Mitochondrial signatures revealed panmixia in <Emphasis Type="Italic">Lutjanus argentimaculatus</Emphasis> (Forsskål 1775)

Mangrove red snapper, Lutjanus argentimaculatus is a commercially important fish. The genetic stock structure of L. argentimaculatus from Indian waters was identified using mitochondrial ATPase 6 and ATPase 8, and cytochrome b (Cytb) genes. A 842 bp region of ATPase 6/8 genes and 1105 bp region of Cytb gene were amplified in 120 samples from six different locations along the Indian coast and obtained 58 and 66 haplotypes, respectively. The high haplotype and low nucleotide diversity values along with mismatch distribution, Tajima’s D and Fu’s \(F_\mathrm{s}\) analysis suggested a genetic bottleneck events or founder effect, with subsequent population expansion in L. argentimaculatus. Coefficient of genetic differentiation \((F_\mathrm{ST})\) values was low and nonsignificant for both ATPase 6/8 gene and Cytb genes indicating low genetic differentiation in L. argentimaculatus which can be managed as a unit stock in Indian waters.     

NMR simulation analysis of statistical effects on quantifying cerebrovascular parameters

Determining tissue structure and composition from the behavior of the NMR transverse relaxation during free induction decay and spin echo formation has seen significant advances in recent years. In particular, the ability to quantify cerebrovascular network parameters such as blood volume and deoxyhemoglobin concentration from the NMR signal dephasing has seen intense focus. Analytical models have been described, based on statistical averaging of randomly oriented cylinders in both the static and slow diffusion regimes. However, the error in estimates obtained from these models when applied to systems in which the statistical assumptions of many, randomly oriented perturbers are violated has not been systematically investigated. Using a deterministic simulation that can include diffusion, we find that the error in estimated venous blood volume fraction and deoxyhemoglobin concentration obtained using a static dephasing regime statistical model is inversely related to the square root of number of blood vessels. The most important implication of this is that the minimum imaging resolution for accurate deoxyhemoglobin and blood volume estimation is not bound by hardware limitations, but rather by the underlying tissue structure.     

Change in dysphagia and laryngeal function after radical radiotherapy in laryngo pharyngeal malignancies — a prospective observational study

BackgroundIntensity modulated radiotherapy (IMRT) has the perceived advantage of function preservation by reduction of toxicities in the treatment of laryngo-pharyngeal malignancies. The aim of the study was to assess changes in dysphagia from baseline (i.e. prior to start of treatment) at three and six months post treatment in patients with laryngo-pharyngeal malignancies treated with radical radiotherapy ± chemotherapy. Functional assessment of other structures involved in swallowing was also studied.Materials and methods40 patients were sampled consecutively. 33 were available for final analysis. Dysphagia, laryngeal edema, xerostomia and voice of patients were assessed at baseline and at three and six months after treatment. Radiation was delivered with simultaneous integrated boost (SIB) using volumetric modulated radiation therapy (VMAT). Concurrent chemotherapy was three weekly cisplatin 100 mg/m².ResultsProportion of patients with dysphagia rose significantly from 45.5% before the start of treatment to 57.6% at three months and 60.6% at six months post treatment (p = 0.019). 67% patients received chemotherapy and addition of chemotherapy had a significant correlation with dysphagia (p = 0.05, r = −0.336). Severity of dysphagia at three and six months correlated significantly with the mean dose received by the superior constrictors (p = 0.003, r = 0.508 and p = 0.024, r = 0.391) and oral cavity (p = 0.001, r = 0.558 and p = 0.003, r = 0.501). There was a significant worsening in laryngeal edema at three and six months post treatment (p < 0.01) when compared to the pre-treatment examination findings with 60.6% of patients having grade two edema at six months. Significant fall in the mean spoken fundamental frequency from baseline was seen at 6 months (p = 0.04), mean fall was 21.3 Hz (95% CI: 1.5–41 Hz) with significant increase in roughness of voice post treatment (p = 0.01).ConclusionThere was progressive worsening in dysphagia, laryngeal edema and voice in laryngo-pharyngeal malignancies post radical radiotherapy ± chemotherapy.     

Fragile X mental retardation protein interactions with the microtubule associated protein 1B RNA

Fragile X mental retardation syndrome, the most common form of inherited mental retardation, is caused by the absence of the fragile X mental retardation protein (FMRP). FMRP has been shown to use its arginine-glycine-glycine (RGG) box to bind to a subset of RNA targets that form a G quadruplex structure. We performed a detailed analysis of the interactions between the FMRP RGG box and the microtubule associated protein 1B (MAP1B) mRNA, a relevant in vivo FMRP target. We show that MAP1B RNA forms an intramolecular G quadruplex structure, which is bound with high affinity and specificity by the FMRP RGG box. We determined that hydrophobic interactions are important in the FMRP RGG box-MAP1B RNA association, with minor contributions from electrostatic interactions. Our findings that at low protein:RNA ratios the RNA G quadruplex structure is slightly stabilized, whereas at high ratios is unfolded, suggest a mechanism by which the FMRP concentration variation in response to a neurotransmitter stimulation event could act as a regulatory switch for the protein function, from translation repressor to translation activator.     

The sensitization of glioma cells to cisplatin and tamoxifen by the use of catechin

Telomerase expression strongly correlates with the grade of malignancy in glioma with inhibition illustrating a definite increase in chemosensitivity. This study was designed to investigate the effects of a green tea derivative, epigallocatechin-3-gallate (EGCG); together with either cisplatin or tamoxifen in glioma, and to investigate whether these effects are mediated through telomerase suppression. EGCG showed a significant cytotoxic effect on 1321N1 cells after 24 h and on U87-MG cells after 72 h (P < 0.001) without significantly affecting the normal astrocytes. Treatment with EGCG inhibited telomerase expression significantly (P < 0.01) and enhanced the effect of cisplatin and tamoxifen in both 1321N1 (P < 0.01) and U87-MG (P < 0.001) cells. EGCG, as a natural product has enormous potential to be an anti-cancer agent capable of enhancing tumour cell sensitivity to therapy.     

Yeast oxysterol-binding proteins: sterol transporters or regulators of cell polarization?

Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) are a conserved family of soluble cytoplasmic proteins that can bind sterols, translocate between membrane compartments, and affect sterol trafficking. These properties make ORPs attractive candidates for lipid transfer proteins (LTPs) that directly mediate nonvesicular sterol transfer to the plasma membrane. To test whether yeast ORPs (the Osh proteins) are sterol LTPs, we studied endoplasmic reticulum (ER)-to-plasma membrane (PM) sterol transport in OSH deletion mutants lacking one, several, or all Osh proteins. In conditional OSH mutants, ER-PM ergosterol transport slowed ~20-fold compared with cells expressing a full complement of Osh proteins. Although this initial finding suggested that Osh proteins act as sterol LTPs, the situation is far more complex. Osh proteins have established roles in Rho small GTPase signaling. Osh proteins reinforce cell polarization and they specifically affect the localization of proteins involved in polarized cell growth such as septins, and the GTPases Cdc42p, Rho1p, and Sec4p. In addition, Osh proteins are required for a specific pathway of polarized secretion to sites of membrane growth, suggesting that this is how Osh proteins affect Cdc42p- and Rho1p-dependent polarization. Our findings suggest that Osh proteins integrate sterol trafficking and sterol-dependent cell signaling with the control of cell polarization.