Hierarchical motor adaptations negotiate failures during force field learning

Humans have the amazing ability to learn the dynamics of the body and environment to develop motor skills. Traditional motor studies using arm reaching paradigms have viewed this ability as the process of ‘internal model adaptation’. However, the behaviors have not been fully explored in the case when reaches fail to attain the intended target. Here we examined human reaching under two force fields types; one that induces failures (i.e., target errors), and the other that does not. Our results show the presence of a distinct failure-driven adaptation process that enables quick task success after failures, and before completion of internal model adaptation, but that can result in persistent changes to the undisturbed trajectory. These behaviors can be explained by considering a hierarchical interaction between internal model adaptation and the failure-driven adaptation of reach direction. Our findings suggest that movement failure is negotiated using hierarchical motor adaptations by humans.     

The CNS stochastically selects motor plan utilizing extrinsic and intrinsic representations

Traditionally motor studies have assumed that motor tasks are executed according to a single plan characterized by regular patterns, which corresponds to the minimum of a cost function in extrinsic or intrinsic coordinates. However, the novel via-point task examined in this paper shows distinct planning and execution stages in motion production and demonstrates that subjects randomly select from several available motor plans to perform a task. Examination of the effect of pre-training and via-point orientation on subject behavior reveals that the selection of a plan depends on previous movements and is affected by constraints both intrinsic and extrinsic of the body. These results provide new insights into the hierarchical structure of motion planning in humans, which can only be explained if the current models of motor control integrate an explicit plan selection stage.     

An In Silico Analysis of Troponin I Mutations in Hypertrophic Cardiomyopathy of Indian Origin

Hypertrophic Cardiomyopathy (HCM) is an autosomal dominant disorder of the myocardium which is hypertrophied resulting in arrhythmias and heart failure leading to sudden cardiac death (SCD). Several sarcomeric proteins and modifier genes have been implicated in this disease. Troponin I, being a part of the Troponin complex (troponin I, troponin C, troponin T), is an important gene for sarcomeric function. Four mutations (1 novel) were identified in Indian HCM cases, namely, Pro82Ser, Arg98Gln, Arg141Gln and Arg162Gln in Troponin I protein, which are in functionally significant domains. In order to analyse the effect of the mutations on protein stability and protein-protein interactions within the Troponin complex, an in silico study was carried out. The freely available X-ray crystal structure (PDB ID: 1JIE) was used as the template to model the protein followed by loop generation and development of troponin complex for both the troponin I wild type and four mutants (NCBI ID: PRJNA194382). The structural study was carried out to determine the effect of mutation on the structural stability and protein-protein interactions between three subunits in the complex. These mutations, especially the arginine to glutamine substitutions were found to result in local perturbations within the troponin complex by creating/removing inter/intra molecular hydrogen bonds with troponin T and troponin C. This has led to a decrease in the protein stability and loss of important interactions between the three subunits. It could have a significant impact on the disease progression when coupled with allelic heterogeneity which was observed in the cases carrying these mutations. However, this can be further confirmed by functional studies on protein levels in the identified cases.     

A Novel Autosomal Recessive GJA1 Missense Mutation Linked to Craniometaphyseal Dysplasia

Craniometaphyseal dysplasia (CMD) is a rare sclerosing skeletal disorder with progressive hyperostosis of craniofacial bones. CMD can be inherited in an autosomal dominant (AD) trait or occur after de novo mutations in the pyrophosphate transporter ANKH. Although the autosomal recessive (AR) form of CMD had been mapped to 6q21-22 the mutation has been elusive. In this study, we performed whole-exome sequencing for one subject with AR CMD and identified a novel missense mutation (c.716G>A, p.Arg239Gln) in the C-terminus of the gap junction protein alpha-1 (GJA1) coding for connexin 43 (Cx43). We confirmed this mutation in 6 individuals from 3 additional families. The homozygous mutation cosegregated only with affected family members. Connexin 43 is a major component of gap junctions in osteoblasts, osteocytes, osteoclasts and chondrocytes. Gap junctions are responsible for the diffusion of low molecular weight molecules between cells. Mutations in Cx43 cause several dominant and recessive disorders involving developmental abnormalities of bone such as dominant and recessive oculodentodigital dysplasia (ODDD; MIM #164200, 257850) and isolated syndactyly type III (MIM #186100), the characteristic digital anomaly in ODDD. However, characteristic ocular and dental features of ODDD as well as syndactyly are absent in patients with the recessive Arg239Gln Cx43 mutation. Bone remodeling mechanisms disrupted by this novel Cx43 mutation remain to be elucidated.     

Development of reproducible regeneration and transformation system for Sesamum indicum

Thalictrum foliolosum is an endemic herb known for its medicinal properties and used for various clinical applications including ophthalmic, skin disease and dyspepsia. Due to its medicinal properties, the plants are uprooted hence can be prone to extinction. In the present study, a reproducible in vitro propagation protocol has been developed using axillary shoot buds and nodal segments. Seedling derived axillary shoot buds were cultured in Murashige and Skoog’s (MS) medium supplemented with 2.24 µmol of 6-benzylaminopurine (BAP) and readily produced maximum shoot (7.2?±?0.40) with the highest percentage of response (91.42%). Also, nodal explants (field-grown plant) developed maximum shoots (3.2?±?0.48) on MS medium containing 4.49 µmol BAP with a combination of 0.54 µmol α-naphthaleneacetic acid (NAA). Best growth and foliage development was achieved at 2.24 µmol BAP with 0.54 µmol NAA in presence of 0.3% activated charcoal and 113.4 µmol ascorbic acid. Micropropagated shoots showed maximum percentage (63.30%) of rooting in half-strength MS medium containing 1.23 µmol indole-3-butyric acid (IBA) and acclimatized in soilrite and leaf manure (2:1) during 4 weeks. Monomorphic bands developed by random amplification of polymorphic DNA (RAPD) and simple sequence repeats (SSR) markers confirmed the genetic stability of in vitro established plants. Additionally, HPLC analysis showed higher benzylisoquinoline (BIQ) alkaloids content in in vitro established plant root extracts. The micropropagation protocol developed in this study provides an alternative strategy for germplasm conservation and protection which at the same time can also be exploits for the production of pharmacologically active compounds.

     

Marker-assisted selection for grain number and yield-related traits of rice (Oryza sativa L.)

Physiology and Molecular Biology of Plants - Continuous rise in the human population has resulted in an upsurge in food demand, which in turn demand grain yield enhancement of cereal crops,...     

Export of adenoviral late mRNA from the nucleus requires the Nxf1/Tap export receptor

One important function of the human adenovirus E1B 55-kDa protein is induction of selective nuclear export of viral late mRNAs. This protein interacts with the viral E4 Orf6 and four cellular proteins to form an infected-cell-specific E3 ubiquitin ligase. The assembly of this enzyme is required for efficient viral late mRNA export, but neither the relevant substrates nor the cellular pathway that exports viral late mRNAs has been identified. We therefore examined the effects on viral late gene expression of inhibition of the synthesis or activity of the mRNA export receptor Nxf1, which was observed to colocalize with the E1B 55-kDa protein in infected cells. When production of Nxf1 was impaired by using RNA interference, the efficiency of viral late mRNA export was reduced to a corresponding degree. Furthermore, synthesis of a dominant-negative derivative of Nxf1 during the late phase of infection interfered with production of a late structural protein. These observations indicate that the Nxf1 pathway is responsible for export of viral late mRNAs. As the infected-cell-specific E3 ubiquitin ligase targets its known substrates for proteasomal degradation, we compared the concentrations of several components of this pathway (Nxf1, Thox1, and Thoc4) in infected cells that did or did not contain this enzyme. Although the concentration of a well-established substrate, Mre11, decreased significantly in cells infected by adenovirus type 5 (Ad5), but not in those infected by the E1B 55-kDa protein-null mutant Hr6, no E1B 55-kDa protein-dependent degradation of the Nxf1 pathway proteins was observed.