bluuebunny/crossref_metadata_2025 huggingface dataset:
Selfish and Altruistic Bacterial Populations Maximize Fitness Under Stress by Local Segregation
Authors: Keymer Juan , Galajda Peter , Malinverni Juliana , Kolter Roberto , Lambert Guillaume , Liao David , Austin Robert
Published: July 2019

Landscapes in ecology have a profound influence on the adaption and evolution of competing populations for resources. We are interested in how altruistic populations survive in the presence of selfish individuals in a non-stirred, closed and complex nutrient landscape. Well-stirred (landscape-free) but closed environments have a depressing future when selfish individuals arise in a population, a fate known as the tragedy of the Commons. Over-exploitation of a well-stirred communal habitat by selfish individuals which do not follow rules of communal self-regulation ends up in the elimination (extinction) of both the original altruistic inhabitants and the selfish population. In the context of bacterial population, the Commons tragedy that occurs is the consumption of limited resources by the individuals, resulting in metabolic stressing of the bacteria and growth advantages to be gained by defection from a ``social contract" of altruistic cooperation. There is no avoidance of this tragedy and the collapse of an original altruistic wild-type population by an emergent selfish population in a well-stirred but closed environment is inevitable. However, there is a fundamental difference between resource exploitation in a well-stirred homogenous commons and in a heterogenous landscape of nutrients which is not stirred. We show here using a non-stirred nanofabricated habitat landscape that altruists and selfish bacteria can in fact coexist, that they can maintain phenotype diversity and avoid the tragedy of the Commons. This emergent spatial segregation of competing populations under stress greatly changes, we believe, our perception of the true sophistication of bacterial response to stress and competition, and has broad implications for the adaptive strategies of higher organisms under stress in complex environments.
The genetic equidistance result of molecular evolution is independent of mutation rates
Authors: Huang Shi
Published: July 2019

The well-established genetic equidistance result shows that sister species are approximately equidistant to a simpler outgroup as measured by DNA or protein dissimilarity. The equidistance result is the most direct evidence, and remains the only evidence, for the constant mutation rate interpretation of this result, known as the molecular clock. However, data independent of the equidistance result have steadily accumulated in recent years that often violate a constant mutation rate. Many have automatically inferred non-equidistance whenever a non-constant mutation rate was observed, based on the unproven assumption that the equidistance result is an outcome of constant mutation rate. Here it is shown that the equidistance result remains valid even when different species can be independently shown to have different mutation rates. A random sampling of 50 proteins shows that nearly all proteins display the equidistance result despite the fact that many proteins have non-constant mutation rates. Therefore, the genetic equidistance result does not necessarily mean a constant mutation rate. Observations of different mutation rates do not invalidate the genetic equidistance result. New ideas are needed to explain the genetic equidistance result that must grant different mutation rates to different species and must be independently testable.
Natural Selection: A Deselection vs Proselection Analysis
Authors: Hardy Raymond
Published: July 2019

Since the dawn of Darwinian evolution theory evolutionists have assumed that evolution favors adaptive traits. In this analysis article the author explores the usefulness of assuming that natural selection works only by disfavoring deleterious traits.
Gender Differential in the Association of Body Mass Index and Abdominal Obesity with Prehypertension and Hypertension in Iranian Adults
Authors: Janghorbani Mohsen , Amini Masoud , Gouya Mohammad Mehdi , Delavari Alireza , Alikhani Siamak , Mahdavi Alireza
Published: July 2019

*Objective:*

The aim of this study was to determine the gender differential in the relationship of body mass index (BMI) and abdominal obesity with blood pressure (BP) and prevalence of hypertension (HTN) and prehypertension (Pre-HTN) among the adult population of Iran.*Design:* A nationwide cross-sectional survey was conducted from December 2004 to February 2005. The selection was conducted by stratified probability cluster sampling through household family members in Iran.*Subjects and Measurements:* Weight, height, waist circumference (WC), and systolic and diastolic BP of 45,082 men and 44,322 women aged 15-65 (mean 39.2) were measured.

*Results:*

The prevalence of HTN was 25.2% in men and 24.8% in women; and 50.1% of men and 39.1% of women were pre-hypertensive. WC and BMI were strongly associated with BP in both genders. Multivariate analysis revealed that both WC and BMI had the stronger association with HTN and Pre-HTN in men than women. Compared to men and women with normal weight, the multivariate-adjusted odds ratio (OR) (95% confidence interval) of HTN was 5.75 (5.13, 6.44) for men and 4.29 (3.95, 4.66) for women with BMI ≥ 30. The multivariate OR of prevalence HTN in men with abdominal obesity compared with men without was 3.76 (3.41, 4.22) and in women, 2.92 (2.73, 3.13).*Conclusion:* These data indicate that both BMI and WC had the stronger association with HTN and Pre-HTN in men than women.
The Effect of a Reduced-Calorie Diet on alpha-2 Adrenergic Receptor Responsiveness in Abdominal Adipose Tissue in Obese Men During Exercise
Authors: Estrada Roy , Schmelz Joseph , Turbow David , Neumann Edith
Published: July 2019

There is at present an imperfect understanding of the effect of diet on availability of inhibitory receptors in fat cells during exercise among obese men.

*Objective:*

The purpose of this study was to determine whether diet results in downregulation of alpha-2 adrenergic receptor ([alpha]~2-AR~) messenger RNA (mRNA), improving metabolism in exercise in obese men. *Design:* One group, pre-test, post-test design.*Measurements:* Subcutaneous abdominal adipose tissue was tested for physiologic response, such as changes in catecholamines and other markers of lipolysis measured during periods of exercise, before and after a 12-week diet. Plasma markers of lipolysis/antilipolytic activity (catecholamines [adrenaline and noradrenaline], NEFA, lactate, glucose, hematocrit, or insulin levels) were analyzed at four points in time in order to determine the effect of exercise on [alpha]~2-AR~ and [beta]-AR responsiveness to sympathetic stimulation.*Subjects:* Otherwise healthy 18 to 45 year old obese men (defined as a body mass index (BMI) over 33 kg/m^2^).

*Results:*

The 12-week reduced calorie diet did not result in improved metabolism. Instead, upregulation of alpha-2 adrenergic receptor ([alpha]~2-AR~) messenger RNA (mRNA) was observed. On average, [alpha]~2-AR~ mRNA levels (ratio of [alpha]~2-AR~ to cyclophilin) in subjects increased by 0.022-0.023 after the diet. The average differences in of [alpha]~2-AR~ mRNA and [beta]-AR mRNA measured before and after diet were both insignificant (M = 0.015) t(4) = -0.911; P > 0.05; (M = 0.0139; t(4) = 0.077; P > 0.05). *Conclusion:* The observed direction of change in [alpha]~2-AR~ mRNA levels, when viewed together with the stability of [beta]-AR mRNA levels, suggests that upregulation of [alpha]~2-AR~ rather than downregulation occurred. Downregulation would account for decreased lipolytic activity during exercise, future study is needed.
14-3-3ζ is Amplified, Overexpressed and Possesses Oncogenic Activities in Head and Neck Squamous Cell Carcinoma
Authors: Lin Mauting , Morrison Carl , Jones Susie , Mohamed Nehad , Bacher Jason , Plass Christoph
Published: July 2019

Gene amplification, a common mechanism for oncogene activation in cancers, has been used in the discovery of novel oncogenes. DNA amplification is frequently observed in head and neck squamous cell carcinomas (HNSCCs) where numerous amplification events and potential oncogenes have already been reported. Recently, we applied restriction landmark genome scanning (RLGS) to study gene amplifications in HNSCC and located novel amplified and uncharacterized regions in primary tumor samples. DNA amplification on 8q22.3, the location of 14-3-3[zeta] (YWHAZ, KCIP-1) is found in 30-40% HNSCC cases. Data obtained from fluorescent in-situ hybridization (FISH) and immunohistochemistry on HNSCC tissue microarrays confirmed frequent low-level 14-3-3[zeta] copy number gains and protein overexpression. 14-3-3[zeta] mRNA was frequently upregulated in patients' tumor tissues. Furthermore, 14-3-3[zeta] RNAi significantly suppressed the growth rate of HNSCC cell lines, and overexpression of 14-3-3[zeta] in HaCaT immortalized human skin keratinocytes promotes its growth, as well as morphological changes. Reduced 14-3-3[zeta] levels increased the G1/G0-phase proportion, decreased the S-phase proportion and the rate of DNA synthesis. Based on this evidence, we suggest that 14-3-3[zeta] is a candidate proto-oncogene and deserves further investigations into its role in HNSCC carcinogenesis.
Peptides as potent antimicrobials tethered to a solid surface: Implications for medical devices
Authors: Gonzalez Ivan , Wong XiXi , DeAlmeida Dilhari , Yurko Raymond , Watkins Simon , Islam Kazi , Montelaro Ronald , El-Ghannam Ahmed , Mietzner Timothy
Published: July 2019

Medical devices are an integral part of therapeutic management; despite their importance, they carry a significant risk of microbial infection. Bacterial attachment to a medical device is established by a single, multiplying organism, leading to subsequent biofilm formation. To date, no preventative measures have impacted the incidence of device-related infection. We report the bidirectional covalent coupling of an engineered cationic antimicrobial peptide (eCAP), WLBU2, to various biological surfaces is accomplished. These surfaces included (i) a carbohydrate-based gel matrix, (ii) a complex polymeric plastic bead, and (iii) a silica-calcium phosphate nanocomposite associated with bone reconstruction. WLBU2-conjugated surfaces are shown to retain potent antimicrobial activity related to bacterial surface adhesion. This study provides proof of principle that covalently coating laboratory and bone-regenerating materials with eCAPs has the potential for decreasing infection rates of implanted devices. These findings have important consequences to the patient management component of our current health care technology.
CD14 Modulates PI3K/AKT/p38-MAPK Licensing of Negative Regulators of TLR Signaling to Restrain Chronic Inflammation
Authors: Sahay Bikash , Patsey Rebeca , Whatley Nicole , Nayak Sasmita , Eggers Christian , Radolf Justin , Sellati Timothy
Published: July 2019

Current thinking emphasizes the primacy of CD14 in facilitating TLR recognition of microbes to initiate proinflammatory signaling events and the importance of p38-MAPK in augmenting such responses. Herein, this paradigm is challenged by demonstrating that recognition of Borrelia burgdorferi not only triggers an inflammatory response in the absence of CD14, but one that is uncontrolled as a consequence of impaired PI3K/AKT/p38-MAPK signaling and negative regulation of TLR2. CD14 deficiency results in hyperphosphorylation of AKT and reduced activation of p38. Such aberrant signaling leads to decreased negative regulation by SOCS1, SOCS3, and CIS thereby engendering a more severe and persistent inflammatory response to B. burgdorferi. Perturbation of this CD14/p38-MAPK-dependent mechanism of immune regulation may underlie development of infectious chronic inflammatory syndromes.
The effects of anti-sense interleukin-5 gene transferred by recombinant adeno-associated virus in allergic rats
Authors: Zeng Daxiong , Cao Yong , Song Qingfeng , Cao Chao , Liu Xiansheng , Xu Yongjian , Xiong Weining
Published: July 2019

The accumulation and infiltration of eosinophils in airways is one of the most important characteristics of asthma, and is mediated partly by secretion of IL-5 from Th2 lymphocytes. It is well known that interleukin-5 (IL-5) played an important role in the regulation of eosinophils. In this study, an anti-sense IL-5 gene transferred by recombinant adeno-associated virus (rAAV-ASIL-5) was prepared to transfect allergic rats. It was found that the expression of IL-5 protein in plasma and BALF were inhibited significantly. The rAAV-ASIL-5-mediated suppression of total cell counts in peripheral blood and BALF were also observed. Moreover, rAAV-ASIL-5 remarkably reduced the eosinophil counts in peripheral blood and BALF, as well as the expression of ECP protein in plasma and BALF. The inflammation in lungs of rAAV-ASIL-5 pretreated rats also became slighter when compared with allergic rats. Otherwise, no apparent pathological damage to vital organs of rats was found. In conclusion, recombinant adeno-associated virus-mediated delivery of anti-sense IL-5 gene inhibited the accumulation of eosinophils and the airways inflammation in rat model of allergic asthma via suppressing IL-5 expression. It suggested the feasibility of rAAV-ASIL-5 in the gene therapy for allergic asthma and other eosinophilic diseases.
Yeast surface 2-hybrid to detect protein-protein interactions via the secretory pathway as a platform for antibody discovery
Authors: Hu Xuebo , Kang Sungkwon , Chen Xiaoyue , Shoemaker Charles , Jin Moonsoo
Published: July 2019

High throughput methods to measure protein-protein interactions will facilitate uncovering pairs of unknown interactions as well as designing new interactions. We have developed a platform to detect protein interactions on the surface of yeast, where one protein (bait) is covalently anchored to the cell wall and the other (prey) is expressed in secretory form. The prey is released either outside of the cells or remains on the cell surface by its binding to the bait. The strength of their interaction is measured by antibody binding to the epitope tag fused to the prey or direct readout of split fluorescence protein complementation. Our novel 'yeast surface 2-hybrid' system was found to differentiate 6-log difference in binding affinities between coiled coil associations and to measure specific interactions of antibodies and antigens. We demonstrate the use of YS2H in exploring activation allostery in integrins and isolating heavy chain only antibodies against botulinum neurotoxin.
Reductive Biotransformation of Ethyl Acetoacetate: A Comparative Studies using Free and Immobilized Whole Yeast Cells
Authors: Kumbhar Amit , Kulkarni Vaibhav , Pande Madhav , Laddha Sachin
Published: July 2019

Bioreduction of ethyl acetoacetate with free and immobilized yeast whole cell was achieved by using water and sucrose combination. After detachment from immobilized beads under basic condition, the corresponding ethyl(S)-(+)-3-hydroxybutanoate was isolated with 98 to 100% yield. Immobilized beads of yeast whole cell were prepared at different temperature which affects the morphology and physiology of the beads for the diffusion of the enzyme, which shown the maximum conversion of the substrate to products as compared to the free yeast whole cell.
Characteristics of oligonucleotide frequencies across genomes: Conservation versus variation, strand symmetry, and evolutionary implications
Authors: Zhang Shang-Hong , Huang Ya-Zhi
Published: July 2019

One of the objectives of evolutionary genomics is to reveal the genetic information contained in the primordial genome (called the primary genetic information in this paper, with the primordial genome defined here as the most primitive nucleic acid genome for earth’s life) by searching for primitive traits or relics remained in modern genomes. As the shorter a sequence is, the less probable it would be modified during genome evolution. For that reason, some characteristics of very short nucleotide sequences would have considerable chances to persist during billions of years of evolution. Consequently, conservation of certain genomic features of mononucleotides, dinucleotides, and higher-order oligonucleotides across various genomes may exist; some, if not all, of these features would be relics of the primary genetic information. Based on this assumption, we analyzed the pattern of frequencies of mononucleotides, dinucleotides, and higher-order oligonucleotides of the whole-genome sequences from 458 species (including archaea, bacteria, and eukaryotes). Also, we studied the phenomenon of strand symmetry in these genomes. The results show that the conservation of frequencies of some dinucleotides and higher-order oligonucleotides across genomes does exist, and that strand symmetry is a ubiquitous and explicit phenomenon that may contribute to frequency conservation. We propose a new hypothesis for the origin of strand symmetry and frequency conservation as well as for the constitution of early genomes. We conclude that the phenomena of strand symmetry and the pattern of frequency conservation would be original features of the primary genetic information.
Secondary water pore formation for proton transport in a ClC exchanger revealed by an atomistic molecular dynamics simulation
Authors: Ko Youn Jo , Jo Won Ho
Published: July 2019

Several prokaryotic ClC proteins have been demonstrated to function as exchangers that transport both chloride ions and protons simultaneously in opposite directions. However, the path of the proton through the ClC exchanger and how the protein brings about the coupled movement of both ions are still unknown. In the present work, we demonstrate that a previously unknown secondary water pore is formed inside a ClC exchanger by using an atomistic molecular dynamics (MD) simulation. From the systematic simulations, it was determined that the glutamate residue exposed to the intracellular solution, E203, plays an important role as a trigger for the formation of the secondary water pore. Based on our simulation results, we conclude that protons in the ClC exchanger are conducted via a water network through the secondary water pore and we propose a new mechanism for the coupled transport of chloride ions and protons.
High Resolution Imaging of the Fusiform Face Area (FFA) Using Nonlinear Classifiers Shows Diagnosticity for Nonface Categories
Authors: Hanson Stephen , Schmidt Arielle
Published: July 2019

How are objects represented in the human visual pathway? This question continues to elude the neuroimaging field due to at least two kinds of problems: first, the relatively low spatial resolution of fMRI and second, the bias inherent in prevailing statistical methods for analyzing the actual diagnosticity of cortical tissue. We collected high-resolution (1mm x 1mm) imaging data of the fusiform face area (FFA) from 4 subjects while they categorized images as 'animal', 'car', 'face', or 'sculpture.' We performed exploratory analysis to determine the nature of the distributions over classes and the similarity structure between classes. The FFA was visualized using nonmetric multidimensional scaling revealing "string-like" sequences of voxels, which appeared in small non-contiguous clusters of categories, intertwined with other categories. Since the feature space appeared highly nonlinear, we trained various statistical classifiers on the class conditional distributions (labelled) and separated the four categories with 100% reliability (over replications) and generalized to out of sample cases with high significance (45% to 51%; p<. 000001, chance=25%). The increased noise inherent in high-resolution neuroimaging data relative to standard resolution resisted any further gains in category performance above 60% (with "FACE" category often having the highest bias per category) even coupled with various feature extraction/selection methods. A sensitivity/diagnosticity analysis for each classifier per voxel showed: (1) reliable (with S.E.<3%) sensitivity present throughout the FFA for all 4 categories, and (2) showed multi-selectivity, that is, many voxels were selective for one category but responded to all 4 categories with some high diagnosticity but at lower intensity. This work further verifies the hypothesis that the FFA is a distributed, object-heterogeneous similarity structure and bolsters the view that the FFA response to "FACE" stimuli in standard resolution may be primarily due to a linear bias, which has resulted from an averaging artifact.
Efficient polyethylenimine-mediated gene delivery proceeds via a caveolar pathway in HeLa cells.
Authors: Gabrielson Nathan , Pack Daniel
Published: July 2019

Most in vivo gene therapies will require cell-specific targeting. Although vector targeting through ligand attachment has met with success in generating gene delivery particles that are capable of specific cellular interactions, little attention has been given to the possible effects of such ligands on subsequent intracellular processing. In this study, we examine the impact of targeting two distinct endocytic routes-the caveolar and clathrin pathways-on polyethylenimine-mediated gene delivery in HeLa cells. Targeting complexes to the caveolar pathway with folic acid and the clathrin pathway with transferrin yields enhanced gene delivery relative to unmodified polyethylenimine. Colocalization studies with caveolin-1 and clathrin heavy chain indicate that the ligands successfully deliver their cargo to the intended pathways. However, inhibition of only the caveolar pathway-whether through the use of small molecule drugs or RNA interference-reduces gene delivery efficiency, suggesting that successful polyethylenimine-mediated gene delivery proceeds via a caveolar pathway in HeLa cells. Transfections in the presence of chloroquine and pH tracking studies suggest that a contributing factor to the success of the caveolar pathway is avoidance of lysosomes. Collectively, these data demonstrate that uptake mechanism and subsequent endocytic processing are important design parameters for gene delivery materials.
Simulations of Antigenic Variability in Influenza A
Authors: Fachada Nuno , Lopes Vitor , Rosa Agostinho
Published: July 2019

Computational models of the immune system (IS) and pathogenic agents have several applications, such as theory testing and validation, or as a complement to first stages of drug trials. One possible application is the prediction of the lethality of new Influenza A strains, which are constantly created due to antigenic drift and shift. Here, we present several simulations of antigenic variability in Influenza A using an agent-based approach, where low level molecular antigen-antibody interactions are explicitly described. Antigenic drift and shift events are analyzed regarding the virulence of emergent strains against the IS. Results are discussed from a qualitative point of view taking into account recent and generally recognized immunology and influenza literature.
The monoclonal antibody nBT062 conjugated to maytansinoids has potent and selective cytotoxicity against CD138 positive multiple myeloma cells in vitro and in vivo
Authors: Ikeda Hiroshi , Hideshima Teru , Lutz Robert , Yasui Hiroshi , Okawa Yutaka , Kiziltepe Tanyel , Vallet Sonia , Pozzi Samantha , Santo Loredana , Perrone Giulia , Fulciniti Mariateresa , Tai Yu-Tzu , Cristea Diana , Raje Noopur , Uherek Christoph , Dälken Benjamin , Aigner Silkie , Osterroth Frank , Munshi Nikhil , Richardson Paul , Anderson Kenneth
Published: July 2019

CD138 (Syndecan1) is highly expressed on multiple myeloma (MM) cells. In this study, we examined the anti-MM effect of murine/human chimeric CD138-specific monoclonal antibody (mAb) nBT062 conjugated with highly cytotoxic maytansinoid derivatives in vitro and in vivo. These agents significantly inhibited growth of CD138-positive MM cell lines and primary tumor cells from MM patients, without cytotoxicity against peripheral blood mononuclear cells from healthy volunteers. In MM cells, they induced G2/M cell cycle arrest followed by apoptosis associated with cleavage of PARP and caspase-3, -8 and -9. Non-conjugated nBT062 completely blocked cytotoxicity induced by nBT062-maytansinoid conjugate, confirming that binding is required for inducing cytotoxicity. Moreover, nBT062-maytansinoid conjugates blocked adhesion of MM cells to bone marrow stromal cells (BMSCs). Co-culture of MM cells with BMSCs, which protects against dexamethasone-induced death, had no impact on the cytotoxicity of the immunoconjugates. Importantly, nBT062-SPDB-DM4 and nBT062-SPP-DM1 significantly inhibited MM tumor growth in vivo in both human multiple myeloma xenograft mouse models and in SCID-human bone grafts (SCID-hu mouse model). These studies provide the preclinical framework supporting evaluation of nBT062-maytansinoid derivatives in clinical trials to improve patient outcome in MM.
Consciousness as Recursive, Spatiotemporal Self-Location
Authors: Peters Frederic
Published: July 2019

At the phenomenal level, consciousness can be described as a singular, unified field of recursive self-awareness, consistently coherent in a particular way; that of a subject located both spatially and temporally in an egocentrically-extended domain, such that conscious self-awareness is explicitly characterized by I-ness, now-ness and here-ness. The psychological mechanism underwriting this spatiotemporal self-locatedness and its recursive processing style involves an evolutionary elaboration of the basic orientative reference frame which consistently structures ongoing spatiotemporal self-location computations as i-here-now. Cognition computes action-output in the midst of ongoing movement, and consequently requires a constant self-locating spatiotemporal reference frame as basis for these computations. Over time, constant evolutionary pressures for energy efficiency have encouraged both the proliferation of anticipative feedforward processing mechansims, and the elaboration, at the apex of the sensorimotor processing hierarchy, of self-activating, highly attenuated recursively-feedforward circuitry processing the basic orientational schema independent of external action output. As the primary reference frame of active waking cognition, this recursive i-here-now processing generates a zone of subjective self-awareness in terms of which it feels like something to be oneself here and now. This is consciousness.
Dynamic Modeling of Vaccinating Behavior as a Function of Individual Beliefs
Authors: Coelho Flávio , Codeço Cláudia
Published: July 2019

Individual perception of vaccine safety is an important factor in determining a person's adherence to a vaccination program and its consequences for disease control. This perception, or belief, about the safety of a given vaccine, is not a static parameter but a variable subject to environmental influence. To complicate matters, perception of risk (or safety) does not correspond to actual risk. In this paper we propose a way to model the dynamics of such beliefs in the context of a realistic epidemiological scenario. The methodology proposed is based on Bayesian inference, and can be extended to model more complex belief systems associated with decision models.
The Central Enigma of Consciousness
Authors: King Chris
Published: July 2019

Abstract: The nature and physical basis of consciousness remains the central enigma of the scientific description of reality in the third millennium. This paper seeks to examine the phenomenal nature of subjective consciousness and elucidate a possible biophysical basis for its existence, in terms of a form of quantum anticipation based on entangled states driven by chaotic sensitivity of global brain dynamics during decision-making processes. Evidence is presented for the evolutionary emergence of chaotic excitation as a universal sense organ in the founding eucaryotes, which then became used in a context-sensitive manner by complex central nervous systems, leading to the dynamical brain.
Lost in information. On the processing of irrelevant signals in normal ageing
Authors: Wascher Edmund , Wild-Wall Nele , Falkenstein Michael
Published: July 2019

Healthy older adults often have problems to ignore irrelevant information. A lack of executive control upon irrelevant signals might be a core deficit affecting also higher level cognitive functions such as working memory. Here we show the origin of that deficit in a cuing task and demonstrate that older adults are not only unable to ignore irrelevant stimuli, but process them like relevant ones. Ample processing time can help to overcome this deficit.
Competent intermediate hosts and genetic re-assortment: what does the ferret and raccoon model tell us about influenza pandemic risk?
Authors: Alexander Paul
Published: July 2019

Avian influenza virus (AI) strains such as H5N1 and H9N2 are endemic among birds and poultry globally and mainly within Eurasia. Human cases have been reported yet the transmission among humans has been inefficient. While swine and pigs have functioned as the primary intermediate host and genetic re-assorter of AI virus, other intermediate and competent hosts may be emerging. This could be potentially disastrous for humans should this lead to the generation of a pandemic strain. This letter to the editor highlights recent findings of AI spread among ferrets and raccoons and the real prospect of genetic re-assortment and evolution among these intermediate non-avian species that could lead to a pandemic strain. These hosts revealed efficient transmission to direct contacts. The implications to humans are staggering. The recent and reported non-avian host findings indicate that there is a steady progression via genetic evolution and adaptation in intermediate hosts, and the potential, for AI virus to eventually acquire the ability to transmit more efficiently to humans and then readily among humans. Further research on the ferret and raccoon models of infection and efficient transmissibility is needed, with a focus on the molecular basis of interspecies transmission and aerosolized spread.
Local and global modes of drug action in biochemical networks
Authors: Schwartz Jean-Marc , Nacher Jose
Published: July 2019

It becomes increasingly accepted that a shift is needed from the traditional target-based approach of drug development to an integrated perspective of drug action in biochemical systems. We here present an integrative analysis of the interactions between drugs and metabolism based on the concept of drug scope. The drug scope represents the set of metabolic compounds and reactions that are potentially affected by a drug. We constructed and analyzed the scopes of all US approved drugs having metabolic targets. Our analysis shows that the distribution of drug scopes is highly uneven, and that drugs can be classified into several categories based on their scopes. Some of them have small scopes corresponding to localized action, while others have large scopes corresponding to potential large-scale systemic action. These groups are well conserved throughout different topologies of the underlying metabolic network. They can furthermore be associated to specific drug therapeutic properties.
Comment on “On the Doubly Hydrogen Bonded Dimer of 7-Azaindole (0.1 M) as a Model for DNA Base Pairs in Acetonitrile Solutions at Rt”
Authors: Kwon Oh-Hoon , Mohammed Omar F.
Published: July 2019

In continuation of comments by Catalán, the latest here questions the steady-state emission spectra of 7-azaindole, and hence the validity of non-concerted proton transfer. In this comment, we show that his results are at fault and not supportive of his claims. We provide possible causes of the misleading claims, including the contamination of the solvent with water moisture. We conclude by calling for an end to such practice, which is counter productive, as it does not follow the scholarly approach of science.
Breeding biology of pond heron in Kerala, South India
Authors: Seedikkoya K , Azeez PA , Abdul Shukkur EA
Published: July 2019

Regular intensive investigations to locate nesting colonies were carried out early monsoon of 1999 up to 2002. For detailed study a few breeding colonies were selected. The nesting trees, nest characteristics, eggs characteristics, incubation, hatching and hatchlings were investigated.Altogether 17 plant species were used for nesting. Nest materials were collected from 24 plant species for building nest. The mean maximum size of the nest material used was 29.05 cm and the mean minimum size was 13.46 cm. The clutch size varied from 2-5 and clutches of three were very common. The maximum and minimum length and breadth of eggs were 48.0 x 32.0 and 33.3 x 24.1 respectively. The weight of eggs varied between 17.8 and 11.2 gm. Both sexes take part in incubation that extended for 18-24 days. Hatching success reached 82%. Their food consisted mainly of fishes and both parents took part in feeding the nestlings.
A population-based study of glutathione-S-transferase M1, T1 and P1 genotypes
Authors: Sivoňová Monika , Waczulíková Iveta , Dobrota Dušan , Matáková Tatiana , Hatok Jozef , Račay Peter , Kliment Ján
Published: July 2019

A retrospective study on healthy, unrelated subjects was conducted in order to estimate population glutathione-S-transferases (GST) genotype frequencies in Slovak population of men and compare our results with already published data (GSEC project)^1^. A further aim of the study was to evaluate frequencies of the GST polymorphisms also in patients with prostate cancer in order to compare the evaluated proportions with those found in the control subjects. Analysis for the GST gene polymorphisms was performed by PCR and PCR-RFLP. We found that the proportions are not significantly different from those estimated in a European multicentre study or from the results published by another group in Slovakia. We found significantly increased age-standardized prostate cancer prevalence rates in the carriers of GSTM1 null genotype (P = 0.037) and trend for such an increase in the carriers of GSTP1 polymorphism when compared with the respective groups of non-carriers. Because understanding of the contribution of GST gene polymorphisms and their interactions with other relevant factors may improve screening diagnostic assays for prostate cancer, we discuss issues of study feasibility, study design, and statistical power, which should be taken into account in planning further trials.
Description of a method for localizing swarming mosquitoes and other insects in 3D space with visualizations
Authors: Manoukis Nicholas
Published: July 2019

Male mosquitoes swarm to find mates, but the characteristics of these swarms have not yet been quantitatively analyzed in the field. This paper describes a simple method used recently to localize individual Anopheles gambiae in a swarm via stereoscopic image analysis of video footage swarms recorded in Doneguebougou, Mali. The methods described here represent a streamlining of simple triangulation for insect localization in the hope that other researchers will be able to apply the method for studying fundamental questions about flying insects or other taxa.
The Heterochromatin Protein 1 positively regulates euchromatic gene expression by RNA binding
Authors: Lucia Piacentini , Fanti Laura , Negri Rodolfo , Del Vescovo Valerio , Fatica Alessandro , Pimpinelli Sergio
Published: July 2019

HP1 is a well known conserved protein involved in heterochromatin formation and gene silencing in different species including humans1-4. A general model has been proposed for heterochromatin formation and epigenetic gene silencing in different species that implies an essential role for HP1. According to the model, histone methyltransferase enzymes (HMTases) methylate the histone H3 at lysine 9 (H3-MeK9), creating selective binding sites for itself and the chromodomain of HP15. This complex is thought to form a higher order chromatin state that represses gene activity. It has also been found that HP1 plays a role in telomere capping6. Surprisingly, recent data have suggested an association of HP1 in gene activity7-10 but the nature of this interaction is still completely obscure. Here we show, that HP1 is required for positive regulation of more than one hundred euchromatic genes by its association with the corresponding RNA transcripts and by its interaction with the well known proteins DDP111, HRB87F12 and PEP13, which belong to different classes of heterogeneous nuclear ribonucleoproteins (hnRNPs) involved in RNA processing . We also found that all these hnRNP proteins also bind heterochromatin and are dominant suppressors of position effect variegation. Our data together, show novel and unexpected functions for HP1 and hnRNPs proteins. All these proteins are in fact involved in both RNA transcript processing and in heterochromatin formation. This suggests that, in general, similar epigenetic mechanisms have a significant role in the metabolism of both RNA and heterochromatin.
Two Rules on the Protein-Ligand Interaction
Authors: Pang Xiaodong , Zhou Linxiang , Zhang Lily , Xu Lina , Zhang Xinyi
Published: July 2019

So far, we still lack a clear molecular mechanism to explain the protein-ligand interaction on the basis of electronic structure of a protein. By combining the calculation of the full electronic structure of a protein along with its hydrophobic pocket and the perturbation theory, we found out two rules on the protein-ligand interaction. One rule is the interaction only occurs between the lowest unoccupied molecular orbitals (LUMOs) of a protein and the highest occupied molecular orbital (HOMO) of its ligand, not between the HOMOs of a protein and the LUMO of its ligand. The other rule is only those residues or atoms located both on the LUMOs of a protein and in a surface pocket of a protein are activity residues or activity atoms of the protein and the corresponding pocket is the ligand binding site. These two rules are derived from the characteristics of energy levels of a protein and might be an important criterion of drug design.
Minimum Information about a Neuroscience Investigation (MINI): Electrophysiology
Authors: Gibson Frank , Overton Paul , Smulders Tom , Schultz Simon , Eglen Stephen , Ingram Colin , Panzeri Stefano , Bream Phil , Whittington Miles , Sernagor Evelyne , Cunningham Mark , Adams Christopher , Echtermeyer Christoph , Simonotto Jennifer , Kaiser Marcus , Swan Daniel , Fletcher Martyn , Lord Phillip
Published: July 2019

This module represents the formalised opinion of the authors and the CARMEN consortium, which identifies the minimum information required to report the use of electrophysiology in a neuroscience study, for submission to the CARMEN system ("http://www.carmen.org.uk":www.carmen.org.uk).
Far-infrared rays control prostate cancer cells in vitro and in vivo
Authors: Shima Hiroki , Yamamoto Shingo , Qiu Jun , Shincho Mayumi , Hirota Seiichi , Yoshikawa Yoshie , Yoshikawa Reigetsu , Hashimoto-Tamaoki Tomoko
Published: July 2019

We introduce a new effective method to control hormone refractory prostate cancer cells by using an activated rubber/resin form (RB), far-infrared ray emitter, with or without sodium butyrate (SB). The growth of three human prostate cancer cell lines (Du145, PC-3 and LNCaP) was suppressed in vitro and in vivo by using RB, and the cells were eradicated with RB + 3 mM SB. G1 arrest and apoptotic pathway proteins were induced by RB with intensified expressions of apoptosis - related mRNA on cDNA microarray. RB radiates far-infrared rays of the 4 to 25 [mu]m wavelengths to an object which exert a favorable influence on a cancer control. These results may render us a new therapeutic modality in hormone refractory prostate cancer.
Proposing a life cycle land use impact calculation methodology
Authors: Achten Wouter , Mathijs Erik , Muys Bart
Published: July 2019

The Life Cycle Assessment (LCA) community is yet to come to a consensus on a methodology to incorporate land use in LCA, still struggling with what exactly should be assessed and which indicators should be used. To solve this problem we start from concepts and models describing how ecosystems function and sustain, in order to understand how land use affects them. Earlier our research group presented a methodology based on the ecosystem exergy concept. This concept as based on the hypothesis that ecosystems develop towards more effective degradation of exergy fluxes passing through the system and is derived from two axioms: the principles of (i) maximum exergy storage and the (ii) maximum exergy dissipation. This concept aiming at the area of protection natural environment is different from conventional exergy analysis in LCA focusing on natural resources. To prevent confusion, the ecosystem exergy concept is further referred to as the MAximum Storage and Dissipation concept (MASD concept). In this paper we present how this concept identifies end-point impacts, mid-point impacts and mid-point indicators. The identified end-point impacts to assess are Ecosystem Structural Quality (ESQ) and Ecosystem Functional Quality (EFQ). In order to quantify these end-point impacts a dynamic multi-indicator set is proposed for quantifying the mid-point impacts on soil fertility, biodiversity and biomass production (quantifying the ESQ) and soil structure, vegetation structure and on-site water balance (quantifying the EFQ). Further we present an impact calculation method suitable for different environmental assessment tools and demonstrate the incorporation of the methodology in LCA.
Frequency and accuracy of weight comments by others, and the association with weight misperception among Hong Kong adolescents
Authors: Lo Wing-Sze , Ho Sai-Yin , Mak Kwok-Kei , Lai Yuen-Kwan , Lam Tai-Hing
Published: July 2019

*Purpose:* To assess the frequency and accuracy of weight comments received from different sources among Chinese adolescents and the relation of weight comments to weight misperception.*Methods:* In the Hong Kong Student Obesity Surveillance (HKSOS) project 2006-07, 22612 form 1 to 7 students (41.5% boys) completed a questionnaire on obesity. Students were asked if they had received serious "too fat" or "too thin" comments over the past 30 days from family members, peers and professionals, and the accuracy of the comments was assessed against the actual weight status. Weight misperception was defined as discordance between the actual and perceived weight status. Logistic regression was used to calculate adjusted odd ratios (ORs) for weight misperception by weight comments received.

*Results:*

One in three students received weight comments, most commonly from mother for both "too fat" and "too thin" comments. Health professional was the most accurate source of weight comments, yet less than half the comments were correct. Receiving incorrect weight comments was significantly associated with weight misperception in all sex-weight status sub-groups, particularly among obese girls. In contrast, student who received correct weight comments were less likely to have weight misperception.

*Conclusions:*

Weight comments were commonly received by Chinese adolescents in Hong Kong, yet most of the comments were inaccurate, and such incorrect comments were associated with weight misperception. Family members, peers and professionals should realize the potential adverse effects of their weight comments and adolescents should be taught how to correctly assess their weight status to reduce misperceptions.
Optical and Electrical Properties of Multi-Walled Carbon Nanotubes Functionalized with Oxadiazole Chromophores
Authors: Yu Bo-Zhang , Ma Ji-Fei , Li Hu-Lin , Zhang Ya-Fei , La Wen-Xin
Published: July 2019

Multi-walled carbon nanotubes (MWCNTs) functionalized with oxadiazole chromophores, 2-(4-aminophenyl)-5-naphthyl-1,3,4-oxadiazole (APND) was prepared by an amide linkage. The resultant MWCNTs-APND and APND were characterized by using FT IR, ^1^H NMR, and XRD analysis to give their structural and crystal information, supporting the successful modification. UV-Vis absorption spectrum of MWCNTs-APND was broadened and significantly red-shifted, and its emission peak was narrower than that of APND, which provided direct evidence for reaction of APND with surface of MWCNTs via [pi]-stacking. The electrical properties demonstrated that there was a perfect ohmic behaviour for membrane of APND, and the thin films of MWCNTs-APND had the same nonlinear properties as MWCNTs within order magnitude of milliampere.
Polyethylenimine-Modified Multiwalled Carbon Nanotubes for Plasmid DNA Gene Delivery
Authors: Yu Bo-Zhang , Ma Ji-Fei , Li Wen-Xin
Published: July 2019

An efficient molecular delivery technique based on the transporting high-molecular-weight PEI 600K-modified multiwalled carbon nanotubes (PEI 600K-MWCNTs) into cell membranes is reported. The PEI 600K-MWCNTs exhibit low cytotoxicity and its associated plasmid DNA (pDNA) is delivered to cells efficiently, and the green fluorescent protein (GFP) levels up to 18 times higher than that of naked DNA were observed.
The Relationship between Physical Activity and Body Mass Index: Issues in Model Specification
Authors: Tiruneh Gizachew
Published: July 2019

*Objective*:

To investigate the best statistical models that describe the effect of physical activity on BMI.*Design*: Cross-sectional analyses of physical activity and BMI data. *Subjects*: 107 obese, overweight, and healthy college students (mean duration of physical activity for the normal, overweight, and obese students: 89, 59, and 24 months, respectively; mean BMI for the normal, overweight, and obese students: 21.61, 27.07, and 35.54 kg/m2, respectively).*Measurements*: Inverse linear, inverse logarithmic, and inverse logistics models were used to analyze survey data for physical activity (measured by both frequency and duration of exercise) and BMI. Gender, age, and physical intensity variables were also statistically controlled.

*Results*:

Coefficients of determination, r-squared, showed the inverse logarithmic model is more accurate in describing the effect of physical activity on BMI than is the inverse linear model. The inverse logistic method also showed physical activity affects BMI.

*Conclusions*:

Although the inverse logarithmic method can be used in some cases, the inverse logistic model seems to be theoretically and empirically best suited in describing the relationship between physical activity and body weight.
3D model of lamprey estrogen receptor with estradiol and 15[alpha]-hydroxy-estradiol
Authors: Baker Michael , Chang David , Chandsawangbhuwana Charlie
Published: July 2019

Lamprey, a basal vertebrate, contains orthologs of the estrogen receptor (ER), progesterone receptor and corticoid receptor. A perplexing property of lamprey is that 15[alpha]-hydroxy-steroids are active steroids. For example, 15[alpha]-hydroxy-estradiol [15[alpha]-OH-E2] is the estrogen, instead of estradiol (E2). To investigate how 15[alpha]-OH-E2 binds lamprey ER, we constructed a 3D model of the lamprey ER with E2 and 15[alpha]-OH-E2. Our 3D model shows that S[delta] on Met-409 can form a hydrogen bond with the 15[alpha]-hydroxyl on 15[alpha]-OH-E2. In human ER[alpha], the corresponding residue Ile-424 has a van der Waals contact with 15[alpha]-OH-E2. BLAST analysis of GenBank indicates that among vertebrate ERs, only lamprey ER contains a methionine at this position. Thus, the contact between S[delta] on Met-409 and 15[alpha]-OH-E2 is unique. Our 3D model of lamprey ER should prove useful in virtual screening of chemical libraries to identify compounds for controlling reproduction in sea lamprey, an environmental pest in the Great Lakes in the USA.