EmbR, a putative transcriptional regulator from Mycobacterium tuberculosis, is homologous to the OmpR class of transcriptional regulators that possess winged helix-turn-helix DNA binding motifs. In contrast to other OmpR-like response regulators that are usually phosphorylated and controlled by histidine kinases, EmbR was recently shown to be phosphorylated by the cognate mycobacterial serine/threonine kinase PknH. Despite the in vitro evidence of phosphorylation and interaction between the kinase and regulator, the physiological function of the PknH-EmbR pair is still unknown. We identify the embCAB operon encoding arabinosyltransferases in M. tuberculosis as the cellular target of EmbR. Phosphorylation of EmbR enhances its DNA binding activity towards promoter regions of embCAB genes. In vivo studies involving expression of PknH in Mycobacterium smegmatis established its positive regulatory effect on transcription of the embCAB operon via phosphorylation of EmbR. Interestingly, increased transcription of embC, catalyzing arabinosylation of lipomannan (LM) to lipoarabinomannan (LAM), results in a high LAM/LM ratio, which in turn is a crucial factor in mycobacterial virulence. The PknH-mediated increase in the transcription of embAB genes significantly alters resistance to ethambutol, a frontline antituberculosis drug known to target embAB genes. These findings and in vivo upregulation of PknH inside the host macrophages suggest a functionally relevant signaling mechanism involving the PknH-EmbR-embCAB system.
The corpus callosum (CC) is the main commissure connecting the cerebral hemispheres. Previous evidence suggests the involvement of CC in the pathophysiology of autism. However, most studies examined the mid-sagittal area and investigations applying more precise methods are warranted. The goal of this investigation is to apply a volumetric method to examine the size of the CC in autism and to identify any association with clinical features. An MRI-based morphometric study of the total CC volume and its 7 subdivisions was conducted and involved 22 children with autism (age range 8.1-12.7 years) and 23 healthy, age-matched controls. Reductions in the total volume of the CC and several of its subdivisions were found in the autism sample. Associations were observed between CC structures and clinical features including social deficits, repetitive behaviors, and sensory abnormalities. Volumetric alterations of the CC observed in this investigation are consistent with midsagittal area tracings of decreased CC size in autism. These findings support the aberrant connectivity hypothesis with possible decrease in interhemispheric communications.
siRNA-mediated knockdown of 40 putative ciliome genes reveals distinct roles in cilia formation, cilia elongation, ciliary transport of different cargoes, and signaling capability. Depletion of a subset of genes allows cilia transport to be uncoupled from cilia formation, whereas most genes are required for efficient signaling function.
Energy distributions are measured for ions emitted upon Coulomb explosion of Ar n clusters (n = 400-900) upon irradiation by intense three-cycle pulses (10 fs) of 800-nm laser light of peak intensity 5 × 10 14 W cm −2 . With few-cycle pulses, there is insufficient time for the cluster to undergo expansion; this results in overall dynamics that are significantly different from those in the many-cycle regime. The peak ion energies are much lower than those obtained when 100-fs pulses of the same intensity are used; they are almost independent of the size of the cluster (over the range 400-900 atoms). Ion yields are measured to be larger in the direction that is perpendicular to the laser-polarization vector than along it. Model molecular dynamics calculations are used to qualitatively rationalize this unexpected anisotropy in terms of shielding by a spatially asymmetric electronic-charge cloud within the cluster.
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