The genome of the crenarchaeon Sulfolobus solfataricus P2 contains 2,992,245 bp on a single chromosome and encodes 2,977 proteins and many RNAs. One-third of the encoded proteins have no detectable homologs in other sequenced genomes. Moreover, 40% appear to be archaeal-specific, and only 12% and 2.3% are shared exclusively with bacteria and eukarya, respectively. The genome shows a high level of plasticity with 200 diverse insertion sequence elements, many putative nonautonomous mobile elements, and evidence of integrase-mediated insertion events. There are also long clusters of regularly spaced tandem repeats. Different transfer systems are used for the uptake of inorganic and organic solutes, and a wealth of intracellular and extracellular proteases, sugar, and sulfur metabolizing enzymes are encoded, as well as enzymes of the central metabolic pathways and motility proteins. The major metabolic electron carrier is not NADH as in bacteria and eukarya but probably ferredoxin. The essential components required for DNA replication, DNA repair and recombination, the cell cycle, transcriptional initiation and translation, but not DNA folding, show a strong eukaryal character with many archaeal-specific features. The results illustrate major differences between crenarchaea and euryarchaea, especially for their DNA replication mechanism and cell cycle processes and their translational apparatus.

Purpose-The effectiveness of resistance exercise for strength improvement among aging persons is inconsistent across investigations, and there is a lack of research synthesis for multiple strength outcomes.Methods-The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. A meta-analysis was conducted to determine the effect of resistance exercise (RE) for multiple strength outcomes in aging adults. Randomized controlled trials and randomized or non-randomized studies among adults ≥ 50 years, were included. Data were pooled using random effect models. Outcomes for 4 common strength tests were analyzed for main effects. Heterogeneity between studies was assessed using the Cochran Q and I 2 statistics, and publication bias was evaluated through physical inspection of funnel plots as well as formal rankcorrelation statistics. A linear mixed model regression was incorporated to examine differences between outcomes, as well as potential study-level predictor variables.Results-Forty-seven studies were included, representing 1079 participants. A positive effect for each of the strength outcomes was determined however there was heterogeneity between studies. Regression revealed that higher intensity training was associated with greater improvement. Strength increases ranged from 9.8 -31.6 kg, and percent changes were 29 ± 2, 24 ± 2, 33 ± 3, and 25 ± 2, respectively for leg press, chest press, knee extension, and lat pull.Conclusions-RE is effective for improving strength among older adults, particularly with higher intensity training. Findings therefore suggest that RE may be considered a viable strategy to prevent generalized muscular weakness associated with ageing.

The ability of the pathogenic fungus Candida albicans to switch from a yeast to a hyphal morphology in response to external signals is implicated in its pathogenicity. We used glass DNA microarrays to investigate the transcription profiles of 6333 predicted ORFs in cells undergoing this transition and their responses to changes in temperature and culture medium. We have identified several genes whose transcriptional profiles are similar to those of known virulence factors that are modulated by the switch to hyphal growth caused by addition of serum and a 37 degrees C growth temperature. Time course analysis of this transition identified transcripts that are induced before germ tube initiation and shut off later in the developmental process. A strain deleted for the Efg1p and Cph1p transcription factors is defective in hyphae formation, and its response to serum and increased temperature is almost identical to the response of a wild-type strain grown at 37 degrees C in the absence of serum. Thus Efg1p and Cph1p are needed for the activation of the transcriptional program that is induced by the presence of serum.

Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and three pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localise to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequencing data identified recessive mutations in PIBF1/CEP90 and C21orf2/LRRC76 as causes of the ciliopathies Joubert and Jeune syndromes. Biochemical approaches place C21orf2 within key ciliopathy-associated protein modules, offering an explanation for the skeletal and retinal involvement observed in individuals with C21orf2-variants. Our global, unbiased approaches provide insights into ciliogenesis complexity and identify roles for unanticipated pathways in human genetic disease.

The alpha-actinin 3 (ACTN3) gene encodes a protein of the Z disk of myofibers, and a polymorphism of ACTN3 results in complete loss of the protein. The ACTN3 genotype (R577X) has been found to be associated with performance in Australian elite athletes (Yang N, MacArthur DG, Gulbin JP, Hahn AG, Beggs AH, Easteal S, and North K. Am J Hum Genet 73: 627-631, 2003). We studied associations between ACTN3 genotype and muscle size [cross-sectional area of the biceps brachii via magnetic resonance imaging (MRI)] and elbow flexor isometric (MVC) and dynamic [1-repetition maximum (1-RM)] strength in a large group of men (N = 247) and women (N = 355) enrolled in a 12-wk standardized elbow flexor/extensor resistance training program of the nondominant arm at one of eight study centers. We found no association between ACTN3 R577X genotype and muscle phenotype in men. However, women homozygous for the ACTN3 577X allele (XX) had lower baseline MVC compared with heterozygotes (P < 0.05) when adjusted for body mass and age. Women homozygous for the mutant allele (577X) demonstrated greater absolute and relative 1-RM gains compared with the homozygous wild type (RR) after resistance training when adjusted for body mass and age (P < 0.05). There was a trend for a dose-response with genotype such that gains were greatest for XX and least for RR. Significant associations were validated in at least one ethnic subpopulation (Caucasians, Asians) and were independent of training volume. About 2% of baseline MVC and of 1-RM strength gain after training were attributable to ACTN3 genotype (likelihood-ratio test P value, P = 0.01), suggesting that ACTN3 is one of many genes contributing to genetic variation in muscle performance and adaptation to exercise.

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The phylogenetic relationships of amoebae are poorly resolved. To address this difficult question, we have sequenced 1,280 expressed sequence tags from Mastigamoeba balamuthi and assembled a large data set containing 123 genes for representatives of three phenotypically highly divergent major amoeboid lineages: Pelobionta, Entamoebidae, and Mycetozoa. Phylogenetic reconstruction was performed on Ϸ25,000 aa positions for 30 species by using maximum-likelihood approaches. All well-established eukaryotic groups were recovered with high statistical support, validating our approach. Interestingly, the three amoeboid lineages strongly clustered together in agreement with the Conosa hypothesis [as defined by T. Cavalier-Smith (1998) Biol. Rev. Cambridge Philos. Soc. 73, 203-266]. Two amitochondriate amoebae, the free-living Mastigamoeba and the human parasite Entamoeba, formed a significant sister group to the exclusion of the mycetozoan Dictyostelium. This result suggested that a part of the reductive process in the evolution of Entamoeba (e.g., loss of typical mitochondria) occurred in its free-living ancestors. Applying this inexpensive expressed sequence tag approach to many other lineages will surely improve our understanding of eukaryotic evolution.

In order to characterize the genome-wide transcriptional response of the hyperthermophilic, aerobic crenarchaeote Sulfolobus solfataricus to UV damage, we used high-density DNA microarrays which covered 3,368 genetic features encoded on the host genome, as well as the genes of several extrachromosomal genetic elements. While no significant up-regulation of genes potentially involved in direct DNA damage reversal was observed, a specific transcriptional UV response involving 55 genes could be dissected. Although flow cytometry showed only modest perturbation of the cell cycle, strong modulation of the transcript levels of the Cdc6 replication initiator genes was observed. Up-regulation of an operon encoding Mre11 and Rad50 homologs pointed to induction of recombinational repair. Consistent with this, DNA double-strand breaks were observed between 2 and 8 h after UV treatment, possibly resulting from replication fork collapse at damaged DNA sites. The strong transcriptional induction of genes which potentially encode functions for pilus formation suggested that conjugational activity might lead to enhanced exchange of genetic material. In support of this, a statistical microscopic analysis demonstrated that large cell aggregates formed upon UV exposure. Together, this provided supporting evidence to a link between recombinational repair and conjugation events.Most organisms meet the challenge of maintaining their genome integrity and ensuring correct replication of their genetic material while protecting themselves against the DNAdamaging effects of UV light. This is reflected in the large number of proteins involved in DNA repair pathways, which are found in all three domains of life: Bacteria, Eukarya, and Archaea. For hyperthermophilic organisms, like many archaea, that dwell at the upper temperature limit of life (48), this challenge might be even more demanding. Studies on mutation frequencies and repair in Archaea have been inspired by the expectation that extremophiles growing under conditions which accelerate spontaneous DNA damage should be particularly proficient in DNA repair (7,14,32). Archaea have also gained special interest because of their unique evolutionary position and their relationship to eukaryotes. Homology in many factors in the systems responsible for transcription and replication has been observed. The homologous, yet simpler, archaeal systems provide a powerful tool for the study of cellular evolution and more complex systems in the eukaryotic nucleus (11). The homology between the eukaryotic and archaeal domains also exists in DNA repair systems (2, 23). For example, potential factors involved in nucleotide excision repair (NER) of UV-induced DNA lesions are, in most archaea, exclusively constituted by homologs of the eukaryotic proteins XPF/XPB/XPD/Fen-1. The in vivo function of this system in archaea has not yet been elucidated, and the system also seems to be incomplete (23, 39). However, Salerno et al. (42) have shown that Sulfolobus can efficiently conduct the repair of photoprodu...