Identification of TEX101-associated Proteins Through Proteomic Measurement of Human Spermatozoa Homozygous for the Missense Variant rs35033974,

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Highlights

• •Missense variant rs35033974 resulted in significantly reduced levels of human TEX101 protein in seminal plasma and spermatozoa.
• •Differential proteomics revealed TEX101-associated testis-specific proteins, including LY6K, which were down-regulated in rs35033974^hh spermatozoa.
• •Deep proteome of human spermatozoa, including some “missing” proteins, was identified.

     

Computation of emotions in man and machines

The importance of emotional expression as part of human communication has been understood since Aristotle, and the subject has been explored scientifically since Charles Darwin and others in the nineteenth century. Advances in computer technology now allow machines to recognize and express emotions, paving the way for improved human–computer and human–human communications.Recent advances in psychology have greatly improved our understanding of the role of affect in communication, perception, decision-making, attention and memory. At the same time, advances in technology mean that it is becoming possible for machines to sense, analyse and express emotions. We can now consider how these advances relate to each other and how they can be brought together to influence future research in perception, attention, learning, memory, communication, decision-making and other applications.The computation of emotions includes both recognition and synthesis, using channels such as facial expressions, non-verbal aspects of speech, posture, gestures, physiology, brain imaging and general behaviour. The combination of new results in psychology with new techniques of computation is leading to new technologies with applications in commerce, education, entertainment, security, therapy and everyday life. However, there are important issues of privacy and personal expression that must also be considered.     

Paravirtualization effect on single- and multi-threaded memory-intensive linear algebra software

Previous studies have revealed that paravirtualization imposes minimal performance overhead on High Performance Computing (HPC) workloads, while exposing numerous benefits for this field. In this study, we are investigating the impact of paravirtualization on the performance of automatically-tuned software systems. We compare peak performance, performance degradation in constrained memory situations, performance degradation in multi-threaded applications, and inter-VM shared memory performance. For comparison purposes, we examine the proficiency of ATLAS, a quintessential example of an autotuning software system, in tuning the BLAS library routines for paravirtualized systems. Our results show that the combination of ATLAS and Xen paravirtualization delivers native execution performance and nearly identical memory hierarchy performance profiles in both single and multi-threaded scenarios. Furthermore, we show that it is possible to achieve memory sharing among OS instances at native speeds. These results expose new benefits to memory-intensive applications arising from the ability to slim down the guest OS without influencing the system performance. In addition, our findings support a novel and very attractive deployment scenario for computational science and engineering codes on virtual clusters and computational clouds.

Inverting the null-hypothesis of speciation: a marine snail perspective

Speciation is currently an intensely debated topic, much more so than 20–30 years ago when most biologists held the view that new species (at least of animals) were formed through the split of evolutionary lineages by the appearance of physical barriers to gene flow. Recent advances have, however, lent both theoretical and empirical support to speciation in the presence of gene flow. Nevertheless, the allopatric hypothesis of speciation is still the default model. The consequence of this is that to support sympatric and parapatric modes of speciation all allopatric alternatives must be rejected, while an allopatric explanation is usually accepted without rejecting possible non-allopatric alternatives. However, classical cases of allopatric speciation can be challenged by alternative non-allopatric explanations, and this begs for a more respectful view of how to deal with all models of speciation. An appealing approach is studying parallel evolution of reproductive barriers, which allows for comparative approaches to distinguish between allopatric and non-allopatric events, and explicit tests of a suitable null-hypothesis. Parallel evolution of reproductive isolation in a strongly polymorphic marine snail species serves as an illustrative example of such an approach. In conclusion, a more balanced debate on allopatric and non-allopatric speciation is needed and an urgent issue is to treat both allopatric and nonallopatric hypotheses critically, rather than using allopatry as the default model of speciation.     

A PAMPA Study of the Permeability‐Enhancing Effect of New Ceramide Analogues

There is a major need in drug discovery for quick, precise, and cost‐effective high‐throughput screening (HTS) systems in the early stages of drug research. The Parallel Artificial Membrane Permeability Assay (PAMPA) aims at predicting the passive membrane properties of drugs. Since 1998, model membranes have been developed to predict gastro‐intestinal absorption or transport through the blood–brain barrier. This paper presents recent results in a project aiming to improve the prediction of transdermal penetration. Using the PAMPA system, we investigated the effect of four newly synthetized ceramide analogues (certramides) on the permeability of three model compounds (ciprofloxacin, nifedipine, and verapamil). The certramides differ in the length of one alkyl chain, while the other alkyl chain and the head group remained the same. A relationship between the membrane concentration of certramides (from 0 to 100%) and the permeability of compounds was found, and the results of different certramides were compared. The strongest effect on permeability was caused by the ceramide analogue CTR(C₁₂–C₁₆). The reproducibility of the experiments and the impact of presence or absence of organic solvents (dodecane and CHCl₃) in the membrane were also investigated.     

Identification of phenylbutyrate-generated metabolites in Huntington disease patients using parallel liquid chromatography/electrochemical array/mass spectrometry and off-line tandem mass spectrometry

Oral sodium phenylbutyrate (SPB) is currently under investigation as a histone deacetylation (HDAC) inhibitor in Huntington disease (HD). Ongoing studies indicate that symptoms related to HD genetic abnormalities decrease with SPB therapy. In a recently reported safety and tolerability study of SPB in HD, we analyzed overall chromatographic patterns from a method that employs gradient liquid chromatography with series electrochemical array, ultraviolet (UV), and fluorescence (LCECA/UV/F) for measuring SPB and its metabolite phenylacetate (PA). We found that plasma and urine from SPB-treated patients yielded individual-specific patterns of approximately 20 metabolites that may provide a means for the selection of subjects for extended trials of SPB. The structural identification of these metabolites is of critical importance because their characterization will facilitate understanding the mechanisms of drug action and possible side effects. We have now developed an iterative process with LCECA, parallel LCECA/LCMS, and high-performance tandem MS for metabolite characterization. Here we report the details of this method and its use for identification of 10 plasma and urinary metabolites in treated subjects, including indole species in urine that are not themselves metabolites of SPB. Thus, this approach contributes to understanding metabolic pathways that differ among HD patients being treated with SPB.     

Inheritance of seed colour in turnip rape (Brassica campestris L.)

Summary A high gene frequency for ps (parallel spindles) is expected in cultivated tetraploid potatoes, S. tuberosum Group Tuberosum, if 2n pollen produced by ancestral diploid plants which were psps was involved in the origin and evolution of the potato. Fifty-six North American cultivars (varieties and advanced selections) were pollinated by diploid clones, either W 5295.7 or W 5337.3 which are homozygous recessive for ps. The segregation ratios in regard to 2n pollen production in derived tetraploid progenies, from 4x×2x crosses, reveal the genotype of ps in the cultivars. Microsporogenesis of 2n pollen producing 4x progeny was observed to avoid an overestimation of the frequency of 2n pollen producing plants due to mechanisms other than parallel spindles. More than 50% of the 56 cultivars are simplex (Pspspsps), since in each of these cultivars about 50% of their progeny produced 2n pollen. The ps gene frequency in the 56 cultivars was estimated as high as 0.69. The high frequency of ps in the tetraploid cultivars clearly supports the hypothesis that 2n pollen produced by plants homozygous recessive for ps have been involved in the origin of cultivated tetraploid potatoes, since a higher frequency of ps in the tetraploid than in the ancestral diploid population can be expected from sexual polyploidization but not from somatic doubling. The importance of meiotic mutants such as ps for the successful evolution of polysomic polyploids is emphasized.     

Transglutaminase stabilizes melanoma adhesion under laminar flow

To resist substantial wall shear stress (WSS) exerted by flowing blood, metastatic melanoma cells can form adhesive contacts with subendothelial extracellular matrix proteins, such as fibronectin (FN). Such contacts may be stabilized by transglutaminase catalyzed-crosslinkage of cell focal adhesion proteins. We analyzed human melanoma cell adhesion under flow by decreasing the flow (WSS) of melanoma cell suspensions and allowing them to adhere to immobilized wheat germ agglutinin or FN. At the wall shear adhesion threshold (WSAT), cell adherence was rapid with no rolling. Following cell adherence, we increased the flow and determined the wall shear detachment threshold (WSDeT). Cells spread and remained adherent on immobilized FN at high WSDeTs (≥ 32.5 dynes/cm²). The high resistance of adherent cells to shear forces suggested that transglutaminase-mediated crosslinking might be involved. Transglutaminase inhibitors monodansylcadaverine and INO-3178 decreased WSAT, and at low concentrations completely inhibited tumor cell spreading and promoted detachment at low WSDeTs (0.67 dynes/cm²). In static adhesion assays, transglutaminase inhibitors decreased cell adhesion to immobilized-FN in a dose-dependent manner and prevented the formation of crosslinked¹²⁵I-FN complex that failed to enter a SDS-polyacrylamide gradient gel. The data suggest that transglutaminase-catalyzed crosslinking, particularly in the presence of WSS, may be important in stabilizing cellular adhesive contacts during adhesion to immobilized-FN.     

Tool use by wild cebus monkeys at Santa Rosa National Park,Costa Rica

Although wild cebus monkeys have been observed to use tools, this behavior has been reported only rarely. No one has systematically examined tool use in wildCebus, and it is not known how prevalent tool use is in the species' natural repertoire. During 300 hr of observation on 21 wild capuchins (Cebus capucinus imitator) at Santa Rosa National Park in Costa Rica, 31 incidents of tool use, including eight different types of tool-use behavior, were observed. These observations indicate that tool use is a notable behavior pattern in this troop. Considering these incidents of tool use in conjunction with other reports on complex food-getting and preparation behavior byCebus suggests that tool use is a manifestation ofCebus' high behavioral adaptability. Since onlyCebus and the great apes (especially chimpanzees) have been observed to show such a diverse tool-use repertoire, to use tools so frequently, or to show such complex food-getting behavior in the wild, these observations also support the notion thatCebus and the great apes have followed a parallel evolutionary development of tool-using capacity.     

Parallel evolution of pairs of dehydrogenase isoenzymes

Summary Lactate dehydrogenase and glycerol 3-phosphate dehydrogenase are metabolically coupled by the anaerobic dismutation of glyceraldehyde 3-phosphate and by the NAD redox state. This causes the concentrations of lactate and glycerol 3-phosphate to accumulate proportionally during anaerobic muscle contraction; these concentrations are high relative to those in aerobic tissues such as liver. We show that the isoenzymes of lactate dehydrogenase and glycerol 3-phosphate dehydrogenase from chicken breast muscle haveKm values for lactate and glycerol 3-phosphate, respectively, that are 10-fold higher than theKm values measured for the lactate dehydrogenase and glycerol 3-phosphate dehydrogenase isoenzymes from chicken liver. The association of proportionally higherKm values with the potential for proportionally higher accumulation of substrates suggests that the isoenzymes of lactate dehydrogenase and glycerol 3-phosphate dehydrogenase from chicken muscle have evolved in parallel as a coupled metabolic unit distinct from the coupled isoenzymes in liver. The parallelism observed for the reduced substrates extends to the oxidized substrates, and to the coenzymes, NAD⁺ and NADH.