Causal mechanisms underlying host specificity in bat ectoparasites

In parasites, host specificity may result either from restricted dispersal capacity or from fixed coevolutionary host-parasite adaptations. Knowledge of those proximal mechanisms leading to particular host specificity is fundamental to understand host-parasite interactions and potential coevolution of parasites and hosts. The relative importance of these two mechanisms was quantified through infection and cross-infection experiments using mites and bats as a model. Monospecific pools of parasitic mites (Spinturnix myoti and S. andegavinus) were subjected either to individual bats belonging to their traditional, native bat host species, or to another substitute host species within the same bat genus (Myotis). The two parasite species reacted differently to these treatments. S. myoti exhibited a clear preference for, and had a higher fitness on, its native host, Myotis myotis. In contrast, S. andegavinus showed no host choice, although its fitness was higher on its native host M. daubentoni. The causal mechanisms mediating host specificity can apparently differ within closely related host-parasite systems.     

Vegetative versus Minimally Conscious States: A Study Using TMS-EEG,Sensory and Event-Related Potentials

Differential diagnoses between vegetative and minimally conscious states (VS and MCS, respectively) are frequently incorrect. Hence, further research is necessary to improve the diagnostic accuracy at the bedside. The main neuropathological feature of VS is the diffuse damage of cortical and subcortical connections. Starting with this premise, we used electroencephalography (EEG) recordings to evaluate the cortical reactivity and effective connectivity during transcranial magnetic stimulation (TMS) in chronic VS or MCS patients. Moreover, the TMS-EEG data were compared with the results from standard somatosensory-evoked potentials (SEPs) and event-related potentials (ERPs). Thirteen patients with chronic consciousness disorders were examined at their bedsides. A group of healthy volunteers served as the control group. The amplitudes (reactivity) and scalp distributions (connectivity) of the cortical potentials evoked by TMS (TEPs) of the primary motor cortex were measured. Short-latency median nerve SEPs and auditory ERPs were also recorded. Reproducible TEPs were present in all control subjects in both the ipsilateral and the contralateral hemispheres relative to the site of the TMS. The amplitudes of the ipsilateral and contralateral TEPs were reduced in four of the five MCS patients, and the TEPs were bilaterally absent in one MCS patient. Among the VS patients, five did not manifest ipsilateral or contralateral TEPs, and three of the patients exhibited only ipsilateral TEPs with reduced amplitudes. The SEPs were altered in five VS and two MCS patients but did not correlate with the clinical diagnosis. The ERPs were impaired in all patients and did not correlate with the clinical diagnosis. These TEP results suggest that cortical reactivity and connectivity are severely impaired in all VS patients, whereas in most MCS patients, the TEPs are preserved but with abnormal features. Therefore, TEPs may add valuable information to the current clinical and neurophysiological assessment of chronic consciousness disorders.     

Interpretable pairwise distillations for generative protein sequence models

Many different types of generative models for protein sequences have been proposed in literature. Their uses include the prediction of mutational effects, protein design and the prediction of structural properties. Neural network (NN) architectures have shown great performances, commonly attributed to the capacity to extract non-trivial higher-order interactions from the data. In this work, we analyze two different NN models and assess how close they are to simple pairwise distributions, which have been used in the past for similar problems. We present an approach for extracting pairwise models from more complex ones using an energy-based modeling framework. We show that for the tested models the extracted pairwise models can replicate the energies of the original models and are also close in performance in tasks like mutational effect prediction. In addition, we show that even simpler, factorized models often come close in performance to the original models.     

Mutation and Evolutionary Rates in Adélie Penguins from the Antarctic

Precise estimations of molecular rates are fundamental to our understanding of the processes of evolution. In principle, mutation and evolutionary rates for neutral regions of the same species are expected to be equal. However, a number of recent studies have shown that mutation rates estimated from pedigree material are much faster than evolutionary rates measured over longer time periods. To resolve this apparent contradiction, we have examined the hypervariable region (HVR I) of the mitochondrial genome using families of Adélie penguins (Pygoscelis adeliae) from the Antarctic. We sequenced 344 bps of the HVR I from penguins comprising 508 families with 915 chicks, together with both their parents. All of the 62 germline heteroplasmies that we detected in mothers were also detected in their offspring, consistent with maternal inheritance. These data give an estimated mutation rate (μ) of 0.55 mutations/site/Myrs (HPD 95% confidence interval of 0.29–0.88 mutations/site/Myrs) after accounting for the persistence of these heteroplasmies and the sensitivity of current detection methods. In comparison, the rate of evolution (k) of the same HVR I region, determined using DNA sequences from 162 known age sub-fossil bones spanning a 37,000-year period, was 0.86 substitutions/site/Myrs (HPD 95% confidence interval of 0.53 and 1.17). Importantly, the latter rate is not statistically different from our estimate of the mutation rate. These results are in contrast to the view that molecular rates are time dependent.     

Activation of glucose transport during simulated ischemia in H9c2 cardiac myoblasts is mediated by protein kinase C isoforms

Glucose transport into cells may be regulated by a variety of conditions, including ischemia. We investigated whether some enzymes frequently involved in the metabolic adaptation to ischemia are also required for glucose transport activation. Ischemia was simulated by incubating during 3 h H9c2 cardiomyoblasts in a serum- and glucose-free medium in hypoxia. Under these conditions 2-deoxy-d-[2,6-³H]-glucose uptake was increased (57% above control levels, p < 0.0001) consistently with GLUT1 and GLUT4 translocation to sarcolemma. Tyrosine kinases inhibition via tyrphostin had no effect on glucose transport up-regulation induced by simulated ischemia. On the other hand, chelerythrine, a broad range inhibitor of protein kinase C isoforms, and rottlerin, an inhibitor of protein kinase C delta, completely prevented the stimulation of the transport rate. A lower activation of hexose uptake (19%, p < 0.001) followed also treatment with Gö6976, an inhibitor of conventional protein kinases C. Finally, PD98059-mediated inhibition of the phosphorylation of ERK 1/2, a downstream mitogen-activated protein kinase (MAPK), only partially reduced the activation of glucose transport induced by simulated ischemia (31%, p < 0.01), while SB203580, an inhibitor of p38 MAPK, did not exert any effect. These results indicate that stimulation of protein kinase C delta is strongly related to the up-regulation of glucose transport induced by simulated ischemia in cultured cardiomyoblasts and that conventional protein kinases C and ERK 1/2 are partially involved in the signalling pathways mediating this process.     

Subcellular Location and Neuronal Release of Diazepam Binding Inhibitor

Diazepam binding inhibitor (DBI), a peptide located in CNS neurons, blocks the binding of benzodiazepines and beta-carbolines to the allosteric modulatory sites of gamma-aminobutyric acid (GABAA) receptors. Subcellular fractionation studies of rat brain indicate that DBI is compartmentalized. DBI-like immunoreactivity is highly enriched in synaptosomes obtained by differential centrifugation in isotonic sucrose followed by a Percoll gradient. In synaptosomal lysate, DBI-like immunoreactivity is primarily associated with synaptic vesicles partially purified by differential centrifugation and continuous sucrose gradient. Depolarization induced by high K+ levels (50 mM) or veratridine (50 microM) released DBI stored in neurons of superfused slices of hypothalamus, hippocampus, striatum, and cerebral cortex. The high K+ level-induced release is Ca2+ dependent, and the release induced by veratridine is blocked by 1.7 microM tetrodotoxin. Depolarization released GABA and Met5-enkephalin-Arg6-Phe7 together with DBI. DBI is also released by veratridine depolarization, in a tetrodotoxin-sensitive fashion, from primary cultures of cerebral cortical neurons, but not from cortical astrocytes. Depolarization fails to release DBI from slices of liver and other peripheral organs. These data support the view that DBI may be released as a putative neuromodulatory substance from rat brain neurons.     

Chromosomal localization of four human zinc finger cDNAs

cDNA clones encoding zinc finger motifs were isolated by screening human placenta and T-cell (Peer) cDNA libraries with zinc finger (ZNF) consensus sequences. Unique cDNA clones were mapped in the human genome by rodent-human somatic cell hybrid analysis and in some cases in situ chromosomal hybridization. ZNF 80 mapped to 3p12-3qter, ZNF 7 was previously mapped to 8q24 and is here shown by in situ hybridization and use of appropriate hybrids to map telomeric to the MYC locus. ZNF 79 mapped to 9q34 centromeric to the ABL gene and between a constitutional chromosomal translocation on the centromeric side and the CML specific ABL translocation on the telomeric side. ZNF77 mapped to 19p while ZNF 78L1 (pT3) mapped to 19q. Chromosome 19 carries many ZNF loci and other genes with zinc finger encoding motifs; the pT3 clone additionally detected a locus designated ZNF 78L2, which mapped to chromosome region 1p, most likely in the region 1p32 where the MYCL and JUN loci map.     

Dexamethasone effects on liver pyruvate kinase

Dexamethasone in the medium perfusin isolated rabbit livers caused a fast-acting and reversible effect on liver pyruvate kinase. The effect was to lower th assayable V activity (units/g tissue) without changing the concentration (nmol/g enzyme protein). In effect, glucocorticoid lowered the specific activity (units/nmol of enzyme) by direct action on liver. The effect on liver pyruvate kinase is mediated by a relatively stable alteration; 30 min after perfusate (with steroid) was replaced by perfusate (without steroid), the effect remained strongly evident.