Proteomic signatures of in vivo muscle oxidative capacity in healthy adults

Adequate support of energy for biological activities and during fluctuation of energetic demand is crucial for healthy aging; however, mechanisms for energy decline as well as compensatory mechanisms that counteract such decline remain unclear. We conducted a discovery proteomic study of skeletal muscle in 57 healthy adults (22 women and 35 men; aged 23–87 years) to identify proteins overrepresented and underrepresented with better muscle oxidative capacity, a robust measure of in vivo mitochondrial function, independent of age, sex, and physical activity. Muscle oxidative capacity was assessed by ³¹P magnetic resonance spectroscopy postexercise phosphocreatine (PCr) recovery time (τ_PCr) in the vastus lateralis muscle, with smaller τ_PCr values reflecting better oxidative capacity. Of the 4,300 proteins quantified by LC‐MS in muscle biopsies, 253 were significantly overrepresented with better muscle oxidative capacity. Enrichment analysis revealed three major protein clusters: (a) proteins involved in key energetic mitochondrial functions especially complex I of the electron transport chain, tricarboxylic acid (TCA) cycle, fatty acid oxidation, and mitochondrial ABC transporters; (b) spliceosome proteins that regulate mRNA alternative splicing machinery, and (c) proteins involved in translation within mitochondria. Our findings suggest that alternative splicing and mechanisms that modulate mitochondrial protein synthesis are central features of the molecular mechanisms aimed at maintaining mitochondrial function in the face of impairment. Whether these mechanisms are compensatory attempt to counteract the effect of aging on mitochondrial function should be further tested in longitudinal studies.     

Leprosy in a prison population: A new active search strategy and a prospective clinical analysis

BackgroundThis study evaluates an active search strategy for leprosy diagnosis based on responses to a Leprosy Suspicion Questionnaire (LSQ), and analyzing the clinical, immunoepidemiological and follow-up aspects for individuals living in a prison population.MethodsA cross-sectional study based on a questionnaire posing 14 questions about leprosy symptoms and signs that was distributed to 1,400 prisoners. This was followed by dermatoneurological examination, anti-PGL-I serology and RLEP-PCR. Those without leprosy were placed in the Non-leprosy Group (NLG, n = 1,216) and those diagnosed with clinical symptoms of leprosy were placed in the Leprosy Group (LG, n = 34).FindingsIn total, 896 LSQ were returned (64%), and 187 (20.9%) of the responses were deemed as positive for signs/symptoms, answering 2.7 questions on average. Clinically, 1,250 (89.3%) of the prisoners were evaluated resulting in the diagnosis of 34 new cases (LG), based on well-accepted clinical signs and symptoms, a new case detection rate of 2.7% within this population, while the NLG were comprised of 1,216 individuals. The confinement time medians were 39 months in the LG while it was 36 months in the NLG (p>0.05). The 31 leprosy cases who responded to the questionnaire (LSQ+) had an average of 1.5 responses. The symptoms “anesthetized skin area” and “pain in nerves” were most commonly mentioned in the LG while “tingling, numbness in the hands/feet”, “sensation of pricks and needles”, “pain in nerves” and “spots on the skin” responses were found in more than 30% of questionnaires in the NLG. Clinically, 88.2% had dysesthetic macular skin lesions and 97.1% presented some peripheral nerve impairment, 71.9% with some degree of disability. All cases were multibacillary, confirming a late diagnosis. Anti-PGL-I results in the LG were higher than in the NLG (p<0.0001), while the RLEP-PCR was positive in 11.8% of the patients.InterpretationOur findings within the penitentiary demonstrated a hidden prevalence of leprosy, although the individuals diagnosed were likely infected while living in their former communities and not as a result of exposure in the prison. The LSQ proved to be an important screening tool to help identify leprosy cases in prisons.     

Combination Therapy for Invasive Fungal Infections

The purpose of this review is to summarize and evaluate relevant literature on combination antifungal therapy for invasive fungal infections (IFIs). Cryptococcal meningitis has the largest body and highest quality in support of combination therapy with amphotericin B and flucytosine. More recent data in treatment of invasive aspergillosis suggest combination therapy with voriconazole and echinocandins may be effective in select patients. Quality studies are needed to define combination therapy in rare mold infections. Multiple strategies have been employed to optimize treatment of the growing incidence of IFIs. With exceptions as noted above, justification for the use of combination antifungal therapy is most often based on uncontrolled and/or underpowered studies, in vitro data, and case reports.     

The contribution of corals to reef structural complexity in Kāne‘ohe Bay

Coral Reefs - The structural complexity of coral reefs provides important ecosystem functions, such as wave attenuation for coastal protection, surfaces for coral growth, and habitat for other...     

Online auction marketplaces as a global pathway for aquatic invasive species

Hydrobiologia - The ornamental aquarium pet trade is a leading pathway for the introduction of aquatic invasive species. In addition to purchasing live organisms in stores, hobbyists are engaging...     

A Highlights from MBoC Selection: Cells surviving fractional killing by TRAIL exhibit transient but sustainable resistance and inflammatory phenotypes

When clonal populations of human cells are exposed to apoptosis-inducing agents, some cells die and others survive. This fractional killing arises not from mutation but from preexisting, stochastic differences in the levels and activities of proteins regulating apoptosis. Here we examine the properties of cells that survive treatment with agonists of two distinct death receptors, tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and anti-FasR antibodies. We find that “survivor” cells are highly resistant to a second ligand dose applied 1 d later. Resistance is reversible, resetting after several days of culture in the absence of death ligand. “Reset” cells appear identical to drug-naive cells with respect to death ligand sensitivity and gene expression profiles. TRAIL survivors are cross-resistant to activators of FasR and vice versa and exhibit an NF-κB–dependent inflammatory phenotype. Remarkably, reversible resistance is induced in the absence of cell death when caspase inhibitors are present and can be sustained for 1 wk or more, also without cell death, by periodic ligand exposure. Thus stochastic differences in cell state can have sustained consequences for sen­sitivity to prodeath ligands and acquisition of proinflammatory phenotypes. The important role played by periodicity in TRAIL exposure for induction of opposing apoptosis and survival mechanisms has implications for the design of optimal therapeutic agents and protocols.     

Isaac Lea's Palaeosauropus (= “Sauropus”) primaevus: A Review of His Discovery

In 1849, Isaac Lea named Sauropus primaevus for footprints from Mount Carbon, Pennsylvania, USA, then the oldest fossil vertebrate footprints reported. In 1902, O. P. Hay constructed a new ichnogenus Palaeosauropus for this ichnospecies. Palaeosauropus has been one of the most frequently reported Mississippian footprint ichnogenera in North America and remains a valid ichnotaxon. The holotype of Palaeosauropus (= “Sauropus”) primaevus (referred to as P. primaevus), consisting of a single manus/pes pair, is described and illustrated in Lea (1853) Lea, I. 1853. On the fossil foot-marks in the Red Sandstones of Pottsville, Schuylkill County, Penna. Transactions of the American Philosophical Society, 10(new series): 307–315.  [Google Scholar] and is housed at the Academy of Natural Sciences in Philadelphia, Pennsylvania (ANS9752). Lea's large specimen of P. primaevus (approximately 86 cm by 53 cm), that included a trackway of six manus/pes pairs, described and illustrated in 1853 and 1855, was a combination of ANS9752 and a second specimen represented by a plaster cast housed at the National Museum of Natural History (USNM487148). Historical documents and examination of the Mauch Chunk Formation at Mount Carbon, Pennsylvania, enabled the identification of Lea's tracksite, originally reported to be a few hundred feet (about 75 m) from the former Mount Carbon Hotel. Our forensic evidence indicates the type locality for P. primaevus is approximately 90 m south from the southwest corner of Centre and Main Streets in Mount Carbon, Pennsylvania, with geographical coordinates of N 40° 40' 25.7”, W 76° 11' 14.9”. The type locality is within the middle member of the Mauch Chunk Formation, a fluvial sequence of late Mississippian (Visean) Age.