Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling

The Rac1 guanosine triphosphatase (GTPase) has been implicated in multiple cellular functions, including actin dynamics, proliferation, apoptosis, adhesion, and migration resulting from signaling by multiple receptors, including the B cell antigen receptor (BCR). We used conditional gene targeting to generate mice with specific Rac1 deficiency in the B cell lineage. In the absence of both Rac1 and the highly related Rac2, B cell development was almost completely blocked. Both GTPases were required to transduce BCR signals leading to proliferation, survival and up-regulation of BAFF-R, a receptor for BAFF, a key survival molecule required for B cell development and maintenance.     

Experimental identification of downhill protein folding

Theory predicts the existence of barrierless protein folding. Without barriers, folding should be noncooperative and the degree of native structure should be coupled to overall protein stability. We investigated the thermal unfolding of the peripheral subunit binding domain from Escherichia coli's 2-oxoglutarate dehydrogenase multienzyme complex (termed BBL) with a combination of spectroscopic techniques and calorimetry. Each technique probed a different feature of protein structure. BBL has a defined three-dimensional structure at low temperatures. However, each technique showed a distinct unfolding transition. Global analysis with a statistical mechanical model identified BBL as a downhill-folding protein. Because of BBL's biological function, we propose that downhill folders may be molecular rheostats, in which effects could be modulated by altering the distribution of an ensemble of structures.     

Kilimanjaro ice core records: evidence of holocene climate change in tropical Africa

Six ice cores from Kilimanjaro provide an approximately 11.7-thousand-year record of Holocene climate and environmental variability for eastern equatorial Africa, including three periods of abrupt climate change: approximately 8.3, approximately 5.2, and approximately 4 thousand years ago (ka). The latter is coincident with the "First Dark Age," the period of the greatest historically recorded drought in tropical Africa. Variable deposition of F- and Na+ during the African Humid Period suggests rapidly fluctuating lake levels between approximately 11.7 and 4 ka. Over the 20th century, the areal extent of Kilimanjaro's ice fields has decreased approximately 80%, and if current climatological conditions persist, the remaining ice fields are likely to disappear between 2015 and 2020.     

Four climate cycles of recurring deep and surface water destabilizations on the Iberian margin

Centennial climate variability over the last ice age exhibits clear bipolar behavior. High-resolution analyses of marine sediment cores from the Iberian margin trace a number of associated changes simultaneously. Proxies of sea surface temperature and water mass distribution, as well as relative biomarker content, demonstrate that this typical north-south coupling was pervasive for the cold phases of climate during the past 420,000 years. Cold episodes after relatively warm and largely ice-free periods occurred when the predominance of deep water formation changed from northern to southern sources. These results reinforce the connection between rapid climate changes at Mediterranean latitudes and century-to-millennial variability in northern and southern polar regions.     

Cross-linking cellular prion protein triggers neuronal apoptosis in vivo

Neuronal death is a prominent, but poorly understood, pathological hallmark of prion disease. Notably, in the absence of the cellular prion protein (PrPC), the disease-associated isoform, PrPSc, appears not to be intrinsically neurotoxic, suggesting that PrPC itself may participate directly in the prion neurodegenerative cascade. Here, cross-linking PrPC in vivo with specific monoclonal antibodies was found to trigger rapid and extensive apoptosis in hippocampal and cerebellar neurons. These findings suggest that PrPC functions in the control of neuronal survival and provides a model to explore whether cross-linking of PrPC by oligomeric PrPSc can promote neuronal loss during prion infection.     

Isotopic evidence for massive oxidation of organic matter following the great oxidation event

The stable isotope record of marine carbon indicates that the Proterozoic Eon began and ended with extreme fluctuations in the carbon cycle. In both the Paleoproterozoic [2500 to 1600 million years ago (Ma)] and Neoproterozoic (1000 to 542 Ma), extended intervals of anomalously high carbon isotope ratios (δ(13)C) indicate high rates of organic matter burial and release of oxygen to the atmosphere; in the Neoproterozoic, the high δ(13)C interval was punctuated by abrupt swings to low δ(13)C, indicating massive oxidation of organic matter. We report a Paleoproterozoic negative δ(13)C excursion that is similar in magnitude and apparent duration to the Neoproterozoic anomaly. This Shunga-Francevillian anomaly may reflect intense oxidative weathering of rocks as the result of the initial establishment of an oxygen-rich atmosphere.     

Molecular characterization of chestnut plants selected for putative resistance to Phytophthora cinnamomi using SSR markers

A set of nine short sequence repeat (SSR) loci was used for the molecular characterization of 32 accessions of 15 chestnut trees selected in the field because of their putative resistance to the ink disease caused by Phytophthora spp. The goal of the present study was to determine the genetic identity of those selected European chestnut trees (Castanea sativa) or interspecific hybrids, considering that hybridization programs between European chestnut and Asiatic species (mainly Japanese chestnut, Castanea crenata) have been carried out in Galicia (Spain) since the early 20th century. The results showed that the analyzed SSR loci were useful to discriminate three Asiatic and the European species of Castanea. The joint information provided by a factorial correspondence analysis (FCA) and the presence of privative alleles allowed the putative molecular assignment of the selected plants to a certain identity. Most of them were determined as hybrids between C. crenata and C. sativa. The individuals coded C036 and C048 were assigned, with a high probability, to C. sativa due to their clustering with accessions of this species and because they had a number of privative alleles of this species. Only a few individuals could not be assigned to any particular genotype.     

Biological activity of peanut (Arachis hypogaea) phytoalexins and selected natural and synthetic Stilbenoids

The peanut plant (Arachis hypogaea L.), when infected by a microbial pathogen, is capable of producing stilbene-derived compounds that are considered antifungal phytoalexins. In addition, the potential health benefits of other stilbenoids from peanuts, including resveratrol and pterostilbene, have been acknowledged by several investigators. Despite considerable progress in peanut research, relatively little is known about the biological activity of the stilbenoid phytoalexins. This study investigated the activities of some of these compounds in a broad spectrum of biological assays. Since peanut stilbenoids appear to play roles in plant defense mechanisms, they were evaluated for their effects on economically important plant pathogenic fungi of the genera Colletotrichum, Botrytis, Fusarium, and Phomopsis. We further investigated these peanut phytoalexins, together with some related natural and synthetic stilbenoids (a total of 24 compounds) in a panel of bioassays to determine their anti-inflammatory, cytotoxic, and antioxidant activities in mammalian cells. Several of these compounds were also evaluated as mammalian opioid receptor competitive antagonists. Assays for adult mosquito and larvae toxicity were also performed. The results of these studies reveal that peanut stilbenoids, as well as related natural and synthetic stilbene derivatives, display a diverse range of biological activities.     

Classification of pumpkin seed oils according to their species and genetic variety by attenuated total reflection Fourier-transform infrared spectroscopy

Attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR), followed by multivariate treatment of the spectral data, was used to classify seed oils of the genus Cucurbita (pumpkins) according to their species as C. maxima, C. pepo, and C. moschata. Also, C. moschata seed oils were classified according to their genetic variety as RG, Inivit C-88, and Inivit C-2000. Up to 23 wavelength regions were selected on the spectra, each region corresponding to a peak or shoulder. The normalized absorbance peak areas within these regions were used as predictors. Using linear discriminant analysis (LDA), an excellent resolution among all categories concerning both Cucurbita species and C. moschata varieties was achieved. The proposed method was straightforward and quick and can be easily implemented. Quality control of pumpkin seed oils is important because Cucurbita species and genetic variety are both related to the pharmaceutical properties of the oils.