Mutations in the UQCC1-Interacting Protein,UQCC2, Cause Human Complex III Deficiency Associated with Perturbed Cytochrome b Protein Expression

Mitochondrial oxidative phosphorylation (OXPHOS) is responsible for generating the majority of cellular ATP. Complex III (ubiquinol-cytochrome c oxidoreductase) is the third of five OXPHOS complexes. Complex III assembly relies on the coordinated expression of the mitochondrial and nuclear genomes, with 10 subunits encoded by nuclear DNA and one by mitochondrial DNA (mtDNA). Complex III deficiency is a debilitating and often fatal disorder that can arise from mutations in complex III subunit genes or one of three known complex III assembly factors. The molecular cause for complex III deficiency in about half of cases, however, is unknown and there are likely many complex III assembly factors yet to be identified. Here, we used Massively Parallel Sequencing to identify a homozygous splicing mutation in the gene encoding Ubiquinol-Cytochrome c Reductase Complex Assembly Factor 2 (UQCC2) in a consanguineous Lebanese patient displaying complex III deficiency, severe intrauterine growth retardation, neonatal lactic acidosis and renal tubular dysfunction. We prove causality of the mutation via lentiviral correction studies in patient fibroblasts. Sequence-profile based orthology prediction shows UQCC2 is an ortholog of the Saccharomyces cerevisiae complex III assembly factor, Cbp6p, although its sequence has diverged substantially. Co-purification studies show that UQCC2 interacts with UQCC1, the predicted ortholog of the Cbp6p binding partner, Cbp3p. Fibroblasts from the patient with UQCC2 mutations have deficiency of UQCC1, while UQCC1-depleted cells have reduced levels of UQCC2 and complex III. We show that UQCC1 binds the newly synthesized mtDNA-encoded cytochrome b subunit of complex III and that UQCC2 patient fibroblasts have specific defects in the synthesis or stability of cytochrome b. This work reveals a new cause for complex III deficiency that can assist future patient diagnosis, and provides insight into human complex III assembly by establishing that UQCC1 and UQCC2 are complex III assembly factors participating in cytochrome b biogenesis.     

The climatic drivers of primary Picea forest growth along the Carpathian arc are changing under rising temperatures

Climatic constraints on tree growth mediate an important link between terrestrial and atmospheric carbon pools. Tree rings provide valuable information on climate‐driven growth patterns, but existing data tend to be biased toward older trees on climatically extreme sites. Understanding climate change responses of biogeographic regions requires data that integrate spatial variability in growing conditions and forest structure. We analyzed both temporal (c. 1901–2010) and spatial variation in radial growth patterns in 9,876 trees from fragments of primary Picea abies forests spanning the latitudinal and altitudinal extent of the Carpathian arc. Growth was positively correlated with summer temperatures and spring moisture availability throughout the entire region. However, important seasonal variation in climate responses occurred along geospatial gradients. At northern sites, winter precipitation and October temperatures of the year preceding ring formation were positively correlated with ring width. In contrast, trees at the southern extent of the Carpathians responded negatively to warm and dry conditions in autumn of the year preceding ring formation. An assessment of regional synchronization in radial growth variability showed temporal fluctuations throughout the 20th century linked to the onset of moisture limitation in southern landscapes. Since the beginning of the study period, differences between high and low elevations in the temperature sensitivity of tree growth generally declined, while moisture sensitivity increased at lower elevations. Growth trend analyses demonstrated changes in absolute tree growth rates linked to climatic change, with basal area increments in northern landscapes and lower altitudes responding positively to recent warming. Tree growth has predominantly increased with rising temperatures in the Carpathians, accompanied by early indicators that portions of the mountain range are transitioning from temperature to moisture limitation. Continued warming will alleviate large‐scale temperature constraints on tree growth, giving increasing weight to local drivers that are more challenging to predict.     

Nucleoli in vaginal cells of hyperestrogenic and hypoestrogenic women

Nucleoli classified according to their functional morphology were investigated in the vaginal cells of 38 hypoestrogenic and 29 hyperestrogenic women to study the effect of estrogen on these cells. While the cells from hyperestrogenic patients were characterized by the presence of a larger number of compact (active) and ring-shaped (less active/resting) nucleoli, vaginal cells from hypoestrogenic women were characterized by the presence of a larger number of micronucleoli (inactive nucleoli).     

Terrestrial insect bioerosion and the possibilities of its fossilization (Holocene to recent,Czech republic)

Cylindrical tunnels, representing bee's nests, are present at and immediately beneath exposed surfaces of Late Cretaceous castellated sandstones in the Czech Republic. The tunnels originated either in weathered rock of overhanging surfaces, or in a thin layer of weathered sandstone formed between hard opaline crusts on rock surfaces and material not affected strongly by recent exogenic processes. Degraded rock crusts, which may bear parts of the biogenic structures, are present in sandy talus deposits usually representing all of the Holocene. Insect “borings” within lithified substrates in terrestrial settings are an unusual phenomenon; their fossilization potential in the Holocene sediments of the Bohemian castellated rocks may be relatively high.     

The role of GTP-binding proteins in mechanochemical movements of microorganisms and their potential to form filamentous structures

Prokaryotic cells contain proteins which form extended chains or multimers that oscillate between monomers and oligomers of varying length. Hydrolysis of nucleoside triphosphates combined with site-specific disposition of substrates and products to monomers and multimers is the driving force of dynamic instability of these molecules. Polymeric structures are connected in some manner to a variety of signaling systems that adhere to the polymeric matrix, including the GTP-binding protein(s), protein kinases and phosphatases, and other proteins or systems that communicate between the cytoplasmic membrane and the cytosol. Flexible organization allowing regulated dynamic movement is one of the key elements in all living cells. In eukaryotic cells actin and tubulin are the two main components of dynamically controlled spatial system. These proteins are noteworthy for their ability to polymerize, reversibly, into filaments or microtubules in association with hydrolysis of ATP or GTP, respectively. As such, they regulate most of the mechanics of cell movement including cell division, cell differentiation, phagocytosis and other dynamic phenomena. Recent evidence revealed that microbial cells create functional domains at specific sites of the cells and can form cytoplasmic tubules and fibers.     

Trace fossils of animal‐plant interactions and “pseudointeractions” from maletín (Bohemian cretaceous basin,Czech Republic)

Old collections of the Upper Cretaceous flora at Maletín yield examples of trace fossils of plant‐arthropod interactions, comparable with recent insect galls. Grooves and ridges, often preserved on leaves at this locality, are (in contradiction to several previous authors) interpreted as traces of burrowing organisms, which originated in soft sediment adjacent to the plant remains lying on a lake floor or buried in the substrate. The leaves functioned in the sediment at the time of burrowing and/or during compaction of the substrate as distinctive laminar bodies with specific physical characteristics and therefore they enabled the preservation of some aspects of ichnofabric otherwise invisible in the surrounding strata.     

Dynamic of apoptosis of cells in duodenal villi infected with <Emphasis Type="Italic">Eimeria acervulina</Emphasis> in broiler chickens

The aim of our study was to evaluate the parasite — host interactions at apoptosis level. We studied histopathological changes and time course of apoptosis in the duodenum during Eimeria acervulina infection. One-day-old broiler chicks were randomly allocated into two equal groups. At the age of two weeks the first group was experimentally infected with a pure suspension of sporulated E. acervulina oocysts. The second group served as a negative control. Tissue samples from the upper part of duodenum were obtained at 0.5, 1, 2, 3, 4, 5 and 6 days post infection. Biopsies of duodenum were studied immunohistochemically using DeadEnd™ Colometric TUNEL System for apoptosis detection in duodenal mucosa. Number of parasites in duodenal epithelium was also investigated. Our experimental results demonstrate: (i) macroscopic and histopathological changes in epithelium detected mainly in proximal segment of duodenum in infected groups; (ii) the number of developmental stages of E. acervulina (DSEA) during our trial increased, reaching the maximum 5 days post infection (dpi) (332.2 ± 16.12) (mean ± SEM), whereas the amount of DSEA declined significantly as late as 6 dpi (124.6 ± 3.91); (iii) the highest apoptosis level was recorded in initiatory 0.5 dpi (13.2 ± 1.02) and on the end of parasite development cycle after 5 dpi (12.6 ± 1.36). Finally, results showed that there was a period of inhibition of apoptosis during infection by E. acervulina.