2D protein electrophoresis: can it be perfected?

23 years after O'Farrel developed two-dimensional gel electrophoresis we still debate if the technique can be improved, or if there are other alternative separation technologies that can challenge its central position in proteomic projects. These questions are relevant as the pharmaceutical industry expects proteomic studies to provide novel protein targets for drug discovery and diagnostics. In our opinion, there are various aspects of the technology that can be improved, including resolution, sample preparation and detection, but so far there is no alternative technique(s) available, or any under development, that can replace it.     

Ensuring quality and access for malaria diagnosis: how can it be achieved?

The replacement of conventional antimalarial drugs with high-cost, artemisinin-based alternatives has created a gap in the successful management of malaria. This gap reflects an increased need for accurate disease diagnosis that cannot be met by traditional microscopy techniques. The recent introduction of rapid diagnostic tests (RDTs) has the potential to meet this need, but successful RDT implementation has been curtailed by poor product performance, inadequate methods to determine the quality of products and a lack of emphasis and capacity to deal with these issues. Economics and a desire for improved case management will result in the rapid growth of RDT use in the coming years. However, for their potential to be realized, it is crucial that high-quality RDT products that perform reliably and accurately under field conditions are made available. In achieving this goal, the shift from symptom-based diagnosis to parasite-based management of malaria can bring significant improvements to tropical fever management, rather than represent a further burden on poor, malaria-endemic populations and their overstretched health services.     

The OXE receptor: a new therapeutic approach for asthma?

The eicosanoid 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) has recently been identified as the ligand for the oxoeicosanoid (OXE) receptor. In vitro and in vivo studies have suggested that 5-oxo-ETE has a role in the asthmatic inflammatory response and it has been shown to stimulate eosinophil migration to the airways. New data suggest that eosinophils have an important role in the pathogenesis of asthma, being required for mucus accumulation, airway hyperresponsiveness and remodelling of the airways. However, there are several mediators that can stimulate the recruitment of eosinophils to the airways and the development of antagonists against the OXE receptor is required to evaluate the potential of the OXE receptor as a new therapeutic approach for asthma.     

MSCs and hyaluronan: Sticking together for new therapeutic potential?

Research involving mesenchymal multipotent/stem/progenitor/stromal/marrow cells (MSCs) have translated to clinical trials at an extraordinary pace. By the time of this review, the public clinical trials database (http://clinicaltrials.gov) has 394 clinical trials listed using MSCs for a very wide range of therapeutic applications. Unexpectedly, the explanation for the increase in clinical trials using MSCs does not lie on a well-defined therapeutic mechanism – dramatic results have been demonstrated in a variety of studies involving different animal models of diseases, often describing discrete therapeutic mechanisms exerted by MSCs. This review will focus on recent data suggesting the involvement of hyaluronic acid (HA) in the beneficial effects of MSCs, evaluate the potential of MSC as modulators of HA and the implications of this modulation for disease therapy.     

What is a desirable statistical energy functions for proteins and how can it be obtained?

Can one obtain a physical energy function for proteins from statistical analysis of protein structures? A direct answer to this question is likely “no”. A less demanding question is whether one can produce a statistical energy function that has the desirable features of a physical-based energy function. Such a desirable energy function would be founded on a physical basis with few or no adjustable parameters, reproduce the known physical characters of amino acid residues, be mostly database independent and transferable, and, more importantly, reasonably accurate in various applications. In this review, we show how such a desirable energy function can be obtained via introducing a simple physical-based reference state called DRIRE (Distance-scaled, Finite, Ideal-gas Reference state).     

The HDL receptor SR-BI: a new therapeutic target for atherosclerosis?

Although high-density lipoprotein (HDL) metabolism is a crucial process for cholesterol homeostasis and coronary heart disease, therapeutic approaches for selective modification of plasma HDL levels are not currently available. The discovery of well-defined cell-surface HDL receptors should provide new avenues for treatment of atherosclerotic cardiovascular disease. In fact, SR-BI, a recently identified receptor for selective HDL cholesterol uptake, is relevant for physiological processes (for example, HDL metabolism, steroidogenesis and biliary cholesterol secretion) and pathophysiological conditions (for example, atherosclerosis) in animal models. If SR-BI has similar activities in humans, it might represent a new therapeutic target for atherosclerosis.     

Human cloning: can it be made safe?

There are continued claims of attempts to clone humans using nuclear transfer, despite the serious problems that have been encountered in cloning other mammals. It is known that epigenetic and genetic mechanisms are involved in clone failure, but we still do not know exactly how. Human reproductive cloning is unethical, but the production of cells from cloned embryos could offer many potential benefits. So, can human cloning be made safe?     

Marine microbial diversity: can it be determined?

Estimates of the order of magnitude for the total number of microbial species on Earth range from 10(3) to 10(9). Despite global dispersal of microorganisms, this number is probably rather large. The total biodiversity of an ecosystem is composed of two elements: first, a set of abundant taxa that carry out most ecosystem functions, grow actively and suffer intense losses through predation and viral lysis. These taxa are retrievable with molecular techniques but are difficult to grow in culture. Second, there is a seed bank of many rare taxa that are not growing or grow extremely slowly, do not experience viral lysis and predation is reduced. Such taxa are seldom retrieved by molecular techniques but many can be grown in culture, which explains the dictum 'everything is everywhere'.     

Remission in psoriatic arthritis: is it possible and how can it be predicted?

Introduction

Since remission is now possible in psoriatic arthritis (PsA) we wished to examine remission rates in PsA patients following anti tumour necrosis factor alpha (TNFα) therapy and to examine possible predictors of response.

Methods

Analysis of a prospective patient cohort attending a biologic clinic, between November 2004 and March 2008, was performed prior to commencing therapy and at regular intervals. Baseline clinical characteristics including demographics, previous disease-modifying antirheumatic drug (DMARD) response, tender and swollen joint counts, early morning stiffness, pain visual analogue score, patient global assessment, C reactive protein (CRP) and health assessment questionnaire (HAQ) were collected.

Results

A total of 473 patients (152 PsA; 321 rheumatoid arthritis (RA)) were analyzed. At 12 months remission, defined according to the disease activity score using 28 joint count and CRP (DAS28-CRP), was achieved in 58% of PsA patients compared to 44% of RA patients, significant improvement in outcome measures were noted in both groups (P < 0.05). Analysis of a subgroup of PsA and RA patients matched for DAS28-CRP at baseline also showed higher numbers of PsA patients achieving remission. Linear regression analysis identified the HAQ at baseline as the best predictor of remission in PsA patients (P < 0.001).

Conclusions

DAS28 remission is possible in PsA patients at one year following anti-TNF therapy, at higher rates than in RA patients and is predicted by baseline HAQ.     

Antibody response and therapy in COVID-19 patients: what can be learned for vaccine development?

Science China Life Sciences - The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide....     

Cholesterol: a potential therapeutic target in Leishmania infection?

Leishmania are obligate intracellular parasites that invade and survive within host macrophages and can result in visceral leishmaniasis, a major public health problem worldwide. The entry of intracellular parasites, in general, involves interaction with the plasma membrane of host cells. Cholesterol in host cell membranes was recently shown to be necessary for binding and internalization of Leishmania and for the efficient presentation of leishmanial antigens in infected macrophages. This article describes the need to explore cyclodextrin-based compounds, which modulate host membrane cholesterol levels, as a possible therapeutic strategy against leishmaniasis in addition to other intracellular parasites.     

Nuclear architecture: Is it important for genome function and can we prove it?

Gene regulation in higher eukaryotes has been shown to involve regulatory sites, such as promoters and enhancers which act at the level of individual genes, and mechanisms which control the functional state of gene clusters. A fundamental question is whether additional levels of genome control exist. Nuclear organization and large-scale chromatin structure may constitute such a level and play an important role in the cell-type specific orchestration of the expression of thousands of genes in eukaryotic cells. Numerous observations indicate a tight correlation between genome activity and nuclear and large-scale chromatin structure. However, causal relationships are rare. Here we explore how these might be uncovered.     

Self-efficacy and diabetes: why is emotional 'education' important and how can it be achieved?

Adequate age-appropriate diabetes knowledge and skills are essential to the success of diabetes self- and parental care. Health professionals have a central role in providing diabetes education. A direct link between diabetes knowledge and diabetes regimen behaviour cannot be assumed. Health professionals have to help children and their parents to develop the emotional concept of 'self-efficacy for diabetes self-care', to ensure optimal diabetes control.