Two new species of diminutive leaf-litter skinks (Squamata: Scincidae: Tytthoscincus) from Gunung Penrissen, Sarawak, Malaysia (northern Borneo)

We describe two new species of skinks from Gunung Penrissen, Sarawak, Malaysia, in northern Borneo, Tytthoscincus batupanggah sp. nov. and T. leproauricularis sp. nov. Morphological and molecular analyses both corroborate the two new species as unique compared to all other Tytthoscincus and additional Sphenomorphus that are candidates for taxonomic placement in the genus Tytthoscincus. Despite their phenotypic similarity and sympatric distribution, a molecular analysis shows that the new species are not sister taxa and exhibit a deep genetic divergence between each of their respective sister taxa. We discuss how historical climatic and geographic processes may have led to the co-distribution of two relatively distantly related phenotypically similar species. In light of these discoveries, we also emphasize the importance of conserving primary montane tropical rainforest for maintaining species diversity

Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies

Ancient Divergence Time Estimates In Eutropis Rugifera Support The Existence Of Pleistocene Barriers On The Exposed Sunda Shelf

Episodic sea level changes that repeatedly exposed and inundated the Sunda Shelf characterize the Pleistocene. Available evidence points to a more xeric central Sunda Shelf during periods of low sea levels, and despite the broad land connections that persisted during this time, some organisms are assumed to have faced barriers to dispersal between land-masses on the Sunda Shelf. Eutropis rugifera is a secretive, forest adapted scincid lizard that ranges across the Sunda Shelf. In this study, we sequenced one mitochondrial (ND2) and four nuclear (BRCA1, BRCA2, RAG1, and MC1R) markers and generated a time-calibrated phylogeny in BEAST to test whether divergence times between Sundaic populations of E. rugifera occurred during Pleistocene sea-level changes, or if they predate the Pleistocene. We find that E. rugifera shows pre-Pleistocene divergences between populations on different Sundaic land-masses. The earliest divergence within E. rugifera separates the Philippine samples from the Sundaic samples approximately 16 Ma; the Philippine populations thus cannot be considered conspecific with Sundaic congeners. Sundaic populations diverged approximately 6 Ma, and populations within Borneo from Sabah and Sarawak separated approximately 4.5 Ma in the early Pliocene, followed by further cladogenesis in Sarawak through the Pleistocene. Divergence of peninsular Malaysian populations from the Mentawai Archipelago occurred approximately 5 Ma. Separation among island populations from the Mentawai Archipelago likely dates to the Pliocene/Pleistocene boundary approximately 3.5 Ma, and our samples from peninsular Malaysia appear to coalesce in the middle Pleistocene, about 1 Ma. Coupled with the monophyly of these populations, these divergence times suggest that despite consistent land-connections between these regions throughout the Pleistocene E. rugifera still faced barriers to dispersal, which may be a result of environmental shifts that accompanied the sea-level changes

Reptiles

A total of 86 species of reptiles are now known from Gunung Penrissen. The earliest account in 1900 (based on his collections in 1899) by William Shelford included 24 species. As with the amphibian fauna, faunal turnover with elevation is distinct, with the lowlands inhabited by generalised Bornean lowland reptiles, the upper (> 1,200 m above sea level) elevations showing several Bornean endemics, including a few only otherwise known from Gunung Kinabalu, in northern Borneo

The effect of intracellular iron concentration and nitrogen monoxide on NRAMP2 expression and non-transferrin-bound iron uptake

Recent studies have demonstrated that the protein product (natural resistance associated macrophage protein 2, Nramp2) encoded by the gene Nramp2 acts as an Fe transporter involved in the uptake of Fe from transferrin (Tf ) and low Mr Fe complexes. Interestingly, there are two splice variants of Nramp2, one with a putative ironresponsive element (IRE) in its 30 untranslated region (UTR) and another without. Due to the importance of Nramp2 in Fe transport, and the presence of an IRE in its 30-UTR, we have examined the effect of Fe-deprivation, Fe-loading, and nitrogen monoxide on the expression of Nramp2 mRNA. These results were compared to the expression of transferrin receptor (TfR) mRNAwhich also has IREs in its 30-UTR and is regulated by Fe and NO via the binding of iron-regulatory proteins (IRPs) to its IREs. Our experiments show that the IRE in Nramp2 mRNA does bind the IRPs in lysates from a mouse fibroblast cell line (LMTK2). Moreover, reverse transcription- PCR (RT-PCR) demonstrated that both the IRE and non-IRE-containing transcripts were present within these cells. However, there was no change in Nramp2 mRNA expression in LMTK2 cells after a 20-h incubation with either the Fe chelator, desferrioxamine (DFO), the Fe donor, ferric ammonium citrate (FAC), or the NO generator, S-nitroso-N-acetylpenicillamine (SNAP). In contrast, these agents caused a marked change in the RNA-binding activity of the IRPs and the expression of TfR mRNA. In addition, both FAC and DFO caused an appropriate change in [59Fe] uptake from [59Fe]Tf, viz., an increase in Fe uptake after exposure to DFO and a decrease after treatment with FAC. As Nramp2 can transport Fe from non-Tf-bound Fe, the effect of preincubation with DFO and FAC was also examined on Fe uptake from [59Fe]nitrilotriacetate and [59Fe]citrate. However, in contrast to the results found for [59Fe]Tf, incubation with DFO and FAC did not result in appropriate regulation of Fe uptake from [59Fe]nitrilotriacetate or [59Fe]citrate. These data demonstrate that non-Tf-bound Fe uptake was not under control of the IRP-IRE system in these cells. Collectively, the results indicate that in LMTK-fibroblasts Nramp2 mRNA expression was not regulated like TfR mRNA

Claudicação em cavalos Crioulos atletas Lameness in athletic Criollo horses

O objetivo deste trabalho foi identificar as principais causas de claudicação em cavalos Crioulos em treinamento para a prova do Freio de Ouro e competições de rédeas. Foram avaliados os registros clínicos de 201 cavalos Crioulos, 5,6 2,1 anos de idade, submetidos a exame físico devido à presença de claudicação ou histórico de baixo rendimento atlético entre os anos de 2002 a 2009. A claudicação foi localizada nos membros torácicos e pélvicos em 47,1% (n=105) e 52,9% (n=118), respectivamente. Nos machos, houve uma predominância de claudicação nos membros pélvicos (60,0%) e nas fêmeas nos membros torácicos (57,1%). Nos membros torácicos, 17,1% (18/105) das alterações foram diagnosticadas proximais à articulação metacarpofalangeana, 14,3% (15/105) na articulação metacarpofalangeana e 68,6% (72/105) estavam localizadas distais à articulação metacarpofalangeana. Nos membros pélvicos, 78,8% (93/118) apresentaram a origem da dor na região do tarso, 17,8% (21/118) proximal ao tarso e 3,4% (4/118) distal ao tarso. As articulações interfalangeanas distais e intertarsiana distal/tarsometatarsiana são importantes fontes de dor e inflamação e estiveram mais frequentemente envolvidas em claudicações de membro torácico e pélvico, respectivamente. Os cavalos Crioulos apresentam problemas de claudicação semelhantes aos descritos em outras raças que participam de provas de rodeio.<br>This study aimed to identify the source of lameness in Criollo horses that are competing in the most important discipline for this breed in Southern Brazil and also in reining competitions. Clinical records of adult Criollo horses (n=201), 5.6 2.1 years of age, that underwent lameness examination due to history of poor performance or lameness between 2002/2009 were analyzed. Lameness was diagnosed in the front limbs in 47.1% (n=105) and in the hind limbs 52.9% of the cases (n=118). In males 60.0% of the lameness cases were located in the hind limbs. In females 57.1% of the lameness cases were located in the front limbs. In the front limbs (47.1%, n=105/201), problems proximal to the fetlock were diagnosed in 17.1% (18/105). Fetlock problems were diagnosed in 14.3% (15/105) and lesions located distal to the fetlock level were seen in 68.6% (72/105) of the lameness cases diagnosed in the front limbs. In the hind limbs, problems located proximal to the tarsus were seen in 17.8% (21/118), 78.8% (93/118) in the tarsus and 3.4% (4/118) of the cases were seen distal to the tarsus. The distal interfalangeal joint in the front limbs and the distal tarsal joints in the hind limbs were the two most important sources of lameness. Criollo horses presented similar lameness problems as described in other show horses (reining, cutting and roping). This is the first lameness study done in Criollo horses and it will help to better understand the musculoskeletal diseases affecting this breed

The Ionized Gas in Nearby Galaxies as Traced by the [NII] 122 and 205 um Transitions

The [NII] 122 and 205 um transitions are powerful tracers of the ionized gas in the ISM: (1) the [NII] 122/205 line ratio can be used to measure the electron density of the low-excitation, ionized gas, and (2) the intensity of these lines is directly related to the flux of ionizing photons, probing the most recent star formation activity. The study of these applications in nearby galaxies is specially relevant now that ALMA can observe both [NII] transitions at z&gt;2. In this talk I will present Herschel observations of these pair of [NII] far-infrared lines in 21 nearby galaxies selected from the KINGFISH and Beyond the Peak samples. I will discuss the reliability of the [NII] lines as star formation tracers, and how the electron density of the ionized gas is related to other relevant ISM properties (e.g., radiation field strength, star formation activity, dust temperature, etc).Astrodynamics & Space Mission