Systematic Mutational Analysis of the Intracellular Regions of Yeast Gap1 Permease

The yeast general amino acid permease Gap1 is a convenient model for studying the intracellular trafficking of membrane proteins. Present at the plasma membrane when the nitrogen source is poor, it undergoes ubiquitin-dependent endocytosis and degradation upon addition of a good nitrogen source, e.g. ammonium. It comprises 12 transmembrane domains (TM) flanked by cytosol-facing N- and C-terminal tails (NT, CT). The NT of Gap1 contains the acceptor lysines for ubiquitylation and its CT includes a sequence essential to exit from the endoplasmic reticulum (ER).Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Metabolic Networks of Sodalis glossinidius: A Systems Biology Approach to Reductive Evolution

Background: Genome reduction is a common evolutionary process affecting bacterial lineages that establish symbiotic or pathogenic associations with eukaryotic hosts. Such associations yield highly reduced genomes with greatly streamlined metabolic abilities shaped by the type of ecological association with the host. Sodalis glossinidius, the secondary endosymbiont of tsetse flies, represents one of the few complete genomes available of a bacterium at the initial stages of this process. In the present study, genome reduction is studied from a systems biology perspective through the reconstruction and functional analysis of genome-scale metabolic networks of S. glossinidius. Results: The functional profile of ancestral and extant metabolic networks sheds light on the evolutionary events underlying transition to a host-dependent lifestyle. Meanwhile, reductive evolution simulations on the extant metabolic network can predict possible future evolution of S. glossinidius in the context of genome reduction. Finally, knockout simulations in different metabolic systems reveal a gradual decrease in network robustness to different mutational events for bacterial endosymbionts at different stages of the symbiotic association. Conclusions: Stoichiometric analysis reveals few gene inactivation events whose effects on the functionality of S. glossinidius metabolic systems are drastic enough to account for the ecological transition from a free-living to hostdependent lifestyle. The decrease in network robustness across different metabolic systems may be associated with th

A molecular analysis of desiccation tolerance mechanisms in the anhydrobiotic nematode Panagrolaimus superbus using expressed sequenced tags

<p>Abstract</p> <p>Background</p> <p>Some organisms can survive extreme desiccation by entering into a state of suspended animation known as anhydrobiosis. <it>Panagrolaimus superbus </it>is a free-living anhydrobiotic nematode that can survive rapid environmental desiccation. The mechanisms that <it>P. superbus </it>uses to combat the potentially lethal effects of cellular dehydration may include the constitutive and inducible expression of protective molecules, along with behavioural and/or morphological adaptations that slow the rate of cellular water loss. In addition, inducible repair and revival programmes may also be required for successful rehydration and recovery from anhydrobiosis.</p> <p>Results</p> <p>To identify constitutively expressed candidate anhydrobiotic genes we obtained 9,216 ESTs from an unstressed mixed stage population of <it>P. superbus</it>. We derived 4,009 unigenes from these ESTs. These unigene annotations and sequences can be accessed at <url>http://www.nematodes.org/nembase4/species_info.php?species=PSC</url>. We manually annotated a set of 187 constitutively expressed candidate anhydrobiotic genes from <it>P. superbus</it>. Notable among those is a putative lineage expansion of the <it>lea </it>(late embryogenesis abundant) gene family. The most abundantly expressed sequence was a member of the nematode specific <it>sxp/ral-2 </it>family that is highly expressed in parasitic nematodes and secreted onto the surface of the nematodes' cuticles. There were 2,059 novel unigenes (51.7% of the total), 149 of which are predicted to encode intrinsically disordered proteins lacking a fixed tertiary structure. One unigene may encode an exo-β-1,3-glucanase (GHF5 family), most similar to a sequence from <it>Phytophthora infestans</it>. GHF5 enzymes have been reported from several species of plant parasitic nematodes, with horizontal gene transfer (HGT) from bacteria proposed to explain their evolutionary origin. This <it>P. superbus </it>sequence represents another possible HGT event within the Nematoda. The expression of five of the 19 putative stress response genes tested was upregulated in response to desiccation. These were the antioxidants <it>glutathione peroxidase, dj-1 </it>and <it>1-Cys peroxiredoxin</it>, an <it>shsp </it>sequence and an <it>lea </it>gene.</p> <p>Conclusions</p> <p><it>P. superbus </it>appears to utilise a strategy of combined constitutive and inducible gene expression in preparation for entry into anhydrobiosis. The apparent lineage expansion of <it>lea </it>genes, together with their constitutive and inducible expression, suggests that LEA3 proteins are important components of the anhydrobiotic protection repertoire of <it>P. superbus</it>.</p

Lesser Tuberosity Avulsions in Adolescents

BACKGROUND: Subscapularis tendon avulsions of the lesser tuberosity are relatively rare and often missed acutely and their characteristic appearance is frequently not recognized or is misinterpreted for an osteochondroma or a neoplastic process. QUESTIONS/PURPOSES: This report reviews our experience with six adolescents who had subscapularis tendon avulsions of the lesser tuberosity. METHODS: Six male adolescents (12–15 years) presented with shoulder pain following history of trauma during amateur sport. Clinical notes including range of motion, strength tests, and pain assessment were reviewed along with imaging studies pre- and post treatment. Treatment consisted of either surgical or conservative measures. RESULTS: Two of the six patients had a large avulsion that simulated an exostosis of the proximal humerus that was misdiagnosed as an osteochondroma at two different outside institutions. All six cases were diagnosed with subscapularis tendon avulsion of the lesser tuberosity following clinical and imaging evaluation at our institution. Five of the patients underwent surgical repair and fixation of the tendon and the lesser tuberosity with suture anchors. One patient was treated conservatively. All patients had a good outcome with recovery of full shoulder strength and motion upon follow-up. CONCLUSION: Clinicians should have a high index of suspicion of lesser tuberosity avulsions in adolescents who present with loss of internal rotation and anterior shoulder pain following traumatic injuries. In addition, an osseous fragment or exostosis along the inferomedial humeral head should suggest a subscapularis tendon avulsion and also should not be confused with an osteochondroma or a neoplastic process. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11420-014-9400-1) contains supplementary material, which is available to authorized users

Relação entre aptidão cardiorrespiratória e indicadores de adiposidade corporal em adolescentes Relationship between cardiorespiratory fitness and indicators of body adiposity in adolescents

OBJETIVO: Analisar a relação entre aptidão cardiorrespiratória e indicadores de adiposidade corporal em adolescentes de ambos os sexos. MÉTODOS: 78 sujeitos (45 rapazes e 33 moças) foram avaliados quanto à massa corporal, estatura e dobras cutâneas tricipital e subescapular. O índice de massa corpórea e a somatória das duas dobras cutâneas foram calculados. A aptidão cardiorrespiratória foi analisada pelo teste de vai-e-vem de 20 metros de vários estágios e a estimativa do consumo máximo de oxigênio foi analisada por uma equação específica. Para a comparação entre os grupos, foi empregado o teste de Mann-Whitney e, para verificar a relação entre a aptidão cardiorrespiratória e os indicadores de adiposidade corporal, utilizou-se o coeficiente de correlação de Spearman. RESULTADOS: Os adolescentes com alta aptidão cardiorrespiratória apresentaram sistematicamente valores mais baixos de gordura corporal em relação a seus pares com baixa aptidão cardiorrespiratória (p<0,05), com diferenças variando entre 36 e 42% para os rapazes e entre 14 e 33% para as moças. Correlações negativas, moderadas e estatisticamente significativas foram verificadas entre os indicadores de aptidão cardiorrespiratória e de adiposidade corporal para ambos os sexos, com exceção do índice de massa corpórea. CONCLUSÕES: Os resultados sugerem que o aumento da adiposidade corporal pode influenciar negativamente a aptidão cardiorrespiratória em adolescentes de ambos os sexos.<br>OBJECTIVE: To analyze the relationship between cardiorespiratory fitness and indicators of body adiposity in adolescents of both genders. METHODS: 78 subjects (45 boys and 33 girls) were evaluated for body mass, height and triceps and subscapular skinfold thickness. Body mass index and the sum of the two skinfolds thickness were determined. The cardiorespiratory fitness was determined by the maximal multistage 20 meters shuttle run test, and the estimate of maximal oxygen uptake was evaluated by a specific equation. Groups were compared by Mann-Whitney test. The Spearman correlation index was applied to verify the relationship between cardiorespiratory fitness and the indicators of body adiposity. RESULTS: The adolescents with high cardiorespiratory fitness presented lower values of body fat than their peers with low cardiorespiratory fitness (p<0.05), with differences varying between 36 to 42% for boys and 14 to 33% for girls. Statistically significant negative and moderate correlations were noted between the indicators of cardiorespiratory fitness and the body adiposity for both genders, with the exception of body mass index. CONCLUSIONS: These results suggest that the body adiposity may have a negative influence on the cardiorespiratory fitness of adolescents of both genders