Lymphatic drainage of cerebrospinal fluid in mammals – are arachnoid granulations the main route of cerebrospinal fluid outflow?

The outflow of the cerebrospinal fluid (CSF) in animals was over the years the subject of detailed analysis. For a long time it was stated that arachnoid granulations of the venous sinuses play a key role in CSF circulation. However, recent studies on this subject have shown that a considerable part of the CSF is drained to the lymphatic vessels. Moreover, disorders in the CSF passage may result in severe central nervous system diseases such as e.g. hydrocephalus. In this paper, we summarize the current knowledge concerning the lymphatic drainage of the CSF in mammals. We present in detail comparative anatomy of different species taking into account cranial and spinal compartment. In addition, we clarified role of the lymphatic vessels in the CSF outflow and the relationship between impairment in this transport and central nervous system diseases. In the author’s opinion knowledge on CSF circulation is still poorly examined and therefore required comment.     

Does beta-lactoglobulin denaturation occur via an intermediate state?

The denaturation of beta-lactoglobulin (BLG) in the presence of urea and GuHCl has been investigated at different pH values with various spectroscopic techniques. The equilibrium denaturation free energy values, obtained by linearly extrapolating the data to vanishing denaturant (DeltaG(D)(H2O)), are compared and discussed. The fit of the spectroscopic data monitoring the denaturation of BLG has been approached, at first, with a two-state model that describes the protein transition from the folded state (at each pH and in the absence of denaturant) to the denatured state, but in particular, along the GuHCl denaturation pathway some evidence is found of the presence of an intermediate state. Time-resolved fluorescence experiments performed on the BLG-ANS (1-anilino-8-naphthalenesulfonate) complex help to understand the results. Fluorescence polarization anisotropy (FPA) measurements accompanying the denaturation process show the presence of a fast rotational diffusion of the ANS probe, and the data are interpreted in terms of local fluctuations of a still structured tract of the denatured protein where the probe is bound.     

Does autoregulation of megakaryocytopoiesis occur?

Although a major regulator of thrombocytopoiesis is the number of circulating platelets, several observations suggest that independent alternative regulatory mechanisms may exist. In some situations there is a curious association of megakaryocytopenia and megakarocytic macrocytosis in spite of normal platelet counts. If macrocytosis is considered as a sign of stimulation, this association suggests a cause and effect relationship between decreased numbers and increased size of megakaryocytes. This thesis was tested by examining the delayed effects of sublethal irradiation and the acute effects of hydroxyurea in mice. It was found that megakaryocytopenia and macromegakaryocytosis occurred together and that platelets counts were either normal or only slightly reduced. Therefore it was concluded that normal numbers of platelets could be produced by decreased numbers of megakaryocytes. Megakaryocytopenia appeared to be compensated, in part, by increased size of megakaryocytes, but the mechanism by which this occurred has not been elucidated. It is postulated that a reduction in the number of cells of the megakaryocytic system is sensed by a homeostatic mechanism that then acts to stimulate the cells that are present. This stimulation may then be manifested as macrocytosis of megakaryocytes.     

Does random collisional cross-linking occur?

In fluid membranes, mobile molecules are thought to collide at high frequencies. Concern has been expressed as to whether these colliding molecules are cross-linked during the chemical cross-linking of membrane molecules, thereby creating problems in interpreting such experiments. Hemoglobin was used as a model to test this possibility. Oligomers larger than the tetramer could be cross-linked depending on factors such as hemoglobin concentration, duration of the cross-linking reaction and the type of reagent. Under certain conditions, however, such as a hemoglobin concentration less than 150 μM or a duration of cross-linking shorter than 15 min, larger oligomers were not detectable. Analysis of these data suggests that the probability of random collisional cross-links under normal conditions is insignificant.     

Does follicular dominance occur in ewes?

The process by which a single follicle is selected to ovulate while others regress is unknown in ewes. If the dominant follicle secretes substances that directly inhibit the growth of other follicles, the superovulatory response to the administration of exogenous gonadotrophins may be blunted. Administration of 1250 iu pregnant mares' serum gonadotrophin (PMSG) before or after the emergence of the dominant follicle in the follicular phase, or 1000 iu PMSG in the presence or absence of a large healthy or atretic follicle during the luteal phase did not affect the induced ovulatory response. Comparisons between the ovary with or without the dominant follicle did not reveal any differences in ovulatory response to PMSG. The in-vitro features (i.e. mitotic index, oestradiol and testosterone production) of follicles ipsilateral or contralateral to the dominant follicle during the early and late follicular phases were also similar. If the dominant follicle secretes substances detrimental to the other follicles, this could be mimicked in vitro. Co-culture of small follicles with the largest follicles in a closed system did not reduce their incorporation of 3H thymidine in granulosa cells, compared with small follicles cultured alone. These data suggest that dominance is probably not operative in sheep. The administration of 500 iu of PMSG during the midfollicular phase increased ovulation rate in Merino ewes, indicating that dominance is essentially passive in ewes and can easily be overcome by raising gonadotrophin concentration.     

Does endocytosis occur in fungal hyphae?

The evidence and arguments for and against the occurrence of endocytosis in fungal hyphae are summarized. The balance of evidence is in favour of the existence of endocytosis. This is supported by an analysis of the recently sequenced Neurospora genome which strongly suggests that this fungus possesses the complex protein machinery required to conduct endocytosis.     

Does protein synthesis occur in the nucleus?

Although it is universally accepted that protein synthesis occurs in the cytoplasm, the possibility that translation can also take place in the nucleus has been hotly debated. Reports have been published claiming to demonstrate nuclear translation, but alternative explanations for these results have not been excluded, and other experiments argue against it. Much of the appeal of nuclear translation is that functional proofreading of newly made mRNAs in the nucleus would provide an efficient way to monitor mRNAs for the presence of premature termination codons, thereby avoiding the synthesis of deleterious proteins. mRNAs that are still in the nucleus-associated fraction of cells are subject to translational proofreading resulting in nonsense-mediated mRNA decay and perhaps nonsense-associated alternate splicing. However, these mRNAs are likely to be in the perinuclear cytoplasm rather than within the nucleus. Therefore, in the absence of additional evidence, we conclude that nuclear translation is unlikely to occur.     

Does respiratory sinus arrhythmia occur in fishes?

The hypothesis that respiratory modulation of heart rate variability (HRV) or respiratory sinus arrhythmia (RSA) is restricted to mammals was tested on four Antarctic and four sub-Antarctic species of fish, that shared close genotypic or ecotypic similarities but, due to their different environmental temperatures, faced vastly different selection pressures related to oxygen supply. The intrinsic heart rate (fH) for all the fish species studied was approximately 25% greater than respiration rate (fV), but vagal activity successively delayed heart beats, producing a resting fH that was synchronized with fV in a progressive manner. Power spectral statistics showed that these episodes of relative bradycardia occurred in a cyclical manner every 2-4 heart beats in temperate species but at >4 heart beats in Antarctic species, indicating a more relaxed selection pressure for cardio-respiratory coupling. This evidence that vagally mediated control of fH operates around the ventilatory cycle in fish demonstrates that influences similar to those controlling RSA in mammals operate in non-mammalian vertebrates.     

Does macrovesicular endocytosis occur in fungal hyphae?

Like most eukaryotic organisms, fungi use endocytosis for nutrition, signal transduction, turnover of plasma membrane molecules, etc. It is generally accepted that in filamentous fungi, as in yeast, invaginations of the plasma membrane of a small size (up to about 100 nm) are formed in the early stages of endocytosis. These invaginations are surrounded by a rigid actin scaffold – an actin patch, and give rise to small primary endocytic vesicles after scission from the plasma membrane. However, in classical mycological studies, complex large-volume invaginations of the plasma membrane – lomasomes – were described in filamentous fungi. In our time, in a number of filamentous basidiomycetes when tracking endocytosis using styryl fluorescent labels, large invaginations of the plasma membrane have been found, presumably forming endocytic macrovesicles after scission. In this paper, for comparison, large-sized types of endocytosis in animal cells are briefly described. Information about tubular endocytic invaginations in fungi is presented. Three types of large invaginations of the plasma membrane, detected at the TEM level in basidiomycetes, are characterized. The main question this paper addresses is whether or not filamentous fungi do have an analogue of animal macropinocytosis – macrovesicular endocytosis. There are some indications that the answer to this question is yes, but further research is needed. The presence of macrovesicular endocytosis may change the well-established beliefs about the cellular organization of filamentous fungi and the physiology of their nutrition.     

Does glycolate decarboxylation occur in intact leaf peroxisomes?

Release of ¹⁴CO₂ during metabolism of [1-¹⁴C]glycolate was studied in purified, intact and Triton X-100-solublized peroxisomes isolated from leaves of Secale cereale. Decarboxylation, apparently resulting from H₂O₂ attack on glyoxylate, was stimulated in both intact and solubilized peroxisomal preparations by the catalase inhibitors aminotriazole and sodium azide. CO₂ evolution was also observed in solubilized peroxisomes in the absence of inhibitor when an amino donor was not provided for conversion of glyoxylate to glycine. Loss of CO₂ from labelled glycolate in the absence of amino donors was reduced by addition of exogenous catalase to the reaction medium.Intact peroxisomes showed no glycolate decarboxylation whether or not amino donors were supplied. It appears that the CO₂ release from glycolate observed in previous investigations may be an artifact of the peroxisomal preparations and the assay systems used, and not a significant factor in photorespiratory metabolism in vivo.     

Monoamine metabolites in human cerebrospinal fluid: indicators of neuronal activity?

Concentrations of monoamine metabolites in human cerebrospinal fluid (CSF) have been widely used as indicators of the level of functional activity in the central monoaminergic neuronal pathways. This article reviews the relationship between the turnover of the neurotransmitter monoamines noradrenaline, serotonin, and dopamine, and the concentrations in CSF of their principal metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA). It attempts to summarise what is known of the effects of various illnesses and drug treatments on the concentrations of these metabolites.     

Does competitive divergence occur if assortative mating is costly?

Most models of sympatric speciation have assumed that assortative mating has no costs. A few studies, however, have shown that the costs for being choosy can prevent such speciation. Here, we investigate the role of the strength of assortment and of the costs for being choosy for a simple genetic model of a single ('magic') trait that mediates both intraspecific competition for a continuum of resources and assortative mating, which is induced by choosy females who preferentially mate with males of similar phenotype. Choosiness may be costly if it is difficult to find a mating partner. Such magic trait models are considered to be most conducive of sympatric speciation. We consider a sexually reproducing population of haploid individuals that is density regulated. The trait is determined by a single locus with multiple alleles. The strength of stabilizing selection (caused by a unimodal resource distribution), the strength of competition, the degree of assortment and the costs for being choosy are independent parameters. We investigate analytically and numerically how these parameters determine the equilibrium and stability structure. In particular, we identify conditions under which no polymorphism at all is maintained as well as conditions under which strong competitive divergence occurs, or the population even splits into two reproductively isolated classes of highly diverse phenotypes. If costs are absent or moderate, genetic variability tends to be minimized at intermediate strengths of assortment, and reproductively isolated classes of phenotypes are a likely result of evolution only for intermediate or strong competition and for very strong assortment. The likelihood of divergence depends relatively weakly on the costs as long as they are not high. With high costs, however, increasingly strong assortment rapidly depletes all genetic variation, and strong competitive divergence is prevented.     

Does super efficient starch absorption promote diverticular disease?

The amount of starch escaping absorption in the small intestine was measured in eight patients with symptomatic diverticular disease and eight controls. Unabsorbed starch was calculated from breath hydrogen measurements after a potato meal compared with the hydrogen response to lactulose. The proportion of unabsorbed starch was low in all the patients (mean 3.3%) and was only about a quarter of that in the controls (12.4%; p less than 0.01). These findings confirm that unabsorbed starch provides an important quantity of carbohydrate reaching the colon and suggest that super efficient starch absorption, by reducing this provision, may promote the development of diverticular disease.     

Does carnitine have a role in fat absorption?

The effect of D-carnitine and tetradecylglycidic acid (TDGA), an inhibitor of carnitine palmitoyltransferase, on intestinal absorption of palmitic acid was determined. The proximal intestinal segment was ligated in adult male rats and filled with 0.5 microCi of 14C-palmitic acid alone or with either D-carnitine or TDGA. Thirty minutes later the radioactivity was determined in the intestinal lumen, intestinal wall and plasma. The absorption of palmitic acid was decreased in the presence of D-carnitine (10 mg/ml) as evidenced by significantly lower levels of radioactivity in the gut wall and the plasma and by significantly greater residual radioactivity in the lumenal contents. L-carnitine had no effect on plasma radioactivity but if D- and L-carnitine were given together the effect of D-carnitine was still in evidence. TDGA also inhibited intestinal absorption of palmitic acid.     

Emerging roles for lymphatics in acute kidney injury: Beneficial or maleficent?

Acute kidney injury, a sudden decline in renal filtration, is a surprisingly common pathology resulting from ischemic events, local or systemic infection, or drug-induced toxicity in the kidney. Unchecked, acute kidney injury can progress to renal failure and even recovered acute kidney injury patients are at an increased risk for developing future chronic kidney disease. The initial extent of inflammation, the specific immune response, and how well inflammation resolves are likely determinants in acute kidney injury-to-chronic kidney disease progression. Lymphatic vessels and their roles in fluid, solute, antigen, and immune cell transport make them likely to have a role in the acute kidney injury response. Lymphatics have proven to be an attractive target in regulating inflammation and immunomodulation in other pathologies: might these strategies be employed in acute kidney injury? Acute kidney injury studies have identified elevated levels of lymphangiogenic ligands following acute kidney injury, with an expansion of the lymphatics in several models post-injury. Manipulating the lymphatics in acute kidney injury, by augmenting or inhibiting their growth or through targeting lymphatic-immune interactions, has met with a range of positive, negative, and sometimes inconclusive results. This minireview briefly summarizes the findings of lymphatic changes and lymphatic roles in the inflammatory response in the kidney following acute kidney injury to discuss whether renal lymphatics are a beneficial, maleficent, or a passive contributor to acute kidney injury recovery.     

Does neonatal gonadectomy affect the sexual differentiation of quail?

This experiment was designed to determine the contribution, if any, of posthatching gonadal hormones to sexual differentiation of behavior in Japanese quail (Coturnix coturnix japonica). Males and females were gonadectomized or sham-operated (controls) prior to age 7 days posthatching. At age 4-9 weeks controls were gonadectomized. All birds were then given 2 weeks of testosterone propionate injections and tested for sexual behavior with female partners. Neonatally gonadectomized females exhibited more male-typical copulatory behavior than control females, but this effect was not statistically significant. Neonatal gonadectomy had no effect on males, and neonatally gonadectomized males exhibited significantly more male-typical copulatory behavior than neonatally gonadectomized females. Although the process of sexual differentiation may extend to a minor degree into the posthatching period in females, nonetheless it is largely complete at hatching in this species.