bluuebunny/crossref_metadata_2025 huggingface dataset:
Dung beetles can eat acorns to increase their fitness
Authors: Verdu Jose R. , Casas Jose L. , Lobo Jorge , Numa Catherine
Published: July 2019

Animals eat different foods in proportions that yield a more favourable balance of nutrients. In spite of known examples of these behaviours across different taxa, the ecological and physiological benefits remain unknown. We identified a surprising dietary shift that confers ecophysiological advantages in a dung beetle species. Thorectes lusitanicus, a Mediterranean ecosystem species adapted to eat dung, is also actively attracted to oak acorns - consuming and burying them. Acorn consumption appears to confer advantages over beetles that do not eat acorns: acorn-fed beetles showed important improvements in fat body mass, haemolymph composition, and ovary development. Beetles incorporating acorns into their diets should have greatly improved resistance to low-temperature conditions and improved reproductive success. In addition to enhancing understanding of the relevance of dietary plasticity to the evolutionary biology of dung beetles, these results open the way to a more general understanding of the ecophysiological implications of differential dietary selection in the context of fitness.
The History, Development and Impact of Computed Imaging in Neurological Diagnosis and Neurosurgery: CT, MRI, and DTI
Authors: Filler Aaron
Published: July 2019

A steady series of advances in physics, mathematics, computers and clinical imaging science have progressively transformed diagnosis and treatment of neurological and neurosurgical disorders in the 115 years between the discovery of the X-ray and the advent of high resolution diffusion based functional MRI. The story of the progress in human terms, with its battles for priorities, forgotten advances, competing claims, public battles for Nobel Prizes, and patent priority litigations bring alive the human drama of this remarkable collective achievement in computed medical imaging.
Enhanced anti-tumor effects of combined MDR1 RNA interference and human sodium/iodide symporter (NIS) radioiodine gene therapy using an adenoviral system in a colon cancer model
Authors: Ahn Sohn Joo , Jeon Yong Hyun , Lee Yong Jin , Lee You La , Lee Sang-Woo , Ahn Byeong-Cheol , Ha Jeoung-Hee , Lee Jaetae
Published: July 2019

Using an adenoviral system as a delivery mediator of therapeutic gene, we investigated the therapeutic effects of the use of combined MDR1 shRNA and human NIS (hNIS) radioiodine gene therapy in a mouse colon xenograft model. In vitro uptake of Tc-99m sestamibi was increased approximately two-fold in cells infected with an adenovirus vector that expressed MDR1 shRNA (Ad-shMDR) and I-125 uptake was 25-fold higher in cells infected with an adenovirus vector that expressed human NIS (Ad-hNIS) as compared to control cells. As compared with doxorubicin or I-131 treatment alone, the combination of doxorubicin and I-131 resulted in enhanced cytotoxicity for both Ad-shMDR and Ad-hNIS infected cells but not for control cells. In vivo uptake of Tc-99m sestamibi and Tc-99m pertechnetate was two-fold and 10-fold higher for Ad-shMDR and Ad-hNIS-infected tumors as compared to tumors infected with a control adenovirus construct that expressed [beta]-galactrosidase (Ad-LacZ), respectively. In mice treated with either doxorubicin or I-131 alone, there was a slight delay in tumor growth as compared to mice treated with Ad-LacZ. However, combination therapy with doxorubicin and I-131 induced further significant inhibition of tumor growth as compared with mice treated with Ad-LacZ. We have demonstrated successful therapeutic efficacy of combined MDR shRNA and hNIS radioiodine gene therapy using an adenoviral vector system in a mouse colon cancer model. Adenovirus-mediated cancer gene therapy using MDR1 shRNA and hNIS would be a useful tool for the treatment of cancer cells expressing multi-drug resistant genes.
Female Scent Signals Enhances Male Resistance to Influenza
Authors: Litvinova Ekaterina , Goncharova Elena , Zaidman Alla , Zenkova Marina , Moshkin Mikhail
Published: July 2019

Scent of receptive females as signal to reproduction stimulate male mice to olfactory search of a potential breeding partner^1, 2^. This searching behavior is coupled with infection risk due to bacterial contamination of the fecal and urine scent marks^4^. The theoretical consideration of host evolution under inevitable parasitic pressures, including helminthes, bacteria, virus etc., predicts adaptations that help protect against parasites associated with breeding^7^. In this study, we propose that acceptation of female signals by male mice leads to adaptive redistribution of immune defense directed to protection against respiratory infection risks. Our results reveal migration of macrophages and neutrophils to upper airways upon exposure to female odor stimulus resulting in increased resistance to influenza virus in male mice. Contrary to widely accepted immunosuppressive function of female sexual signals, our data provide the first demonstration of the adaptive immunological response to female odor stimulus through induction of nonspecific immune response in upper airways.
Connectivity reflects coding: A model of voltage-based spike-timing-dependent-plasticity with homeostasis
Authors: Clopath Claudia , Büsing Lars , Vasilaki Eleni , Gerstner Wulfram
Published: July 2019

Electrophysiological connectivity patterns in cortex often show a few strong connections in a sea of weak connections. In some brain areas a large fraction of strong connections are bidirectional, in others they are mainly unidirectional. In order to explain these connectivity patterns, we use a model of Spike-Timing-Dependent Plasticity where synaptic changes depend on presynaptic spike arrival and the postsynaptic membrane potential. The model describes several nonlinear effects in STDP experiments, as well as the voltage dependence of plasticity under voltage clamp and classical paradigms of LTP/LTD induction. We show that in a simulated recurrent network of spiking neurons our plasticity rule leads not only to receptive field development, but also to connectivity patterns that reflect the neural code: for temporal coding paradigms strong connections are predominantly unidirectional, whereas they are bidirectional under rate coding. Thus variable connectivity patterns in the brain could reflect different coding principles across brain areas.
mRNA diffusion explains protein gradients in Drosophila early development
Authors: Dilao Rui , Murro Daniele
Published: July 2019

We propose a new model describing the production and the establishment of the stable gradient of the Bicoid protein along the antero-posterior axis of the embryo of Drosophila. In this model, we consider that bicoid mRNA diffuses along the antero-posterior axis of the embryo and the protein is produced in the ribosomes localized near the syncytial nuclei. Bicoid protein stays localized near the syncytial nuclei as observed in experiments.We calibrate the parameters of the mathematical model with experimental data taken during the cleavage stages 11 to 14 of the developing embryo of Drosophila. We obtain good agreement between the experimental and the model gradients, with relative errors in the range 5-8%. The inferred diffusion coefficient of bicoid mRNA is in the range 4.6 x 10^-12^ - 1.5 x10^-11^ m^2^s^-1^, in agreement with the theoretical predictions and experimental measurements for the diffusion of macromolecules in the cytoplasm. We show that the model based on the mRNA diffusion hypothesis is consistent with the known observational data, supporting the recent experimental findings of the gradient of bicoid mRNA in Drosophila [Spirov et al. (2009) Development 136:605-614].
In silico analysis for the presence of HARDY an Arabidopsis drought tolerance DNA binding transcription factor product in chromosome 6 of Sorghum bicolor genome
Authors: Shanker Arun , Maheswari M , Yadav S , Ventateswarlu B
Published: July 2019

Expression of the Arabidopsis HARDY (hrd) DNA binding transcription factor (555 bp present on chromosome 2) has been shown to increase WUE in rice by Karaba et al 2007 (PNAS, 104:15270–15275). We conducted a detail analysis of the complete sorghum genome for the similarity/presence of either DNA, mRNA or protein product of the Arabidopsis HARDY (hrd) DNA binding transcription factor (555 bp present on chromosome 2). Chromosome 6 showed a sequence match of 61.5 percent positive between 61 and 255 mRNA residues of the query region. Further confirmation was obtained by TBLASTN which showed that chromosome 6 of the sorghum genome has a region between 54948120 and 54948668 which has 80 amino acid similarities out of the 185 residues. A homology model was constructed and verified using Anolea, Gromos and Verify3D. Scanning the motif for possible activation sites revealed that there was a protein kinase C phosphorylation site between 15th and 20th residue. The study indicates the possibility of the presence of a DNA binding transcription factor in chromosome 6 of Sorghum bicolor with 60 percent similarity to that of Arabidopsis hrd DNA binding transcription factor.
Automated ocular artifact removal: comparing regression and component-based methods
Authors: Schloegl Alois , Ziehe Andreas , Müller Klaus-Robert
Published: July 2019

Objective:

The aim is to compare various fully automated methods for reducing ocular artifacts from EEG recordings.

Methods:

Seven automated methods including regression, six component-based methods for reducing ocular artifacts have been applied to 36 data sets from two different labs. The influence of various noise sources is analyzed and the ratio between corrected and uncorrected EEG spectra, has been used to quantify the distortion. Results: The results show that not only regression but also component-based methods are vulnerable to over- or under-compensation and can cause significant distortion of EEG. Despite common belief, component-based methods did not demonstrate an advantage over the simple regression method. Conclusion: The newly proposed evaluation criterion showed to be an effective approach to evaluate 252 results from 36 data sets and 7 different methods. Significance: Currently, the regression method provides the most robust and stable results and is therefore the state-of-the-art-method for fully automated reduction of ocular artifacts.
Dating the cyanobacterial ancestor of the chloroplast
Authors: Falcon Luisa , Magallon Susana , Castillo Amanda
Published: July 2019

Cyanobacteria have played a pivotal role in the history of life on Earth being the first organism to carry out oxygenic photosynthesis, which changed atmospheric chemistry and allowed the evolution of Eukarya. Chloroplasts are the cellular organelles of photoautotrophic eukaryotes in which photosynthesis is conducted. Although the initial suggestion from Mereschkowsky (1905) that cyanobacteria are the ancestors of chloroplasts was greeted with skepticism, the idea is now widely accepted. Here we attempt to resolve and date the cyanobacterial ancestry of the chloroplast using phylogenetic analysis and molecular clocks, because until now, the long-standing question of, from which, among the vast diversity of cyanobacteria, did chloroplasts evolve, has not been resolved. We found that chloroplasts form a monophyletic lineage, are most closely related to subsection I, N2-fixing unicellular cyanobacteria (Order Chroococcales), and heterocyst-forming Order Nostocales cyanobacteria are their sister group. The appearance of Nostocales and of Chroococcales occurred during the Paleoproterozoic, and chloroplasts appeared in the mid-Proterozoic. The capability of N2-fixation in cyanobacteria appeared once during the late Archaen and early Proterozoic eons. Furthermore, we found that oxygen-evolving cyanobacteria could have appeared in the Archean. Our results suggest that a free-living cyanobacterium with the capacity to store starch via oxygenic CO2 fixation, and to fix atmospheric N2, would be a very important intracellular acquisition, which, as can be recounted today from several lines of evidence, would have become the chloroplast by endosymbiosis.
On biological homochirality
Authors: Wallace Rodrick
Published: July 2019

Generalizing Landau's spontaneous symmetry breaking arguments using the standard groupoid approach to stereochemistry allows reconsideration of the origin of biological homochirality. On Earth, limited metabolic free energy density may have served as a low temperature analog to 'freeze' the system into the set of simplest homochiral transitive groupoids representing reproductive chemistries. These engaged in Darwinian competition until a single configuration survived. Subsequent path dependent evolutionary process licked in this initial condition. Astrobiological outcomes, in the presence of higher initial metabolic free energy densities, could well be considerably richer, perhaps of mixed chirality. One result would be a complicated distribution of biological chirality across a statistically large sample of extraterrestrial stereochemistry, in contrast with a recent prediction of a racemic average.
MicroDNAs and Transcriptional Regulation
Authors: sheikhnejad Reza
Published: July 2019

Synthetic "microDNAs (MIDs)"is a new class of ~ 20-25 nucleotide-long DNAs capable of repressing the activity of the target gene at the level of transcription by mechanisms that have not been clarified yet. However they are designed to target non-coding regions of the cancer causing genes, thus interfering with transcription. The inhibition might be possible through the direct binding of MIDs to cis-regulatory sites and/or to some Transcription Factors (TF) that normally activate transcription. Synthetic MIDs in some ways are similar to the newly discovered microRNAs a mechanism by which cell regulates its genetic activities at post-transcriptional level. Synthetic MIDs can provide a powerful tool to prevent massive production of mRNA by undesired gene activities. Therefore drugs are not required to interact with overwhelming number of mRNA and microRNA copies that may present unwanted side effects. In vitro studies suggest that the inhibition of the target gene starts after the first round of DNA replication, usually 24 hours after treatment depending on cell doubling time. Cell growth suppression maximizes at day 6 or 7 and the inhibition effect is sustained for weeks. We have shown that blocking of both bcl-2 and k-ras transcription by their specific microDNA Inhibitors induced apoptosis in HL60 leukemia cells and B-cell lymphomas.
Topological network alignment uncovers biological function and phylogeny
Authors: Kuchaiev Oleksii , Milenkovic Tijana , Memisevic Vesna , Hayes Wayne , Przulj Natasa
Published: July 2019

Sequence comparison and alignment has had an enormous impact on our understanding of evolution, biology, and disease. Comparison and alignment of biological networks will likely have a similar impact. Existing network alignments use information external to the networks, such as sequence, because no good algorithm for purely topological alignment has yet been devised. In this paper, we present a novel algorithm based solely on network topology, that can be used to align any two networks. We apply it to biological networks to produce by far the most complete topological alignments of biological networks to date. We demonstrate that both species phylogeny and detailed biological function of individual proteins can be extracted from our alignments. Topology-based alignments have the potential to provide a completely new, independent source of phylogenetic information. Our alignment of the protein-protein interaction networks of two very different species—yeast and human—indicate that even distant species share a surprising amount of network topology with each other, suggesting broad similarities in internal cellular wiring across all life on Earth.
Dyslexia and the assessment of visual attention
Authors: Skoyles John , Skottun Bernt
Published: July 2019

Visual stream segregation has been proposed as a method to measure visual attention in dyslexia. Another task proposed to do this is the line-motion illusion. Both tasks, it is observed, can be carried out with spatially distributed stimuli. This, however, appears inconsistent with these tasks being linked speci?cally to attentional processes since this would require them to spatially focus cognitive resources. Also, both line-motion and visual stream segregation involve the perception of movement raising the possibility that what is actually measured by these tasks is not attention but some aspect of motion perception.
The land surface water and energy budgets over the Tibetan Plateau
Authors: Xu Li
Published: July 2019

Tibetan Plateau plays an important role in the Asian Monsoon and global general circulation system. Due to the lack of quantitative observations and complicated cold season processes in high elevation terrain, however, the land surface water and energy budgets are still unexplored over this special region. In this study, the water and energy balances are analyzed in detail based on recently released land surface “reanalysis” data produced by NASA Global Land Data Assimilation System by three different land models, which first ingest all available ground and satellite data into the data assimilation system over the Tibetan Plateau. The major land surface energy and water components in the annual variability are compared. The model and data assimilation skills and deficiencies are also discussed. The total heat fluxes in the transition from heat source to heat sink is observed at the west edge of the TP during winter. But, the area and intensity is far less than the previous hypothesized. The Budyko curve for hydrology indicates that the TP is a typical dry and arid climate where evaporation is mainly controlled by precipitation.
Spike processing model of the brain
Authors: Brown Robert
Published: July 2019

The timing of a spike within a specific time period is used to identify a place in space (input terminal) and/or sense changes in energy or position in the environment, and is used to determine the motion of an actuator or the activation of a place in space (output terminal). The timing of a spike is specified by a sensor or a time delay memory cell that is preset (predetermined) or set through experience (empirical). Time delay memory cells are arranged in decoding networks that activate specific output terminals based upon the timing of incoming spike trains, or arranged in encoding networks that generate spike trains from activated input terminals. These spike trains form semi-axes that can transmit large quantities of information in one direction through a single conductor, and are essential in the transmission of information from peripheral neurons to and from the brain through the spinal chord.
Chemotherapy effects on brain glucose metabolism at rest
Authors: Baudino Bruno , D’Agata Federico , Castellano Giancarlo , Caroppo Paola , Cauda Simona , Parente Antonella , Manfredi Matteo , Geda Elisabetta , Orsi Laura , Cauda Franco , Castelli Lorys , Sacco Katiuscia , Ardito Rita , Torta Riccardo , Bisi Gianni
Published: July 2019

Background:

A growing number of studies reports that chemotherapy may impair brain functions inducing cognitive changes which can persist in a subset of cancer survivors.Aims: To investigate the neural basis of the chemotherapy-induced neurobehavioral changes by means of metabolic imaging and voxel-based statistical parametric mapping analyses.

Methods:

We studied the resting brain [18]FDG-PET/CT images of 43 adult cancer patients with solid (n=12, 28%) or hematologic malignancies (n=31, 72%); 12 patients were studied prior to chemotherapy (No chemotherapy) while treated patients were divided into two matched subgroups: Early High (<9 months after chemotherapy, >6 chemotherapy cycles, n=10), and Late Low (>9 months after chemotherapy, <6 chemotherapy cycles, n=21).

Findings:

Compared to No chemotherapy, the Early High subgroup showed a significant bilateral (p<0.05) lower regional cerebral metabolic rate of glucose metabolism in both the prefrontal cortices and white matter, cerebellum, posterior medial cortices and limbic regions. A similar pattern emerged in the Early High versus Low Late comparison, while no significant result was obtained in the Low Late versus No chemotherapy comparison. The number of cycles and the post-chemotherapy time were negatively and positively correlated, respectively, with a set of these same brain regions.

Interpretation:

The present study shows that chemotherapy induces significant transient changes in the glucose metabolism of multiple cerebral cortical and white matter regions with a prevailing involvement of the prefrontal cortex. The severity of these changes are significantly related with the number of chemotherapy cycles and a subset of brain regions seems to present longer lasting, but more subtle, metabolic changes.
Expression cartography of human tissues using self organizing maps
Authors: Wirth Henry , Löffler Markus , von Bergen Martin , Binder Hans
Published: July 2019

Background:

The availability of parallel, high-throughput microarray and sequencing experiments poses a challenge how to best arrange and to analyze the obtained heap of multidimensional data in a concerted way. Self organizing maps (SOM), a machine learning method, enables the parallel sample- and gene-centered view on the data combined with strong visualization and second-level analysis capabilities. The paper addresses aspects of the method with practical impact in the context of expression analysis of complex data sets.

Results:

The method was applied to generate a SOM characterizing the whole genome expression profiles of 67 healthy human tissues selected from ten tissue categories (adipose, endocrine, homeostasis, digestion, exocrine, epithelium, sexual reproduction, muscle, immune system and nervous tissues). SOM mapping reduces the dimension of expression data from ten thousands of genes to a few thousands of metagenes where each metagene acts as representative of a minicluster of co-regulated single genes. Tissue-specific and common properties shared between groups of tissues emerge as a handful of localized spots in the tissue maps collecting groups of co-regulated and co-expressed metagenes. The functional context of the spots was discovered using overrepresentation analysis with respect to pre-defined gene sets of known functional impact. We found that tissue related spots typically contain enriched populations of gene sets well corresponding to molecular processes in the respective tissues. Analysis techniques normally used at the gene-level such as two-way hierarchical clustering provide a better signal-to-noise ratio and a better representativeness of the method if applied to the metagenes. Metagene-based clustering analyses aggregate the tissues into essentially three clusters containing nervous, immune system and the remaining tissues.

Conclusions:

The global view on the behavior of a few well-defined modules of correlated and differentially expressed genes is more intuitive and more informative than the separate discovery of the expression levels of hundreds or thousands of individual genes. The metagene approach is less sensitive to a priori selection of genes. It can detect a coordinated expression pattern whose components would not pass single-gene significance thresholds and it is able to extract context-dependent patterns of gene expression in complex data sets.
Collective Animal Behavior from Bayesian Estimation and Probability Matching
Authors: Perez-Escudero Alfonso , de Polavieja Gonzalo
Published: July 2019

Animals living in groups make movement decisions that depend, among other factors, on social interactions with other group members. Our present understanding of social rules in animal collectives is mainly based on empirical fits to observations, with less emphasis in obtaining first-principles approaches that allow their derivation. Here we show that patterns of collective decisions can be derived from the basic ability of animals to make probabilistic estimations in the presence of uncertainty. We build a decision-making model with two stages: Bayesian estimation and probabilistic matching.In the first stage, each animal makes a Bayesian estimation of which behavior is best to perform taking into account personal information about the environment and social information collected by observing the behaviors of other animals. In the probability matching stage, each animal chooses a behavior with a probability equal to the Bayesian-estimated probability that this behavior is the most appropriate one. This model derives very simple rules of interaction in animal collectives that depend only on two types of reliability parameters, one that each animal assigns to the other animals and another given by the quality of the non-social information. We test our model by obtaining theoretically a rich set of observed collective patterns of decisions in three-spined sticklebacks, Gasterosteus aculeatus, a shoaling fish species. The quantitative link shown between probabilistic estimation and collective rules of behavior allows a better contact with other fields such as foraging, mate selection, neurobiology and psychology, and gives predictions for experiments directly testing the relationship between estimation and collective behavior.
Efficient Replication of Over 180 Genetic Associations with Self-Reported Medical Data
Authors: Francke Uta , Naughton Brian , Mountain Joanna , Wojcicki Anne , Tung Joyce , Do Chuong , Hinds David , Kiefer Amy , Macpherson J. Michael , Eriksson Nicholas , Chowdry Arnab
Published: July 2019

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

In vitro antibacterial studies were carried out using hexane, dichloromethane and methanol extract of leaves of Centella asiatica by disc-diffusion method against gram-positive and gram-negative bacteria. The methanol and dichloromethane extracts of leaf showed a broad spectrum antibacterial activity. Thus the results substantiate the traditional usage of this plant as a medicine.
3DScape: three dimensional visualization plug-in for Cytoscape
Authors: Wang Qi
Published: July 2019

3DScape is the first plug-in which enables three-dimensional network visualization in Cytoscape. The extra dimension is useful in accommodating, visualizing, and distinguishing larger networks with multiple crossing connections.Special features in 3DScape include 3D layout algorithms, mapping onto 3D models and animation effects on a series of expression data. 3DScape is available at http://www.rendware.com
Complex Systems Analysis of Cell Cycling Models in Carcinogenesis
Authors: Baianu I.
Published: July 2019

A new approach to the modular, complex systems analysis of nonlinear dynamics in cell cycling network transformations involved in carcinogenesis is proposed. Carcinogenesis is a complex process that involves dynamically inter-connected biomolecules in the intercellular, membrane, cytosolic, nuclear and nucleolar compartments that form numerous inter-related pathways referred to as networks.The variable biotopology of such dynamic networks is highly complex, and has a number of interesting properties that can be formally characterized at one level of organization by mathematical structures called 'biogroupoids'.One such family of pathways contains the cell cyclins. Cyclins are proteins that link several critical pro-apoptotic and other cell cycling/ division components, including the tumor suppressor gene TP53 and its product, the Thomsen-Friedenreich antigen (T antigen), Rb, mdm2, c-Myc, p21, p27, Bax, Bad and Bcl-2, which all play major roles in carcinogenesis of many cancers. A novel theoretical analysis is thus possible based on recently published studies of cyclin signaling, with special emphasis placed on the roles of cyclins D1 and E, suggests novel clinical trials and rational therapies of cancer through reestablishment of cell cycling inhibition in metastatic cancer cells.
Early Diagnosis of Alzheimer's disease by NIRF Spectroscopy and Nuclear Medicine
Authors: Baianu I.
Published: July 2019

There is an urgent need for the early detection of diseases such as Alzheimer’s (AD) and Cancers in order to enable their successful treatment. Cancer is the second major cause of death after Heart Disease, and AD is the third major cause of death with major, human and financial/economics trillion dollar consequences for the society. Nuclear Medicine is concerned with applications in Medicine of Nuclear Science and Engineering techniques and knowledge. Three major Nuclear Medicine techniques that are established for diagnostic and research purposes are: Positron Emission Tomography (PET) and CAT/CT, Nuclear Magnetic Resonance Imaging (NMRI/MRI). However, these three techniques have also major limitations in terms of either cost or image resolution, as well as patient irradiation in the case of CAT/CT and PET. On the other hand, Near Infrared Chemical Imaging Microspectroscopy and certain Fluorescence spectroscopic techniques are capable of single cancer cell and/or single molecule detection and/or imaging. Such powerful capabilities, combined with low cost of diagnostics, make these novel techniques very attractive means for early detection of diseases such as cancer and Alzheimer’s, that are promising to reduce the fatality rate of patients through adequate diagnosis and treatment of such diseases at early stages.Currently NIH provides only inadequate funding for the clinical and research aspects of these novel investigation and clinical diagnostic techniques by FT-NIRS and Fluorescence spectrocopy for early detection of Alzheimer's and Cancers.
Berberine induces caspase-independent cell death in colon tumor cells through activation of apoptosis-inducing factor
Authors: Wilson Keith , Polk D. Brent , Yan Fang , Wang Lihong , Liu Liping , Shi Yan , Cao Hamwei , Chaturvedi Rupesh , Hu Tianhui
Published: July 2019

Berberine, an isoquinoline alkaloid derived from plants, is a traditional medicine for treating bacterial diarrhea and intestinal parasite infections. Although berberine has recently been shown to suppress growth of several tumor cell lines, information regarding the effect of berberine on colon tumor growth is limited. Here, we investigated the mechanisms underlying the effects of berberine on regulating the fate of colon tumor cells, specifically the immorto Min mouse colonic epithelial (IMCE) cells carrying the Apcmin mutation, and of normal colon epithelial cells, namely young adult mouse colon (YAMC) epithelial cells. Berberine decreased colon tumor colony formation in agar, and induced cell death and LDH release in a time- and concentration-dependent manner in IMCE cells. In contrast, YAMC cells were not sensitive to berberine-induced cell death. Berberine did not stimulate caspase activation, and PARP cleavage and berberine-induced cell death were not affected by a caspase inhibitor in IMCE cells. Rather, berberine stimulated a caspase-independent cell death mediator, apoptosis-inducing factor (AIF) release from mitochondria and nuclear translocation in a ROS production-dependent manner. Amelioration of berberine-stimulated ROS production or suppression of AIF expression blocked berberine-induced cell death and LDH release in IMCE cells. Furthermore, two targets of ROS production in cells, cathepsin B release from lysosomes and PARP activation were induced by berberine. Blockage of either of these pathways decreased berberine-induced AIF activation and cell death in IMCE cells. Thus, berberine-stimulated ROS production leads to cathepsin B release and PARP activation-dependent AIF activation, resulting in caspase-independent cell death in colon tumor cells. Notably, normal colon epithelial cells are less susceptible to berberine-induced cell death, which suggests the specific inhibitory effects of berberine on colon tumor cell growth.
Transcriptional memory emerges from cooperative histone modifications
Authors: Binder Hans , Steiner Lydia , Rohlf Thimo , Prohaska Sonja , Galle Joerg
Published: July 2019

Background

Transcriptional regulation in cells makes use of diverse mechanisms to ensure that functional states can be maintained and adapted to variable environments; among them are chromatin-related mechanisms. While mathematical models of transcription factor networks controlling development are well established, models of transcriptional regulation by chromatin states are rather rare despite they appear to be a powerful regulatory mechanism.

Results

We here introduce a mathematical model of transcriptional regulation governed by histone modifications. This model describes binding of protein complexes to chromatin which are capable of reading and writing histone marks. Molecular interactions between these complexes and DNA or histones create a regulatory switch of transcriptional activity possessing a regulatory memory. The regulatory states of the switch depend on the activity of histone (de-) methylases, the structure of the DNA-binding regions of the complexes, and the number of histones contributing to binding.We apply our model to transcriptional regulation by trithorax- and polycomb- complex binding. By analyzing data on pluripotent and lineage-committed cells we verify basic model assumptions and provide evidence for a positive effect of the length of the modified regions on the stability of the induced regulatory states and thus on the transcriptional memory.

Conclusions

Our results provide new insights into epigenetic modes of transcriptional regulation. Moreover, they implicate well-founded hypotheses on cooperative histone modifications, proliferation induced epigenetic changes and higher order folding of chromatin which await experimental validation. Our approach represents a basic step towards multi-scale models of transcriptional control during development and lineage specification.
Antiviral Effects of a Synthetic Aluminium-Magnesium Silicate on Avian Influenza Virus
Authors: Ezeibe Madike , Egbuji Anthony , Okoroafor Obianuju , Eze James , Ijabo Omadi , Ngene Augustine , Eze Ikechukwu , Ugonabo Joeseph , Sanda Mary , Mbuko Ijeoma
Published: July 2019

Effects of a synthetic Aluminium-Magnesium Silicate (AMS) on Avian Influenza Virus (AIV) were tested. Equal amounts of H5N1 AIV samples and of AMS were mixed, left one hour, at room temperature before centrifuging. The supernatants were remeasured and tested for viral titre, for Mean Death Time (MDT) and Embryo Mortality Rate (EMR) of chicken eggs. Volumes of the viral samples reduced at rate of 23.4 &177; 5.48 %. Viral titres reduced significantly (P from HA, 73 &177; 32.72 to 1.4 &177;0.43). Also, mortality of infected embryos reduced from 100 % to 65% while MDT of those that died, increased significantly (P = 0.001) from 76 &177; 4.38 to 130 &177;17.27 hours. When incubation with AMS was repeated on portions of the same sample, MDT increased from 64 to 104 hours with the portion incubated once. Two AIV portions on which incubation with AMS was repeated could not kill chick embryos.
Early exposure to environmental toxin contributes to neuronal vulnerability and axonal pathology in a model of familial ALS
Authors: Lee Grace , Shaw Christopher
Published: July 2019

Adult onset amyotrophic lateral sclerosis (ALS) arises due to progressive and irreversible functional deficits to the central nervous system, specifically the loss of motor neurons. Sporadic ALS causality is not well understood, but is almost certainly of multifactorial origin involving a combination of genetic and environmental factors. The discovery of endemic ALS in the native Chamorro population of Guam during the 1950s and the co-occurrence of parkinsonism and dementia in some patients led to searches for an environmental toxins that could be responsible. In the present paper, we report that an environmental neurotoxin enhances mutant superoxide dismutase (SOD)-induced spinal motor neuron death and pathology and induces motor axon abnormalities. These results cumulatively confirm earlier findings that exposure to an environmental toxin is sufficient to produce the disease phenotype and indicate a role for gene-environment interaction in some forms of the disease.
The BRIF (Bioresource Research Impact Factor) as a tool for improving bioresource sharing in biomedical research
Authors: Bravo Elena , Cambon-Thomsen Anne , Gourraud Pierre-Antoine , Hofman Paul , Harris Jennifer , Mabile Laurence , Dalgleish Raymond , Thorisson Gudmundur , Deschênes Mylène , Hewitt Robert , Munoz-Fernandes Maria Angeles , Carpenter Jane
Published: July 2019

The central aim of the BRIF (Bioresource Research Impact Factor) initiative is to construct a quantitative parameter to evaluate bioresources, modeled to some degree on the Journal Impact Factor (JIF), and to provide guidance and methodology for optimizing recognition of bioresources, their use and their sharing at international level. To implement this concept an international working group has been set up. Specific tasks have been assigned to several sub-groups: BRIF digital identifier schemes; BRIF parameters, measures and indicators; journal guidelines for resource citing and referencing; policies for bioresource access and sharing. These are discussed in the present manuscript.
Detection of BCR-ABL kinase domain mutations in CD34+ cells from newly diagnosed chronic phase CML patients and their association with imatinib resistance
Authors: Taj Abid , Khalid Muhammad , Qayyum Abdul , Qin Weng , ur-Rehman Najeeb , Khalid Ahmad , Ferhan Muhammad , Khan Mahwish , Baig Shahid , Iqbal Zafar , Jamil Abid , Shah Ijaz , Akhtar Tanveer , Aleem Aamer , Abbad Muhammad , Naqvi Mubashar , ul-Haq Riaz , Tahir Ammara , Iqbal Mudassar , Gill Tariq
Published: July 2019

BCR-ABL kinase domain (KD) mutations, the most common cause of imatinib resistance, are infrequently detected in newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML) patients. Recent studies indicate pre-existing mutations (PEMs) can be detected in a higher percentage of CML patients using CD34+ stem/progenitor cells, and these mutations may correlate with imatinib resistance. We investigated KD mutations in CD34+ stem cells from 100 CP-CML patients by multiplex ASO-PCR and sequencing ASO-PCR products at the time of diagnosis. PEMs were detected in 32/100 patients and included F311L, M351T, and T315I. After a median follow-up of 30 months (range 8-48), all patients with PEMs exhibited imatinib resistance. Of 68 patients without PEMs, 24 developed imatinib resistance. Mutations were detected in 21 of these patients by ASO-PCR and KD sequencing. All 32 patients with PEMs had the same mutations. In imatinib-resistant patients without PEMs, we detected F311L, M351T, Y253F, and T315I mutations. All imatinib-resistant patients without T315I and Y253F mutations responded to imatinib dose escalation. In conclusion, BCR-ABL PEMs can be detected in a substantial number of CP-CML patients when investigated using CD34+ stem/progenitor cells. These mutations are associated with imatinib resistance, and mutation testing using CD34+ cells may facilitate improved, patient-tailored treatment.
Accurate Reconstruction of Molecular Phylogenies for Proteins Using Codon and Amino Acid Unified Sequence Alignments (CAUSA)
Authors: Niu Yingbo , Hu Jingjie , Wang Xiaolong , Fu Yu , Zhao Yue , Wang Qi , Pedamallu Chandra Sekhar , Xu Shuang-yong
Published: July 2019

Based on molecular clock hypothesis, and neutral theory of molecular evolution, molecular phylogenies have been widely used for inferring evolutionary history of organisms and individual genes. Traditionally, alignments and phylogeny trees of proteins and their coding DNA sequences are constructed separately, thus often different conclusions were drawn. Here we present a new strategy for sequence alignment and phylogenetic tree reconstruction, codon and amino acid unified sequence alignment (CAUSA), which aligns DNA and protein sequences and draw phylogenetic trees in a unified manner. We demonstrated that CAUSA improves both the accuracy of multiple sequence alignments and phylogenetic trees by solving a variety of molecular evolutionary problems in virus, bacteria and mammals. Our results support the hypothesis that the molecular clock for proteins has two pointers existing separately in DNA and protein sequences. It is more accurate to read the molecular clock by combination (additive) of these two pointers, since the ticking rates of them are sometimes consistent, sometimes different. CAUSA software were released as Open Source under GNU/GPL license, and are downloadable free of charge from the website www.dnapluspro.com.
NPY Levels In Type 1 Diabetic Men of Different Duration.
Authors: Giumelli Claudio , Ferri Teore , Minelli Roberta , Volpi Lavinia , Volpi Riccardo , Araldi Anna , Cataldo Simona , Magotti Maria Grazia , Capretti Luigi , Chiodera Paolo , Coiro Vittorio
Published: July 2019

Background:

The aim of the present study was to evaluate whether the different duration of type 1 diabetes mellitus influences basal NPY secretion. Design: The NPY concentrations were measured in sixty-eight men with insulin-dependent diabetes mellitus (IDDM) (duration: group 1 (n.21) <5 years (range 2-4 years); group 2 (n.24) >5 years and <10 years (range: 6-9 years); group 3 (n.29) >10 years (range: 11-14 years)) and in age matched normal control subjects (n. 30).

Results:

The NPY levels were significantly lower in group 3 than in group 2 and 1 and in the control group, in group 2 than in group 1 and in the control group and in group 1 than control group. Conclusion: These results support the view that the duration of diabetes may have a modulatory role in the decreased basal NPY secretion observed in diabetics.
The transcription factor NFIL3 controls regulatory T-cell function and stability
Authors: Kim Hyeong Su , Sohn Hyogon , Jang Sung Woong , Lee Gap Ryol
Published: July 2019

Regulatory T (Treg) cells are a CD4 T-cell subset with an important role in immune tolerance; however, the mechanisms underlying Treg cell differentiation and function are incompletely understood. Here, we show that NFIL3/E4BP4, a transcription factor, plays a key role in Treg cell differentiation and function. Microarray analysis showed that Treg cells had lower Nfil3 expression than all other CD4 T-cell subsets. Overexpression of Nfil3 in Treg cells led to diminished expression of Foxp3 and other signature Treg genes, including Il2ra, Icos, Tnfrsf18, and Ctla4. Furthermore, Nfil3-overexpressing Treg cells exhibited impaired immunosuppressive activity in vitro and in vivo. We discovered that NFIL3 directly binds to and negatively regulates the expression of Foxp3. In addition, bisulfite sequencing revealed that NFIL3 induces methylation at Foxp3 locus regulatory CpG sites, which contributes to the control of Treg cell stability. Together, these data indicate that NFIL3 impairs Treg cell function through the downregulation of Foxp3 expression.
Probing the reconstructed Fermi surface of antiferromagnetic BaFe2As2 in one domain
Authors: Watson Matthew D. , Dudin Pavel , Rhodes Luke C. , Evtushinsky Daniil V. , Iwasawa Hideaki , Aswartham Saicharan , Wurmehl Sabine , Büchner Bernd , Hoesch Moritz , Kim Timur K.
Published: July 2019

A fundamental part of the puzzle of unconventional superconductivity in the Fe-based superconductors is the understanding of the magnetic and nematic instabilities of the parent compounds. The issues of which of these can be considered the leading instability, and whether weak- or strong-coupling approaches are applicable, are both critical and contentious. Here, we revisit the electronic structure of BaFe2As2 using angle-resolved photoemission spectroscopy (ARPES). Our high-resolution measurements of samples “detwinned” by the application of a mechanical strain reveal a highly anisotropic 3D Fermi surface in the low-temperature antiferromagnetic phase. By comparison of the observed dispersions with ab initio calculations, we argue that overall it is magnetism, rather than orbital/nematic ordering, which is the dominant effect, reconstructing the electronic structure across the Fe 3d bandwidth. Finally, using a state-of-the-art nano-ARPES system, we reveal how the observed electronic dispersions vary in real space as the beam spot crosses domain boundaries in an unstrained sample, enabling the measurement of ARPES data from within single antiferromagnetic domains, and showing consistence with the effective mono-domain samples obtained by detwinning.
Bromodomain inhibitor JQ1 reversibly blocks IFN-γ production
Authors: Gibbons Hunter R. , Mi Deborah J. , Farley Virginia M. , Esmond Tashawna , Kaood Mary B. , Aune Thomas M.
Published: July 2019

As a class, ‘BET’ inhibitors disrupt binding of bromodomain and extra-terminal motif (BET) proteins, BRD2, BRD3, BRD4 and BRDT, to acetylated histones preventing recruitment of RNA polymerase 2 to enhancers and promoters, especially super-enhancers, to inhibit gene transcription. As such, BET inhibitors may be useful therapeutics for treatment of cancer and inflammatory disease. For example, the small molecule BET inhibitor, JQ1, selectively represses MYC, an important oncogene regulated by a super-enhancer. IFN-γ, a critical cytokine for both innate and adaptive immune responses, is also regulated by a super-enhancer. Here, we show that JQ1 represses IFN-γ expression in TH1 polarized PBMC cultures, CD4+ memory T cells, and NK cells. JQ1 treatment does not reduce activating chromatin marks at the IFNG locus, but displaces RNA polymerase II from the locus. Further, IFN-γ expression recovers in polarized TH1 cultures following removal of JQ1. Our results show that JQ1 abrogates IFN-γ expression, but repression is reversible. Thus, BET inhibitors may disrupt the normal functions of the innate and adaptive immune response.