Identification of RAPD markers linked to the gene PM 1 for resistance to powdery mildew in wheat

 Powdery mildew caused by Blumeria graminis DC. f. sp. triticiém. Marchal is an important disease of wheat (Triticum aestivum L. em Thell). We report here the identification of three random amplified polymorphic DNA (RAPD) markers closely linked to a gene for resistance to B. graminis in wheat. RAPD-PCR (polymerase chain reaction) analysis was conducted using bulked segregant analysis of closely related lines developed from a segregating F₅ family. The F₅ family was derived from a cross between the susceptible cultivar Clark and the resistant line Zhengzhou 871124. Genetic analysis indicated that resistance of Zhengzhou 871124 to powdery mildew is conferred by the gene Pm1. After performing RAPD-PCR analysis with 1300 arbitrary 10-mer primers and agarose-gel electrophoresis, two RAPD markers, UBC320₄₂₀ and UBC638₅₅₀, were identified to be co-segregating with the disease resistance. No recombinants were observed between either of the RAPD markers and the gene for resistance to powdery mildew after analysis of 244 F₂ plants. The third RAPD marker, OPF12₆₅₀, was identified with denaturing gradient-gel electrophoresis (DGGE), and was determined to be 5.4±1.9 cM from the resistance gene. UBC320₄₂₀ and UBC638₅₅₀ were present in wheat powdery mildew differential lines carrying the gene Pm1, suggesting linkage between these markers and the Pm1 resistance gene. Co-segregation between Pm1 and the two markers UBC320₄₂₀ and UBC638₅₅₀ was confirmed in a segregating population derived from a cross with CI14114, the wheat differential line carrying Pm1. The method of deriving closely related lines from inbred families that are segregating for a trait of interest should find wide application in the identification of DNA markers linked to important plant genes. The RAPD marker UBC638₅₅₀ was converted to a sequence tagged site (STS). RAPD markers tightly linked to target genes may facilitate selection and enable gene pyramiding for powdery mildew resistance in wheat breeding programs. Received: 10 December 1995 / Accepted: 13 September 1996     

HLA haplotypes in dizygotic twin pairs: are dizygotic twins more similar than sibs?

It has been suggested that dizygotic twin pairs share two HLA haplotypes more often than ordinary siblings and thus might be genetically more alike. We tested this hypothesis in dizygotic twin pairs from the Danish Twin Registry. A total of 114 (60 female and 54 male) same-sexed healthy twin pairs aged 18-45 years participated. Dizygosity was established by means of DNA sequencing of nine polymorphic markers. HLA-A, B and Cw specificities were typed with serology, and if data were inconclusive, with DNA typing. If twin partners had the same HLA-types, they were assumed to share two haplotypes. If they had 1 HLA A, B and C antigen group in common they were assumed to share one haplotype and if they had no HLA types in common they were assumed to share zero haplotypes. Since HLA-types from parents were unavailable we could not test for identity-by-descent and thus had a risk of overestimating the number of twins sharing two haplotypes. A Chi-square test was used to compare observed numbers in each haplotype sharing group with the expected numbers. Twenty-nine (expected 28.5) twin pairs had two HLA-types in common, 52 (expected 57) had one HLA-type in common and 33 (expected 28.5) had zero HLA-types in common, p = 0.56. Our data show that DZ twins are not more similar than sibs from different pregnancies in general.     

Repercussions of the COVID-19 pandemic on athletes: a cross-sectional study

The COVID-19 pandemic has presented significant challenges and implications for the sports community. Thus, this study aimed to describe the prevalence of COVID-19 in Brazilian athletes and identify the epidemiological, clinical, athletic, life and health factors associated with the disease in these individuals. A cross-sectional study was performed involving 414 athletes from 22 different sports using an online questionnaire from August to November 2020. The association between the athletes’ characteristics and COVID-19 was evaluated using a logistic regression model. The prevalence of COVID-19 was 8.5%, although only 40% of athletes reported having been tested. Being under 27 years of age (3-fold), having children (~5-fold), having a teammate test positive for COVID-19 (2.5-fold), and smoking (14-fold) were associated with a possible higher risk of disease. Almost 20% of athletes self-reported musculoskeletal injuries during the period of the pandemic that was studied. Athletes with a university education (P = 0.02), a profession other than sports (P < 0.001), those from a low-income family (P = 0.01), and public health system users (P = 0.04) were significantly less frequently tested for COVID-19, whereas international competitors, athletes who received a wage, and athletes who had a teammate who tested positive for COVID-19 were 2-, 3-, and 15-fold more likely to be tested for COVID-19, respectively. Approximately 26% of the athletes who tested negative or were untested reported more than three characteristic COVID-19 symptoms, and 11% of athletes who tested positive for COVID-19 were asymptomatic. The identification of modifiable (have children, smoking, and teammates positively tested) and non-modifiable (age under 27 years) factors related to COVID-19 in athletes can contribute to implementing surveillance programmes to decrease the incidence of COVID-19 in athletes and its negative impacts in sports.     

NEIL3-Dependent Regulation of Cardiac Fibroblast Proliferation Prevents Myocardial Rupture

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Interactions between cognitive and sensory load while planning and controlling complex gait adaptations in Parkinson’s disease

Background

Recent research has argued that removal of relevant sensory information during the planning and control of simple, self-paced walking can result in increased demand on central processing resources in Parkinson’s disease (PD). However, little is known about more complex gait tasks that require planning of gait adaptations to cross over an obstacle in PD.

Methods

In order to understand the interaction between availability of visual information relevant for self-motion and cognitive load, the current study evaluated PD participants and healthy controls while walking toward and stepping over an obstacle in three visual feedback conditions: (i) no visual restrictions; (ii) vision of the obstacle and their lower limbs while in complete darkness; (iii) vision of the obstacle only while in complete darkness; as well as two conditions including a cognitive load (with a dual task versus without a dual task). Each walk trial was divided into an early and late phase to examine changes associated with planning of step adjustments when approaching the obstacle.

Results

Interactions between visual feedback and dual task conditions during the obstacle approach were not significant. Patients with PD had greater deceleration and step time variability in the late phase of the obstacle approach phase while walking in both dark conditions compared to control participants. Additionally, participants with PD had a greater number of obstacle contacts when vision of their lower limbs was not available specifically during the dual task condition. Dual task performance was worse in PD compared to healthy control participants, but notably only while walking in the dark regardless of visual feedback.

Conclusions

These results suggest that reducing visual feedback while approaching an obstacle shifts processing to somatosensory feedback to guide movement which imposes a greater demand on planning resources. These results are key to fully understanding why trips and falls occur in those with PD.

     

Multivalent nanobodies targeting death receptor 5 elicit superior tumor cell killing through efficient caspase induction

Multiple therapeutic agonists of death receptor 5 (DR5) have been developed and are under clinical evaluation. Although these agonists demonstrate significant anti-tumor activity in preclinical models, the clinical efficacy in human cancer patients has been notably disappointing. One possible explanation might be that the current classes of therapeutic molecules are not sufficiently potent to elicit significant response in patients, particularly for dimeric antibody agonists that require secondary cross-linking via Fcγ receptors expressed on immune cells to achieve optimal clustering of DR5. To overcome this limitation, a novel multivalent Nanobody approach was taken with the goal of generating a significantly more potent DR5 agonist. In the present study, we show that trivalent DR5 targeting Nanobodies mimic the activity of natural ligand, and furthermore, increasing the valency of domains to tetramer and pentamer markedly increased potency of cell killing on tumor cells, with pentamers being more potent than tetramers in vitro. Increased potency was attributed to faster kinetics of death-inducing signaling complex assembly and caspase-8 and caspase-3 activation. In vivo, multivalent Nanobody molecules elicited superior anti-tumor activity compared to a conventional DR5 agonist antibody, including the ability to induce tumor regression in an insensitive patient-derived primary pancreatic tumor model. Furthermore, complete responses to Nanobody treatment were obtained in up to 50% of patient-derived primary pancreatic and colon tumor models, suggesting that multivalent DR5 Nanobodies may represent a significant new therapeutic modality for targeting death receptor signaling.     

Similar hypotensive responses to resistance exercise with and without blood flow restriction

Low intensity resistance exercise (RE) with blood flow restriction (BFR) has gained attention in the literature due to the beneficial effects on functional and morphological variables, similar to those observed during traditional RE without BFR, while the effects of BFR on post-exercise hypotension remain unclear. The aim of the present study was to compare the blood pressure (BP) response of trained normotensive individuals to RE with and without BFR. In this cross-over randomized trial, eight male subjects (23.8 ± 4 years, 74 ± 3 kg, 174 ± 4 cm) completed two exercise protocols: traditional RE (3 x 10 repetitions at 70% one-repetition maximum [1-RM]) and low intensity RE (3 x 15 repetitions at 20% 1-RM) with BFR. Blood pressure measurements were performed after 15 min of seated rest (0), immediately after and 10 min, 20 min, 30 min, 40 min, 50 min and 60 min after the experimental sessions. Similar hypotensive effects for systolic BP (SBP) were observed for both protocols (P < 0.05) after exercise, with no differences between groups (P > 0.05) and no statistically significant difference for diastolic BP (P > 0.05). These results suggest that in normotensive trained individuals, both traditional RE and RE with BFR induce hypotension for SBP, which is important to prevent cardiovascular disturbances.