General morphology, classification and biology of Cerambycidae

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Diseases caused by mutations in mitochondrial carrier genes SLC25: A review

In the 1980s, after the mitochondrial DNA (mtDNA) had been sequenced, several diseases resulting from mtDNA mutations emerged. Later, numerous disorders caused by mutations in the nuclear genes encoding mitochondrial proteins were found. A group of these diseases are due to defects of mitochondrial carriers, a family of proteins named solute carrier family 25 (SLC25), that transport a variety of solutes such as the reagents of ATP synthase (ATP, ADP, and phosphate), tricarboxylic acid cycle intermediates, cofactors, amino acids, and carnitine esters of fatty acids. The disease-causing mutations disclosed in mitochondrial carriers range from point mutations, which are often localized in the substrate translocation pore of the carrier, to large deletions and insertions. The biochemical consequences of deficient transport are the compartmentalized accumulation of the substrates and dysfunctional mitochondrial and cellular metabolism, which frequently develop into various forms of myopathy, encephalopathy, or neuropathy. Examples of diseases, due to mitochondrial carrier mutations are: combined D-2-and L-2-hydroxyglutaric aciduria, carnitine-acylcarnitine carrier deficiency, hyperornithinemia-hyperammonemia-homocitrillinuria (HHH) syndrome, early infantile epileptic encephalopathy type 3, Amish microcephaly, aspartate/glutamate isoform 1 deficiency, congenital sideroblastic anemia, Fontaine progeroid syndrome, and citrullinemia type II. Here, we review all the mitochondrial carrier-related diseases known until now, focusing on the connections between the molecular basis, altered metabolism, and phenotypes of these inherited disorders

Mitochondrial transport and metabolism of the vitamin B-derived cofactors thiamine pyrophosphate, coenzyme A, FAD and NAD+, and related diseases: A review

Multiple mitochondrial matrix enzymes playing key roles in metabolism require cofactors for their action. Due to the high impermeability of the mitochondrial inner membrane, these cofactors need to be synthesized within the mitochondria or be imported, themselves or one of their precursors, into the organelles. Transporters belonging to the protein family of mitochondrial carriers have been identified to transport the coenzymes: thiamine pyrophosphate, coenzyme A, FAD and NAD+, which are all structurally similar to nucleotides and derived from different B-vitamins. These mitochondrial cofactors bind more or less tightly to their enzymes and, after having been involved in a specific reaction step, are regenerated, spontaneously or by other enzymes, to return to their active form, ready for the next catalysis round. Disease-causing mutations in the mitochondrial cofactor carrier genes compromise not only the transport reaction but also the activity of all mitochondrial enzymes using that particular cofactor and the metabolic pathways in which the cofactor-dependent enzymes are involved. The mitochondrial transport, metabolism and diseases of the cofactors thiamine pyrophosphate, coenzyme A, FAD and NAD+ are the focus of this review

A turn propensity scale for transmembrane helices.

Using a model protein with a 40 residue hydrophobic transmembrane segment, we have measured the ability of all the 20 naturally occurring amino acids to form a tight turn when placed in the middle of the hydrophobic segment. Turn propensities in a transmembrane helix are found to be markedly different from those of globular proteins, and in most cases correlate closely with the hydrophobicity of the residue. The turn propensity scale may be used to improve current methods for membrane protein topology prediction

Los valles tectónicos recientes de Rubielos de la Cerida (Teruel)

[Resumen] La actividad tectónica cuaternaria y reciente ha dado lugar en este área a un conjunto de depresiones alargadas de orientación submeridiana, enmarcadas por fallas, que constituyen valles tectónicos[Abstract] Quaternary and recent tectonic activity led to a series of elongated depressions in the studied area of roughly N-S orientation, framed by faults, and developping as tectonic valleys

Welcome to the family: Identification of the nad+ transporter of animal mitochondria as member of the solute carrier family slc25

Subcellular compartmentation is a fundamental property of eukaryotic cells. Communication and metabolic and regulatory interconnectivity between organelles require that solutes can be transported across their surrounding membranes. Indeed, in mammals, there are hundreds of genes encoding solute carriers (SLCs) which mediate the selective transport of molecules such as nucleotides, amino acids, and sugars across biological membranes. Research over many years has identified the localization and preferred substrates of a large variety of SLCs. Of particular interest has been the SLC25 family, which includes carriers embedded in the inner membrane of mitochondria to secure the supply of these organelles with major metabolic intermediates and coen-zymes. The substrate specificity of many of these carriers has been established in the past. However, the route by which animal mitochondria are supplied with NAD+ had long remained obscure. Only just recently, the existence of a human mitochondrial NAD+ carrier was firmly established. With the realization that SLC25A51 (or MCART1) represents the major mitochondrial NAD+ carrier in mammals, a long-standing mystery in NAD+ biology has been resolved. Here, we summarize the functional importance and structural features of this carrier as well as the key observations leading to its discovery

Evidence for Non-Essential Salt Bridges in the M-Gates of Mitochondrial Carrier Proteins

Mitochondrial carriers, which transport metabolites, nucleotides, and cofactors across the mitochondrial inner membrane, have six transmembrane α-helices enclosing a translocation pore with a central substrate binding site whose access is controlled by a cytoplasmic and a matrix gate (M-gate). The salt bridges formed by the three PX[DE]XX[RK] motifs located on the odd-numbered transmembrane α-helices greatly contribute to closing the M-gate. We have measured the transport rates of cysteine mutants of the charged residue positions in the PX[DE]XX[RK] motifs of the bovine oxoglutarate carrier, the yeast GTP/GDP carrier, and the yeast NAD+ transporter, which all lack one of these charged residues. Most single substitutions, including those of the non-charged and unpaired charged residues, completely inactivated transport. Double mutations of charged pairs showed that all three carriers contain salt bridges non-essential for activity. Two double substitutions of these non-essential charge pairs exhibited higher transport rates than their corre-sponding single mutants, whereas swapping the charged residues in these positions did not increase activity. The results demonstrate that some of the residues in the charged residue positions of the PX[DE]XX[KR] motifs are important for reasons other than forming salt bridges, probably for playing specific roles related to the substrate interaction-mediated conformational changes leading to the M-gate opening/closing

Paleoambientes holocenos del valle de Tafí (Noroeste Argentino) a partir de registros morfosedimentarios y geoarqueológicos

El valle de Tafí es una pequeña cuenca intermontana de las Sierras Pampeanas del Noroeste Argentino. Los estudios geomorfológicos efectuados han permitido reconocer la existencia de registros morfosedimentarios del Holoceno de gran interés para la reconstrucción paleoambiental regional. El estudio de las principales acumulaciones de laderas, terrazas fluviales y conos aluviales aportó numerosos registros geoarqueológicos, restos paleontológicos, cenizas volcánicas, así como dataciones 14C y de termoluminiscencia, de interés para elaborar una secuencia paleoambiental. Estos datos, junto a antecedentes y la elaboración de cartografía geomorfológica permiten diferenciar 4 unidades morfosedimentarias. La etapa más antigua (H1) comprende el Holoceno inferior y medio (ca.13000-ca. 4200 BP) subdividida en dos subunidades (H1a y H1b), de diferente signo ambiental, separadas por un evento volcánico (V0) datado en ca. 10000 BP. El final de H1b queda delimitado por otro aporte de tefras en ca.4200 BP, cuando esta unidad comenzaba a quedar individualizada por una fase de incisión. La etapa H2 abarca desde ca.4200 BP hasta ca.630 BP alcanzando notable extensión en el valle. La presencia de ocupación humana durante este periodo (Culturas Tafí y Santa María) y las características de los sedimentos indican una gran influencia de la acción antrópica en su formación. Finalmente, dos unidades menores (H3 y H4) cubren los últimos siglos de la secuencia holocena, separadas por fases de incisión intermedias. Los datos del conjunto holoceno han sido puestos en relación con la evolución paleoclimática regional e integrados en los principales eventos de carácter global. The Tafi Valley is a small basin located in the northern sector of the Sierras Pampeanas in Northwest Argentina. The geomorphological studies made in the area showed the presence of very representative Holocene morpho-sedimentary records, which are useful for regional paleoenvironmental reconstruction. The study of the main slope accumulations, fluvial terraces, and alluvial fans provided several geoarchaeological records, paleontological remains, and volcanic ash layers as well as radiocarbon and thermoluminescence datings. We used all these data to construct a paleoenvironmental sequence. This sequence was also accompanied by some previously obtained data and detailed geomorphological cartography. Four morphosedimentary units were identified. The oldest unit (H1) comprises the Early and Middle Holocene (ca. 13000 - ca. 4200 BP). It could be divided into two sub-stages (H1a and H1b), with different environmental signs. They appear separated by a tephra layer (V0) dated ca. 10000 BR The end of sub-stage H1b is limited by another ash layer (V1) dated ca. 4200 BR By that time, an incision process had already started separating this sub-stage from the next one. Stage H2 spans from ca. 4200 BP to ca. 630 BP, and extends vastly throughout the valley. It was possible to identify several features of human settlements (Tafi and Santa Maria Cultures) corresponding to that period. The characteristics of the sediments indicate a strong anthropogenic influence during its formation. Finally, two minor units (H3 and H4) cover the last centuries of the Holocene sequence, separated by incision phases. The Holocene set was related to the regional and global paleoclimatic evolution

Morfología de vertientes y neotectónica en el Macizo de Javalambre (provincia de Teruel)

[Resumen] El modelado actual de las vertientes del macizo de Javalambre es consecuencia de tres tipos principales de procesos que actúan a partir de su elevación a comienzos del Plioceno -superior: (a) la dinámica periglaciar, (b) una etapa de activida~ tect6nica ocurrida hacia el Pleistoceno medio-superior, y (c) deslizamientos gravitacionales, translacionales y rotacionales producidos a favor de un sustrato plástico en las áreas de mayor incisión de la red -fluvial.Abstract] The present slope form in Javalambre area results from three principal types of processes which are active after its elevation in the early Upper Pliocene: (a) periglacial dynamics, (b) a tectonic phase in Middle-Upper Pleistocene, and (c) gravitational, translational and rotational landslides generated over plastic rocks in zones with a intensive fluvial incisio

New Insights into the Evolution and Gene Structure of the Mitochondrial Carrier Family Unveiled by Analyzing the Frequent and Conserved Intron Positions

Mitochondrial carriers (MCs) belong to a eukaryotic protein family of transporters that in higher organisms is called the solute carrier family 25 (SLC25). All MCs have characteristic triplicated sequence repeats forming a 3-fold symmetrical structure of a six-transmembrane α-helix bundle with a centrally located substrate-binding site. Biochemical characterization has shown that MCs altogether transport a wide variety of substrates but can be divided into subfamilies, each transporting a few specific substrates. We have investigated the intron positions in the human MC genes and their orthologs of highly diversified organisms. The results demonstrate that several intron positions are present in numerous MC sequences at the same specific points, of which some are 3-fold symmetry related. Many of these frequent intron positions are also conserved in subfamilies or in groups of subfamilies transporting similar substrates. The analyses of the frequent and conserved intron positions in MCs suggest phylogenetic relationships not only between close but also distant homologs as well as a possible involvement of the intron positions in the evolution of the substrate specificity diversification of the MC family members