Role of steroids and immunosuppression and effects of interferon beta-1b in multiple sclerosis.

Corticosteroids, corticotropin, azathioprine, cyclophosphamide, and IFN-beta 1b have each had a substantial effect on the care of patients with multiple sclerosis and the design of subsequent clinical trials of experimental therapeutics for MS. The use of MRI scanning and more sensitive clinical outcome measures will possibly enable us to complete clinical trials in a fraction of the time required for earlier trials. The release of Betaseron, which favorably alters the attack rate in ambulatory patients with relapsing-remitting MS has brought a sense of renewed optimism to patients with MS, their families, and their care providers. New promising therapies for chronic progressive MS and biologic products possibly capable of enhancing the effects of IFN-beta 1b in patients with relapsing MS are setting the stage for additional important therapeutic advances in this disease.     

Coral-associated nitrogen fixation rates and diazotrophic diversity on a nutrient-replete equatorial reef

The role of diazotrophs in coral physiology and reef biogeochemistry remains poorly understood, in part because N₂ fixation rates and diazotrophic community composition have only been jointly analyzed in the tissue of one tropical coral species. We performed field-based ¹⁵N₂ tracer incubations during nutrient-replete conditions to measure diazotroph-derived nitrogen (DDN) assimilation into three species of scleractinian coral (Pocillopora acuta, Goniopora columna, Platygyra sinensis). Using multi-marker metabarcoding (16S rRNA, nifH, 18S rRNA), we analyzed DNA- and RNA-based communities in coral tissue and skeleton. Despite low N₂ fixation rates, DDN assimilation supplied up to 6% of the holobiont’s N demand. Active coral-associated diazotrophs were chiefly Cluster I (aerobes or facultative anaerobes), suggesting that oxygen may control coral-associated diazotrophy. Highest N₂ fixation rates were observed in the endolithic community (0.20 µg N cm⁻² per day). While the diazotrophic community was similar between the tissue and skeleton, RNA:DNA ratios indicate potential differences in relative diazotrophic activity between these compartments. In Pocillopora, DDN was found in endolithic, host, and symbiont compartments, while diazotrophic nifH sequences were only observed in the endolithic layer, suggesting a possible DDN exchange between the endolithic community and the overlying coral tissue. Our findings demonstrate that coral-associated diazotrophy is significant, even in nutrient-rich waters, and suggest that endolithic microbes are major contributors to coral nitrogen cycling on reefs.Subject terms: Microbial ecology, Biogeochemistry, Stable isotope analysis     

CC-chemokine receptor 5 polymorphism and age of onset in familial multiple sclerosis

 Multiple sclerosis (MS) is a common disease of the central nervous system characterized by myelin loss and progressive neurological dysfunction. An underlying genetic susceptibility plays a clear role in the etiology of MS, likely acting in concert with an undefined environmental exposure. Full-genome screenings in multiplex MS families have identified several susceptibility regions, supporting a polygenic model for MS. Among these regions, evidence for weak linkage was observed at 3p/3cen suggesting the presence of an MS gene(s) of modest effect. Encoded here are two chemokine receptors, CCR5 and CCR2B. We examined the chromosome 3p21–24 region in 125 MS families (322 total affecteds and 200 affected sib-pairs), and performed genetic analyses of CCR5 and CCR2B loci and two nearby markers (D3S1289 and D3S1300) using both linkage- and association-based tests. No evidence of linkage to MS was observed for any of the tested markers. Affected relative-pair (SimIBD) and sib-pair analyses (ASPEX), and association testing (sib-TDT) for each locus were also not significant. However, age of onset was approximately 3 years later in patients carrying the CCR5 Δ 32 deletion (P=0.018 after controlling for gender effects). Thus, chemokine receptor expression may be associated with differential disease onset in a subset of patients, and may provide a therapeutic target to modulate inflammatory demyelination. Received: 27 October 1999 / Revised: 9 December 1999     

STUDIES ON ACETYLCHOLINESTERASE OF RAT BRAIN SYNAPTOSOMAL PLASMA MEMBRANES

Abstract— A fluorimetric assay has been used to examine some kinetic properties of AChE from synaptosomal plasma membranes prepared from rat brain. The AChE bound to the plasma membranes was compared to that solubilized with Triton X-100 and found to be essentially the same with respect to Michaelis constant and inhibitor constants for several AChE inhibitors. The two forms of the enzyme had slightly different pH optima. The kinetic studies revealed no evidence that synaptosomal plasma membrane AChE has allosteric properties. The solubilized enzyme was further purified by affinity chromatography.     

Prolonged Grief Disorder: Psychometric Validation of Criteria Proposed for DSM-V and ICD-11

Background

Bereavement is a universal experience, and its association with excess morbidity and mortality is well established. Nevertheless, grief becomes a serious health concern for a relative few. For such individuals, intense grief persists, is distressing and disabling, and may meet criteria as a distinct mental disorder. At present, grief is not recognized as a mental disorder in the DSM-IV or ICD-10. The goal of this study was to determine the psychometric validity of criteria for prolonged grief disorder (PGD) to enhance the detection and potential treatment of bereaved individuals at heightened risk of persistent distress and dysfunction.

Methods and Findings

A total of 291 bereaved respondents were interviewed three times, grouped as 0–6, 6–12, and 12–24 mo post-loss. Item response theory (IRT) analyses derived the most informative, unbiased PGD symptoms. Combinatoric analyses identified the most sensitive and specific PGD algorithm that was then tested to evaluate its psychometric validity. Criteria require reactions to a significant loss that involve the experience of yearning (e.g., physical or emotional suffering as a result of the desired, but unfulfilled, reunion with the deceased) and at least five of the following nine symptoms experienced at least daily or to a disabling degree: feeling emotionally numb, stunned, or that life is meaningless; experiencing mistrust; bitterness over the loss; difficulty accepting the loss; identity confusion; avoidance of the reality of the loss; or difficulty moving on with life. Symptoms must be present at sufficiently high levels at least six mo from the death and be associated with functional impairment.

Conclusions

The criteria set for PGD appear able to identify bereaved persons at heightened risk for enduring distress and dysfunction. The results support the psychometric validity of the criteria for PGD that we propose for inclusion in DSM-V and ICD-11. Please see later in the article for Editors'' Summary     

Sub-annual fluorescence measurements of coral skeleton: relationship between skeletal luminescence and terrestrial humic-like substances

Coral Reefs - Some massive coral core slices reveal luminescent bands under ultraviolet light, which have been attributed to terrestrial humic acids in the skeleton. Coral luminescence has...