A Case of Graves' Disease Combined with Hantaan Virus Infection

Graves' disease (GD) is generally presented by thyrotoxicosis with hyperthyroidism, and it is an organ-specific autoimmune disease induced by thyroid-stimulating hormone receptor autoantibodies. However, among diverse etiologies, viral infections have been suggested to trigger or to be involved in the pathogenesis of GD. Hantaan virus infection causing hemorrhagic fever with renal syndrome (HFRS) is common in South Korea and its pathogenesis is suggested to be an immunologic mechanism. We have experienced a patient who was diagnosed as HFRS with thyrotoxicosis. So we herein report the case as GD combined with the hantaan virus infection

Diurnal differences in human muscle isometric force and rate of force development in vivo are associated with differential phosphorylation of sarcomeric M-band proteins.

The maximum force of skeletal muscle exhibits circadian variation that is associated with time-of-day differences in athletic performance. We investigated whether the diurnal difference in force is associated with the post-translational state of muscle proteins. Twenty physically active men (mean ± SD; age 26.0 ± 4.4 y, height 177.3 ± 6.8 cm, body mass 75.1 ± 8.2.8 kg) completed 5 familiarisation sessions where-in they practiced all maximal efforts. Thereafter they performed experimental sessions, in the morning (08:00 h) and evening (17:00 h), counterbalanced in order of administration and separated by at least 72 h. Rectal, skin, muscle temperatures and ratings of perceived effort measurements where made after the subjects had reclined for 30 min (rest) and after the 5-min cycle ergometry warm-ups and prior to the measurement of knee extensor maximal voluntary isometric contraction (MVIC; including twitch-interpolation) and peak rate of force development (RFD). Data handling: 10 subjects from the cohort of 20 volunteered for muscle biopsy procedures, hence only their data is reported for temperature, MVIC and RFD to align with proteomic analyses. Samples of vastus lateralis were collected immediately after exercise and were analysed by ‘top-down’ and ‘bottom-up’ proteomic methods. Rectal and muscle temperatures were higher at rest in the evening (mean difference of 0.51°C and 0.69°C; p<0.05) than in the morning. MVIC force in the evening was significantly greater than in the morning (mean difference of 67 N, 9.3%; p<0.05), similarly peak RFD (mean difference of 1080 N/s, 15.3%; p<0.05) was improved in the evening. 2D gel analysis encompassed 122 proteoforms and discovered 6 statistically significant (p<0.05; false discovery rate [FDR] = 10%) diurnal differences. Phosphopeptide analysis identified 1,693 phosphopeptides and detected 140 phosphopeptides from 104 proteins that were more phosphorylated (p<0.05, FDR=22%) in the morning vs. evening. Myomesin 2, muscle creatine kinase and the C-terminus of titin, exhibited the most robust (FDR<10%) diurnal differences. In summary, the effects of time of day where seen in measures of rectal and muscle temperature and muscle performance. Exercise in the morning, compared to the evening, coincided with greater phosphorylation of M-band-associated proteins in human muscle. These protein modifications may alter M-band structure and disrupt force transmission, thus potentially explaining the lower force output in the morning

Effect of substrate thermal resistance on space-domain microchannel

In recent years, Fluorescent Melting Curve Analysis (FMCA) has become an almost ubiquitous feature of commercial quantitative PCR (qPCR) thermal cyclers. Here a micro-fluidic device is presented capable of performing FMCA within a microchannel. The device consists of modular thermally conductive blocks which can sandwich a microfluidic substrate. Opposing ends of the blocks are held at differing temperatures and a linear thermal gradient is generated along the microfluidic channel. Fluorescent measurements taken from a sample as it passes along the micro-fluidic channel permits fluorescent melting curves to be generated. In this study we measure DNA melting temperature from two plasmid fragments. The effects of flow velocity and ramp-rate are investigated, and measured melting curves are compared to those acquired from a commercially available PCR thermocycler

An N-acetyl--glucosamine binding lectin from Bandeiraea Simplicifolia seeds

A second lectin with a high activity for nonreducing 2-acetamido-2-deoxy-[alpha]--glucopyranosyl residues has been isolated from the seed extracts of Bandeiraea simplicifolia by affinity chromatography on chitin. The lectin is a glycoprotein of subunit molecular weight 30,000. Some properties of the new lectin are reported.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/21643/1/0000027.pd

Determinants of pre-vaccination antibody responses to SARS-CoV-2: a population-based longitudinal study (COVIDENCE UK)

BACKGROUND: Prospective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking. METHODS: We did a prospective population-based study in SARS-CoV-2 vaccine-naive UK adults recruited between May 1 and November 2, 2020, without a positive swab test result for SARS-CoV-2 prior to enrolment. Information on 88 potential sociodemographic, behavioural, nutritional, clinical and pharmacological risk factors was obtained through online questionnaires, and combined IgG/IgA/IgM responses to SARS-CoV-2 spike glycoprotein were determined in dried blood spots obtained between November 6, 2020, and April 18, 2021. We used logistic and linear regression to estimate adjusted odds ratios (aORs) and adjusted geometric mean ratios (aGMRs) for potential determinants of SARS-CoV-2 seropositivity (all participants) and antibody titres (seropositive participants only), respectively. RESULTS: Of 11,130 participants, 1696 (15.2%) were seropositive. Factors independently associated with  higher risk of SARS-CoV-2 seropositivity included frontline health/care occupation (aOR 1.86, 95% CI 1.48–2.33), international travel (1.20, 1.07–1.35), number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.29, 1.06–1.57, P-trend = 0.01), body mass index (BMI) ≥ 25 vs. < 25 kg/m(2) (1.24, 1.11–1.39), South Asian vs. White ethnicity (1.65, 1.10–2.49) and alcohol consumption ≥15 vs. 0 units/week (1.23, 1.04–1.46). Light physical exercise associated with  lower risk (0.80, 0.70–0.93, for ≥ 10 vs. 0–4 h/week). Among seropositive participants, higher titres of anti-Spike antibodies associated with factors including BMI ≥ 30 vs. < 25 kg/m(2) (aGMR 1.10, 1.02–1.19), South Asian vs. White ethnicity (1.22, 1.04–1.44), frontline health/care occupation (1.24, 95% CI 1.11–1.39), international travel (1.11, 1.05–1.16) and number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.12, 1.02–1.23, P-trend = 0.01); these associations were not substantially attenuated by adjustment for COVID-19 disease severity. CONCLUSIONS: Higher alcohol consumption and lower light physical exercise represent new modifiable risk factors for SARS-CoV-2 infection. Recognised associations between South Asian ethnic origin and obesity and higher risk of SARS-CoV-2 seropositivity were independent of other sociodemographic, behavioural, nutritional, clinical, and pharmacological factors investigated. Among seropositive participants, higher titres of anti-Spike antibodies in people of South Asian ancestry and in obese people were not explained by greater COVID-19 disease severity in these groups. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02286-4

On malfunctioning software

Artefacts do not always do what they are supposed to, due to a variety of reasons, including manufacturing problems, poor maintenance, and normal wear-and-tear. Since software is an artefact, it should be subject to malfunctioning in the same sense in which other artefacts can malfunction. Yet, whether software is on a par with other artefacts when it comes to malfunctioning crucially depends on the abstraction used in the analysis. We distinguish between “negative” and “positive” notions of malfunction. A negative malfunction, or dysfunction, occurs when an artefact token either does not (sometimes) or cannot (ever) do what it is supposed to. A positive malfunction, or misfunction, occurs when an artefact token may do what is supposed to but, at least occasionally, it also yields some unintended and undesirable effects. We argue that software, understood as type, may misfunction in some limited sense, but cannot dysfunction. Accordingly, one should distinguish software from other technical artefacts, in view of their design that makes dysfunction impossible for the former, while possible for the latter

Predictions and recent results in susy on the lattice

In this brief review, I summarize the current theoretical knowledge in supersymmetry on the lattice, with special emphasis on recent results in the framework of N=1 supersymmetric Yang Mills theory, Wess-Zumino model and Yang-Mills theory with extended supersymmetries.Comment: 15 pages. Invited brief review for Modern Physics Letters A. Minor change

Structure–function studies of a plant tyrosyl-DNA phosphodiesterase provide novel insights into DNA repair mechanisms of Arabidopsis thaliana

TDP1 (tyrosyl-DNA phosphodiesterase 1), a member of the PLD (phospholipase D) superfamily, catalyses the hydrolysis of a phosphodiester bond between a tyrosine residue and the 3′-phosphate of DNA. We have previously identified and characterized the AtTDP gene in Arabidopsis thaliana, an orthologue of yeast and human TDP1 genes. Sequence alignment of TDP1 orthologues revealed that AtTDP has both a conserved C-terminal TDP domain and, uniquely, an N-terminal SMAD/FHA (forkhead-associated) domain. To help understand the function of this novel enzyme, we analysed the substrate saturation kinetics of full-length AtTDP compared with a truncated AtTDP mutant lacking the N-terminal FHA domain. The recombinant AtTDP protein hydrolysed a single-stranded DNA substrate with Km and kcat/Km values of 703±137 nM and (1.5±0.04)×109M−1·min−1 respectively. The AtTDP-(Δ1–122) protein (TDP domain) showed kinetic parameters that were equivalent to those of the full-length AtTDP protein. A basic amino acid sequence (RKKVKP) within the AtTDP-(Δ123–605) protein (FHA domain) was necessary for nuclear localization of AtTDP. Analysis of active-site mutations showed that a histidine and a lysine residue in each of the HKD motifs were critical for enzyme activity. Vanadates, inhibitors of phosphoryl transfer reactions, inhibited AtTDP enzymatic activity and retarded the growth of an Arabidopsis tdp mutant. Finally, we showed that expression of the AtTDP gene could complement a yeast tdp1Δrad1Δ mutant, rescuing the growth inhibitory effects of vanadate analogues and CPT (camptothecin). Taken together, the results of the present study demonstrate the structure-based function of AtTDP through which AtTDP can repair DNA strand breaks in plants