Rapamycin and Ageing: When,for How Long,and How Much?

正The mechanistic target of rapamycin(mTOR)is a nutrient and growth factor responsive kinase that modulates lifespan in species from yeast to mice(Johnson et al.,2013b).mTOR exists in two complexes within cells,mTOR complexⅠ(mTORC1)and mTOR complex 2(mTORC2)(Laplante and Sabatini,2012).Abundant evidence suggests that mTORC1is the primary mTOR complex involved in regulating longevity:mutations that reduce the     

Mitochondria--a nexus for aging, calorie restriction, and sirtuins?

Recent studies of calorie restriction in several organisms demonstrate an increase in mitochondrial activity that is associated with the salutary effects of this dietary restriction regimen. In this Essay, I speculate on how an increase in mitochondrial activity might provide benefit and discuss how diet, mitochondria, and sirtuins might interact in a pathway to slow aging and associated diseases.     

Environment–richness relationships for mammals,birds, reptiles,and amphibians at global and regional scales

Climate has been routinely indicated as a major determinant of broad-scale species richness patterns for a variety of taxa, but studies vary widely in attributing richness variation to the broad-scale distribution of energy, water, ecosystem productivity, habitat heterogeneity, or some combination thereof. Here, I report global and regional environment–richness relationships for the four classes of terrestrial vertebrates (mammals, birds, reptiles, amphibians) using identical sample units and the same set of climate (temperature, precipitation, annual actual evapotranspiration), productivity (normalized difference vegetation index), and topographic (elevation range) variables. My results strongly support concomitant availability of energy and water as the principal constraint on global richness for all vertebrate groups except reptiles, which are largely constrained by temperature. However, environment–richness models for all taxonomic groups varied widely when applied to single (continental-scale) biogeographic realms. In particular, I found strong support for the ‘water–energy dynamics hypothesis’ that models richness as a function of ambient energy (temperature) in high latitudes and water availability (precipitation) at low latitudes, partially independent of productivity. Ectotherm groups were more constrained by temperature than endotherms, and amphibians were more constrained by water availability than other groups. Although habitat heterogeneity, measured as elevation range, was a consistent contributor to global and regional richness models for all groups, its contribution was always minor compared to other variables. I conclude that temperature and water availability are key variables for modeling broad-scale vertebrate richness, but there remains significant room for taxon-specific modeling approaches and for the inclusion of non-climate factors related to evolutionary history and faunal assembly in different regions.     

Correlation Relation for the Membrane Transport ParametersLp, σ, and ω

We derive a formula for the correlation of the three practical transportparameters L_p, , and appearing in Kedem-Katchalskyequations. It has a form = KL_p/v_s(1-), where K = 0.0306 is a universal constant independent ofthe choice of a membrane and a solute. It can be used to calculate the valueof any of these parameters, provided the other two and the molar volume of the solute are known. The formula couldbe very useful, in particular when measurements of the parameters aredifficult or even impossible.     

Entrails,heart, brain,limbs, and lymphatics- a recipe for success?

A recent Juan March Foundation workshop entitled Developmental Mechanisms in Vertebrate Organogenesis brought 50 developmental biologists together in Madrid to share some of their latest findings. Discussion topics included ectodermal organs such as the central nervous system (CNS) and skin, mesodermal organs such as the heart, limb, vasculature, and kidney, and endodermal organs such as the pancreas and liver. Discussions extended into the late hours of the night as the meeting participants indulged in tasting some of their favorite organs, in the form of Spanish delicacies.     

Agroforestry and Biodiversity Conservation – Traditional Practices, Present Dynamics, and Lessons for the Future

The environmental services that agroforestry practices can provide, and especially their potential contribution to the conservation of biodiversity, have only recently attracted wider attention among agroforestry and conservation scientists. This new view is consistent with the ecosystem approach to natural resource management advocated by the Convention on Biological Diversity. This collection of six papers, which is based on a Workshop held in June–July 2004, brings together studies of biodiversity impacts of traditional agroforestry practices from Central and South America, Africa and Asia. The contributions highlight the considerable potential of traditional agroforestry practices to support biodiversity conservation, but also show their limits. These include the importance of sufficient areas of natural habitat and of appropriate hunting regulations for maintaining high levels of biodiversity in agroforestry land use mosaics, as well as the critical role of markets for tree products and of a favourable policy environment for agroforestry land uses. In combination the case studies suggest that maintaining diversity in approaches to management of agroforestry systems, along with a pragmatic, undogmatic view on natural resource management, will provide the widest range of options for adapting to changing land use conditions.     

A direct,ratiometric, and quantitative MALDI–MS assay for protein methyltransferases and acetyltransferases

Protein methylation and acetylation play important roles in biological processes, and misregulation of these modifications is involved in various diseases. Therefore, it is critical to understand the activities of the enzymes responsible for these modifications. Herein we describe a sensitive method for ratiometric quantification of methylated and acetylated peptides via MALDI–MS by direct spotting of enzymatic methylation and acetylation reaction mixtures without tedious purification procedures. The quantifiable detection limit for peptides with our method is approximately 10 fmol. This is achieved by increasing the signal-to-noise ratio through the addition of NH₄H₂PO₄ to the matrix solution and reduction of the matrix α-cyanohydroxycinnamic acid concentration to 2 mg/ml. We have demonstrated the application of this method in enzyme kinetic analysis and inhibition studies. The unique feature of this method is the simultaneous quantification of multiple peptide species for investigation of processivity mechanisms. Its wide buffer compatibility makes it possible to be adapted to investigate the activity of any protein methyltransferase or acetyltransferase.     

N-α-PGP and PGP,potential biomarkers and therapeutic targets for COPD

Background

Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder for which new diagnostic and therapeutic approaches are required. Hallmarks of COPD are matrix destruction and neutrophilic airway inflammation in the lung. We have previously described two tri-peptides, N-α-PGP and PGP, which are collagen fragments and neutrophil chemoattractants. In this study, we investigate if N-α-PGP and PGP are biomarkers and potential therapeutic targets for COPD.

Methods

Induced sputum samples from COPD patients, healthy controls and asthmatics were examined for levels of N-α-PGP and PGP using mass spectrometry and for the ability to generate PGP de novo from collagen. Proteases important in PGP generation in the lung were identified by the use of specific inhibitors in the PGP generation assay and by instillation of proteases into mouse lungs. Serum levels of PGP were compared between COPD patients and controls.

Results

N-α-PGP was detected in most COPD sputum samples but in no asthmatics or controls. PGP was detected in a few controls and in all COPD sputum samples, where it correlated with levels of myeloperoxidase. COPD sputum samples had the ability to generate N-α-PGP and PGP de novo from collagen. PGP generation by COPD sputum was blocked by inhibitors of matrix metalloproteases (MMP''s) 1 and 9 and prolyl endopeptidase. MMP''s 1 and 9 and prolyl endopeptidase acted synergistically to generate PGP in vivo when instilled into mouse lungs. Serum levels of PGP were also significantly higher in COPD patients than in controls

Conclusion

N-α-PGP and PGP may represent novel diagnostic tests and biomarkers for COPD. Inhibition of this pathway may provide novel therapies for COPD directed at the chronic, neutrophilic, airway inflammation which underlies disease progression.     

Bacterial Diversity and Bioprospecting for Cold-Active Lipases,Amylases and Proteases,from Culturable Bacteria of Kongsfjorden and Ny-Ålesund,Svalbard, Arctic

Culturable bacterial diversity of seven marine sediment samples of Kongsfjorden and a sediment and a soil sample from Ny-Ålesund, Svalbard, Arctic was studied. The bacterial abundance in the marine sediments of Kongsfjorden varied marginally (0.5 × 10³–1.3 × 10⁴ cfu/g sediment) and the bacterial number in the two samples collected from the shore of Ny-Ålesund also was very similar (0.6 × 10⁴ and 3.4 × 10⁴, respectively). From the nine samples a total of 103 bacterial isolates were obtained and these isolates could be grouped in to 47 phylotypes based on the 16S rRNA gene sequence belonging to 4 phyla namely Actinobacteria, Bacilli, Bacteroidetes and Proteobacteria. Representatives of the 47 phylotypes varied in their growth temperature range (4–37°C), in their tolerance to NaCl (0.3–2 M NaCl) and growth pH range (2–11). Representatives of 26 phylotypes exhibited amylase and lipase activity either at 5 or 20°C or at both the temperatures. A few of the representatives exhibited amylase and/or lipase activity only at 5°C. None of the phylotypes exhibited protease activity. Most of the phylotypes (38) were pigmented. Fatty acid profile studies indicated that short chain fatty acids, unsaturated fatty acids, branched fatty acids, the cyclic and the cis fatty acids are predominant in the psychrophilic bacteria.     

Synthesis and binding affinity of novel mono- and bivalent morphinan ligands for κ, μ, and δ opioid receptors

A novel series of homo- and heterodimeric ligands containing κ/μ agonist and μ agonist/antagonist pharmacophores joined by a 10-carbon ester linker chain were synthesized and evaluated for their in vitro binding affinity at κ, μ, and δ opioid receptors, and their functional activities were determined at κ and μ receptors in [(35)S]GTPγS functional assays. Most of these compounds had high binding affinity at μ and κ receptors (K(i) values less than 1nM). Compound 15b, which contains butorphan (1) at one end of linking chain and butorphanol (5) at the other end, was the most potent ligand in this series with binding affinity K(i) values of 0.089nM at the μ receptor and 0.073nM at the κ receptor. All of the morphinan-derived ligands were found to be partial κ and μ agonists; ATPM-derived ligands 12 and 11 were found to be full κ agonists and partial μ agonists.     

MTCS for Cancer and AIDS Treatment,A Brief Introduction

Modified Trichosanthin (MTCS) is a new drug for treating cancer, AIDS and other viral infectionsdeveloped with protein engineering technologies. Its pre-clinical research works were completed by ShanghaiInstitute for Biological Sciences (formerly Shanghai Institute of Cell Biology), Chinese Academy of Sciences.This project is currently seeking partnership world-wide.HIGH ANTI-CANCER ACTIVITY AND LOW TOXICITY MTCS is a powerful inhibitant to a broad variety of human cancer cells, e.g., leukemia, stomach cancer,hepatoma, lung cancer, colon cancer, breast cancer, kidney cancer, melanoma, and brain cancer, etc. Studyresults indicated the presence of MTCS specific binding receptors on the membrane of cancer cells. MTCSinduces cancer cellular apoptosis through binding with these receptors. No such receptor is present on normalbody cells. Therefore no toxic effects in normal body cells can be observed even at a concentration severalhundred times higher than that used in treatments.     

Adolescents’ Use of Care for Behavioral and Emotional Problems: Types,Trends, and Determinants

Objective

While adolescents use various types of care for behavioral and emotional problems, evidence on age trends and determinants per type is scarce. We aimed to assess use of care by adolescents because of behavioral and emotional problems, overall and by type, and its determinants, for ages 10–19 years.

Methods

We obtained longitudinal data on 2,230 adolescents during ages 10–19 from four measurements regarding use of general care and specialized care (youth social care and mental healthcare) in the preceding 6 months, the Child Behavior Checklist (CBCL) and Youth Self-Report, and child and family characteristics. We analyzed data by multilevel logistic regression.

Results

Overall rates of use increased from 20.1% at age 10/11 to 32.2% at age 19: general care was used most. At age 10/11 use was higher among boys, at age 19 among girls. Use of general care increased for both genders, whereas use of specialized care increased among girls but decreased among boys. This differential change was associated with CBCL externalizing and internalizing problems, school problems, family socioeconomic status, and parental divorce. Preceding CBCL problems predicted more use: most for mental health care and least for general care. Moreover, general care was used more frequently by low and medium socioeconomic status families, with odds ratios (95%-confidence intervals): 1.52 (1.23;1.88) and 1.40 (1.17;1.67); youth social care in case of parental divorce, 2.07 (1.36;3.17); and of special education, 2.66 (1.78;3.95); and mental healthcare in case of special education, 2.66 (1.60;4.51).

Discussion

Adolescents with behavioral and emotional problems use general care most frequently. Overall use increases with age. Determinants of use vary per type.     

Programs,databases, and expert systems for human geneticists — a survey

We present an overview of the variety of databases and programs that offer substantial aid to medical and molecular geneticists. Databases and expert systems for genetic diseases and birth defects, programs for segregation and linkage analysis, certain DNA and protein sequence databases, and information resources in general for molecular biology are addressed. These systems cannot be used effectively without the newly developed techniques of information exchange based on international computer networks. A short introduction is given to the Internet and to European institutions and organizations that offer help with the aquisition and use of bioinformatic resources.