ABO exon and intron analysis in individuals with the A(weak)B phenotype reveals a novel O(1v)-A(2 )hybrid allele that causes four missense mutations in the A transferase

BACKGROUND: Since the cloning in 1990 of cDNA corresponding to mRNA transcribed at the blood-group ABO locus, polymorphisms due to ethnic and/or phenotypic variations have been reported. Some subgroups have been explained at the molecular level, but unresolved samples are frequently encountered in the reference laboratory. RESULTS: ABO blood grouping discrepancies were investigated serologically and by ABO genotyping [duplex polymerase-chain-reaction (PCR) – restriction-fragment-length-polymorphism (RFLP) and PCR – allele-specific-primer (ASP) across intron 6] and DNA sequencing of the ABO gene and its proposed regulatory elements. Blood samples from five individuals living in Portugal, Switzerland, Sweden and the USA were analysed. These individuals were confirmed to be of Black ethnic origin and had the unusual A(weak)B phenotype but appeared to have the A(2)B genotype without previously reported mutations associated with weak A or B expression. Sequencing of this A allele (having 467C>T and 1061delC associated with the common A(2 )[A201] allele) revealed three mutations regularly encountered in the O(1v )[O02] allele: 106C>T (Val36Phe), 188G>A (Arg63His), 220C>T (Pro74Ser) in exons 3, 4 and 5, respectively. The additional presence of 46G>A (Ala16Thr) was noted, whilst 189C>T that normally accompanies 188G>A in O(1v )was missing, as were all O(1v)-related mutations in exons 6 and 7 (261delG, 297A>G, 646T>A, 681G>A, 771C>T and 829G>A). On screening other samples, 46G>A was absent, but two new O alleles were found, a Jordanian O(1 )and an African O(1v )allele having 188G>A but lacking 189C>T. Sequencing of introns 2, 3, 4 and 5 in common alleles (A(1 )[A101], A(2), B [B101], O(1), O(1v)and O(2 )[O03]) revealed 7, 12, 17 and 8 polymorphic positions, respectively, suggesting that alleles could be defined by intronic sequences. These polymorphic sites allowed definition of a breakpoint in intron 5 where the O(1v)-related sequence was fused with A(2 )to form the new hybrid. Intron 6 has previously been sequenced. Four new mutations were detected in the hybrid allele and these were subsequently also found in intron 6 of A(2 )alleles in other Black African samples. CONCLUSIONS: A novel O(1v)-A(2 )hybrid was defined by ABO exon/intron analysis in five unrelated individuals of African descent with the A(weak)B blood group phenotype

The Long-Term Ergogenic Effect of Long Acting ?2-Agonists

Background: The WADA List of Banned Substances and Methods stipulates that athletes can use up to 54 µg inhaled Formoterol and inhaled Salmeterol as directed by the manufacturer. It is unknown whether large daily therapeutic doses of Formoterol and Salmeterol can improve sprint and strength performance. Purpose: To investigate the impact of inhaling 100 µg of Salmeterol (SAL) or 12 µg of Formoterol (FOR) twice daily over a 5 week period on sprint, strength and power performance. Methods: In a randomised single blind study 24 male and 15 female non-asthmatic and active participants were recruited (mean ± SD; Males age 28.0 ± 5.5 years; weight 72.1 ± 10.5 Kg; height 164.7 ± 7.1 cm; Females age 24.1 ± 4.1 years; weight 65.4 ± 9.5 Kg; height 168.0 ± 4.3 cm). Participants completed three standardised whole body strength and power training sessions per week for five weeks. All the training sessions were supervised by a personal trainer who recorded work performed in each session. During the five week training period participants were assigned to either SAL, FOR or a placebo (PLA) group. Participants took their inhaler twice per day as instructed. Participants completed assessments of sprint, strength and power at week 0 and after 5 weeks of strength and power training. The assessments included 30 m sprint, vertical jump, 1 RM bench press, 1 RM leg press, peak torque flexion and extension, anthropometric evaluation and Rest-Q questionnaires. Mixed Model Repeated Measures ANOVA were performed to investigate the changes in the sprint, strength and power assessments between groups over the course of the 5 week training session. Results: 30 m Sprint time was significantly lower in FOR group (– 0.29 ± 0.11 s; p=0.049) and SAL (– 0.35 ± 0.05 s; p=0.04) when compared with compared with Placebo (+0.01 ± 0.11 s; P=0.000). No significant change was found in 1RM Leg, Squat and Bench Press or during Isokinetic evaluation performed at 60° range in flex/ext movement. Jump performance as well as anthropometric measures didn’t differ between groups. Discussion: The significant changes in FOR and SAL 30m sprint time when compared to PLA suggest the long term use of inhaled ?2-agonnists may provide ergogenic advantage. This finding suggests a review of the use of inhaled doses of FOR and SAL by athletes in training and official competition may be necessary

Does the Relationship between Age and Brain Structure Differ in Youth with Conduct Disorder?

Conduct disorder (CD) is characterised by persistent antisocial and aggressive behaviour and typically emerges in childhood or adolescence. Although several authors have proposed that CD is a neurodevelopmental disorder, very little evidence is available about brain development in this condition. Structural brain alterations have been observed in CD, and some indirect evidence for delayed brain maturation has been reported. However, no detailed analysis of age-related changes in brain structure in youth with CD has been conducted. Using cross-sectional MRI data, this study aimed to explore differences in brain maturation in youth with CD versus healthy controls to provide further understanding of the neurodevelopmental processes underlying CD. 291 CD cases (153 males) and 379 healthy controls (160 males) aged 9–18 years (Mage = 14.4) were selected from the European multisite FemNAT-CD study. Structural MRI scans were analysed using surface-based morphometry followed by application of the ENIGMA quality control protocols. An atlas-based approach was used to investigate group differences and test for group-by-age and group-by-age-by-sex interactions in cortical thickness, surface area and subcortical volumes. Relative to healthy controls, the CD group showed lower surface area across frontal, temporal and parietal regions as well as lower total surface area. No significant group-by-age or group-by-age-by-sex interactions were observed on any brain structure measure. These findings suggest that CD is associated with lower surface area across multiple cortical regions, but do not support the idea that CD is associated with delayed brain maturation, at least within the age bracket considered here.</p

Discovery and Computational Modelling of Adsorbent Polymers that Effectively Immobilize SARS-CoV-2 with Potential Practical Applications

Viral translocation is considered a common way for respiratory viruses to spread and contaminate the surrounding environment. Thus, the discovery of non-eluting polymers that immobilize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) upon contact provides an opportunity to develop new coating materials for better infection control. Here, virion binding polymers are discovered from an existing monomer library via experimental high-throughput screening. Among them, poly(2-diethylamino) ethyl acrylate (pDEAEA) demonstrates dual-function: binding virions strongly and its speed to inactivate adsorbed SARS-CoV-2. Computational models are built based on the experimental screening data. Polymers which are predicted to be pro-adsorption by the virtual screening are poly(1-4-[5-(4-methoxyphenyl)-1H-pyrazol-3-yl]-piperidin-1-yl]-prop-2-en-1-one) (pMPPPP), poly(1-(6-isobutyloctahydropyrrolo[3,4-d]azepin-2(1H)-yl)-2-methylprop-2-en-1-one) (piBOHPAMP) and poly(N-(3-((1-benzylpiperidin-4-yl)oxy)propyl)acrylamide) (pBPOPAm), and these are found to adsorb virions. However, due to limitations in the diversity of structures in the training set, the computational models are unable to predict adsorption of virions for all polymer structures. Summarily, these findings indicate the utility of the methodology to identify coating polymers that effectively immobilize SARS-CoV-2 with potential practical applications (e.g. water and air filtration)

Haploinsufficiency of CYP8B1 associates with increased insulin sensitivity in humans

10.1172/JCI152961The Journal of clinical investigation13221e152961

Self-reported diabetes in older people: comparison of prevalences and control measures

OBJECTIVE The objective of this study was to analyze the prevalence of diabetes in older people and the adopted control measures. METHODS Data regarding older diabetic individuals who participated in the Health Surveys conducted in the Municipality of Sao Paulo, SP, ISA-Capital, in 2003 and 2008, which were cross-sectional studies, were analyzed. Prevalences and confidence intervals were compared between 2003 and 2008, according to sociodemographic variables. The combination of the databases was performed when the confidence intervals overlapped. The Chi-square (level of significance of 5%) and the Pearson’s Chi-square (Rao-Scott) tests were performed. The variables without overlap between the confidence intervals were not tested. RESULTS The age of the older adults was 60-69 years. The majority were women, Caucasian, with an income of between > 0.5 and 2.5 times the minimum salary and low levels of schooling. The prevalence of diabetes was 17.6% (95%CI 14.9;20.6) in 2003 and 20.1% (95%CI 17.3;23.1) in 2008, which indicates a growth over this period (p at the limit of significance). The most prevalent measure adopted by the older adults to control diabetes was hypoglycemic agents, followed by diet. Physical activity was not frequent, despite the significant differences observed between 2003 and 2008 results. The use of public health services to control diabetes was significantly higher in older individuals with lower income and lower levels of education. CONCLUSIONS Diabetes is a complex and challenging disease for patients and the health systems. Measures that encourage health promotion practices are necessary because they presented a smaller proportion than the use of hypoglycemic agents. Public health policies should be implemented, and aimed mainly at older individuals with low income and schooling levels. These changes are essential to improve the health condition of older diabetic patients

Genome-wide Association Study Identifies Two Susceptibility Loci for Osteosarcoma

Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. In order to better understand the genetic etiology of osteosarcoma, we performed a multi-stage genome-wide association study (GWAS) consisting of 941 cases and 3,291 cancer-free adult controls of European ancestry. Two loci achieved genome-wide significance: rs1906953 at 6p21.3, in the glutamate receptor metabotropic 4 [GRM4] gene (P = 8.1 ×10-9), and rs7591996 and rs10208273 in a gene desert on 2p25.2 (P = 1.0 ×10-8 and 2.9 ×10-7). These two susceptibility loci warrant further exploration to uncover the biological mechanisms underlying susceptibility to osteosarcoma

Thermoregulation and fluid balance during a 30-km march in 60-versus 80-year-old subjects

The presence of impaired thermoregulatory and fluid balance responses to exercise in older individuals is well established. To improve our understanding on thermoregulation and fluid balance during exercise in older individuals, we compared thermoregulatory and fluid balance responses between sexagenarians and octogenarians during prolonged exercise. Forty sexagenarians (60 ± 1 year) and 36 octogenarians (81 ± 2 year) volunteered to participate in a 30-km march at a self-selected pace. Intestinal temperature (T in) and heart rate were recorded every 5 km. Subjects reported fluid intake, while urine output was measured and sweat rate was calculated. Octogenarians demonstrated a lower baseline T in and a larger exercise-induced increase in T in compared to sexagenarians (1.2 ± 0.5 °C versus 0.7 ± 0.4 °C, p  0.05). These results suggest that thermoregulatory responses deteriorate with advancing age, while fluid balance is regulated appropriately during a 30-km walking march under moderate ambient conditions