Turnover kinetics of Photosystem I measured by the electrochromic effect in Chlorella

The rise kinetics of the absorption changes induced at 515 nm and 480 nm by a flash were studied using two types of xenon flashes of different durations. The ‘slow’ rise of the absorption change ($\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}\text{= 15–20 μ}\text{s}$) observed by Cox and Delosme (1978 C.R. Acad. Sci. (Paris) Sér. D 282, 775–778) and Joliot P., Delosme, R. and Joliot, A. ((1977) Biochim. Biophys. Acta 459, 47–57) was found to be due to double hits occurring in the reaction centers of System I during the flash.The turnover kinetics of the reaction centers of System I after a short flash were studied by a double flash method. They are in agreement with a second order reaction between P⁺-700 and its electron donor.     

Seven-year follow-up of infliximab therapy in rheumatoid arthritis patients with severe long-standing refractory disease: attrition rate and evolution of disease activity

Introduction

This study is based on the results from a Belgian expanded access program in which patients with active refractory and erosive rheumatoid arthritis (RA) were treated with intravenous infusions of infliximab in combination with methotrexate. The objectives of this study were to evaluate the continuation rate of infliximab and its clinical effect over a 7-year period and to document the reasons for discontinuation.

Methods

Between 2000 and 2001, 511 patients with severe and refractory RA were enrolled and treated with infliximab. After 7 years, apart from routine clinical follow-up, treating rheumatologists were asked to complete a questionnaire designed specifically for the present study to evaluate the current therapy with infliximab, the level of disease activity (Disease Activity Score in 28 joints [DAS28]) and the reasons for infliximab discontinuation.

Results

After 7 years, 160 of 511 patients (31%) were still on infliximab treatment. The major reasons for infliximab discontinuation included lack of efficacy (104 patients), adverse events (107 patients) and elective change of therapy (70 patients). The majority of cases of treatment discontinuation for safety reasons occurred during the first 2 years. In contrast, discontinuation due to ineffectiveness showed a more constant rate over the 7-year period. Mean DAS for patients still on treatment with infliximab decreased from 5.7 (standard error [SE] 0.1) at baseline to 3.0 (SE 0.1) at year 4 and remained that low until year 7 (3.0 [SE 0.1]). Low disease activity (defined as DAS28 <3.2) was present in 60.9% of patients, and 45.5% achieved remission (DAS28 <2.6). DAS28 at the time of treatment discontinuation due to ineffectiveness decreased over the 7-year period from 5.6 (SE 0.3) in 2001 to 4.8 (SE 0.3) in 2008.

Conclusions

This observational study revealed that patients who continue to receive infliximab experience sustained clinical benefit. The majority of safety issues occurred during the first 2 years of infliximab therapy. We observed that the DAS at the time of therapy discontinuation showed a trend to decrease over time.     

High levels of Paleolithic Y-chromosome lineages characterize Serbia

Whether present-day European genetic variation and its distribution patterns can be attributed primarily to the initial peopling of Europe by anatomically modern humans during the Paleolithic, or to latter Near Eastern Neolithic input is still the subject of debate. Southeastern Europe has been a crossroads for several cultures since Paleolithic times and the Balkans, specifically, would have been part of the route used by Neolithic farmers to enter Europe. Given its geographic location in the heart of the Balkan Peninsula at the intersection of Central and Southeastern Europe, Serbia represents a key geographical location that may provide insight to elucidate the interactions between indigenous Paleolithic people and agricultural colonists from the Fertile Crescent. In this study, we examine, for the first time, the Y-chromosome constitution of the general Serbian population. A total of 103 individuals were sampled and their DNA analyzed for 104 Y-chromosome bi-allelic markers and 17 associated STR loci. Our results indicate that approximately 58% of Serbian Y-chromosomes (I1-M253, I2a-P37.2 and R1a1a-M198) belong to lineages believed to be pre-Neolithic. On the other hand, the signature of putative Near Eastern Neolithic lineages, including E1b1b1a1-M78, G2a-P15, J1-M267, J2-M172 and R1b1a2-M269 accounts for 39% of the Y-chromosome. Haplogroup frequency distributions in Western and Eastern Europe reveal a spotted landscape of paleolithic Y chromosomes, undermining continental-wide generalizations. Furthermore, an examination of the distribution of Y-chromosome filiations in Europe indicates extreme levels of Paleolithic lineages in a region encompassing Serbia, Bosnia-Herzegovina and Croatia, possibly the result of Neolithic migrations encroaching on Paleolithic populations against the Adriatic Sea.     

Nicotine-induced Ca<Superscript>2+</Superscript>-myristoyl Switch of Neuronal Ca<Superscript>2+</Superscript> Sensor VILIP-1 in Hippocampal Neurons: A Possible Crosstalk Mechanism for Nicotinic Receptors

Visinin-like protein (VILIP-1) belongs to the neuronal Ca²⁺ sensor family of EF-hand Ca²⁺-binding proteins that regulate a variety of Ca²⁺-dependent signal transduction processes in neurons. It is an interaction partner of α4β2 nicotinic acetylcholine receptor (nAChR) and increases surface expression level and agonist sensitivity of the receptor in oocytes. Nicotine stimulation of nicotinic receptors has been reported to lead to an increase in intracellular Ca²⁺ concentration by Ca²⁺-permeable nAChRs, which in turn might lead to activation of VILIP-1, by a mechanism described as the Ca²⁺-myristoyl switch. It has been postulated that this will lead to co-localization of the proteins at cell membranes, where VILIP-1 can influence functional activity of α4-containing nAChRs. In order to test this hypothesis we have investigated whether a nicotine-induced and reversible Ca²⁺-myristoyl switch of VILIP-1 exists in primary hippocampal neurons and whether pharmacological agents, such as antagonist specific for distinct nAChRs, can interfere with the Ca²⁺-dependent membrane localization of VILIP-1. Here we report, that only α7- but not α4-containing nAChRs are able to elicit a Ca²⁺-dependent and reversible membrane-translocation of VILIP-1 in interneurons as revealed by employing the specific receptor antagonists dihydro-beta-erythroidine and methylallylaconitine. The nAChRs are associated with processes of synaptic plasticity in hippocampal neurons and they have been implicated in the pathology of CNS disorders, including Alzheimer’s disease and schizophrenia. VILIP-1 might provide a novel functional crosstalk between α4- and α7-containing nAChRs.     

A QTL on chromosome 3q23 influences processing speed in humans

Processing speed is a psychological construct that refers to the speed with which an individual can perform any cognitive operation. Processing speed correlates strongly with general cognitive ability, declines sharply with age and is impaired across a number of neurological and psychiatric disorders. Thus, identifying genes that influence processing speed will likely improve understanding of the genetics of intelligence, biological aging and the etiologies of numerous disorders. Previous genetics studies of processing speed have relied on simple phenotypes (eg, mean reaction time) derived from single tasks. This strategy assumes, erroneously, that processing speed is a unitary construct. In the present study, we aimed to characterize the genetic architecture of processing speed by using a multidimensional model applied to a battery of cognitive tasks. Linkage and QTL‐specific association analyses were performed on the factors from this model. The randomly ascertained sample comprised 1291 Mexican‐American individuals from extended pedigrees. We found that performance on all three distinct processing‐speed factors (Psychomotor Speed; Sequencing and Shifting and Verbal Fluency) were moderately and significantly heritable. We identified a genome‐wide significant quantitative trait locus (QTL) on chromosome 3q23 for Psychomotor Speed (LOD = 4.83). Within this locus, we identified a plausible and interesting candidate gene for Psychomotor Speed (Z = 2.90, P = 1.86 × 10^?03).