Recent Surveys in the Forests of Ulu Segama Malua, Sabah, Malaysia, Show That Orang-utans (P. p. morio) Can Be Maintained in Slightly Logged Forests

BACKGROUND: Today the majority of wild great ape populations are found outside of the network of protected areas in both Africa and Asia, therefore determining if these populations are able to survive in forests that are exploited for timber or other extractive uses and how this is managed, is paramount for their conservation. METHODOLOGY/PRINCIPAL FINDINGS: In 2007, the "Kinabatangan Orang-utan Conservation Project" (KOCP) conducted aerial and ground surveys of orang-utan (Pongo pygmaeus morio) nests in the commercial forest reserves of Ulu Segama Malua (USM) in eastern Sabah, Malaysian Borneo. Compared with previous estimates obtained in 2002, our recent data clearly shows that orang-utan populations can be maintained in forests that have been lightly and sustainably logged. However, forests that are heavily logged or subjected to fast, successive coupes that follow conventional extraction methods, exhibit a decline in orang-utan numbers which will eventually result in localized extinction (the rapid extraction of more than 100 m(3) ha(-1) of timber led to the crash of one of the surveyed sub-populations). Nest distribution in the forests of USM indicates that orang-utans leave areas undergoing active disturbance and take momentarily refuge in surrounding forests that are free of human activity, even if these forests are located above 500 m asl. Displaced individuals will then recolonize the old-logged areas after a period of time, depending on availability of food sources in the regenerating areas. CONCLUSION/SIGNIFICANCE: These results indicate that diligent planning prior to timber extraction and the implementation of reduced-impact logging practices can potentially be compatible with great ape conservation

PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution.

Mosaicism is increasingly recognized as a cause of developmental disorders with the advent of next-generation sequencing (NGS). Mosaic mutations of PIK3CA have been associated with the widest spectrum of phenotypes associated with overgrowth and vascular malformations. We performed targeted NGS using 2 independent deep-coverage methods that utilize molecular inversion probes and amplicon sequencing in a cohort of 241 samples from 181 individuals with brain and/or body overgrowth. We identified PIK3CA mutations in 60 individuals. Several other individuals (n = 12) were identified separately to have mutations in PIK3CA by clinical targeted-panel testing (n = 6), whole-exome sequencing (n = 5), or Sanger sequencing (n = 1). Based on the clinical and molecular features, this cohort segregated into three distinct groups: (a) severe focal overgrowth due to low-level but highly activating (hotspot) mutations, (b) predominantly brain overgrowth and less severe somatic overgrowth due to less-activating mutations, and (c) intermediate phenotypes (capillary malformations with overgrowth) with intermediately activating mutations. Sixteen of 29 PIK3CA mutations were novel. We also identified constitutional PIK3CA mutations in 10 patients. Our molecular data, combined with review of the literature, show that PIK3CA-related overgrowth disorders comprise a discontinuous spectrum of disorders that correlate with the severity and distribution of mutations

KV7/KCNQ Channels Are Functionally Expressed in Oligodendrocyte Progenitor Cells

Background: KV7/KCNQ channels are widely expressed in neurons and they have multiple important functions, including control of excitability, spike afterpotentials, adaptation, and theta resonance. Mutations in KCNQ genes have been demonstrated to associate with human neurological pathologies. However, little is known about whether K V7/KCNQ channels are expressed in oligodendrocyte lineage cells (OLCs) and what their functions in OLCs. Methods and Findings: In this study, we characterized KV7/KCNQ channels expression in rat primary cultured OLCs by RT-PCR, immunostaining and electrophysiology. KCNQ2-5 mRNAs existed in all three developmental stages of rat primary cultured OLCs. K V7/KCNQ proteins were also detected in oligodendrocyte progenitor cells (OPCs, early developmental stages of OLCs) of rat primary cultures and cortex slices. Voltage-clamp recording revealed that the IM antagonist XE991 significantly reduced KV7/KCNQ channel current (IK(Q)) in OPCs but not in differentiated oligodendrocytes. In addition, inhibition of K V7/KCNQ channels promoted OPCs motility in vitro. Conclusions: These findings showed that K V7/KCNQ channels were functionally expressed in rat primary cultured OLCs an

Aag DNA Glycosylase Promotes Alkylation-Induced Tissue Damage Mediated by Parp1

Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER) is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG) mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag−/− mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage.National Institutes of Health (U.S.) (NIH grant R01-CA075576)National Institutes of Health (U.S.) (NIH grant R01-CA055042)National Institutes of Health (U.S.) (NIH grant R01-CA149261)National Institutes of Health (U.S.) (NIH grant P30-ES00002)National Institutes of Health (U.S.) (NIH grant P30-ES02109)National Center for Research Resources (U.S.) (grant number M01RR-01066)National Center for Research Resources (U.S.) (grant number UL1 RR025758, Harvard Clinical and Translational Science Center

The stability against freezing of an internal liquid-water ocean in Callisto

Depto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEpu