High thermal tolerance in high-elevation species and laboratory-reared colonies of tropical bumble bees

Bumble bees are key pollinators with some species reared in captivity at a commercial scale, but with significant evidence of population declines and with alarming predictions of substantial impacts under climate change scenarios. While studies on the thermal biology of temperate bumble bees are still limited, they are entirely absent from the tropics where the effects of climate change are expected to be greater. Herein, we test whether bees' thermal tolerance decreases with elevation and whether the stable optimal conditions used in laboratory-reared colonies reduces their thermal tolerance. We assessed changes in the lower (CTMin) and upper (CTMax) critical thermal limits of four species at two elevations (2600 and 3600 m) in the Colombian Andes, examined the effect of body size, and evaluated the thermal tolerance of wild-caught and laboratory-reared individuals of Bombus pauloensis. We also compiled information on bumble bees' thermal limits and assessed potential predictors for broadscale patterns of variation. We found that CTMin decreased with increasing elevation, while CTMax was similar between elevations. CTMax was slightly higher (0.84°C) in laboratory-reared than in wild-caught bees while CTMin was similar, and CTMin decreased with increasing body size while CTMax did not. Latitude is a good predictor for CTMin while annual mean temperature, maximum and minimum temperatures of the warmest and coldest months are good predictors for both CTMin and CTMax. The stronger response in CTMin with increasing elevation, and similar CTMax, supports Brett's heat-invariant hypothesis, which has been documented in other taxa. Andean bumble bees appear to be about as heat tolerant as those from temperate areas, suggesting that other aspects besides temperature (e.g., water balance) might be more determinant environmental factors for these species. Laboratory-reared colonies are adequate surrogates for addressing questions on thermal tolerance and global warming impacts

Tricolored Lattice Gauge Theory with Randomness: Fault-Tolerance in Topological Color Codes

We compute the error threshold of color codes, a class of topological quantum codes that allow a direct implementation of quantum Clifford gates, when both qubit and measurement errors are present. By mapping the problem onto a statistical-mechanical three-dimensional disordered Ising lattice gauge theory, we estimate via large-scale Monte Carlo simulations that color codes are stable against 4.5(2)% errors. Furthermore, by evaluating the skewness of the Wilson loop distributions, we introduce a very sensitive probe to locate first-order phase transitions in lattice gauge theories.Comment: 12 pages, 5 figures, 1 tabl

Incremental bounded model checking for embedded software

Program analysis is on the brink of mainstream usage in embedded systems development. Formal verification of behavioural requirements, finding runtime errors and test case generation are some of the most common applications of automated verification tools based on bounded model checking (BMC). Existing industrial tools for embedded software use an off-the-shelf bounded model checker and apply it iteratively to verify the program with an increasing number of unwindings. This approach unnecessarily wastes time repeating work that has already been done and fails to exploit the power of incremental SAT solving. This article reports on the extension of the software model checker CBMC to support incremental BMC and its successful integration with the industrial embedded software verification tool BTC EMBEDDED TESTER. We present an extensive evaluation over large industrial embedded programs, mainly from the automotive industry. We show that incremental BMC cuts runtimes by one order of magnitude in comparison to the standard non-incremental approach, enabling the application of formal verification to large and complex embedded software. We furthermore report promising results on analysing programs with arbitrary loop structure using incremental BMC, demonstrating its applicability and potential to verify general software beyond the embedded domain

In vitro and in vivo effects of Pelargonium sidoides DC. root extract EPs® 7630 and selected constituents against SARS-CoV-2 B.1, Delta AY.4/AY.117 and Omicron BA.2

The occurrence of immune-evasive SARS-CoV-2 strains emphasizes the importance to search for broad-acting antiviral compounds. Our previous in vitro study showed that Pelargonium sidoides DC. root extract EPs® 7630 has combined antiviral and immunomodulatory properties in SARS-CoV-2-infected human lung cells. Here we assessed in vivo effects of EPs® 7630 in SARS-CoV-2-infected hamsters, and investigated properties of EPs® 7630 and its functionally relevant constituents in context of phenotypically distinct SARS-CoV-2 variants. We show that EPs® 7630 reduced viral load early in the course of infection and displayed significant immunomodulatory properties positively modulating disease progression in hamsters. In addition, we find that EPs® 7630 differentially inhibits SARS-CoV-2 variants in nasal and bronchial human airway epithelial cells. Antiviral effects were more pronounced against Omicron BA.2 compared to B.1 and Delta, the latter two preferring TMPRSS2-mediated fusion with the plasma membrane for cell entry instead of receptor-mediated low pH-dependent endocytosis. By using SARS-CoV-2 Spike VSV-based pseudo particles (VSVpp), we confirm higher EPs® 7630 activity against Omicron Spike-VSVpp, which seems independent of the serine protease TMPRSS2, suggesting that EPs® 7630 targets endosomal entry. We identify at least two molecular constituents of EPs® 7630, i.e., (−)-epigallocatechin and taxifolin with antiviral effects on SARS-CoV-2 replication and cell entry. In summary, our study shows that EPs® 7630 ameliorates disease outcome in SARS-CoV-2-infected hamsters and has enhanced activity against Omicron, apparently by limiting late endosomal SARS-CoV-2 entry

Library of Seleno-Compounds as Novel Agents against Leishmania Species

The in vitro leishmanicidal activities of a series of 48 recently synthesized selenium derivatives against Leishmania infantum and Leishmania braziliensis parasites were tested using promastigotes and intracellular amastigote forms. The cytotoxicity of the tested compounds for J774.2 macrophage cells was also measured in order to establish their selectivity. Six of the tested compounds (compounds 8, 10, 11, 15, 45, and 48) showed selectivity indexes higher than those of the reference drug, meglumine antimonate (Glucantime), for both Leishmania species; in the case of L. braziliensis, compound 20 was also remarkably selective. Moreover, data on infection rates and amastigote numbers per macrophage showed that compounds 8, 10, 11, 15, 45, and 48 were the most active against both Leishmania species studied. The observed changes in the excretion product profile of parasites treated with these six compounds were also consistent with substantial cytoplasmic alterations. On the other hand, the most active compounds were potent inhibitors of Fe superoxide dismutase (Fe-SOD) in the two parasite species considered, whereas their impact on human CuZn-SOD was low. The high activity, low toxicity, stability, low cost of the starting materials, and straightforward synthesis make these compounds appropriate molecules for the development of affordable antileishmanicidal agents

Multilevel Deconstruction of the In Vivo Behavior of Looped DNA-Protein Complexes

Protein-DNA complexes with loops play a fundamental role in a wide variety of cellular processes, ranging from the regulation of DNA transcription to telomere maintenance. As ubiquitous as they are, their precise in vivo properties and their integration into the cellular function still remain largely unexplored. Here, we present a multilevel approach that efficiently connects in both directions molecular properties with cell physiology and use it to characterize the molecular properties of the looped DNA-lac repressor complex while functioning in vivo. The properties we uncover include the presence of two representative conformations of the complex, the stabilization of one conformation by DNA architectural proteins, and precise values of the underlying twisting elastic constants and bending free energies. Incorporation of all this molecular information into gene-regulation models reveals an unprecedented versatility of looped DNA-protein complexes at shaping the properties of gene expression.Comment: Open Access article available at http://www.plosone.org/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1371%2Fjournal.pone.000035

Dietary Nitrate Ingestion Does Not Improve Neuromuscular Performance in Male Sport Climbers

Beetroot juice (BJ) is commonly used as an ergogenic aid in endurance and team sports, however, the effect of this supplement on climbing performance is barely studied. The purpose of the current study was to investigate the effect of acute BJ ingestion on neuromuscular and biochemical variables in amateur male sport climbers. Ten physically active sport climbers (28.8 ± 3.7 years) underwent a battery of neuromuscular tests consisting of the half crimp test, the pull�up to failure test, the isometric handgrip strength test, the countermovement jump (CMJ) and the squat jump (SJ). Participants performed the neuromuscular test battery twice in a cross-over design separated by 10 days, 150 min after having consumed either 70-mL of BJ (6.4 mmol NO3-) or a 70-mL placebo (0.0034 mmol NO3-). In addition, nitrate (NO3-) and nitrite (NO2-) saliva concentrations were analysed, and a side effect questionnaire related to ingestion was administrated. No differences were reported in particular neuromuscular variables measured such as the CMJ (p = 0.960; ES = 0.03), the SJ (p = 0.581; ES = −0.25), isometric handgrip strength (dominant/non dominant) (p = 0.459–0.447; ES = 0.34–0.35), the pull-up failure test (p = 0.272; ES = 0.51) or the maximal isometric half crimp test (p = 0.521–0.824; ES = 0.10–0.28). Salivary NO3- and NO2- increased significantly post BJ supplementation compared to the placebo (p < 0.001), while no side effects associated to ingestion were reported (p = 0.330–1.000) between conditions (BJ/placebo ingestion). Acute dietary nitrate supplementation (70-mL) did not produce any statistically significant improvement in neuromuscular performance or side effects in amateur sport climbers