bluuebunny/crossref_metadata_2025 huggingface dataset:
Representing an Object by Interchanging What with Where
Authors: Ahn Jong-Hoon , Lee Yillbyung
Published: July 2019

Exploring representations is a fundamental step towards understanding vision. The visual system carries two types of information along separate pathways: One is about what it is and the other is about where it is. Initially, the what is represented by a pattern of activity that is distributed across millions of photoreceptors, whereas the where is 'implicitly' given as their retinotopic positions. Many computational theories of object recognition rely on such pixel-based representations, but they are insufficient to learn spatial information such as position and size due to the implicit encoding of the where information. Here we try transforming a retinal image of an object into its internal image via interchanging the what with the where, which means that patterns of intensity in internal image describe the spatial information rather than the object information. To be concrete, the retinal image of an object is deformed and turned over into a negative image, in which light areas appear dark and vice versa, and the object's spatial information is quantified with levels of intensity on borders of that image. Interestingly, the inner part excluding the borders of the internal image shows the position and scale invariance. In order to further understand how the internal image associates the what and where, we examined the internal image of a face which moves or is scaled on the retina. As a result, we found that the internal images form a linear vector space under the object translation and scaling. In conclusion, these results show that the what-where interchangeability might play an important role for organizing those two into internal representation of brain.
Diamond nanowires, a new approach towards next generation electrochemical gene sensor platforms
Authors: Yang Nianjun , Uetsuka Hiroshi , Yu Jiuhong , Osawa Eiji , Tokuda Norio , Nebel Christoph
Published: July 2019

A novel bio-sensing platform is introduced by combination of a) geometrically controlled DNA bonding using vertically aligned diamond nano-wires and b) the superior electrochemical sensing properties of diamond as transducer material. Ultra-hard vertically aligned diamond nanowires are electrochemically modified to bond phenyl linker-molecules to their tips which provide mesospacing for DNA molecules on the transducer. The nano-wires are generated by reactive ion etching of metallically boron doped atomically smooth single crystalline CVD diamond. Surface properties are characterized by atomic force, scanning electron and scanning tunneling microcopy. Electro- and biochemical sensor properties are investigated using cyclic and differential pulse voltammetry as well as impedance spectroscopy with Fe(CN)63-/4- as redox mediators which reveal sensitivities of 2 pM on 3 mm2 sensor areas and superior DNA bonding stability over 30 hybridization/denaturation cycles. The fabrication of "all diamond" ultra-micro-electrode (UME) arrays and multi-gene sensors are discussed taking into account the unique properties of diamond.
The Control Fallacy: Why OA Out-Innovates the Alternative
Authors: Wilbanks John
Published: July 2019

This article examines the relationship between Open Access to the scholarly literature and innovation. It traces the ideas of "end to end" network principles in the Internet and the World Wide Web and applies them to the scholarly biomedical literature. And the article argues for the importance of relieving not just price barriers but permission barriers.
A Report of the Mosquito Host Range of Pythium guiyangense Su
Authors: Su Xiaoqing
Published: July 2019

Mosquito causes problems in both disease transmission and disturbance to people's daily life. The controlling methods used now are mainly application of chemical pesticides which result in serious harm to environment. Biological control of the pest is one of the ideal ways. But, lack of suitable agent makes it difficult to extend this technique in wider scope. Pythium guiyangense Su is a newly found fungal pathogen of mosquitoes and is promising for practical use. Here we summarize a list of mosquitoes that can be infected by the fungus so far, which shows the potential significance of the application of the fungus in the future.
How gut sampling and microbial invasiveness/noninvasiveness provides mucosal immunity with a nonmolecular pattern means to distinguish commensals from pathogens: A review
Authors: Skoyles John
Published: July 2019

Mucosal immunity distinguishes not only different microbial antigens but also separates those of pathogens from those of commensals. How this is done is unknown. The present view is that the pathogen/commensal determination of antigens depends upon as yet to be discovered molecular patterns. Here I review the biological feasibility that it also involves the detection of the invasive differences in their motility towards the gut wall when they are sampled by differently biased methods. By their nature, pathogens and commensals have different motility – invasive and noninvasive – in regard to the epithelium. The immune system is in a position to detect such motility differences. This biological opportunity arises since different microbe sampling methods can “catch” different groups of microbes depending upon how their motility interacts with the epithelium. A biological method biased to sample those with invasive motility—pathogens—could be achieved by ‘honey pot traps’ that preferentially (but not exclusively) sample microbes that have a taxis to breaches in the epithelium. A biological method biased to sample those that are noninvasive—commensals—could be done by capturing microbes that are passively and stably residing in the biofilm “offshore” of the epithelium. Such differential sampling strategies would seem to relate to those carried out respectively by (i) M-cells (working with subepithelial dome dendritic cells), and (ii) sub- and intraepithelial dendritic cells.The interactions of antigen presentation can be arranged so that the immune system links antigens from biased microbial sampling with pathogenic or commensal appropriate immune responses. Such immune classification could feasibly occur biologically through a winner-take-all competition between inhibiting and activating antigen presentation. Winner-takes-all types of processing classification are already known to underlie the biologically interactions between neurons that classify sensory inputs making it also plausible that they are exploited by the immune system. In pathogen identification, M-cell antigens would be activating and biofilm antigens inhibitory, and vise versa for commensal identification. This winner-take-all competition between antigen presentation would act to amplify small statistical biases in the two samples linked to invasiveness/noninvasiveness into a reliable pathogen/commensal distinction. This process would both complement, and acts as independent guarantor, upon the alternative pathogenicity/commensality recognition provided by molecular pattern recognition.
Developing Language Abilities by a Non-verbal Training : A fMRI Study
Authors: Lefebvre Laurent , Balériaux Danielle , Paquier Philippe , Lowenthal Francis
Published: July 2019

The language ability is a critical aspect of experimental design in functional imaging studies. Today, it is commonly accepted that the brain structures underlying the language are more distributed than the traditional Broca’s and Wernicke’s areas. Currently, some other areas as the premotor cortex, the supplementary motor area, the cerebellum or subcortical structures, notably, are recognised. However, a lesser studied question is to define if it is possible to observe a reorganisation of the activation observed during language tasks when the subjects have been trained to develop non-verbal abilities. Particularly, Bates and Ellman (1996) claim that probabilistic regularities are the basis of the language acquisition processing.
Desynchronization of pathological low-frequency brain activity by the hypnotic drug zolpidem.
Authors: Hall Stephen , Yamawaki Naoki , Fisher Alison , Clauss Ralf , Woodhall Gavin , Stanford Ian
Published: July 2019

Reports of the beneficial effects of the hypnotic imidazopyridine, zolpidem, described in persistent vegetative state^1, 2^ have been replicated recently in brain-injured and cognitively impaired patients^3-7^. Previous single photon emission computed tomography (SPECT) studies have suggested that sub-sedative doses of zolpidem increased regional cerebral perfusion in affected areas^5, 8^, implying enhanced neuronal metabolic activity; which has led to speculation that zolpidem 'reawakens' functionally dormant cortex. However, a neuronal mechanism by which this hypnotic drug affords benefits to brain injured patients has yet to be demonstrated. Here, we report the action of sub-sedative doses of zolpidem on neuronal network oscillatory activity in human brain, measured using pharmaco-magnetoencephalography (pharmaco-MEG). Study participant JP suffered a stroke in 1996, causing major damage to the left hemisphere that impaired aspects of both motor and cognitive function. Pharmaco-MEG analyses revealed robust and persistent pathological theta (4-10Hz) and beta (15-30Hz) oscillations within the lesion penumbra and surrounding cortex. Administration of zolpidem (5mg) reduced the power of pathological theta and beta oscillations in all regions of the lesioned hemisphere. This desynchronizing effect correlated well with zolpidem uptake (occurring approximately 40 minutes after acute administration) and was coincident with marked improvements in cognitive and motor function. Control experiments revealed no effect of placebo, while a structurally unrelated hypnotic, zopiclone, administered at a comparable dose (3.5mg) elicited widespread increases in cortical oscillatory power in the beta (15-30Hz) band without functional improvement. These results suggest that in JP, specific motor and cognitive impairments are related to increased low-frequency oscillatory neuronal network activity. Zolpidem is unique amongst hypnotic drugs in its ability to desynchronize such pathological low-frequency activity, thereby restoring cognitive function.
The Broad Spectrum HDAC Inhibitor PCI-24781 Induces Caspase- and ROS-Dependent Apoptosis and is Synergistic with Bortezomib in Lymphoma
Authors: Bhalla Savita , Balasubramanian Sriram , David Kevin , Sirisawad Mint , Buggy Joseph , Mauro Lauren , Prachand Sheila , Miller Richard , Gordon Leo , Evens Andrew
Published: July 2019

We investigated the cytotoxicity and biology of the novel broad-spectrum hydroxamic acid-based histone deacetylase inhibitor (HDACi), PCI-24781. PCI-24781 was studied alone and combined with bortezomib in Hodgkin lymphoma (L428) and non-Hodgkin's lymphoma cell lines (Ramos, HF1, SUDHL4). PCI-24781 induced dose-dependent apoptosis that was associated with prominent G0/G1 arrest, decreased S-phase, increased p21 protein expression, and production of reactive oxygen species (ROS). Furthermore, PCI-24781-induced apoptosis was shown to be ROS- and caspase-dependent. Combined PCI-24781 and bortezomib exposure resulted in strong synergistic apoptosis in all cell lines (combination indices 0.19-0.6). Furthermore, compared to either agent alone, PCI-24781/bortezomib resulted in increased caspase cleavage, mitochondrial depolarization, and histone hyperacetylation. Microarray analyses showed that PCI-24781 alone significantly downregulated several antioxidant genes, proteasome components, and NF-kappaB pathway genes, effects which were enhanced further with bortezomib. RT-PCR confirmed downregulation of NF-kappaB targets NF-kappaB1 (p105), c-Myc, and IkappaB-kinase subunits, while gel-shift showed decreased NF-kappaB DNA-binding activity. Taken together, these results suggest that increased oxidative stress and NF-kappaB inhibition, leading to caspase activation and apoptosis, are likely responsible for the activity of PCI-24781 as well as the observed synergy with bortezomib. These data indicate that PCI-24781 has potential therapeutic value in lymphoma as a single-agent and combined with bortezomib.
Specification of spatial relationships in directed graphs of cell signaling networks
Authors: Lipshtat Azi , Neves Susana , Iyengar Ravi
Published: July 2019

Graph theory provides a useful and powerful tool for the analysis of cellular signaling networks. Intracellular components such as cytoplasmic signaling proteins, transcription factors and genes are connected by links, representing various types of chemical interactions that result in functional consequences. However, these graphs lack important information regarding the spatial distribution of cellular components. The ability of two cellular components to interact depends not only on their mutual chemical affinity but also on co-localization to the same subcellular region. Localization of components is often used as a regulatory mechanism to achieve specific effects in response to different receptor signals. Here we describe an approach for incorporating spatial distribution into graphs, and for the development of mixed graphs where links are specified by mutual chemical affinity as well as colocalization. We suggest that such mixed graphs will provide more accurate descriptions of functional cellular networks and their regulatory capabilities and aid in the development of large-scale predictive models of cellular behavior.
Accumulation of Neural Activity in the Posterior Insula Encodes the Passage of Time
Authors: Wittmann Marc , Simmons Alan , Aron Jennifer , Paulus Martin
Published: July 2019

The experience of time, i.e. the estimation of duration, is fundamental for perception and behavior and, therefore, essential for the survival of the individual organism. Over the last decades, neuroimaging, neurophysiological and clinical neuropsychological studies have pointed to many different brain areas involved in the processing of time. However, the core neural substrates and the processes accounting for the encoding of duration, which could form a timekeeping mechanism (essentially, a neural clock), are still unknown. Here we present evidence of neurophysiological activity in circumscribed areas of the human brain that is involved in the encoding of duration. Time-activity curves of neural activation derived from event-related functional magnetic resonance imaging (fMRI) during a time estimation task show that bilateral posterior insula as well as superior temporal and inferior parietal cortices build up activation when individuals are presented with 9 or 18 seconds tone intervals. Since the build up of neuronal activation peaks at the end of the interval, it appears that this accumulator-type activity encodes duration. Because of the close connection between posterior insula and ascending internal body signals, the accumulation of physiological changes in body states might constitute our experience of time. These results could be the starting point for a neural model of human time perception in the multiple-seconds range in which specific brain regions accumulate brain activity for the representation of duration.
Introduction of Transmembrane Inner Ear (tmie) Gene Can Recover the Hearing Impairment and Abnormal Behavior in the Circling Mouse
Authors: Shin Mi Jung , Lee Jeong-Han , Yu Dong Hoon , Kim Bong Soo , Kim Hei Jung , Kim Sung Hyun , Kim Myoung Ok , Park Channy , Hyun Byung-Hwa , Lee Sanggyu , Suh Jun-Gyo , So Hong-Seob , Park Raekil , Ryoo Zae Young
Published: July 2019

The spontaneous mutant circling mouse (cir/cir) shows a circling behavior and hearing loss. We produced transgenic mice overexpressing the causative gene, transmembrane inner ear (tmie), for the phenotypic rescue of the circling mouse. Through the continuous breeding with circling mice, the cir/cir homozygous mice carrying the transgene (cir/cir-tg) were produced. The rescued cir/cir -tg mice were able to swim in the water with proper orientation and did not show any circling behavior like wild type mice. Western blot and immunohistochemical analysis exhibited that the transgenic tmie was expressed in the inner ear. Inner and outer hair cells were recovered in the cochlea and spiral ganglion neurons were also recovered in the rescued mice. Auditory brainstem response (ABR) test demonstrated that the cir/cir -tg mice are able to respond to sound. This study demonstrates that tmie transgene can recover the hearing impairment and abnormal behavior in the circling mouse.
A coordinated phosphorylation cascade initiated by MSK1 directs RAR alpha recruitment to target gene promoters
Authors: Bruck Nathalie , Vitoux Dominique , Ferry Christine , Duong Vanessa , Bauer Annie , de The Hughes , Rochette-Egly Cecile
Published: July 2019

The nuclear retinoic acid (RA) receptor alpha (RAR&x03B1;) is a transcriptional transregulator that controls the expression of specific gene subsets through binding at response elements and dynamic interactions with coregulators, which are coordinated by the ligand. Here, we highlighted a novel paradigm in which the transcription of RAR&x03B1;-target genes is controlled by phosphorylation cascades initiated by the rapid RA activation of the p38MAPK/MSK1 pathway. We demonstrate that MSK1 phosphorylates RAR&x03B1; at S369 located in the Ligand Binding Domain, allowing the binding of TFIIH and thereby phosphorylation of the N-terminal domain at S77 by cdk7/cyclin H. MSK1 also phosphorylates Histone H3 at S10. Finally, the phosphorylation cascade initiated by MSK1 is required for the recruitment of RAR&x03B1;/TFIIH complexes to response elements and subsequently for RAR&x03B1; target genes activation. Cancer cells characterized by a deregulated p38MAPK/MSK1 pathway, do not respond to RA, outlining the essential contribution of the RA-triggered phosphorylation cascade in RA signaling.
A Physiological Role for Amyloid Beta Protein: Enhancement of Learning and Memory
Authors: Morley John , Farr Susan , Banks William , Johnson Steven , Yamada Kelvin , Xu Lin
Published: July 2019

Amyloid beta protein (A[beta]) is well recognized as having a significant role in the pathogenesis of Alzheimer's disease (AD). The reason for the presence of A[beta] and its physiological role in non-disease states is not clear. In these studies, low doses of A[beta] enhanced memory retention in two memory tasks and enhanced acetylcholine production in the hippocampus in vivo. We then tested whether endogenous A[beta] has a role in learning and memory in young, cognitively intact mice by blocking endogenous A[beta] in healthy 2-month-old CD-1 mice. Blocking A[beta] with antibody to A[beta] or DFFVG (which blocks A[beta] binding) or decreasing A[beta] expression with an antisense directed at the A[beta] precursor APP all resulted in impaired learning in T-maze foot-shock avoidance. Finally, A[beta]1-42 facilitated induction and maintenance of long term potentiation in hippocampal slices, whereas antibodies to A[beta] inhibited hippocampal LTP. These results indicate that in normal healthy young animals the presence of A[beta] is important for learning and memory.
A Targeted Therapeutic Rescues Botulinum Toxin-A Poisoned Neurons
Authors: Ray Prabhati , Singh Bal Ram , Ray Radharaman , Zhang Peng , Li Dan , Keller James , Adler Michael
Published: July 2019

Botulinum neurotoxin (BoNT), a Category A biothreat agent, is the most potent poison known to mankind. Currently no antidote is available to rescue poisoned synapses. BoNT acts specifically by blocking neurotransmission primarily at peripheral nerve-muscle junctions causing severe flaccid muscle paralysis, which is fatal if proper medical care is not provided. The neurotoxin acts by specifically entering the presynaptic nerve endings where it interferes with the biochemical machinery involved in the process of neurotransmitter release, i.e., neuroexocytosis. Most serotypes of BoNT are known to remain active for weeks to months after entering the nerves, but BoNT/A is the most potent and long lasting in causing muscle paralysis. An effective medical countermeasure strategy requires developing a drug that could rescue poisoned neuromuscular synapses, and would include its efficient delivery specifically to presynaptic nerve terminals. Here we report rescuing of botulinum poisoned nerve cells by Mastoparan-7 (Mas-7), a peptide constituent of bee venom, that was delivered through a drug delivery vehicle (DDV) constructed from the non-toxic fragment of botulinum neurotoxin itself. We found that Mas-7 that was delivered into BoNT/A intoxicated cultured mouse spinal cord cells restored over 40% of stimulated neurotransmitter release. The rescue of the cell poisoning did not occur from inhibition of the endopeptidase activity of BoNT/A against its well known substrate, SNAP-25 that is mechanistically involved in the exocytosis process. Rather, Mas-7 induced a physiological host response apparently unrelated to SNAP-25, but linked to the phospholipase signal transduction pathway. In addition to providing the first effective antidote against botulism, our results open new avenues to study the mechanism of exocytosis, and also to examine an alternative cellular mechanism of botulinum neurotoxin action. An effective BoNT-based DDV can also be utilized for drug delivery against many neuronal and neuromuscular disorders.
Dimension-based attention in the recognition of facial identity and facial expression
Authors: Lin Zhicheng
Published: July 2019

Although the human visual system is constantly flooded with sensory information, the brain is remarkable in inferring structures from the massive inputs and selectively attending to behaviorally relevant information. However, how the two processes interact remains largely unknown. Can top-down attention efficiently select the task-relevant dimension (e.g. gender) during face recognition to override interference in the task-irrelevant dimension (e.g. expression)? To address this issue, participants were asked to classify real face images according to gender or expression, which were preceded by other faces (masked priming task) or words (face-word Stroop task). Results show that face classification was 1) affected by the task-relevant but not the task-irrelevant dimension of the preceding faces, and 2) modulated by words depicting the task-relevant but not the task-irrelevant dimension of the face. These results suggest that high level dimensions such as facial expression and facial identity can serve as units of attentional selection, possibly due to the late binding of the two dimensions.
Optimization of the Ugi reaction using parallel synthesis and automated liquid handling
Authors: Bradley Jean-Claude , Mirza Khalid , Owens Kevin , Osborne Tom , Williams Antony
Published: July 2019

The Ugi reaction has proved to be a convenient way to quickly create diverse libraries of compounds. It involves the reaction of an amine, an aldehyde, a carboxylic acid and an isonitrile typically in methanol at room temperature. The Ugi reaction has often been used as a tool in the synthesis of pharmacologically active molecules. It has been observed that Ugi products sometimes precipitate in pure form from the reaction mixture. This is a very fortunate outcome since the reaction can then be easily scaled up without requiring costly purification procedures such as chromatography. It would be most beneficial to optimize the Ugi product yield as obtained directly from filtering the reaction mixture without further treatment. To this end we utilized a 48-slot Mettler-Toledo MiniBlock equipped with filtration tubes. A Mettler-Toledo MiniMapper automated liquid handler was used to deliver the reagents and solvent. The parameters of interest were the concentration, the solvent composition and the excess of some of the reagents. This work was performed under Open Notebook Science conditions and links to relevant laboratory notebook pages are provided.
Proposing a life cycle land use impact calculation methodology
Authors: Achten Wouter , Vandenbempt Pieter , Lemaître Patrick , 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. Earlier our research group presented a methodology based on the ecosystem exergy concept. The ecosystem exergy concept suggests that ecosystems develop towards more effective degradation of energy fluxes passing through the system. The concept is argued to be derivable from two axioms: the principles of (i) maximum exergy storage and the (ii) maximum exergy dissipation. In this paper we present a methodology to assess impacts of human induced land use occupation, in which we make a difference between functional and structural land use impacts. The methodology follows a dynamic multi-indicator approach looking at mid-point impacts on soil fertility, soil structure, biomass production, vegetation structure, on-site water balance and biodiversity. The impact scores are calculated as a relative difference with a reference system. We propose to calculate the impact by calculating the land quality change between the former and the actual land use relative to the quality of the potential natural vegetation. Impact scores are then aggregated, as endpoint impacts, in (i) structural land use impact (exergy storage capacity) and (ii) functional land use impact (exergy dissipation capacity). For aggregation of the relative mid-point impact scores no characterization factor is used. In order to fit this impact calculation in the LCA framework the end-point impact scores are multiplied by a LCA component, a component that enables us to report the impact per functional unit.
Working memory: Is it the new IQ?
Authors: Alloway Tracy Packiam , Alloway Ross
Published: July 2019

Working memory, our ability to process and remember information, is linked to a range of cognitive activities from reasoning tasks to verbal comprehension. There is also extensive evidence of the relationship between working memory and learning outcomes. However, some researchers suggest that working memory is simply a proxy for IQ and does not make a unique contribution to learning outcomes. Here we show that children's working memory skills at 5 years of age was the best predictor of reading, spelling, and math outcomes six years later. IQ, in contrast, accounted for a smaller portion of unique variance to reading and math skills, and was not a significant predictor of spelling performance. Our results demonstrate that working memory is not a proxy for IQ, but rather represents a dissociable cognitive skill with unique links to learning outcomes. Critically, we find that working memory at the start of formal education is a more powerful predictor of subsequent academic success than IQ. This result has important implications for education, particularly with respect to developing intervention and training. It appears that we should target our efforts in developing working memory skills in order to see gains in learning.
Identification of 22 novel mutations in patients with Glanzmann's thrombasthenia
Authors: Kannan Meganathan , Ahmad Firdos , Yadav Birendra , Ethayathulla Abdul , Kumar Rajive , Choudhry Ved , Saxena Renu
Published: July 2019

Glanzmann's thrombasthenia (GT) is an autosomal recessive inherited platelet function defect that characterized by reduction in, or absence of, platelet aggregation in response to multiple physiologic agonists. GT is characterized by normal platelet count, prolonged bleeding time, and abnormal clot retraction. The defect is caused by mutations in the genes encoding GPIIb or GPIIIa that result in qualitative or quantitative abnormalities of the platelet membrane GPIIb/IIIa. GT occurs in high frequency in certain ethnic populations with an increased incidence of consanguinity, such as Indians, Iranians, Iraqi Jews, Palastinian and Jordanian Arabs and French gypsies. Forty-five unrelated patients of GT were enrolled in the study to identify the causative molecular defects and also to correlate the genotype with the phenotype. Molecular modeling was performed for the novel missense mutations. The current study identifies 22 novel mutations in these patients. Missense mutations were identified as the defects responsible for most of the GT patients (59%). Even though missense was common, the study concludes that the genetic defect is heterogeneous in nature and difficult to design a DNA marker for carrier detection in GT.
Estimating body Mass and Nutritional Status from Subadult Hominin Skeletons
Authors: Robbins Gwendolyn
Published: July 2019

Hominin body size and shape are key components to reconstructing phylogeny, life history, adaptation, and behavior in ancestral populations^1^. For adults, geometric properties of the femoral midshaft cross-section are used to infer locomotor behavior^2-5^, subsistence practices^6-7^, and functional adaptations^8-10^. Recently research has focused on patterns of compact bone ontogeny, particularly in regard to changes in bone strength with the acquisition of bipedal locomotion^11-13^ and examining population differences in ontogenetic trajectories for subadult humans^14-16^ and Neandertals^16^. Because femoral midshaft geometry is primarily shaped by biomechanical strains-weight bearing, locomotion, and muscle action-ontogenetic research requires estimates of body mass from the skeleton. Currently we use the width of the distal end of the femur to estimate subadult body mass but articular ends are constrained by pressures for joint congruence. Here I demonstrate the strong and consistent scaling relationship between body mass and femoral torsional strength (J) derived from measurement of midshaft cross-section geometry. Bone ends are most significantly affected by locomotor strain during the second year of life, during the initial acquisition of obligate bipedalism, after that time they are increasingly constrained by joint congruence. Results of a comparison of body mass for body size in prehistoric populations support the hypothesis that the midshaft is also a more sensitive indicator of population differences in body mass and activity levels during ontogeny. The femoral midshaft can be used to detect starvation and growth disruption in past populations because there is a mechano-biological interaction effect whereby disruptions in nutritional, metabolic and hormonal status lead to low body mass and activity levels^1, 11-13, 17-22^.
Tumor induction by disruption of the Dnmt1, PCNA and UHRF1 interactions.
Authors: Hervouet Eric , Lalier Lisenn , Debien Emilie , Cheray Mathilde , Geairon Audrey , Rogniaux Helene , Vallette Francois , Cartron Pierre-Francois
Published: July 2019

The low level of DNA methylation in tumors compared to the level of DNA methylation in their normal-tissue counterparts or global DNA hypomethylation was one of the first epigenetic alterations to be found in human cancer^1,2^. While the contribution of genome hypomethylation in cancer development and progression is explained by several mechanisms: chromosomal instability, loss of imprinting, and reactivation of transposable elements^3, 4^, the molecular causes of genome hypomethylation remain unclear. Indeed, despite the central roles of the DNA methyltransferases (Dnmts) in the establishment and maintenance of the DNA methylation, no clear consensus appears between the reduction of the Dnmts expression and the genome hypomethylation in human cancers^5^. Nevertheless, the cancer-associated genome hypomethylation could be explained by the disruption of interactions existing between Dnmts and the DNA replication and DNA repair proteins because these interactions play a crucial role in the DNA methylation in mammalian cells^6-8^. We here demonstrate that the disruption of the Dnmt1/PCNA and Dnmt1/UHRF1 interactions induce the genome hypomethylation and act as oncogenic factors promoting the tumorigenesis. We also identify the Akt- and/or PKC-mediated phosphorylations of Dnmt1 as both initiators of these disruptions and as a hallmark conferring poor prognosis in glioma patients.
Global warming affected some morphological characters of Pistachio trees (Pistacia vera L.)
Authors: Javanshah Amanollah
Published: July 2019

Pistachio is one of the main horticulture crops in Iran where have the first cultivation and exportation position in the world. Climate change has already affected species distribution shifts in many parts of the world and more impacts are expected for the future, yet few studies have aimed for a general understanding of the regional basis for species vulnerability. In this research meteorology data of four months (December, January, February and March) from 1991 to 2008 and Phenology data of six pistachio cultivars that ranked in 3 groups: early flowering (Kalehghoochi and Ahmadaghaei), mid flowering (Momtaz and Amiri) and late flowering (Akbari and Shahpasand) during summer of 1997, 2001-5, and 2007 were studied in Kerman province. The evaluated factors included leaf area, normal and abnormal leaves. The results showed the mean of temperature on March has significant increasing during 1991 to 2008 and fluctuations between years increased after 1999 in December, January and February. Phenological characters including leaf area and number of normal and abnormal leaves were different each year that abnormality leaves in early and late flowering cultivars had negative correlation with mean temperature of December and mid flowering cultivars had positive correlation with mean temperature of February. The level of leaf area changing in Ahamadaghaei cultivar was less than other cultivars but kallehghoochi and Akbari had the highest range which can probably be a good marker for determining the effects of temperature changes in winter on production level.
Polar Mapper: a computational tool for integrated visualization of protein interaction networks and mRNA expression data
Authors: Gonçalves Joana P. , Grãos Mário , Valente Andre
Published: July 2019

Polar Mapper is a computational application for exposing the architecture of protein interaction networks. It facilitates the system-level analysis of mRNA expression data in the context of the underlying protein interaction network. Preliminary analysis of a human protein interaction network and comparison of yeast oxidative stress and heat shock gene expression responses are addressed as case studies.
Down-regulation of Survivin enhances sensitivity to BPR0L075 in human cancer cells via caspase-independent mechanisms
Authors: Cheung Chun Hei Antonio , Kuo Ching-Chuan , Chang Chi-Yen , Coumar Mohane Selvaraj , Hsieh Hsing-Pang , Chang Jang-Yang
Published: July 2019

Background:

BPR0L075 [6-methoxy-3-(3',4',5'-trimethoxy-benzoyl)-1H-indole] is a novel anti-cancer compound. It inhibits tubulin polymerization and induces mitochondrial-dependent apoptosis in various human cancer cells with different multi-drug resistance (MDR) status. Over-expression of an anti-apoptotic molecule, survivin, causes drug-resistance in various cancers. Survivin inhibits apoptosis by interfering caspase-3 and promotes cell growth by stabilizing microtubule networks. Here, we determined the effects of down-regulation of survivin in BPR0L075 (L075) treatment. Methods: Western blot analysis was used to determine the expression level of survivin in L075-untreated/-treated human oral carcinoma KB and nasopharyngeal carcinoma HONE-1 cancer cells. siRNA was used to down-regulate endogenous survivin. MTT cell viability assay, real-time caspase-3 activity assay and immuno-fluorescence microscopy were used to analyze downstream effects.

Results:

Survivin expression was up-regulated in both KB and HONE-1 cells in response to L075 treatment. Down-regulation of survivin induced hyper-sensitivity to L075 in KB and re-stored sensitivity to L075 in KB-derived L075-resistant KB-L30 cancer cells. At the molecular level, down-regulation of survivin induced changes in microtubule dynamics in both KB and KB-L30 cells. Surprisingly, down-regulation of survivin did not enhance the activity of caspase-3 in L075 therapy. Instead, down-regulation of survivin induced translocation of the apoptosis-inducing factor (AIF) from cytoplasm to nucleus. Conclusion: Down-regulation of survivin improved drug sensitivity to L075 in both KB and L075-resistant KB-L30 cancer cells, possibly through a tubulin-dependent and caspase-independent mechanism. We suggest that combining BPR0L075 and survivin inhibitor may give better clinical outcome than the use of BPR0L075 monotherapy in future clinical trials.
Rabbit Muscle Actin Polymerization changes by Ultraviolet –B radiation
Authors: Mukherjee Anita , Attri Arun Kumar
Published: July 2019

Increase in Ultraviolet-B flux from the Sun has the potential to alter the protein in mammals. Rabbit muscle was processed and filtered to extract G-actin, which was tested for its protein concentration before exposing to UV-B. It was found that polymerization of actin does get affected exposure of actin monomers to UV-B radiation. Inside the cell, there are many actin binding proteins which might be playing crucial role in G-actin to F-actin formation.
Nucleosome-mediated cooperativity between transcription factors
Authors: Mirny Leonid
Published: July 2019

Cooperative binding of transcription factors (TFs) to cis-regulatory regions (CRRs) is essential for precision of gene expression in development and other processes. The classical model of cooperativity requires direct interactions between TFs, thus constraining the arrangement of TFs sites in a CRR. On the contrary, genomic and functional studies demonstrate a great deal of flexibility in such arrangements with variable distances, numbers of sites, and identities of the involved TFs. Such flexibility is inconsistent with the cooperativity by direct interactions between TFs. Here we demonstrate that strong cooperativity among non-interacting TFs can be achieved by their competition with nucleosomes. We find that the mechanism of nucleosome-mediated cooperativity is mathematically identical to the Monod-Wyman-Changeux (MWC) model of cooperativity in hemoglobin. This surprising parallel provides deep insights, with parallels between heterotropic regulation of hemoglobin (e.g. Bohr effect) and roles of nucleosome-positioning sequences and chromatin modifications in gene regulation. Characterized mechanism is consistent with numerous experimental results, allows substantial flexibility in and modularity of CRRs, and provides a rationale for a broad range of genomic and evolutionary observations. Striking parallels between cooperativity in hemoglobin and in transcription regulation point at a new design principle that may be used in range of biological systems.
Emergence and Fixing of Antiviral Resistance in Influenza A Via Recombination and Hitch Hiking
Authors: Niman Henry
Published: July 2019

The dramatic rise of oseltamivir resistance in the H1N1 serotype in the 2007/2008 season and the fixing of H274Y in the 2008/2009 season has raised concerns regarding individuals at risk for seasonal influenza, as well as development of similar resistance in the H5N1 serotype. Previously, oseltamivir resistance produced changes in H1N1 and H3N2 at multiple positions in treated patients. In contrast, the recently reported resistance involved patients who had not recently taken oseltamivir. Moreover, the resistance was limited to the H1N1 which had acquired H274Y. Using phylogenetic analysis I show that the fixing of H274Y was due to hitch hiking on a genetic background that acquired key changes from another circulating sub-clade. H274Y jumped from clade 2C (Hong Kong/2562/2006-like) to clade 1 (New Caledonia/20/1999-like) to clade 2B (Brisbane/59/2007-like) which included multiple introductions. Sub-clades that had acquired key changes on the neuramindase and hemagglutinin genes expanded and fixed of H274Y on H1N1. These changes led to the spread of adamantane resistance on clade 2C outside of Asia, followed by the spread of oseltamivir resistance in 2007/2008 and the fixing of H274Y in 2008/2009. The hemagglutinin change, A193T, was a key component and the coincident polymorphism, S193F, was linked to the fixing of adamantane resistance in H3N2. The aggregation of key polymorphisms onto different genetic backgrounds supports a mechanism of homologous recombination between co-circulating influenza sub-clades, and provides a rationale for the prediction of vaccine targets and emergence of antiviral resistance.
Predictability engenders more efficient neural responses
Authors: Eagleman David , Pariyadath Vani , Churchill Sara
Published: July 2019

The neural response to a stimulus diminishes with repeated presentations, a phenomenon known as repetition suppression. We here use neuroimaging to demonstrate that repetition suppression appears to be a special case of "prediction suppression"--that is, the brain shows diminishing activity when subsequent stimuli in a train are predictable. This demonstration supports the hypothesis that the brain dynamically leverages prediction to minimize energy consumption.
Cognitive epidemiology of ethnic health and the CHRM2 vagal vigour hypothesis
Authors: Frye Roy
Published: July 2019

Ethnic populations representing areas throughout California were compared regarding cognitive ability, socioeconomic position, and mortality. Cognition and socioeconomic position were inversely correlated with mortality. The single nucleotide polymorphism rs8191992 in the M2 muscarinic receptor gene (CHRM2) was previously linked to IQ and modulation of vagal tone. The CHRM2 vagal vigour hypothesis posits that variation at rs8191992 alters the binding site for a brain-expressed microRNA (hsa-mir-383) thereby changing expression of brain M2 muscarinic receptors to cause pleiotropic effects on cognition and vagus nerve signalling which then affects health via the vagal cholinergic anti-inflammatory pathway. This may help explain ethnic health differences, including the Hispanic Health Paradox, since ethnic differences in rs8191992 allele frequencies correspond to ethnic differences in systemic inflammation and mortality. The rs8191992 A-allele may contribute to the clustering of low IQ and low vagal tone with higher substance abuse, externalizing psychopathology, depression, systemic inflammation, metabolic syndrome, and cardiovascular disease.
The Necessity of Darwin
Authors: Sessions Stanley , Macgregor Herbert
Published: July 2019

February 12th, 2009 was Charles Darwin's 200th birthday, and November 2009 represents the 150th anniversary of the publication of his transformative book, The Origin of Species. It seems a good time to look back and assess Darwin's legacy within the perspective of current knowledge of genetics, cytogenetics, and molecular biology in general. Although a comprehensive understanding of evolution would no doubt have emerged eventually, it is difficult to imagine how anyone could have matched Darwin’s prodigious and sustained efforts, as well as his talent for explaining things in simple terms.
Contaminant Trapping Behind Large Dams: A Mini-Review
Authors: Rayne Sierra , Friesen Ken
Published: July 2019

It appears likely that the installation of many large dams on major rivers worldwide over the past century has led to large and complex contaminant loadings becoming trapped in the sediments behind these dams. Future planned large dam removal efforts or unintentional breaches may result in substantial contaminant releases downstream. We review the current state of the art regarding knowledge of contaminant loadings behind large dams and potential downstream impacts following dam breaches.
Geometric bionics: Lotus effect helps polystyrene nanotube films get good blood compatibility
Authors: Mao Chun , Zhao Wen-Bo , Luo Wen-Ping , Liang Cun-Xia , Hou Xiao-Mei , Huang Xiao-Hua , Liu Hong-Ke , Xiao Ying-Hong , Bao Jian-Chun , Shen Jian
Published: July 2019

Various biomaterials have been widely used for manufacturing biomedical applications including artificial organs, medical devices and disposable clinical apparatus, such as vascular prostheses, blood pumps, artificial kidney, artificial hearts, dialyzers and plasma separators, which could be used in contact with blood^1^. However, the research tasks of improving hemocompatibility of biomaterials have been carrying out with the development of biomedical requirements^2^. Since the interactions that lead to surface-induced thrombosis occurring at the blood-biomaterial interface become a reason of familiar current complications with grafts therapy, improvement of the blood compatibility of artificial polymer surfaces is, therefore a major issue in biomaterials science^3^. After decades of focused research, various approaches of modifying biomaterial surfaces through chemical or biochemical methods to improve their hemocompatibility were obtained^1^. In this article, we report that polystyrene nanotube films with morphology similar to the papilla on lotus leaf can be used as blood-contacted biomaterials by virtue of Lotus effect^4^. Clearly, this idea, resulting from geometric bionics that mimicking the structure design of lotus leaf, is very novel technique for preparation of hemocompatible biomaterials.
Learning alters theta-nested gamma oscillations in inferotemporal cortex
Authors: Kendrick Keith , Zhan Yang , Fischer Hanno , Nicol Alister , Zhang Xuejuan , Feng Jianfeng
Published: July 2019

How coupled brain rhythms influence cortical information processing to support learning is unresolved. Local field potential and neuronal activity recordings from 64- electrode arrays in sheep inferotemporal cortex showed that visual discrimination learning increased the amplitude of theta oscillations during stimulus presentation. Coupling between theta and gamma oscillations, the theta/gamma ratio and the regularity of theta phase were also increased, but not neuronal firing rates. A neural network model with fast and slow inhibitory interneurons was developed which generated theta nested gamma. By increasing N-methyl-D-aspartate receptor sensitivity similar learning-evoked changes could be produced. The model revealed that altered theta nested gamma could potentiate downstream neuron responses by temporal desynchronization of excitatory neuron output independent of changes in overall firing frequency. This learning-associated desynchronization was also exhibited by inferotemporal cortex neurons. Changes in theta nested gamma may therefore facilitate learning-associated potentiation by temporal modulation of neuronal firing.
Enhanced display of scientific articles using extended metadata
Authors: Page Roderic
Published: July 2019

Although the Web has transformed science publishing, scientific papers themselves are still essentially "black boxes", with much of their content intended for human readers only. Typically, computer-readable metadata associated with an article is limited to bibliographic details. By expanding article metadata to include taxonomic names, identifiers for cited material (e.g., publications, sequences, specimens, and other data), and geographical coordinates, publishers could greatly increase the scientific value of their digital content. At the same time this will provide novel ways for users to discover and navigate through this content, beyond the relatively limited linkage provided by bibliographic citation.As a proof of concept, my entry in the Elsevier Grand Challenge extracted extended metadata from a set of articles from the journal Molecular Phylogeny and Evolution and used it to populate a entity-attribute-value database. A simple web interface to this database enables an enhanced display of the content of an article, including a map of localities mentioned either explicitly or implicitly (through links to geotagged data), taxonomic coverage, and both data and citation links. Metadata extraction was limited to information listed in tables in the articles (such as GenBank sequences and specimen codes), the body of the article wasn't used. This restriction was deliberate, in order to demonstrate that making extended metadata available doesn't require a journal's publisher to make the full-text freely available (although this is desirable for other reasons).