The Development of Computational Biology in South Africa: Successes Achieved and Lessons Learnt

Bioinformatics is now a critical skill in many research and commercial environments as biological data are increasing in both size and complexity. South African researchers recognized this need in the mid-1990s and responded by working with the government as well as international bodies to develop initiatives to build bioinformatics capacity in the country. Significant injections of support from these bodies provided a springboard for the establishment of computational biology units at multiple universities throughout the country, which took on teaching, basic research and support roles. Several challenges were encountered, for example with unreliability of funding, lack of skills, and lack of infrastructure. However, the bioinformatics community worked together to overcome these, and South Africa is now arguably the leading country in bioinformatics on the African continent. Here we discuss how the discipline developed in the country, highlighting the challenges, successes, and lessons learnt.     

Comparison of ultrasonographic characteristics of deep abdominal muscles in women with and without chronic neck pain: a case-control study

Objectives:To compare ultrasonography (USG) parameters of deep abdominal muscles (transversus abdominis-TrA, internal obliques-IO) between women with and without chronic neck pain (CNP).Methods:Women with CNP (n=18; mean-age=37.7 years; mean-BMI=22.7 kg/m²) and asymptomatic individuals (n=18; mean-age=36.1 years; mean-BMI=21.8 kg/m²) participated in the study. The activation of the deep neck flexors (ADNF) was measured using cranio-cervical flexion test. Muscle thickness, changes in thickness (ΔT), and contraction ratio (CR) of deep abdominal muscles were evaluated by ultrasonography device in two conditions: standard-protocol and during ADNF. For each condition, ultrasound image of abdominal muscles was captured at rest and during abdominal draw-in manoeuvre (ADIM).Results:Comparative statistics revealed no significant difference between groups regarding ultrasonography parameters in the standard-protocol (p>0.05). Besides, there was no difference in the CR of TrA and IO between groups in the two conditions. However, women with CNP showed less muscle thickness of TrAADIM during ADNF than the asymptomatic participants (p<0.05). The CNP group also had decreased ΔT of TrA(ADIM-rest) during ADNF compared to the asymptomatic group (p<0.05).Conclusions:The ultrasonography parameters of TrA suggest that motor control in the lumbar region is altered in women with CNP. The combination of cervical stabilization exercises with ADIM can be a novel strategy in the treatment of CNP.     

Induction of oxidative stress, lysosome activation and autophagy by nanoparticles in human brain-derived endothelial cells

Different types of NPs (nanoparticles) are currently under development for diagnostic and therapeutic applications in the biomedical field, yet our knowledge about their possible effects and fate in living cells is still limited. In the present study, we examined the cellular response of human brain-derived endothelial cells to NPs of different size and structure: uncoated and oleic acid-coated iron oxide NPs (8-9 nm core), fluorescent 25 and 50 nm silica NPs, TiO2 NPs (21 nm mean core diameter) and PLGA [poly(lactic-co-glycolic acid)]-PEO [poly(ethylene oxide)] polymeric NPs (150 nm). We evaluated their uptake by the cells, and their localization, generation of oxidative stress and DNA-damaging effects in exposed cells. We show that NPs are internalized by human brain-derived endothelial cells; however, the extent of their intracellular uptake is dependent on the characteristics of the NPs. After their uptake by human brain-derived endothelial cells NPs are transported into the lysosomes of these cells, where they enhance the activation of lysosomal proteases. In brain-derived endothelial cells, NPs induce the production of an oxidative stress after exposure to iron oxide and TiO2 NPs, which is correlated with an increase in DNA strand breaks and defensive mechanisms that ultimately induce an autophagy process in the cells.     

A silent H-bond can be mutationally activated for high-affinity interaction of BMP-2 and activin type IIB receptor

Background  

Bone morphogenetic proteins (BMPs) are key regulators in the embryonic development and postnatal tissue homeostasis in all animals. Loss of function or dysregulation of BMPs results in severe diseases or even lethality. Like transforming growth factors β (TGF-βs), activins, growth and differentiation factors (GDFs) and other members of the TGF-β superfamily, BMPs signal by assembling two types of serine/threonine-kinase receptor chains to form a hetero-oligomeric ligand-receptor complex. BMP ligand receptor interaction is highly promiscuous, i.e. BMPs bind more than one receptor of each subtype, and a receptor bind various ligands. The activin type II receptors are of particular interest, since they bind a large number of diverse ligands. In addition they act as high-affinity receptors for activins but are also low-affinity receptors for BMPs. ActR-II and ActR-IIB therefore represent an interesting example how affinity and specificity might be generated in a promiscuous background.     

Structure analysis of bone morphogenetic protein-2 type I receptor complexes reveals a mechanism of receptor inactivation in juvenile polyposis syndrome

Bone morphogenetic proteins regulate many developmental processes during embryogenesis as well as tissue homeostasis in the adult. Signaling of bone morphogenetic proteins (BMPs) is accomplished by binding to two types of serine/threonine kinase transmembrane receptors termed type I and type II. Because a large number of ligands signal through a limited number of receptors, ligand-receptor interaction in the BMP superfamily is highly promiscuous, with a ligand binding to various receptors and a receptor binding many different BMP ligands. In this study we investigate the interaction of BMP-2 with its two high affinity type I receptors, BMP receptors IA (BMPR-IA) and BMPR-IB. Interestingly, 50% of the residues in the BMP-2 binding epitope of the BMPR-IA receptor are exchanged in BMPR-IB without a decrease in binding affinity or specificity for BMP-2. Our structural and functional analyses show that promiscuous binding of BMP-2 to both type I receptors is achieved by inherent backbone and side-chain flexibility as well as by variable hydration of the ligand-receptor interface enabling the BMP-2 surface to adapt to different receptor geometries. Despite the high degree of amino acid variability found in BMPR-IA and BMPR-IB binding equally to BMP-2, three single point missense mutations in the ectodomain of BMPR-IA cannot be tolerated. In juvenile polyposis syndrome these mutations have been shown to inactivate BMPR-IA. On the basis of our biochemical and biophysical analyses, we can show that the mutations, which are located outside the ligand binding epitope, alter the local or global fold of the receptor, thereby inactivating BMPR-IA and causing a loss of the BMP-2 tumor suppressor function in colon epithelial cells.     

Sterine in Trichosanthes kirilowii

Four Δ⁵-sterols and six Δ⁷-sterols were isolated from the seed oil of Trichosanthes kirilowii and identified as campesterol, sitosterol, stigmasterol, Δ⁷-campesterol, Δ⁷-stigmasterol, Δ^7,22-stigmastadienol, 24-ethylcholesta-5,25-diene-3β-ol, 24-ethylcholesta-7,24(25)-diene-3β-ol, 24-ethylcholesta-7,25-diene-3β-ol, and 24-ethylcholesta-7,22,25-trine-3β-ol.     

Preparation and physiological properties of alkyl esters of 2,3-dihydroxypropionic acid

In order to investigate the physiological behavior of alkyl esters of 2,3-dihydroxypropionic acid two such compounds have been synthesized. One of them, the 1-dodecylester of 2,3-ditetradecyloxypropionic acid was subjected to digestion by pancreatic lipase. The substance remained unaffected. For an in vivo experiment a doubly labelled homolog, the [1'-14C]decyl ester of 2,3-di[1'-3H]hexadecyloxypropionic acid was synthesized. This compound was fed by stomach tube to three groups of male albino rats. The experimental animals were killed after 2,4 and 6 h, those of the control groups after 6 h. Blood, urine, small intestines and livers were examined for radioactivity. From the recovery rates it could be derived that the molecule had been metabolized and absorbed. Obviously, the alkyl chain labelled with 14C was split off first and the alkyl chains labelled with 3H were split off thereafter. As the substance is metabolized in vivo it cannot be utilized as a 'non-fattening fat'.