The Homing Frog: High Homing Performance in a Territorial Dendrobatid Frog Allobates femoralis (Dendrobatidae)

Dendrobatidae (dart‐poison frogs) exhibit some of the most complex spatial behaviors among amphibians, such as territoriality and tadpole transport from terrestrial clutches to widely distributed deposition sites. In species that exhibit long‐term territoriality, high homing performance after tadpole transport can be assumed, but experimental evidence is lacking, and the underlying orientation mechanisms are unknown. We conducted a field translocation experiment to test whether male Allobates femoralis, a dendrobatid frog with paternal extra‐territorial tadpole transport, are capable of homing after experimental removal, as well as to quantify homing success and speed. Translocated individuals showed a very high homing success for distances up to 200 m and successfully returned from up to 400 m. We discuss the potential orientation mechanisms involved and selective forces that could have shaped this strong homing ability.     

Outreach Syphilis Testing Services by Different Health Providers to Female Sex Workers in Southern China

Health providers have played important roles on delivering prevention and care services to control syphilis in China. The current study was aimed to evaluate the performance of different health providers in providing outreach syphilis testing services to female sex workers (FSWs). The current study carried out during April to August 2009 in Liuzhou was aimed to investigate the services delivered by two different types of clinics in China. A total of 1,808 FSWs recruited from sex work venues were included in the study. Prevalence of positive syphilis test (6.4%) among FSWs accessed by the local center for disease control outreach teams (CDC teams) was significantly lower than that (9.3%) among FSWs accessed by the local reproductive health hospital outreach teams (RHH teams). As compared with CDC teams, RHH teams had more FSWs to be successfully referred to the designated STD clinics for further syphilis confirmation and intervention (85.7% vs. 26.7%, P<0.001). These findings indicate that RHH teams may be more efficient than CDC teams to provide outreach-based services to FSWs. Participation of the reproductive health providers or other medical facilities in outreach services to FSWs should be considered in developing intervention programs in China.     

Whole Genome SNP Genotyping and Exome Sequencing Reveal Novel Genetic Variants and Putative Causative Genes in Congenital Hyperinsulinism

Congenital hyperinsulinism of infancy (CHI) is a rare disorder characterized by severe hypoglycemia due to inappropriate insulin secretion. The genetic causes of CHI have been found in genes regulating insulin secretion from pancreatic β-cells; recessive inactivating mutations in the ABCC8 and KCNJ11 genes represent the most common events. Despite the advances in understanding the molecular pathogenesis of CHI, specific genetic determinants in about 50 % of the CHI patients remain unknown, suggesting additional locus heterogeneity. In order to search for novel loci contributing to the pathogenesis of CHI, we combined a family-based association study, using the transmission disequilibrium test on 17 CHI patients lacking mutations in ABCC8/KCNJ11, with a whole-exome sequencing analysis performed on 10 probands. This strategy allowed the identification of the potential causative mutations in genes implicated in the regulation of insulin secretion such as transmembrane proteins (CACNA1A, KCNH6, KCNJ10, NOTCH2, RYR3, SCN8A, TRPV3, TRPC5), cytosolic (ACACB, CAMK2D, CDKAL1, GNAS, NOS2, PDE4C, PIK3R3) and mitochondrial enzymes (PC, SLC24A6), and in four genes (CSMD1, SLC37A3, SULF1, TLL1) suggested by TDT family-based association study. Moreover, the exome-sequencing approach resulted to be an efficient diagnostic tool for CHI, allowing the identification of mutations in three causative CHI genes (ABCC8, GLUD1, and HNF1A) in four out of 10 patients. Overall, the present study should be considered as a starting point to design further investigations: our results might indeed contribute to meta-analysis studies, aimed at the identification/confirmation of novel causative or modifier genes.     

RedOx Status,Proteasome and APEH: Insights into Anticancer Mechanisms of t10,c12-Conjugated Linoleic Acid Isomer on A375 Melanoma Cells

This study describes the investigation of the efficiency of conjugated linoleic acid (CLA) isomers in reducing cancer cells viability exploring the role of the oxidative stress and acylpeptide hydrolase (APEH)/proteasome mediated pathways on pro-apoptotic activity of the isomer trans10,cis12 (t10,c12)-CLA. The basal activity/expression levels of APEH and proteasome (β-5 subunit) were preliminarily measured in eight cancer cell lines and the functional relationship between these enzymes was clearly demonstrated through their strong positive correlation. t10,c12-CLA efficiently inhibited the activity of APEH and proteasome isoforms in cell-free assays and the negative correlation between cell viability and caspase 3 activity confirmed the pro-apoptotic role of this isomer. Finally, modulatory effects of t10,c12-CLA on cellular redox status (intracellular glutathione, mRNA levels of antioxidant/detoxifying enzymes activated through NF-E2-related factor 2, Nrf2, pathway) and on APEH/β-5 activity/expression levels, were investigated in A375 melanoma cells. Dose- and time-dependent variations of the considered parameters were established and the resulting pro-apoptotic effects were shown to be associated with an alteration of the redox status and a down-regulation of APEH/proteasome pathway. Therefore, our results support the idea that these events are involved in ROS-dependent apoptosis of t10,c12-CLA-treated A375 cells. The combined inhibition, triggered by t10,c12-CLA, via the modulation of APEH/proteasome and Nrf2 pathway for treating melanoma, is suggested as a subject for further in vivo studies.     

Gut microbiota composition before infection determines the Salmonella super- and low-shedder phenotypes in chicken

Heterogeneity of infection and extreme shedding patterns are common features of animal infectious diseases. Individual hosts that are super-shedders are key targets for control strategies. Nevertheless, the mechanisms associated with the emergence of super-shedders remain largely unknown. During chicken salmonellosis, a high heterogeneity of infection is observed when animal-to-animal cross-contaminations and reinfections are reduced. We hypothesized that unlike super-shedders, low-shedders would be able to block the first Salmonella colonization thanks to a different gut microbiota. The present study demonstrates that (i) axenic and antibiotic-treated chicks are more prone to become super-shedders; (ii) super or low-shedder phenotypes can be acquired through microbiota transfer; (iii) specific gut microbiota taxonomic features determine whether the chicks develop a low- and super-shedder phenotype after Salmonella infection in isolator; (iv) partial protection can be conferred by inoculation of four commensal bacteria prior to Salmonella infection. This study demonstrates the key role plays by gut microbiota composition in the heterogeneity of infection and pave the way for developing predictive biomarkers and protective probiotics.     

Oncosuppressor methylation: a possible key role in colon metastatic progression

K‐RAS and BRAF gene mutations are mandatory to set anti‐EGFR therapy in metastatic colorectal cancer (mCRC) patients. Due to the relationship of these mutations with tumor epigenotype, we hypothesized the potential role of oncosuppressor methylation of genes involved in K‐RAS/BRAF pathway (CDKN2A, RASSF1A, and RARbeta suppressor genes) in inhibiting EGFR signaling cascade. Primary tumor and synchronous liver metastatic tissues of 75 mCRC patients were characterized for promoter methylation by QMSP and for K‐RAS and BRAF mutations. RARbeta, RASSF1A, and CDKN2A genes were methylated in 82%, 35%, and 26% of primary tumors, respectively. RASSF1A resulted significantly more frequently methylated in liver metastasis than in primary site (P = 0.015), while RARbeta was significantly lower methylated in distant metastasis (P = 1.2 × 10^?6). As regards methylation content, RASSF1A methylation status was significantly higher in liver metastasis with respect to primary tumor (P = 0.000) underlying the role of this gene in liver metastatic progression. In our series K‐RAS and BRAF were mutated in 39% and 4% of cases, respectively. Methylation frequencies seemed to be unrelated to gene mutations; on the other hand, RASSF1A mean content methylation resulted significantly higher in liver than in primary tumor (288.78 vs. 56.23, respectively, P = 0.05) only in K‐RAS wild‐type cases sustaining a specific role of this gene in metastatic site thus supporting its function in strengthening the apoptotic role of K‐RAS. These evidences held the role of oncosuppressor methylation in both colon tumorigenesis and progression and suggested that epigenetic events should be taken into account when biological therapies in mCRC patients have to be set. J. Cell. Physiol. 226: 1934–1939, 2011. © 2010 Wiley‐Liss, Inc.