Intraspecific phylogenetic analysis of Siberian woolly mammoths using complete mitochondrial genomes

We report five new complete mitochondrial DNA (mtDNA) genomes of Siberian woolly mammoth (Mammuthus primigenius), sequenced with up to 73-fold coverage from DNA extracted from hair shaft material. Three of the sequences present the first complete mtDNA genomes of mammoth clade II. Analysis of these and 13 recently published mtDNA genomes demonstrates the existence of two apparently sympatric mtDNA clades that exhibit high interclade divergence. The analytical power afforded by the analysis of the complete mtDNA genomes reveals a surprisingly ancient coalescence age of the two clades, approximately 1-2 million years, depending on the calibration technique. Furthermore, statistical analysis of the temporal distribution of the (14)C ages of these and previously identified members of the two mammoth clades suggests that clade II went extinct before clade I. Modeling of protein structures failed to indicate any important functional difference between genomes belonging to the two clades, suggesting that the loss of clade II more likely is due to genetic drift than a selective sweep.     

The Cretaceous superchron geodynamo: observations near the tangent cylinder

If relationships exist between the frequency of geomagnetic reversals and the morphology, secular variation, and intensity of Earth's magnetic field, they should be best expressed during superchrons, intervals tens of millions of years long lacking reversals. Here we report paleomagnetic and paleointensity data from lavas of the Cretaceous Normal Polarity Superchron that formed at high latitudes near the tangent cylinder that surrounds the solid inner core. The time-averaged field recorded by these lavas is remarkably strong and stable. When combined with global results available from lower latitudes, these data define a time-averaged field that is overwhelmingly dominated by the axial dipole (octupole components are insignificant). These observations suggest that the basic features of the geomagnetic field are intrinsically related. Superchrons may reflect times when the nature of core-mantle boundary heat flux allows the geodynamo to operate at peak efficiency.     

Store-operated calcium entry in neuroglia

Neuroglial cells are homeostatic neural cells. Generally, they are electrically non-excitable and their activation is associated with the generation of complex intracellular Ca²⁺ signals that define the “Ca²⁺ excitability” of glia. In mammalian glial cells the major source of Ca²⁺ for this excitability is the lumen of the endoplasmic reticulum (ER), which is ultimately (re)filled from the extracellular space. This occurs via store-operated Ca²⁺ entry (SOCE) which is supported by a specific signaling system connecting the ER with plasmalemmal Ca²⁺ entry. Here, emptying of the ER Ca²⁺ store is necessary and sufficient for the activation of SOCE, and without Ca²⁺ influx via SOCE the ER store cannot be refilled. The molecular arrangements underlying SOCE are relatively complex and include plasmalemmal channels, ER Ca²⁺ sensors, such as stromal interaction molecule, and possibly ER Ca²⁺ pumps (of the SERCA type). There are at least two sets of plasmalemmal channels mediating SOCE, the Ca²⁺-release activated channels, Orai, and transient receptor potential (TRP) channels. The molecular identity of neuroglial SOCE has not been yet identified unequivocally. However, it seems that Orai is predominantly expressed in microglia, whereas astrocytes and oligodendrocytes rely more on TRP channels to produce SOCE. In physiological conditions the SOCE pathway is instrumental for the sustained phase of the Ca²⁺ signal observed following stimulation of metabotropic receptors on glial cells.     

Staying awake – a genetic region that hinders α2 adrenergic receptor agonist‐induced sleep

How external stimuli prevent the onset of sleep has been little studied. This is usually considered to be a non‐specific type of phenomenon. However, the hypnotic drug dexmedetomidine, an agonist at α₂ adrenergic receptors, has unusual properties that make it useful for investigating this question. Dexmedetomidine is considered to produce an ‘arousable’ sleep‐like state, so that patients or animals given dexmedetomidine become alert following modest stimulation. We hypothesized that it might be more difficult to make mice unconscious with dexmedetomidine if there was a sufficient external stimulus. Employing a motorized rotating cylinder, which provided a continuous and controlled arousal stimulus, we quantitatively measured the ability of such a stimulus to prevent dexmedetomidine loss of righting reflex in two inbred strains of mice (C57BL/6 and 129X1). We found that whereas the C57BL/6 strain required a strong stimulus to prevent dexmedetomidine‐induced hypnosis, the 129X1 strain stayed awake even with minimal stimuli. Remarkably, this could be calibrated as a simple threshold trait, i.e. a binary ‘yes–no’ response, which after crossing the two mouse strains behaved as a dominant‐like trait. We carried out a genome‐wide linkage analysis on the F₂ progeny to determine if the ability of a stimulus to prevent dexmedetomidine hypnosis could be mapped to one or more chromosomal regions. We identified a locus on chromosome 4 with an associated Logarithm of Odds score exceeding the pre‐established threshold level. These results show that complex traits, such as the ability of a stimulus to reverse drug‐induced hypnosis, may have precise genetic determinants.     

Basic presynaptic functions in hippocampal neurons are not affected by acute or chronic lithium treatment

Lithium is an effective mood-stabilizer in the treatment of bipolar affective disorder. While glycogen synthase kinase 3-mediated and inositol depletion-dependent effects of lithium have been described extensively in literature, there is very little knowledge about the consequences of lithium treatment on vesicle recycling and neurotransmitter availability. In the present study we have examined acute and chronic effects of lithium on synaptic vesicle recycling using primary hippocampal neurons. We found that exocytosis of readily releasable pool vesicles as well as recycling pool vesicles was unaffected by acute and chronic treatment within the therapeutic range or at higher lithium concentrations. Consistent with this observation, we also noticed that the network activity and number of active synapses within the network were also not significantly altered after lithium treatment. Taken together, as lithium treatment does not affect synaptic vesicle release at even high concentrations, our data suggest that therapeutic effects of lithium in bipolar affective disorder are not directly related to presynaptic function.     

Location and architecture of an antibody-binding site of influenza A virus nucleoprotein

Amino acid positions recognized by monoclonal antibodies (MAbs) in the influenza A virus nucleoprotein (NP) have been reported. As these residues were scattered in the three-dimensional (3D) structure of NP, no patterns of the architecture of antibody-binding sites could be inferred. Here, we used site-specific mutagenesis and ELISA to screen the amino acids surrounding position 470 recognized by the MAb 3/1 as a linear epitope. Ten amino acid residues involved in the reaction of NP with the MAb 3/1 and the MAb 469/6 were identified. Our data are the first to outline a compact site recognized by MAbs in the 3D structure of the influenza virus NP.