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.     

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.     

Transmitter release in hippocampal slices from rats with limbic seizures produced by systemic administration of kainic acid

The systemic injection of kainic acid (KA) has been shown to destroy neurons in the hippocampus and to induce limbic-type seizure activity. However, little is known on the neurochemical events that are associated with this convulsant effect. In the present work we studied the spontaneous and the K⁺-stimulated release of labeled -aminobutyric acid (GABA), glutamate, serotonin and dopamine, in hippocampal slices of KA-treated rats, at the moment of clinical seizures (2 h) and 72 h later. At the onset of convulsions we found a 40–45% decrease in the K⁺-stimulated release of GABA. The release of the other neurotransmitters was not significantly affected by KA treatment. After 72 h GABA release was still reduced by 30–40%. It is concluded that the epileptogenic effect of KA in the hippocampus is probably related to a diminished inhibitory GABAergic neurotransmission.     

Tissue water relations in elfin cloud forest tree species of Serrania de Macuira,Guajira, Colombia

Summary Diurnal courses of stomatal conductance, leaf water potential, and the components of tissue water potential were measured in six canopy species in an elfin cloud forest. High values of stomatal conductance were measured on cloudy days and during early morning and late afternoon of sunny days. Decreases in stomatal conductance with increases in vapour pressure deficit may have been a response to avoid further water deficits and suggested a stomatal response to changes in relative humidity. Daily transpiration varied between 470 and 1014 g m^-2 day^-1 during cloudy days and between 532 and 944 g m^-2 day^-1 during clear days. Stomatal conductance may have also responded to changes in leaf water potential, which was minimum at noon. The minimum tissue water potential measured in the field was -1.8 MPa in Myrcianthes fragrans, and the minimum turgor pressure was 0.49 MPa also in M. fragrans. There was a correlation between the osmotic potential and the minimum tissue water potential, suggesting that osmotic potential plays a major role in the maintenance of turgor in these species, in spite of the great variability in the elastic properties of leaf tissues. Turgor pressure decreased during the day following the course of water potential but never approached the turgor loss point, as it has been measured in some lowland rain forest trees. This is a strong indication that elfin cloud forest trees do not suffer severe water deficits, and that small tree stature is not directly related to water shortage.     

Regional brain GABA metabolism and release during hepatic coma produced in rats chronically treated with carbon tetrachloride

Hepatic coma was induced in rats chronically treated with CCl₄, by means of a single injection of ammonium acetate. The activities of glutamate decarboxylase (GAD) and GABA transaminase (GABA-T), as well as the synaptosomal uptake and release of [³H]GABA, were measured in the following brain areas of the comatose rats: cortex, striatum, hypothalamus, hippocampus, midbrain and cerebellum. Hepatic coma was associated with a general decrease of GAD activity, whereas GABA-T activity was diminished only in the hypothalamus, striatum and midbrain. During hepatic coma, the K⁺-stimulated [³H]GABA release was notably diminished in the striatum and cerebellum, whereas a significant increase was observed in the hippocampus. [³H]GABA uptake increased in most regions after CCl₄ treatment, independently of the presence of coma. The results indicate that GABAergic transmission seems to be decreased in most cerebral regions during hepatic coma.     

Agyria — pachygyria and Miller-Dieker syndrome: clinical,genetic and chromosome studies

Summary Twelve cases of lissencephaly are reported. A high resolution chromosome study was performed on each in order to detect small chromosomal anomalies, undetectable with routine techniques. Only one case was shown to have an unbalanced karyotype with a microdeletion of the short arm of chromosome 17(del 17p). This child also had symptoms of the Miller-Dieker syndrome, consisting of lissencephaly, characteristic facies, pre- and post-natal growth retardation and other birth defects. As proposed by Dobyns, it seems justifiable to classify lissencephalies into four different groups, according to other clinical manifestations and results of chromosome studies.     

Towards an explanation of carboxylation/oxygenation bifunctionality in Rubisco. Transition structure for the carboxylation reaction of 2,3,4-pentanetriol

We construct a theoretical model of the transition structure for the carboxylation reaction of ribulose-1,5-biphosphate catalyzed by Rubisco. This is a first-order saddle point on the energy hypersurface for the nucleophilic attack of carbon dioxide on CH₃-(CHOH)₃-CH₃ at the C2 center.Ab initio analytical gradients methods at a 4-31G basis set level are used.The carbon framework and oxygens of the stationary structure superpose with the corresponding atoms of 2-carboxyarabinitol-1,5-biphosphate, which is a transition state analog that has recently been highly refined with X-ray methods. The hydroxyl group in C3 iscis to the C2 oxygen. The C3 center is somewhat pyramidized, the dienol O2-C2-C3-O3 is not planar.The geometry of the transition state allows for simple explanations of both the enolization of Rubisco's substrate ribulose-1,5-biphosphate, O₃PO-CH2-CO-(CHOH)₂-CH₂-OPO₃ and oxygenation reaction. The former is due to the pyramidal deformation at C3 and out of plane of O2-C2-C3-O3 framework: the enoliation is intramolecular and is probably enhanced by proton tunnelling. The latter is related with the fact that a rotation around an ethylene-like bond brings the triplet state down in energy. The reactive skeleton has a stationary geometry in the triplet state not very different from the one obtained in the global transition structure. There, the triplet is only 9 kcal/mol above the singlet. The spin densities at C2 and C3 centers clearly indicate the place where oxygenation will take place.