bluuebunny/crossref_metadata_2025 huggingface dataset:
Silent Spring - the lost call
Authors: Quinn Michael , Ottinger Mary Ann
Published: July 2019

The "silence" in Rachel Carson's Silent Spring1 alludes to the demise of bird populations through reproductive problems and death resulting from exposure to the pesticides of that time, many of which are endocrine active. Endocrine disrupting chemicals (EDCs) are compounds which may interfere with the endocrine system, producing effects that may disrupt the physiologic function of hormones. Early research on EDC exposure in humans and wildlife has focused mainly on reproductive effects of estrogenic chemicals, however recent studies have revealed that effects of estrogenic as well as non-estrogen active chemicals are often more far reaching than the reproductive system, and even mild exposures experienced early in development may have detrimental effects that are maintained throughout adulthood. Here we show trenbolone acetate, an androgen active environmental contaminant used as a growth promoter for cattle, to cause a literal silence in Japanese quail (Coturnix japonica) chicks following a one time embryonic exposure. Vocalizations were not merely lessened; this is the first study to demonstrate an environmental contaminant to cause a complete abolishment of the ability to vocalize. Since many reasons for vocalization in birds are directly linked to survival of the individual and species, the potential for detrimental population effects is a grave possibility for many avian species that may encounter androgen active chemicals in the environment. Many androgen active EDCs are persistent and ubiquitous in distribution, thereforechances for exposure to these chemicals in birds may be high. We hope that powerful, yet subtle effects like the ones presented here will encourage further research with EDCs to expand beyond the traditional focus of reproductive effects of estrogenic chemicals.
On the reliability of Bayesian posterior clade probabilities in phylogenetic analysis
Authors: Jones Graham
Published: July 2019

This article discusses possible reasons why posterior clade probabilities obtained from Bayesian phylogenetic analyses might be inaccurate. It attempts to list all possible sources of uncertainty and error in Bayesian phylogenetic analysis. The choice of priors on trees has been suggested by several authors as a cause of inaccurate posterior clade probabilities. I argue strongly for using priors based on biological knowledge. Two possible sources of bias which do not seem to have been published before are also discussed. One is a computational problem and the other related to majority rule consensus trees.
Tendril, adhesive disc and super adhesive effect of climbing plant
Authors: Deng Wenli
Published: July 2019

Understanding the super adhesion mechanism of biological system is of great scientific interest and a prerequisite for bioinspired design of adhesive systems. To investigate the versatile climbing plant requires the development of new methods. Here I present strategies to fully study the super adhesive effect of climbing plant Parthenocissus tricuspidata by the first time measuring the mass and the attached area of single adhesive disc, by further determining the microscopic structure and the adhesive strength of single adhesive disc and by finally elucidating the adhesion mechanism in cellular and molecular level using the classical theories and the proposed new hypothesis and model. I have measured that a single mature adhesive disc has an average mass of only about 0.0005 g, an average attached area of about 1.22 sq mm and an adhesive force of about 13.7 N. I have found that a single adhesive disc can on average support a weight produced together by the stem, leaf, branchlet and tendril which is 260 times greater than its own weight during the growing, and can sustain the maximum pulling force which is 2,800,000 times higher than that produced by its own weight. Microscopic experiments show some new microstructures which have never been reported and reveal that the adhesive disc has super adhesive property which inspires us to fabricate a lot of mimic adhesives that have potential applications in biomedical science, bioelectronics and space science and technology.
Eukaryotic translation initiation machinery can operate in a prokaryotic-like mode without eIF2
Authors: Shatsky Ivan , Terenin Ilya , Dmitriev Sergey , Andreev Dmitri
Published: July 2019

Unlike prokaryotes, a specialized eukaryotic initiation factor 2 (eIF2), in the form of the ternary complex eIF2*GTP*Met-tRNAiMet is utilized to deliver the initiator tRNA to the ribosome within all eukaryotic cells1. Phosphorylation of eIF2 is known to be central to the global regulation of protein synthesis under stress conditions and infection2. Another distinctive feature of eukaryotic translation is scanning of mRNA 5'-leaders, whose origin in evolution may be relevant to the appearance of eIF2 in eukaryotes. Translation initiation on the hepatitis C virus (HCV) internal ribosome entry site (IRES) occurs without scanning3,4. Whether these unique features of the HCV IRES account for the formation of the final 80S initiation complex is unknown. Here we show that the HCV IRES-directed translation can occur without either eIF2 or its GTPase activating protein eIF5. In addition to the general eIF2- and eIF5-dependent pathway of 80S complex assembly, the HCV IRES makes use of a prokaryotic-like pathway which involves eIF5B, the analogue of bacterial IF25,6, instead of eIF2. This switch from a eukaryotic-like mode of AUG selection to a "bacterial" one occurs when eIF2 is inactivated by phosphorylation, a way with which host cells counteract infection. The relative resistance of HCV IRES-directed translation to eIF2 phosphorylation may represent one more line of defense used by this virus against host antiviral responses and can contribute to the well known resistance of HCV to interferon based therapy.
Shelling the Voronoi interface of protein-protein complexes predicts residue activity and conservation
Authors: Bouvier Benjamin , Grünberg Raik , Nilges Michael , Cazals Frederic
Published: July 2019

The accurate description of protein-protein interfaces remains a challenging task. Traditional criteria, based on atomic contacts or changes in solvent accessibility, tend to over or underpredict the interface itself and cannot discriminate active from less relevant parts. A recent simulation study by Mihalek and co-authors (2007, JMB 369, 584-95) concluded that active residues tend to be `dry', that is, insulated from water fluctuations. We show that patterns of `dry' residues can, to a large extent, be predicted by a fast, parameter-free and purely geometric analysis of protein interfaces. We introduce the shelling order of Voronoi facets as a straightforward quantitative measure of an atom's depth inside an interface. We analyze the correlation between Voronoi shelling order, dryness, and conservation on a set of 54 protein-protein complexes. Residues with high shelling order tend to be dry; evolutionary conservation also correlates with dryness and shelling order but, perhaps not surprisingly, is a much less accurate predictor of either property. Voronoi shelling order thus seems a meaningful and efficient descriptor of protein interfaces. Moreover, the strong correlation with dryness suggests that water dynamics within protein interfaces may, in first approximation, be described by simple diffusion models.
Shelling the Voronoi interface of protein-protein complexes predicts residue activity and conservation
Authors: Bouvier Benjamin , Grünberg Raik , Nilges Michael , Cazals Frederic
Published: July 2019

The accurate description and analysis of protein-protein interfaces remains a challenging task. Traditional definitions, based on atomic contacts or changes in solvent accessibility, tend to over- or underpredict the interface itself and cannot discriminate active from less relevant parts.We here extend a fast, parameter-free and purely geometric definition of protein interfaces and introduce the shelling order of Voronoi facets as a novel measure for an atom's depth inside the nterface. Our analysis of 54 protein-protein complexes reveals a strong correlation between Voronoi Shelling Order (VSO) and water dynamics. High Voronoi Shelling Order coincides with residues that were found shielded from bulk water fluctuations in a recent molecular dynamics study. Yet, VSO predicts such "dry" residues at dramatically reduced cost and without consideration of forcefields or dynamics. More central interface positions are often also increasingly enriched for hydrophobic residues. Yet, this hydrophobic centering is not universal and does not mirror the far stronger geometric bias of water fluxes. The seemingly complex water dynamics at protein interfaces appears thus largely controlled by geometry. Sequence analysis supports the functional relevance of both dry residues and residues with high VSO, both of which tend to be more conserved. However, upon closer inspection, the spatial distribution of conservation argues against the arbitrary dissection into core or rim and thus refines previous results. Voronoi Shelling Order reveals clear geometric patterns in protein interface composition, function and dynamics and facilitates the comparative analysis of protein-protein interactions.
Sensitivity Analysis of Self-Identified Race and Ethnicity (SIRE): Screening for Single Nucleotide Polymorphisms.
Authors: Miles Toni , Hanson Stephen , Kidd LaCreis , Connor Avonne , Jortani Saeed
Published: July 2019

Within the realm of medical care, Self-Identified Race and Ethnicity (SIRE) categories are promoted as an inexpensive tool to identify underlying genotypic diversity. Scientific opinion is divided about the adequacy of SIRE to serve this function. If genetic diversity can guide medical decisions, it is important to know the effectiveness of genetic screening via SIRE. Proper development of self-reported measures such as SIRE requires sensitivity and specificity studies. These types of formal evaluation are largely absent for SIRE. To begin this formal process, we estimate the sensitivity of SIRE in screening for variant Single Nucleotide Polymorphism (SNP). Our results indicate that the current use of SIRE is inadequate to screen for selected biotransformation related SNP in the N-Acetyl Transferase pathway. The widespread usage of SIRE to screen for genotypic diversity could promote erroneous assignment of patients to disease risk or therapeutic categories.
Isoprene Emission and Carbon Dioxide Protect Aspen Leaves from Heat Stress
Authors: Darbah Joseph , Sharkey Thomas , Karnosky David
Published: July 2019

High temperature, especially above 35oC, is known to reduce leaf photosynthetic rate in many tree species. This study investigated the effect of high temperature on isoprene-emitting (aspen) and non- emitting (birch) trees under ambient and elevated CO2 under open field conditions. Aspen trees tolerate heat better than birch trees and elevated CO2 protects both species against moderate heat stress. The increased thermotolerance in aspen trees compared to the birch trees may result from the aspen's ability to produce isoprene. Elevated CO2 increased carboxylation capacity, photosynthetic electron transport capacity and triose phosphate use in both birch and aspen trees. High temperature decreased all of these parameters in birch regardless of CO2 treatment but only photosynthetic electron transport and triose phosphate use at ambient CO2 were reduced in aspen. As temperature rises, non-isoprene-emitting trees will be at a disadvantage and biological diversity and species richness might be lost in some ecosystems. Our results indicate that isoprene emitting tree species will have an advantage over non-isoprene emitting ones under high temperatures.
Tumor-associated EGFR over-expression specifically activates Stat3 and Smad7 resulting in desensitization of TGF-β signaling
Authors: Luwor Rodney , Taylor Lauren , Wang Bo , Zhu Hong-Jian
Published: July 2019

Transforming Growth Factor-[beta] (TGF-[beta]) and Epidermal Growth Factor (EGF) signaling pathways are both independently implicated as key regulators in tumor formation and progression. Here, we demonstrate that activation of the tumor-associated and over-expressed EGFR desensitizes TGF-[beta] signaling and its cytostatic regulation through specific Stat3 activation and Smad7 induction. In normal and tumor human cell lines, reduction of TGF-[beta]-mediated Smad2 phosphorylation, nuclear translocation and Smad3 target gene activation were observed where EGFR is over-expressed, but not in cells which expressed EGFR at normal levels. The EGFR downstream signaling molecules phosphatidyinositol-3 Kinase (PI3K) or mitogen-activated protein kinase/ERK kinase (MEK) are not responsible for the down-regulation of TGF-[beta] signaling since blockade of them by specific pharmacological inhibitors LY294002 and U0126 had little effects on the sensitivity of TGF-[beta] signaling. We identified Stat3 as a signaling molecule activated specifically and persistently by over-expressed EGFR, but not by normal levels. Importantly, Stat3 is responsible for the reduced TGF-[beta] sensitivity, since its knockdown by siRNA restored TGF-[beta] signaling sensitivity. Furthermore, over-expressed EGFR, through Stat3 activates Smad7 promoter activity, increasing its protein levels, which is a negative regulator of TGF-[beta] signaling. Consequently, cells were re-sensitized to TGF-[beta] when Smad7 expression was reduced using siRNA. Therefore we establish a novel EGFR-Stat3-Smad7-TGF-[beta] signaling molecular axis where tumor-associated over-expression of EGFR in epithelial cells results in hyperactivation of Stat3, which activates Smad7 expression, compromising the TGF-[beta]'s cytostatic regulation of epithelium and consequent tumor formation.
New Spontaneous Model of Fibrodysplasia Ossificans Progressiva
Authors: Rothschild Bruce , Martin Larry , Timm Robert
Published: July 2019

We report the first known example of spontaneous, naturally occurring fibrodysplasia ossificans progressiva (FOP) in a mammal. The Southeast Asian mouse deer of the genus Tragulus (Artiodactyla: Tragulidae) have an osseous sheath covering the lower back and upper thigh region consistent with the clinical definition of FOP. This heterotophic bone deposition is sex related apparently with a genetic basis - it only occurs in males and is lacking in females; it is present in all adults males, including both wild obtained and zoo bred animals. Tragulus may offer the opportunity to examine many of the disease's most significant attributes experimentally.
Role and immunomodulatory profile of histamine receptors by H1 and H2 antagonists
Authors: Tripathi Trivendra , Shahid Mohd. , Siddiqui Mashiatullah , Khan Rahat
Published: July 2019

The present study was designed to delineate the immunomodulatory role of histamine receptors (H1- and H2-) on induction of antibody response to sheep red blood cells (SRBC), as well as the antibody generation profile, in rabbit system, systemically. The rabbits in two groups received pheniramine (H1-receptor antagonist) and ranitidine (H2-receptor antagonist), respectively, via intramuscular route and were immunized with SRBC intravenously to evaluate suppression or enhancement of antibody responses in sem. A third, control group, received vehicle and were immunized in a similar manner. Histamine released from effector cells (mast cells and basophils) in vivo during inflammatory reactions could influence a detectable antibody response to SRBC as early as day 7-postimmunization (post-I), which lasted until day 28- post-I. Pheniramine-treated rabbits had significantly (&42;Pa ≤ 0.05 and &42;&42;Pa ≤ 0.01) more suppressed total serum antibody (IgM + IgG) to SRBC as compared to ranitidine-treated ad cotrol rabbits, while ranitidine-treated rabbits showed different pattern (suppressed or enhanced) during the whole study period. Ranitidine suppressed total antibody level at days 7- and 14- post-I, and enhanced at days 21- and 28- post-I. IgM suppression at day 7- and enhancement at days 14-, 21- and 28- post-I, while IgG suppression during whole study period, as compared to control group was significant (&42;Pa ≤ 0.05 and &42;&42;Pa ≤ 0.01) as assessed by direct hemagglutination assay&42; ad whole SBC-ELISA method&42;&42;. Here we report that histamine receptor type 2 (H2R)-antagonists have a dominant role on immunosuppression and in immunoregulation of humoral immune responses. Histamine receptor type 2 (H2R)-antagonists are mainly involved in B cell differentiation and proliferation over histamine receptor type 1 (H1R)-antagonists.
Dual expression recombinase based (DERB) single vector system for high throughput screening and verification of protein interactions in living cells
Authors: Lu JianPing , Beatty Laura , Pinthus Jehonathan
Published: July 2019

Identification of novel protein interactions and their mediators is fundamental in understanding cellular processes and is necessary for protein-targeted therapy. Evidently high throughput formatting of these applications in living cells would be beneficial, however no adequate system exists. We present a novel platform technology for the high throughput screening and verification of protein interactions in living cells. The platform's series of Dual Expression Recombinase Based (DERB) destiny vectors individually encode two sets of recombinase recognizable sequences for inserting the protein open reading frame (ORF) of interest, two sets of promoters and reporter tags in frame with the ORFs for detecting interactions. Introduction into living cells (prokaryotic and eukaryotic) enables the detection of protein interactions by fluorescence resonance energy transfer (FRET) or bimolecular fluorescence complementation (BiFC). The DERB platform shows advantages over current commercialized systems by DERB vectors validated through proof-of-principle experiments and the identification of an unknown interaction.
Posterior parietal cortex controls spatial attention through modulation of anticipatory alpha rhythms
Authors: Capotosto Paolo , Babiloni Claudio , Romani Gian Luca , Corbetta Maurizio
Published: July 2019

A dorsal fronto-parietal network, including regions in intra-parietal sulcus (IPS) and frontal eye field (FEF), has been hypothesized to control the allocation of spatial attention to environmental stimuli. One putative mechanism of control is the de-synchronization of electroencephalography (EEG) alpha rhythms (~8-12 Hz) in parieto-occipital cortex in anticipation of a visual target. We show that brief interference by transcranial magnetic stimulation (rTMS) with preparatory activity in right IPS or right FEF while subjects attend to a spatial location impairs identification of target stimuli ~2 seconds later. Moreover, the visual deficit relates to the disruption of anticipatory (pre-stimulus) alpha desynchronization and its topography in parieto-occipital cortex. After right IPS stimulation, the degree to which alpha desynchronization is suppressed predicts the speed of visual identification. These results demonstrate the causal role of posterior parietal cortex in the control of visuo-spatial attention exerted through the synchronization of visual neurons.
Altruism among relatives and non-relatives
Authors: Rachlin Howard , Jones Bryan
Published: July 2019

The amount of their own monetary reward that undergraduate participants claimed they were willing to forgo, in order to give $75 to another person, decreased hyperbolically as social distance increased between the participant and the other person. Relatives tended to be ranked at closer social distances than were non-relatives. However, even at the same social distance, participants were willing to forgo significantly more money for the benefit of relatives than for the benefit of non-relatives. These results imply that altruism is determined by factors in addition to social distance.
Chemical Physics of Phonons & Superconductivity: A Heuristic Approach
Authors: Bucknum Michael
Published: July 2019

Several lines of thought are pursued in an attempt to further clarify the role played by phonons in the theory of superconductivity. The central results of BCS theory are examined in the context of anharmonicity in the phonon motion and the role that Badger's rule of spectroscopy can play in simplifying and making more chemically intuitive the nature of the mechanism of superconductivity.
Chemical Topology of Crystalline Matter and the Transcendental Numbers ϕ , e and π
Authors: Bucknum Michael , Castro Eduardo
Published: July 2019

This work is intended as a review and extension of the seminal work in chemical topology developed by the crystallographer A.F. Wells in the 20th century.
Structural dynamics and divergence of the polygalacturonase gene family in land plants
Authors: Kwon Soon-Jae , Son Jae-Han , Park Kyong-Cheul , Oh Hae-Young , Kim Pyeung-Hyeun , Byeon Woo-Hyeon , Kim Nam-Soo
Published: July 2019

A distinct feature of eukaryotic genomes is the presence of gene families. The polygalacturonase (PG) (EC3.2.1.15) gene family is one of the largest gene families in plants. PG is a pectin-digesting enzyme with a glycoside hydrolase 28 domain. It is involved in numerous plant developmental processes. The evolutionary processes accounting for the functional divergence and the specialized functions of PGs in land plants are unclear. Here, phylogenetic and gene structure analysis of PG genes in algae and land plants revealed that land plant PG genes resulted from differential intron gain and loss, with the latter event predominating. PG genes in land plants contained 15 homologous intron blocks and 13 novel intron blocks. Intron position and phase were not conserved between PGs of algae and land plants but conserved among PG genes of land plants from moss to vascular plants, indicating that the current introns in the PGs in land plants appeared after the split between unicellular algae and multicelluar land plants. These findings demonstrate that the functional divergence and differentiation of PGs in land plants is attributable to intronic loss. Moreover, they underscore the importance of intron gain and loss in genomic adaptation to selective pressure.
GESTATION LENGTH OF KARI SHEEP
Authors: Ahmad Sohail
Published: July 2019

Previously, the concept of a gestation period of sheep shorter than 121 days was unheard of in the field of sheep biology. Our findings during a farmers’ survey in the Lotkho area of Chitral, Pakistan, revealed that the sheep native to the region, locally called “Kari”, gestates for a period of only three months. This duration is 25-40% short of the usual gestation length and is shorter than ever recorded for the species. The mean and mode gestation length (GL) was 110 and 92 days respectively and was concentrated in three distinct clusters: day 87-95, 120-123 and 151-153, accounting for 52% of all observations. GL was influenced by location, season of conception and lambing and the interaction of location with season; had an estimated repeatability of zero. The mean lambing interval was 224.7 ±5.24 days, ranging between 109 and 467 days. During a trial conducted in a controlled environment, only three out of the 27 copulated ewes conceived, and gestated in 113, 125 and 145 days respectively. Gestation length during the trial supported field findings. The results suggest that GL in Kari sheep is unusual as many ewes gestated in three months, with variations of up to 5 months. Genotype by environment interaction is a possibility. However, reasons for the findings are still not clear and further controlled studies should be carried out to establish and further explore the factor(s) responsible for this unusual and unique manifestation of the Kari with regards to its gestation length.
Dynamic gating in the nucleus accumbens: Behavioral state-dependent synchrony with the prefrontal cortex and hippocampus
Authors: Hussain Rifat , Gruber Aaron , O’Donnell Patricio
Published: July 2019

Contextual and sensory information, goals, and the motor plan to achieve them are integrated in the nucleus accumbens (NA). Although this integration needs flexibility to operate in a variety of environments, models of NA function rarely consider changing behavioral states. Here, intracellular recordings in anesthetized rats revealed rapid changes in the synchronization between NA up states and prefrontal cortical (PFC) local field potentials (LFPs). The synchronization of the NA with the PFC and ventral hippocampus also varied over time in awake rats, depending on the behavioral state of the animal: NA LFPs followed hippocampal theta rhythms during spatial exploration, but not during an operant task when they were instead synchronized with slower PFC rhythms. These data indicate that the ability of the NA to follow cortical inputs can rapidly change, allowing for a mechanism that could select an optimal response for a given behavioral condition.
On the status of the Michaelis-Menten equation and its implications for enzymology
Authors: Chandrasekhar Sosale
Published: July 2019

The Michaelis-Menten equation (MME) is considered to be the fundamental equation describing the rates of enzyme-catalysed reactions, and thus the 'physicochemical key' to understanding all life processes. It is the basis of the current view of enzymes as generally proteinaceous macromolecules that bind the substrate reversibly at the active site, and convert it to the product in a relatively slow overall sequence of bonding changes ('turnover'). The manifested 'saturation kinetics', by which the rate of the enzymic reaction (essentially) increases linearly with the substrate concentration ([S]) at low [S] but reaches a plateau at high [S], is apparently modelled by the MME. However, it is argued herein that the apparent success of the MME is misleading, and that it is fundamentally flawed by its equilibrium-based derivation (as can be shown mathematically). Thus, the MME cannot be classed as a formal kinetic equation vis-a-vis the law of mass action, as it does not involve the 'incipient concentrations' of enzyme and substrate; indeed, it is inapplicable to the reversible interconversion of substrate and product, not leading to the expected thermodynamic equilibrium constant. Furthermore, the principles of chemical reactivity do not necessarily lead from the above two-step model of enzyme catalysis to the observed 'saturation kinetics': other assumptions are needed, plausibly the inhibition of product release by the substrate itself. (Ironically, thus, the dramatic graphical representation of the MME encrypts its own fundamental flaw!) Perhaps the simplest indictment of the MME, however, lies in its formulation that the rate of the enzymic reaction tends towards a maximum of k~cat~[E~o~] in the 'saturation regime'. This implies - implausibly - that the turnover rate constant k~cat~ can be known from the overall rate, but independently of the dissociation constant (K~M~) of the binding step. (Many of these arguments have been presented previously in preliminary form.)
Constraints of FL Motif on the Targeting and Function of Sodium-Bicarbonate Cotransporter 1
Authors: Li Hong , Shawki Ali , Park YoonKyung , Li Emily Y , Hahm Kyung-Soo , Collier Joel H. , Mackenzie Bryan , Soleimani Manoocher
Published: July 2019

A C-terminal dihydrophobic FL motif plays a vital role in the basolateral targeting of sodium bicarbonate cotransporter 1. To further characterize the role of dihydrophobic FL motif, 1). the FL motif in wild type (PFLS) was reversed to LF (PLFS), 2). the FL motif (PFLS) was shifted upstream (FLPS), and 3). the FL motif (PFLS) was shifted downstream (PSFL). The wild type (PFLS) and its mutant (PLFS) were exclusively expressed on the basolateral membrane by con-focal microscopy, however, the mutant (FLPS) and (PSFL) were predominantly mistargeted to the apical membrane and the cytoplasm, respectively. Functional studies showed that the mutant (PSFL) displayed a remarkably reduced current (p value<0.05 vs wild type). The mutant (PSFL) displayed a more reduced membrane surface expression than the wild type and was co-localized with ER marker. The protein sequence spanning FL motif in kNBC1 C-terminal cytoplasmic tail shows a helical structure, mutants (PLFS) and (PSFL) reduce a-helical contents by circular dichroism study. Reversed FL isn't a constraint for basolateral targeting, but shifting it upstream and downstream are ones.
Ablation of smooth muscle myosin heavy chain SM2 increases smooth muscle contractility and results in postnatal death in mice
Authors: Chi Mei , Zhou Yingbi , Vedamoorthyrao Srikanth , Babu Gopal , Periasamy Muthu
Published: July 2019

The smooth muscle myosin heavy chains (SMHC) are motor proteins powering smooth muscle contraction. Alternate splicing of SHMC gene at the C-terminus produces SM1, and SM2 myosin isoforms; SM2 (200 kDa) contains a unique 9-amino-acid sequence at the carboxyl terminus, whereas SM1 (204 kDa) has a 43 amino acid non-helical tail region. To date the functional difference between C-terminal isoforms has not been established; therefore, we used an exon-specific gene targeting strategy and generated a mouse model specifically deficient in SM2. Deletion of exon-41 of the SMHC gene resulted in a complete loss of SM2 in homozygous (SM2^-/-^) mice, accompanied by a concomitant down-regulation of SM1 in bladders. While heterozygous (SM2^+/-^) mice appeared normal and fertile, SM2^-/-^ mice died within 30 days after birth. The peri-mortal SM2^-/-^ mice showed reduced body weight, distention of the bladder and alimentary tract, and end-stage hydronephrosis. Interestingly, strips from SM2^-/-^ bladders showed increased contraction to K^+^ depolarization or M3 receptor activation. These results suggest that SM2 myosin has a distinct functional role in smooth muscle, and the deficiency of SM2 increases smooth muscle contractility, and causes dysfunctions of smooth muscle organs, including the bladder that leads to the end-stage hydronephrosis and postnatal death.
Human microglial cells synthesize albumin in brain
Authors: Ahn Sung-Min , Byun Kyunghee , Cho Kun , Kim Jin Young , Yoo Jong Shin , Kim Deokhoon , Paek Sun Ha , Kim Seung , Simpson Richard , Lee Bonghee
Published: July 2019

Albumin has been implicated in Alzheimer's disease since it can bind to and transport amyloid beta, the causative agent; albumin is also a potent inhibitor of amyloid beta polymerization. In a pilot phase study of Human Brain Proteome Project, we found evidence that albumin may be synthesized in immortalized human microglial cells, human primary microglial cells, and human fetal and adult brain tissues. We also found the synthesis and secretion is enhanced upon microglial activation by Amyloid [beta]~1-42~, lipopolysaccharide treatment or human Alzheimer's brain.
Chronobiology of Epilepsy
Authors: Talathi Sachin , Hwang Dong-Uk , Ditto William , Spano Mark , Sepulveda Hector , Mareci Tom , Carney Paul
Published: July 2019

A fine balance between neuronal excitation and inhibition governs the physiological state of the brain. It has been hypothesized that when this balance is lost as a result of excessive excitation or reduced inhibition, pathological states such as epilepsy emerge. Decades of investigation have shown this to be true in vitro. However, in vivo evidence of the emerging imbalance during the "latent period" between the initiation of injury and the expression of the first spontaneous behavioral seizure has not been demonstrated. Here, we provide the first demonstration of this emerging imbalance between excitation and inhibition in vivo by employing long term, high temporal resolution, and continuous local field recordings from microelectrode arrays implanted in an animal model of limbic epilepsy. We were able to track both the inhibitory and excitatory postsynaptic field activity during the entire latent period, from the time of injury to the occurrence of the first spontaneous epileptic seizure. During this latent period we observe a sustained increase in the firing rate of the excitatory postsynaptic field activity, paired with a subsequent decrease in the firing rate of the inhibitory postsynaptic field activity within the CA1 region of the hippocampus. Firing rates of both excitatory and inhibitory CA1 field activities followed a circadian- like rhythm, which is locked near in-phase in controls and near anti-phase during the latent period. We think that these observed changes are implicated in the occurrence of spontaneous seizure onset following injury.
Investigating the frontoparietal network in mental calculation in primary school children - An fMRI study
Authors: Mondt Katrien , Balériaux Danielle , Metens Thierry , Paquier Philippe , Van de Craen Piet , Denolin Vincent
Published: July 2019

The frontoparietal network activated during calculation processing is investigated in a pediatric population. Subjects assessed correctness of two and three operand equations. Besides traditional frontoparietal activation, clear activation of sites associated with error processing was observed.
A Bacterial Enzyme Catalyzing Double Reduction of a β,δ-Diketo Ester with Unprecedented Stereoselectivity
Authors: Wu Xuri , Liu Nan , He Yunmian , Chen Yijun
Published: July 2019

Various ketoreductases exclusively participate in all common biological events, and they are a class of important biocatalysts for the production of chiral alcohols. While many types of ketoreductase have been extensively studied and their functions, properties and utilities have been well known, the capability of stereoselectively reducing two carbonyl groups in the same diketohexanoate ester molecule to form a dihydroxy product by a single ketoreductase has not been evidently characterized. Here we show that a unique and novel enzyme, diketoreductase, was cloned from Acinetobacter baylyi, heterogeneously expressed in Escherichia coli and purified to homogeneity. The diketoreductase is up to 78% homologous to bacterial 3-hydroxyacyl coenzyme-A reductases. However, recombinant diketoreductase does not reduce HMG-CoA, showing that the inference of function of enzymes like the diketoreductase based on sequence homology may be in error. The enzyme directly converts a β,δ-diketo ester to the corresponding dihydroxy ester. More remarkably, our results demonstrate that the recombinant enzyme possesses unprecedented stereoselectivity with both diastereomeric and enantiomeric excesses of greater than 99%. This new enzyme is of immediate value in developing a practical biocatalytic route to the side chains of statin drugs, such as Lipitor®.
"Ribopepzymes" are probably a link from ribozymes to protein enzymes
Authors: Sheng Yongjie , Jiang Dazhi , Zeng Zhen , Pan Feng , Zhang Jin
Published: July 2019

The evolutionary relationship between RNA- and protein-based biocatalysts was key to the evolution of living systems. This relationship is thought to have depended upon the transfer of both genetic information and catalytic function in living systems. We investigated whether ribozymes could transfer genetic information and catalytic function at the chemical level. We identified a family of peptides encoded by ribozymes: 13-residue peptide encoded by the hammerhead ribozyme, a 19-residue peptide encoded by the genomic hepatitis delta virus (HDV+) ribozyme, a 25-residue peptide encoded by the antigenomic HDV (HDV-) ribozyme, a 15-residue peptide encoded by the smallest trans-acting genomic HDV (SHDV) ribozyme, and a 22-residue peptide encoded by an open reading frame (ORF) of RNase P. We show that all these peptides possess the ability to cleave single-stranded RNA substrates. Furthermore, we expressed a 56-residue peptide encoded by an intact ORF (616-783) of the VS ribozyme, and found that it has single-stranded RNA cleavage activity as well. Because these catalytic peptides arise from a ribozyme-based code and their catalytic activity is ribonuclease-like, we have designated these peptides as "ribopepzymes". Ribopepzymes could be a link from ribozymes to protein enzymes in the early origin and evolution of enzymes. They also may provide a basis for designed, divergent evolution of enzyme function.
Genetic similarity promotes evolution of cooperation under lethal intergroup competition
Authors: Smirnov Oleg , Orbell John
Published: July 2019

Altruism (helping others at a cost to oneself) may evolve via group selection if the cost of altruism to the individual is compensated for by growth differences among groups when (1) there is high genetic variation among members of different groups; (2) more altruistic groups grow faster and (3) between-group migration is low. Nevertheless, group selection may not fully explain the actual evolution of helping behaviour if between-group migration was sufficiently common to have reduced between-group genetic variance. Lethal intergroup competition, which amplifies such growth differences between groups, appears to have been frequent in humans'; ancestral environments and could bear importantly on the evolution of altruism. Here we show that between-group migration and resulting genetic similarity can promote the evolution of costly helping behavior in the context of lethal intergroup conflict, albeit by selection at the individual level and not by group selection. The standard group selection models do not capture such basic elements of lethal intergroup competition as the possibility of an individual's altruism being critical to the group's success when that possibility is inversely proportional to genetic variation among members of the competing groups.
Colored filters improve exclusion of perceptual noise in visually symptomatic dyslexics
Authors: Northway Nadia , Manahilov Velitchko , Simpson William
Published: July 2019

Dyslexic individuals have deficits in detecting visual stimuli embedded in high levels of perceptual noise. Here we show that visually symptomatic dyslexics, who otherwise had elevated contrast thresholds for discriminating symbols in visual noise, had thresholds similar to non-dyslexics when wearing colored filters. These findings provide evidence that colored filters, which minimize the visual distortions and discomfort of dyslexics when reading, improve dyslexics' noise exclusion to normal levels.
The genetic equidistance result of molecular evolution is independent of mutation rates
Authors: Huang Shi
Published: July 2019

The genetic equidistance result shows that sister species are approximately equidistant to an outgroup as measured by DNA or protein dissimilarity. The equidistance result is the most direct evidence, and remains the only evidence, for the constant mutation rate interpretation of this result, known as the molecular clock. However, data independent of the equidistance result have steadily accumulated in recent years that often violate a constant mutation rate. Many have automatically inferred non-equidistance whenever a non-constant mutation rate was observed, based on the unproven assumption that the equidistance result is an outcome of constant mutation rate. Here it is shown that the equidistance result remains valid even when different species can be independently shown to have different mutation rates. A random sampling of 50 proteins shows that nearly all proteins display the equidistance result despite the fact that many proteins have non-constant mutation rates. Therefore, the genetic equidistance result does not necessarily mean a constant mutation rate. Observations of different mutation rates do not invalidate the genetic equidistance result.
Inverse relationship between genetic diversity and epigenetic complexity
Authors: Huang Shi
Published: July 2019

Early studies of molecular evolution revealed a correlation between genetic distance and time of species divergence. This observation provoked the molecular clock hypothesis and in turn the ‘Neutral Theory’, which however remains an incomplete explanation since it predicts a constant mutation rate per generation whereas empirical evidence suggests a constant rate per year. Data inconsistent with the molecular clock hypothesis have steadily accumulated in recent years that show no correlation between genetic distance and time of divergence. It has therefore become a challenge to find a testable idea that can reconcile the seemingly conflicting data sets. Here, an inverse relationship between genetic diversity and epigenetic complexity was deduced from a simple intuition in building complex systems. Genetic diversity, i.e., genetic distance or dissimilarity in DNA or protein sequences between individuals or species, is restricted by the complexity of epigenetic programs. This inverse relationship logically deduces the maximum genetic diversity hypothesis, which suggests that macroevolution from simple to complex organisms involves a punctuational increase in epigenetic complexity that in turn causes a punctuational loss in genetic diversity. The hypothesis explains a diverse set of biological phenomena, including both for and against the correlation between genetic distance and time of divergence.
Hot Cradle of El Niño
Authors: Sun Liguang , Xie Zhouqing
Published: July 2019

Here we propose that the El Niño is originated in the region of west-east oriented Galapagas ocean ridge and hydrothermal plumes. This region has a distinct tectonic structure: the subductions of ocean ridges go under continental volcanic activity zones; a special geographic location: equatorial ocean currents almost coincide with ocean ridge; and a unique south-north oriented convergent epi-continent ocean currents. The striking correlation between El Niño, seismic and submarine volcanic activities in this area and earth rotation speed changes strongly suggests that the sea floor near Peru coast sounds the "Hot Cradle" of El Niño.
Towards a cognitive definition of colour vision
Authors: Skorupski Peter , Chittka Lars
Published: July 2019

In recent years, colour vision abilities have been rather generously awarded to vari-ous invertebrates and even bacteria. This uncertainty of when to diagnose colour vi-sion stems in part from confusing what colour vision can do with what it is. What col-our vision can do is discriminate wavelength independent of intensity. However, if we take this as a definition of what colour vision is, then we might indeed be obliged to conclude that some plants and bacteria have colour vision. Moreover, there is a simi-lar confusion of what are necessary and what are sufficient mechanisms and behav-ioural abilities for colour vision. To humans, seeing in colour means seeing an image in which objects/lights have chromatic attributes - in contrast to the sensation that we have when viewing monochrome movies, or our experience in dim light when only rod vision is possible. The necessary basic equipment for this is to have at least two types of photoreceptors that differ in spectral sensitivity, and at least one type of spectrally opponent cell to compare the signals from the photoreceptors. Clearly, however, a necessary additional prerequisite for colour vision is to have vision, which entails the identification of shapes, sizes and locations of objects in the world. Thus if an animal has colour vision, it should see an image in which distinct objects/lights have colour attributes. This distinguishes colour vision from what has historically been called wavelength-specific behaviour: a type of behaviour triggered by fixed configurations of spectral receptor signals; however, we discuss difficulties in diagnosing wavelength specific behaviour as an indicator of the absence of colour vision.
Connecting Seed Lists of Mammalian Proteins Using Steiner Trees
Authors: White Amelia , Ma’ayan Avi
Published: July 2019

Multivariate experiments and genomics studies applied to mammalian cells often produce lists of genes or proteins altered under treatment/disease vs. control/normal conditions. Such lists can be identified in known protein-protein interaction networks to produce subnetworks that “connect” the genes or proteins from the lists. Such subnetworks are valuable for biologists since they can suggest regulatory mechanisms that are altered under different conditions. Often such subnetworks are overloaded with links and nodes resulting in connectivity diagrams that are illegible due to edge overlap. In this study, we attempt to address this problem by implementing an approximation to the Steiner Tree problem to connect seed lists of mammalian proteins/genes using literature-based protein-protein interaction networks. To avoid over-representation of hubs in the resultant Steiner Trees we assign a cost to Steiner Vertices based on their connectivity degree. We applied the algorithm to lists of genes commonly mutated in colorectal cancer to demonstrate the usefulness of this approach.
Cerebral malaria admissions in Papua New Guinea may show inter-annual cyclicity: An example of about a 1.5-year cycle for malaria incidence in Burundi
Authors: Dimitrov Borislav , Atanassova Penka
Published: July 2019

Best available descriptions of malaria incidence and mortality dynamics are important to better plan and evaluate the implementation of programs to monitor (e.g., remote sensing) and control the disease, especially in endemic zones. This was stressed recently by Cibulskis et al (2007) in the view of completeness of monthly reporting for cerebral malaria admissions in Papua New Guinea (latitude 6 degree S, 1987-1996). Notably, regardless of the rate of its completeness, the temporal dynamics of admissions was preserved over the years, however, neither raw data nor results on further analyses about eventual inter-annual cyclic components (periods T>1 year) were provided despite obvious graphical patterns for such a specific time structure (chronome). Interestingly, in a recent analysis by Gomez-Elipe et al (2007) on monthly malaria notifications in Burundi, at almost the same latitude (province of Karuzi, >3 degree S, 1997-2001), the data have shown neither trend not periodic oscillations beyond a 6-month (0.5-year) period. Since the graphical representation of both data sets have indicated an eventual existence of inter-annual variations, and because both are located at the same latitude zone, we have further analyzed the data from Burundi for such periodic oscillations. By using a periodogram regression analysis, we discovered a multicomponent cyclic chronome with periods above 12 months (T=17.5-18.0, 27.5 and 65.0-65.5 months, all at p<0.05). Notably, the most strong cyclic pattern at p<0.002 in the periodogram of the detrended malaria rates in Burundi remained only that with a peak at about 1.5 years (period T=17.5-18.0 months, R=0.51, z=5.3). It is possible that likely inter-annual cyclic patterns might exist also in the time structure for cerebral malaria admissions in Papua New Guinea and, if confirmed, these may be found very useful in epidemic forecasting and programs implementation. We explored these cyclic variations and also discussed possible associations with environmental factors exhibiting alike cyclicity.
A Paradigm for Biology's Next Revolution
Authors: Young Fredric
Published: July 2019

A recent essay on biology's next revolution described attributes of a future theory of biology that would replace post hoc modeling with an interplay between quantitative prediction and experimental test, more characteristic of the physical sciences1. The article suggested that flux from the environment whether it be energy, chemicals metabolites, or genes is a defining characteristic of life. The essay also suggests that an interdisciplinary approach to collective phenomena centered on statistical mechanics and dynamical systems theory will be required to make use of this perspective. Over the last 30 years we have developed an approach to drug discovery and translational research that is based on a paradigm for complex systems modeling that fits the description in the essay. The approach is a new paradigm because it focuses on the control of non-equilibrium flux, rather than genes. It has now been used to identify potential therapies for unmet medical needs that are currently being tested in phase II clinical trials.