Anopheles darlingi polytene chromosomes: revised maps including newly described inversions and evidence for population structure in Manaus

Salivary gland polytene chromosomes of 4th instar Anopheles darlingi Root were examined from multiple locations in the Brazilian Amazon. Minor modifications were made to existing polytene photomaps. These included changes to the breakpoint positions of several previously described paracentric inversions and descriptions of four new paracentric inversions, two on the right arm of chromosome 3 and two on the left arm of chromosome 3 that were found in multiple locations. A total of 18 inversions on the X (n = 1) chromosome, chromosome 2 (n = 7) and 3 (n = 11) were scored for 83 individuals from Manaus, Macapá and Porto Velho municipalities. The frequency of 2Ra inversion karyotypes in Manaus shows significant deficiency of heterozygotes (p < 0.0009). No significant linkage disequilibrium was found between inversions on chromosome 2 and 3. We hypothesize that at least two sympatric subpopulations exist within the An. darlingi population at Manaus based on inversion frequencies

ICAR: endoscopic skull‐base surgery

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Insight into the development of a carbonate platform through a multi-disciplinary approach - A case study from the Upper Devonian slope deposits of Mount Freikofel (Carnic Alps, Austria/Italy)

The development and behavior of Million year-scaled depositional sequences recorded within Palaeozoic carbonate platform has remained poorly examined. Therefore, the understanding of palaeoenvironmental changes that occur in geological past is still limited. We herein undertake a multi-disciplinary approach (sedimentology, conodont biostratigraphy, magnetic susceptibility and geochemistry) of a long-term succession in the Carnic Alps which offers new insights into the peculiar evolution of one of the best example of Palaeozoic carbonate platform in Europe. The Freikofel section, located in the central part of the Carnic Alps represents an outstanding succession in a fore-reef setting, extending from the latest Givetian (indet. falsiovalis conodont Zones) to the early Famennian (Lower crepida conodont Zone). Sedimentological analysis allowed to propose a sedimentary model dominated by distal slope and fore-reef slope deposits. The most distal setting is characterized by an autochthonous pelagic sedimentation showing local occurrence of thin-bedded turbiditic deposits. In the fore-reef slope, in a more proximal setting, there is an accumulation of various autochthonous and allochthonous fine- to coarse-grained sediments originated from the interplay of gravity-flow currents derived from the shallow-water and deeper-water area. The temporal evolution of microfacies in the Freikofel section evolves in two main steps corresponding to the Freikofel (Unit 1) and the Pal (Unit 2) Limestones. Distal slope to fore-reef lithologies and associate changes are from base to top of the section: (U1) thick bedded litho- and bioclastic breccia beds with local fining upward sequence and fine-grained mudstone intercalations corresponding, in the fore-reef setting, to the dismantlement of the Eifelian – Frasnian carbonate platform during the early to late Frasnian time (falsiovalis to rhenana superzones) with one of the causes being the Late Givetian major rift pulse; (U2) occurrence of thin-bedded red nodular and cephalopod-bearing limestones with local lithoclastic grainstone intercalations corresponding to a significant deepening of the area and the progressive withdrawal of sedimentary influxes toward the basin, in relation with late Frasnian sea-level rise. Magnetic susceptibility and geochemical analyses were also performed along the Freikofel section and demonstrate the inherent-parallel link existing between variation in magnetic susceptibility values and proxy for terrestrial input. Interpretation of magnetic susceptibility in term of palaeoenvironmental processes reflect that even though distality remains the major parameter influencing magnetic susceptibility values, carbonate production and water agitation also play an important role.Grants IGCP 580 and NAP0017 (DP, ACDS), the FWF P 23775-B17 (TS and EK

Pharmacological BACE1 and BACE2 inhibition induces hair depigmentation by inhibiting PMEL17 processing in mice

Melanocytes of the hair follicle produce melanin and are essential in determining the differences in hair color. Pigment cell-specific MELanocyte Protein (PMEL17) plays a crucial role in melanogenesis. One of the critical steps is the amyloid-like functional oligomerization of PMEL17. Beta Site APP Cleaving Enzyme-2 (BACE2) and γ-secretase have been shown to be key players in generating the proteolytic fragments of PMEL17. The β-secretase (BACE1) is responsible for the generation of amyloid-β (Aβ) fragments in the brain and is therefore proposed as a therapeutic target for Alzheimer's disease (AD). Currently BACE1 inhibitors, most of which lack selectivity over BACE2, have demonstrated efficacious reduction of amyloid-β peptides in animals and the CSF of humans. BACE2 knock-out mice have a deficiency in PMEL17 proteolytic processing leading to impaired melanin storage and hair depigmentation. Here, we confirm BACE2-mediated inhibition of PMEL17 proteolytic processing in vitro in mouse and human melanocytes. Furthermore, we show that wildtype as well as bace2(+/-) and bace2(-/-) mice treated with a potent dual BACE1/BACE2 inhibitor NB-360 display dose-dependent appearance of irreversibly depigmented hair. Retinal pigmented epithelium showed no morphological changes. Our data demonstrates that BACE2 as well as additional BACE1 inhibition affects melanosome maturation and induces hair depigmentation in mice

Inter-group violence among early Holocene hunter-gatherers of West Turkana, Kenya

The nature of inter-group relations among prehistoric hunter-gatherers remains disputed, with arguments in favour and against the existence of warfare before the development of sedentary societies. Here we report on a case of inter-group violence towards a group of hunter-gatherers from Nataruk, west of Lake Turkana, which during the late Pleistocene/early Holocene period extended about 30 km beyond its present-day shore. Ten of the twelve articulated skeletons found at Nataruk show evidence of having died violently at the edge of a lagoon, into which some of the bodies fell. The remains from Nataruk are unique, preserved by the particular conditions of the lagoon with no evidence of deliberate burial. They offer a rare glimpse into the life and death of past foraging people, and evidence that warfare was part of the repertoire of inter-group relations among prehistoric hunter-gatherers