Rapid evolution and copy number variation of primate RHOXF2, an X-linked homeobox gene involved in male reproduction and possibly brain function

<p>Abstract</p> <p>Background</p> <p>Homeobox genes are the key regulators during development, and they are in general highly conserved with only a few reported cases of rapid evolution. <it>RHOXF2 </it>is an X-linked homeobox gene in primates. It is highly expressed in the testicle and may play an important role in spermatogenesis. As male reproductive system is often the target of natural and/or sexual selection during evolution, in this study, we aim to dissect the pattern of molecular evolution of <it>RHOXF2 </it>in primates and its potential functional consequence.</p> <p>Results</p> <p>We studied sequences and copy number variation of <it>RHOXF2 </it>in humans and 16 nonhuman primate species as well as the expression patterns in human, chimpanzee, white-browed gibbon and rhesus macaque. The gene copy number analysis showed that there had been parallel gene duplications/losses in multiple primate lineages. Our evidence suggests that 11 nonhuman primate species have one <it>RHOXF2 </it>copy, and two copies are present in humans and four Old World monkey species, and at least 6 copies in chimpanzees. Further analysis indicated that the gene duplications in primates had likely been mediated by endogenous retrovirus (ERV) sequences flanking the gene regions. In striking contrast to non-human primates, humans appear to have homogenized their two <it>RHOXF2 </it>copies by the ERV-mediated non-allelic recombination mechanism. Coding sequence and phylogenetic analysis suggested multi-lineage strong positive selection on <it>RHOXF2 </it>during primate evolution, especially during the origins of humans and chimpanzees. All the 8 coding region polymorphic sites in human populations are non-synonymous, implying on-going selection. Gene expression analysis demonstrated that besides the preferential expression in the reproductive system, <it>RHOXF2 </it>is also expressed in the brain. The quantitative data suggests expression pattern divergence among primate species.</p> <p>Conclusions</p> <p><it>RHOXF2 </it>is a fast-evolving homeobox gene in primates. The rapid evolution and copy number changes of <it>RHOXF2 </it>had been driven by Darwinian positive selection acting on the male reproductive system and possibly also on the central nervous system, which sheds light on understanding the role of homeobox genes in adaptive evolution.</p

1,2-Bis(1,3-dithiol-2-yl­idene)hydrazine

The title mol­ecule, C6H4N2S4, has a crystallographically imposed centre of symmetry located at the mid-point of the N—N single bond. The mol­ecule is essentially planar: the two five-membered rings form a dihedral angle of 0.17 (6)°. The crystal packing exhibits short inter­molecular S⋯S contacts of 3.549 (2) Å

Transcriptome analysis of Deinagkistrodon acutus venomous gland focusing on cellular structure and functional aspects using expressed sequence tags

BACKGROUND: The snake venom gland is a specialized organ, which synthesizes and secretes the complex and abundant toxin proteins. Though gene expression in the snake venom gland has been extensively studied, the focus has been on the components of the venom. As far as the molecular mechanism of toxin secretion and metabolism is concerned, we still knew a little. Therefore, a fundamental question being arisen is what genes are expressed in the snake venom glands besides many toxin components? RESULTS: To examine extensively the transcripts expressed in the venom gland of Deinagkistrodon acutus and unveil the potential of its products on cellular structure and functional aspects, we generated 8696 expressed sequence tags (ESTs) from a non-normalized cDNA library. All ESTs were clustered into 3416 clusters, of which 40.16% of total ESTs belong to recognized toxin-coding sequences; 39.85% are similar to cellular transcripts; and 20.00% have no significant similarity to any known sequences. By analyzing cellular functional transcripts, we found high expression of some venom related genes and gland-specific genes, such as calglandulin EF-hand protein gene and protein disulfide isomerase gene. The transcripts of creatine kinase and NADH dehydrogenase were also identified at high level. Moreover, abundant cellular structural proteins similar to mammalian muscle tissues were also identified. The phylogenetic analysis of two snake venom toxin families of group III metalloproteinase and serine protease in suborder Colubroidea showed an early single recruitment event in the viperids evolutionary process. CONCLUSION: Gene cataloguing and profiling of the venom gland of Deinagkistrodon acutus is an essential requisite to provide molecular reagents for functional genomic studies needed for elucidating mechanisms of action of toxins and surveying physiological events taking place in the very specialized secretory tissue. So this study provides a first global view of the genetic programs for the venom gland of Deinagkistrodon acutus described so far and an insight into molecular mechanism of toxin secreting. All sequences data reported in this paper have been submitted into the public database [GenBank: DV556511-DV565206]

Comparison of Efficacy and Safety of Lispro and Aspart Evaluated by Continuous Glucose Monitoring System in Patients with Newly Diagnosed Type 2 Diabetes

Objective. To compare the effect of the rapid-acting insulin analogues (RAIAs) aspart (NovoRapid) and lispro (Prandilin) on glycemic variations by continuous glucose monitoring system (CGMS) in patients within newly diagnosed type 2 diabetes mellitus (T2DM) receiving continuous subcutaneous insulin infusion (CSII) and metformin intensive therapy. Methods. This is a single-blind randomized controlled trial. A total of 110 patients with newly diagnosed T2DM and with hemoglobin A1c (HbA1c%) above 9% was hospitalized and randomly divided into two groups: group Asp (NovoRapid group) and group Lis (Prandilin group). They all received CSII and metformin therapy. Treatments were maintained for 2-3 weeks after the glycaemic target was reached. C-peptide and insulin and fructosamine were determined. CGMS was continuously applied for 4 days after reaching the glycemic target. Results. There were no significant differences in daily dosages of insulin, fasting plasma C-P and 2 h postprandial C-P and insulin, and fructosamine at the baseline and endpoint between the groups Asp and Lis. No significant differences were seen in the 24 h mean amplitude of glycemic excursions (MAGE), 24 h mean blood glucose (MBG), the standard deviation of the MBG (SDBG), fasting blood glucose, number of glycemic excursion (NGE), and the incidence of hypoglycemia between the two groups. Similarly, no significant differences were found in areas under the curve (AUC) of glucose above 10.0 mmol/L or the decremental area over the curve (AOC) of glucose below 3.9 mmol/L between the two groups. Conclusions. Lispro and aspart had the similar ability to control the glycemic variations in patients with newly diagnosed T2DM. This study was registered with ClinicalTrials.gov, number ChiCTR-IPR-17010338

Novel Chromosomal Aberration as Evidence of Clonal Evolution in a Case of Relapsed Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a heterogeneous group of diseases with a multitude of molecular genetic aberrations and variable clinical outcome. Clonal chromosomal abnormalities have been identified in over 50% of AML cases, and have been regarded as one of the most important prognostic markers. We present a case of a 28-year-old Caucasian woman with AML without maturation, diploid karyotype, that was resistant to multiple chemotherapies and relapsed after matched unrelated stem cell transplantation. Conventional cytogenetic analysis performed on bone marrow specimens revealed 46,XX,t(2;16)(p21;p11.2),t(11;14)(p13;p11.2). The t(11;14)(p13;p11.2) was confirmed by fluorescence in situ hybridization using a whole chromosome paint probe for chromosome 11. Morphologically, the bone marrow was hypercellular with trilineage hypoplasia and 84% blasts. Flow cytometry analysis showed that the blasts were of myeloid immunophenotype. Molecular studies detected internal tandem duplication of the FLT3 gene and a mutation in exon 12 of the NPM1 gene. The patient then received monotherapy with AC220, achieved a brief remission, and died of relapsed disease 23 months after initial diagnosis. This

Novel cancerization marker, TP53, and its role in distinguishing normal tissue adjacent to cancerous tissue from normal tissue adjacent to benign tissue

Foundation of Xiamen Science and Technology Bureau [3502Z20104032, 3502Z20100002]; Medical innovation Foundation of Fujian Health Department [2011-CXB-38]; Natural Science Foundation of Fujian Province [2010J05137, 2012J01414]; National Natural Science Foundation of China [81272445, 61100106]Background: The histopathological and molecular heterogeneity of normal tissue adjacent to cancerous tissue (NTAC) and normal tissue adjacent to benign tissue (NTAB), and the availability of limited specimens make deciphering the mechanisms of carcinogenesis challenging. Our goal was to identify histogenetic biomarkers that could be reliably used to define a transforming fingerprint using RNA in situ hybridization. Methods: We evaluated 15 tumor-related RNA in situ hybridization biomarkers using tumor microarray and samples of seven tumor-adjacent normal tissues from 314 patients. Biomarkers were determined using comprehensive statistical methods (significance of support vector machine-based artificial intelligence and area under curve scoring of classification distribution). Results: TP53 was found to be a most reliable index (P 87%) for distinguishing NTAC from NTAB, according to the results of a significance panel (BCL10, BECN1, BRCA2, FITH, PTCH11 and TP53). Conclusions: The genetic alterations in TP53 between NTAC and NTAB may provide new insight into the field of cancerization and tumor transformation