Glioblastoma (GBM) is the highest-grade form of glioma, as well as one of the most aggressive types of cancer, exhibiting rapid cellular growth and highly invasive behavior. Despite significant ...advances in diagnosis and therapy in recent decades, the outcomes for high-grade gliomas (WHO grades III-IV) remain unfavorable, with a median overall survival time of 15-18 months. The concept of cancer stem cells (CSCs) has emerged and provided new insight into GBM resistance and management. CSCs can self-renew and initiate tumor growth and are also responsible for tumor cell heterogeneity and the induction of systemic immunosuppression. The idea that GBM resistance could be dependent on innate differences in the sensitivity of clonogenic glial stem cells (GSCs) to chemotherapeutic drugs/radiation prompted the scientific community to rethink the understanding of GBM growth and therapies directed at eliminating these cells or modulating their stemness. This review aims to describe major intrinsic and extrinsic mechanisms that mediate chemoradioresistant GSCs and therapies based on antineoplastic agents from natural sources, derivatives, and synthetics used alone or in synergistic combination with conventional treatment. We will also address ongoing clinical trials focused on these promising targets. Although the development of effective therapy for GBM remains a major challenge in molecular oncology, GSC knowledge can offer new directions for a promising future.
Biodiversity loss from deforestation may be partly offset by the expansion of secondary forests and plantation forestry in the tropics. However, our current knowledge of the value of these habitats ...for biodiversity conservation is limited to very few taxa, and many studies are severely confounded by methodological shortcomings. We examined the conservation value of tropical primary, secondary, and plantation forests for 15 taxonomic groups using a robust and replicated sample design that minimized edge effects. Different taxa varied markedly in their response to patterns of land use in terms of species richness and the percentage of species restricted to primary forest (varying from 5% to 57%), yet almost all between-forest comparisons showed marked differences in community structure and composition. Cross-taxon congruence in response patterns was very weak when evaluated using abundance or species richness data, but much stronger when using metrics based upon community similarity. Our results show that, whereas the biodiversity indicator group concept may hold some validity for several taxa that are frequently sampled (such as birds and fruit-feeding butterflies), it fails for those exhibiting highly idiosyncratic responses to tropical land-use change (including highly vagile species groups such as bats and orchid bees), highlighting the problems associated with quantifying the biodiversity value of anthropogenic habitats. Finally, although we show that areas of native regeneration and exotic tree plantations can provide complementary conservation services, we also provide clear empirical evidence demonstrating the irreplaceable value of primary forests.
Type 2 diabetes (T2DM) is associated with chronic low-grade inflammation. Adipose tissue (AT) may represent an important site of inflammation. 3T3-L1 studies have demonstrated that lipopolysaccharide ...(LPS) activates toll-like receptors (TLRs) to cause inflammation. For this study, we 1) examined activation of TLRs and adipocytokines by LPS in human abdominal subcutaneous (AbdSc) adipocytes, 2) examined blockade of NF-kappaB in human AbdSc adipocytes, 3) examined the innate immune pathway in AbdSc AT from lean, obese, and T2DM subjects, and 4) examined the association of circulating LPS in T2DM subjects. The findings showed that LPS increased TLR-2 protein expression twofold (P<0.05). Treatment of AbdSc adipocytes with LPS caused a significant increase in TNF-alpha and IL-6 secretion (IL-6, CONTROL: 2.7+/-0.5 vs. LPS: 4.8+/-0.3 ng/ml; P<0.001; TNF-alpha,
1.0+/-0.83 vs. LPS: 32.8+/-6.23 pg/ml; P<0.001). NF-kappaB inhibitor reduced IL-6 in AbdSc adipocytes (
2.7+/-0.5 vs. NF-kappaB inhibitor: 2.1+/-0.4 ng/ml; P<0.001). AbdSc AT protein expression for TLR-2, MyD88, TRAF6, and NF-kappaB was increased in T2DM patients (P<0.05), and TLR-2, TRAF-6, and NF-kappaB were increased in LPS-treated adipocytes (P<0.05). Circulating LPS was 76% higher in T2DM subjects compared with matched controls. LPS correlated with insulin in controls (r=0.678, P<0.0001). Rosiglitazone (RSG) significantly reduced both fasting serum insulin levels (reduced by 51%, P=0.0395) and serum LPS (reduced by 35%, P=0.0139) in a subgroup of previously untreated T2DM patients. In summary, our results suggest that T2DM is associated with increased endotoxemia, with AT able to initiate an innate immune response. Thus, increased adiposity may increase proinflammatory cytokines and therefore contribute to the pathogenic risk of T2DM.
BACKGROUND: Titi monkeys, Callicebus, comprise the most species-rich primate genus—34 species are currently recognised, five of them described since 2005. The lack of molecular data for titi monkeys ...has meant that little is known of their phylogenetic relationships and divergence times. To clarify their evolutionary history, we assembled a large molecular dataset by sequencing 20 nuclear and two mitochondrial loci for 15 species, including representatives from all recognised species groups. Phylogenetic relationships were inferred using concatenated maximum likelihood and Bayesian analyses, allowing us to evaluate the current taxonomic hypothesis for the genus. RESULTS: Our results show four distinct Callicebus clades, for the most part concordant with the currently recognised morphological species-groups—the torquatus group, the personatus group, the donacophilus group, and the moloch group. The cupreus and moloch groups are not monophyletic, and all species of the formerly recognized cupreus group are reassigned to the moloch group. Two of the major divergence events are dated to the Miocene. The torquatus group, the oldest radiation, diverged c. 11 Ma; and the Atlantic forest personatus group split from the ancestor of all donacophilus and moloch species at 9–8 Ma. There is little molecular evidence for the separation of Callicebus caligatus and C. dubius, and we suggest that C. dubius should be considered a junior synonym of a polymorphic C. caligatus. CONCLUSIONS: Considering molecular, morphological and biogeographic evidence, we propose a new genus level taxonomy for titi monkeys: Cheracebus n. gen. in the Orinoco, Negro and upper Amazon basins (torquatus group), Callicebus Thomas, 1903, in the Atlantic Forest (personatus group), and Plecturocebus n. gen. in the Amazon basin and Chaco region (donacophilus and moloch groups).
The Amazon Basin plays key roles in the carbon and water cycles, climate change, atmospheric chemistry, and biodiversity. It has already been changed significantly by human activities, and more ...pervasive change is expected to occur in the coming decades. It is therefore essential to establish long-term measurement sites that provide a baseline record of present-day climatic, biogeochemical, and atmospheric conditions and that will be operated over coming decades to monitor change in the Amazon region, as human perturbations increase in the future. The Amazon Tall Tower Observatory (ATTO) has been set up in a pristine rain forest region in the central Amazon Basin, about 150 km northeast of the city of Manaus. Two 80 m towers have been operated at the site since 2012, and a 325 m tower is nearing completion in mid-2015. An ecological survey including a biodiversity assessment has been conducted in the forest region surrounding the site. Measurements of micrometeorological and atmospheric chemical variables were initiated in 2012, and their range has continued to broaden over the last few years. The meteorological and micrometeorological measurements include temperature and wind profiles, precipitation, water and energy fluxes, turbulence components, soil temperature profiles and soil heat fluxes, radiation fluxes, and visibility. A tree has been instrumented to measure stem profiles of temperature, light intensity, and water content in cryptogamic covers. The trace gas measurements comprise continuous monitoring of carbon dioxide, carbon monoxide, methane, and ozone at five to eight different heights, complemented by a variety of additional species measured during intensive campaigns (e.g., VOC, NO, NO2, and OH reactivity). Aerosol optical, microphysical, and chemical measurements are being made above the canopy as well as in the canopy space. They include aerosol light scattering and absorption, fluorescence, number and volume size distributions, chemical composition, cloud condensation nuclei (CCN) concentrations, and hygroscopicity. In this paper, we discuss the scientific context of the ATTO observatory and present an overview of results from ecological, meteorological, and chemical pilot studies at the ATTO site.
Mitochondrial DNA remains a cornerstone for molecular ecology, especially for study species from which high‐quality tissue samples cannot be easily obtained. Methods using mitochondrial markers are ...usually reliant on reference databases, but these are often incomplete. Furthermore, available mitochondrial genomes often lack crucial metadata, such as sampling location, limiting their utility for many analyses. Here, we assembled 205 new mitochondrial genomes for platyrrhine primates, most from the Amazon and with known sampling locations. We present a dated mitogenomic phylogeny based on these samples along with additional published platyrrhine mitogenomes, and use this to assess support for the long‐standing riverine barrier hypothesis (RBH), which proposes that river formation was a major driver of speciation in Amazonian primates. Along the Amazon, Negro, and Madeira rivers, we found mixed support for the RBH. While we identified divergences that coincide with a river barrier, only some occur synchronously and also overlap with the proposed dates of river formation. The most compelling evidence is for the Amazon river potentially driving speciation within bearded saki monkeys (Chiropotes spp.) and within the smallest extant platyrrhines, the marmosets and tamarins. However, we also found that even large rivers do not appear to be barriers for some primates, including howler monkeys (Alouatta spp.), uakaris (Cacajao spp.), sakis (Pithecia spp.), and robust capuchins (Sapajus spp.). Our results support a more nuanced, clade‐specific effect of riverine barriers and suggest that other evolutionary mechanisms, besides the RBH and allopatric speciation, may have played an important role in the diversification of platyrrhines.
In the present study we tested if a series of 18 rapids on the upper Madeira River form an effective barrier to gene flow, and in particular if they delimit the distribution of the boto Inia ...boliviensis—which it is believed to occurs only in the Bolivian sub-basin, above the rapids—and I. geoffrensis, which occurs throughout the Amazon basin and below the upper Madeira River rapids. We analyzed 125 individuals from the Madeira River basin sampled from upstream and downstream of the rapids. As the two species are morphologically similar, we used diagnostic molecular characters from known reference specimens to assign individuals to species. We observed that all individuals of Inia from the Bolivian sub-basin up to almost the mouth of the Madeira River belong to the species I. boliviensis. Therefore we concluded that the rapids do not delimit the distribution of I. boliviensis upstream and I. geoffrensis downstream of the rapids as previously hypothesized. Since we registered I. boliviensis along almost the entire length of the Madeira River, we estimated gene flow, time of divergence and effective population sizes of the upstream (Bolivian) and downstream (Madeira River) groups of I. boliviensis using IMa2. We concluded that gene flow is uni-directional from the upstream to the downstream group. Divergence time between the two groups was estimated to have occurred ~122 thousand years ago. The coalescent effective population size for the upstream group was estimated at ~131 thousand individuals, while for the downstream group it was estimated at ~102 thousand individuals. Recently two dams have been constructed in the region of the rapids; neither has a mechanism that will maintain connectivity between the upstream and downstream regions, and together with anthropogenic alterations to the hydrodynamic regime and ecology of the river will likely pose serious long-term and short-term consequences for I. boliviensis and other aquatic taxa.
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•We describe a new species of Plecturocebus of the eastern Amazon Clade.•Genomic-wide (ddRADseq) and mitochondrial data support monophyly of the new species.•The new species is sister ...to P. moloch + P. vieirai.•We predict a total loss of 86% of the new species habitat in the next 24 years.•The new species can be categorised as Critically Endangered under IUCN A3c criterion.
The taxonomy of the titi monkeys (Callicebinae) has recently received considerable attention. It is now recognised that this subfamily is composed of three genera with 33 species, seven of them described since 2002. Here, we describe a new species of titi, Plecturocebus, from the municipality of Alta Floresta, Mato Grosso, Brazil. We adopt an integrative taxonomic approach that includes phylogenomic analyses, pelage characters, and locality records. A reduced representation genome-wide approach was employed to assess phylogenetic relationships among species of the eastern Amazonian clade of the Plecturocebus moloch group. Using existing records, we calculated the Extent of Occurrence (EOO) of the new species and estimated future habitat loss for the region based on predictive models. We then evaluated the species’ conservation status using the IUCN Red list categories and criteria. The new species presents a unique combination of morphological characters: (1) grey agouti colouration on the crown and dorsal parts; (2) entirely bright red-brown venter; (3) an almost entirely black tail with a pale tip; and (4) light yellow colouration of the hair on the cheeks contrasting with bright red-brown hair on the sides of the face. Our phylogenetic reconstructions based on maximum-likelihood and Bayesian methods revealed well-supported species relationships, with the Alta Floresta taxon as sister to P. moloch + P. vieirai. The species EOO is 10,166,653 ha and we predict a total habitat loss of 86% of its original forest habitat under a “business as usual” scenario in the next 24 years, making the newly discovered titi monkey a Critically Endangered species under the IUCN A3c criterion. We give the new titi monkey a specific epithet based on: (1) clear monophyly of this lineage revealed by robust genomic and mitochondrial data; (2) distinct and diagnosable pelage morphology; and (3) a well-defined geographical distribution with clear separation from other closely related taxa. Urgent conservation measures are needed to safeguard the future of this newly discovered and already critically endangered primate.
Five pilot-scale steam explosion pretreatments of sugarcane bagasse followed by alkaline delignification were explored. The solubilised lignin was precipitated with 98% sulphuric acid. Most of the ...pentosan (82.6%), and the acetyl group fractions were solubilised during pretreatment, while 90.2% of cellulose and 87.0% lignin were recovered in the solid fraction. Approximately 91% of the lignin and 72.5% of the pentosans contained in the steam-exploded solids were solubilised by delignification, resulting in a pulp with almost 90% of cellulose. The acidification of the black liquors allowed recovery of 48.3% of the lignin contained in the raw material. Around 14% of lignin, 22% of cellulose and 26% of pentosans were lost during the process. In order to increase material recovery, major changes, such as introduction of efficient condensers and the reduction in the number of washing steps, should be done in the process setup.
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