Differential Dynamics at Glycosidic Linkages of an Oligosaccharide as Revealed by 13C NMR Spin Relaxation and Stochastic Modeling

Among biomolecules, carbohydrates are unique in that not only can linkages be formed through different positions but the structures may also be branched. The trisaccharide \uf062-D-Glcp-(1\uf0ae3)[\uf062-D-Glcp-(1\uf0ae2)]-\uf061-D-Manp-OMe represents a model of a branched vicinally disubstituted structure. A 13C site-specific isotopologue with labeling in each of the two terminal glucosyl residues enabled acquisition of high-quality 13C NMR relaxation parameters T1, T2 and heteronuclear NOE, with standard deviations of \uf0a3 0.5%. For interpretation of the experimental NMR data a diffusive chain model was used in which the dynamics of the glycosidic linkages is coupled to the global reorientation motion of the trisaccharide. Brownian dynamics simulations relying on the potential of mean force at the glycosidic linkages were employed to evaluate spectral densities of the spin probes. Calculated NMR relaxation parameters showed very good agreement with experimental data, deviating < 3%. The resulting dynamics is described by correlation times of 196 ps and 174 ps for the \uf062-(1\uf0ae2)- and \uf062-(1\uf0ae3)-linked glucosyl residues, respectively, i.e., different and linkage dependent. Notably, the devised computational protocol was performed without any fitting of parameters

Gravitational Radiation from Triple Star Systems

We have studied the main features of the gravitational radiation generated by an astrophysical system constituted of three compact objects attracting one another (only via gravitational interaction) in such a manner that stable orbits do exist. We have limited our analysis to systems that can be treated with perturbative methods. We show the profile of the gravitational waves emitted by such systems. These results can be useful within the framework of the new gravitational astronomy which will be made feasible by means of the new generation of gravitational detectors such as LISA in a no longer far future.Comment: 10 pages plus 9 postscript figures; revtex; accepted for publication in Int. J. Mod. Phys.

The protein tyrosine phosphatase receptor type R gene is an early and frequent target of silencing in human colorectal tumorigenesis

BACKGROUND: Tumor development in the human colon is commonly accompanied by epigenetic changes, such as DNA methylation and chromatin modifications. These alterations result in significant, inheritable changes in gene expression that contribute to the selection of tumor cells with enhanced survival potential. RESULTS: A recent high-throughput gene expression analysis conducted by our group identified numerous genes whose transcription was markedly diminished in colorectal tumors. One of these, the protein-tyrosine phosphatase receptor type R (PTPRR) gene, was dramatically downregulated from the earliest stages of cellular transformation. Here, we show that levels of both major PTPRR transcript variants are markedly decreased (compared with normal mucosal levels) in precancerous and cancerous colorectal tumors, as well in colorectal cancer cell lines. The expression of the PTPRR-1 isoform was inactivated in colorectal cancer cells as a result of de novo CpG island methylation and enrichment of transcription-repressive histone-tail marks, mainly H3K27me3. De novo methylation of the PTPRR-1 transcription start site was demonstrated in 29/36 (80%) colorectal adenomas, 42/44 (95%) colorectal adenocarcinomas, and 8/8 (100%) liver metastases associated with the latter tumors. CONCLUSIONS: Epigenetic downregulation of PTPRR seems to be an early alteration in colorectal cell transformation, which is maintained during the clonal selection associated with tumor progression. It may represent a preliminary step in the constitutive activation of the RAS/RAF/MAPK/ERK signalling, an effect that will later be consolidated by mutations in genes encoding key components of this pathway

Ecological Connectivity for Amphibians Under Climate Change

Campos, F. S., Lourenço-de-Moraes, R., Ruas, D. S., Mira-Mendes, C. V., Franch, M., Llorente, G. A., ... Cabral, P. (2019). Searching for Networks: Ecological Connectivity for Amphibians Under Climate Change. Environmental Management, 65(1), 46-61. https://doi.org/10.1007/s00267-019-01240-0Ecological connectivity depends on key elements within the landscape, which can support ecological fluxes, species richness and long-term viability of a biological community. Landscape planning requires clear aims and quantitative approaches to identify which key elements can reinforce the spatial coherence of protected areas design. We aim to explore the probability of the ecological connectivity of forest remnants and amphibian species distributions for current and future climate scenarios across the Central Corridor of the Brazilian Atlantic Forest. Integrating amphibian conservation, climate change and ecological corridors, we design a landscape ranking based on graph and circuit theories. To identify the sensitivity of connected areas to climate-dependent changes, we use the Model for Interdisciplinary Research on Climate by means of simulations for 2080–2100, representing a moderated emission scenario within an optimistic context. Our findings indicate that more than 70% of forest connectivity loss by climate change may drastically reduce amphibian dispersal in this region. We show that high amphibian turnover rates tend to be greater in the north-eastern edges of the corridor across ensembles of forecasts. Our spatial analysis reveals a general pattern of low-conductance areas in landscape surface, yet with some well-connected patches suggesting potential ecological corridors. Atlantic Forest reserves are expected to be less effective in a near future. For improved conservation outcomes, we recommend some landscape paths with low resistance values across space and time. We highlight the importance of maintaining forest remnants in the southern Bahia region by drafting a blueprint for functional biodiversity corridors.authorsversionpublishe

Lasing of Moir\'e Trapped MoSe2_2/WSe2_2 Interlayer Excitons Coupled to a Nanocavity

Moir\'e trapped interlayer excitons (IXs) in heterobilayer transition metal dichalcogenides currently attract strong interest due to their potential for non-classical light generation, coherent spin-photon interfaces and exploring novel correlated phases of electrons. Here, we report lasing of moir\'e trapped IXs by integrating a pristine hBN-encapsulated MoSe$_2$/WSe$_2$ heterobilayer in a high-Q ($>10^4$) nanophotonic cavity. We control the detuning between the IX line and the cavity mode with a magnetic field and measure the dipolar coupling strength to the cavity mode to be $78 \pm 4\ \mathrm{\mu eV}$, fully consistent with the 82 $\mathrm{\mu eV}$ predicted by theory. The emission from the cavity mode shows clear threshold-like behaviour. We observe a superlinear power dependence accompanied by a narrowing of the linewidth as the distinct features of lasing. The onset and prominence of these threshold-like behaviours are significant at resonance whilst weak off-resonance. Our results show that a lasing transition can be induced in interacting moir\'e trapped IXs with macroscopic coherence extending over the lengthscale of the cavity mode. Such systems raise interesting perspectives for low-power switching and synaptic nanophotonic devices using 2D materials

Effect of liming and fertilizers on the growth and nutrition of 12-month old Teak (Tectona grandis L.) grown on acidic soil of Peru

Peru has a great potential for forestry plantations, nevertheless, importations of this type of products are getting very expensive. Soils under forest are acidic and infertile to support sustainable economically valuable forest tree species such as teak.  Information is lacking on proper fertility management in forest plantations such as teak. Therefore, the objective of this study was to explore the effect of lime, and organic and inorganic fertilizers on the early growth and nutrient composition of 12-month old teak grown on acidic soil of Peru. The soil under field study was acidic with a pH of 4.99, low in fertility. A factorial design of 2x3: Lime (No Lime and Liming) and fertilizer (organic, inorganic and mixture), with 9 repetitions was adopted. Tree biometric parameters (height, diameter, biomass) and N, P, K, Ca, Mg, Fe, Cu, Mn, Zn foliar concentrations were determined during early the growth of teak. Treatments with addition of dolomite lime favored higher biometric parameters, and use of organic fertilizers promoted more growth than inorganic fertilizers. In the case of nutrients, no major differences were observed between limed and unlimed treatments while organic fertilizer promoted Ca, K and S nutrition. The results show that the application of lime and organic fertilizers is essential for the successful management and establishment of teak plants in acidic soils of Peru

PHOX2B-Mediated Regulation of ALK Expression: In Vitro Identification of a Functional Relationship between Two Genes Involved in Neuroblastoma

BACKGROUND: Neuroblastoma (NB) is a severe pediatric tumor originating from neural crest derivatives and accounting for 15% of childhood cancer mortality. The heterogeneous and complex genetic etiology has been confirmed with the identification of mutations in two genes, encoding for the receptor tyrosine kinase Anaplastic Lymphoma Kinase (ALK) and the transcription factor Paired-like Homeobox 2B (PHOX2B), in a limited proportion of NB patients. Interestingly, these two genes are overexpressed in the great majority of primary NB samples and cell lines. These observations led us to test the hypothesis of a regulatory or functional relationship between ALK and PHOX2B underlying NB pathogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Following this possibility, we first confirmed a striking correlation between the transcription levels of ALK, PHOX2B and its direct target PHOX2A in a panel of NB cell lines. Then, we manipulated their expression in NB cell lines by siRNA-mediated knock-down and forced over-expression of each gene under analysis. Surprisingly, PHOX2B- and PHOX2A-directed siRNAs efficiently downregulated each other as well as ALK gene and, consistently, the enhanced expression of PHOX2B in NB cells yielded an increment of ALK protein. We finally demonstrated that PHOX2B drives ALK gene transcription by directly binding its promoter, which therefore represents a novel PHOX2B target. CONCLUSIONS/SIGNIFICANCE: These findings provide a compelling explanation of the concurrent involvement of these two genes in NB pathogenesis and are going to foster a better understanding of molecular interactions at the base of the disease. Moreover, this work opens new perspectives for NBs refractory to conventional therapies that may benefit from the design of novel therapeutic RNAi-based approaches for multiple gene targets