Lifelong Expression of Apolipoprotein D in the Human Brainstem: Correlation with Reduced Age-Related Neurodegeneration

The lipocalin apolipoprotein D (Apo D) is upregulated in peripheral nerves following injury and in regions of the central nervous system, such as the cerebral cortex, hippocampus, and cerebellum, during aging and progression of certain neurological diseases. In contrast, few studies have examined Apo D expression in the brainstem, a region necessary for survival and generally less prone to age-related degeneration. We measured Apo D expression in whole human brainstem lysates by slot-blot and at higher spatial resolution by quantitative immunohistochemistry in eleven brainstem nuclei (the 4 nuclei of the vestibular nuclear complex, inferior olive, hypoglossal nucleus, oculomotor nucleus, facial motor nucleus, nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve, and Roller`s nucleus). In contrast to cortex, hippocampus, and cerebellum, apolipoprotein D was highly expressed in brainstem tissue from subjects (N = 26, 32−96 years of age) with no history of neurological disease, and expression showed little variation with age. Expression was significantly stronger in somatomotor nuclei (hypoglossal, oculomotor, facial) than visceromotor or sensory nuclei. Both neurons and glia expressed Apo D, particularly neurons with larger somata and glia in the periphery of these brainstem centers. Immunostaining was strongest in the neuronal perinuclear region and absent in the nucleus. We propose that strong brainstem expression of Apo D throughout adult life contributes to resistance against neurodegenerative disease and age-related degeneration, possibly by preventing oxidative stress and ensuing lipid peroxidation.     

40S Ribosome Biogenesis Co-Factors Are Essential for Gametophyte and Embryo Development

Ribosome biogenesis is well described in Saccharomyces cerevisiae. In contrast only very little information is available on this pathway in plants. This study presents the characterization of five putative protein co-factors of ribosome biogenesis in Arabidopsis thaliana, namely Rrp5, Pwp2, Nob1, Enp1 and Noc4. The characterization of the proteins in respect to localization, enzymatic activity and association with pre-ribosomal complexes is shown. Additionally, analyses of T-DNA insertion mutants aimed to reveal an involvement of the plant co-factors in ribosome biogenesis. The investigated proteins localize mainly to the nucleolus or the nucleus, and atEnp1 and atNob1 co-migrate with 40S pre-ribosomal complexes. The analysis of T-DNA insertion lines revealed that all proteins are essential in Arabidopsis thaliana and mutant plants show alterations of rRNA intermediate abundance already in the heterozygous state. The most significant alteration was observed in the NOB1 T-DNA insertion line where the P-A3 fragment, a 23S-like rRNA precursor, accumulated. The transmission of the T-DNA through the male and female gametophyte was strongly inhibited indicating a high importance of ribosome co-factor genes in the haploid stages of plant development. Additionally impaired embryogenesis was observed in some mutant plant lines. All results support an involvement of the analyzed proteins in ribosome biogenesis but differences in rRNA processing, gametophyte and embryo development suggested an alternative regulation in plants.     

Cost-Effectiveness Analysis of the Bivalent and Quadrivalent Human Papillomavirus Vaccines from a Societal Perspective in Colombia

Objective

To compare costs and effectiveness of three strategies used against cervical cancer (CC) and genital warts: (i) Screening for CC; (ii) Bivalent Human Papillomavirus (HPV) 16/18 vaccine added to screening; (iii) Quadrivalent HPV 6/11/16/18 vaccine added to screening.

Methods

A Markov model was designed in order to simulate the natural history of the disease from 12 years of age (vaccination) until death. Transition probabilities were selected or adjusted to match the HPV infection profile in Colombia. A systematic review was undertaken in order to derive efficacy values for the two vaccines as well as for the operational characteristics of the cytology test. The societal perspective was used. Effectiveness was measured in number of averted Disability Adjusted Life Years (DALYS).

Results

At commercial prices reported for 2010 the two vaccines were shown to be non-cost-effective alternatives when compared with the existing screening strategy. Sensitivity analyses showed that results are affected by the cost of vaccines and their efficacy values, making it difficult to determine with certainty which of the two vaccines has the best cost-effectiveness profile. To be ‘cost-effective’ vaccines should cost between 141 and 147 USD (Unite States Dollars) per vaccinated girl at the most. But at lower prices such as those recommended by WHO or the price of other vaccines in Colombia, HPV vaccination could be considered very cost-effective.

Conclusions

HPV vaccination could be a convenient alternative for the prevention of CC in Colombia. However, the price of the vaccine should be lower for this vaccination strategy to be cost-effective. It is also important to take into consideration the willingness to pay, budgetary impact, and program implications, in order to determine the relevance of a vaccination program in this country, as well as which vaccine should be selected for use in the program.     

DPT tautomerization of the long A∙A* Watson-Crick base pair formed by the amino and imino tautomers of adenine: combined QM and QTAIM investigation

Combining quantum-mechanical (QM) calculations with quantum theory of atoms in molecules (QTAIM) and using the methodology of sweeps of the energetic, electron-topological, geometric and polar parameters, which describe the course of the tautomerization along the intrinsic reaction coordinate (IRC), we showed for the first time that the biologically important A?A* base pair (C_s symmetry) formed by the amino and imino tautomers of adenine (A) tautomerizes via asynchronous concerted double proton transfer (DPT) through a transition state (TS), which is the A⁺?A^? zwitterion with the separated charge, with C_s symmetry. The nine key points, which can be considered as electron-topological “fingerprints” of the asynchronous concerted A?A*?A*?A tautomerization process via the DPT, were detected and completely investigated along the IRC of the A?A*?A*?A tautomerization. Based on the sweeps of the H-bond energies, it was found that intermolecular antiparallel N6Н?N6 (7.01 kcal mol^?1) and N1H?N1 (6.88 kcal mol^?1) H-bonds are significantly cooperative and mutually reinforce each other. It was shown for the first time that the A?A*?A*?A tautomerization is assisted by the third C2H?HC2 dihydrogen bond (DHB), which, in contrast to the two others N6H?N6 and N1H?N1 H-bonds, exists within the IRC range from ?2.92 to 2.92 Å. The DHB cooperatively strengthens, reaching its maximum energy 0.42 kcal mol^?1 at IRC?=??0.52 Å and minimum energy 0.25 kcal mol^?1 at IRC?=??2.92 Å, and is accompanied by strengthening of the two other aforementioned classical H-bonds. We established that the C2H?HC2 DHB completely satisfies the electron-topological criteria for H-bonding, in particular Bader’s and all eight “two-molecule” Koch and Popelier’s criteria. The positive value of the Grunenberg’s compliance constant (5.203 Å/mdyn) at the TS_A?A*?A*?A proves that the C2H?HC2 DHB is a stabilizing interaction. NBO analysis predicts transfer of charge from σ(C2–H) bonding orbital to σ*(H–C2) anti-bonding orbital; at this point, the stabilization energy E⁽²⁾ is equal to 0.19 kcal mol^?1 at the TS_A?A*?A*?A.     

Occurrence of Fatty Acid Short‐Chain‐Alkyl Esters in Fruits of Celastraceae Plants

Small amounts of a mixture of fatty acid short‐chain‐alkyl esters (FASCAEs) were obtained from the fruits of twelve plant species of Celastraceae family, and in five of them the FASCAEs were present not only in the arils but also in the seeds. These mixtures contained 32 individual FASCAE species, which formed four separate fractions, viz. FA methyl, ethyl, isopropyl, and butyl esters (FAMEs, FAEEs, FAIPEs, and FABEs, resp.). The FASCAE acyl components included the residues of 16 individual C₁₄–C₂₄ saturated, mono‐, di‐, and trienoic FAs. Linoleic, oleic, and palmitic acids, and, in some cases, also α‐linolenic acid predominated in FAMEs and FAEEs, while myristic acid was predominant in FAIPEs. It can be suggested that, in the fruit arils of some plant species, FAMEs and FAEEs were formed at the expense of a same FA pool characteristic of a given species and were strongly different from FAIPEs and FABEs esters regarding the mechanism of their biosynthesis. However, as a whole, the qualitative and quantitative composition of various FASCAE fractions, as well as their FA composition, varied considerably depending on various factors. Therefore, separate FASCAE fractions seem to be synthesized from different FA pools other than those used for triacylglycerol formation.     

Genetic variation in dopamine‐related gene expression influences motor skill learning in mice

Several neurodevelopmental disorders with a strong genetic basis, including attention‐deficit/hyperactivity disorder, autism spectrum disorders and developmental coordination disorder, involve deficits in fine motor skills. This phenotype may depend on heritable variation in components of the dopamine (DA) system, which is known to play a critical role in motor skill learning. In this study, we took advantage of two inbred strains of mice (BALB/c and C57BL/6) that differ markedly in the number of midbrain DA neurons in order to investigate the influence of such naturally occurring genetic variation on the acquisition and performance of fine motor skills. Gene expression analysis of midbrain, frontal cortex and striatum showed significant differences in the expression of presynaptic and postsynaptic dopaminergic (DAergic) markers (e.g. tyrosine hydroxylase, DA transporter, DA D4 receptor, DA D5 receptor and DARPP‐32) between these two strains. BALB/c mice had lower learning rate and performance scores in a complex skilled reaching task when compared with C57BL/6 mice. A negative correlation was found between the motor learning rate and level of DARPP‐32 mRNA expression in the frontal cortex contralateral to the trained forelimb. The rate of motor learning was also negatively correlated with the levels of DARPP‐32 and DA D1 receptor mRNAs in the striatum. Our results suggest that genetically driven variation in frontostriatal DAergic neurotransmission is a major contributor to individual differences in motor skill learning. Moreover, these findings implicate the D1R/cAMP/DARPP‐32 signaling pathway in those neurodevelopmental disorders that are associated with fine motor skill deficits.     

The need for standardization in wildlife science: home range estimators as an example

Individual studies in wildlife science are indicative rather than conclusive. Although multiple studies can be meta-analyzed in such a way that scientific hypotheses can be tested, robust meta-analyses are often difficult or impossible if variables of interest are not measured in a uniform manner. We hypothesized that measurements, even of basic and unequivocal variables, are rarely standardized in wildlife sciences. We tested this assumption by reviewing randomly selected papers that describe the home range of mammals (n?=?25) and birds (n?=?25). In these papers, home ranges were calculated using 11 methods and 8 computer programs. The number of radiolocations used to calculate home ranges varied from 9 to >2,000. By estimating home ranges for two radiotelemetry data sets, we demonstrate that home ranges are not comparable if different methods are used and that estimates of home range are not standardized. We assume that measurements of other biological variables are even less consistent across studies. In order to advance wildlife sciences, we believe that standardization initiatives are required at an international level.     

Transcriptional Cofactor TBLR1 Controls Lipid Mobilization in White Adipose Tissue

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Highlights? TBLR1 controls cAMP-dependent lipolysis in adipocytes ? Adipocyte-specific deletion of TBLR1 in mice impairs fasting-induced lipolysis ? Lack of TBLR1 in adipocytes aggravates diet-induced obesity and metabolic dysfunction ? TBLR1 mRNA levels in WAT are elevated under lipolytic conditions in mice and humans