bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractContextual 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

AbstractThe 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

AbstractA 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

AbstractThe 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

AbstractAlbumin 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

AbstractA 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

AbstractThe 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

AbstractVarious 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

AbstractThe 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

AbstractAltruism (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

AbstractDyslexic 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

AbstractThe 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

AbstractEarly 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

AbstractHere 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

AbstractIn 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

AbstractMultivariate 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

AbstractBest 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.