Past and future approaches to ischemia-reperfusion lesion associated with liver transplantation

Ischemia-reperfusion (I/R) injury associated with liver transplantation remains a serious complication in clinical practice, in spite of several attempts to solve the problem. The present review focuses on the complexity of I/R injury, summarizing conflicting results obtained from the literature about the mechanisms responsible for it. We also review the therapeutic strategies designed in past years to reduce I/R injury, attempting to explain why most of them have not been applied clinically. These strategies include improvements in pharmacological treatments, modifications of University of Wisconsin (UW) preservation solution based on a variety of additives, and gene therapy. Finally, we will consider new potential protective strategies using trimetazidine, 5-amino-4-imidazole carboxamide riboside (AICAR), melatonin, modulators of the renin-angiotensin system (RAS) and the phosphatidylinositol-3-OH kinase (PI3K)-Akt and the p42/p44 extracellular signal-regulated kinases (Erk 1/2) pathway. These strategies have shown promising results for I/R injury but have not been tested in experimental liver transplantation to date. Moreover, we will review ischemic preconditioning, taking into account the recent clinical studies that suggest that this surgical strategy could be appropriate for liver transplantation.     

Structural and Functional Analysis of Human SOD1 in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with familial inheritance (fALS) in 5% to 10% of cases; 25% of those are caused by mutations in the superoxide dismutase 1 (SOD1) protein. More than 100 mutations in the SOD1 gene have been associated with fALS, altering the geometry of the active site, protein folding and the interaction between monomers. We performed a functional analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in 124 fALS SOD1 mutants. Eleven different algorithms were used to estimate the functional impact of the replacement of one amino acid on protein structure: SNPs&GO, PolyPhen-2, SNAP, PMUT, Sift, PhD-SNP, nsSNPAnalyzer, TANGO, WALTZ, LIMBO and FoldX. For the structural analysis, theoretical models of 124 SNPs of SOD1 were created by comparative modeling using the MHOLline workflow, which includes Modeller and Procheck. Models were aligned with the native protein by the TM-align algorithm. A human-curated database was developed using the server side include in Java, JMOL. The results of this functional analysis indicate that the majority of the 124 natural mutants are harmful to the protein structure and thus corroborate the correlation between the reported mutations and fALS. In the structural analysis, all models showed conformational changes when compared to wild-type SOD1, and the degree of structural alignment varied between them. The SOD1 database converge structural and functional analyses of SOD1; it is a vast resource for the molecular analysis of amyotrophic lateral sclerosis, which allows the user to expand his knowledge on the molecular basis of the disease. The SOD1 database is available at http://bioinfogroup.com/database.     

Aqueous and solid complexes of iron(III) with hyaluronic acid. Potentiometric titrations and infrared spectroscopy studies

The coordination of iron(III) ion to hyaluronic acid (Hyal) in aqueous solutions and solid state was accomplished by potentiometric titrations and infrared spectroscopy. The potentiometric titration studies provided the binding constants for the complexes found in the systems and the speciation of these species according to the variation of pH values. The complexes found presented a complexing ability through both the chelating moieties of Hyal (via the N-glucosamine and D-glucoronic acid), showing no special preference for either one while in solid state, but when in aqueous solution the complexation via the N-glucosamine moiety was the preferred, forming two complexed species, ML and ML(2) (log K(ML)=8.2 and log K(ML2)=7.9). The presence of a mu-oxo complex via the D-glucoronic acid was also detected in both aqueous (log K=6.7) and solid states via the N-glucosamine and D-glucoronic acid simultaneously linked to two Hyal chains. A structure for this latter complex was suggested. The results indicated that these complexes could be used in eliminating the excess iron(III) in living organisms.     

Crayfish learning abilities: how does familiarization period affect the capture rate of a new prey item?

This study explores the effect of the length of learning period on capture rate of a previously unfamiliar prey by an invasive freshwater crayfish (Procambarus clarkii). Juvenile crayfish were subjected to different periods of contact (learning period) with a larvae prey (Chaoborus sp.). The length of the learning period significantly affected the number of prey consumed by the predator. Our results indicate that the naive crayfish require less than 12 h to learn to maximize capture rate of this prey. The learning coefficient, adopted in the present study, may be useful in exploring predation capabilities of alien species in newly invaded habitats.     

The Biology and Thermal Requirements of the Fennel Aphid Hyadaphis foeniculi (Passerini) (Hemiptera: Aphididae)

The relationship between the insect development rate and temperature was established very early and represents an important ecological variable for modeling the population dynamics of insects. The accurate determination of thermal constant values and the lower and upper developmental thresholds of Hyadaphis foeniculi (Passerini) (Hemiptera: Aphididae) on fennel (Foeniculum vulgare Miller (Apiales: Apiaceae)) crops would obviously benefit the effective application of control measures. This paper is a study of the biology and thermal requirements of H. foeniculi. Winged insects were collected from fennel crops at the Embrapa Algodão in Campina Grande, Paraíba. Nymphs (age ≤24 h) produced by winged insects were subjected to constant temperatures of 15, 20, 25, 28, 30 or 33°C, a photophase of 12 h and a relative humidity of 70±10%. The results of the study showed that at temperatures between 15 and 30°C, H. foeniculi nymphs were able to develop normally. The four instars were found at all temperatures tested. However, temperatures of 3 and 33°C were lethal to the nymphs. The nymph stage development time varied from 5 (30°C) to 19 (15°C) days. The influence of temperature on the development time is dependent on the instar. The base temperature (Tb) and the thermal constant (K) for the nymph stage were estimated at 11.2°C and 107.5 degree-days, respectively. The shortest nymph development stage was observed at 30°C, and the highest nymph viability (85.0%) was observed at 28°C. This information can be used for developing phenological models based on the temperature and development rate relationships so that outbreaks of H. foeniculi in the fennel crop can be predicted, therefore improving the application of control programs targeting this fennel pest.     

Changes in Photosynthetic Performance of Ceratonia Siliqua in Summer

Photosynthetica - In carob tree (Ceratonia siliqua) radiant energy saturated net photosynthetic rate (P N) during summer was about 10 % of the spring values. This was accompanied by a reduction in...     

Thermodynamic Framework of the Interaction between Protein and Solvent Drives Protein Folding

Abstract

We use internal coordinate molecular mechanics calculations to study the impact of abasic sites on the conformation and the mechanics of the DNA double helix. Abasic sites, which are common mutagenic lesions, are shown to locally modify both the groove geometry and the curvature of DNA in a sequence dependent manner. By controlled twisting and bending, it is also shown that these lesions modify the deformability of the duplex, generally increasing its flexibility, but again to an extent which depends on the nature of the abasic site and on the surrounding base sequence. Both the conformational and mechanical influence of this type of DNA damage may be significant for recognition and repair mechanisms.     

Apoptosis in transgenic mice expressing the P301L mutated form of human tau

The rTg4510 mouse is a tauopathy model, characterized by massive neurodegeneration in Alzheimer's disease (AD)-relevant cortical and limbic structures, deficits in spatial reference memory, and progression of neurofibrillary tangles (NFT). In this study, we examined the role of apoptosis in neuronal loss and associated tau pathology. The results showed that DNA fragmentation and caspase-3 activation are common in the hippocampus and frontal cortex of young rTg4510 mice. These changes were associated with cleavage of tau into smaller intermediate fragments, which persist with age. Interestingly, active caspase-3 was often co-localized with cleaved tau. In vitro, fibrillar Abeta(1-42) resulted in nuclear fragmentation, caspase activation, and caspase-3-induced cleavage of tau. Notably, incubation with the antiapoptotic molecule tauroursodeoxycholic acid abrogated apoptosis-mediated cleavage of tau in rat cortical neurons. In conclusion, caspase-3-cleaved intermediate tau species occurred early in rTg54510 brains and preceded cell loss in Abeta-exposed cultured neurons. These results suggest a potential role of apoptosis in neurodegeneration.     

AIR: A batch-oriented web program package for construction of supermatrices ready for phylogenomic analyses

Background  

Large multigene sequence alignments have over recent years been increasingly employed for phylogenomic reconstruction of the eukaryote tree of life. Such supermatrices of sequence data are preferred over single gene alignments as they contain vastly more information about ancient sequence characteristics, and are thus more suitable for resolving deeply diverging relationships. However, as alignments are expanded, increasingly numbers of sites with misleading phylogenetic information are also added. Therefore, a major goal in phylogenomic analyses is to maximize the ratio of information to noise; this can be achieved by the reduction of fast evolving sites.