How does a legume nodule work?

Nitrogen fixation in legume root nodules requires biochemical cooperation between the plant and Rhizobium cells. Bacteroids contribute the N₂-fixing system and haem for leghaemoglobin, but apart from the production of the globin moiety of leghaemoglobin and the assimilation and export of the NH₃ produced, little is known about the contributions of the plant. It now appears that the plant cell may regulate the type and/or quantity of carbon compounds supplied to the Rhizobium bacteroids.     

How does gene expression clustering work?

Clustering is often one of the first steps in gene expression analysis. How do clustering algorithms work, which ones should we use and what can we expect from them?     

The increased cardiovascular risk in rheumatoid arthritis: when does it start?

Established rheumatoid arthritis (RA) is associated with a doubled cardiovascular risk. However, data about the cardiovascular risk in early RA are scarce. Preclinical atherosclerosis can be reliably assessed with the carotid intima media thickness (cIMT), and the cIMT is a well-validated predictor of cardiovascular events. The cIMT was therefore used in a recent controlled, prospective study in patients with early RA. Surprisingly, an increased cardiovascular risk at baseline could not be demonstrated whereas cIMT progression appeared to be comparable with the general population. Obviously, this study underscores the need for further large-scale investigations to solve the emerging discrepancy with the existing literature.     

What is MRI bone oedema in rheumatoid arthritis and why does it matter?

MRI bone oedema occurs in various forms of inflammatory and non-inflammatory arthritis and probably represents a cellular infiltrate within bone. It is common in early rheumatoid arthritis and is associated with erosive progression and poor functional outcome. Histopathological studies suggest that a cellular infiltrate comprising lymphocytes and osteoclasts may be detected in subchondral bone and could mediate the development of erosions from the marrow towards the joint surface. There is emerging evidence from animal models that such an infiltrate corresponds with MRI bone oedema, pointing towards the bone marrow as a site for important pathology driving joint damage in rheumatoid arthritis.     

What is MRI bone oedema in rheumatoid arthritis and why does it matter?

MRI bone oedema occurs in various forms of inflammatory and non-inflammatory arthritis and probably represents a cellular infiltrate within bone. It is common in early rheumatoid arthritis and is associated with erosive progression and poor functional outcome. Histopathological studies suggest that a cellular infiltrate comprising lymphocytes and osteoclasts may be detected in subchondral bone and could mediate the development of erosions from the marrow towards the joint surface. There is emerging evidence from animal models that such an infiltrate corresponds with MRI bone oedema, pointing towards the bone marrow as a site for important pathology driving joint damage in rheumatoid arthritis.     

How to manage rheumatoid arthritis according to classic biomarkers and polymorphisms?

Objectives

Single nucleotide polymorphisms (SNPs), genetic background, and epigenetics play important roles in rheumatoid arthritis (RA). These factors can be useful in RA diagnosis, prognosis, and treatment response evaluation, particularly with the growing trends in personalized medicine. Therefore, categorizing classic genes and SNPs in RA can present an appropriate guideline for RA management.

Discussion

Prognostic and diagnostic biomarkers play important roles in RA diagnosis and treatment. Categorizing SNPs is not an easy process yet, but selecting classic SNPs can be useful worldwide, according to basic similarities that exist in genomes. In this review, we compiled some of these RA-associated SNPs and biomarkers in a table, according to newly identified factors. The role of epigenetics in RA is undeniable; using epigenetic biomarkers like histone deacetylase (HDACs) can be useful in RA diagnosis and treatment. miRs such as miR-146a, miR-155, and miR-222 are useful in diagnosis and can be used in treatment by interfering with other factors’ functions. Interleukins (ILs) seem to be good prognostic and diagnostic markers and can be targeted in RA treatment.

Conclusion

Using multiple types of biomarkers, such as genes, SNPs, and epigenetic biomarkers like HDACs can be useful in RA management and treatment. PTPN22, HLA-DR polymorphisms, miRs, and HDACs are considerable in RA susceptibility; hence, they can be valuable biomarkers in future studies. This article gathered separate information from approximately 100 articles to present useful biomarkers and polymorphisms in one review.

     

Cytokines in rheumatoid arthritis: is it all TNF-alpha?

Anti-TNF-alpha therapy has shown clear efficacy in the treatment of rheumatoid arthritis (RA). Since some patients do not respond and the treatment is suspensive, combination therapy may be of interest. Other cytokines produced by monocytes such as IL-1, IL-12, IL-18 are also involved. The secretion of these cytokines is regulated by subsets of T-lymphocytes. Among these, IL-17 producing Th1 cells appear to contribute directly to the destructive process. Furthermore, this T-cell contribution enhances the action of monocyte derived proinflammatory cytokines. Using models of human RA synovium inflammation and bone resorption, ex vivo results suggest that combination therapy may be of interest. Acting on more than one cytokine may increase the percentage of responding RA patients as well as the degree of individual patient response.     

Interleukin-18: a therapeutic target in rheumatoid arthritis?

Interleukin 18 (IL-18), a member of the IL-1 superfamily of cytokines has been demonstrated to be an important mediator of both innate and adaptive immune responses. Several reports have implicated its role in the pathogenesis of rheumatoid arthritis (RA). Although biologic therapy is firmly established in the treatment of a number of inflammatory diseases including RA, partial and non-responder patients constitute residual unmet clinical need. The aim of this article is to briefly review the biology of, and experimental approaches to IL-18 neutralisation, together with speculation as to the relative merits of IL-18 as an alternative to existing targets.     

Which component of sulphasalazine is active in rheumatoid arthritis?

Sulphasalazine is known to be effective as a second line agent in the treatment of rheumatoid arthritis. The two chemical constituents of sulphasalazine (sulphapyridine and 5-aminosalicylic acid) were assessed separately in the treatment of rheumatoid arthritis. Over 24 weeks sulphapyridine showed a pronounced second line effect comparable with sulphasalazine and with a similar toxicity profile, whereas 5-aminosalicylic acid showed only a weak first line effect. Thus sulphapyridine appears to be the active moiety responsible for the second line effect of sulphasalazine in rheumatoid arthritis. The efficacy of the antibacterial component of sulphasalazine yet again permits speculation about the role of a bacterial pathogen in the aetiopathogenesis of rheumatoid disease.     

Androgens in rheumatoid arthritis: when are they effectors?

Neither hormone receptor genes nor plasma androgens seem significantly altered in female subjects before they became affected by rheumatoid arthritis (RA) and, therefore, do not seem to play a role as risk factors for its development. However, serum testosterone levels are inversely correlated with RA activity and dehydro-epiandrosterone sulfate (DHEAS) plasma levels are inversely correlated with both disease duration and clinical severity in patients already affected by active RA. In particular, gonadal and adrenal androgens (that is, testosterone and DHEAS) are significantly decreased in inflamed synovial tissue/fluids during active disease as a consequence of the inflammatory reaction, which supports a pro-inflammatory milieu in RA joints. Recently, male gender has been found to be a major predictor of remission in early RA.     

Interleukin-18: a therapeutic target in rheumatoid arthritis?

Interleukin 18 (IL-18), a member of the IL-1 superfamily of cytokines has been demonstrated to be an important mediator of both innate and adaptive immune responses. Several reports have implicated its role in the pathogenesis of rheumatoid arthritis (RA). Although biologic therapy is firmly established in the treatment of a number of inflammatory diseases including RA, partial and non-responder patients constitute residual unmet clinical need. The aim of this article is to briefly review the biology of, and experimental approaches to IL-18 neutralisation, together with speculation as to the relative merits of IL-18 as an alternative to existing targets.     

Modulating social behavior with oxytocin: How does it work? What does it mean?

Among its many roles in body and brain, oxytocin influences social behavior. Understanding the precise nature of this influence is crucial, both within the broader theoretical context of neurobiology, social neuroscience and brain evolution, but also within a clinical context of disorders such as anxiety, schizophrenia, and autism. Research exploring oxytocin's role in human social behavior is difficult owing to its release in both body and brain and its interactive effects with other hormones and neuromodulators. Additional difficulties are due to the intricacies of the blood-brain barrier and oxytocin's instability, which creates measurement issues. Questions concerning how to interpret behavioral results of human experiments manipulating oxytocin are thus made all the more pressing. The current paper discusses several such questions. We highlight unresolved fundamental issues about what exactly happens when oxytocin is administered intranasally, whether such oxytocin does in fact reach appropriate receptors in brain, and whether central or peripheral influences account for the observed behavioral effects. We also highlight the deeper conceptual issue of whether the human data should be narrowly interpreted as implicating a specific role for oxytocin in complex social cognition, such a generosity, trust, or mentalizing, or more broadly interpreted as implicating a lower-level general effect on general states and dispositions, such as anxiety and social motivation. Using several influential studies, we show how seemingly specific, higher-level social-cognitive effects can emerge via a process by which oxytocin's broad influence is channeled into a specific social behavior in a context of an appropriate social and research setting. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.