Msx1 Gene Variant - its Association in Isolated Hypodontia: A Case Control Genetic study!!!

INTRODUCTION:

Non-syndromic tooth agenesis is a congenital anomaly with significant medical, psychological, and social ramifications. There is sufficient evidence to hypothesize that locus for this condition can be identified by candidate genes.

AIM OF THE STUDY:

The aim of this study was to test whether MSX1 671 T > C gene variant was involved in etiology of non-syndromic tooth agenesis in Raichur patients.

MATERIALS AND METHODS:

Blood samples were collected with informed consent from 50 subjects having non-syndromic tooth agenesis and 50 controls. Genomic deoxyribonucleic acid (DNA) was extracted from the blood samples, polymerase chain reaction (PCR) was performed, and restriction fragment length polymorphism (RFLP) was performed for digestion products that were evaluated.

RESULTS:

The results showed positive correlation between MSX1671 T > C gene variant and non-syndromic tooth agenesis in Raichur patients.

CONCLUSION:

MSX1 671 T > C gene variant may be a good screening marker for non-syndromic tooth agenesis in Raichur patients.     

Overexpression of a chitinase gene in transgenic peanut confers enhanced resistance to major soil borne and foliar fungal pathogens

A chitinase gene from rice (Rchit) was introduced into three varieties of peanut through Agrobacterium-mediated genetic transformation resulting in 30 transgenic events harboring the Rchit gene. Stable integration and expression of the transgenes were confirmed using PCR, RT-PCR and Southern blot analysis. Progeny derived from selfing of the primary transgenic events revealed a Mendelian inheritance pattern (3:1) for the transgenes. The chitinase activity in the leaves of the transgenic events was 2 to 14-fold greater than that in the non-transformed control plants. Seeds of most transgenic events showed 0–10 % A. flavus infection during in vitro seed inoculation bioassays. Transgenic peanut plants evaluated for resistance against late leaf spot (LLS) and rust using detached leaf assays showed longer incubation, latent period and lower infection frequencies when compared to their non-transformed counterparts. A significant negative correlation existed between the chitinase activity and the frequency of infection to the three tested pathogens. Three progenies from two transgenic events displayed significantly higher disease resistance for LLS, rust and A. flavus infection and are being advanced for further evaluations under confined field conditions to confirm as sources to develop peanut varieties with enhanced resistance to these fungal pathogens.     

IL-10- and TGFβ-mediated Th9 Responses in a Human Helminth Infection

Background

Th9 cells are a subset of CD4⁺ T cells that express the protoypical cytokine, IL-9. Th9 cells are known to effect protective immunity in animal models of intestinal helminth infections. However, the role of Th9 cells in human intestinal helminth infections has never been examined.

Methodology

To examine the role of Th9 cells in Strongyloidis stercoralis (Ss), a common intestinal helminth infection, we compared the frequency of Th9 expressing IL-9 either singly (mono-functional) or co-expressing IL-4 or IL-10 (dual-functional) in Ss-infected individuals (INF) to frequencies in uninfected (UN) individuals.

Principal Findings

INF individuals exhibited a significant increase in the spontaneously expressed and/or antigen specific frequencies of both mono- and dual-functional Th9 cells as well as Th2 cells expressing IL-9 compared to UN. The differences in Th9 induction between INF and UN individuals was predominantly antigen-specific as the differences were no longer seen following control antigen or mitogen stimulation. In addition, the increased frequency of Th9 cells in response to parasite antigens was dependent on IL-10 and TGFx since neutralization of either of these cytokines resulted in diminished Th9 frequencies. Finally, following successful treatment of Ss infection, the frequencies of antigen-specific Th9 cells diminished in INF individuals, suggesting a role for the Th9 response in active Ss infection. Moreover, IL-9 levels in whole blood culture supernatants following Ss antigen stimulation were higher in INF compared to UN individuals.

Conclusion

Thus, Ss infection is characterized by an IL-10- and TGFβ dependent expansion of Th9 cells, an expansion found to reversible by anti-helmintic treatment.     

Crk II silencing down-regulates IGF-IR and inhibits migration and invasion of prostate cancer cells

Crk (C10 regulator of kinase) adaptor proteins are highly expressed in many types of human cancers and often contribute to aggressive cancer phenotypes. Crk II, a member of CRK family, has been reported to regulate cell migration and metastasis in breast cancer cells. However, its role in other cancer types has not been reported. In this study, we investigated the molecular function of Crk II in prostate cancer (PCa) cells (CWR-22rv1) in vitro and using a mouse tumor model. Results showed that Crk II knockdown by shRNA-mediated silencing (Crk II-shRNA) in the PCa cells significantly inhibited both cancer cell migration and invasion in cell culture study. Crk II-shRNA cancer cells also significantly decreased colony formation in vitro, but had no significant reduction of tumor volume after 4 weeks of cancer cell xenografting in vivo when compared to the scramble control. Interestingly, Crk II-shRNA cancer cells showed a greatly reduced level of insulin-like growth factor 1 receptor (IGF-1R) and decreased signaling of the IGF-1R/PI3K/Akt axis upon IGF-1 ligand stimulation. A close interaction between Crk II and IGF-1R was demonstrated upon co-immunoprecipitation of IGF-1R with Crk II protein. Further, treatment of cells with either proteosomal degradation or protein synthesis inhibitor showed higher proportion of ubiquitin-associated IGF-1R and faster degradation of IGF-1R in Crk II-shRNA cells in comparison with that in the control cancer cells. Taken together, these data suggest that Crk II plays an important role in the regulation of IGF-1R protein stability and affects downstream of IGF-1R signaling pathways. Therefore, targeting Crk-II can block IGF-1R growth signaling and suppress cancer cell invasion and progression.     

First Report of Botryosphaeria dothidea on Mangifera indica L. in Gujarat

A leaf spot disease was observed on Mangifera indica L. located in the region of Rajkot, Gujarat, India. The symptoms included the appearance of small, circular to oval dark brown necrotic sunken spots on the leaves. The fungus formed grey to dark grey on potato dextrose agar and conidia were single‐celled, ovoid or oblong. On the basis of mycological characteristics, pathogenicity test and molecular identification using 28S rDNA sequence and internal transcribed spacer (ITS), the fungus was identified as Botryosphaeria dothidea. To the best of our knowledge, this is the first report of leaf spot on M. indica tree caused by Botryoshaeria dothidea in Gujarat, India.     

Metallic Slit–Loaded Ring Resonator–Based Plasmonic Demultiplexer with Large Crosstalk

Plasmonics - Photonics provides a key solution to limit the myriads of challenges offered by existing silicon technology. Here, we propose a simple 2-channel Plasmonic demultiplexer with...     

Comparative Nuclear Proteomics Analysis Provides Insight into the Mechanism of Signaling and Immune Response to Blast Disease Caused by Magnaporthe oryzae in Rice

Modulation of plant immune system by extrinsic/intrinsic factors and host‐specific determinants fine‐tunes cellular components involving multiple organelles, particularly nucleus to mount resistance against pathogen attack. Rice blast, caused by hemibiotrophic fungus Magnaporthe oryzae, is one of the most devastating diseases that adversely affect rice productivity. However, the role of nuclear proteins and their regulation in response to M. oryzae remains unknown. Here, the nucleus‐associated immune pathways in blast‐resistant rice genotype are elucidated. Temporal analysis of nuclear proteome is carried out using 2‐DE coupled MS/MS analysis. A total of 140 immune responsive proteins are identified associated with nuclear reorganization, cell division, energy production/deprivation, signaling, and gene regulation. The proteome data are interrogated using correlation network analysis that identified significant functional modules pointing toward immune‐related coinciding processes through a common mechanism of remodeling and homeostasis. Novel clues regarding blast resistance include nucleus‐associated redox homeostasis and glycolytic enzyme–mediated chromatin organization which manipulates cell division and immunity. Taken together, the study herein provides evidence that the coordination of nuclear function and reprogramming of host translational machinery regulate resistance mechanism against blast disease.     

Late‐onset retinal degeneration pathology due to mutations in CTRP5 is mediated through HTRA1

Late‐onset retinal degeneration (L‐ORD) is an autosomal dominant macular degeneration characterized by the formation of sub‐retinal pigment epithelium (RPE) deposits and neuroretinal atrophy. L‐ORD results from mutations in the C1q‐tumor necrosis factor‐5 protein (CTRP5), encoded by the CTRP5/C1QTNF5 gene. To understand the mechanism underlying L‐ORD pathology, we used a human cDNA library yeast two‐hybrid screen to identify interacting partners of CTRP5. Additionally, we analyzed the Bruch's membrane/choroid (BM‐Ch) from wild‐type (Wt), heterozygous S163R Ctrp5 mutation knock‐in (Ctrp5^S163R/wt), and homozygous knock‐in (Ctrp5^S163R/S163R) mice using mass spectrometry. Both approaches showed an association between CTRP5 and HTRA1 via its C‐terminal PDZ‐binding motif, stimulation of the HTRA1 protease activity by CTRP5, and CTRP5 serving as an HTRA1 substrate. The S163R‐CTRP5 protein also binds to HTRA1 but is resistant to HTRA1‐mediated cleavage. Immunohistochemistry and proteomic analysis showed significant accumulation of CTRP5 and HTRA1 in BM‐Ch of Ctrp5^S163R/S163R and Ctrp5^S163R/wt mice compared with Wt. Additional extracellular matrix (ECM) components that are HTRA1 substrates also accumulated in these mice. These results implicate HTRA1 and its interaction with CTRP5 in L‐ORD pathology.     

In vitro and in silico molecular interaction of multiphase nanoparticles containing inositol hexaphosphate and jacalin: Therapeutic potential against colon cancer cells (HCT-15)

Inositol hexaphosphate (IP6) is a natural constituent found in almost all cereals and legumes. It is known to cause numerous antiangiogenic manifestations. Notwithstanding its great potential, it is underutilized due to the chelation and rapid excretion from the body. Jacalin is another natural constituent obtained from seeds of jackfruit and can target disaccharides overexpressed in tumor cells. The current study was in-quested to develop and evaluate a surface-modified gold nanoparticulate system containing IP6 and jacalin which may maximize the apoptotic effect of IP6 against HCT-15 cell lines. IP6 loaded jacalin-pectin-gold nanoparticles (IJP-GNPs) were developed through reduction followed by incubation method. The developed formulation was tested for various in vitro and in silico studies to investigate its potential. HCT-15 cells when exposed to IJP-GNP resulted in significant apoptotic effects in dose as well as time-dependent manner, as measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, micronucleus, and reactive oxygen species assay. IJP-GNP displayed cell cycle arrest at the G0/G1 phase. To further explore the mechanism of chemoprevention, in silico studies were performed. The docking results revealed that the interactive behavior of IP6, P-GNP, and jacalin could target and inhibit the tumor formation activity, supported by in vitro studies. Taken together, all the findings suggested that IP6 loaded nanoparticles may increase the hope of future drug delivery strategy for targeting colon cancer.     

Tackling the plant proteome: practical approaches, hurdles and experimental tools

The study of complex biological questions through comparative proteomics is becoming increasingly attractive to plant biologists as the rapidly expanding plant genomic and expressed sequence tag databases provide improved opportunities for protein identification. This review focuses on practical issues associated with comparative proteomic analysis, including the challenges of effective protein extraction and separation from plant tissues, the pros and cons of two-dimensional gel-based analysis and the problems of identifying proteins from species that are not recognized models for functional genomic studies. Specific points are illustrated using data from an ongoing study of the tomato and pepper fruit proteomes.