Insight into morphological and molecular variations across Iranian spinach landraces

Molecular Biology Reports - Spinach is salt-tolerant leafy vegetable stemmed from central Asia. It has been well adapted to different climates of Iran. We aimed to study genetic diversity between...     

Perspectives on the use of multiple sclerosis risk genes for prediction

Objective

A recent collaborative genome-wide association study replicated a large number of susceptibility loci and identified novel loci. This increase in known multiple sclerosis (MS) risk genes raises questions about clinical applicability of genotyping. In an empirical set we assessed the predictive power of typing multiple genes. Next, in a modelling study we explored current and potential predictive performance of genetic MS risk models.

Materials and Methods

Genotype data on 6 MS risk genes in 591 MS patients and 600 controls were used to investigate the predictive value of combining risk alleles. Next, the replicated and novel MS risk loci from the recent and largest international genome-wide association study were used to construct genetic risk models simulating a population of 100,000 individuals. Finally, we assessed the required numbers, frequencies, and ORs of risk SNPs for higher discriminative accuracy in the future.

Results

Individuals with 10 to 12 risk alleles had a significantly increased risk compared to individuals with the average population risk for developing MS (OR 2.76 (95% CI 2.02–3.77)). In the simulation study we showed that the area under the receiver operating characteristic curve (AUC) for a risk score based on the 6 SNPs was 0.64. The AUC increases to 0.66 using the well replicated 24 SNPs and to 0.69 when including all replicated and novel SNPs (n = 53) in the risk model. An additional 20 SNPs with allele frequency 0.30 and ORs 1.1 would be needed to increase the AUC to a slightly higher level of 0.70, and at least 50 novel variants with allele frequency 0.30 and ORs 1.4 would be needed to obtain an AUC of 0.85.

Conclusion

Although new MS risk SNPs emerge rapidly, the discriminatory ability in a clinical setting will be limited.     

Mapping the Interactions between the Alzheimer’s Aβ-Peptide and Human Serum Albumin beyond Domain Resolution

Human serum albumin (HSA) is a potent inhibitor of Aβ self-association and this novel, to our knowledge, function of HSA is of potential therapeutic interest for the treatment of Alzheimer’s disease. It is known that HSA interacts with Aβ oligomers through binding sites evenly partitioned across the three albumin domains and with comparable affinities. However, as of this writing, no information is available on the HSA-Aβ interactions beyond domain resolution. Here, we map the HSA-Aβ interactions at subdomain and peptide resolution. We show that each separate subdomain of HSA domain 3 inhibits Aβ self-association. We also show that fatty acids (FAs) compete with Aβ oligomers for binding to domain 3, but the determinant of the HSA/Aβ oligomer interactions are markedly distinct from those of FAs. Although salt bridges with the FA carboxylate determine the FA binding affinities, hydrophobic contacts are pivotal for Aβ oligomer recognition. Specifically, we identified a site of Aβ oligomer recognition that spans the HSA (494–515) region and aligns with the central hydrophobic core of Aβ. The HSA (495–515) segment includes residues affected by FA binding and this segment is prone to self-associate into β-amyloids, suggesting that sites involved in fibrilization may provide a lead to develop inhibitors of Aβ self-association.     

Polarization Controlling of Multi Resonant Graphene-Based Microstrip Antenna

Plasmonics - In this paper, a graphene-based patch antenna is proposed. The antenna structure is designed so that each of the various antenna sections affected by chemical potential changes can...     

Clostridium difficile Modulates Host Innate Immunity via Toxin-Independent and Dependent Mechanism(s)

Clostridium difficile infection (CDI) is the leading cause of hospital and community-acquired antibiotic-associated diarrhoea and currently represents a significant health burden. Although the role and contribution of C. difficile toxins to disease pathogenesis is being increasingly understood, at present other facets of C. difficile-host interactions, in particular, bacterial-driven effects on host immunity remain less studied. Using an ex-vivo model of infection, we report that the human gastrointestinal mucosa elicits a rapid and significant cytokine response to C. difficile. Marked increase in IFN-γ with modest increase in IL-22 and IL-17A was noted. Significant increase in IL-8 suggested potential for neutrophil influx while presence of IL-12, IL-23, IL-1β and IL-6 was indicative of a cytokine milieu that may modulate subsequent T cell immunity. Majority of C. difficile-driven effects on murine bone-marrow-derived dendritic cell (BMDC) activation were toxin-independent; the toxins were however responsible for BMDC inflammasome activation. In contrast, human monocyte-derived DCs (mDCs) released IL-1β even in the absence of toxins suggesting host-specific mediation. Infected DC-T cell crosstalk revealed the ability of {"type":"entrez-nucleotide","attrs":{"text":"R20291","term_id":"774925","term_text":"R20291"}}R20291 and 630 WT strains to elicit a differential DC IL-12 family cytokine milieu which culminated in significantly greater Th1 immunity in response to {"type":"entrez-nucleotide","attrs":{"text":"R20291","term_id":"774925","term_text":"R20291"}}R20291. Interestingly, both strains induced a similar Th17 response. Elicitation of mucosal IFN-γ/IL-17A and Th1/Th17 immunity to C. difficile indicates a central role for this dual cytokine axis in establishing antimicrobial immunity to CDI.     

Nanobody-based chimeric receptor gene integration in Jurkat cells mediated by PhiC31 integrase

The crucial role of T lymphocytes in anti-tumor immunity has led to the development of novel strategies that can target and activate T cells against tumor cells. Recombinant DNA technology has been used to generate non-MHC-restricted chimeric antigen receptors (CARs). Here, we constructed a panel of recombinant CAR that harbors the anti-MUC1 nanobody and the signaling and co-signaling moieties (CD3ζ/CD28) with different spacer regions derived from human IgG3 with one or two repeats of the hinge sequence or the hinge region of FcγRII. The PhiC31 integrase system was employed to investigate if the recombination efficiency could be recruited for high and stable expression of T cell chimeric receptor genes. The effect of nuclear localization signal (NLS) and two different promoters (CMV and CAG) on efficacy of PhiC31 integrase in human T cell lines was evaluated. The presence of integrase in combination with NLS, mediated up to 7.6 and 8.5 fold increases in CAR expression in ZCHN-attB and ZCHHN-attB cassette integrated T cells, respectively. Our results showed that highly efficient and stable transduction of the Jurkat cell line by PhiC31 integrase is a feasible modality for generating anti-cancer chimeric T cells for use in cancer immunotherapy.     

Intrabasin variation in allometry coefficients of Lenkoran Capoeta capoeta gracilis (Keyserling, 1861) in the Gorganroud basin,southeast Caspian Sea,Iran

It is believed that streams of a basin may contribute to stream‐specific variation in allometry coefficients related to between‐habitat differences. To test intra‐basin variation of the allometry coefficients of Lenkorn Capoeta capoeta gracilis (Keyserling, 1861), a total of 1731 individuals were sampled in six streams of the Gorganroud basin (southeast Caspian Sea) between April and May 2008. Values of b ranged from 2.647 for males of Chelchai to 2.964 for females of Madarsou, indicating negative allometric growth for the fish in the basin. There were variations in the allometry coefficient among the considered groups, which can be interpreted as species’ response to different habitats. To the best knowledge of the authors, this study documents the comparative reference on variation of allometry coefficient of Capoeta capoeta gracilis in southeast Caspian streams.     

Identification of genes associated with kernel size in almond [Prunus dulcis (Mill.) D.A. Webb] using RNA-Seq

Plant Growth Regulation - Almond is a stone fruit crop belonging to the Rosaceae family, cultivated in the temperate region of the world for its high nutritive valued fruits. In today’s...     

Sodium nitroprusside: its beneficial role in drought stress tolerance of “Mexican lime” (Citrus aurantifolia (Christ.) Swingle) under in vitro conditions

In Vitro Cellular & Developmental Biology - Plant - As a novel antioxidant, sodium nitroprusside (SNP) can be used to reduce the adverse effects of various abiotic stresses, especially drought...