Are there errors in glycogen biosynthesis and is laforin a repair enzyme?

Glycogen, a branched polymer of glucose, is well known as a cellular reserve of metabolic energy and/or biosynthetic precursors. Besides glucose, however, glycogen contains small amounts of covalent phosphate, present as C2 and C3 phosphomonoesters. Current evidence suggests that the phosphate is introduced by the biosynthetic enzyme glycogen synthase as a rare alternative to its normal catalytic addition of glucose units. The phosphate can be removed by the laforin phosphatase, whose mutation causes a fatal myoclonus epilepsy called Lafora disease. The hypothesis is that glycogen phosphorylation can be considered a catalytic error and laforin a repair enzyme.     

Are differences in FSH concentrations involved in the control of ovulation rate in Romanov and Ile-de-France ewes?

Despite differences in FSH concentrations ranging from 1.5 ng/ml (Romanov ewes) to 4 ng/ml (Ile-de-France ewes) between the follicular and luteal phases, follicular growth (numbers of follicles growing, growth rates, maximum size reached) was morphologically similar between the two stages of the cycle. Injection of 750 i.u. hCG at Day 6 or 16 of the cycle triggered ovulation of 4.1 +/- 0.7 and 4.0 +/- 1.3 follicles in Romanov and 2.2 +/- 0.5 and 1.7 +/- 0.5 follicles in Ile-de-France ewes, respectively, demonstrating that functional differentiation was similar between the two stages of the cycle. As gonadotrophin environment differs between these two stages of the cycle, this suggests that there is a wide flexibility in the amount of gonadotrophins required to trigger terminal follicular growth and that ovarian requirements for gonadotrophins might work through thresholds. When Romanov and Ile-de-France ewes were given similar amounts of exogenous gonadotrophins (1250 i.u. PMSG, 750 i.u. hCG) after hypophysectomy, ovulation rates were close to the usual values (Romanov, 5.5 +/- 3.9; Ile-de-France, 1.4 +/- 0.5), demonstrating that differences in gonadotrophin concentrations during the follicular phase do not play a major role in the high ovulation of the Romanov compared to the Ile-de-France ewes.     

What is signal and what is noise in the brain?

The response of a cortical neuron to a stimulus can show a very large variability when repeatedly stimulated by exactly the same stimulus. This has been quantified in terms of inter-spike-interval (ISI) statistics by several researchers (e.g., [Softky, W., Koch, C., 1993. The highly irregular firing of cortical cells is inconsistent with temporal integration of random EPSPs. J. Neurosci. 13(1), 334-350.]). The common view is that this variability reflects noisy information processing based on redundant representation in large neuron populations. This view has been challenged by the idea that the apparent noise inherent in brain activity that is not strictly related or temporally coupled to the experiment could be functionally significant. In this work we examine the ISI statistics and discuss these views in a recently published model of interacting cortical areas [Knoblauch, A., Palm, G., 2002. Scene segmentation by spike synchronization in reciprocally connected visual areas. I. Local effects of cortical feedback. Biol. Cybernet. 87(3), 151-167.]. From the results of further single neuron simulations we can isolate temporally modulated synaptic input as a main contributor for high ISI variability in our model and possibly in real neurons. In contrast to alternative mechanisms, our model suggests a function of the temporal modulations for short-term binding and segmentation of figures from background. Moreover, we show that temporally modulated inputs lead to ISI statistics which fit better to the neurophysiological data than alternative mechanisms.     

Does the difference in the timing of eclosion of the fruit fly Drosophila melanogaster reflect differences in the circadian organization?

The eclosion rhythm of a laboratory population of Drosophila melanogaster was studied under 12h light, 12h dark (LD 12:12) cycles. Although most of the flies were found to eclose just after “lights on” in LD 12:12, termed within gate (WG) flies, a few flies were found to eclose nearly 10h after peak eclosion, termed outside gate (OG) flies. The circadian parameters of the clocks controlling oviposition rhythms in the WG and the OG flies were estimated to understand the cause of such differences in the timing of eclosion. The distribution of the fraction of individual flies exhibiting single, multiple, and no significant period in the WG flies was significantly different from distribution in the OG flies. Compared to the WG flies, more OG flies were found to exhibit oviposition rhythm with multiple periodicity, whereas more WG flies exhibited an oviposition rhythm with a single significant period. The fraction of flies with arrhythmic oviposition was similar in both the WG and the OG flies. Free-running period τ in constant darkness (DD) and the phase angle difference ψ in LD 12:12 for the oviposition rhythm of WG and OG flies were significantly different. These results suggest that the differences in the time of eclosion between the flies eclosing within the gate and outside the gate of eclosion are probably due to differences in the circadian system controlling eclosion, which is reflected by the differences in their oviposition rhythm. (Chronobiology International, 18(4), 601-612, 2001)     

Does the timing of attainment of maturity influence sexual size dimorphism and adult sex ratio in turtles?

The attainment of sexual maturity has been shown to affect measures of sexual size dimorphism (SSD) and adult sex ratios in several groups of vertebrates. Using data for turtles, we tested the model that sex ratios are expected to be male‐biased when females are larger than males and female‐biased when males are larger than females because of the relationship of each with the attainment of maturity. Our model is based on the premise that the earlier‐maturing sex remains smaller, on average throughout life, and predominates numerically unless the sexes are strongly affected by differential mortality, differential emigration, and immigration, or biased primary sex ratios. Based on data for 24 species in seven families, SSD and sex ratios were significantly negatively correlated for most analyses, even after the effect of phylogenetic bias was removed. The analyses provide support for the model that SSD and adult sex ratios are correlated in turtles as a result of simultaneous correlation of each with sexual differences in attainment of maturity (bimaturism). Environmental sex determination provides a possible mechanism for the phenomenon in turtles and some other organisms. © 2014 The Authors. Biological Journal of the Linnean Society published by John Wiley & Sons Ltd on behalf of The Linnean Society of London, Biological Journal of the Linnean Society, 2014, 112 , 142–149.     

Changes in dialysate concentrations of glutamate and GABA in the brain: an index of volume transmission mediated actions?

Brain microdialysis has become a frequently used method to study the extracellular concentrations of neurotransmitters in specific areas of the brain. For years, and this is still the case today, dialysate concentrations and hence extracellular concentrations of neurotransmitters have been interpreted as a direct index of the neuronal release of these specific neurotransmitter systems. Although this seems to be the case for neurotransmitters such as dopamine, serotonin and acetylcholine, the extracellular concentrations of glutamate and GABA do not provide a reliable index of their synaptic exocytotic release. However, many microdialysis studies show changes in extracellular concentrations of glutamate and GABA under specific pharmacological and behavioural stimuli that could be interpreted as a consequence of the activation of specific neurochemical circuits. Despite this, we still do not know the origin and physiological significance of these changes of glutamate and GABA in the extracellular space. Here we propose that the changes in dialysate concentrations of these two neurotransmitters found under specific treatments could be an expression of the activity of the neurone-astrocyte unit in specific circuits of the brain. It is further proposed that dialysate changes of glutamate and GABA could be used as an index of volume transmission mediated actions of these two neurotransmitters in the brain. This hypothesis is based firstly on the assumption that the activity of neurones is functionally linked to the activity of astrocytes, which can release glutamate and GABA to the extracellular space; secondly, on the existence of extrasynaptic glutamate and GABA receptors with functional properties different from those of GABA receptors located at the synapse; and thirdly, on the experimental evidence reporting specific electrophysiological and neurochemical effects of glutamate and GABA when their levels are increased in the extracellular space. According to this concept, glutamate and GABA, once released into the extracellular compartment, could diffuse and have long-lasting effects modulating glutamatergic and/or GABAergic neurone-astrocytic networks and their interactions with other neurotransmitter neurone networks in the same areas of the brain.     

Success of ectoparasites: how important is timing of host contact?

Hosts often differ in their degree of parasitism and their expression of resistance. Yet very little is known about how the availability (and allocation) of resources to parasites at pre-infective stages influences their success in initiating parasitism, or in inducing and succumbing to resistance from hosts. We studied a damselfly-mite association to address how experimental variation in the age of first contact with hosts (timing) influenced subsequent parasite fitness. We demonstrate that timing influenced the ability of larval mites to make the transition to parasitism, but was not associated with measures of physiological resistance by hosts. Timing presumably relates to the availability of resources remaining for individuals to exploit their hosts. More research is needed on the importance of such factors, from variation in host resistance and parasite success and, ultimately, to the numbers and distributions of parasites on hosts.     

What is new in the treatment of hypospadias?

Hypospadias is a congenital anomaly characterized by a ventrally placed urethral meatus in a more proximal position on the midline than its normal position in the glanular part of the penis. In 1961, C. E. Horton and C. J. Devine, Jr., developed single-stage modern surgical techniques, namely, local skin flaps and free skin grafts, for urethra reconstruction in hypospadias repair, which may be applied to almost any case with different localizations of the meatus. Later, two new methods, advancement of the urethra and preputial island flap techniques, were added to the surgical algorithm. Because acceptable results were observed, the authors have insisted on using these four techniques for all hypospadias cases since 1972. Complication rates (mainly fistula formation) were quite high (50 percent) in their early series of adults as a result of erection and hematoma formation. The complication rate of their patient population, which is now mainly composed of preschool children, has decreased to 7 to 8 percent, primarily as a result of careful selection of appropriate techniques for each individual case, the development of better surgical materials and equipment, and taking necessary precautions for postoperative care. A brief summary of modern hypospadias repair techniques is presented in four major classes. The results of the authors' 30-year experience and the precautions necessary to avoid postoperative complications are evaluated. The authors conclude that the four modern techniques and their modifications should be performed meticulously for successful hypospadias repair.     

Phylogeography of the capercaillie in Eurasia: what is the conservation status in the Pyrenees and Cantabrian Mounts?

The Western capercaillie (Tetrao urogallus) is a keystone species of Palearctic boreal and altitude coniferous forests. With the increase of mountain leisure activities and habitat loss, populations are declining in most mountain ranges in Western Europe. Recent work has shown that the populations from the Pyrenees and Cantabrian Mountains survived a severe bottleneck during the 19th century, and are still considered as threatened due to habitat fragmentation and isolation with other populations. We present an extensive phylogeographic study based on mitochondrial DNA sequence (control region) extracted non-invasively from faeces collected throughout the species range (from western European mountains to central and eastern Europe, Fenno-Scandia, Russia and Siberia). We also compared our results with DNA sequences of closely related black-billed capercaillie (T. parvirostris). We found that populations from Pyrenees and Cantabrians are closely related but are different from all other capercaillie populations that form a homogenous clade. Therefore, we consider that these South-Western populations should be considered as forming an Evolutionary Significant Unit that needs an appropriate management at a local scale. We also discuss the possible locations of glacial refugia and subsequent colonisation routes in Eurasia, with a Western “aquitanus” lineage from Iberia and Balkans, and an Eastern “urogallus” lineage from Southern Asia. This work might have important implication for capercaillie conservation strategies to define important areas for conservation, and to prevent possible exchange or introductions of individuals originated from other lineages. Electronic Supplementary Material The online version of this article (doi: ) contains supplementary material, which is available to authorized users.     

Immunocytochemical localization and concentrations of the α and γ subunits of 7S-nerve growth factor in the submandibular gland of the mouse

Summary For unexplained reasons, nerve growth factor (NGF) exists in very high concentrations in the submandibular gland of the mouse. The NGF in the gland, called 7S-NGF, is a non-covalent complex of three protein subunits, named -, - and -NGF. All the known biological activity resides in the -NGF subunit, and previous studies have shown that -NGF is present in much greater concentrations in the male submandibular gland than in the female gland. The higher concentration in the male is due to the fact that -NGF is synthesized in the granular tubule cells of the submandibular gland. These cells are much more numerous in the male gland.In contrast to -NGF, neither the concentrations of and subunits nor their cellular localization in the mouse submandibular gland have been established. In this study, radioimmunoassays specific for . and subunits determined that both are present in much higher concentrations in the male gland. Immunocytochemical work localized both subunits in the granular tubule cell in the male and female submandibular gland. This indicates that all the components of 7S-NGF exist in a single cell type in the gland and suggests that 7S-NGF can be formed within this cell and secreted as a complex into the saliva.     

Prominent ears in children younger than 4 years of age: what is the appropriate timing for otoplasty?

The present study was conducted to determine whether otoplasty performed in children younger than 4 years of age has an acceptable long-term outcome. This two-part study consisted of (1) a questionnaire mailed to 481 members of the American Association of Plastic Surgeons to ask their opinion on the timing of otoplasty, and (2) a consecutive series of 12 patients who had otoplasty performed before the age of 4 years. The survey demonstrated that the majority (57 percent) of the respondents perform otoplasty on patients who are aged 5 years or older. The prospective series consisted of 12 patients ranging in age from 9 months to 3 years at the time of the procedure. Otoplasty was bilateral in nine patients and unilateral in three patients. Length of follow-up ranged from 21 months to 7(1/2) years, with a median follow-up of 41 months. Growth following otoplasty was evaluated in three patients who underwent unilateral otoplasty by measuring the length of both ears at the time of final follow-up. No difference in ear length was noted between the sides that were and were not operated on during a follow-up period of 46 to 63 months. Noticeable recurrence was noted in only one (8 percent) of 12 patients. In response to a follow-up questionnaire to the patients' families, all respondents (n = 10) stated that if again asked to choose the timing of otoplasty in their children, they would opt to have it performed at the same age of younger than 4 years. Otoplasty can be safely performed at ages younger than previously thought without interfering with growth of the operated ear.     

Relationships between the incidence of pre-ovulatory behaviour and the concentrations of oestradiol-17β and progesterone in bovine plasma

The incidence of eleven components of behaviour exhibited by 24 British Friesian heifers, housed in three groups of eight, was recorded for 24 days. All observed behaviour involved the participation of two individuals, these being within groups. The identity of the heifer initiating each behavioural event and that of the one receiving it was recorded. Thus the incidence of 11 “initiating” components and 11 “receiving” components, in effect the incidence of 22 different (but related) components, was recorded throughout an oestrous cycle for all heifers.Components were classified into four groups: standing, mounting, initiating behaviour (other than mounting) and receiving behaviour (other than standing). There was a peak in the incidence of all four groups around the time of oestrus, standing being uniquely, and mounting very highly, associated with the state of oestrus.Plasma oestradiol-17β levels rose steadily during 4 days to a peak, at about the time of onset of the greatly increased incidence of behaviour at oestrus, when progesterone levels were low. Oestradiol-17β levels then declined rapidly to a low level within 12 h of the end of the period of increased incidence of behaviour. No correlation was found between the magnitude of individual, peak, pre-oestrus levels of plasma oestradiol-17β and the incidence of any of the four groups of behavioural components.It is suggested that the limits of the time period when oestrous behaviour is shown are controlled mainly by oestradiol-17β, probably by the timing of its retention by receptors in cells of target brain tissues. The incidence of behavioural events during this period is, however, in part controlled by the presence or absence of a second oestrous heifer.A second smaller peak of plasma oestradiol-17β occurred 5 days after oestrus, when plasma progesterone was about one-third of peak luteal phase levels. No increase in incidence of behaviour was associated with this oestradiol-17β peak.     

How does inactivation change timing of replication in the human X chromosome?

Summary The kinetics of replication of the inactive (late replicating) X chromosome (LRX) were studied in karyotypically normal lymphocytes and human amniotic fluid cells. Both cell types were successively pulse labeled with 1-h or 1/2-h thymidine pulses in an otherwise BrdU-substituted S phase after partial synchronization of the cultures at G₁/S. For the first time with this technique, the entire sequence of replication was analyzed for the LRX from the beginning to the end of the S phase, with special reference to mid S (R-band to G-band transition replication). The inactive X is the last chromosome of the metaphase to start replication, with a delay of 1 or 2h, after which time a thymidine pulse results in R-type patterns. In mid S, the inactive X is the first chromosome to switch to G-type replication (without overlapping of both types and without any detectable replication pause). Until the end of S, a thymidine pulse results in G-type patterns. To rule out artifacts that might arise by the synchronization of cultures in these experiments, controls were carried out with BrdU pulses and the BrdU antibody technique without synchronization. In the course of replication, no fundamental difference was seen between the two different cell types examined. In contrast to studies using continuos labeling, this study did not reveal an interindividual difference of replication kinetics in the LRXs of the seven individuals studied; thus it is concluded that the inactive X chromosome shows only one characteristic course of replication.     

When can embryos learn? A test of the timing of learning in embryonic amphibians

Learning is crucial to the survival of organisms across their life span, including during embryonic development. We set out to determine when learning becomes possible in amphibian development by exposing spotted salamander (Ambystoma maculatum) embryos to chemical stimuli from a predator (Ambystoma opacum), nonpredator (Lithobates clamitans), or control at developmental stages 16–21 or 36–38 (Harrison 1969 ). Once exposures were completed and embryos hatched, we recorded the number of movements and time spent moving of individuals in both groups and all treatments. There was no significant difference in number of movements or time spent moving among any of the treatments. The groups that were exposed to predator stimuli and a blank control at stages 36–38 were also tested to determine whether there was a difference in refuge preference or difference in survivorship when exposed to a predator (marbled salamander). There was no difference in survival or refuge preference between individuals; however, all individuals preferred vegetated over open areas regardless of treatment type. We discuss hypotheses for the absence of embryonic learning in this species and suggest it may be the result of the intensity of the predator–prey interaction between the predator, large marbled salamander larvae, and the prey, spotted salamander larvae.     

Metabolic and hedonic drives in the neural control of appetite: who is the boss?

Obesity is on the rise in all developed countries, and a large part of this epidemic has been attributed to excess caloric intake, induced by ever present food cues and the easy availability of energy dense foods in an environment of plenty. Clearly, there are strong homeostatic regulatory mechanisms keeping body weight of many individuals exposed to this environment remarkably stable over their adult life. Other individuals, however, seem to eat not only because of metabolic need, but also because of excessive hedonic drive to make them feel better and relieve stress. In the extreme, some individuals exhibit addiction-like behavior toward food, and parallels have been drawn to drug and alcohol addiction. However, there is an important distinction in that, unlike drugs and alcohol, food is a daily necessity. Considerable advances have been made recently in the identification of neural circuits that represent the interface between the metabolic and hedonic drives of eating. We will cover these new findings by focusing first on the capacity of metabolic signals to modulate processing of cognitive and reward functions in cortico-limbic systems (bottom-up) and then on pathways by which the cognitive and emotional brain may override homeostatic regulation (top-down).