Two-dimensional localization in GeSn.

Localization behaviour is a characteristic feature of thep-type GeSn quantum well (QW) system in a metal-insulator-semiconductor device. The transition to strongly localized behaviour is abrupt with thermally activated conductivity and a high temperature intercept of 0.12 ×e2h-1at a hole carrier density 1.55 × 1011cm-2. The activation energy for the conductivity in the localized state is 0.40 ± 0.05 meV compared to an activation energy of ∼0.1 meV for conductivity activation to a mobility edge at carrier densities >1.55 × 1011cm-2. Insulating behaviour can occur from a system that behaves as though it is in a minimum metallic state, albeit at high temperature, or from a conductivity greater than a minimum metallic state behaviour showing that local disorder conditions with local differences in the density of states are important for the onset of localization. In the presence of a high magnetic field, thermally activated conductivity is present down to Landau level filling factor <1/2but without a magnetic-field-dependent carrier density or a variable range hopping (VRH) transport behaviour developing even with conductivity ≪e2h-1. In the localized transport regime inp-type doped Ge0.92Sn0.08QWs the VRH mechanism is suppressed at temperatures >100 mK and this makes this two-dimensional system ideal for future many body localization studies in disordered hole gases that can be thermally isolated from a temperature reservoir.

Regenerative medicines: A new regulatory paradigm for South Africa.

Clinicians are increasingly using regenerative medicines to repair, replace, regenerate or rejuvenate lost, damaged or diseased genes, cells, tissues or organs. In South Africa, access to these novel gene therapies and cell and tissue-based products is limited. The human leukocyte antigen (HLA) diversity and a paucity of suitable HLA-identical unrelated donors, results in limited access to haematopoietic stem and progenitor cell transplantation (HSPCT). Cell-based products could increase this access. Genetic diversity can also manifest in local or region-specific rare congenital disorders, and in vivo gene therapies hold the promise of developing treatments and cures for these debilitating disorders. South Africa has a disproportionate mortality rate due to non-natural causes, with many surviving with permanent injuries and disabilities. Tissue-engineered cell-based products have the potential to restore many of those affected and improve quality of life and productivity. These factors create an urgency for South Africa to develop regenerative medicines to address the country's unique needs and to provide access to these new and innovative treatment modalities. Achieving this objective requires a well-coordinated effort by multiple stakeholders and role players. A critical component of a regenerative medicine ecosystem is establishing an enabling regulatory framework for these new classes of medicines. Here we provide a brief profile of South Africa, including its genetic diversity, economy, the impact of the burden of disease, health policy and the healthcare system. We address the regulation of medicines, how the existing framework can accommodate regenerative medicines, and the steps needed to establish a future regulatory framework.

Mesenchymal Stromal Cells: a Possible Reservoir for HIV-1?

The introduction of antiretroviral therapy (ART) and highly active antiretroviral therapy (HAART) has transformed human immunodeficiency virus (HIV)-1 into a chronic, well-managed disease. However, these therapies do not eliminate all infected cells from the body despite suppressing viral load. Viral rebound is largely due to the presence of cellular reservoirs which support long-term persistence of HIV-1. A thorough understanding of the HIV-1 reservoir will facilitate the development of new strategies leading to its detection, reduction, and elimination, ultimately leading to curative therapies for HIV-1. Although immune cells derived from lymphoid and myeloid progenitors have been thoroughly studied as HIV-1 reservoirs, few studies have examined whether mesenchymal stromal/stem cells (MSCs) can assume this function. In this review, we evaluate published studies which have assessed whether MSCs contribute to the HIV-1 reservoir. MSCs have been found to express the receptors and co-receptors required for HIV-1 entry, albeit at levels of expression and receptor localisation that vary considerably between studies. Exposure to HIV-1 and HIV-1 proteins alters MSC properties in vitro, including their proliferation capacity and differentiation potential. However, in vitro and in vivo experiments investigating whether MSCs can become infected with and harbour latent integrated proviral DNA are lacking. In conclusion, MSCs appear to have the potential to contribute to the HIV-1 reservoir. However, further studies are needed using techniques such as those used to prove that cluster of differentiation (CD)4+ T cells constitute an HIV-1 reservoir before a reservoir function can definitively be ascribed to MSCs. MSCs may contribute to HIV-1 persistence in vivo in the vasculature, adipose tissue, and bone marrow by being a reservoir for latent HIV-1. To harbour latent HIV-1, MSCs must express HIV-1 entry markers, and show evidence of productive or latent HIV-1 infection. The effect of HIV-1 or HIV-1 proteins on MSC properties may also be indicative of HIV-1 infection.

When cells become medicines: A South African perspective.

The discovery of human leucocyte antigen (HLA), serological matching and HLA-typing techniques, combined with the development of immunosuppressive medicines and improvements in infection control, have opened the way to cell, tissue and vascularised organ transplantation. Since the early 1960s, more than a million haematopoietic progenitor cell (HPC) transplantations have been performed worldwide to restore haematopoiesis and support immune system recovery after bone marrow ablation. HPC transplantation uses minimally manipulated autologous or allogeneic cells to restore the homologous functions of bone marrow. Research in biological sciences supported by new technologies is increasingly translated into therapeutic products intended to augment, repair, replace or regenerate genes, cells, tissues, organs and metabolic processes in the body. These products are referred to as regenerative medicine therapies or advanced therapy medicinal products, and include gene therapies, cell-based therapies and engineered tissue products.

Viruses, variants and vaccines.

The current SARS-CoV-2 pandemic has brought a number of major global clinical, sociological and economic issues into sharp focus. We address some of these issues, focusing on short-term factors such as virus mutations and vaccine efficacy, and also considering the longer-term implications of the current pandemic. We discuss societal responses to the presence of a pathogen that will probably remain in circulation for decades or longer, and to future new emergent viruses.

Interactions and non-magnetic fractional quantization in one-dimension.

In this Perspective article, we present recent developments on interaction effects on the carrier transport properties of one-dimensional (1D) semiconductor quantum wires fabricated using the GaAs/AlGaAs system, particularly the emergence of the long predicted fractional quantization of conductance in the absence of a magnetic field. Over three decades ago, it was shown that transport through a 1D system leads to integer quantized conductance given by N·2e2/h, where N is the number of allowed energy levels (N = 1, 2, 3, …). Recent experiments have shown that a weaker confinement potential and low carrier concentration provide a testbed for electrons strongly interacting. The consequence leads to a reconfiguration of the electron distribution into a zigzag assembly which, unexpectedly, was found to exhibit quantization of conductance predominantly at 1/6, 2/5, 1/4, and 1/2 in units of e2/h. These fractional states may appear similar to the fractional states seen in the Fractional Quantum Hall Effect; however, the system does not possess a filling factor and they differ in the nature of their physical causes. The states may have promise for the emergent topological quantum computing schemes as they are controllable by gate voltages with a distinct identity.

The impact of obesity on the cellular and molecular pathophysiology of COVID-19.

Emerging evidence reveals a strong association between COVID-19 and obesity in terms of disease severity, need for hospitalisation and risk of mortality. In this review, we discuss cellular and molecular mechanisms potentially contributing to the pathophysiology of COVID-19 in obese patients. Understanding the relationship between COVID-19 and obesity is pertinent for the clinical management of these patients.

Research in COVID-19 times: The way forward.

The COVID-19 pandemic has had a major impact on research at universities. Universities around the world, including in South Africa, have been or are still closed as part of national lockdown strategies. Students have not been attending classes or doing hands-on experimental work, and students and academics have been working from home. Many thousands of students have had their university education interrupted, and for them, the resumption of learning programmes online, and where possible in research laboratories, is critically important. There is no question that as we emerge from lockdown we will not be entering a world that resembles a 'norm' as lived in the pre-COVID-19 era, and many changes will be required. Here we discuss the importance of research, the urgency to get things up and running again, and strategies that will need to be implemented to ensure that research activities continue. At the same time, it is necessary to ensure that students and staff are not exposed to risk in their research endeavours, which will require the development and implementation of risk management plans.

A prospective observational study of developmental outcomes in survivors of neonatal hypoxic ischaemic encephalopathy in South Africa.

BACKGROUND: Neonatal hypoxic ischaemic encephalopathy (NHIE) is an important cause of long-term handicap in survivors. There is limited information on the burden of handicap from NHIE in sub-Saharan Africa. OBJECTIVES: To determine the developmental outcomes in survivors of NHIE in South Africa (SA). METHODS: In this prospective observational study, the developmental outcomes in 84 infants who had survived hypoxic ischaemic encephalopathy (the NHIE group) were compared with those in 64 unaffected infants (the control group). The Bayley Scales of Infant Development version III were used for assessment of developmental outcomes. RESULTS: Significant differences were found between the developmental outcomes of the two groups, with a significantly lower composite language score and higher proportions with language, motor and cognitive developmental delays in the NHIE group than in the control group. Cerebral palsy (CP) was present in 13 of the infants with NHIE (15.5%) and none in the control group (p<0.001). CP was associated with developmental delay, and also with the severity of NHIE. Therapeutic hypothermia (TH) was administered in 58.3% of the study group, but although it was associated with lower rates of CP and developmental delay than in the group without TH, the only significant difference was for delay on the language subscale. CONCLUSIONS: Survivors of NHIE in SA are at risk of poor developmental outcomes.

Privacy rights of human research participants in South Africa must be taken seriously.

Letter by Thaldar and Townsend, following an article by the same authors (Thaldar D, Townsend B. Genomic research and privacy: A response to Staunton et al. S Afr Med J 2020;110(3):172-174. https://doi.org/10.7196/SAMJ.2020.v110i3.14431) and both commenting on an article by Staunton et al. (Staunton C, Adams R, Botes M, et al. Safeguarding the future of genomic research in South Africa: Broad consent and the Protection of Personal Information Act No. 4 of 2013. S Afr Med J 2019;109(7):468-470. https://doi.org/10.7196/SAMJ.2019.v109i7.14148); and response to article and letter by Staunton et al.

The impact of obesity on the cellular and molecular pathophysiology of COVID-19.

Emerging evidence reveals a strong association between COVID-19 and obesity in terms of disease severity, need for hospitalisation and risk of mortality. In this review, we discuss cellular and molecular mechanisms potentially contributing to the pathophysiology of COVID-19 in obese patients. Understanding the relationship between COVID-19 and obesity is pertinent for the clinical management of these patients.

Rapid evolution of our understanding of the pathogenesis of COVID-19: Implications for therapy.

COVID-19 severity appears to lie in its propensity to cause a hyperinflammatory response, attributed to the cytokine release syndrome (CRS) or 'cytokine storm', although the exact role of the CRS remains to be fully elucidated. Hyperinflammation triggers a hypercoagulable state, also thought to play a key role in COVID-19 pathogenesis. Disease severity is linked to age, sex and comorbid conditions, which in turn may be linked to oxidative stress and pre-existing depletion of nicotinamide adenine dinucleotide (NAD+). There is increasing evidence that the host genome may determine disease outcome. Since most information pertaining to COVID-19 has thus far been extrapolated from the 'global North', similar studies in African populations are warranted. Many studies are aimed at finding a therapeutic strategy based on scientific rationale. Some promising results have emerged, e.g. the use of corticosteroids in severe acute respiratory distress syndrome (ARDS).

The Effect of Early Rounds of ex vivo Expansion and Cryopreservation on the Adipogenic Differentiation Capacity of Adipose-Derived Stromal/Stem Cells.

Multipotent adipose-derived stromal/stem cells (ASCs) are candidates for use in cellular therapies for the treatment of a variety of conditions/diseases. Ex vivo expansion of freshly isolated ASCs may be necessary prior to clinical application to ensure that clinically relevant cell numbers are administered during treatment. In addition, cryopreserving cells at early passages allows for storage of freshly isolated cells for extended periods of time before expanding these cells for clinical usage. There are however several concerns that these laboratory-based procedures may alter the characteristics of the cells and in so doing decrease their regenerative potential. In this study we report on the impact of early rounds of cryopreservation (P0) and ex vivo expansion (P0 to P5) on the phenotypic characteristics and adipogenic differentiation potential of ASCs. Our results show that ASCs that upregulate CD36 expression during adipogenic differentiation gradually decrease with increasing expansion rounds. The consequent decrease in adipogenic differentiation capacity was evident in both gene expression and flow cytometry-based phenotypic studies. Successive rounds of expansion did not however alter cell surface marker expression of the cells. We also show that early cryopreservation of ASCs (at P0) does not affect the adipogenic differentiation potential of the cells.

Primary immunodeficiency in Africa - a review.

BACKGROUND: Efforts have been made worldwide to improve awareness and treatment of primary immunodeficiency (PID). This has also gained momentum on the African continent albeit at a slower pace. Objective. This review reports on the current status of PID on the African continent regarding its prevalence, distribution, genetic mutations and challenges in diagnosis and treatment of affected patients. Method. We evaluated all studies published from the African continent in the field of PID dealing with prevalence, epidemiology, case reports and genetic findings. Results. The prevalence of PID on the African continent has been estimated to be as high as 902 631 individuals. PID still is mostly underdiagnosed in Africa and although progress has been made in parts of the continent many challenges still remain regarding awareness, diagnosis, registration and care of these patients. Conclusion. Given the unique genetic mutations reported in PID patients on the African continent and the feasibility of hematopoietic stem cell transplantation and gene therapy, increased awareness should be encouraged and new therapeutic options considered.

Gene and cell therapy in South Africa: Current status and future prospects.

South Africa has a high disease burden resulting from communicable and non-communicable diseases. Current therapeutic interventions rarely result in a cure and the associated lifelong treatment places a considerable strain on an overburdened health sector. Gene and cell therapies present novel alternatives to disease management, offering the promise of a single treatment and a lifelong cure. Although challenges remain, investment in the field has started to bear fruit, with a number of gene and cell therapeutics reaching the market in the past decade. To take full advantage of these developments, it is important that a proactive approach to nurturing appropriate human and material resources is adopted in the country.

Human leukocyte antigen (HLA) diversity and clinical applications in South Africa.

The major histocompatibility complex, known as the human leukocyte antigen (HLA) complex in humans, forms an integral component of adaptive T cell immunity by presenting self and non-self peptides to the T cell receptor, thereby allowing clonal expansion of responding peptide-specific CD4+ and CD8+ T cells. HLA likewise forms an integral part of the innate immune response through the binding of killer-cell immunoglobulin-like receptor (KIR) molecules, which regulate the response of natural killer (NK) cells. The HLA complex is found on the short arm of chromosome 6 and is the most polymorphic region in the human genome. Africans are genetically more diverse than other populations; however, information on HLA diversity among southern Africans, including South African populations, is limited. Paucity of African HLA data limits our understanding of disease associations, the ability to identify donor-recipient matches for transplantation and the development of disease-specific vaccines. This review discusses the importance of HLA in the clinical setting in South Africans and highlights how tools such as HLA imputation might augment standard HLA typing methods to increase our understanding of HLA diversity in our populations, which will better inform disease association studies, donor recruitment strategies into bone marrow registries and our understanding of human genetic diversity in South Africa.