WHICH EVOLUTIONARY FORCES DICTATE CODON USAGE IN HUMAN TESTIS SPECIFIC GENES?

Objective: Unequal usage of synonymous codons encoding an amino acid is termed as codon usage bias. Synonymous codon usage bias is an inevitable phenomenon in organismic taxa across the three domains of life, i.e. plants, animals and microbes. Here we report the codon usage pattern in human testis-specific genes found in Y chromosome. Testis-specific genes are associated with several dysfunctions, such as gonadal sex reversion, infertility, gonadoblastoma and non-syndromic hearing impairment.Methods: We used bioinformatics approaches to analyze codon usage bias in human testis-specific genesResults: Highly significant negative correlation was found between ICDI and tAI (r=-0.939**, p<0.01). Moreover, highly significant positive correlation between A% and A3% (r =0.774*, p<0.05), T and T3% (r=0.894**, p<0.01), GC% and GC3% (r = 0.897**, p<0.01) suggest that mutation pressure played an important role in codon usage pattern of these genes. However, significant positive correlation between G and G3 % (r =0.936**, p<0.01), G and C3 (r=0.557, p>0.05) but negative correlation between GC and T3 % (r=-0.960**, p<0.01) indicate the role of natural selection on codon bias. Variation of codon usage pattern was also evident in different genes from principal component analysis (PCA).Conclusion: Codon usage bias in human testis-specific genes is low. These genes are rich in GC content. Both natural selection and mutation pressure affect the codon usage bias in these genes.Keywords: Codon usage bias, Mutation pressure, Natural selectio

Engineering room-temperature multiferroicity in Bi and Fe codoped BaTiO3

Fe doping into BaTiO3, stabilizes the paraelectric hexagonal phase in place of the ferroelectric tetragonal one [P. Pal et al. Phys. Rev. B, 101, 064409 (2020)]. We show that simultaneous doping of Bi along with Fe into BaTiO3 effectively enhances the magnetoelectric (ME) multiferroic response (both ferromagnetism and ferroelectricity) at room-temperature, through careful tuning of Fe valency along with the controlled-recovery of ferroelectric-tetragonal phase. We also report systematic increase in large dielectric constant values as well as reduction in loss tangent values with relatively moderate temperature variation of dielectric constant around room-temperature with increasing Bi doping content in Ba1-xBixTi0.9Fe0.1O3 (0<x<0.1), which makes the higher Bi-Fe codoped sample (x=0.08) promising for the use as room-temperature high-k dielectric material. Interestingly, x=0.08 (Bi-Fe codoped) sample is not only found to be ferroelectrically (~20 times) and ferromagnetically (~6 times) stronger than x=0 (only Fe-doped) at room temperature, but also observed to be better insulating (larger bandgap) with indirect signatures of larger ME coupling as indicated from anomalous reduction of magnetic coercive field with decreasing temperature. Thus, room-temperature ME multiferroicity has been engineered in Bi and Fe codoped BTO (BaTiO3) compounds.Comment: 16 pages, 17 figure

Abnormal Blink Reflex and Intermuscular Coherence in Writer's Cramp

Background: Writer's cramp (WC) is a task-specific focal hand dystonia presenting with pain, stiffness and/or tremor while writing. We explored the involvement of cortical and brainstem circuits by measuring intermuscular coherence (IMC) and pre-pulse inhibition (PPI) of the blink reflex.Methods: IMC was measured in 10 healthy controls and 20 WC patients (10 with associated tremor) while they performed a precision grip task at different force levels. Blink responses were evaluated in 9 healthy controls and 10 WC patients by stimulating the right supraorbital nerve and recording surface EMG from the orbicularis oculi muscles bilaterally. PPI involved conditioning this stimulation with a prior shock to the right median nerve (100 ms interval), and measuring the reduction in the R2 component of the blink reflex.Results: Significant IMC at 3–7 Hz was present in WC patients, but not in healthy controls. Compared to healthy controls, in WC patients the R2 component of the blink reflex showed significantly less PPI. IMC at 3–7 Hz could reliably discriminate WC patients from healthy controls.Conclusion: Cortical or sub-cortical circuits generating theta (3–7 Hz) oscillations might play an important role in the pathogenesis of WC. Moreover, the lack of PPI implicates abnormalities in brainstem inhibition in the emergence of WC. IMC may merit further development as an electrodiagnostic test for focal dystonia

Phase-field modeling of grain-boundary grooving and migration under electric current and thermal gradient

Grain-boundary migration, void formation as well as associated hillock formation are important mechanisms which lead to the failure of interconnects in the microelectronic packages. An understanding of the underlying physics of each of the phenomena can allow better design of interconnects. In this paper, we formulate a new phase-field model based on a grand-potential formalism for studying the phenomena of grain-boundary grooving under the combined influence of pure diffusion controlled transport, electric current and thermal gradient. We separately investigate the contributions of each of the stimuli towards the process of grain-boundary migration and hillock formation, by performing phase-field simulations as well as comparing with analytical theories. Additionally, we qualitatively reproduce the phenomena observed in experiments on polycrystalline metals, wherein electromigration and thermomigration may act in unison or against each other towards their contributions in grooving, hillocking and void growth. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved

Botulinum Toxin: An Update on Pharmacology and Newer Products in Development

Since its introduction as a treatment for strabismus, botulinum toxin (BoNT) has had a phenomenal journey and is now recommended as first-line treatment for focal dystonia, despite short-term clinical benefits and the risks of adverse effects. To cater for the high demand across various medical specialties, at least six US Food and Drug Administration (FDA)-approved formulations of BoNT are currently available for diverse labelled indications. The toxo-pharmacological properties of these formulations are not uniform and thus should not be used interchangeably. Synthetic BoNTs and BoNTs from non-clostridial sources are not far from clinical use. Moreover, the study of mutations in naturally occurring toxins has led to modulation in the toxo-pharmacokinetic properties of BoNTs, including the duration and potency. We present an overview of the toxo-pharmacology of conventional and novel BoNT preparations, including those awaiting imminent translation from the laboratory to the clinic

Codon usage bias and phylogenetic analysis of mitochondrial ND1 gene in pisces, aves, and mammals

<p>The mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 (MT-ND1) gene is a subunit of the respiratory chain complex I and involved in the first step of the electron transport chain of oxidative phosphorylation (OXPHOS). To understand the pattern of compositional properties, codon usage and expression level of mitochondrial ND1 genes in pisces, aves, and mammals, we used bioinformatic approaches as no work was reported earlier. In this study, a perl script was used for calculating nucleotide contents and different codon usage bias parameters. The codon usage bias of MT-ND1 was low but the expression level was high as revealed from high ENC and CAI value. Correspondence analysis (COA) suggests that the pattern of codon usage for MT-ND1 gene is not same across species and that compositional constraint played an important role in codon usage pattern of this gene among pisces, aves, and mammals. From the regression equation of GC12 on GC3, it can be inferred that the natural selection might have played a dominant role while mutation pressure played a minor role in influencing the codon usage patterns. Further, ND1 gene has a discrepancy with cytochrome B (CYB) gene in preference of codons as evident from COA. The codon usage bias was low. It is influenced by nucleotide composition, natural selection, mutation pressure, length (number) of amino acids, and relative dinucleotide composition. This study helps in understanding the molecular biology, genetics, evolution of MT-ND1 gene, and also for designing a synthetic gene.</p

Effect of central lesions on a spinal circuit facilitating human wrist flexors

Abstract A putative spinal circuit with convergent inputs facilitating human wrist flexors has been recently described. This study investigated how central nervous system lesions may affect this pathway. We measured the flexor carpi radialis H-reflex conditioned with stimulation above motor threshold to the extensor carpi radialis at different intervals in fifteen patients with stroke and nine with spinal cord injury. Measurements after stroke revealed a prolonged facilitation of the H-reflex, which replaced the later suppression seen in healthy subjects at longer intervals (30–60 ms). Measurements in patients with incomplete spinal cord injury at cervical level revealed heterogeneous responses. Results from patients with stroke could represent either an excessive facilitation or a loss of inhibition, which may reflect the development of spasticity. Spinal cord injury results possibly reflect damage to the segmental interneuron pathways. We report a straightforward method to assess changes to spinal circuits controlling wrist flexors after central nervous system lesion

Interphase anisotropy effects on lamellar eutectics: A numerical study

International audienceIn directional solidification of binary eutectics, it is often observed that two-phase lamellar growth patterns grow tilted with respect to the direction z of the imposed temperature gradient. This crystallographic effect depends on the orientation of the two crystal phases α and β with respect to z. Recently, an approximate theory was formulated that predicts the lamellar tilt angle as a function of the anisotropy of the free energy of the solid(α)-solid(β) interphase boundary. We use two different numerical methods – phase-field (PF) and dynamic boundary-integral (BI) – to simulate the growth of steady periodic patterns in two dimensions as a function of the angle θR between z and a reference crystallographic axis for a fixed relative orientation of α and β crystals, that is, for a given anisotropy function (Wulff plot) of the interphase boundary. For Wulff plots without unstable interphase-boundary orientations, the two simulation methods are in excellent agreement with each other, and confirm the general validity of the previously proposed theory. In addition, a crystallographic “locking” of the lamellae onto a facet plane is well reproduced in the simulations. When unstable orientations are present in the Wulff plot, it is expected that two distinct values of the tilt angle can appear for the same crystal orientation over a finite θR range. This bistable behavior, which has been observed experimentally, is well reproduced by BI simulations, but not by the PF model. Possible reasons for this discrepancy are discussed