The molecular architecture of the ciliary transition zones.

Cilia and flagella are specialized eukaryotic organelles projecting from the surface of eukaryotic cells that play a central role in various physiological processes, including cell motility, sensory perception, and signal transduction. At the base of these structures lies the ciliary transition zone, a pivotal region that functions as a gatekeeper and communication hub for ciliary activities. Despite its crucial role, the intricacies of its architecture remain poorly understood, especially given the variations in its organization across different cell types and species. In this review, we explore the molecular architecture of the ciliary transition zone, with a particular focus on recent findings obtained using cryotomography and super-resolution imaging techniques.

Enantioselectivity in the enzymatic dehydration of malate and tartrate: Mirror image specificities of structurally similar dehydratases.

Malate (2-hydroxysuccinic acid) and tartrate (2,3-dihydroxysuccinic acid) are chiral substrates; the former existing in two enantiomeric forms (R and S) while the latter exists as three stereoisomers (R,R; S,S; and R,S). Dehydration by stereospecific hydrogen abstraction and antielimination of the hydroxyl group yield the achiral products fumarate and oxaloacetate, respectively. Class-I fumarate hydratase (FH) and L-tartrate dehydratase (L-TTD) are two highly conserved enzymes belonging to the iron-sulfur cluster hydrolyase family of enzymes that catalyze reactions on specific stereoisomers of malate and tartrate. FH from Methanocaldococcus jannaschii accepts only (S)-malate and (S,S)-tartrate as substrates while the structurally similar L-TTD from Escherichia coli accepts only (R)-malate and (R,R)-tartrate as substrates. Phylogenetic analysis reveals a common evolutionary origin of L-TTDs and two-subunit archaeal FHs suggesting a divergence during evolution that may have led to the switch in substrate stereospecificity preference. Due to the high conservation of their sequences, a molecular basis for switch in stereospecificity is not evident from analysis of crystal structures of FH and predicted structure of L-TTD. The switch in enantiomer preference may be rationalized by invoking conformational plasticity of the amino acids interacting with the substrate, together with substrate reorientation and conformer selection about the C2C3 bond of the dicarboxylic acid substrates. Although classical models of enzyme-substrate binding are insufficient to explain such a phenomenon, the enantiomer superposition model suggests that a minor reorientation in the active site residues could lead to the switch in substrate stereospecificity.

A study of electrocardiographic and 2D echocardiographic changes in type 2 diabetes mellitus patients without cardiovascular symptoms.

Context: Cardiovascular diseases in diabetic patients are mostly asymptomatic due to autonomic neuropathy. Many patients with left ventricular dysfunction remain undiagnosed and untreated until advance disease causes disability. This delay could be avoided if screening techniques are used to identify left ventricular dysfunction in its preclinical phase. Aims: This study was undertaken to find out the incidence of electrocardiographic (ECG) and 2D echocardiographic (2 D Echo) abnormalities in diabetic patients without cardiovascular symptoms. The correlation of control of diabetes with these abnormalities was also studied. Settings and Design: A hospital-based, cross-sectional observational study. Methods and Material: Type 2 diabetic patients (outpatient and indoor) without cardiovascular symptoms like palpitations, chest pain, syncope, and breathlessness were included in the study. Their ECG and 2D Echo findings were noted and correlated with their blood sugar levels. Statistical Analysis Used: Chi-square test. Results: Type 2 diabetic patients without cardiovascular symptoms had significant abnormal findings on ECG and 2D Echo. Control of postprandial blood sugar level was of primary importance to prevent cardiovascular abnormalities. Conclusions: Type 2 diabetics without cardiovascular symptoms must be screened for cardiovascular abnormalities so that early interventions can be done to prevent further progression to symptomatic cardiovascular abnormalities. There is a significant number of people having normal ECG but abnormal 2D Echo and vice versa, so not only ECG but also 2D Echo should be done to predict cardiovascular risk in type 2 diabetic patients without cardiovascular symptoms.