucknum Michael , Castro Eduardo , Wen Bin
Published: July 2019

Described herein is a novel crystalline pattern in space group Ammm, that is a model of a C allotrope. This so-called isoglitter structure-type is a model of a graphite-diamond hybrid. A DFT geometry optimization and band structure calculation indicates that the lattice is metallic in a C realization.