bluuebunny/crossref_metadata_2025 huggingface dataset:
Implications of uncertainty for Canada’s commercial hunt of harp seals (Pagophilus groenlandicus)
Authors: Leaper Russell , Matthews Justin
Published: July 2019

The Canadian government's current management procedure for harp seals is described by Fisheries and Oceans Canada as using the Precautionary Approach. Employing a similar underlying population model, we simulated the effects of uncertainty involving bias in estimates of human induced mortality, natural mortality, and pup production estimates as a set of robustness trials. Our results indicated that for the range of annual total allowable catches (TAC) considered and set for Canada’s commercial harp seal hunt (250,000 – 350,000), there were plausible circumstances under which the government's management procedures failed to meet their own conservation objectives. By contrast, a precautionary management regime should be robust to such levels of uncertainty. For some scenarios the current management strategy, although not fully specified, is likely to maintain a high TAC despite a declining population. In particular, once a high TAC has been set, the assessments are unlikely to provide the necessary evidence that the TAC should be reduced until the population is at a low level. Hence there is a substantial risk that the population may be depleted below the ‘minimum’ (N50) and ‘critical’ (N30) population reference points. There is a need for a management procedure based on risk analysis to be fully specified and tested. In the interim, reducing TACs to within limits calculated from a well-established precautionary procedure, such as Potential Biological Removal, would be a step towards more precautionary management.
Intra- and inter-individual genetic differences in gene expression
Authors: Cowley Mark , Cotsapas Chris , Williams Rohan , Chan Eva , Pulvers Jeremy , Liu Michael , Luo Oscar , Nott David , Little Peter
Published: July 2019

Genetic variation is known to influence the amount of mRNA produced by a gene. Given that the molecular machines control mRNA levels of multiple genes, we expect genetic variation in the components of these machines would influence multiple genes in a similar fashion. In this study we show that this assumption is correct by using correlation of mRNA levels measured independently in the brain, kidney or liver of multiple, genetically typed, mice strains to detect shared genetic influences. These correlating groups of genes (CGG) have collective properties that account for 40-90% of the variability of their constituent genes and in some cases, but not all, contain genes encoding functionally related proteins. Critically, we show that the genetic influences are essentially tissue specific and consequently the same genetic variations in the one animal may up-regulate a CGG in one tissue but down-regulate the same CGG in a second tissue. We further show similarly paradoxical behaviour of CGGs within the same tissues of different individuals. The implication of this study is that this class of genetic variation can result in complex inter- and intra-individual and tissue differences and that this will create substantial challenges to the investigation of phenotypic outcomes, particularly in humans where multiple tissues are not readily available.
The impact of Bt cotton on poor households in rural India
Authors: Subramanian Arjunan , Qaim Matin
Published: July 2019

The impact of genetically modified (GM) crops on the poor in developing countries is still the subject of controversy. While previous studies have examined direct productivity effects of Bacillus thuringiensis (Bt) cotton and other GM crops, little is known about wider socioeconomic outcomes. We develop a microeconomic modeling approach and use comprehensive survey data from India to analyze welfare and distribution effects in a typical village economy. Bt cotton adoption increases aggregate employment with interesting gender implications. Likewise, aggregate household incomes rise, including for poor and vulnerable farmers, suggesting that Bt cotton contributes to poverty reduction and rural development.
Selective insectivory in Nymphaea nouchali Burm. f.
Authors: Tetali Pundarikakshudu , Sutar Shrikant , Tetali Sujata
Published: July 2019

Carnivorous plants comprise roughly 0.24 percent of the flowering plants, or 640 species represented in 12 families. Yet they are regarded as miracula naturae. Over fifty percent of these taxa are represented in a single family, namely Lentibulariaceae. Carnivorous plants are generally insectivorous, and carnivory in flowering plants is generally found in taxa that are adapted to nutrient-deficient habitats. The extra nutrients such plants acquire by special ways serve merely as supplements. The origin and evolution of carnivorous plants is a mystery in the phylogenetic tree of angiosperms, they often appear without a clear linkage. Here, we report that Nymphaea nouchali Burm. f. (a cultivar of var. cernua), a large aquatic member of the family Nymphaeaceae, indulges in a primitive form of insectivory and represents the missing evolutionary link. To the best of our knowledge, an insectivorous flower was not reported in flowering plants before.
The unique mouse pollination in an orchid species
Authors: Wang Yong , Zhang Yang , Ma Xiao-Kai , Dong Li
Published: July 2019

The Chinese orchid, Cymbidium serratum, is pollinated by the wild mountain mouse Rattus fulvescens. The flowers use both odor and colour as attractants, and provide labellum as food reward for the pollinators. The mice pollinate the flowers during their endeavour to eat the labellums.
Affymetrix probes containing runs of contiguous guanines are not gene-specific
Authors: Upton Graham , Langdon William , Harrison Andrew
Published: July 2019

High Density Oligonucleotide arrays (HDONAs), such as the Affymetrix HG-U133A GeneChip, use sets of probes chosen to match specified genes, with the expectation that if a particular gene is highly expressed then all the probes in the designated probe set will provide a consistent message signifying the gene's presence. However, we demonstrate by data mining thousands of CEL files from NCBI's GEO database that 4G-probes (defined as probes containing sequences of four or more consecutive guanine (G) bases) do not react in the intended way. Rather, possibly due to the formation of G-quadruplexes, most 4G-probes are correlated, irrespective of the expression of the thousands of genes for which they were separately intended. It follows that 4G-probes should be ignored when calculating gene expression levels. Furthermore, future microarray designs should make no use of 4G-probes.
Systems biology of energetic and atomic costs in the yeast transcriptome, proteome, and metabolome
Authors: Barton Michael , Papp Balazs , Delneri Daniel , Oliver Stephen , Rattray Magnus , Bergman Casey
Published: July 2019

Proteins vary in their cost to the cell and natural selection may favour the use of proteins that are cheaper to produce. We develop a novel approach to estimate the amino acid biosynthetic cost based on genome-scale metabolic models, and directly investigate the effects of biosynthetic cost on transcriptomic, proteomic and metabolomic data in Saccharomyces cerevisiae. We find that our systems approach to formulating biosynthetic cost produces a novel measure that explains similar levels of variation in gene expression compared with previously reported cost measures. Regardless of the measure used, the cost of amino acid synthesis is weakly associated with transcript and protein levels, independent of codon usage bias. In contrast, energetic costs explain a large proportion of variation in levels of free amino acids. In the economy of the yeast cell, there appears to be no single currency to compute the cost of amino acid synthesis, and thus a systems approach is necessary to uncover the full effects of amino acid biosynthetic cost in complex biological systems that vary with cellular and environmental conditions.
A reassessment of the Carnot cycle and the concept of entropy
Authors: Chandrasekhar Sosale
Published: July 2019

It is argued that the Carnot cycle is a highly inaccurate representation of a steam engine, and that the net work obtained in its operation would be zero. This conclusion is also supported by an elementary mathematical approach, which re-examines the work done in the four individual steps of the cycle. An important consequence of this is that the concept of entropy, originally proposed on the basis of the Carnot theorem, may not be a fundamentally valid thermodynamic quantity. Also, the experimental approach generally adopted in the determination of entropy is questionable, and the importance of increasing randomness in natural processes not universally valid. In fact, a more viable basis, at least vis-à-vis chemical reactions, appears to be the ratio of mass to energy, which is apparently maximized in the case of a spontaneous process.
Immunogenicity of human spermatozoa
Authors: Chatterjee Jhinuk
Published: July 2019

Investigation and experimental design of the study was basically aimed at developing insight into the antigenicity of spermatozoa-associated proteins. Apart from studying the natural antigenicity of washed whole spermatozoa, their immunogenicity was also demonstrated in vitro. The whole live spermatozoa were immobilized and agglutinated in vitro by the antibodies they induced in the laboratory model - a female rabbit. A regular immunization routine induced a high titre of antisperm polyclonal antibodies. To prepare a spermatozoa specific antigen which will not produce a cross-reacting antibody against other human tissues, only the motile and live spermatozoa were selected for antigen preparation. In investigation the laboratory-bred female rabbits were used as the bioactive system of production of antisperm antibody. Agglutination of whole spermatozoa has been observed on slides. The technique though simple is highly eloquent; clumping of spermatozoa confirms the existence of antisperm antibodies in the serum under examination. The results show that nature and pattern of immobilization of active motile spermatozoa are different as observed in different graphs of immobilization. The variation in spermatozoal population in antigen distribution on individual spermatozoa is reflected in different patterns of agglutination.
Immunogenicity of human spermatozoa
Authors: Chatterjee Jhinuk , Chattopadhyay Sukumar
Published: July 2019

Investigation and experimental design of the study was basically aimed at developing insight into the antigenicity of spermatozoa-associated proteins. Apart from studying the natural antigenicity of washed whole spermatozoa, their immunogenicity was also demonstrated in vitro. The whole live spermatozoa were immobilized and agglutinated in vitro by the antibodies they induced in the laboratory model - a female rabbit. A regular immunization routine induced a high titre of antisperm polyclonal antibodies. To prepare a spermatozoa specific antigen which will not produce a cross-reacting antibody against other human tissues, only the motile and live spermatozoa were selected for antigen preparation. In investigation the laboratory-bred female rabbits were used as the bioactive system of production of antisperm antibody. Agglutination of whole spermatozoa has been observed on slides. The technique though simple is highly eloquent; clumping of spermatozoa confirms the existence of antisperm antibodies in the serum under examination. The results show that nature and pattern of immobilization of active motile spermatozoa are different as observed in different graphs of immobilization. The variation in spermatozoal population in antigen distribution on individual spermatozoa is reflected in different patterns of agglutination.
Reduced contribution of the ipsilateral primary motor cortex to force modulation with short-term motor learning in humans: An NIRS study
Authors: Shibuya Kenichi , Iwadate Masako , Sadamoto Tomoko
Published: July 2019

How is muscle force modulated during hand exercise? Oxygenation in the contralateral primary motor cortex (M1) has been observed to vary considerably across trials of repetitive handgrip exercise. No linear relationship was observed between the average value of oxygenation determined by a block design study and the force of the handgrip. We found reduced oxygenation in the ipsilateral M1 and unchanged oxygenation in the contralateral M1 during repetitive static handgrip exercises (40% and 60% maximal voluntary contraction; 10 s exercise/75 s rest; 5 sets), which might be due to short-term motor learning. These results support the hypothesis that the ipsilateral M1 might functionally compensate for the contralateral M1 in force modulation during unilateral exercises.
A Study on the Origin of Peroxisomes: Possibility of Actinobacteria Symbiosis
Authors: Narendra Duhita , Satoshi Saruhashi , Kazuo Hamada , Daisuke Miyata , Tokumasa Horiike , Takao Shinozawa
Published: July 2019

The origin of peroxisomes as having developed from the endoplasmic reticulum (ER) was proposed on the basis of the similarity between some peroxisomal proteins and ER proteins, and the localization of some peroxisomal proteins on the ER. To study the evolutionary distance between peroxisomes and ER and Prokaryotes, we carried out a phylogenetic analysis of CDC48 (cell division control 48) and its homologs, including ER-localized CDC48, CDC48 homologs in Prokaryotes and peroxisome-localized PEX1 and PEX6. A similarity search analysis of peroxisomal protein sequences to prokaryotic protein sequences using BLAST at several thresholds (E-values) was also done. We propose Actinobacteria symbiosis for the origin of peroxisomes based on the following evidence: (1) PEX1 and PEX6 are close in distance to CDC48 homologs in Actinobacteria, and these distances are closer than to ER-localized CDC48. (2) Actinobacteria proteins show the highest degree of similarity to peroxisomal proteins compared with other prokaryotes.
The non-obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine
Authors: Buchwalow Igor , Cacanyiova Sona , Neumann Joachim , Samoilova Vera , Boecker Werner , Kristek Frantisek
Published: July 2019

The concept of Endothelium Derived Relaxing Factor (EDRF), put forward by Furchgott in the earlier 80s of the past century, implies that nitric oxide (NO) produced by NO synthase (NOS) in the endothelium in response to acetylcholine (ACh) passively diffuses to the underlying vascular smooth muscle cells (VSMC) thereby reducing vascular tension. It was thought that VSMC do not express NOS by themselves, but to the time of those studies immunohistochemical techniques were not what they are now. State-of-the-art immunohistochemistry permits nowadays to localize NOS both to the endothelium and to VSMC. However, the principal question remained unanswered, is the NO generation by VSMC physiologically relevant? We hypothesized that the destruction of the vascular wall anatomical integrity by rubbing the blood vessel intimal surface may increase vascular superoxides that, in turn, reduce NO bioactivity. To address this issue, we examined ACh-induced vasorelaxation in endothelium-deprived blood vessels under protection against oxidative stress and found that superoxide scavengers - tempol and N-acetyl-L-cysteine - restored vasodilatory responses to ACh in endothelium-deprived blood vessels without influencing the vascular wall tension in intact blood vessels. Herewith we provided the first evidence that VSMC can release NO in amounts sufficient to account for the vasorelaxatory response to ACh. In contrast to the commonly accepted concept of the obligatory role of endothelial cells in the relaxation of arterial smooth muscle, the local NO generation by VSMC can modulate vascular functions in an endothelium-independent manner.
A novel regulator of the p53-mediated mitochondrial apoptotic pathway
Authors: Ahn Bo Young , Trinh Diane , Zajchowski Laura , Kim Sung-Woo
Published: July 2019

The p53 tumor suppressor protein induces apoptosis in response to genotoxic and environmental stress. Recent studies have revealed the existence of a transcription-independent mitochondrial p53 apoptosis pathway, however the mechanism regulating p53 translocation to mitochondria and subsequent initiation of apoptosis was not known. Here, we show that Tid1, also known as mtHsp40 or Dnaja3, interacts with p53 and directs its translocation to mitochondria in cells exposed to hypoxia. Overexpression of Tid1 in tumor cells promoted mitochondrial localization of both wildtype and mutant forms of p53 and was able to restore the pro-apoptotic activity of mutant p53 proteins that were otherwise unable to induce apoptosis. Tid1's mitochondrial signal sequence and DnaJ domain were both required for the movement of the p53-Tid1 complex from the cytosol to the mitochondria. Our findings establish Tid1 as a novel regulator of p53 localization and apoptotic function.
Satellite Images Show the Movement of Floating Sargassum in the Gulf of Mexico and Atlantic Ocean
Authors: Gower Jim , King Stephanie
Published: July 2019

The question of the origin, distribution and fate of the floating seaweed Sargassum has fascinated sailors and scientists from the time of Columbus. Observations from ships are hampered by the large and variable area over which Sargassum is dispersed. Here we use satellite imagery to present the first mapping of the full distribution and movement of the population of Sargassum in the Gulf of Mexico and western Atlantic in the years 2002 to 2008. For the first time, we show a seasonal pattern in which Sargassum originates in the northwest Gulf of Mexico in spring of each year, is advected into the Atlantic in about July, appearing east of Cape Hatteras as a "Sargassum jet", and ending northeast of the Bahamas in February of the following year. This pattern appears consistent with historical surveys. Future satellite observations will show whether this pattern repeats in all or most years.
Natural evidence for garnet-spinel transition (GST) in the Earth's mantle
Authors: Su BenXun
Published: July 2019

This study based on compiled world-wide garnet peridotite data confirms the GST in high P and T conditions, which was obtained from Al-free experimental system (MgO-Cr~2~O~3~-SiO~2~) by Klemme (2004). A new spinel-phase peridotite zone, garnet peridotite discontinuous zone, is defined, and another GST, although no experimental data, is principally and presumably proposed to exist. The garnet inclusion-bearing spinel harzburgite from Lashaine (Tanzania) provides the first evidence for the existence of ultra-high spinel zone and is explained as recrystallized minerals hosting the interacted residue of ancient oceanic lithosphere subducted into the great depth of more than 220km. These previously unexpected findings are generating great challenges to phase transition in extreme conditions and to our understanding of layered-structure of the Earth. In addition, coexistent five-phase peridotite is suggested to be naturally useful tool to constrain the GST.
New Evidence for Early Silk in the Indus Civilization
Authors: Good Irene , Kenoyer Jonathan Mark , Meadow Richard
Published: July 2019

Silk is an important economic fiber, and is generally considered to have been the exclusive cultural heritage of China. Silk weaving is evident from the Shang period, though the earliest evidence for silk textiles in ancient China dates to more than a millennium earlier. New study of fibers from Harappan bronze artifacts reveals surprising early evidence for knowledge of silkworking in South Asia, the earliest evidence in the world for any silk outside China, and roughly contemporaneous with the earliest Chinese evidence for silk. This important new finding brings into question the traditional historical notion of sericulture as being an exclusively Chinese invention.
Effects of processes at the population and community level on carbon dynamics of an ecosystem model
Authors: Sierra Carlos , Harmon Mark
Published: July 2019

Ecological processes at the population and community level are often ignored in biogeochemical models, however, the effects of excluding these processes at the ecosystem level is uncertain. In this study we analyzed the set of behaviors that emerge after introducing population and community processes into an ecosystem carbon model. We used STANDCARB, a hybrid model that incorporates population, community, and ecosystem processes to predict carbon dynamics over time. Our simulations showed that at the population level, colonization and mortality rates can limit the maximum biomass achieved during a successional sequence. Specifically, colonization rates control temporal lags in the initiation of carbon accumulation, and mortality rates can have important effects on annual variation in live biomass. At the community level, differences in species traits and changes in species composition over time introduced significant changes in carbon dynamics. Species with different set of parameters, such as growth and mortality rates, introduce patterns of carbon accumulation that could not be reproduced using a single species with the average of parameters of multiple species or by simulating the most abundant species (strategies commonly employed in terrestrial biogeochemical models). We conclude that omitting population and community processes from biogeochemical models introduces an important source of uncertainty that can impose important limitations for predictions of future carbon balances.
On the Doubly hydrogen bonded dimer of 7-azaindole (0.1 M) as a model for DNA base pairs in acetonitrile solutions at rt
Authors: Catalan Javier
Published: July 2019

Multiple H-bonded base-pairing as a fundamental element of DNA structure was first described by Watson and Crick using stable keto tautomer forms. In their analysis, they considered the possibility of mutations via tautomeric proton transfer shifts. Among other phenomena, such shifts can be caused by electronic excitation; for example, anomalous adenine-cytosine pairing may be a result of two-proton phototautomerism. One suitable model base pair for two-proton translocating tautomerization is the C2h dimer of 7-azaindole (7AI) proposed by Taylor et al. in 1969. The most salient contribu&x00AC;tion of their work was that the double proton transfer in such a dimer occurs in a concerted manner. After the strong controversy raised in 1995 by the proposal of Douhal et al. of a stepwise mechanism for the process was overcome, its concerted nature has been strongly supported by available evidence (see references and references therein). Very recently, however, Kwon and Zewail claimed to have obtained new supportive evidence that the proton phototransfer in 7AI dimer in polar solvents is in fact a stepwise rather than concerted process. In this communication, we conducted a systematic spectroscopic study of the dimerization of 7AI at a 0.1 M concentration in acetonitrile that may allow us to demonstrate whether the 0.1 M 7AI solutions in acetonitrile at room temperature used by Kwon and Zewail contained enough 7AI doubly hydrogen bonded dimer to enable its photoselection and hence its photophysical characterization with femtosecond / fluorescence spectroscopy.
MR Neurography and Diffusion Tensor Imaging: Origin, History and Impact
Authors: Filler Aaron
Published: July 2019

Objective

– Methods were invented that made it possible to image peripheral nerves in the body and to image neural tracts in the brain. Over a 15 year period, these techniques – MR Neurography and Diffusion Tensor Imaging – were then deployed in the clinical and research community and applied to about 50,000 patients. Within this group, about 5,000 patients having MR Neurography were carefully tracked on a prospective basis.

Method

– In the study group a uniform imaging methodology was applied and all images were reviewed and registered by referral source, clinical indication, efficacy of imaging and quality. Various classes of image findings were identified and subjected to a variety of small targeted prospective outcome studies. Those findings demonstrated to be clinically significant were then tracked in the larger clinical volume data set.

Results

– MR Neurography demonstrates mechanical distortion of nerves, hyperintensity consistent with nerve irritation, nerve swelling, discontinuity, relations of nerves to masses, and image features revealing distortion of nerve at entrapment points. These findings are often clinically relevant and warrant full consideration in the diagnostic process. They result in specific pathologic diagnoses that are comparable to electrodiagnostic testing in clinical efficacy.

Conclusions

– MR Neurography and DTI neural tract imaging have been validated as indispensable clinical diagnostic methods that provide reliable anatomical pathological information. There is no alternative diagnostic method in many situations. With the elapse of 15 years, tens of thousands of imaging studies, and hundreds of publications, these methods should no longer be considered experimental.
MR Neurography and Diffusion Tensor Imaging: Origin, History and Impact
Authors: Filler Aaron
Published: July 2019

*Objective:*

Methods were invented that made it possible to image peripheral nerves in the body and to image neural tracts in the brain. Over a 15 year period, these techniques – MR Neurography and Diffusion Tensor Imaging – were then deployed in the clinical and research community and applied to about 50,000 patients. Within this group, about 5,000 patients having MR Neurography were carefully tracked on a prospective basis.*Method:* In the study group a uniform imaging methodology was applied and all images were reviewed and registered by referral source, clinical indication, efficacy of imaging and quality. Various classes of image findings were identified and subjected to a variety of small targeted prospective outcome studies. Those findings demonstrated to be clinically significant were then tracked in the larger clinical volume data set.

*Results:*

MR Neurography demonstrates mechanical distortion of nerves, hyperintensity consistent with nerve irritation, nerve swelling, discontinuity, relations of nerves to masses, and image features revealing distortion of nerve at entrapment points. These findings are often clinically relevant and warrant full consideration in the diagnostic process. They result in specific pathologic diagnoses that are comparable to electrodiagnostic testing in clinical efficacy.

*Conclusions:*

MR Neurography and DTI neural tract imaging have been validated as indispensable clinical diagnostic methods that provide reliable anatomical pathological information. There is no alternative diagnostic method in many situations. With the elapse of 15 years, tens of thousands of imaging studies, and hundreds of publications, these methods should no longer be considered experimental.
A common subcortical oscillatory network contributes to recovery after spinal cord injury
Authors: Nishimura Yukio , Morichika Yosuke , Isa Tadashi
Published: July 2019

Recent studies in monkeys showed that when the direct cortico-motoneuronal connection was transected at mid-cervical segments, remaining, indirect cortico-motoneuronal pathways compensated for finger dexterity within one to three months. To elucidate the changes in dynamic properties of neural circuits during the recovery, we investigated the cortico-muscular and inter-muscular couplings of activities throughout the recovery course. Activities of antagonist muscle pairs showed co-activation during the second postoperative week, and oscillated coherently at frequencies of 30-46 Hz (gamma-band) by one month postoperatively. Such gamma-band inter-muscular coherence was not observed preoperatively, but became prominent and distributed widely over proximal and distal muscles with the recovery. Neither the gamma-band cortico-muscular coupling (14-30 Hz) observed before lesion, nor a gamma-band oscillation was observed in bilateral motor cortex after lesion. Thus, we propose that an unknown, subcortical oscillator, independent of cortical oscillation, commonly recruits hand/arm muscles and may underlie functional recovery of dexterous finger movements.
On the Coding of Negative Quantities in Cortical Circuits
Authors: Ballard Dana , Jehee Janneke
Published: July 2019

Mullers Law of specific nerve energies introduced the idea that nerves transmit information about specific sensory features. This concept has been refined by the notion of 'labeled lines,' specific cells that capture sub-features of a sensory or motor stimulus, such as Hubel and Weisel's opponent color cells. Such features can be visualized as coding a signed quantity that has positive and negative components that are encoded with separate nerve cells. We show that there are two important consequences when learning receptive field using signed codings in circuits. The first is that in feedback circuits even simple operations need to be distributed across multiple distinct pathways. The second consequence is that such pathways are necessarily dynamic. Synaptic weights change during learning and must break and grow new circuit connections because the weights need to change sign during receptive field formation.
Function, Role, and Disposition in Basic Formal Ontology
Authors: Arp Robert , Smith Barry
Published: July 2019

Numerous research groups are now utilizing Basic Formal Ontology (BFO) as an upper-level framework to assist in the organization and integration of biomedical information. This paper provides elucidation of the three BFO categories of function, role, and disposition, and considers two proposed sub-categories of artifactual function and bio-logical function. The motivation is to help advance the coherent treatment of functions, roles, and dispositions, to help provide the potential for more detailed classification, and to shed light on BFO’s general structure and use.
11-amino-5-N-methyl-7-fluorine- quindoline derivatives: The Potential Anti-angiogenic Agents Targeting G-quadruplex Structure in Vascular Endothelial Cell Growth Factor
Authors: Ou Tian-miao , Lu Yu-jing , Wang Xiao-dong , An Zeng-yun , Li Yan-ping , Huang Zhi-shu , Gu Lian-quan
Published: July 2019

Vascular endothelial growth factor (VEGF), a pluripotent cytokine and angiogenic growth factor, plays crucial roles in embryonic development and tumour progression, and is over-expressed in many types of cancer and generally associated with tumour progression and survival rate. The polypurine/polypyrimide sequence located upstream (-89 to -43) of the promoter region of the human VEGF gene that can form specific G-quadruplex structures and raise the possibility for transcriptional control of the VEGF gene by G-quadruplex ligands. In the present study, we investigated the interaction between the 5-N-methyl-7-fluorine-quindoline derivatives (11-amino-5-N-methyl-7-fluorine- quindoline derivatives) and the G-rich sequence in VEGF's promoter and the subsequent effects on the biological functions of VEGF. We found the strong interaction between the 5-N-methyl-7-fluorine-quindoline derivatives and the G-rich DNA of VEGF, and this interaction might significantly influence the biological functions of VEGF, including the transcription and expression of VEGF, cell proliferation and apoptosis, and the stimulation of angiogenesis in chick embryo.
An experimental and modelling exploration of the host-sanction hypothesis in legume-rhizobia mutualism
Authors: Marco Diana , Carbajal Juan , Cannas Sergio , Perez-Arnedo Rebeca , Hidalgo-Perea Angeles , Olivares Jose , Ruiz-Sainz Jose , Sanjuán Juan
Published: July 2019

Despite the importance of mutualism as a key ecological process, its persistence in nature is difficult to explain since the existence of exploitative, 'cheating' partners that could erode the interaction is common. By analogy with the proposed policing strategy stabilizing intraspecific cooperation, host sanctions against non N2 fixing, cheating symbionts have been proposed as a force stabilizing mutualism in legume-Rhizobium symbiosis. Following this proposal, penalizations would include decreased nodular rhizobial viability and/or early nodule senescence in nodules occupied by cheating rhizobia. In this work, we analyze the stability of Rhizobium-legume symbiosis when "cheating" strains are present, using an experimental and modelling approach. We used split-root experiments with soybean plants inoculated with two rhizobial strains, a cooperative, normal N2 fixing strain and an isogenic non-fixing, “perfect” cheating mutant derivative that lacks nitrogenase activity but has the same nodulation abilities inoculated to split-root plants. We found no experimental evidence of functioning plant host sanctions to cheater rhizobia based on nodular rhizobia viability and nodule senescence and maturity molecular markers. Based on these experiments, we developed a population dynamic model with and without the inclusion of plant host sanctions. We show that plant populations persist in spite of the presence of cheating rhizobia without the need of incorporating any sanction against the cheater populations in the model, under the realistic assumption that plants can at least get some amount of fixed N2 from the effectively mutualistic rhizobia occupying some nodules. Inclusion of plant sanctions merely reduces the time needed for reaching plant population equilibrium and leads to the unrealistic effect of ultimate extinction of cheater strains in soil. Our simulation results are in agreement with increasing experimental evidence and theoretical work showing that mutualisms can persist or even improve in presence of cheating partners.
Reinforcement learning in populations of spiking neurons
Authors: Urbanczik Robert , Senn Walter
Published: July 2019

Population coding is widely regarded as a key mechanism for achieving reliable behavioral responses in the face of neuronal variability. But in standard reinforcement learning a flip-side becomes apparent. Learning slows down with increasing population size since the global reinforcement becomes less and less related to the performance of any single neuron. We show that, in contrast, learning speeds up with increasing population size if feedback about the populationresponse modulates synaptic plasticity in addition to global reinforcement. The two feedback signals (reinforcement and population-response signal) can be encoded by ambient neurotransmitter concentrations which vary slowly, yielding a fully online plasticity rule where the learning of a stimulus is interleaved with the processing of the subsequent one. The assumption of a single additional feedback mechanism therefore reconciles biological plausibility with efficient learning.
Structural basis of the allosteric trigger of the Hsp70 chaperone proteins.
Authors: Bhattacharya Akash , Kurochkin Alexander , Yip Grover , Bertelsen Eric , Zuiderweg Erik
Published: July 2019

This work solves a decades-old dilemma that stood in the way of understanding the allosteric mechanism of Hsp70 (heat shock 70 kDa) chaperone proteins. Hsp70s are central to protein folding, refolding, and trafficking in organisms ranging from Archae to Homo Sapiens, both at normal and at stressed cellular conditions. Hsp70s are comprised of two main domains: a 44 kDa N-terminal nucleotide-binding domain (NBD), and a 25 kDa substrate-binding domain (SBD) that harbors the substrate binding site. The nucleotide binding site in the NBD and the substrate binding site in the SBD are allosterically linked: ADP binding promotes substrate binding, while ATP binding promotes substrate release. It has long been a goal of structural biology to characterize the nature of the allosteric coupling in these proteins. However, even the most sophisticated X-ray crystallography studies of the isolated NBD could show no difference in overall conformation between the ATP and ADP state. Hence the dilemma: how is the state of the nucleotide communicated between NBD and SBD? The solution of the dilemma is especially interesting in light of the fact that Hsp70s are ancient proteins, and amongst the first allosteric proteins in nature.Here we report a solution NMR study of the NBD of the Hsp70 from Thermus thermophilus, in the APO, ADP and AMP-PNP states, where the latter is a non-hydrolysable ATP analogue. Using the modern NMR methods of residual dipolar coupling analysis, we discovered that the nucleotide binding cleft opens up by as much as 20 degrees between the AMP-PNP (closed) and ADP (open) state. We also discover that a surface cleft, hypothesized to be essential for the allosteric coupling between NBD and SBD, echoes these changes. Hence, the nature of the allosteric trigger and coupling for Hsp70 chaperones is revealed here for the first time, solving the dilemma.
Is the innate bio-protection power against human virus the same between males and females? A conclusion based on blood donor data of HTLV-I infection and case data of infectious diseases
Authors: Eshima Nobuoki , Tabata Minoru , Higuchi Yasunori , Karukaya Shigeru
Published: July 2019

Human T-cell leukemia virus type I (HTLV-I) is a retrovirus that causes adult T-cell leukemia. The male-to-female transmission is stronger than the reverse, so the carrier proportion of women is greater than that of men. On the other hand, since the mother-to-child transmission route via the breast-feeding is common for baby boys and girls, it has been thought the HTLV-I proportions of boys and girls are the same until now. A question arises as to whether the ‘innate protection powers against human virus’ are the same between males and females. We utilize HTLV-I infection blood donor data in 1995-1998 and case data of main infectious diseases such as influenza, mumps, herpangina, hand-hoot-and-mouse disease, chicken pox, etc. Blood donor data in 1995-1998, which were provided by Japan Red Cross Society of Oita, Japan, are summarized into the frequency table with respect to gender and age. The age groups are < 20, 20 < age , 30 < age , 40 < age , and > 50 years old. The comparison of carrier proportions of males and females under 20 years old is made with a two-sided statistical test and for the other groups one-sided tests are carried out. In case data published from the National Institute of Infectious Diseases, Japan, comparisons of the incidence rates of males and females in infectious diseases are carried out with two-sided tests. The present paper shows that the HTLV-I carrier proportion of girls is less than that that of boys. It implies that in HTLV-I the mother-to-child transmission probability of females is less than that of males. With respect to the other main infectious diseases, the majority of cases are under twenty years old, and the incidence rates of females are also significantly less than those of males. According to the present findings, it follows that the female’s innate protection power against HTLV-I is stronger than that of males, and the conclusion may become a valid proposition for general human virus.
Population genomics of domestic and wild yeasts
Authors: Carter David , Liti Gianni , Moses Alan , Parts Leopold , James Stephen , Davey Robert , Roberts Ian , Blomberg Anders , Warringer Jonas , Burt Austin , Koufopanou Vassiliki , Tsai Isheng , Bergman Casey , Bensasson Douda , O’Kelly Michael , van Oudenaarden Alexander , Barton David , Bailes Elizabeth , Jones Matthew , Quail Michael , Goodhead Ian , Sims Sarah , Smith Frances , Durbin Richard , Louis Edward
Published: July 2019

The natural genetics of an organism is determined by the distribution of sequences of its genome. Here we present one- to four-fold, with some deeper, coverage of the genome sequences of over seventy isolates of the domesticated baker's yeast, Saccharomyces cerevisiae, and its closest relative, the wild S. paradoxus, which has never been associated with human activity. These were collected from numerous geographic locations and sources (including wild, clinical, baking, wine, laboratory and food spoilage). These sequences provide an unprecedented view of the population structure, natural (and artificial) selection and genome evolution in these species. Variation in gene content, SNPs, indels, copy numbers and transposable elements provide insights into the evolution of different lineages. Phenotypic variation broadly correlates with global genome-wide phylogenetic relationships however there is no correlation with source. S. paradoxus populations are well delineated along geographic boundaries while the variation among worldwide S. cerevisiae isolates show less differentiation and is comparable to a single S. paradoxus population. Rather than one or two domestication events leading to the extant baker's yeasts, the population structure of S. cerevisiae shows a few well defined geographically isolated lineages and many different mosaics of these lineages, supporting the notion that human influence provided the opportunity for outbreeding and production of new combinations of pre-existing variation.
Mechanisms to overcome ecosystem nitrogen and phosphorus limitation
Authors: Ostertag Rebecca
Published: July 2019

Nutrients limit plant growth in many ecosystems, and many species develop adaptations to either obtain more nutrients or to avoid losses. Much past ecological work has focused either on temperate nitrogen-limited systems or has addressed infertile soils as a single entity, rather than addressing the nature of the limitation. Although low nitrogen (N) and phosphorus (P) soils are found worldwide, the consequences of N and P limitation for plants may vary due to fundamental differences in the soil mobility, availability, uptake, and cellular uses of N and P. Using a well-studied chronosequence in the Hawaiian Islands, which contains both low N and P soils but which is dominated by similar plant communities, foliar N and P plant responses to fertilization were examined across a diverse group of species and life forms. Here it is shown that in response to N fertilization, foliar N concentrations do not significantly increase. In contrast, P fertilization leads to highly elevated foliar P concentrations and lower N:P values. This accumulation of P is evident across all species, occurs regardless of site fertility, results in increased concentrations of P in both inorganic and organic forms, and may be highly advantageous due to the patchy nature of soil P availability. Results indicate that greater variation in foliar P than foliar N after fertilization transcends soil nutrient availability and may be widespread among ecosystems. Such P accumulation means that N and P concentrations may not be in close association after pulses of soil P. It also provides a mechanism whereby ecosystem P limitation may be overcome with external inputs more easily than N limitation and points for the need to think about N and P limitation not just as infertile stressful conditions for plants, but as two fundamentally different phenomena.
In vivo evidence for NMDA receptor mediated excitotoxicity in a murine genetic model of Huntington Disease
Authors: Heng Mary , Detloff Peter , Wang Phillip , Tsien Joe , Albin Roger
Published: July 2019

N-methyl-D-aspartate receptor (NMDAR) mediated excitotoxicity is implicated as a proximate cause of neurodegeneration in Huntington Disease (HD). However, this hypothesis has not been tested rigorously in vivo. NMDAR NR2B-subunits are the predominant NR2 subunit expressed by the striatal medium spiny neurons that degenerate in HD. To test this hypothesis, we crossed a well validated murine genetic model of HD (Hdh(CAG)150) with a transgenic line overexpressing NMDAR NR2B-subunits. In the resulting double mutant line, we show exacerbation of selective striatal neuron degeneration. These results provide the first direct in vivo evidence of NR2B-NMDAR mediated excitotoxicity in the context of HD. Our results are consistent with prior suggestions that direct and/or indirect interactions of mutant huntingtin with NMDARs are a proximate cause of neurodegeneration in HD.
Depolarization increases cellular light transmission
Authors: Tomita Minoru , Suzuki Norihiro , Tomita Yutaka , Toriumi Haruki , Osada Takashi , Unekawa Miyuki , Tatarishvili Jemal
Published: July 2019

Application of optical methods to human brain tissue in vivo, e.g., measuring oxyhemoglobin and deoxyhemoglobin concentration changes with near-infrared spectroscopy (NIRS), requires the a priori assumption that background optical properties remain unchanged during measurements1,2. However, fundamental knowledge about light scattering by brain cells per se remains sparse; many factors influence light transmission changes through living brain tissue, bringing into question what is being measured. We have observed slow wave-ring spreads of light transmission changes on the rat cerebral cortex during potassium-induced cortical spreading depression (CSD) and ascribed them to squeezing-out of blood from capillaries by swollen brain cells3,4. However, in rat hippocampal slices, where no blood components were involved, similar light transmission changes were observed during K+-induced CSD and ascribed to cell swelling and dendritic beading5,6,7. Here we show that two-dimensional light scattering changes occur through suspensions of osmotically swollen (depolarized) red blood cells, apparently arising from light scattering changes at the less curved, swollen surface of the steep electrochemical gradient coupled with water activity difference across the plasmic membrane. These optical property changes are likely to be relevant to interpretation of photometry or spectroscopy findings of brain tissue in vivo, where neurons are polarizing and depolarizing during brain function.
Significance tests for comparing digital gene expression profiles
Authors: Varuzza Leonardo , Gruber Arthur , Pereira Carlos
Published: July 2019

Most of the statistical tests currently used to detect differentially expressed genes are based on asymptotic results, and perform poorly for low expression tags. Another problem is the common use of a single canonical cutoff for the significance level (p-value) of all the tags, without taking into consideration the type II error and the highly variable character of the sample size of the tags. This work reports the development of two significance tests for the comparison of digital expression profiles, based on frequentist and Bayesian points of view, respectively. Both tests are exact, and do not use any asymptotic considerations, thus producing more correct results for low frequency tags than the chi-square test. The frequentist test uses a tag-customized critical level which minimizes a linear combination of type I and type II errors. A comparison of the Bayesian and the frequentist tests revealed that they are linked by a Beta distribution function. These tests can be used alone or in conjunction, and represent an improvement over the currently available methods for comparing digital profiles.