The Expanded mtDNA Phylogeny of the Franco-Cantabrian Region Upholds the Pre-Neolithic Genetic Substrate of Basques

The European genetic landscape has been shaped by several human migrations occurred since Paleolithic times. The accumulation of archaeological records and the concordance of different lines of genetic evidence during the last two decades have triggered an interesting debate concerning the role of ancient settlers from the Franco-Cantabrian region in the postglacial resettlement of Europe. Among the Franco-Cantabrian populations, Basques are regarded as one of the oldest and more intriguing human groups of Europe. Recent data on complete mitochondrial DNA genomes focused on macrohaplogroup R0 revealed that Basques harbor some autochthonous lineages, suggesting a genetic continuity since pre-Neolithic times. However, excluding haplogroup H, the most representative lineage of macrohaplogroup R0, the majority of maternal lineages of this area remains virtually unexplored, so that further refinement of the mtDNA phylogeny based on analyses at the highest level of resolution is crucial for a better understanding of the European prehistory. We thus explored the maternal ancestry of 548 autochthonous individuals from various Franco-Cantabrian populations and sequenced 76 mitogenomes of the most representative lineages. Interestingly, we identified three mtDNA haplogroups, U5b1f, J1c5c1 and V22, that proved to be representative of Franco-Cantabria, notably of the Basque population. The seclusion and diversity of these female genetic lineages support a local origin in the Franco-Cantabrian area during the Mesolithic of southwestern Europe, ∼10,000 years before present (YBP), with signals of expansions at ∼3,500 YBP. These findings provide robust evidence of a partial genetic continuity between contemporary autochthonous populations from the Franco-Cantabrian region, specifically the Basques, and Paleolithic/Mesolithic hunter-gatherer groups. Furthermore, our results raise the current proportion (≈15%) of the Franco-Cantabrian maternal gene pool with a putative pre-Neolithic origin to ≈35%, further supporting the notion of a predominant Paleolithic genetic substrate in extant European populations.     

Stabilizing ER Ca2+ Channel Function as an Early Preventative Strategy for Alzheimer’s Disease

Alzheimer’s disease (AD) is a devastating neurodegenerative condition with no known cure. While current therapies target late-stage amyloid formation and cholinergic tone, to date, these strategies have proven ineffective at preventing disease progression. The reasons for this may be varied, and could reflect late intervention, or, that earlier pathogenic mechanisms have been overlooked and permitted to accelerate the disease process. One such example would include synaptic pathology, the disease component strongly associated with cognitive impairment. Dysregulated Ca²⁺ homeostasis may be one of the critical factors driving synaptic dysfunction. One of the earliest pathophysiological indicators in mutant presenilin (PS) AD mice is increased intracellular Ca²⁺ signaling, predominantly through the ER-localized inositol triphosphate (IP₃) and ryanodine receptors (RyR). In particular, the RyR-mediated Ca²⁺ upregulation within synaptic compartments is associated with altered synaptic homeostasis and network depression at early (presymptomatic) AD stages. Here, we offer an alternative approach to AD therapeutics by stabilizing early pathogenic mechanisms associated with synaptic abnormalities. We targeted the RyR as a means to prevent disease progression, and sub-chronically treated AD mouse models (4-weeks) with a novel formulation of the RyR inhibitor, dantrolene. Using 2-photon Ca²⁺ imaging and patch clamp recordings, we demonstrate that dantrolene treatment fully normalizes ER Ca²⁺ signaling within somatic and dendritic compartments in early and later-stage AD mice in hippocampal slices. Additionally, the elevated RyR2 levels in AD mice are restored to control levels with dantrolene treatment, as are synaptic transmission and synaptic plasticity. Aβ deposition within the cortex and hippocampus is also reduced in dantrolene-treated AD mice. In this study, we highlight the pivotal role of Ca²⁺ aberrations in AD, and propose a novel strategy to preserve synaptic function, and thereby cognitive function, in early AD patients.     

The red-crab bloom off the west coast of Baja California, Mexico

Hydroacoustic data indicate that the benthic red crab Pleuroncodesplanipes(Stimpson, 1860) rises from the bottom towards the surfaceat dusk from very compacted patches settled on the continentalshelf. The behaviour is fast and abrupt, lasting >60 min.     

Alkyl-dihydroxyacetone phosphate synthase and dihydroxyacetone phosphate acyltransferase form a protein complex in peroxisomes.

Dihydroxyacetone phosphate (GrnP) acyltransferase and alkyl-GrnP synthase are the key enzymes involved in the biosynthesis of ether phospholipids. Both enzymes are located on the inside of the peroxisomal membrane. Here we report evidence for a direct interaction between these enzymes obtained by the use of chemical cross-linking. After cross-linking and immunoblot analysis alkyl-GrnP synthase could be detected in a 210-kDa complex which was located entirely on the lumenal side of the peroxisomal membrane. Two-dimensional SDS/PAGE demonstrated that GrnP-acyltransferase is also cross-linked in a 210-kDa complex. Co-immunoprecipitation confirmed that the two enzymes interact, in a heterotrimeric complex. Furthermore, alkyl-GrnP synthase can form a homotrimeric complex in the absence of GrnP-acyltransferase as was demonstrated by immunoblot analysis after cross-linking experiments with either GrnP-acyltransferase deficient human fibroblast homogenates or recombinant (His)6-tagged alkyl-GrnP synthase. We conclude that alkyl-GrnP synthase interacts selectively with GrnP-acyltransferase in a heterotrimeric complex and in the absence of GrnP-acyltransferase can also form a homotrimeric complex.     

Immunocytochemical localization of the elongation factor Tu in E. coli cells

The localization of the elongation factor Tu (EF-Tu) in ultrathin cryosections of E. coli cells was determined with the electron microscope using a highly specific immunological labelling technique. EF-Tu is distributed almost homogeneously throughout the cytoplasm. Although it has often been suggested that EF-Tu could be part of a putative prokaryotic cytoskeleton, we did not find any evidence for supramolecular assemblies, such as fibres or filaments, containing a large amount of EF-Tu. EF-Tu was not observed in association with the outer cell membrane and periplasmic space. A topological relationship with the inner membrane is not apparent in our micrographs. In cells in which the EF-Tu level is raised significantly, the protein piles up in discrete cell regions.     

Electromyogram and force during stimulated fatigue tests of muscles in dominant and non-dominant hands

Mechanical and electrical properties were studied for the first dorsal interosseous muscle of the dominant (d-FDI) and non-dominant hand (nd-FDI). Observations were made before, during and after a fatigue test, fatigue being evoked by percutaneous electrical stimulation of the ulnar nerve. The test consisted of 30 Hz bursts of ten supramaximal 0.1 ms pulses, repeated once a second for 5 min. The measurements included the amplitude of the first and fifth compound muscle action potentials (M-waves) within bursts, the peak burst force and the amplitude and time course of single twitches. At the end of the fatigue test, burst force had decreased to about the same extent in the FDI of both hands. The final decline in first M-wave amplitude was, however, significantly more pronounced for the nd-FDI than for the d-FDI. There were no longer any significant discrepancies between the two muscles after a subsequent recovery-period of 15 min. Comparisons among nd-FDI of various individuals demonstrated the presence of significant inter-individual differences in fatigue-related force-drop without any associated differences in M-wave decline. Intra-individual variability was similar for fatigue-related force-drop and M-wave decline.     

Detection of Infectious Astroviruses in Water

A method based on the infection of CaCo-2 cells and molecular hybridization with a specific cDNA probe has been developed for the detection of infectious astroviruses in environmental samples. By this procedure wild-type astroviruses have been detected in water from an area where a concurrent gastroenteritis outbreak was reported.     

Chrysonila sitophila (TFB-27441): A hyperlignolytic strain

Summary C. sitophila strain TFB-27441 showed 2–3 times higher lignolytic activity thanPhanerochaete chrysosporium (BKM-F-1767 strain). Lignin had a marked effect on the ligninase activity indicating that some induction or activation mechanism is involved in lignin degradation byC. sitophila.     

Temperature profiles of growth and ethanol tolerance of the xylose-fermenting yeasts Candida shehatae and Pichia stipitis

Summary The effect of different ethanol concentrations on the growth of Candida shehatae and Pichia stipitis with xylose as substrate was evaluated in a temperature gradient incubator. The upper limit of the temperature profiles of ethanol tolerance of both yeast strains were similar, although P. stipitis appeared to have a slightly higher ethanol tolerance in the higher temperature range. An increase in the ethanol concentration severely depressed the maximum growth temperature, and also increased the minimum growth temperature slightly. The ethanol tolerance limit of 46–48 g·l^-1 occurred within a narrow temperature plateau of 11 to 22° C. The low ethanol tolerance of these pentose fermenting yeasts is detrimental for commercial ethanol production from hemicellulose hydrolysates.