High energy electron diffraction instrument with tunable camera length.

Ultrafast electron diffraction (UED) stands as a powerful technique for real-time observation of structural dynamics at the atomic level. In recent years, the use of MeV electrons from radio frequency guns has been widely adopted to take advantage of the relativistic suppression of the space charge effects that otherwise limit the temporal resolution of the technique. Nevertheless, there is not a clear choice for the optimal energy for a UED instrument. Scaling to beam energies higher than a few MeV does pose significant technical challenges, mainly related to the inherent increase in diffraction camera length associated with the smaller Bragg angles. In this study, we report a solution by using a compact post-sample magnetic optical system to magnify the diffraction pattern from a crystal Au sample illuminated by an 8.2 MeV electron beam. Our method employs, as one of the lenses of the optical system, a triplet of compact, high field gradients (>500 T/m), small-gap (3.5 mm) Halbach permanent magnet quadrupoles. Shifting the relative position of the quadrupoles, we demonstrate tuning the magnification by more than a factor of two, a 6× improvement in camera length, and reciprocal space resolution better than 0.1 Å-1 in agreement with beam transport simulations.

Association of adverse and positive childhood experiences with health-related quality of life in adolescents.

OBJECTIVES: To investigate the independent impacts of adverse childhood experiences (ACEs) and positive childhood experiences (PCEs) on the health-related quality of life (HRQOL) of Chinese adolescents, and to explore the potential moderating role of PCEs in the association between ACEs and HRQOL. STUDY DESIGN: This was a cross-sectional study. METHODS: We surveyed 6982 students aged 11-20 in Guangzhou, China, from November to December 2021. Adolescents self-reported their ACEs, PCEs, and HRQOL by the Childhood Trauma Questionnaire Short Form, the Adverse Childhood Experiences-International Questionnaire, the Benevolent Childhood Experiences Scale, and the Paediatric Quality of Life Inventory Version 4.0, respectively. Multivariable linear regressions were performed to examine the associations between ACEs, PCEs, and HRQOL controlled for adolescents' age, gender, single-child status, boarding school attendance, primary caregivers, as well as parental age and occupational status. Likelihood-ratio tests were further applied to explore the moderating role of PCEs. RESULTS: In the models that considered both ACEs and PCEs, ACEs were significantly associated with lower HRQOL scores in all dimensions, summary scales, and total scale (ß = -13.88, 95% confidence interval [CI]: -14.82, -12.94 for total scale). Conversely, exposure to an above-average number of PCEs was associated with higher HRQOL scores in all measured aspects (ß = 7.20, 95%CI: 6.57, 7.84 for total scale). PCEs significantly moderated the association between ACEs and all HRQOL dimensions, summary scales, and total scale, except school functioning. CONCLUSION: ACEs and PCEs exert independent and opposite impacts on adolescents' HRQOL. PCEs could mitigate the negative impacts of ACEs. Enhancing resilience, like PCEs, may contribute to improving the HRQOL among adolescents who have exposed to ACEs.

Hypertriglyceridaemic-waist phenotype and risk of diabetes in people with impaired fasting glucose in primary care: a cohort study.

AIM: We aimed to determine the prospective association between baseline triglyceridaemic-waist phenotypes and diabetic mellitus incidence in individuals with impaired fasting glucose seen in primary care. METHODS: A cohort of 1101 participants (84.4% of the recruited individuals) with impaired fasting glucose were recruited from three primary care clinics during regular follow-ups to monitor their chronic conditions. Baseline triglyceridaemic-waist phenotypes were divided into four groups: (1) normal waistline and triglyceride level (n = 252); (2) isolated central obesity (n = 518); (3) isolated high triglyceride level (n = 80); and (4) central obesity with high triglyceride level (i.e. hypertriglyceridaemic-waist phenotype) (n = 251). The presence of diabetes at follow-up was determined by fasting plasma glucose (≥ 7.0 mmol/l) and/or 2-h 75-g oral glucose tolerance test (≥ 11.1 mmol/l) and/or HbA1c (47.5 mmol/mol; ≥ 6.5%) according to American Diabetes Association diagnostic criteria. Multivariable Cox proportional hazards regressions were established to assess the impact of different triglyceridaemic-waist phenotypes on time to diabetes onset. RESULTS: After a mean follow-up period of 6.5 months (sd 4.7 months), the number of diabetes cases was significantly higher in the group with hypertriglyceridaemic-waist phenotype (52.2%) compared with the other three phenotype groups (group 1: 28.2%; group 2: 34.6%; group 3: 30.0%). Only the hypertriglyceridaemic-waist phenotype showed an increased risk of developing diabetes (hazard ratio 1.581, 95% CI 1.172-2.134; P = 0.003) compared with the group with normal waistline and triglyceride level after controlling for confounders. CONCLUSIONS: The combination of central obesity and hypertriglyceridaemia is associated with > 50% risk of progression to diabetes within 6 months among individuals with impaired fasting glucose seen in primary care.

Objectively measured sedentary time, physical activity and kidney function in people with recently diagnosed Type 2 diabetes: a prospective cohort analysis.

AIM: To assess the prospective association between objectively measured physical activity and kidney function over 4 years in people with Type 2 diabetes. METHODS: Individuals (120 women and 206 men) participating in the ADDITION-Plus trial underwent assessment of sedentary time (SED-time), time spent in moderate-to-vigorous-intensity physical activity (MVPA) and total physical activity energy expenditure (PAEE) using a combined heart rate and movement sensor, and kidney function [estimated glomerular filtration rate (eGFR), serum creatinine and urine albumin-to-creatinine ratio (ACR)] at baseline and after 4 years of follow-up. Multivariate regression was used to quantify the association between change in SED-time, MVPA and PAEE and kidney measures at four-year follow-up, adjusting for change in current smoking status, waist circumference, HbA1c , systolic blood pressure, triglycerides and medication usage. RESULTS: Over 4 years, there was a decline in eGFR values from 87.3 to 81.7 ml/min/1.73m(2) (P < 0.001); the prevalence of reduced eGFR (eGFR < 60 ml/min/1.73m(2) ) increased from 6.1 to 13.2% (P < 0.001). There were small increases in serum creatinine (median: 81-84 µmol/l, P < 0.001) and urine ACR (median: 0.9-1.0 mg/mmol, P = 0.005). Increases in SED-time were associated with increases in serum creatinine after adjustment for MVPA and cardiovascular risk factors (ß = 0.013, 95% CI: 0.001, 0.03). Conversely, increases in PAEE were associated with reductions in serum creatinine (ß = -0.001, 95% CI: -0.003, -0.0001). CONCLUSION: Reducing time spent sedentary and increasing overall physical activity may offer intervention opportunities to improve kidney function among individuals with diabetes. (Trial Registry no. ISRCTN 99175498).

Aquaporin-4 autoantibodies cause asymptomatic aquaporin-4 loss and activate astrocytes in mouse.

BACKGROUND: Neuromyelitis optica (NMO) is a central nervous system inflammatory demyelinating disorder. Up to 90% of patients are seropositive for aquaporin-4 autoantibodies (AQP4 Ab). The pathogenetic mechanisms underlying clinical onset and relapse of NMO are uncertain. OBJECTIVE: Study the pathogenicity of AQP4 Ab in the absence of complement activation. METHODS: Female C57BL/6N mice (human IgG cannot activate mouse complements) pretreated with complete Freund's adjuvant (CFA, day 0) and pertussis toxin (PTx, day 0 and day 2) were transferred with IgG isolated from serum of healthy subjects or NMO patients (AQP4 Ab-positive or negative) intraperitoneally (day 7-9). Mice were observed for signs of experimental autoimmune encephalomyelitis (EAE) by standard 6-grade EAE scores. Spinal cord was obtained at day 11 for immunohistochemistry. RESULTS: None of the mice had clinical signs of encephalomyelitis, inflammatory cells infiltration or demyelination of spinal cord. CFA and PTx induce BBB breakdown evidenced by leakage of human IgG into cord parenchyma. Patchy areas of AQP4 loss were observed in spinal cord of mice transferred with IgG from AQP4 Ab-positive NMO patients but not in mice transferred with IgG from AQP4 Ab-negative NMO patients or healthy subjects; but there was no loss of glial fibrillary acidic protein immunoreactivity in all mice. Markedly increased proliferation of astrocytic processes suggestive of astrocytic activation was observed in mice transferred with IgG from AQP4 Ab-positive patients. CONCLUSION: AQP4 Ab cause asymptomatic AQP4 loss and astrocytic activation but not myelitis, demyelination or astrocytic cytotoxicity in spinal cord of mouse in the absence of complement activation.

Sequence and expression of the murine Hoxd-3 homeobox gene.

Murine Hoxd-3 (Hox 4.1) genomic DNA and cDNA and Hoxa-3 (Hox 1.5) cDNA were cloned and sequenced. The homeodomains of Hoxd-3 and Hoxa-3 and regions before and after the homeodomain are highly conserved. Both Hoxa-3 and Hoxa-3 proteins have a proline-rich region that contains consensus amino acid sequences for binding to Src homology 3 domains of some signal transduction proteins. Northern blot analysis of RNA from 8- to 11-day-old mouse embryos revealed a 4.3-kb species of Hoxd-3 RNA, whereas a less abundant 3.0-kb species of Hoxd-3 RNA was found in RNA from 9- to 11-day-old embryos. Two species of Hoxd-3 poly(A)+ RNA, 4.3 and 6.0 kb in length, were found in poly(A)+ RNA from adult mouse kidney, but not in RNA from other adult tissues tested. Hoxd-3 mRNA was detected by in situ hybridization in 12-, 14-, and 17-day-old mouse embryos in the posterior half of the myelencephalon, spinal cord, dorsal root ganglia, first cervical vertebra, thyroid gland, kidney tubules, esophagus, stomach, and intestines.

Murine Hox-1.11 homeobox gene structure and expression.

The Hox-1.11 gene encodes a protein 372 amino acid residues long that contains a conserved pentapeptide, a homeodomain, and an acidic region. The amino acid sequence of the homeodomain of Hox-1.11 is identical to that of Hox-2.8, and the N-terminal and C-terminal regions of Hox-1.11 are similar to those of human HOX2H, which is the equivalent of murine Hox-2.8. The Hox-1.11 gene was shown to reside on murine chromosome 6, which contains the Hox-1 cluster of homeobox genes. One species of Hox-1.11 poly(A)+ RNA approximately 1.7 kb long was detected in mouse embryos, which is most abundant in 12-day-old embryos and progressively decreases during further embryonic development. The most anterior expression of Hox-1.11 poly(A)+ RNA in 12- to 14-day-old mouse embryos was shown by in situ hybridization to be in the mid and posterior hindbrain. Hox-1.11 poly(A)+ RNA also is expressed in the VII and VIII cranial ganglia, spinal cord, spinal ganglia, larynx, lungs, vertebrae, sternum, and intestine.

Human cDNA clones for an alpha subunit of Gi signal-transduction protein.

Two cDNA clones were obtained from a lambda gt11 cDNA human brain library that correspond to alpha i subunits of G signal-transduction proteins (where alpha i subunits refer to the alpha subunits of G proteins that inhibit adenylate cyclase). The nucleotide sequence of human brain alpha i is highly homologous to that of bovine brain alpha i [Nukada, T., Tanabe, T., Takahashi, H., Noda, M., Haga, K., Haga, T., Ichiyama, A., Kangawa, K., Hiranaga, M., Matsuo, H. & Numa, S. (1986) FEBS Lett. 197, 305-310] and the predicted amino acid sequences are identical. However, human and bovine brain alpha i cDNAs differ significantly from alpha i cDNAs from human monocytes, rat glioma, and mouse macrophages in amino acid (88% homology) and nucleotide (71-75% homology) sequences. In addition, the nucleotide sequences of the 3' untranslated regions of human and bovine brain alpha i cDNAs differ markedly from the sequences of human monocyte, rat glioma, and mouse macrophage alpha i cDNAs. These results suggest there are at least two classes of alpha i mRNA.

Human cDNA clones for four species of G alpha s signal transduction protein.

lambda gt11 cDNA libraries derived from human brain were screened with oligonucleotide probes for recombinants that code for alpha subunits of G signal transduction proteins. Eleven alpha s clones were detected with both probes and characterized. Four types of alpha s cDNA were cloned that differ in nucleotide sequence in the region that corresponds to amino acid residues 71-88. The clones differ in the codon for alpha s amino acid residue 71 (glutamic acid or aspartic acid), the presence or absence of codons for the next 15 amino acid residues, and the presence or absence of an adjacent serine residue. S1 nuclease protection experiments revealed at least two forms of alpha s mRNA. A mechanism for generating four species of alpha s mRNA by alternative splicing of precursor RNA is proposed.