University of Coimbra

About: University of Coimbra is a education organization based out in Coimbra, Portugal. It is known for research contribution in the topics: Population & Context (language use). The organization has 14318 authors who have published 43067 publications receiving 994733 citations. The organization is also known as: UC & Universidade dos Estudos Gerais.

Structure of mycobacterial maltokinase, the missing link in the essential GlgE-pathway

Abstract: A novel four-step pathway identified recently in mycobacteria channels trehalose to glycogen synthesis and is also likely involved in the biosynthesis of two other crucial polymers: intracellular methylglucose lipopolysaccharides and exposed capsular glucan. The structures of three of the intervening enzymes - GlgB, GlgE, and TreS - were recently reported, providing the first templates for rational drug design. Here we describe the structural characterization of the fourth enzyme of the pathway, mycobacterial maltokinase (Mak), uncovering a eukaryotic-like kinase (ELK) fold, similar to methylthioribose kinases and aminoglycoside phosphotransferases. The 1.15 A structure of Mak in complex with a non-hydrolysable ATP analog reveals subtle structural rearrangements upon nucleotide binding in the cleft between the N- and the C-terminal lobes. Remarkably, this new family of ELKs has a novel N-terminal domain topologically resembling the cystatin family of protease inhibitors. By interfacing with and restraining the mobility of the phosphate-binding region of the N-terminal lobe, Mak's unusual N-terminal domain might regulate its phosphotransfer activity and represents the most likely anchoring point for TreS, the upstream enzyme in the pathway. By completing the gallery of atomic-detail models of an essential pathway, this structure opens new avenues for the rational design of alternative anti-tubercular compounds.

The determinants of export performance: A review of the research in the literature between 1998 and 2005

Abstract: Considerable attention has been paid to the determinants of export performance. However, despite this research effort in identifying and examining the influence of such determinants, the literature is characterized by fragmentation and diversity, hindering theory development and practical advancement in the field. This paper attempts to review and synthesize the knowledge on the subject. As a result, this study reviews and evaluates 52 articles published between 1998 and 2005 to assess the determinants of export performance. The assessment reveals that: (a) more studies have been conducted outside the USA; (b) the majority of the studies focus on manufacturing firms, with relatively few studies examining the service sector; (c) the majority of the export studies continue to focus on small to medium-sized firms; (d) there is a continuous increase in the sample size; (e) despite the problems that may arise from the use of single informants, it seems that none of the studies reviewed here collected data from more than one informant in the firm; (f) an increasing number of studies have been using the export venture as the unit of analysis; (g) the level of statistical sophistication has improved; (h) the use of control and moderating variables in export performance studies has increased; (i) more studies have started to include the external environment in their models, including domestic market characteristics; and (j) market orientation as a key determinant of export performance emerges in this review. Finally, conclusions are drawn, along with some suggestions for further research.

Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease

Abstract: Mutations in the glucocerebrosidase gene (GBA) are associated with Gaucher's disease, the most common lysosomal storage disorder. Parkinsonism is an established feature of Gaucher's disease and an increased frequency of mutations in GBA has been reported in several different ethnic series with sporadic Parkinson's disease. In this study, we evaluated the frequency of GBA mutations in British patients affected by Parkinson's disease. We utilized the DNA of 790 patients and 257 controls, matched for age and ethnicity, to screen for mutations within the GBA gene. Clinical data on all identified GBA mutation carriers was reviewed and analysed. Additionally, in all cases where brain material was available, a neuropathological evaluation was performed and compared to sporadic Parkinson's disease without GBA mutations. The frequency of GBA mutations among the British patients (33/790 = 4.18%) was significantly higher (P = 0.01; odds ratio = 3.7; 95% confidence interval = 1.12–12.14) when compared to the control group (3/257 = 1.17%). Fourteen different GBA mutations were identified, including three previously undescribed mutations, K7E, D443N and G193E. Pathological examination revealed widespread and abundant α-synuclein pathology in all 17 GBA mutation carriers, which were graded as Braak stage of 5–6, and had McKeith's limbic or diffuse neocortical Lewy body-type pathology. Diffuse neocortical Lewy body-type pathology tended to occur more frequently in the group with GBA mutations compared to matched Parkinson's disease controls. Clinical features comprised an early onset of the disease, the presence of hallucinations in 45% (14/31) and symptoms of cognitive decline or dementia in 48% (15/31) of patients. This study demonstrates that GBA mutations are found in British subjects at a higher frequency than any other known Parkinson's disease gene. This is the largest study to date on a non-Jewish patient sample with a detailed genotype/phenotype/pathological analyses which strengthens the hypothesis that GBA mutations represent a significant risk factor for the development of Parkinson's disease and suggest that to date, this is the most common genetic factor identified for the disease.

Ubiquitin tag for sperm mitochondria

Abstract: Like other mammals, humans inherit mitochondria from the mother only, even though the sperm contributes nearly one hundred mitochondria to the fertilized egg. In support of the idea that this strictly maternal inheritance of mitochondrial DNA arises from the selective destruction of sperm mitochondria1,2, we show here that sperm mitochondria inside fertilized cow and monkey eggs are tagged by the recycling marker protein ubiquitin3. This imprint is a death sentence that is written during spermatogenesis and executed after the sperm mitochondria encounter the egg's cytoplasmic destruction machinery.