Dose-response studies on the spermatogonial stem cells of the rhesus monkey (Macaca mulatta) after X irradiation

Studies of the dose response of the spermatogonial stem cells in the rhesus monkey were performed at intervals of 130 and 160 days after graded doses of X irradiation. The D0 of the spermatogonial stem cells was established using the total numbers of the type A spermatogonia that were present at 130 and 160 days after irradiation and was found to be 1.07 Gy; the 95% confidence interval was 0.90-1.34 Gy.     

Trace-Level Detection of Explosive Molecules with Triangular Silver Nanoplates-Based SERS Substrates

We report a simple route to design highly sensitive triangular silver nanoplates (TSNPs)-based SERS substrate for the trace-level detection of explosive molecules. The size-dependent localized surface plasmon resonance (LSPR) tunability for the synthesis of TSNPs is achieved by controlling reaction kinetics and seed volume in a modified seed-mediated approach. The computed extinction spectra of TSNP, using the finite-difference time-domain (FDTD) method, are in excellent agreement with the experimental results, therefore assisting further in the investigation of the plasmonic properties of TSNP. The higher electric field enhancement offered by TSNP is systematically investigated by performing the FDTD simulations for various sizes and corner rounding of TSNP. The FDTD results show that the dipolar plasmon resonance wavelength, size, and corner rounding of TSNP are the principal contributing factors for designing the high-performance SERS substrate. Herein, we have used a portable Raman system for the SERS-based detection of three important explosive molecules: picric acid (PA), ammonium nitrate (AN), and 2, 4-dinitrotoluene (DNT). The TSNP-based SERS substrates display excellent intensity enhancement factors of?~?10⁷ for rhodamine 6G (R6G) and PA and?~?10⁵ for AN. The high sensitivity of SERS substrate with limit-of-detection (LOD) of value 2.3?×?10^?11 M for PA and 3.1?×?10^?8 M for AN and effective batch-to-batch reproducibility for DNT, thus offering its potentials for field detection of explosive molecules at trace-level.

     

The extracellular signal-regulated kinase 3 (mitogen-activated protein kinase 6 [MAPK6])-MAPK-activated protein kinase 5 signaling complex regulates septin function and dendrite morphology

Mitogen-activated protein kinase-activated protein (MAPKAP) kinase 5 (MK5) deficiency is associated with reduced extracellular signal-regulated kinase 3 (ERK3) (mitogen-activated protein kinase 6) levels, hence we utilized the MK5 knockout mouse model to analyze the physiological functions of the ERK3/MK5 signaling module. MK5-deficient mice displayed impaired dendritic spine formation in mouse hippocampal neurons in vivo. We performed large-scale interaction screens to understand the neuronal functions of the ERK3/MK5 pathway and identified septin7 (Sept7) as a novel interacting partner of ERK3. ERK3/MK5/Sept7 form a ternary complex, which can phosphorylate the Sept7 regulators Binders of Rho GTPases (Borgs). In addition, the brain-specific nucleotide exchange factor kalirin-7 (Kal7) was identified as an MK5 interaction partner and substrate protein. In transfected primary neurons, Sept7-dependent dendrite development and spine formation are stimulated by the ERK3/MK5 module. Thus, the regulation of neuronal morphogenesis is proposed as the first physiological function of the ERK3/MK5 signaling module.     

Selection and cloning of poly(rC)-binding protein 2 and Raf kinase inhibitor protein RNA activators of 2',5'-oligoadenylate synthetase from prostate cancer cells

The antiviral and antitumor functions of RNase L are enabled by binding to the allosteric effectors 5′-phosphorylated, 2′,5′-linked oligoadenylates (2-5A). 2-5A is produced by interferon-inducible 2′,5′-oligoadenylate synthetases (OAS) upon activation by viral double-stranded RNA (dsRNA). Because mutations in RNase L have been implicated as risk factors for prostate cancer, we sought to determine if OAS activators are present in prostate cancer cells. We show that prostate cancer cell lines (PC3, LNCaP and DU145), but not normal prostate epithelial cells (PrEC), contain RNA fractions capable of binding to and activating OAS. To identify the RNA activators, we developed a cDNA cloning strategy based on stringent affinity of RNAs for OAS. We thus identified mRNAs for Raf kinase inhibitor protein (RKIP) and poly(rC)-binding protein 2 (PCBP2) that bind and potently activate OAS. In addition, human endogenous retrovirus (hERV) envelope RNAs were present in PC3 cells that bind and activate OAS. Analysis of several gene expression profiling studies indicated that PCBP2 RNA was consistently elevated in metastatic prostate cancer. Results suggest that OAS activation may occur in prostate cancer cells in vivo stimulated by cellular mRNAs for RKIP and PCBP2.     

A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus

The expression of imprinted genes is mediated by allele-specific epigenetic modification of genomic DNA and chromatin, including parent of origin-specific DNA methylation. Dysregulation of these genes causes a range of disorders affecting pre- and post-natal growth and neurological function. We investigated a cohort of 12 patients with transient neonatal diabetes whose disease was caused by loss of maternal methylation at the TNDM locus. We found that six of these patients showed a spectrum of methylation loss, mosaic with respect to the extent of the methylation loss, the tissues affected and the genetic loci involved. Five maternally methylated loci were affected, while one maternally methylated and two paternally methylated loci were spared. These patients had higher birth weight and were more phenotypically diverse than other TNDM patients with different aetiologies, presumably reflecting the influence of dysregulation of multiple imprinted genes. We propose the existence of a maternal hypomethylation syndrome, and therefore suggest that any patient with methylation loss at one maternally-methylated locus may also manifest methylation loss at other loci, potentially complicating or even confounding the clinical presentation.Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at .     

Plant regeneration from alginate-encapsulated shoot tips of Spilanthes acmella (L.) Murr., a medicinally important and herbal pesticidal plant species

This article demonstrates the plantlet regeneration from alginate-encapsulated shoot tips of Spilanthes acmella. Shoot tip explants excised from in vitro proliferated shoots were encapsulated in calcium alginate beads. The best gel complexation for encapsulation of shoot tips was achieved using 3% sodium alginate and 100 mM calcium chloride. Maximum percent response for the conversion of encapsulated shoot tips into plantlets was obtained on growth regulator-free full-strength liquid MS (Murashige and Skoog, Physiol Plant 15:473–497, 1962) medium. The addition of MS nutrients in alginate matrix was found to have pronounced effect on shoot and root emergence from alginate beads. Encapsulated shoot tips could be stored at low temperature (4°C) up to 60 days. Plantlets regenerated from encapsulated shoot tips were acclimatized successfully. The present synthetic seed technology could be useful in large-scale propagation as well as short-term conservation and germplasm distribution and exchange of Spilanthes acmella. S. K. Singh and M. K. Rai contributed equally to this work.     

Alterations in Biochemical Parameters During Subacute Toxicity of Fluoride Alone and in Conjunction with Aluminum Sulfate in Goats

Fluoride toxicity is a serious health problem in many parts of the globe. In present study, sodium fluoride at 20 mg/kg alone and in conjunction with aluminum sulfate at 150 mg/kg was administered orally daily for 30 days in healthy goats of group 1 and 2, respectively, to access the alterations in the various biochemical parameters during subacute toxicity of fluoride alone and in conjunction with aluminum sulfate. In Group 1, significant alterations in plasma glucose, blood urea nitrogen (BUN), creatinine, total protein, albumin, globulin, albumin/globulin ratio, magnesium, and sodium were observed on different days of exposure from their pre-exposure values. However, no significant changes were observed in plasma calcium, phosphorus, and potassium on different days of exposure of sodium fluoride. Similar type of biochemical alterations were noticed in the goats of Group 2 except BUN, total protein magnesium, and sodium. On the basis of results, it could be concluded that sodium fluoride alone and in conjunction with aluminum sulfate produced significant alterations in the various biochemical parameters of the body. Part of M.V.Sc. research conducted in Division of Pharmacology and Toxicology, F.V.Sc. and A.H., SKUAST-J, R.S. Pura, Jammu-181102, J&K, INDIA.     

Mutations in the transmembrane natriuretic peptide receptor NPR-B impair skeletal growth and cause acromesomelic dysplasia, type Maroteaux

The homodimeric transmembrane receptor natriuretic peptide receptor B (NPR-B [also known as guanylate cyclase B, GC-B, and GUC2B]; gene name NPR2) produces cytoplasmic cyclic GMP from GTP on binding its extracellular ligand, C-type natriuretic peptide (CNP). CNP has previously been implicated in the regulation of skeletal growth in transgenic and knockout mice. The autosomal recessive skeletal dysplasia known as "acromesomelic dysplasia, type Maroteaux" (AMDM) maps to an interval that contains NPR2. We sequenced DNA from 21 families affected by AMDM and found 4 nonsense mutations, 4 frameshift mutations, 2 splice-site mutations, and 11 missense mutations. Molecular modeling was used to examine the putative protein change brought about by each missense mutation. Three missense mutations were tested in a functional assay and were found to have markedly deficient guanylyl cyclase activity. We also found that obligate carriers of NPR2 mutations have heights that are below the mean for matched controls. We conclude that, although NPR-B is expressed in a number of tissues, its major role is in the regulation of skeletal growth.