Intrinsic curvature: a marker of millimeter-scale tangential cortico-cortical connectivity?

In this paper, we draw a link between cortical intrinsic curvature and the distributions of tangential connection lengths. We suggest that differential rates of surface expansion not only lead to intrinsic curvature of the cortical sheet, but also to differential inter-neuronal spacing. We propose that there follows a consequential change in the profile of neuronal connections: specifically an enhancement of the tendency towards proportionately more short connections. Thus, the degree of cortical intrinsic curvature may have implications for short-range connectivity.     

The roles and expression of HOXA/Hoxa10 gene: A prospective marker of mammalian female fertility?

This review addresses the influence of homebox A10/a10 (HOXA/Hoxa10) gene on reproductive tract anatomy and functional fertility in mammalian species, and discusses major endocrine and environmental regulators of HOXA/Hoxa10 expression. Female reproductive efficiency or success is a function of several factors including the ovulation and fertilization rate, and uterine receptivity. A family of HOX/Hox genes establishes the segmental identity of the reproductive tract during embryogenesis and retains its physiological plasticity in sexually mature animals and humans. In particular, the HOXA/Hoxa10 gene is an intrinsic component of implantation, decidualization, and immunomodulation in the adult uterus. It was, therefore, suggested that knowledge of HOXA/Hoxa10 regulation might be essential in navigating molecular mechanisms with the aim of enhancing female reproductive potential. However, a recent study in pigs revealed a lack of associations between endometrial HOXA10 expression and reproductive tract morphology, and very poor correlations with sows’ fertility metrics. Retinoic acid mainly regulates 3’ HOX/Hox paralogs but may also modify the expression of downstream HOX/Hox genes, including HOXA/Hoxa10. Sex steroids directly regulate HOXA/Hoxa10 expression. The vitamin D receptor pathway modulates HOXA/Hoxa10 expression in the adult reproductive tract. Lastly, endocrine disruptors such as diethylstilbestrol, methoxychlor, bisphenol A, and isoflavones were shown to alter HOXA/Hoxa10 expression, thus affecting reproductive competence of the female.     

Corticosteroid receptors in lymphocytes: a possible marker of brain involution?

A similarity has recently been found between the regulation of corticosteroid receptors in brain and in lymphoid tissue. We have studied the regulation of corticosteroid receptors in human mononuclear leukocytes as a possible marker of brain involution. Type I corticosteroid receptors are down regulated by excess of mineralocorticoids (primary and secondary hyperaldosteronism, pseudohyperaldosteronism) and of glucocorticoids (Cushing's syndrome). Type II corticosteroid receptors are not reduced by excess of endogenous corticostiroids (Cushing's syndrome). In normal adults there is a direct significant correlation between plasma cortisol and Type I and between plasma cortisol and Type II receptors in mononuclear leukocytes, while in Cushing's syndrome the correlation is inverse between plasma cortisol at 8 a.m. and Type II receptors. In an aged population the mean numbers of Type I and of Type II receptors are lower and plasma cortisol is higher than in adult controls, but the increase of plasma cortisol is not followed by a clinical picture of hypercorticism. Corticosteroid Type I and Type II receptors are inversely correlated with age. After dexamethasone suppression (1 mg at 11 p.m.) Type I receptors always decrease in controls while the response of Type II is not homogeneous. In an aged group of patients, both receptors are reduced by dexamethasone. We conclude that the decrease with age of corticosteroid receptors is possibly related to a physiological involution of corticosteroid receptors and that this reduction does increase plasma cortisol concentration, without affecting the glucocorticoid effector mechanism.     

Mammalian target of rapamycin (mTOR): a central regulator of male fertility?

Mammalian target of rapamycin (mTOR) is a central regulator of cellular metabolic phenotype and is involved in virtually all aspects of cellular function. It integrates not only nutrient and energy-sensing pathways but also actin cytoskeleton organization, in response to environmental cues including growth factors and cellular energy levels. These events are pivotal for spermatogenesis and determine the reproductive potential of males. Yet, the molecular mechanisms by which mTOR signaling acts in male reproductive system remain a matter of debate. Here, we review the current knowledge on physiological and molecular events mediated by mTOR in testis and testicular cells. In recent years, mTOR inhibition has been explored as a prime strategy to develop novel therapeutic approaches to treat cancer, cardiovascular disease, autoimmunity, and metabolic disorders. However, the physiological consequences of mTOR dysregulation and inhibition to male reproductive potential are still not fully understood. Compelling evidence suggests that mTOR is an arising regulator of male fertility and better understanding of this atypical protein kinase coordinated action in testis will provide insightful information concerning its biological significance in other tissues/organs. We also discuss why a new generation of mTOR inhibitors aiming to be used in clinical practice may also need to include an integrative view on the effects in male reproductive system.     

Lenticulostriatal vasculopathy - a marker for congenital cytomegalovirus infection?

Lenticulostriate vasculopathy (LSV) is an ultrasound (US) visible lesion of the brain, which appears as echogenic streaks or spots in the arteries of thalamus and basal ganglia. LSV has varied etiology. Transfontanelar Color Doppler (TFCD) can easily display lenticulostriatal blood flow and assess: stage I LSV with present flow within echogenic changes and stage II LSV in which the flow disappears, despite a presence of streaks and spots, which at this stage most probably correspond to calcification. The objectives of this study are to determine: (1) Whether there are differences in distribution (unilateral or bilateral) and presence (during first year of age) of TFCD flow between congenital CMV infection positive and negative group of children with LSV (2) Could US and TFCD findings of LSV be an indication for further investigation of possible congenital CMV infection, because of their variable and often adverse neurodevelopmental outcome? We examined and followed-up 98 infants with LSV One group (37/98) with congenital CMV infection and second (61/98) negative. All infants had clinical signs of neuromotor delay and ultrasound and TFCD markers of LSV Our study shows that most of the patients from both groups had TFCD visible flow at the age of 0-4 months. In majority of them in both groups, at the age of 5-8 months, there was no more visible flow. TFCD showed no statistically significant difference among congenital CMV infection positive group and negative group, nor in youngest age period (0-4 months), nor in later course of flow in LSV unilaterally or bilaterally. Although the LSV presents nonspecific marker for intracranial infection (ICI), all infants presenting with LSV should be evaluated for possible ICI. Thus, the Doppler findings of LSV in infants require a detailed examination, monitoring and follow-up of neuromotor outcome.     

Biometry of Cenomanian–Turonian placoliths: a proxy for changes of fertility and surface‐water temperature?

Most publications discussing Cenomanian–Turonian calcareous nannofossils focus on abundance fluctuations across the boundary interval. So far, there have been no studies that deal with the influence of palaeoenvironmental changes on the size of common Cenomanian–Turonian nannofossil taxa. The genera Biscutum, Broinsonia, Prediscosphaera, Retecapsa and Watznaueria have therefore been analysed from 19 samples of Cenomanian–Turonian age from the Goban Spur, northeast Atlantic. The genus Biscutum shows a slight decrease of mean length from 4.14 μm in the Cenomanian to 3.94 μm in the Turonian. Broinsonia is marked by a decrease from 6.07 μm in the Cenomanian to 5.64 μm in the Turonian. On the other hand, Prediscospheara increases in size from 4.98 μm in the Cenomanian to 5.61 μm in the Turonian. Two genera (Retecapsa, Watznaueria) show no significant changes in their mean length. The mean size of Biscutum is perhaps controlled by nutrients, where larger specimens may have preferred the more fertile palaeoenvironment of the Late Cenomanian. The size decrease of Biscutum in the Turonian is probably related to reduced nutrient availability. The genus Prediscosphaera spp., may have favoured low‐fertility conditions, as its mean size increases in the Turonian. A worldwide decline of the frequency of Broinsonia spp. during the Cenomanian–Turonian transition implies that this genus is not solely controlled by the nutrient content. The size of Broinsonia spp. may have been therefore influenced by the latest Cenomanian warming event. The increase in sea‐surface temperature may have been unfavourable for Broinsonia spp. as reflected by decreasing mean size and frequency. □Calcareous nannofossils, biometry, morphometry, Oceanic Anoxic Event 2.     

Plasma ubiquinol-10 as a marker for disease: is the assay worthwhile?

Ubiquinol-10 and ubiquinone-10 were measured in plasma of patients with several pathologies known to be associated with increased oxidative stress. Plasma ubiquinol-10, expressed as a percentage of total ubiquinol-10 + ubiquinone-10, was found to be significantly lower in hyperlipidaemic patients and in patients with liver diseases than in age-matched control subjects. In contrast, no decrease in ubiquinol-10 was detected in plasma of patients with coronary heart disease and Alzheimer's disease. Except for ubiquinol-10, no other lipophilic antioxidant was found to be decreased in patients with liver diseases. These data suggest that the level of ubiquinol-10 in human plasma may serve as a marker for liver dysfunction, reflecting its diminished reduction by the liver rather than increased consumption by oxidants.     

Free DNA in urine: a new marker for bladder cancer? Preliminary data

The aim of the present preliminary study was to investigate the presence of free DNA (FDNA) in urine as a possible marker for the diagnosis of bladder cancer. Naturally voided morning urine specimens were collected from 57 patients with suspected bladder cancer before cystoscopy. A standard urine test was performed; the specimens were then processed in order to obtain a quantitative evaluation of the presence of free DNA in the urine. Twenty-two patients were excluded from the study because they had leukocyturia and/or bacteriuria. Free DNA concentrations higher than 250 ng/mL were found in all 16 patients showing bladder cancer at cystoscopy and in seven (36.8%) of the 19 patients with negative cystoscopy. Urinary FDNA seems to have an excellent sensitivity: we observed no false negative cases and 36.8% false positive cases. By contrast, only 6.25% of the bladder cancer patients had positive urine cytology. Our results seem promising, although further studies and larger numbers are needed to define urinary free DNA as a reliable marker of bladder cancer.     

In-depth review: is hepcidin a marker for the heart and the kidney?

Iron is an essential trace element involved in oxidation–reduction reactions, oxygen transport and storage, and energy metabolism. Iron in excess can be toxic for cells, since iron produces reactive oxygen species and is important for survival of pathogenic microbes. There is a fine-tuning in the regulation of serum iron levels, determined by intestinal absorption, macrophage iron recycling, and mobilization of hepatocyte stores versus iron utilization, primarily by erythroid cells in the bone marrow. Hepcidin is the major regulatory hormone of systemic iron homeostasis and is upregulated during inflammation. Hepcidin metabolism is altered in chronic kidney disease. Ferroportin is an iron export protein and mediates iron release into the circulation from duodenal enterocytes, splenic reticuloendothelial macrophages, and hepatocytes. Systemic iron homeostasis is controlled by the hepcidin–ferroportin axis at the sites of iron entry into the circulation. Hepcidin binds to ferroportin, induces its internalization and intracellular degradation, and thus inhibits iron absorption from enterocytes, and iron release from macrophages and hepatocytes. Recent data suggest that hepcidin, by slowing or preventing the mobilization of iron from macrophages, may promote atherosclerosis and may be associated with increased cardiovascular disease risk. This article reviews the current data regarding the molecular and cellular pathways of systemic and autocrine hepcidin production and seeks the answer to the question whether changes in hepcidin translate into clinical outcomes of all-cause and cardiovascular mortality, and cardiovascular and renal end-points.

     

Glycogen metabolism loss: a common marker of parasitic behaviour in bacteria?

We searched 55 completely sequenced bacterial genomes for glycogen synthesis and degradation enzymes. A significant proportion of these bacteria appears to lack glycogen metabolism capability. Interestingly, these bacteria are parasitic, symbiotic or fastidious (i.e. difficult to culture outside their normal environment). It is suggested that the lack of bacterial glycogen metabolism is a trait associated with parasitic behaviour in bacteria.     

Heritability of cellular radiosensitivity: a marker of low-penetrance predisposition genes in breast cancer?

Many inherited cancer-prone conditions show an elevated sensitivity to the induction of chromosome damage in cells exposed to ionizing radiation, indicative of defects in the processing of DNA damage. We earlier found that 40% of patients with breast cancer and 5%-10% of controls showed evidence of enhanced chromosomal radiosensitivity and that this sensitivity was not age related. We suggested that this could be a marker of cancer-predisposing genes of low penetrance. To further test this hypothesis, we have studied the heritability of radiosensitivity in families of patients with breast cancer. Of 37 first-degree relatives of 16 sensitive patients, 23 (62%) were themselves sensitive, compared with 1 (7%) of 15 first-degree relatives of four patients with normal responses. The distribution of radiosensitivities among the family members showed a trimodal distribution, suggesting the presence of a limited number of major genes determining radiosensitivity. Segregation analysis of 95 family members showed clear evidence of heritability of radiosensitivity, with a single major gene accounting for 82% of the variance between family members. The two alleles combine in an additive (codominant) manner, giving complete heterozygote expression. A better fit was obtained to a model that includes a second, rarer gene with a similar, additive effect on radiosensitivity, but the data are clearly consistent with a range of models. Novel genes involved in predisposition to breast cancer can now be sought through linkage studies using this quantitative trait.     

Who gets the gametes? An argument for a points system for fertility patients

This paper argues that the convention of allocating donated gametes on a ‘first come, first served’ basis should be replaced with an allocation system that takes into account more morally relevant criteria than waiting time. This conclusion was developed using an empirical bioethics methodology, which involved a study of the views of 18 staff members from seven U.K. fertility clinics, and 20 academics, policy‐makers, representatives of patient groups, and other relevant professionals, on the allocation of donated sperm and eggs. Against these views, we consider some nuanced ways of including criteria in a points allocation system. We argue that such a system is more ethically robust than ‘first come, first served’, but we acknowledge that our results suggest that a points system will meet with resistance from those working in the field. We conclude that criteria such as a patient's age, potentially damaging substance use, and parental status should be used to allocate points and determine which patients receive treatment and in what order. These and other factors should be applied according to how they bear on considerations like child welfare, patient welfare, and the effectiveness of the proposed treatment.     

Fouling of gastropods: a role for parasites?

A sample of mud snails Hydrobia ulvae (Prosobranchia) from an intertidal population revealed that the shells of trematode-infected specimens were especially likely to be fouled with epibionts. Experimentally trematode-infected Biomphalaria glabrata (Pulmonata) appeared to be especially prone to develop epigrowth in comparison with uninfected conspecifics as well. These findings suggest an interaction between trematode infections and epibiosis in aquatic gastropods. The two most likely explanations for this are (1) that trematode infections weakens the snails' natural defences against epibionts, or (2) that the defences against epibionts also are effective against invading trematodes, causing snail specimens with a particularly good fouling defence to be less likely to become infected.