Effects of viral infection on contraction of the diaphragm in mice

Isometric contractile properties of isolated phrenic nerve-diaphragm muscle preparations were used to study the effects of picornavirus infections on diaphragm muscle function. Properties of muscles from virus-inoculated and control mice were similar during brief contractions. However, when subjected to a series of fatiguing contractions by indirect or direct stimulation, muscles of mice inoculated with a paralytic variant of encephalomyocarditis (EMC) virus showed a greater rate of fatigue and a reduced capacity to recover from fatigue than did muscles from uninoculated control mice or muscles from mice inoculated with a nonparalytic coxsackievirus B3 (CVB3). Mice paralyzed by EMC virus infection had high titers of virus in the brain and similar titers of virus in diaphragm muscle as found in diaphragm muscles of CVB3-inoculated mice. The results indicate that EMC virus infection of mice leads to increased fatigability of the diaphragm muscle and that there are both neural and muscular components of this enhanced fatigue.     

Bimodal effect of phorbol ester on B cell activation. Implication for the role of protein kinase C.

The role of protein kinase C PKC in B cell activation is controversial. These studies were undertaken to determine whether protein kinase C has a stimulatory or inhibitory role in B cell activation. We found that treatment of B cells for a short period of time (30 min) with the PKC activator phorbol 12,13-dibutyrate (PDBU) primed the cells for enhanced proliferative responses to anti-immunoglobulin (anti-Ig) antibody whereas treatment for a longer period of time (3 h or more) resulted in suppression of proliferation. The enhanced proliferative response to treatment of B cells with PDBU for short periods of time was associated with inhibition of anti-Ig-stimulated increases in phosphatidyl 4,5-bisphosphate (PIP2) hydrolysis and inhibition of increases in [Ca2+]i, indicating that activation of PKC per se might be sufficient for enhancing B cell activation. The time-dependent effect of phorbol esters on the inhibition of B cell proliferation was found to be closely correlated with the kinetics of disappearance of PKC as measured by Western blot and by enzymatic activity but not with inhibition of [Ca2+]i and PIP2. These data demonstrate a bimodal time-dependent effect of PDBU on B cell activation and suggest that (a) the inhibitory effect of phorbol ester on anti-Ig-induced proliferation may be due to the disappearance of PKC rather than to the inhibition of PIP2 and Ca2+; and (b) the early activation of PKC is a stimulatory rather than an inhibitory signal in the induction of B lymphocyte proliferation by anti-Ig.     

A microRNA miR-34a-Regulated Bimodal Switch Targets Notch in Colon Cancer Stem Cells

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Highlights? miR-34a regulates colon cancer stem cell asymmetric division ? miR-34a generates a sharp threshold response ? miR-34a converts Notch signaling into a toggle switch ? Binary Notch levels specify self-renewal versus differentiation     

Genetic similarities within and between human populations

The proportion of human genetic variation due to differences between populations is modest, and individuals from different populations can be genetically more similar than individuals from the same population. Yet sufficient genetic data can permit accurate classification of individuals into populations. Both findings can be obtained from the same data set, using the same number of polymorphic loci. This article explains why. Our analysis focuses on the frequency, omega, with which a pair of random individuals from two different populations is genetically more similar than a pair of individuals randomly selected from any single population. We compare omega to the error rates of several classification methods, using data sets that vary in number of loci, average allele frequency, populations sampled, and polymorphism ascertainment strategy. We demonstrate that classification methods achieve higher discriminatory power than omega because of their use of aggregate properties of populations. The number of loci analyzed is the most critical variable: with 100 polymorphisms, accurate classification is possible, but omega remains sizable, even when using populations as distinct as sub-Saharan Africans and Europeans. Phenotypes controlled by a dozen or fewer loci can therefore be expected to show substantial overlap between human populations. This provides empirical justification for caution when using population labels in biomedical settings, with broad implications for personalized medicine, pharmacogenetics, and the meaning of race.     

Recent horizontal transfer of mellifera subfamily mariner transposons into insect lineages representing four different orders shows that selection acts only during horizontal transfer

We report the isolation and sequencing of genomic copies of mariner transposons involved in recent horizontal transfers into the genomes of the European earwig, Forficula auricularia; the European honey bee, Apis mellifera; the Mediterranean fruit fly, Ceratitis capitata; and a blister beetle, Epicauta funebris, insects from four different orders. These elements are in the mellifera subfamily and are the second documented example of full-length mariner elements involved in this kind of phenomenon. We applied maximum likelihood methods to the coding sequences and determined that the copies in each genome were evolving neutrally, whereas reconstructed ancestral coding sequences appeared to be under selection, which strengthens our previous hypothesis that the primary selective constraint on mariner sequence evolution is the act of horizontal transfer between genomes.     

Induction of luteolysis in the mare with a prostaglandin analogue

Five mares were administered 0.5 to 2.0 mg of a prostaglandin analogue, RS 9390 (Syntex), during nine estrous cycles in February and March. Luteolysis as measured by peripheral plasma progesterone occurred in four cycles, transitory luteolysis following 0.5 mg RS 9390 in two cycles, while functional corpora lutea were not present in three cycles. In 8 out of 9 of these cycles the mares returned to estrus 1.5 to 5 days following treatment. It appears that RS 9390 can be used as a regulator of cycle length in mares.     

Free amino acids and protein concentrations in reproductive tract fluids of the mare

Uterine tubal fluids (UTF) were collected daily over a 214-day period (March through August) from three mares. Individual UTF samples identified by day of estrous cycle for five complete cycles within this six-month span were analyzed for free amino acids and total protein. Biochemical comparisons were made to blood plasma by drawing samples daily from each mare. Free amino acids and total protein were determined also on follicular fluids collected from three different mares on days 5 and 6 of standing estrus.The free amino acid level of UTF was significantly greater than was the amino acid concentration in blood plasma or follicular fluid. The highest concentration of amino acids in UTF was on day 13. Cyclic trends were observed for the amino acids, histidine, methionine, half-cystine, serine, proline, glycine, alanine, isolecine, and leucine. Glycine and alanine were found in the highest concentrations in UTF, peaking on day 17 of the estrous cycle. Protein concentration in UTF was highest on day 13 and lowest on days 7 and 19. Protein values for diestrus (33.1 mg/ml) were significantly greater (p<0.05) than for estrus (28.0 mg/ml).