In 2017, potato tubers suspected of being infected with the bacterium 'Candidatus Liberibacter solanacearum' were received from the Animal and Plant Health Inspection Service in the United States. A ...total of 368 chipping tubers were observed for internal symptoms of zebra chip disease, which is associated with 'Ca. L. solanacearum' infection in the United States, Mexico, Central America, and New Zealand. A single tuber sliced at the stem end showed classic zebra chip symptoms of darkened medullary rays, with streaking and necrotic flecking. The symptomatic tuber was confirmed positive for the bacterium by polymerase chain reaction targeting three different 'Ca. L. solanacearum' genes. Sequence analysis of these three genes, and subsequent BLAST analysis, identified the pathogen with 99, 98, and 97% identity to 'Ca. L. solanacearum' for the 16S ribosomal RNA gene, 50S ribosomal proteins L10/L12 genes, and the outer membrane protein gene, respectively. Sequence analysis did not identify the sample as one of the six known haplotypes of 'Ca. L. solanacearum,' indicating that a seventh haplotype of the pathogen was identified. This new haplotype, designated haplotype F, is now the third haplotype of the bacterium that infects Solanum tuberosum in the United States.
Interactions of cytochrome c (cyt c) with cardiolipin (CL) partially unfold the protein, activating its peroxidase function, a critical event in the execution of apoptosis. However, structural ...features of the altered protein species in the heterogeneous ensemble are difficult to probe with ensemble averaging. Analyses of the dye-to-heme distance distributions P(r) from time-resolved FRET (TR-FRET) have uncovered two distinct types of CL-bound cyt c conformations, extended and compact. We have combined TR-FRET, fluorescence correlation spectroscopy (FCS), and biolayer interferometry to develop a systematic understanding of the functional partitioning between the two conformations. The two subpopulations are in equilibrium with each other, with a submillisecond rate of conformational exchange reflecting the protein folding into a compact non-native state, as well as protein interactions with the lipid surface. Electrostatic interactions with the negatively charged lipid surface that correlate with physiologically relevant changes in CL concentrations strongly affect the kinetics of cyt c binding and conformational exchange. A predominantly peripheral binding mechanism, rather than deep protein insertion into the membrane, provides a rationale for the general denaturing effect of the CL surface and the large-scale protein unfolding. These findings closely relate to cyt c folding dynamics and suggest a general strategy for extending the time window in monitoring the kinetics of folding.
Large experimental programmes in the fields of nuclear and particle physics search for evidence of physics beyond that explained by current theories. The observation of the Higgs boson completed the ...set of particles predicted by the standard model, which currently provides the best description of fundamental particles and forces. However, this theory's limitations include a failure to predict fundamental parameters, such as the mass of the Higgs boson, and the inability to account for dark matter and energy, gravity, and the matter-antimatter asymmetry in the Universe, among other phenomena. These limitations have inspired searches for physics beyond the standard model in the post-Higgs era through the direct production of additional particles at high-energy accelerators, which have so far been unsuccessful. Examples include searches for supersymmetric particles, which connect bosons (integer-spin particles) with fermions (half-integer-spin particles), and for leptoquarks, which mix the fundamental quarks with leptons. Alternatively, indirect searches using precise measurements of well predicted standard-model observables allow highly targeted alternative tests for physics beyond the standard model because they can reach mass and energy scales beyond those directly accessible by today's high-energy accelerators. Such an indirect search aims to determine the weak charge of the proton, which defines the strength of the proton's interaction with other particles via the well known neutral electroweak force. Because parity symmetry (invariance under the spatial inversion (x, y, z) → (-x, -y, -z)) is violated only in the weak interaction, it provides a tool with which to isolate the weak interaction and thus to measure the proton's weak charge
. Here we report the value 0.0719 ± 0.0045, where the uncertainty is one standard deviation, derived from our measured parity-violating asymmetry in the scattering of polarized electrons on protons, which is -226.5 ± 9.3 parts per billion (the uncertainty is one standard deviation). Our value for the proton's weak charge is in excellent agreement with the standard model
and sets multi-teraelectronvolt-scale constraints on any semi-leptonic parity-violating physics not described within the standard model. Our results show that precision parity-violating measurements enable searches for physics beyond the standard model that can compete with direct searches at high-energy accelerators and, together with astronomical observations, can provide fertile approaches to probing higher mass scales.
Older adult physical activity (PA) levels obtained from the International Physical Activity Questionnaire-Short Form (IPAQ) and accelerometry (ACC) were compared. Mean difference scores between ...accumulated or bout ACC PA and the IPAQ were computed. Spearman rank-order correlations were used to assess relations between time spent in PA measured from ACC and self-reported form of the IPAQ, and percentage agreement across measures was used to classify meeting or not meeting PA recommendations. The IPAQ significantly underestimated sitting and overestimated time spent in almost all PA intensities. Group associations across measures revealed significant relations in walking, total PA, and sitting for the whole group (r = .29-.36, p < .05). Significant relationships between bout ACC and IPAQ walking (r = .28-.39, p < .05) were found. There was 40-46% agreement between measures for meeting PA recommendations. The IPAQ appears not to be a good indicator of individual older adult PA behavior but is better suited for larger population-based samples.
Postmenopausal bone loss often leads to osteoporosis and fragility fractures. Bone mass can be increased by the first 34 amino acids of human parathyroid hormone (PTH), parathyroid hormone‐related ...protein (PTHrP), or by a monoclonal antibody against sclerostin (Scl‐Ab). Here, we show that PTH and Scl‐Ab reduce the expression of microRNA‐19a and microRNA‐19b (miR‐19a/b) in bone. In bones from patients with lower bone mass and from osteoporotic mice, miR‐19a/b expression is elevated, suggesting an inhibitory function in bone remodeling. Indeed, antagonizing miR‐19a/b in vivo increased bone mass without overt cytotoxic effects. We identified TG‐interacting factor 1 (Tgif1) as the target of miR‐19a/b in osteoblasts and essential for the increase in bone mass following miR‐19a/b inhibition. Furthermore, antagonizing miR‐19a/b augments the gain in bone mass by PTH and restores bone loss in mouse models of osteoporosis in a dual mode of action by supporting bone formation and decreasing receptor activator of NF‐κB ligand (RANKL)‐dependent bone resorption. Thus, this study identifies novel mechanisms regulating bone remodeling, which opens opportunities for new therapeutic concepts to treat bone fragility.
Synopsis
Due to low bone mass, osteoporosis leads to fractures. Current drugs increase bone mass but have limitations. Thus, additional medicines are needed. Here we established anti‐sense oligonucleotide‐based microRNA‐19a/b inhibition to increase bone mass in osteoporosis by a novel dual mode of action.
Post‐menopausal osteoporosis is caused by an increased osteoclast‐dependent bone resorption and a reduced osteoblast‐mediated bone formation often leading to fragility fractures that are associated with an increased morbidity and mortality.
Patients with osteoporosis are frequently treated with anti‐resorptive drugs or anabolic agents such as PTH 1‐34 or an anti‐sclerostin antibody to increase bone mass.
We uncovered that PTH 1‐34 and an anti‐sclerostin antibody reduced the expression of microRNA‐19a and microRNA‐19b (miR‐19a/b) in bone.
Human bones with lower bone mass and bones from osteoporotic mice displayed an increased miR‐19a/b expression.
Anti‐sense oligonucleotide‐mediated miR‐19a/b inhibition augmented the PTH 1‐34‐induced gain in bone mass and reconstituted low bone mass in osteoporosis in mice by supporting bone formation and decreasing bone resorption.
Due to low bone mass, osteoporosis leads to fractures. Current drugs increase bone mass but have limitations. Thus, additional medicines are needed. Here we established anti‐sense oligonucleotide‐based microRNA‐19a/b inhibition to increase bone mass in osteoporosis by a novel dual mode of action.
Maintaining the huge grid computing facilities for LHC experiments and replacing their hardware every few years has been very expensive. The California State University (CSU) ATLAS group recently ...received $250,000 AWS cloud credit from the CSU Chancellor's Office to build the first virtual US ATLAS Tier 3 to explore cloud solutions for ATLAS. We will use this award to set up full ATLAS computing environments on the cloud for ATLAS physics analysis frame works, MC generation, simulation and production. We will also develop policies for ATLAS members to submit jobs to the cloud and develop an economic model focused especially on the cost effectiveness of cloud solutions for ATLAS through extensive real user experience. The results will help ATLAS computing and physics communities decide future directions with incoming LHC upgrades.
Broadly HIV-1-neutralizing antibodies (BnAbs) display one or more unusual traits, including a long heavy chain complementarity-determining region 3 (HCDR3), polyreactivity, and high levels of somatic ...mutations. These shared characteristics suggest that BnAb development might be limited by immune tolerance controls. It has been postulated that HIV-1-infected individuals with autoimmune disease and defective immune tolerance mechanisms may produce BnAbs more readily than those without autoimmune diseases. In this study, we identified an HIV-1-infected individual with SLE who exhibited controlled viral load (<5,000 copies/ml) in the absence of controlling HLA phenotypes and developed plasma HIV-1 neutralization breadth. We collected memory B cells from this individual and isolated a BnAb, CH98, that targets the CD4 binding site (CD4bs) of HIV-1 envelope glycoprotein 120 (gp120). CH98 bound to human antigens including dsDNA, which is specifically associated with SLE. Anti-dsDNA reactivity was also present in the patient's plasma. CH98 had a mutation frequency of 25% and 15% nt somatic mutations in the heavy and light chain variable domains, respectively, a long HCDR3, and a deletion in the light chain CDR1. The occurrence of anti-dsDNA reactivity by a HIV-1 CD4bs BnAb in an individual with SLE raises the possibility that some BnAbs and SLE-associated autoantibodies arise from similar pools of B cells.
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