Anti-MAST4 monoclonal antibody Made to order

To date, genome-wide single nucleotide polymorphism (SNP) and copy number variant (CNV) association studies of autism spectrum disorders (ASDs) have led to promising signals but not to easily interpretable or translatable results. Our own genome-wide association study (GWAS) showed significant association to an intergenic SNP near Semaphorin 5A (SEMA5A) and provided evidence for reduced expression of the same gene. In a novel GWAS follow-up approach, we map an expression regulatory pathway for a GWAS candidate gene, SEMA5A, in silico by using population expression and genotype data sets. We find that the SEMA5A regulatory network significantly overlaps rare autism-specific CNVs. The SEMA5A regulatory network includes previous autism candidate genes and regions, including MACROD2, A2BP1, MCPH1, MAST4, CDH8, CADM1, FOXP1, AUTS2, MBD5, 7q21, 20p, USH2A, KIRREL3, DBF4B and RELN, among others. Our results provide: (i) a novel data-derived network implicated in autism, (ii) evidence that the same pathway seeded by an initial SNP association shows association with rare genetic variation in ASDs, (iii) a potential mechanism of action and interpretation for the previous autism candidate genes and genetic variants that fall in this network, and (iv) a novel approach that can be applied to other candidate genes for complex genetic disorders. We take a step towards better understanding of the significance of SEMA5A pathways in autism that can guide interpretation of many other genetic results in ASDs.

Objective: Osteolytic lesion (OL) and bone damage are common complications in multiple myeloma (MM). This study aimed to analyze the occurrence of OL in MM patient groups of different ages and genders. Patients and methods: We performed a retrospective study of 762 MM patients admitted to West China Hospital from 2009 to 2014 to investigate the association between OL occurrence with patients' ages and genders. The presence or absence of OL was confirmed by X-ray, computed tomography (CT) or magnetic resonance imaging (MRI) examination. We also downloaded MM patients' published gene expression profiles and performed microarray-based analyses to identify differentially regulated genes and signaling pathways. Finally, we examined target gene expressions in MM bone marrow (BM) biopsies through immunohistochemistry (IHC). Results: We calculated the frequency of OL in female and male MM patients with different age cut-offs. From West China Hospital data, we found that in young female MM patients aged under 55, the frequency of OL was 16.67%, significantly lower than the frequencies in other groups of patients (young males: 3438%; old males: 31.04%; old females: 29.24%; p < .05). The same was true in another independent MM cohort. Microarray-based analyses showed that Microtubule Associated Serine/Threonine Kinase Family Member 4 (MAST4), an estrogen responsive gene, expression was up-regulated in MM patients without OL and in young female MM patients (p < .05). The expression of MAST4 in MM BM was confirmed by IHC. The perspective of cell signaling network suggested that MAST4 might interact with phosphatase and tensin homolog (PEEN) and control the expression of a panel of osteoclast-regulatory cytokines, such as TNFSF11 and CCL2. Conclusions: Young female (<55 years) MM patients have significantly lower OL frequency than other groups. MAST4 gene expression is thought to be associated with this phenomenon. (C) 2018 Elsevier Inc. All rights reserved.