Disruption of fast axonal transport is a pathogenic mechanism for intraneuronal amyloid beta.

The pathological mechanism by which Abeta causes neuronal dysfunction and death remains largely unknown. Deficiencies in fast axonal transport (FAT) were suggested to play a crucial role in neuronal dysfunction and loss for a diverse set of dying back neuropathologies including Alzheimer's disease (AD), but the molecular basis for pathological changes in FAT were undetermined. Recent findings indicate that soluble intracellular oligomeric Abeta (oAbeta) species may play a critical role in AD pathology. Real-time analysis of vesicle mobility in isolated axoplasms perfused with oAbeta showed bidirectional axonal transport inhibition as a consequence of endogenous casein kinase 2 (CK2) activation. Conversely, neither unaggregated amyloid beta nor fibrillar amyloid beta affected FAT. Inhibition of FAT by oAbeta was prevented by two specific pharmacological inhibitors of CK2, as well as by competition with a CK2 substrate peptide. Furthermore, perfusion of axoplasms with active CK2 mimics the inhibitory effects of oAbeta on FAT. Both oAbeta and CK2 treatment of axoplasm led to increased phosphorylation of kinesin-1 light chains and subsequent release of kinesin from its cargoes. Therefore pharmacological modulation of CK2 activity may represent a promising target for therapeutic intervention in AD.

Genetic analysis of semen production traits of Japanese Black and Holstein bulls: genome-wide marker-based estimation of genetic parameters and environmental effect trends.

The semen production traits of bulls from 2 major cattle breeds in Japan, Holstein and Japanese Black, were analyzed comprehensively using genome-wide markers. Weaker genetic correlations were observed between the 2 age groups (1 to 3 yr old and 4 to 6 yr old) regarding semen volume and sperm motility compared with those observed for sperm number and motility after freeze-thawing. The preselection of collected semen for freezing had a limited effect. Given the increasing importance of bull proofs at a young age because of genomic selection and the results from preliminary studies, we used a multiple-trait model that included motility after freeze-thawing with records collected at young ages. Based on variations in contemporary group effects, accounting for both seasonal and management factors, Holstein bulls may be more sensitive than Japanese Black bulls to seasonal environmental variations; however, the seasonal variations of contemporary group effects were smaller than those of overall contemporary group effects. The improvement of motilities, recorded immediately after collection and freeze-thawing, was observed in recent years; thus, good management and better freeze-thawing protocol may alleviate seasonal phenotypic differences. The detrimental effects of inbreeding were observed in all traits of both breeds; accordingly, the selection of candidate bulls with high inbreeding coefficients should be avoided per general recommendations. Semen production traits have never been considered for bull selection. However, negative genetic trends were observed. The magnitudes of the estimated h were comparable to those of other economically important traits. A single-step genomic BLUP will provide more accurate predictions of breeding values compared with BLUP; thus, marker genotype information is useful for estimating the genetic merits of bulls for semen production traits. The selection of these traits would improve sperm viability, a component related to breeding success, and alleviate negative genetic trends.

Testicular disruption in the As (aspermia) mutant rat, with special reference to the aggregate of ribosomes.

The morphology of the testis of the mutant As (aspermia) strain rat with severely interrupted spermatogenesis was investigated in the present study. The most advanced development in spermatogenesis was observed at the step 8 at which spermatids had basally-oriented acrosomes. Multinucleate giant cells derived from round spermatids were frequently encountered within the seminiferous tubules. The functionally normal status of the blood-testis barrier between adjacent Sertoli cells was confirmed by morphological and lanthanum tracer studies. By light microscopy, a peculiar structure was found within the pachytene spermatocyte, consisting of numerous particles of approximately 25 nm in diameter. By histochemical and electron microscopic studies, this structure was identified as an aggregate of ribosomes. Neither immature spermatogenic cells up to the pachytene phase, nor Sertoli cells nor interstitial regions showed a recognizable abnormality. It seems that the testicular disruption in the As mutant rat is due to the abnormality in the protein synthetic pathway in pachytene spermatocytes.