When brain clocks lose track of time: cause or consequence of neuropsychiatric disorders

Patients suffering from neuropsychiatric disorders often exhibit a loss of regulation of their biological rhythms which leads to altered sleep/wake cycle, body temperature rhythm and hormonal rhythms. Whereas these symptoms have long been considered to result from the pathology of the underlying disease, increasing evidence now indicates that the circadian system may be more directly involved in the etiology of psychiatric disorders. This emerging view originated with the discovery that the genes involved in the generation of biological rhythms are expressed in many brain structures where clocks function-and perhaps malfunction. It is also due to the interesting phenotypes of clock mutant mice. Here we summarize recent reports showing that alteration of circadian clocks within key brain regions associated with neuropsychiatric disorders may be an underlying cause of the development of mental illness. We discuss how these alterations take place at both systems and molecular levels.     

Sucrose exposure in early life alters adult motivation and weight gain

The cause of the current increase in obesity in westernized nations is poorly understood but is frequently attributed to a 'thrifty genotype,' an evolutionary predisposition to store calories in times of plenty to protect against future scarcity. In modern, industrialized environments that provide a ready, uninterrupted supply of energy-rich foods at low cost, this genetic predisposition is hypothesized to lead to obesity. Children are also exposed to this 'obesogenic' environment; however, whether such early dietary experience has developmental effects and contributes to adult vulnerability to obesity is unknown. Using mice, we tested the hypothesis that dietary experience during childhood and adolescence affects adult obesity risk. We gave mice unlimited or no access to sucrose for a short period post-weaning and measured sucrose-seeking, food consumption, and weight gain in adulthood. Unlimited access to sucrose early in life reduced sucrose-seeking when work was required to obtain it. When high-sugar/high-fat dietary options were made freely-available, however, the sucrose-exposed mice gained more weight than mice without early sucrose exposure. These results suggest that early, unlimited exposure to sucrose reduces motivation to acquire sucrose but promotes weight gain in adulthood when the cost of acquiring palatable, energy dense foods is low. This study demonstrates that early post-weaning experience can modify the expression of a 'thrifty genotype' and alter an adult animal's response to its environment, a finding consistent with evidence of pre- and peri-natal programming of adult obesity risk by maternal nutritional status. Our findings suggest the window for developmental effects of diet may extend into childhood, an observation with potentially important implications for both research and public policy in addressing the rising incidence of obesity.     

You Wnt some,you lose some: oncogenes in the Wnt signaling pathway

The highly regulated Wnt signaling cascade plays a decisive role during embryonic patterning and cell-fate determination. The inappropriate expression of Wnt target genes, resulting from deregulation of this pathway, is also implicated in tumorigenesis. Thus, regulation of this pathway is of paramount importance. The Wnt signals are extracellularly regulated by a diverse group of antagonists, cofactors and coreceptors. In the cytoplasm, beta-catenin, a key effector of the Wnt signaling cascade, is highly regulated by a large and fascinating complex of proteins. In the nucleus, activation of target genes is regulated by a complex interplay of activators, repressors and other proteins. Recently, new factors in this pathway have been identified and the interplay and mechanisms of action of key players have been better characterized. Collectively, this represents an important step forward in our understanding of the role of Wnt signaling in development and oncogenesis.     

Focusing on the genetics of hearing: you ain't heard nothin' yet

The complexity of genetic pathways for hearing is beginning to be amenable to unraveling by systematic functional genomic analysis. Genome-wide mutagenesis studies in the mouse are beginning to shed further light on the structure and regulation of the machinery of hearing.     

Parent-offspring conflict theory,signaling of need,and weight gain in early life

Human growth in early life has major implications for fitness. During this period, the mother regulates the growth of her offspring through placental nutrition and lactation. However, parent-offspring conflict theory predicts that offspring are selected to demand more resources than the mother is selected to provide. This general issue has prompted the development of begging theory, which attempts to find the optimal levels of offspring demand and parental provisioning. Several models have been proposed to account for begging behavior, whether by biochemical or behavioral pathways, including: (1) blackmail of parents; (2) scramble competition between multiple offspring; (3) honest signaling of nutritional need; and (4) honest signaling of offspring worth. These models are all supported by data from nonhuman animals, with species varying according to which model is relevant. This paper examines the evidence that human suckling and crying signal nutritional demand, need, and worth to the mother. While suckling provides hormonal stimulation of breast milk production and signals hunger, crying fulfills a different role, with evidence suggesting that it signals both worth and need for resources (nutrition and thermoregulation). The role of signaling in nutritional demand is examined in the context of three common health problems that have traditionally been assumed to have physiological rather than behavioral causes: excess weight gain, failure to thrive, and colic. The value of such an evolutionary approach lies in its potential to enhance behavioral management of these conditions.     

Specific for apurine-apyrimidine DNA endodeoxyribonuclease from the rat brain

Endodeoxyribonuclease was detected in rat neocortex chromatin. The partly purified enzyme was found to influence the superhelical apurine-apyrimidine DNA 50 times as effectively as compared to the native substrate. The enzyme hydrolyzes the phosphodiester bond with the formation of 3'-OH- and 5'-phosphate terminal groups. The enzyme-hydrolyzed DNA is an effective primer for DNA-polymerase I from E. coli. It was assumed that DNAase from rat brain chromatin is an apurine-apyrimidine endonuclease II.     

Discrimination of timbre in early auditory responses of the human brain

Background

The issue of how differences in timbre are represented in the neural response still has not been well addressed, particularly with regard to the relevant brain mechanisms. Here we employ phasing and clipping of tones to produce auditory stimuli differing to describe the multidimensional nature of timbre. We investigated the auditory response and sensory gating as well, using by magnetoencephalography (MEG).

Methodology/Principal Findings

Thirty-five healthy subjects without hearing deficit participated in the experiments. Two different or same tones in timbre were presented through conditioning (S1) – testing (S2) paradigm as a pair with an interval of 500 ms. As a result, the magnitudes of auditory M50 and M100 responses were different with timbre in both hemispheres. This result might support that timbre, at least by phasing and clipping, is discriminated in the auditory early processing. The second response in a pair affected by S1 in the consecutive stimuli occurred in M100 of the left hemisphere, whereas both M50 and M100 responses to S2 only in the right hemisphere reflected whether two stimuli in a pair were the same or not. Both M50 and M100 magnitudes were different with the presenting order (S1 vs. S2) for both same and different conditions in the both hemispheres.

Conclusions/Significances

Our results demonstrate that the auditory response depends on timbre characteristics. Moreover, it was revealed that the auditory sensory gating is determined not by the stimulus that directly evokes the response, but rather by whether or not the two stimuli are identical in timbre.     

得与失:苦苣苔科新的属级界定与分类系统——中国该科植物之变迁(英文)

过去20年对苦苣苔科植物的分子系统学研究已经极大地拓展了对这个科的种间关系与属一级之界定的理解。该文提供了一个苦苣苔科植物新分类系统,与传统的经典形态学分类系统比较,这一新系统被认为能更好地反映科下分类单元彼此之间的自然关系。众多传统意义上的属被分割、合并或者重新定义,这些巨大的分类变动正在影响着中国的苦苣苔科植物系统分类。此外,基于最近采集的材料,一些新属得以建立,一方面说明在中国还有相当多的野外工作需要做;而另一方面则再次证明了中国的苦苣苔科植物多样性是如此之丰富。在此,针对目前已经完成的工作和分类结论,对中国苦苣苔科植物的新分类系统进行了总结与概述,并深入地讨论了部分传统分类学上存在困惑的疑难属。     

How to lose a kink and gain a helix: pH independent conformational changes of the fusion domains from influenza hemagglutinin in heterogeneous lipid bilayers

We have simulated two conformations of the fusion domain of influenza hemagglutinin (HA) within explicit water, salt, and heterogeneous lipid bilayers composed of POPC:POPG (4:1). Each conformation has seven different starting points in which the initial peptide structure is the same for each conformation, but the location across the membrane normal and lipid arrangement around the peptide are varied, giving a combined total simulation time of 140 ns. For the HA5 conformation (primary structure from recent NMR spectroscopy at pH = 5), the peptide exhibits a stable and less kinked structure in the lipid bilayer compared to that from the NMR studies. The relative fusogenic behavior of the different conformations has been investigated by calculation of the relative free energy of insertion into the hydrophobic region of lipid bilayer as a function of the depth of immersion. For the HA7 conformations (primary structure from recent NMR spectroscopy at pH = 7.4), while the N-terminal helix preserves its initial structure, the flexible C-terminal chain produces a transient helical motif inside the lipid bilayer. This conformational change is pH-independent, and is closely related to the peptide insertion into the lipid bilayer.     

Apoptosis and autophagy as mechanisms of dinoflagellate symbiont release during cnidarian bleaching: every which way you lose

Cnidarian bleaching results from the breakdown in the symbiosis between the host cnidarian and its dinoflagellate symbiont. Coral bleaching in recent years has increasingly caused degradation and mortality of coral reefs on a global scale. Although much is understood about the environmental causes of bleaching, the underlying cellular mechanisms of symbiont release that drive the process are just beginning to be described. In this study, we investigated the roles of two cellular pathways, host cell apoptosis and autophagy, in the bleaching process of the symbiotic anemone Aiptasia pallida. Host cell apoptosis was experimentally manipulated using gene knockdown of an anemone caspase by RNA interference, chemical inhibition of caspase using ZVAD-fmk and an apoptosis-inducer wortmannin. Autophagy was manipulated by chemical inhibition using wortmannin or induction using rapamycin. The applications of multiple single treatments resulted in some increased bleaching in anemones under control conditions but no significant drop in bleaching in individuals subjected to a hyperthermic stress. These results indicated that no single pathway is responsible for symbiont release during bleaching. However, when multiple inhibitors were applied simultaneously to block both apoptosis and autophagy, there was a significant reduction in bleaching in heat-stressed anemones. Our results allow us to formulate a model for cellular processes involved in the control of cnidarian bleaching where apoptosis and autophagy act together in a see-saw mechanism such that if one is inhibited the other is induced. Similar interconnectivity between apoptosis and autophagy has previously been shown in vertebrates including involvement in an innate immune response to pathogens and parasites. This suggests that the bleaching response could be a modified immune response that recognizes and removes dysfunctional symbionts.     

Using physiology and behaviour to understand the responses of fish early life stages to toxicants

The use of early life stages of fishes (embryos and larvae) in toxicity testing has been in existence for a long time, generally utilizing endpoints such as morphological defects and mortality. Behavioural endpoints, however, may represent a more insightful evaluation of the ecological effects of toxicants. Indeed, recent years have seen a considerable increase in the use of behavioural measurements in early life stages reflecting a substantial rise in zebrafish Danio rerio early life‐stage toxicity testing and the development of automated behavioural monitoring systems. Current behavioural endpoints identified for early life stages in response to toxicant exposure include spontaneous activity, predator avoidance, capture of live food, shoaling ability and interaction with other individuals. Less frequently used endpoints include measurement of anxiogenic behaviours and cognitive ability, both of which are suggested here as future indicators of toxicant disruption. For many simple behavioural endpoints, there is still a need to link behavioural effects with ecological relevance; currently, only a limited number of studies have addressed this issue. Understanding the physiological mechanisms that underlie toxicant effects on behaviour so early in life has received far less attention, perhaps because physiological measurements can be difficult to carry out on individuals of this size. The most commonly established physiological links with behavioural disruption in early life stages are similar to those seen in juveniles and adults including sensory deprivation (olfaction, lateral line and vision), altered neurogenesis and neurotransmitter concentrations. This review highlights the importance of understanding the integrated behavioural and physiological response of early life stages to toxicants and identifies knowledge gaps which present exciting areas for future research.     

A new baleen whale from the Late Miocene of Denmark and early mysticete hearing

Abstract:  The extinct mysticete fauna of the North East Atlantic is primarily known from the abundant but fragmented Belgian specimens. Compared to the well-preserved contemporary mysticete fauna from deposits in North America, there are only few near complete European Miocene mysticete fossils. Presented here is a new, almost complete fossil baleen whale Uranocetus gramensis gen. et sp. nov. from the Upper Miocene Gram Formation in South West Denmark. It is the first stem-balaenopterid that has an initial stage of reduction in the mandibular cavity and a rostral configuration that is intermediate between that of other stem-balaenopterids and true balaenopterids. It is likely that Uranocetus used a gulp feeding technique that approaches that of balaenopterids. Details of the periotic and mandibular morphology place Uranocetus in the family Diorocetidae Steeman 2007. The large mandibular cavity in Uranocetus and most other extinct mysticetes, when compared to the reduced condition in recent mysticetes, is not an indication that early mysticetes used odontocete-like echolocation. In Uranocetus and a distantly related mysticete, high frequency sounds in the range odontocetes use for echolocation would suffer a significant volume loss across the lateral mandibular wall on the passage towards the inner ear. A reduction in the mandibular cavity in separate evolutionary lineages of mysticetes may be the result of a shift towards the use of low frequency sounds.     

“Can breast feeding help you in later life? Evidence from German military heights in the early 20th century”

Considerable literature exists on the benefits of breast feeding on the health and survival of infants and young children, but there is less on the effects on later life outcomes. One such measure of health and well-being that has received attention in the historical literature is terminal adult stature. Information on height is rather widely available; however, it is much more difficult to obtain data on breast feeding. One country that does have such information is Imperial Germany (1871-1919). A number of physicians and local health officials collected information on the incidence and duration of breast feeding early in the 20th century, particularly because of concern about the unusually high infant mortality rates in parts of Germany. Hallie Kintner has surveyed the published results of these studies. The information on the prevalence of breast feeding for the period 1903/10 has been inputed into a database of demographic and economic variables for the counties (Regierungsbezirke) of Germany (1850-1939). There are also published data on heights of military recruits from the Imperial German military forces in 1906. These can be linked to areas in the database and related to breast feeding practices and infant mortality both contemporaneously and approximately 20 years previous to 1906. Results indicate a significant effect of infant feeding practices on later life outcomes operating through infant health conditions, proxied by the infant mortality rate.