Spermiogenesis in the bluegill (Lepomis macrochirus): a study of cytoplasmic events including cell volume changes and cytoplasmic elimination

The process involved in the reduction of both nuclear and cytoplasmic volume was investigated in the bluegill (Lepomis macrochirus), a teleost fish. Young spermatids contained centrally positioned nuclei which, with time, moved toward the cell surface to become eccentrically positioned. Chromatin condensation was initiated from a region near the implantation fossa, whereas at the opposite pole of the nucleus an area sparse in heterochromatin (clear area) was noted. The nuclear membrane lying adjacent to the clear area dissolved and subsequently reformed, yielding a nucleus with a reduced volume. During this process, packets of cytoplasm surrounded by a double membrane were formed along the future midpiece. The packets of cytoplasm migrated toward the cell surface, protruded from the surface, and were extruded into the spermatocyst lumen. These structures, termed residual bodies, were subsequently endocytosed, accumulated into large phagocytic vacuoles, and eventually degraded by the nearby Sertoli cell. When the spermatocyst ruptured, spermatozoa containing sparse cytoplasm were released into the excurrent duct system. During spermiogenesis, both the nuclear and cytoplasmic volumes decreased substantially (80%, 92% respectively) leading to an overall 87% reduction in total cell volume.     

Spermiogenesis in the bullfrog (Rana catesbeiana): a study of cytoplasmic events including cell volume changes and cytoplasmic elimination

The process by which spermatid cytoplasmic volume is reduced and cytoplasm eliminated during spermiogenesis was investigated in the bullfrog Rana catesbeiana. At early phases of spermiogenesis, newly formed, rounded spermatids were found within spermatocysts. As acrosomal development, nuclear elongation, and chromatin condensation occurred, spermatid nuclei became eccentric within the cell. A cytoplasmic lobe formed from the caudal spermatid head and flagellum and extended toward the seminiferous tubule lumen. The cytoplasmic lobe underwent progressive condensation whereby most of its cytoplasm became extremely electron dense and contrasted sharply with numerous electron-translucent vesicles contained therein. At the completion of spermiogenesis, many spermatids with their highly condensed cytoplasm still attached were released from their Sertoli cell into the lumen of the seminiferous tubule. There was no evidence of the phagocytosis of residual bodies by Sertoli cells. Because spermatozoa are normally retained in the testis in winter and are not released until the following breeding season, sperm were induced to traverse the duct system with a single injection of hCG. Some spermatids remained attached to their cytoplasm during the sojourn through the testicular and kidney ducts; however, by the time the sperm reached the Wolffian duct, separation had occurred. The discarded cytoplasmic lobe (residual body) appeared to be degraded with the epithelium of the Wolffian duct. It was determined that the volume of the spermatid was reduced by 87% during spermiogenesis through a nuclear volume decrease of 76% and cytoplasmic volume decrease of 95.3%.     

Cell-cycle checkpoints that ensure coordination between nuclear and cytoplasmic events in Saccharomyces cerevisiae

Cytoskeletal organization is crucial for several aspects of cell-cycle progression but cytoskeletal elements are quite sensitive to environmental perturbations. Two novel checkpoint controls monitor the function of the actin and microtubule systems in budding yeast and operate to delay cell-cycle progression in response to cytoskeletal perturbations. In cells whose actin cytoskeleton has been perturbed, bud formation is frequently delayed and the morphogenesis checkpoint introduces a compensatory delay of nuclear division until a bud has been formed. In cells whose microtubule cytoskeleton has been perturbed, anaphase spindle elongation often occurs entirely within the mother cell, and the post-anaphase nuclear migration checkpoint introduces a compensatory delay of cytokinesis until one pole of the anaphase nucleus enters the bud. Recent studies indicate that regulators of entry into mitosis are localized to the daughter side of the mother-bud neck whereas regulators of exit from mitosis are localized to the spindle pole bodies. Thus, specific cell-cycle regulators are well-placed to monitor whether a cell has formed a bud and whether a daughter nucleus has been delivered accurately to the bud following mitosis.     

The nuclear envelope as an integrator of nuclear and cytoplasmic architecture

Initially perceived as little more than a container for the genome, our view of the nuclear envelope (NE) and its role in defining global nuclear architecture has evolved significantly in recent years. The recognition that certain human diseases arise from defects in NE components has provided new insight into its structural and regulatory functions. In particular, NE defects associated with striated muscle disease have been shown to cause structural perturbations not just of the nucleus itself but also of the cytoplasm. It is now becoming increasingly apparent that these two compartments display co-dependent mechanical properties. The identification of cytoskeletal binding complexes that localize to the NE now reveals a molecular framework that can seamlessly integrate nuclear and cytoplasmic architecture.     

Cyclooxygenase-dependent signalling: molecular events and consequences

Non-steroidal anti-inflammatory drugs (NSAIDs) currently attract large interest. Next to pain relief, NSAIDs have important anti-thrombotic and anti-oncogenic effects. NSAIDs exert their action by inhibition of cyclooxygenase, the enzyme responsible for the production of prostanoids. Prostanoid signal transduction is still poorly understood, but it has become clear that these inflammatory lipids influence cellular physiology at three different levels: (1) activation of a 7 x transmembrane receptor coupled to heterotrimeric G proteins, (2) the inhibition of inflammation by activating corticosteroid-like receptors, (3) participation in receptor protein tyrosine kinase signal transduction. In this review prostanoid signalling at these three different levels will be reviewed and the relevance in (patho)physiological processes will be evaluated.     

Thymosins: both nuclear and cytoplasmic proteins

A simple procedure based on perchloric acid extraction has been developed for the preparation and purification of bovine prothymosin alpha and thymosins beta 4 and beta 9 in high yields. Spectroscopic observations show these proteins to be non-folding at neural pH. The cellular locations of human prothymosin alpha, rat parathymosin and calf thymosin beta 4, all so-called 'thymic hormones', have been studied by injection into the cytoplasm of Xenopus oocytes, followed by separate monitoring of nuclear and cytoplasmic concentrations. It is shown that human prothymosin alpha and rat parathymosin both migrate to the nucleus whilst thymosin beta 4 remains in the cytoplasm. The peptide (1-88) of calf prothymosin alpha is shown not to accumulate in the Xenopus nucleus, demonstrating that the C-terminal 21 residues, which include a KKQK sequence, are required for nuclear migration. The present data, in association with existing evidence of wide tissue distribution and the lack of signal peptides, indicate that these proteins do not behave as hormones in the usual sense of the word. It is suggested that thymosin beta 4 should be grouped separately from the pro- and parathymosins.     

Centrosomal and cytoplasmic Cdc2/cyclin B1 activation precedes nuclear mitotic events

The activation of cdc2/cyclin B is the trigger for entry into mitosis. The mechanism of cdc2/cyclin B activation is complex, but the final step is the dephosphorylation of the Thr14 and Tyr15 residues on the cdc2 subunit, catalyzed by a member of the Cdc25 family of phosphatases. Cdc2/cyclin B1 accumulates at the centrosome in late G2 phase and has been implicated in the conversion of the centrosome from an interphase to a mitotic microtubule organizing center. Here we demonstrate biochemically that cdc2/cyclin B1 accumulates at the centrosome in late G2 as the inactive, phosphotyrosine 15 form and that the centrosomal cdc2/cyclin B1 can be activated in vitro by recombinant cdc25B. We provide evidence that a portion of the cdc2/cyclin B1 translocated into the nucleus in prophase is the inactive tyrosine-15-phosphorylated form. At this time the centrosomal and cytoplasmic cdc2/cyclin B1 is already active. This provides evidence that the activation of cdc2/cyclin B1 is initiated in the cytoplasm and that full activation of the translocated pool occurs in the nucleus.     

H-ras(val12) induces cytoplasmic but not nuclear events of the cell cycle in small Xenopus oocytes.

Microinjection of H-ras(val12) protein into fully grown Xenopus oocytes has been shown to induce meiotic maturation. In the present study, mRNA encoding the mutant ras protein was injected into both fully grown (stage 6) and growing (stage 4) oocytes. The mRNA induced nuclear breakdown in stage 6 oocytes, as expected. However, the mRNA induced neither nuclear breakdown nor maturation promoting factor when injected into stage 4 oocytes. Instead, the response in stage 4 oocytes included an activation pulse of calcium, cortical granule breakdown, elevation of the vitelline envelope, and abortive cleavage furrows, all of which are characteristics of the activation response in mature eggs. In addition, the injected mRNA led to increased rates of endogenous protein synthesis and the migration of subcortical organelles into the oocyte interior. These observations are discussed relative to the suggestion that oncogenic ras protein leads to an increase in both diacylglycerol and inositol trisphosphate, which then regulate the various cytoplasmic events described.     

Universal grammar and the Baldwin effect: a hypothesis and some philosophical consequences

Grammar is now widely regarded as a substantially biological phenomenon, yet the problem of language evolution remains a matter of controversy among Linguists, Cognitive Scientists, and Evolutionary Theorists alike. In this paper, I present a new theoretical argument for one particular hypothesis—that a “Language Acquisition Device” of the sort first posited by Noam Chomsky might have evolved via the so-called “Baldwin Effect”. Close attention to the workings of that mechanism, I argue, helps to explain a previously mysterious feature of the Language Acquisition Device—the sheer variety of languages it allows the child to learn—thereby revealing a far stronger case than adherents of the hypothesis have previously supposed. A further unheralded consequence of the hypothesis is a conceptual shift in the Chomskyan understanding of language, wherein the essentially public nature of language is freshly emphasised. This has the effect of bringing the Chomskyan view into closer accord with Saussurean accounts of language, as well as with recent trends in evolutionary theory.     

Muscular contraction and cytoplasmic streaming: A new general hypothesis

Several experiments point out that some crossbridges remain attached to the thin filaments at rest. It is assumed, in this paper, that these cross-bridges exert mechanical tractions on the thin filaments, directed from the thin to the thick filaments. When contraction is triggered off, a conformational change of the attached crossbridges is induced by the chemical energy released from ATP splitting. This conformational change leads to the reduction of the mechanical tensions. The electrostatic repulsive forces between the filaments become therefore automatically preponderant. This phenomenon induces a sideways expansion of the filament lattice and, taking into account the elasticity of muscle, a contraction in the direction of the filaments. This model accounts for the most important physiological and thermodynamical properties of muscle (tension-length curves, responses to quick stretch and quick release, Fenn effect, Hill's relation, behaviour of skinned fibres). It is directly applicable to all kinds of muscles and to cytoplasmic streaming, provided only actin, but not necessarily myosin, filaments are present in the cell.     

The cyclic behavior of a cytoplasmic factor controlling nuclear membrane breakdown

The activity of a cytoplasmic factor (MPF), capable of inducing nuclear membrane breakdown (germinal vesicle breakdown) when injected into amphibian oocytes, has been studied during the course of early cleavage in amphibian embryos. Mature egg cytoplasm was found to contain high levels of this activity, but this was quickly lost after fertilization or artificial activation. MPF activity later reappeared in the egg cytoplasm and started to cycle with time. The peak of embryonic MPF activity during each cycle coincided with the time the embryonic nuclei were entering the G2-M transition, i.e., mitosis. However, in colchicine-arrested embryos, this activity remained at an elevated level and no longer oscillated. The timing of the appearance and disappearance of this activity appeared to be under the control of the cytoplasm because such behavior was still observed in enucleated eggs. Continued protein synthesis in the embryo was required for the reappearance, but not for the disappearance, of this activity. MPF, previously thought to be restricted to oocyte maturation, may play a more general role in controlling nuclear membrane breakdown during mitosis as well as meiosis.     

The nuclear nurture and cytoplasmic nature of localized mRNPs

From yeast to mammals, evidence has emerged in recent years highlighting the essential role played by the nuclear "history" of a messenger RNA in determining its cytoplasmic fate. mRNA localization, translation and stability in the cytoplasm are often pre-destined in the nucleus, and directed by the composition and architecture of nuclear assembled mRNA-protein complexes. In this review we focus on nuclear-acquired RNA-binding proteins and complexes that participate in determining the journey of localized mRNAs.     

The methylation of adenovirus-specific nuclear and cytoplasmic RNA.

Each poly(A) containing cytoplasmic AD-2 MRNA contains at its 5' terminus the general structure m7 GpppN1 pN2p or m7 GpppN1mpN2mpNp as well as an average of 4 m6A and 0.5-1 m5C residues per molecule. Almost all of the N1m residues are adenine derivatives including Am, m6Am and probably m26,6Am. The N2m is mostly Cm but small amounts of the other three methylated bases are also present. All the methylated constitutents of mRNA are distant from the 3' terminal poly(A). The amount of m6A appears to be greater in larger mRNA than in smaller mRNA. Nuclear Ad-2 specific RNA also contains caps, m6A, and m5C with about twice as much m6A relative to caps as cytoplasmic mRNA. The similarity of Ad-2 nuclear and mRNA to HeLa hnRNA and mRNA suggests that adenovirus mRNA production is a good model for eukaryotic mRNA production.     

The association of hypertriglyceridemia with cardiovascular events and pancreatitis: a systematic review and meta-analysis

Background

Hypertriglyceridemia may be associated with important complications. The aim of this study is to estimate the magnitude of association and quality of supporting evidence linking hypertriglyceridemia to cardiovascular events and pancreatitis.

Methods

We conducted a systematic review of multiple electronic bibliographic databases and subsequent meta-analysis using a random effects model. Studies eligible for this review followed patients longitudinally and evaluated quantitatively the association of fasting hypertriglyceridemia with the outcomes of interest. Reviewers working independently and in duplicate reviewed studies and extracted data.

Results

35 studies provided data sufficient for meta-analysis. The quality of these observational studies was moderate to low with fair level of multivariable adjustments and adequate exposure and outcome ascertainment. Fasting hypertriglyceridemia was significantly associated with cardiovascular death (odds ratios (OR) 1.80; 95% confidence interval (CI) 1.31-2.49), cardiovascular events (OR, 1.37; 95% CI, 1.23-1.53), myocardial infarction (OR, 1.31; 95% CI, 1.15-1.49), and pancreatitis (OR, 3.96; 95% CI, 1.27-12.34, in one study only). The association with all-cause mortality was not statistically significant.

Conclusions

The current evidence suggests that fasting hypertriglyceridemia is associated with increased risk of cardiovascular death, MI, cardiovascular events, and possibly acute pancreatitis. Précis: hypertriglyceridemia is associated with increased risk of cardiovascular death, MI, cardiovascular events, and possibly acute pancreatitis