Molecular Analysis of the Magnocellular Neuroendocrine Phenotype: from the Micropunch to Laser Microdissection

Microdissection of selected regions of central nervous system (CNS) has provided the basis of modern chemoarchitectonics. Laser microdissection is a modern variant of the “Palkovits punch” technique and used together with gene array analysis has revolutionalized CNS molecular analysis. Here we describe the use of such an approach to elucidate molecules selectively expressed in magnocellular neuroendocrine cells (MCNs) in the supraoptic nucleus (SON). We found 123 genes that are preferentially expressed in the SON, and of these, 89 were substantially osmoregulated in their expression. One of these, C1q domain containing 1, is a novel gene that is osmoregulated much more than even vasopressin itself.Special Issue Dedicated to Miklós Palkovits.     

Anatomy of the Hypophysiotropic Somatostatinergic and Growth Hormone-releasing Hormone System Minireview

The central control of growth hormone (GH) secretion from the pituitary gland is ultimately achieved by the interaction between two hypothalamic neurohormones, somatostatin which inhibits and growth hormone-releasing hormone (GHRH) which stimulates GH release. The regulation of the somatostatin and GHRH release from the hypothalamus is regulated by a range of other neuropeptides, neurotransmitters, neurohormones. In this mini review we attempt to provide a short summary covering the anatomy and chemical characteristics of the various cell populations regulating GH secretion as a tribute to Miklós Palkovits who pioneered the field of functional neuroanatomy of hypothalamic networks.Special Issue Dedicated to Miklós Palkovits.     

Immunohistochemical Distribution and Subcellular Localization of the Somatostatin Receptor Subtype 1 (sst1) in the Rat Hypothalamus

The aim of the present study was to examine the cellular and sub-cellular distribution of the somatostatin (SRIF) receptor subtype sst1 in the rat hypothalamus. Receptors were immunolabeled using an antibody directed against an antigenic sequence in the N-terminus of the receptor. Immunopositive neuronal cell bodies and dendrites were observed throughout the mediobasal hypothalamus, including the medial preoptic area, paraventricular, periventricular, and arcuate nuclei. Immunoreactive axons and axon terminals were also observed in the median eminence, suggesting that sst1 is also located pre-synaptically. Electron microscopic examination of the arcuate nucleus revealed a predominant association of immunoreactive sst1 with perikarya and dendrites. Most immunoreactive receptors were intracellular and localized to tubulovesicular compartments and organelles such as the Golgi apparatus, but 14% were associated with the plasma membrane. Of the latter, 47% were apposed to abbuting afferent axon terminals and 20% localized immediately adjacent to an active synaptic zone. These results demonstrate a widespread distribution of sst1 receptors in rat hypothalamus. They also show that somatodendritic sst1 receptors in the arcuate nucleus are ideally poised to mediate SRIF’s modulation of afferent synaptic inputs, including central SRIF effects on growth hormone-releasing hormone neurons documented in this area.Special Issue Dedicated to Miklós Palkovits.     

The Study of Golgi Apparatus in Alzheimer’s Disease

Alzheimer’s disease is an irreversible, progressive neurodegenerative disorder leading invariably to death, usually within 7–10 years after diagnosis and is the leading cause of dementia in the elderly. Not only is Alzheimer’s disease a tragic disease in which people suffer from neurodegeneration in the years to come, it also becomes an incredible burden on the public health system. However, there is currently no effective treatment to halt the progression or prevent the onset of Alzheimer’s disease. This is partly due to the fact that the complex pathophysiology of Alzheimer’s disease is not yet completely understood. Recently, Golgi apparatus is found to play an important role in Alzheimer’s disease. In this review, we discuss the changes of Golgi apparatus during clinical progression and pathological development of Alzheimer’s disease. First, changes of Golgi apparatus size in Alzheimer’s disease are summarized. We then address the role of Golgi apparatus in the neuropathology of Alzheimer’s disease. Finally, the role of Golgi apparatus in the pathogenesis of Alzheimer’s disease is discussed. Understanding the contribution of Golgi apparatus dysfunction to Alzheimer’s disease and its pathophysiological basis will significantly impact our ability to develop more effective therapies for Alzheimer’s disease.     

Benford’s law applied to aerobiological data and its potential as a quality control tool

Benford’s phenomenological law gives the expected frequencies of the first significant digits of any given series of numbers. According to this law, the frequency of 1 is higher than that of 2; this in turn appears more often 3, and so on. Similarly, Benford’s law can also be applied to the first two significant digits (i.e., from 10 to 99), and so on. Here, we show that gross data sets of daily pollen counts from three aerobiological stations (located in European cities with different features regarding vegetation and climatology) fit Benford’s law for the first significant digits, but this is not always true for the data transformed by a correction factor used in aerobiological studies. That is to say, the biases introduced by rounding and lower and upper built-in limits in pollen counts are detected by Benford’s law analysis. The analysis of the first two significant digits from transformed data is better explained by a Power law than Benford’s law. We propose that Benford’s law could be used as a quality control tool for numerical aerobiological data sets.     

Marker-assisted rationalisation of genetic resource collections: a case study in flax using AFLPs

Removing redundant germplasm from collections is one of the options for genebanks to increase the efficiency of their genetic resource management. Molecular characterisation of germplasm is thereby becoming more and more important to verify suspected duplication. AFLPs were used to characterise 29 flax accessions of material derived from research activities (hereafter termed ’’breeder’s line”). Based on similar accession names, the breeder’s lines could be classified into three series (’M 25’, ’Ru’ and ’Rm’) that were expected to contain redundancies. In addition, 12 reference cultivars were analysed. A total number of 144 polymorphic bands (59.8%) were scored among the 164 individuals investigated. In general, relatively high levels of intra-accession variation were found, even for the cultivars examined. This finding was not in line with the low outcrossing rates reported for flax. A cluster analysis grouped the ’Ru’ and ’Rm’ series together, indicating their close genetic relationship. An analysis of molecular variance (AMOVA) showed a significant group effect (fibre/oil flax) only for ’M 25’, explaining 34% of the variation observed within this series. For the cultivars 40.5% of the variation was distributed among accessions within groups and all pairwise comparisons were significantly different, except for one case. Both for the series of breeder’s lines and the cultivars the major part of the variation was distributed among individuals within accessions. This component constituted 80.7% and 83.6% of the total variation for the ’Ru’ and ’Rm’ series, respectively. Pairwise comparisons of accessions were performed by AMOVA in order to identify redundant germplasm. Stepwise bulking of accessions until all remaining accessions were significantly different showed that the 29 accessions of breeder’s lines could be reduced to 14. Only a small negative effect of this bulking approach on the among-population component of variance was observed, showing a reduction of 2.6%. Results are discussed in relation to improving the efficiency of collection management. Received: 25 June 2000 / Accepted: 27 October 2000     

Words,antibodies and their interactions

Jerne’s idiotypic network theory stresses the importance of antibody-to-antibody interactions and provides possible explanations for self-tolerance and increased diversity in the immune repertoire. In this paper, we use an immune network model to build a user profile for adaptive information filtering. Antibody-to-antibody interactions in the profile’s network model correlations between words in text. The user profile has to be able to represent a user’s multiple interests and adapt to changes in them over time. This is a complex and dynamic engineering problem with clear analogies to the immune process of self-assertion. We present a series of experiments investigating the effect of term correlations on the user’s profile performance. The results show that term correlations can encode additional information, which has a positive effect on the profile’s ability to assess the relevance of documents to the user’s interests and to adapt to changes in them.     

Where does heteroclisis come from? Evidence from Romanian dialects

This study examines some cases of heteroclisis in the history of Romanian dialects, and concludes that the data call for a reconsideration of Stump’s distinction (Language 82:279–322, 2006) between ‘cloven’ heteroclisis, where the intraparadigmatic ‘split’ is aligned with some morphosyntactic feature distinction, and ‘fractured’ heteroclisis, where this is not the case and the pattern of heteroclisis is purely morphological. Stump’s account creates the impression that the ‘cloven’ variety is universally predominant, and that the ‘fractured’ variety tends to follow very closely the available ‘cloven’ patterns of the language. I shall suggest, instead, that the ‘fractured-only’ situation may in fact underlie heteroclisis cross-linguistically, the phenomenon being in general sensitive not directly to morphosyntactic content, but rather to characteristic, and often purely ‘morphomic’, patterns of stem-allomorphy. Research for this paper was undertaken as part of the Arts and Humantities Research Council-funded project Autonomous Morphology in Diachrony: comparative evidence from the Romance Languages, currently being conducted at Oxford University.     

Willingness to engage in casual sex

Sexually dimorphic mate selection strategies were examined in 200 university students reporting their willingness to engage in casual sexual encounters with hypothetical individuals of the opposite sex. Using a questionnaire format, the possibility of forming a long-term relationship was manipulated, while risk of disease, pregnancy, and detection was eliminated across all conditions. In addition, potential partners varied in level of attractiveness, and in personality and behavioral characteristics. As expected, men reported a greater anticipated willingness to engage in sexual intercourse across all conditions compared with women. The possibility of forming a long-term relationship elevated women’s, but not men’s, willingness for sexual intercourse. While a potential partner’s attractiveness had a significant positive overall effect on responses, reducing their relative attractiveness had a greater negative impact on men’s responses. Reference to the parental qualities of a potential partner significantly increased women’s, but not men’s, anticipated willingness for sexual intercourse. Describing a hypothetical partner as non-aggressive (safe) marginally increased women’s willingness (p<.09) and did not affect men’s responses. The wording of items relevant to this condition may have resulted in the potential partner sounding "wimpy" rather than nonaggressive, and this may have reduced the expected effect of this manipulation. The possibility that women may trade off personality and behavioral characteristics with attractiveness to a greater degree than men when assessing potential mates is considered.     

Cancer,Viruses, and Mass Migration: Paul Berg’s Venture into Eukaryotic Biology and the Advent of Recombinant DNA Research and Technology, 1967–1980

The existing literature on the development of recombinant DNA technology and genetic engineering tends to focus on Stanley Cohen and Herbert Boyer’s recombinant DNA cloning technology and its commercialization starting in the mid-1970s. Historians of science, however, have pointedly noted that experimental procedures for making recombinant DNA molecules were initially developed by Stanford biochemist Paul Berg and his colleagues, Peter Lobban and A. Dale Kaiser in the early 1970s. This paper, recognizing the uneasy disjuncture between scientific authorship and legal invention in the history of recombinant DNA technology, investigates the development of recombinant DNA technology in its full scientific context. I do so by focusing on Stanford biochemist Berg’s research on the genetic regulation of higher organisms. As I hope to demonstrate, Berg’s new venture reflected a mass migration of biomedical researchers as they shifted from studying prokaryotic organisms like bacteria to studying eukaryotic organisms like mammalian and human cells. It was out of this boundary crossing from prokaryotic to eukaryotic systems through virus model systems that recombinant DNA technology and other significant new research techniques and agendas emerged. Indeed, in their attempt to reconstitute ‹life’ as a research technology, Stanford biochemists’ recombinant DNA research recast genes as a sequence that could be rewritten thorough biochemical operations. The last part of this paper shifts focus from recombinant DNA technology’s academic origins to its transformation into a genetic engineering technology by examining the wide range of experimental hybridizations which occurred as techniques and knowledge circulated between Stanford biochemists and the Bay Area’s experimentalists. Situating their interchange in a dense research network based at Stanford’s biochemistry department, this paper helps to revise the canonized history of genetic engineering’s origins that emerged during the patenting of Cohen–Boyer’s recombinant DNA cloning procedures.     

Luminance-dependence of spatial vision in budgerigars (<Emphasis Type="Italic">Melopsittacus undulatus</Emphasis>) and Bourke’s parrots (<Emphasis Type="Italic">Neopsephotus bourkii</Emphasis>)

Budgerigars (Melopsittacus undulatus) and Bourke’s parrots (Neopsephotus bourkii) are closely related birds with different activity patterns. Budgerigars are strictly diurnal while Bourke’s parrots are active in dim twilight. Earlier studies show that the intensity threshold of colour vision is similar in both species while Bourke’s parrots have larger eyes with a higher density of rods than budgerigars. In this study, we investigate whether this could be an adaptation for better spatial vision in dim light. We used two alternative forced-choice experiments to determine the spatial acuity of both species at light intensities ranging from 0.08 to 73 cd/m². We also determined the spatial contrast sensitivity function (CSF) for bright light in Bourke’s parrots and compare it to existing data for budgerigars. The spatial acuity of Bourke’s parrots was found to be similar to that of budgerigars at all light levels. Also the CSF of Bourke’s parrots is similar to that of budgerigars with a sensitivity peak located between 2.1 and 2.6 cycles/degree. Our findings do not support the hypothesis that Bourke’s parrots have superior spatial acuity in dim light compared to budgerigars and the adaptive value of the relatively rod-rich and large eyes of Bourke’s parrots remains unclear.     

Maynard Smith on the levels of selection question

The levels of selection problem was central to Maynard Smith’s work throughout his career. This paper traces Maynard Smith’s views on the levels of selection, from his objections to group selection in the 1960s to his concern with the major evolutionary transitions in the 1990s. The relations between Maynard Smith’s position and those of Hamilton and G.C. Williams are explored, as is Maynard Smith’s dislike of the Price equation approach to multi-level selection. Maynard Smith’s account of the ‘core Darwinian principles’ is discussed, as is his debate with Sober and Wilson (1998) over the status of trait-group models, and his attitude to the currently fashionable concept of pluralism about the levels of selection.     

Deep cerebellar neurons mirror the spinal cord’s gain to implement an inverse controller

Smooth and coordinated motion requires precisely timed muscle activation patterns, which due to biophysical limitations, must be predictive and executed in a feed-forward manner. In a previous study, we tested Kawato’s original proposition, that the cerebellum implements an inverse controller, by mapping a multizonal microcomplex’s (MZMC) biophysics to a joint’s inverse transfer function and showing that inferior olivary neuron may use their intrinsic oscillations to mirror a joint’s oscillatory dynamics. Here, to continue to validate our mapping, we propose that climbing fiber input into the deep cerebellar nucleus (DCN) triggers rebounds, primed by Purkinje cell inhibition, implementing gain on IO’s signal to mirror the spinal cord reflex’s gain thereby achieving inverse control. We used biophysical modeling to show that Purkinje cell inhibition and climbing fiber excitation interact in a multiplicative fashion to set DCN’s rebound strength; where the former primes the cell for rebound by deinactivating its T-type Ca2⁺ channels and the latter triggers the channels by rapidly depolarizing the cell. We combined this result with our control theory mapping to predict how experimentally injecting current into DCN will affect overall motor output performance, and found that injecting current will proportionally scale the output and unmask the joint’s natural response as observed by motor output ringing at the joint’s natural frequency. Experimental verification of this prediction will lend support to a MZMC as a joint’s inverse controller and the role we assigned underlying biophysical principles that enable it.     

Ecosystem carbon stocks and their changes in China’s grasslands

The knowledge of carbon (C) stock and its dynamics is crucial for understanding the role of grassland ecosystems in China’s terrestrial C cycle. To date, a comprehensive assessment on C balance in China’s grasslands is still lacking. By reviewing published literature, this study aims to evaluate ecosystem C stocks (both vegetation biomass and soil organic C) and their changes in China’s grasslands. Our results are summarized as follows: (1) biomass C density (C stock per area) of China’s grasslands differed greatly among previous studies, ranging from 215.8 to 348.1 g C m⁻² with an average of 300.2 g C m⁻². Likewise, soil C density also varied greatly between 8.5 and 15.1 kg C m⁻². In total, ecosystem C stock in China’s grasslands was estimated at 29.1 Pg C. (2) Both the magnitude and direction of ecosystem C changes in China’s grasslands differed greatly among previous studies. According to recent reports, neither biomass nor soil C stock in China’s grasslands showed a significant change during the past 20 years, indicating that grassland ecosystems are C neutral. (3) Spatial patterns and temporal dynamics of grassland biomass were closely correlated with precipitation, while changes in soil C stocks exhibited close associations with soil moisture and soil texture. Human activities, such as livestock grazing and fencing could also affect ecosystem C dynamics in China’s grasslands.     

Efficient social contracts and group selection

We consider the Stag Hunt in terms of Maynard Smith’s famous Haystack model. In the Stag Hunt, contrary to the Prisoner’s Dilemma, there is a cooperative equilibrium besides the equilibrium where every player defects. This implies that in the Haystack model, where a population is partitioned into groups, groups playing the cooperative equilibrium tend to grow faster than those at the non-cooperative equilibrium. We determine under what conditions this leads to the takeover of the population by cooperators. Moreover, we compare our results to the case of an unstructured population and to the case of the Prisoner’s Dilemma. Finally, we point to some implications our findings have for three distinct ideas: Ken Binmore’s group selection argument in favor of the evolution of efficient social contracts, Sewall Wright’s Shifting Balance theory, and the equilibrium selection problem of game theory.     

The ecolabel and sustainable development

Abstract  The goal of the different national and supranational ecolabelling programs is to encourage consumers to choose products which are the least damaging to the environment. It is clear that the involvement of product and service users is essential to the establishment of sustainable consumption patterns. For this reason, ecolabelling must necessarily limit any risks of uncertainty. To this end, labels must take into account all the impacts of a product’s life cycle and use a reliable and verifiable evaluation method. In general, the organizations in charge of ecolabelling programs claim that a multi-criteria approach is used to define the exact labelling criteria appropriate for the product categories in question. These organizations generally maintain that their approach is based on the completion of exhaustive and complete life cycle analyses, which take into account all of the impacts caused by a product throughout its life cycle. And yet, the real situation is often far less clear-cut, and these simplified approaches, which tend to reconcile economic realism and methodological coherence, constitute the usual procedure for criteria definition. Thus, the procedures involved in criteria development often rely on a ‘semi-qualitative’ approach to the life cycle which uses both qualitative and quantitative data in order to identify the product’s significant stages on the environment. Presently, the ecolabel is a ‘non-verifiable expert property’ for the consumer. The ecolabel’s lack of objectivity in its criteria and its lack of transparency, resulting from non standardized methods whose accuracy cannot be measured, can only damage this sustainable development tool’s credibility. In effect, the primary hindrance to ecolabel development lies precisely within this difficulty of finding a compromise between economic feasibility and the scientific and methodological rigor which are indispensable to the label’s credibility and veracity.     

Functional genomics as a tool in virus research

Genomics is the study of an organism’s entire genome. It started out as a great scientific endeavor in the 1990s which aimed to sequence the complete genomes of certain biological species. However viruses are not new to this field as complete viral genomes have routinely been sequenced since the past thirty years. The ‘genomic era’ has been said to have revolutionized biology. This knowledge of full genomes has created the field of functional genomics in today’s post-genomic era, which, is in most part concerned with the studies on the expression of the organism’s genome under different conditions. This article is an attempt to introduce its readers to the application of functional genomics to address and answer several complex biological issues in virus research.     

Human energy

In the midst of big-oil record profits and growing debate on global warming, the Chevron Corporation launched its “Human Energy” public relations campaign. In television commercials and print advertisements, Chevron portrays itself as a compassionate entity striving to solve the planet’s energy crisis. Yet, the first term in this corporate oxymoron misleadingly reframes the significance of the second, suggesting that the corporation has a renewed focus. In depicting Chevron as a green/human organization, the “Human Energy” campaign obscures from view the corporation’s more unsightly products, policies, and practices. Reflection, however, on our own complicity in sustaining energy corporations and their activities undermines binary thinking and signals that the compulsion to denounce is insufficient. This article explores Chevron’s media campaign and one organized reaction to it. This counter-campaign both redeployed Chevron’s imagery and underscored our collusion and responsibility—tactics seeking to loosen the taut inevitability-of-oil story at Chevron’s core.     

A test of Rensch’s rule in dwarf chameleons (Bradypodion spp.), a group with female-biased sexual size dimorphism

Rensch’s rule describes a pattern of allometry in sexual size dimorphism (SSD): when males are the larger sex (male-biased SSD), SSD increases with increasing body size, and when females are the larger sex (female-biased SSD), SSD decreases with increasing body size. While this expectation generally holds for taxa with male-biased or mixed SSD, examples of allometry for SSD consistent with Rensch’s rule in groups with primarily female-biased SSD are remarkably rare. Here, I show that the majority of dwarf chameleons (Bradypodion spp.) have female-biased SSD. In accordance with Rensch’s rule, the group exhibits an allometric slope of log(female size) on log(male size) less than one, although statistical significance is dependent on the phylogenetic comparative method used. In this system, this pattern is likely due to natural selection on both male and female body size, combined with fecundity selection on female body size. In addition to quantifying SSD and testing Rensch’s rule in dwarf chameleons, I discuss reasons why Rensch’s rule may only rarely apply to taxa with female-biased SSD.     

A critical evaluation of copper metabolism in indian wilson’s disease children with special reference to their phenotypes and relatives

Wilson’s disease is an autosomal recessive disorder of copper accumulation in various organs, with most common clinical manifestations such as hepatic, neurological, and renal dysfunctions. Serum copper and ceruloplasmin in Wilson’s disease were significantly lower as compared to normals, controls, and relatives of Wilson’s disease patients, whereas marked hypercupriuria (145 ± 7 μg/24 h) was observed in Wilson’s children only. A good correlation (r = 0.92) was found between non-ceruloplasmin-bound copper and 24-h urinary copper excretion in Wilson’s disease patients. Further, copper studies among the different phenotypes of Wilson’s disease revealed substantially low serum ceruloplasmin and a marked hypercupriuria in Wilson’s disease children associated with renal tubular acidosis as compared to the patients with either hepatological or neurological manifestations. Serum ceruloplasmin levels in 14 patients of Wilson’s disease were between 14 and 20 mg/dL. These patients of Wilson’s disease were confirmed by measuring liver biopsy copper, which was about nine times higher than normal hepatic copper content. During the family screening by copper studies, four asymptomatic siblings were diagnosed for Wilson’s disease. These subjects were then started on D-penicillamine therapy because presymptomatic treatment prevents progression of the disease complications.