Kinase gene fusions in defined subsets of melanoma

Genomic rearrangements resulting in activating kinase fusions have been increasingly described in a number of cancers including malignant melanoma, but their frequency in specific melanoma subtypes has not been reported. We used break‐apart fluorescence in situ hybridization (FISH) to identify genomic rearrangements in tissues from 59 patients with various types of malignant melanoma including acral lentiginous, mucosal, superficial spreading, and nodular. We identified four genomic rearrangements involving the genes BRAF, RET, and ROS1. Of these, three were confirmed by Immunohistochemistry (IHC) or sequencing and one was found to be an ARMC10‐BRAF fusion that has not been previously reported in melanoma. These fusions occurred in different subtypes of melanoma but all in tumors lacking known driver mutations. Our data suggest gene fusions are more common than previously thought and should be further explored particularly in melanomas lacking known driver mutations.     

Bigger is better: age class-specific survival rates in long-lived turtles increase with size

Vital rates for small, non-breeding individuals are important components of population dynamics for many species, but often individuals of these sizes are difficult to locate, capture, and track. As such, biologists frequently lack reliable estimates of juvenile survival because sample sizes and recapture rates for this life stage are low. Long-lived animals often take many years to reach sexual maturity and spend much of this time in the smaller size classes, making them sensitive to changes in survival rates. We estimated the survival rates of all size classes for the northern map turtle (Graptemys geographica) using a mark-recapture dataset with >3,500 captures from 2019–2021 and 210 nests from 2018–2021. As turtle size increased, annual survival probability increased regardless of sex. Estimated annual survival probability for turtles >18 cm long (i.e., adult females >15 years) was about 0.95, over 4 times higher than turtles that were 3 cm long (i.e., hatchlings <1 year; 0.22 annual survival probability). Although we did not observe a difference in survival probability between sexes of any size class, adult females are nearly twice the size of adult males, leading to an increased annual survival probability for females of 0.95, compared to 0.80 for males. Changes in adult survival had the greatest influence on population estimates over time, with temporary decreases, such as those due to poaching or an environmental disaster, potentially leading to unrecoverable decreases in the overall population size. Our study provides detailed survival rates for all size classes in a long-lived turtle, which are necessary to assess population stability and can be used to determine the most effective conservation or management practices.     

Numb proteins specify asymmetric cell fates via an endocytosis- and proteasome-independent pathway

Numb proteins are evolutionarily conserved signaling molecules that make the daughter cells different after asymmetric divisions by segregating to only one daughter. They contain distinct binding motifs for alpha-adaptin (alpha-Ada) and proteins with Eps15 homology (EH) domains, which regulate endocytosis, and for E3 ubiquitin ligases, which target proteins for proteasome-mediated degradation. In Drosophila melanogaster, Numb acts by inhibiting Notch activity to cause a bias in Notch-mediated cell-cell communication. These findings have led to the hypothesis that Numb modulates Notch signaling by using endocytosis and proteasomes to directly reduce Notch protein levels at the cell surface. Here we show that two Drosophila EH proteins, Eps15 homologue 1 (EH1) and the dynamin-associated 160-kDa protein (Dap160), negatively regulate Notch signaling. However, neither elimination of the binding motifs for endocytic proteins nor simultaneous reduction of proteasome activity affects the activity of Numb proteins. Our findings indicate that an endocytosis- and proteasome-independent pathway may mediate Numb signaling in asymmetric cell fate specification.     

Modelling,inference and big data in biophysics

In recognition of the increasing importance of big data in biophysics, a new session called ‘Modelling, inference, big data’ is incorporated into the IUPAB/EBSA Congress on 18 July 2017 at Edinburgh, UK.     

Fish reduce anuran abundance and decrease herpetofaunal species richness in wetlands

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HIV-2 Integrase Variation in Integrase Inhibitor-Na?ve Adults in Senegal,West Africa

Background

Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs) raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance.

Methods

We PCR amplified and analyzed 122 HIV-2 integrase consensus sequences from 39 HIV-2–infected, INI-naive adults in Senegal, West Africa. We assessed genetic variation and canonical mutations known to confer INI-resistance in HIV-1.

Results

No amino acid-altering mutations were detected at sites known to be pivotal for INI resistance in HIV-1 (integrase positions 143, 148 and 155). Polymorphisms at several other HIV-1 INI resistance-associated sites were detected at positions 72, 95, 125, 154, 165, 201, 203, and 263 of the HIV-2 integrase protein.

Conclusion

Emerging genotypic and phenotypic data suggest that HIV-2 is susceptible to the new class of HIV integrase inhibitors. We hypothesize that intrinsic HIV-2 integrase variation at “secondary” HIV-1 INI-resistance sites may affect the genetic barrier to HIV-2 INI resistance. Further studies will be needed to assess INI efficacy as part of combination antiretroviral therapy in HIV-2–infected patients.