bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of herb mixture supplementation in ratio on milk yield, milk composition and its technological suitability
Authors: Grega T. , Sady M. , Kraszewski J.
Published: November 2009

Investigations were carried out on milk cows of Black -and- White breed being in 2-nd lactation 30-120 day after parturition. Experiment was performed during winter feeding season (corn silage, fodder beet silage, super beet pulp, concentrate, meadow hay). Cows of the experimental group received supplement (5% of concentrate) of the herb mixture in feeding ratio. The composition of this mixture was as follows: Urtica dioica, Fructus carvi, Pradix teraxaci, Agrimonio eupatoria, Matrica chamomilla. The obtained results show that supplementation of the diet by herb mixture induced increase of the following parameters: milk yield (+2 kg), fat content (+0,04%), protein content (+0,06%), citric acid (+0,10%), whey proteins (+0,02%), casein (+0,04%), dry matter (+0,12%), non fat dry matter (+0,07%). It was stated that in the experimental milk non-saturated fatty acid level was higher (+20%), in opposite to lower level of saturated fatty acids (-15%) and total cholesterol (-25%). The beneficial effect of herb mixture supplementation on the results of rennet-fermentation test, fermentation test, Sehern' s test and heat stability was stated in the experimental group milk.
Methods for determination of the conformation of chicken carcass
Authors: Hopic Senad , Pavlovski Zlatica , Skrbic Zdenka , Lukic Milos
Published: November 2009

With the exception of shank length, significant differences in regard to all conformation measures were established in case of observed conformation measures. Statistically significant differences were established in all investigated traits by use of g/mm index. By application of Jaap index, significances were expressed in case of shank length and thigh girth. Hybro chickens had considerably longer shanks, whereas the thigh girth was considerably greater on Arbor Acres carcasses. - The highest deviation of absolute conformation measures was achieved by formation of mixed model of variance analysis. Also, significances were established, as well as by application of Jaap index, in case of shank length and thigh girth, however, both measures were considerably higher on carcasses of Hybro chickens.
Strategies to control high pathogenic avian influenza (HPAI) in the Belgian poultry sector
Authors: Vandendriessche Y. , Gellynck X. , Saatkamp H. , Viaene J.
Published: November 2009

High Pathogenic Avian Influenza (HPAI) may pose a major threat for the Belgium poultry sector, as an outbreak of HPAI results in tremendous economic losses. In order to reduce the economic damage for an outbreak, different strategies to control HPAI are evaluated. In a first stage the structure of the Belgium poultry sector is described and risks are analyzed. The actual risks are dependent of the intensive character of poultry farming in Belgium, the large number of transport movements of living poultry, the presence of sensitive nature areas and the border with the Netherlands where the poultry density is even larger. In a second stage the possible intervention strategies are evaluated. Starting from the current regulation, two strategies are worked out: stamping out and emergency vaccination. The success of emergency vaccination is associated with the correct identification of compartments at risk, prompt deployment of emergency vaccines, rapid enforcement of appropriate complementary control measures and also the level of being ready. In a third stage an economic analysis of control strategies for HPAI outbreaks is made. Results suggest that from an economic point of view, stamping-out is at farm level a better option then emergency vaccination within the current context.
Mineral nutrition of modern poultry genotypes
Authors: Lukic M. , Pavlovski Z. , Skrbic Z.
Published: November 2009

In the latest research relating to mineral nutrition of poultry, the interest in several nutrients is prevailing for which in ordinary diets additional sources are necessary. In mineral nutrition of layers constantly the calcium (Ca) requirements are reviewed as one of the most important factors influencing the quality of eggs and bones, in regard to adequate level, source and particle size of added Ca, as well as mutual balance with other nutrients, primarily vitamin D, phosphorus (P) and certain micro-elements. Also, efforts are directed towards possibility and justification for use of new source of vitamin D, existing recommendations related to P are reviewed as well as increase of possibility for adoption of phytine bound phosphorus in diets using enzyme phytase, as well as investigation of organic forms of certain micro-element sources. Certain researches which combine the latest studies of the mineral nutrition of poultry are especially interesting also for practical application. Contrary to layers, focus of research of mineral nutrition of broilers is on phosphorus and application of enzyme phytase. In general, researches of the mineral nutrition of modern poultry genotypes are always actual, considering that their objective is to support genetic progress with adequate nutrition, but also to solve increasing problems relating to product quality, metabolic disorders and ecology.
Biological potential of fecundity of sows
Authors: Wähner M. , Brüssow K.P.
Published: November 2009

The profitability of pig production considerably depends on the number of born alive and fostered piglets. The development regarding the number of piglets born for German Landrace (DL), Large White (DE) and Pietrain (PI) in Germany during 1980 - 2006 is limited (DL: 10.4 - 11.0; DE: 11.0 - 11.0; PI: 10.2 - 10.0). Comparing international data, variations between 10.2 to 13.6 piglets born alive are observed. Reproductive performance in sows is mainly determined by (1) the number of ovulated follicles and fertilized oocytes, (2) the divvy of surviving embryos and foetuses, and (3) the morphological and functional performance of the uterus to support foetal development up to birth. The question whether the ovary and/or uterus are limiting factors can be answered as followed. The pool of ovarian follicles is not the limiting one, although only about 0.5 % of oocytes present in the ovary are ovulated during the sows' lifetime. Selection for ovulation rate increases the number of ovulating follicles, but not of piglets born alive. Limiting is the uterine capacity. This physical, biochemical and morphological limitation of the uterus include space, nutrients, gas exchange and surface of the placenta. Although a relationship exists between uterine dimension and the number of foetuses/piglets, uterine length alone is not a prerequisite of higher uterine capacity. Placental efficiency (indicating how much gram foetus is supported by one gram placenta) and the degree of placental blood supply appear to be essentially for litter size. At present, the (really) assumed potential of fecundity is 15.0 piglets born alive, 2.4 litters/year, <10 % losses and 32.5 piglets per sow/year (compared to current data of 11.1, 2.26, 13.8 and 21.5, respectively).
Animals and philosophers: Preface to my critics
Authors: Krstic Predrag
Published: November 2009

The author is here seeking to expose his book Philosophical Animal zoographical persuasion to philosophy, to his own remorseless analysis - and that way defend the book from potential criticism by the others. On the other hand, the author believes that this will open up the space for discussion about the book and themes that book provokes. This discussion is not going to be mere neatly registered response and/or appropriate praise but a contribution inspired by the book, resonating back to it.
Politisation de la pensée deleuzienne, position de minorité dans le marxisme
Authors: Blan Sibertan
Published: November 2009

(francuski) Repartant de la premi?re courbe d'?laboration du concept de 'devenir- Mineur' de Deleuze et Guattari (de Kafka Pour une litt?rature mineure ? Mille plateaux), nous interrogeons le rapport entre les deux lignes de probl?matisation de ce concept: une analyse des antagonismes historiques dont les minorit?s sociales sont aujourd'hui le lieu 'surd?termin?' l'identification d'un type de position au sein des modes collectifs d'?nonciation. Par l?, nous soulevons ?galement le probl?me de ce que peut signifier politiquement occuper une position de minorit? dans le discours (th?orique, litt?raire, philosophique?). C'est en ce sens que nous confrontons les luttes de minorit?s au sch?me de la lutte des classes, que nous examinons certains liens (liens de prolongement, d'int?gration, mais aussi de diff?renciation) entre les processus de 'prol?tarisation' et de 'minoration', et que nous reposons sur cette base la question d'un nouvel internationalisme.
The birth of Russian intelligentsia from the spirit of the enlightenment: Alexander Radishchev
Authors: Subotic Milan
Published: November 2009

This text is the second part of a study about Alexander Radishchev, one of the leading representatives of Enlightenment in Russia's XVIII Century. Starting with explanation of the 'enlightened absolutism' of Catherine the Great, the author analyses the political and social ideas presented in Radishchev's book Journey from St. Petersburg to Moscow. Considering Radishchev as a 'father of Russian intelligentsia', the author stress that Radishchev's social criticism anticipated the later phenomenon of 'dissidence'.
Efficiency of the process of cryogenic air separation into the components
Authors: Mitovski Milance , Mitovski Aleksandra
Published: November 2009

The separation process of atmospheric air into its components by means of cryogenic low-pressure procedure, which takes place in the Oxygen plant in the Copper Mining and Smelting Complex, yields various products of different quantities and purities. Proper assessment of the energy consumption, hence assignments production cost of individual products may present considerable problem. For that goal, the least invested technical operation was adopted as criteria, and was restrained for all costs of production and distribution of specific energy. Case study was carried out in the Oxygen factory by monitoring producing parameters for the process in the 2007 year. Based on the monitoring of production parameters and their costs for 20 months in the period 2004-2005, correlation equations for power consumption in the total monthly amount and per mass of produced gaseous oxygen were created. The energy and exergy efficiency of the air separation process into the components are expressed as the ratio of input and useful energy and exergy of the process. On the basis of the adopted criteria, the assignments of energy consumption and production costs for cryogenic air separation process into the components are as follows: 82.59% for gaseous oxygen, 14.04% for liquid oxygen, 1.39% for gaseous nitrogen and 1.98% for liquefied nitrogen. The air separation efficiency is achieved in the amount of energy 0.0872-0.1179 and exergy 0.0537-0.1247. Power consumption per mass of the products in 2007 year is 1325.059 kWh/t of liquid oxygen, 828.765 kWh/t of liquid nitrogen, 429.812 kWh/t of gaseous oxygen and 309.424 kWh/t of nitrogen gas. Production costs of the technical gases at the dawn of the factory are: 6730.69 RSD/t of liquid oxygen, 4209.74 RSD/t of liquid nitrogen, 2183.25 RSD/t of gaseous oxygen and 1571.73 RSD/t of gaseous nitrogen.
Capital Market Prices, Management Forecasts, and Earnings Management
Authors: Beyer Anne
Published: November 2009

ABSTRACT: I analyze a manager's optimal earnings forecasting strategy and optimal earnings management policy in a setting where both the mean and the variance of the distribution generating the firm's cash flows are unknown. The analysis shows that the equilibrium price of the firm is a function of the manager's forecast, the firm's reported earnings, and the squared error in the manager's earnings forecast. The model contains several predictions, including: (1) the manager manipulates earnings to reduce his forecast error at the earnings announcement date; (2) the firm's stock price is more sensitive to the firm's actual earnings announcement than to the manager's forecast; and (3) controlling for the level of reported earnings and the magnitude of the earnings surprise, the firm's price is higher when it has a positive surprise at the earnings announcement date than when it has a negative surprise.
Organizational Design and Control across Multiple Markets: The Case of Franchising in the Convenience Store Industry
Authors: Campbell Dennis , Datar Srikant M. , Sandino Tatiana
Published: November 2009

ABSTRACT: Many companies operate units that are dispersed across different types of markets, serving significantly divergent customer bases. Such dispersion is likely to compromise headquarters' ability to control local managers' behavior and satisfy the needs of different customer types. In this study we find that market-type dispersion is an important determinant of the delegation of decision rights and the provision of incentives. Using a sample of convenience store chains, we show that market-type dispersion is positively associated with the degree of franchising at the chain level as well as the probability of franchising a given store within a chain. Our results are robust to alternative definitions of market-type dispersion and to other determinants of franchising such as the stores' geographic dispersion. Additional analyses suggest that chains that do not franchise cope with market-type dispersion by decentralizing operations from headquarters to their stores and providing their store managers higher variable pay.
Who Really Matters? Revenue Implications of Stakeholder Satisfaction in a Health Insurance Company
Authors: Chen Clara Xiaoling
Published: November 2009

ABSTRACT: This study examines the revenue implications of satisfaction measures in a setting with multiple stakeholders. I obtain a proprietary database from a leading health insurance company that measures satisfaction levels of multiple stakeholders, including: (1) clients that purchase insurance plans for their employees, (2) patients who use the insurance plans, and (3) doctors who provide medical services. Using multi-stakeholder satisfaction data over a 20-quarter period, I find that satisfaction measures are multi-dimensional, and that future revenues are positively associated with certain, but not all, dimensions of client, patient, and doctor satisfaction. Drawing on stakeholder theory, I predict that the revenue implications of stakeholder satisfaction vary with the power of different stakeholder groups. Specifically, I examine the moderating effects of the percentage of voluntary patients, business unit age, and market penetration on the relation between stakeholder satisfaction and future revenues, finding evidence consistent with my prediction.
The Quality of Analysts' Cash Flow Forecasts
Authors: Givoly Dan , Hayn Carla , Lehavy Reuven
Published: November 2009

ABSTRACT: This study examines properties of analysts' cash flow forecasts and compares them to those exhibited by analysts' earnings forecasts. Our results indicate that analysts' cash flow forecasts are less accurate than analysts' earnings forecasts and improve at a slower rate during the forecast period. Further, cash flow forecasts appear to be a nai¨ve extension of analysts' earnings forecasts, thus providing limited information on expected changes in working capital. We also find that analysts' forecasts of cash flows are of limited information content and are only weakly associated with stock returns. Finally, estimating expected accruals as the difference between analysts' earnings forecasts and their cash flow forecasts does not result in a better detection of earnings management than achieved by commonly used accrual models.
Improving Investors' Forecast Accuracy when Operating Cash Flows and Accruals Are Differentially Persistent
Authors: Hewitt Max
Published: November 2009

ABSTRACT: This study uses an experiment to examine (1) what factors give rise to investors' inability to fully incorporate operating cash flows and accruals into their earnings forecasts, and (2) what conditions help to improve investors' forecast accuracy when operating cash flows and accruals exhibit differential persistence. I investigate how decomposing the forecasting task and altering the presentation format combine to enable analysts and nonprofessional investors to acquire and accurately process financial statement information when operating cash flows and accruals are differentially persistent. I find that the earnings forecasts of analysts and M.B.A. students are more accurate only when participants are required to provide separate forecasts for operating cash flows and accruals and the income statement is altered to present the disaggregated cash and accrual components of earnings.
Effect of Direct Renin Inhibition on Renal Hemodynamic Function, Arterial Stiffness, and Endothelial Function in Humans With Uncomplicated Type 1 Diabetes
Authors: Cherney David Z.I. , Lai Vesta , Scholey James W. , Miller Judith A. , Zinman Bernard , Reich Heather N.
Published: November 2009

OBJECTIVE

Blockade of the renin-angiotensin system (RAS) plays an important role in preventing end-organ injury associated with diabetes. The recent development of direct renin inhibitors (DRIs) provides a new approach to block the RAS, but the effects of DRIs on renal and systemic vascular function in uncomplicated type 1 diabetes have not been elucidated.

RESEARCH DESIGN AND METHODS

Renal hemodynamic function (inulin and paraaminohippurate clearance), augmentation index and pulse wave velocity, endothelial dependent vasodilatation (flow-mediated dilation [FMD]), and endothelial independent vasodilatation (response to sublingual nitroglycerin) were evaluated before and after administration of aliskiren (300 mg daily for 30 days) in 10 adult subjects with uncomplicated type 1 diabetes during clamped euglycemia (4–6 mmol/l) and hyperglycemia (9–11 mmol/l).

RESULTS

In response to the DRI, plasma renin activity decreased (from 0.40 to 0.13 ng · ml−1 · h−1, P < 0.05) and plasma renin increased (from 5.2 to 75.0 ng/l, P < 0.05). Peripheral and central blood pressures decreased, and effective renal plasma flow and glomerular filtration rate increased during clamped euglycemia and hyperglycemia (P < 0.05). The carotid augmentation index during clamped euglycemia decreased (from 26 ± 6 to 20 ± 5%, P < 0.05) as did pulse wave velocity during clamped hyperglycemia (from 7.8 ± 0.6 to 6.8 ± 0.5 m/s, P < 0.05). In response to the DRI, FMD increased during both clamped euglycemia (from 1.92 ± 1.13 to 5.55 ± 0.81%) and hyperglycemia (from 1.86 ± 0.98 to 5.63 ± 0.62) as did the vasodilatory response to sublingual nitroglycerin.

CONCLUSIONS

DRIs exert a renal vasodilatory effect and improve parameters of systemic vascular function, suggesting that blockade of the RAS with this new class of agents has important functional effects in subjects with uncomplicated type 1 diabetes.
Methionine in pattern control of Hydra
Authors: Berking Stefan , Hoffmann Uwe , Schäfer Mathias , Herrmann Klaus
Published: November 2009

The fresh water polyp Hydra is noted for its ability to regenerate missing body parts. Transplantation experiments indicate that the control of regeneration includes signalling over long distances. These signals appear to include diffusible morphogens, activators and inhibitors. In order to elucidate the nature of such signals, tissue of polyps was homogenized and fractionated. The fractions were tested for their ability to hinder head regeneration. The active factor within these fractions was determined to be methionine. Both the active fractions and L-methionine were found to antagonize not only head regeneration but also foot regeneration. Budding, the asexual means of reproduction, is antagonized. L-methionine acts in micromolar concentrations while the stereoisomer D-methionine does not. L-methionine may act by providing a methyl group in transmethylation processes.
Spring migration timing of Sylvia warblers in Tatarstan (Russia) 1957–2008
Authors: Askeyev Oleg , Sparks Tim , Askeyev Igor , Tryjanowski Piotr
Published: November 2009

The timing of when migrant birds return to breed is a key component of studies of the impact of climate change upon bird populations. However, such data are not distributed evenly across the World, and in the Northern Hemisphere are underrepresented in Asia and the east of Europe. Therefore, to help rectify this bias, we analysed first arrival dates (FAD) of four species of Sylvia warblers (Blackcap Sylvia atricapilla, Whitethroat S.communis, Lesser Whitethroat S.curruca and Garden Warbler S.borin) collected in the Tatarstan Republic of Russia between 1957 and 2008. Over the whole period the species returned to their breeding sites between three and six days earlier; these trends were significant except for Whitethroat. Advances in arrival were especially apparent in the two earlier species, Blackcap and Lesser Whitethroat, mainly because local temperatures for March had risen substantially. Except for Whitethroat, FADs were significantly related to temperatures in the African wintering ground and/or in Tatarstan. Whilst significant correlations occurred between FADs of some of the species, there was considerable variability in these relationships indicating a species-specific response to rising temperatures. Changes in FADs in this eastern extremity of Europe were smaller than in Central and Western Europe.
Investigation of saturated and aromatic hydrocarbon resistance mechanisms in Pseudomonas aeruginosa IBBML1
Authors: Lăzăroaie Mihaela
Published: November 2009

Pseudomonas aeruginosa IBBML1, isolated from Poeni petroleum sludge, was able to tolerate and degrade both saturated (n-hexane, n-heptane, n-hexadecane, cyclohexane) and aromatic (benzene, ethylbenzene, propylbenzene, xylene isomers, styrene) hydrocarbons. Molecular studies have revealed that the high hydrocarbon resistance of Pseudomonas aeruginosa IBBML1 could be due to the action of members of the HAE1 (hydrophobe/amphiphile efflux 1) family of transporters. It is further possible that additional mechanisms may account for the tolerance of Pseudomonas aeruginosa IBBML1 to hydrocarbons, and a combination of short-term and long-term mechanisms may act together in the adaptation of Pseudomonas aeruginosa IBBML1 cells to saturated and aromatic hydrocarbons. β-galactosidase activity measurements revealed that there was significant induction of the lacZ gene in Pseudomonas aeruginosa IBBML1 cells grown in the presence of either 5% and 10% (v/v) saturated or aromatic hydrocarbons, compared with control (cells incubated without hydrocarbons). Rhodamine 6G accumulation in Pseudomonas aeruginosa IBBML1 cells grown in the presence of 5% and 10% (v/v) saturated hydrocarbons was higher than rhodamine 6G accumulation in cells grown in the presence of 5% and 10% (v/v) aromatic hydrocarbons. The study of cellular and molecular modifications to Pseudomonas aeruginosa IBBML1 induced by 5% and 10% (v/v) saturated and aromatic hydrocarbons revealed a complex response of bacterial cells to the presence of different hydrophobic substrates in the culture medium.
GFP markers for studying D. melanogaster spermatogenesis
Authors: Nerusheva Olga , Dorogova Natalia , Omelyanchuk Leonid
Published: November 2009

Localization of a set of chimeric GFP proteins in D. melanogaster spermatogenesis has been studied. In the collection used, the proteins with detectable germ-line expression frequently occur to be involved in mRNA maturation. According to the cellular localization, proteins fall into three groups, namely, the protein Rtc1, involved in splicing, displays an exclusively nuclear localization; the proteins Squid (splicing and mRNA transport), Pabp2 (polyadenylation), and Hrb98DE (splicing and mRNA transport) change their localization during germ-line development; and the protein Imp (mRNA localization) is located exclusively in the cytoplasm. The distribution of Rtc1, Squid and Hrb98DE in the spermatocyte nuclei is morphologically similar to the distribution of splicing bodies, the so-called splicing factor compartments. The proteins Imp and Hrb98DE at the stage of elongation are localized to a specialized structure in the caudal region of cyst; this region corresponds to the site of the highest synthetic activity in the cyst cells at this developmental stage.
MART-1 transcript is absent in PBMCs from Vitiligo patients
Authors: Bam Marpe , Bagchi Tamishraha
Published: November 2009

Mechanisms occurring in the thymus and periphery are responsible for the generation and maintenance of tolerance in the immune system. Various reports have shown that the existence of an antigen in the peripheral circulation results in tolerance induction towards that protein. These observations imply that the lack of a self antigen can lead to induction of autoimmunity. Previously we have reported that Tyrosinase related protein-2 (TRP-2) transcripts from peripheral blood mononuclear cells (PBMCs) are absent in vitiligo patients but present in healthy individuals. Here, we show that MART1 (Melanoma antigen recognized by T cells) transcripts are not detected in the PBMCs of vitiligo patients but is detected in healthy controls. Our result suggests that as MART1 is not expressed in the PBMCs, MART1 is also not available for induction and maintenance of peripheral tolerance in vitiligo patients. We therefore conclude that nonexpression of MART1 in PBMCs of vitiligo patients may be somehow responsible for the tolerance breakdown finally resulting in the induction of autoimmunity seen against these self antigens in vitiligo.
Voice-supported Electronic Health Record for Temporomandibular Joint Disorders
Authors: Dostalova T. , Zvarova J. , Nagy M. , Seydlova M. , Hanzlicek P. , Kriz P. , Smidl L. , Trmal J. , Hippmann R.
Published: November 2009

Objectives: To identify support of structured data entry for an electronic health record application in temporomandibular joint disorders.

Methods: The methods of structuring information in dentistry are described and the interactive DentCross component is introduced. A system of structured voice-supported data entry in electronic health record on several real cases in the field of dentistry is performed. The connection of this component to the MUDRLite electronic health record is described.

Results: The use of DentVoice, an application which consists of the electronic health record MUDRLite and the voice-controlled interactive component DentCross, to collect dental information required by temporomandibular joint disorders is shown.

Conclusions: The DentVoice application with the DentCross component showed the practical ability of the temporomandibular joint disorder treatment support.
Mosaicism
Authors: Robinson Wendy P.
Published: November 2009

Chromosome mosaicism is observed in all types of human tissues, and can be a difficult finding to interpret in the genetics clinic. Prenatally diagnosed mosaicism is particularly challenging as the range of possible outcomes extends from normal to fetal malformation and/or in utero death, while there is little the clinician can do to assess the effects on in utero fetal development. As very low levels of abnormal cells may be “normal,” the interpretation of a mosaic finding needs to be carefully considered in terms of the patient phenotype, the type and origin of the abnormality, and the extent of abnormal cells. Microchimerism, which can for example occur through exchange of cells between mother and fetus, can also lead to genetically distinct cell types within an individual, and is gaining a reputation for being involved in a wide range of autoimmune conditions. Much further work is needed to understand the long‐term effects of low‐level mosaicism and microchimerism in humans.
Beckwith–Wiedemann syndrome
Authors: Tycko Benjamin , Mannens Marcel
Published: November 2009

Beckwith–Wiedemann syndrome (BWS) is a well‐studied human overgrowth disorder, associated with visceromegaly, exomphalos, and predisposition to Wilms tumor and other pediatric cancers.BWSis a clinical syndrome, not a single disorder. Phenotypic heterogeneity is prominent, and we now appreciate that this reflects an underlying molecular heterogeneity. The syndrome can be caused by various molecular defects, which lead to altered expression of certain imprinted genes on chromosome 11p15. Multiple studies have revealed striking epigenotype–phenotype correlations, in which exomphalos tracks with one type of imprinting defect, affecting theCDKN1Cgene, while Wilms tumor predisposition tracks with a different imprinting defect, affecting theIGF2andH19genes. Here we review the clinical and molecular features ofBWSand summarize the data from these recent investigations. We also review the fascinating association ofBWSwith twinning, and discuss preliminary studies suggesting an increased frequency ofBWSin children conceived by in vitro fertilization. Lastly, we provide an update on the more general role of imprinted genes as growth rheostats in mammalian development.
Imprinting in
P
rader–
W
illi and
A
ngelman syndromes
Authors: Horsthemke Bernhard , Buiting Karin
Published: November 2009

The Prader–Willi syndrome (PWS) and Angelman syndrome (AS) are two distinct neurogenetic diseases that are caused by the loss of function of imprinted genes on the proximal long arm of human chromosome 15. The identification of small deletions in a subgroup of patients in whom the loss of gene function is due to an incorrect imprint on the paternal or the maternal chromosome 15, respectively, has lead to the definition of a bipartite imprinting center that regulates in cis imprint resetting and imprint maintenance in the whole domain. These findings have been confirmed and extended in knockout and transgenic mice. In the majority of patients with an imprinting defect, the incorrect imprint has arisen without a DNA sequence change, probably as the result of stochastic errors of the imprinting process. It is possible that the error rate is affected by genetic and exogenous factors.
Imprinting and behavior
Authors: Curley James P. , Keverne Eric B.
Published: November 2009

There is accumulating evidence for the role of imprinted genes in the regulation of mammalian behavior. Many imprinted genes are expressed in the brain and are important for its development. In particular, it appears that paternally and maternally expressed genes are critical for the normal development of the hypothalamus/limbic system and cortex/striatum respectively. Furthermore, several imprinted genes have been identified as candidate genes for human behavioral disorders. More recent research has focused on the behavioral phenotypic effects in mice carrying targeted mutations of specific imprinted genes. Two of these, the paternally expressed
Mest/Peg1
and
Peg3
genes, have been shown to regulate maternal care.
Epigenetic reprogramming in germ cells and preimplantation embryos
Authors: Kierszenbaum Abraham L.
Published: November 2009

DNA methylation and histone modifications are major epigenetic modifications with a major impact on gametogenesis and early embryo development. A key objective during these events is to erase and reprogram the methylation patterns to enable the developmental potential of the gametes and embryogenesis. A disruption of epigenetic reprogramming can lead to the dysregulation of developmental processes and to various diseases. Understanding the chronology and mechanism of epigenetic reprogramming during gametogenesis and in early development can lead to advances in therapeutic cloning and clinical intervention through assisted reproductive technology.
Epigenetic inheritance and
RNAi
at the centromere and heterochromatin
Authors: Caruana Scott Kristin S. , Sullivan Beth A.
Published: November 2009

RNA interference (RNAi) is a conserved gene silencing mechanism by which double‐stranded RNA (dsRNA) are processed into short interfering RNAs (siRNAs) that regulate gene expression and posttranscriptional modifications of histones. In fission yeast and vertebrates, RNAi is important for heterochromatin formation and silencing at centromeric regions. In this article, we discuss the landmark studies describing RNAi‐induced silencing at centromeres, and the multiprotein complexes that process centromeric repeats and recruit proteins that remodel and maintain centromeric heterochromatin. Finally, we briefly mention the genomic location of centromeres and the functional relevance for regulating essential chromosomal processes such as kinetochore assembly.
Techniques in genomic imprinting research
Authors: Gray Todd A.
Published: November 2009

Contemporary assays to evaluate candidate‐imprinted genes are varied, but they generally fall into two categories: those that assess monoallelic expression and those that assess DNA methylation. Parental origin‐dependent expression is the most definitive test for imprinted gene determination. Alternatively, cytosine DNA methylation is a measurable epigenetic feature that correlates with gene transcription and thus commonly serves as a DNA‐based indicator of monoallelic expression. Outlined below are approaches that examine both differential expression by RT‐PCR of transcribed polymorphisms, and differential cytosine methylation by amplification of bisulfite‐converted genomic DNA.
Information content in gene mapping
Authors: Nicolae Dan L.
Published: November 2009

Most of the gene mapping studies have missing or incomplete information, for example, uncertain identical‐by‐descent sharing in linkage projects or unknown phase in haplotype‐based association studies. Measures of the information content can help in designing experiments, selecting follow‐up strategies, and in understanding the loss of power due to incomplete information.
Approach to rare monogenic and chromosomal disorders
Authors: Williams Marc S.
Published: November 2009

While the scope of medical genetics has changed dramatically in the last 40 years, geneticists are still frequently called upon to evaluate patients with suspected monogenic or chromosomal disorders. This chapter will introduce the reader to the techniques used in the genetics clinic to arrive at a diagnosis. The importance of making a specific diagnosis will also be discussed.
Immunity and tolerance induction in gene therapy
Authors: Davoust Jean , Bertho Nicolas , Masurier Carole , Gross David
Published: November 2009

Gene and cell therapies are promising for long‐term reconstitution of diseased tissues, and for restoration of therapeutic levels of circulating proteins, correcting inherited genetic disorders. Among the fundamental biological questions raised, the immune response to gene therapy is of great importance as it can hinder the success of gene correction. The onset of an immune response depends on the mutational genotype in each patient; the strength of antitransgene responses may also vary depending on gene delivery methods, based on plasmids, viral vectors or cell vectors, and on the route of injection. As a result, in most gene therapy protocols, the immune system will detect the packaging viral proteins and the transgene itself, causing humoral and cellular responses, which may lead to complete eradication of the corrected cells whenever the transgene protein behaves as a truly foreign antigen, that is, its sequence is partially or completely absent from the host. In this review, we will consider three main goals of immunology research in the field of gene therapy, namely, (1) deciphering dendritic cell/viral vector interactions, (2) inducing antigen‐specific tolerance for long‐term reconstitution of diseased tissues, and (3) monitoring immune responses to gene transfer in humanized animal models carrying HLA transgenes.
Adenovirus vectors
Authors: Lusky Monika
Published: November 2009

Recombinant Adenovirus (Ad) vectors provide a highly versatile system of mammalian gene transfer and are widely used in basic research, in vaccine development, and for a variety of gene therapy applications, particularly for cancer gene therapy. These applications are facilitated by several important advantages of Ad over other vectors, including convenient and simple methods of vector construction, the efficient infection of quiescent cells, and their capacity to incorporate large segments of heterologous DNA. The number of gene therapy trials employing Ad vectors is expanding very rapidly. In parallel, developing Ad vectors for gene therapy has tremendously advanced our knowledge in Ad biology on viral tropism, duration of gene expression, toxicity, and immunogenicity. These advances have suggested a differential application of the different types of replication‐deficient and replication‐competent Ad vectors in gene medicine.
Microelectrophoresis devices for
DNA
sequencing
Authors: Ehrlich Daniel J. , Aborn James H. , El‐Difrawy Sameh A. , Gismondi Elizabeth A. , Lam Roger , McKenna Brian , O'Neil Thomas
Published: November 2009

Microfabricated instruments for DNA electrophoresis are poised to provide significant sequencing capability in the near term. The state of the art and key remaining issues for this technology are reviewed.
Mapping complex disease phenotypes
Authors: Collier David A.
Published: November 2009

Identifying genetic risk alleles for complex diseases has proved much more difficult than the identification of genetic risk alleles for single‐gene disorders. The mapping of complex phenotypes has required the development of new approaches to linkage analysis, the use of nonhuman models of disease, and new approaches to the fine mapping of disease genes, including genome‐wide association analysis. In this review, recent developments in these approaches are discussed in detail.
Haplotype mapping
Authors: Montpetit Alexandre , Chagnon Fanny , Hudson Thomas J.
Published: November 2009

Common human diseases such as asthma, diabetes, schizophrenia, and cancer are a major burden to industrialized nations in terms of clinical, social, and economic impacts. Understanding the contribution of genetic variants to the etiology of common diseases may bring improvements in preventive strategies, diagnostic tools, and therapies. To date, more than 1200 genes involved in the progression of simple rare Mendelian diseases have been identified. However, for common diseases, factors such as genetic heterogeneity, incomplete penetrance, gene‐gene, and gene‐environment interactions have hindered family based positional cloning strategies used for disease gene identification. Consequently, the detection of genetic variants leading to common diseases is still a major challenge for the biomedical community in 2004, despite the knowledge of the complete sequence of the human genome. Refinements to the existing gene‐mapping methods are thus necessary to overcome the existing hurdles. In this review, we will discuss the advantages and limitations of haplotype mapping in the search for common disease‐causing genes.
Transcriptional promoters
Authors: Wasserman Wyeth W.
Published: November 2009

Transcription serves as a primary mechanism for regulating the activity of most genes in the human genome. Multiple regulatory mechanisms act together to influence the rate of initiation of transcription from specific regions in genes termed promoters. Genes may contain multiple promoters, and promoters may contain multiple sites of transcript initiation. A brief biochemical background is presented, followed by an overview of the properties of promoters that facilitate laboratory detection and bioinformatics prediction.
Systematic mutagenesis of nonmammalian model species
Authors: van den Heuvel Marcel , Sattelle David
Published: November 2009

The recent accumulation of whole‐genome sequence information has led to the notion that the degree of evolutionary conservation between diverse organisms is very high. The number of genes going from a fly to human is only about twofold, and many of these “new” genes are duplicates of genes already existing, not novel genes. This in fact means that organisms that have been thoroughly studied using genetics offer a direct entrance into the function of highly conserved genes. Two of such organisms stand out because of the sophistication and thoroughness of the studies, the worm,Caenorhabditis elegans, and the fly,Drosophila melanogaster. This review attempts to give these two organisms a place in the current drive in gene function analysis.
TheMycoplasmas – a congruent path toward minimal life functions
Authors: Papazisi Leka , Peterson Scott N.
Published: November 2009

TheMycoplasmasare a group of pathogenic bacteria with highly reduced genomes.The genomic era has allowed comparison ofMycoplasmagenomes to one another and to less‐related genomes. Genomic analysis of this bacterial group reveals several interesting aspects of minimal genome characteristics that have allowed us to devise a specific model to account for aspects of reductive evolution in theMycoplasmas.
Reliability and utility of single nucleotide polymorphisms for genetic association studies
Authors: Pearce C. Leigh , Hirschhorn Joel N.
Published: November 2009

Single‐nucleotide polymorphisms (SNPs) are the most common type of genetic variation in the human genome. Significant efforts have been made to attempt to understand their association to common diseases and complex traits. Genetic association studies, however, have been plagued by inconsistent results. The reliability of SNP‐based association studies is reviewed in the light of their limited success. The validity, comprehensiveness, and usefulness of the public SNP database (dbSNP) is evaluated, followed by a detailed discussion of why these studies have proven so difficult to replicate. Potential approaches to minimize the inconsistency across studies are considered. We show that while the coverage of the public SNP database is adequate to conduct comprehensive and meaningful association studies, methodological concerns must be taken into account.
ManufacturingESTlibraries
Authors: Soares Marcelo B. , Bonaldo Maria F.
Published: November 2009

Here we address problems that occur systematically during the manufacturing of EST libraries, and that have an impact on the analysis and interpretation of EST data. We discuss their cause, consequences, and diagnostic features.
Using oligonucleotide arrays
Authors: Mitchell Lindsay W. , Hoffman Eric P.
Published: November 2009

Nucleic acid sequence microarrays have become one of the first highly parallel, genome‐wide technologies to mature into a tool used routinely by biologists in many fields of research. The principle, covered in more detail elsewhere in this volume, is to hybridize a complex solution of labeled mRNA transcripts from cells or tissues onto a solid support containing thousands or millions of segments of unique DNA. The extent of hybridization of each mRNA sequence in the solution to the target “feature” is proportional to the concentration of that specific mRNA in the solution. This “extent of hybridization” to each feature is quantified (signal) by detection tools, which then calculate the relative concentration of the mRNA in the original solution. Affymetrix arrays are factory manufactured microarrays of 25‐mer oligonucleotides. Construction of the arrays is accomplished by in situ photochemistry, allowing about 1 million distinct features to be synthesized on 1.2 cM
2
quartz supports. The bioinformatics‐driven design and production of Affymetrix arrays has made them increasingly popular in both academic and pharmaceutical arenas, and has allowed the development of quality control and standard operating procedures (QC/SOP). This specialist review discusses the design and production of Affymetrix arrays, preparation of target tissue and hybridization, methods of quantifying resulting hybridization data (probe set algorithms), experimental design considerations, and emerging public access databases.
Integrating genotypic, molecular profiling, and clinical data to elucidate common human diseases
Authors: Schadt Eric E. , Sachs Alan
Published: November 2009

The identification of genes and, more generally, gene networks underlying common human diseases remain one of the primary objectives in the biomedical and life sciences. Success in reconstructing gene networks underlying complex physiological traits and identifying the key drivers of these traits will largely rest on integrative approaches that combine data from multiple different sources. Key to this integration will be the development and application of sophisticated algorithms to mine the diversity of data. Here we review an integrative genomics approach that enhances the utility of genetics approaches commonly used to dissect complex traits. This integrative genomics approach takes into account genotypic, molecular profiling, and clinical data in segregating populations to identify the key drivers of disease and reconstruct disease‐specific gene networks.
The use of external controls in microarray experiments
Authors: van Helvoort Joop M.L.M. , van Leenen Dik , Holstege Frank C.P.
Published: November 2009

Accuracy in reporting expression levels or differences therein is an important issue for microarray technology. Here we discuss the reasons for using external RNA controls for the optimization of nearly every aspect of microarray technology. The main conclusion is that external RNA controls offer an extremely versatile system that does not suffer from the disadvantages of other approaches and also lend themselves for assessing accuracy within every subsequent microarray experiment after optimization. We describe what external controls are, how they can contribute toward systematic analysis of accuracy, and how such controls should be implemented. Other uses of external controls such as normalization, determining sensitivity, and reporting absolute mRNA copies per cell are also discussed.
Quadrupole mass analyzers: theoretical and practical considerations
Authors: Kero Frank A. , Pedder Randall E. , Yost Richard A.
Published: November 2009

Mass spectrometry is perhaps the key core methodology for proteomics, and the quadrupole mass analyzer is currently the most widely used mass analyzer in proteomic applications of mass spectrometry. The theory of quadrupole mass analyzers (and of the related quadrupole and multipole devices used to confine and transmit beams of ions into and between mass analyzers) can lend valuable insight into practical considerations for effective use of mass spectrometry.
Basic techniques for the use of reverse phase protein microarrays for signal pathway profiling
Authors: Espina Virginia , Calvert Valerie S. , Wulfkuhle Julia , Liotta Lance A. , Petricoin Emanuel F.
Published: November 2009

Ultimately, disease‐related genetic defects are manifested on a protein level, involving derangements in protein function and the information flow within diseased cells and the surrounding tissue microenvironment. New classes of protein microarrays have been recently developed using highly sensitive, specific technology, and can be used to generate a “wiring diagram” of information flow mediated through posttranslational modification driven networks. Through the combined use of laser capture microdissection of pure populations of tumor cells obtained from patient biopsies, these arrays can provide the foundation for the development of individualized combinatorial therapies of molecular inhibitors to target tumor‐specific deranged pathways regulating key biologic processes including proliferation, differentiation, apoptosis, immunity, and metastasis. In the future, therapies can be tailored to the specific deranged molecular circuitry of an individual patient's disease. The successful transition of these technologies from research tools to integrated clinical diagnostic platforms will require ongoing continued development, development of reference standards, and optimization with rigorous standardization development and quality‐control procedures.