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Papers by Martin Braddock

Cell, Sep 1, 1990

Replication of HIV-1 depends on the viral Tat protein, which functions via a target sequence, TAR... more Replication of HIV-1 depends on the viral Tat protein, which functions via a target sequence, TAR, present in the proviral long terminal repeat (LTR) and at the 5' end of viral mRNAs. We have shown that Tat potentiates the expression of TAR-containing RNAs, but only when Tat and the TAR-containing RNA are present in the nucleus. We now show that a small change in the TAR loop abolishes nuclear potentiation by Tat. Furthermore, the HIV-1 U3 region induces expression incompetence in mRNA synthesized by this promoter. RNAs of identical structure are, however, translated efficiently when produced from the CMV-IE promoter. The Tat-TAR system appears, therefore, to rescue the expression potential of HIV-1 LTR-directed RNA.

Studia Humana

The recent success of the Mars 2020 project and the high quality images relayed back to Earth hav... more The recent success of the Mars 2020 project and the high quality images relayed back to Earth have provided further impetus and expectations for human missions to Mars. To support space agency and private enterprise plans to establish a sustainable colony on Mars in the 2030s, synthetic biology may play a vital role to enable astronaut self-sufficiency. In this review, we describe some aspects of where synthetic biology may inform and guide in situ resource utilisation strategies. We address the nature of Martian regolith and describe methods by which it may be rendered fit for purpose to support growth and yield of bioengineered crops. Lastly, we illustrate some examples of innate human adaptation which may confer characteristics desirable in the selection of colonists and with a future looking lens, offer potential targets for human enhancement.

Journal of Cell Science, 1995

The regulation of human cytomegalovirus (hCMV) and human immunodeficiency virus (HIV) gene expres... more The regulation of human cytomegalovirus (hCMV) and human immunodeficiency virus (HIV) gene expression has been studied in single intact mammalian cells. Viral promoters were placed upstream of the firefly luciferase reporter gene and the resulting hybrid reporter constructs were stably integrated into the HeLa cell genome. A highly sensitive photon-counting camera system was used to study the level of gene expression in single intact cells. Luciferase expression was studied in the absence of activators of viral gene expression, in the presence of the HIV-1 TAT trans-activator protein, or in the presence of sodium butyrate, a non-viral activator of gene expression. In the absence of any activator of gene expression, while expression was undetectable in most cells, significant levels of basal luciferase activity were observed in a few cells, indicating heterogeneity in gene expression in the cell population. In the presence of the general activator of viral gene expression, sodium but...

Current Drug Discovery Technologies, 2020

Journal of Ergonomics, 2017

Physiology, 2001

Destruction of bone tissue due to disease and inefficient bone healing after traumatic injury may... more Destruction of bone tissue due to disease and inefficient bone healing after traumatic injury may be addressed by tissue engineering techniques. Growth factor, cytokine protein, and gene therapies will be developed, which, in conjunction with suitable carriers, will regenerate missing bone or help in cases of defective healing.

Arthritis & rheumatology (Hoboken, N.J.), 2018

Rheumatoid arthritis (RA) is a chronic and degenerative autoimmune joint disease that leads to di... more Rheumatoid arthritis (RA) is a chronic and degenerative autoimmune joint disease that leads to disability, reduced quality of life, and increased mortality. Although several synthetic and biologic disease-modifying antirheumatic drugs are available, there is still a medical need for novel drugs that control disease progression. As only 10% of experimental drug candidates for treatment of RA that enter phase I trials are eventually registered by the Food and Drug Administration, there is an immediate need for translational tools to facilitate early decision-making in drug development. In this study, we aimed to determine if the inability of fostamatinib (a small molecule inhibitor of Syk) to demonstrate sufficient efficacy in phase III of a previous clinical study could have been predicted earlier in the development process. Biomarkers of bone, cartilage, and interstitial matrix turnover (C-telopeptide of type I collagen [CTX-I], matrix metalloproteinase-derived types I, II, and III ...

The Lancet. Respiratory medicine, Jan 18, 2018

The role of interleukin 13 in airway inflammation and remodelling in asthma is unclear. Tralokinu... more The role of interleukin 13 in airway inflammation and remodelling in asthma is unclear. Tralokinumab is a human monoclonal antibody that neutralises interleukin 13. We aimed to evaluate whether tralokinumab would have an effect on airway eosinophilic infiltration, blood and sputum eosinophil concentrations, eosinophil activation, and airway remodelling. We did a multicentre, double-blind, randomised, placebo-controlled phase 2 trial at 15 centres across the UK, Denmark, and Canada. We enrolled participants of either sex aged 18-75 years with inadequately controlled moderate-to-severe asthma for 12 months or more, requiring treatment with inhaled corticosteroids at a stable dose. We randomly assigned participants (1:1) to receive tralokinumab (300 mg) or placebo by an interactive web-based system or voice response system. Participants and study personnel were masked to treatment allocation. Both tralokinumab and placebo were administered subcutaneously every 2 weeks. The primary outc...

Biochemical Society Transactions, 2002

Oncotarget, Jan 22, 2016

To evaluate the association between sex-specific serum high sensitive C reactive protein (hsCRP) ... more To evaluate the association between sex-specific serum high sensitive C reactive protein (hsCRP) levels and NAFLD in a large population-based study. From Q1 to Q4, the incidence ratios were 21.1 (95% CI 17.5 24.7), 18.6 (95% CI 16.5 20.8), 24.8 (95% CI 22.4 27.2) and 31.1 (95% CI 28.5 33.6) in males and 6.2 (95% CI 4.4 8.0), 6.0 (95% CI 5.1 7.1), 11.4 (95% CI 9.2 13.7) and 19.5 (95% CI 16.1 22.9) in females. Compared with a 1.7-fold increase (Q4 vs Q2) in males, actuarial incidence increased 3.3-fold (Q4 vs Q2) in females. After adjusting for known confounding variables in this study, in the longitudinal population, compared with the reference group, those in Q1, Q3, and Q4 had HRs of 1.63 (95% CI 1.29-2.05), 1.11 (95% CI 0.93-1.31), 1.14 (95% CI 0.97-1.35) in male and 1.77 (95% CI 1.25-2.49), 1.22 (95% CI 0.93-1.59), 1.36 (95% CI 1.03-1.80) in female for NAFLD, respectively. 8618 subjects from Wenzhou Medical Center of Wenzhou People's Hospital were included. Sex specific hsCRP...

Basic Research in Cardiology, 2016

Clinical Investigation, 2015

Drug Discovery and Evaluation: Pharmacological Assays, 2015

Metabolism: clinical and experimental, 2015

Non-alcoholic fatty liver disease (NAFLD) includes a cluster of liver disorders ranging from simp... more Non-alcoholic fatty liver disease (NAFLD) includes a cluster of liver disorders ranging from simple fatty liver to non-alcoholic steatohepatitis (NASH) and cirrhosis. Due to its liver and vascular complications, NAFLD has become a public health problem with high morbidity and mortality. The pathogenesis of NAFLD is considered a "multi-hit hypothesis" that involves lipotoxicity, oxidative stress, endoplasmic reticulum stress, a chronic inflammatory state and mitochondrial dysfunction. Fibroblast growth factor 21 (FGF21) is a member of the fibroblast growth factor family with multiple metabolic functions. FGF21 directly regulates lipid metabolism and reduces hepatic lipid accumulation in an insulin-independent manner. Several studies have shown that FGF21 can ameliorate the "multi-hits" in the pathogenesis of NAFLD. The administration of FGF21 reverses hepatic steatosis, counteracts obesity and alleviates insulin resistance in rodents and nonhuman primates. Using s...

Nucleic Acids Research, 1994