Myocardial energy depletion and dynamic systolic dysfunction in hypertrophic cardiomyopathy

Evidence indicates that anatomical and physiological phenotypes of hypertrophic cardiomyopathy (HCM) stem from genetically mediated, inefficient cardiomyocyte energy utilization, and subsequent cellular energy depletion. However, HCM often presents clinically with normal left ventricular (LV) systolic function or hyperkinesia. If energy inefficiency is a feature of HCM, why is it not manifest as resting LV systolic dysfunction? In this Perspectives article, we focus on an idiosyncratic form of reversible systolic dysfunction provoked by LV obstruction that we have previously termed the 'lobster claw abnormality' — a mid-systolic drop in LV Doppler ejection velocities. In obstructive HCM, this drop explains the mid-systolic closure of the aortic valve, the bifid aortic pressure trace, and why patients cannot increase stroke volume with exercise. This phenomenon is characteristic of a broader phenomenon in HCM that we have termed dynamic systolic dysfunction. It underlies the development of apical aneurysms, and rare occurrence of cardiogenic shock after obstruction. We posit that dynamic systolic dysfunction is a manifestation of inefficient cardiomyocyte energy utilization. Systolic dysfunction is clinically inapparent at rest; however, it becomes overt through the mechanism of afterload mismatch when LV outflow obstruction is imposed. Energetic insufficiency is also present in nonobstructive HCM. This paradigm might suggest novel therapies. Other pathways that might be central to HCM, such as myofilament Ca2+ hypersensitivity, and enhanced late Na+ current, are discussed

Wolbachia Symbiont Infections Induce Strong Cytoplasmic Incompatibility in the Tsetse Fly Glossina morsitans

Tsetse flies are vectors of the protozoan parasite African trypanosomes, which cause sleeping sickness disease in humans and nagana in livestock. Although there are no effective vaccines and efficacious drugs against this parasite, vector reduction methods have been successful in curbing the disease, especially for nagana. Potential vector control methods that do not involve use of chemicals is a genetic modification approach where flies engineered to be parasite resistant are allowed to replace their susceptible natural counterparts, and Sterile Insect technique (SIT) where males sterilized by chemical means are released to suppress female fecundity. The success of genetic modification approaches requires identification of strong drive systems to spread the desirable traits and the efficacy of SIT can be enhanced by identification of natural mating incompatibility. One such drive mechanism results from the cytoplasmic incompatibility (CI) phenomenon induced by the symbiont Wolbachia. CI can also be used to induce natural mating incompatibility between release males and natural populations. Although Wolbachia infections have been reported in tsetse, it has been a challenge to understand their functional biology as attempts to cure tsetse of Wolbachia infections by antibiotic treatment damages the obligate mutualistic symbiont (Wigglesworthia), without which the flies are sterile. Here, we developed aposymbiotic (symbiont-free) and fertile tsetse lines by dietary provisioning of tetracycline supplemented blood meals with yeast extract, which rescues Wigglesworthia-induced sterility. Our results reveal that Wolbachia infections confer strong CI during embryogenesis in Wolbachia-free (GmmApo) females when mated with Wolbachia-infected (GmmWt) males. These results are the first demonstration of the biological significance of Wolbachia infections in tsetse. Furthermore, when incorporated into a mathematical model, our results confirm that Wolbachia can be used successfully as a gene driver. This lays the foundation for new disease control methods including a population replacement approach with parasite resistant flies. Alternatively, the availability of males that are reproductively incompatible with natural populations can enhance the efficacy of the ongoing sterile insect technique (SIT) applications by eliminating the need for chemical irradiation

Measurements of charged current lepton universality and |Vus| using tau lepton decays to e- (e) ( ), - ( ) ( ), - ( ), and K- ( ).

9 pages, 12 encapsulated postscript figures, submitted to Physical Review LettersInternational audienceUsing 467 $fb^{-1}$ of $e^+e^-$ annihilation data collected with the BaBar detector, we measure $\frac{{\cal{B}}(\tau^- \to \mu^- \bar{\nu}_\mu \nu_\tau)}{{\cal{B}}(\tau^- \to e^- \bar{\nu}_e \nu_\tau)} = (0.9796 \pm 0.0016 \pm 0.0036)$, $\frac{{\cal{B}}(\tau^- \to \pi^- \nu_\tau)}{{\cal{B}}(\tau^- \to e^- \bar{\nu}_e \nu_\tau)} = (0.5945 \pm 0.0014 \pm 0.0061)$, and \frac{{\cal{B}}(\tau^- \to \K^- \nu_\tau)}{{\cal{B}}(\tau^- \to e^- \bar{\nu}_e \nu_\tau)} = (0.03882 \pm 0.00032 \pm 0.00057), where the uncertainties are statistical and systematic, respectively. From these precision measurements we test the Standard Model assumption of $\mu$-$e$ and $\tau$-$\mu$ charged current lepton universality and also obtain a value for $|V_{us}| = 0.2255 \pm 0.0024$, which is consistent with the prediction from the unitarity of the Cabibbo-Kobayashi-Maskawa matrix

Improved Limits on the Lepton-Flavor Violating Decays τ−→l−l+l−

A search for the neutrinoless, lepton-flavor violating decay of the tau lepton into three charged leptons has been performed using 376     fb − 1 of data collected at an e + e − center-of-mass energy around 10.58 GeV with the BABAR detector at the SLAC PEP-II storage rings. In all six decay modes considered, the numbers of events found in data are compatible with the background expectations. Upper limits on the branching fractions are set in the range ( 4 - 8 ) × 10 − 8 at 90% confidence level

Measurement of the branching fraction ratios and CP asymmetries in B-→ D0 CP K-decays

We present a preliminary study of $B^- \to D^0_{CP} \pi^-$ and $B^- \to D^0_{CP} K^-$ decays, with the $D^0_{CP}$ reconstructed in the CP-odd eigenstates $K_s \pi^0$, $K_s \omega$, in the CP-even eigenstates $K^+ K^-$, $\pi^+ \pi^-$, and in the (non-CP) flavor eigenstate $K^\mp \pi^\pm$. Using a sample of about 382 million Y(4S) decays into BBbar pairs, collected with the BABAR detector operating at the PEP-II asymmetric-energy B Factory at SLAC, we measure the ratios of the branching fractions R_CP+- and the direct CP asymmetries A_CP+-. The results are: R_CP- = 0.81 \pm 0.10 (stat) \pm 0.05 (syst) R_CP+ = 1.07 \pm 0.10 (stat) \pm 0.04 (syst) A_CP- = -0.19 \pm 0.12 (stat) \pm 0.02 (syst) A_CP+ = 0.35 \pm 0.09 (stat) \pm 0.05 (syst

Middle cretaceous foraminifera and biostratigraphy of Western Siberia

7 pages, 4 postscript figures, submitted to PRLWe present partial branching fractions for inclusive charmless semileptonic B decays Bbar --> X_u ell nubar, and the determination of the CKM matrix element |V_{ub}|. The analysis is based on a sample of 383 million Y(4S) decays into B Bbar pairs collected with the BaBar detector at the PEP-II e+ e- storage rings. We select events using either the invariant mass M_X of the hadronic system, the invariant mass squared, q^2, of the lepton and neutrino pair, the kinematic variable P_+ or one of their combinations. We then determine partial branching fractions in limited regions of phase space: Delta B = (1.18 +- 0.09_{stat.} +- 0.07_{sys.} +- 0.01_{theo.}) x 10^{-3} (M_X 8 GeV^2/c^4). Corresponding values of |V_{ub}| are extracted using several theoretical calculations

BioTIME 2.0: Expanding and Improving a Database of Biodiversity Time Series

Motivation Here, we make available a second version of the BioTIME database, which compiles records of abundance estimates for species in sample events of ecological assemblages through time. The updated version expands version 1.0 of the database by doubling the number of studies and includes substantial additional curation to the taxonomic accuracy of the records, as well as the metadata. Moreover, we now provide an R package (BioTIMEr) to facilitate use of the database. Main Types of Variables Included The database is composed of one main data table containing the abundance records and 11 metadata tables. The data are organised in a hierarchy of scales where 11,989,233 records are nested in 1,603,067 sample events, from 553,253 sampling locations, which are nested in 708 studies. A study is defined as a sampling methodology applied to an assemblage for a minimum of 2 years. Spatial Location and Grain Sampling locations in BioTIME are distributed across the planet, including marine, terrestrial and freshwater realms. Spatial grain size and extent vary across studies depending on sampling methodology. We recommend gridding of sampling locations into areas of consistent size. Time Period and Grain The earliest time series in BioTIME start in 1874, and the most recent records are from 2023. Temporal grain and duration vary across studies. We recommend doing sample-level rarefaction to ensure consistent sampling effort through time before calculating any diversity metric. Major Taxa and Level of Measurement The database includes any eukaryotic taxa, with a combined total of 56,400 taxa. Software Format csv and. SQL

Method development for the simultaneous determination of carboxylic acids, phenolic compounds, and sorbic acid in white wines

A reversed phase liquid chromatographic method was developed for the simultaneous determination of carboxylic acids and phenolics in white wines. The samples, diluted, were injected onto a Spherisorb ODS-2 column with a gradient of sulfuric acid (pH 2.5)/methanol as mobile phase. A diode array detector was used which was set at 210nm for carboxylic acids and altered to 278nm, during the run, far phenolics and sorbic acid. The identification of compounds was based on retention time, co-chromatography and UV spectrum. Some clean-up methods (sep-pak C-18 and an ion exchange column) mere tested and did not improve the results. The analysis was simple, with no sample preparation. Application of this method was illustrated by analyses of Brazilian Welchriesling wines.21449150