bluuebunny/crossref_metadata_2025 huggingface dataset:
Movement patterns of endangered Roanoke logperch (Percina rex)
Authors: Roberts J. H. , Rosenberger A. E. , Albanese B. W. , Angermeier P. L.
Published: January 2008

Abstract –  Using mark–recapture methods, we studied movements of endangered Roanoke logperch (Percina rex Jordan & Evermann), a benthic darter, at 12 riffle–run sites over a 9‐year‐long period in the Roanoke River, Virginia, USA. Our primary objective was to characterise movements among transects within sites, but we opportunistically recorded two between‐site movements as well. Our recapture rate was low (22 of 485 marked fish), but most recaptured fish exhibited movements between tagging and recapture, relocating either to another transect within a site (12 fish) or to another site altogether (two fish). Within sites, Roanoke logperch exhibited fidelity over time to the areas in which they were initially marked. These restricted areas were lengthier than transects (>15 m) but shorter than entire riffle–runs (<150 m). The two between‐site movements were extensive (3.2 and 2.5 km), observed over a long mark–recapture interval (2 and 5 years, respectively), and may have represented migratory or dispersal movements. Their detection required an unusually extensive study design. Both small‐ and large‐scale movements fulfil important ecological functions for Roanoke logperch, and greater study of such movements in this and other darter species is needed to inform conservation choices.
Maturational tempo differences in relation to the timing of the onset of puberty in girls
Authors: Pantsiotou S , Papadimitriou A , Douros K , Priftis K , Nicolaidou P , Fretzayas A
Published: January 2008

Aim: To determine maturational tempo differences related to the timing of pubertal onset in girls.

Methods: We studied longitudinally 307 prepubertal Greek schoolgirls. Age at onset of puberty (B2), peak height velocity (PHV) and age at menarche were recorded. Age at onset of puberty quartiles were determined in order to define girls as early maturers (<9.2 years) and late maturers (>10.6 years). Due to dropout from the study, results for menarche are reported for 182 girls.

Results: Median (1st–3rd quartile) time span from B2 to PHV was longer for early maturers than for average and late maturers, 1.6 (1.0–2.2) years, 1.1 (0.7–1.7) years and 0.9 (0.3–1.1) years, respectively, p < 0.001). There was no significant difference in PHV, in the time interval from PHV to menarche and in adult height (for 75 girls) with respect to whether girls matured early, average or late.

Conclusion: A compensatory delay in the maturational tempo in early‐maturing girls and a catch‐up mechanism in late‐maturing girls was shown. The maturational differences manifest as differences in the time span from the onset of puberty to PHV. Early pubertal maturation in girls does not compromise adult height and is not always followed by early menarche.
Adverse reactions to milk in infants
Authors: Kvenshagen Bente , Halvorsen Ragnhild , Jacobsen Morten
Published: January 2008

Aim: To study the age when symptoms of adverse reactions to milk occur, in premature and term children, the debut of various symptoms, immunoglobulin E (IgE)‐ and non‐IgE‐mediated reactions and the frequency of tolerance at 1 year.

Methods: Six hundred and eight children, 193 premature and 416 term infants, were followed. Symptomatic children were invited to a clinical examination. The criteria for the diagnosis were: histories of suspected cow's milk allergy (CMA) and proven IgE‐mediated reactions to cow's milk or positive elimination/challenge tests.

Results: Twenty‐seven out of 555 (4.9%) were diagnosed with adverse reactions to cow's milk. All had symptoms before 6 months of age. The main symptoms were: pain behaviour (13), gastrointestinal symptoms (7), respiratory symptoms, (6) and atopic dermatitis (1). One child had proven IgE to cow's milk. Premature and term infants displayed the same symptoms and age of debut. Thirteen children were tolerant to cow's milk at 1 year.

Conclusion: Adverse reactions to milk start early in life, with pain behaviour, gastrointestinal, and respiratory symptoms being the most common, and rarely atopic dermatitis. Non‐IgE‐mediated reactions were the most frequent. Symptoms and age of debut were the same in premature and term infants. Half of the children tolerated cow's milk at age 1.
Follow‐up after paediatric intensive care treatment: parental posttraumatic stress
Authors: Bronner Madelon B , Knoester Hennie , Bos Albert P , Last Bob F , Grootenhuis Martha A
Published: January 2008

Aim: To study the prevalence of posttraumatic stress in parents after an acute admission to a paediatric intensive care unit (PICU) and to determine risk factors for the development of posttraumatic stress.

Methods: Parents completed posttraumatic stress questionnaires three months after their child's discharge. This questionnaire measures both symptoms of posttraumatic stress disorder (PTSD) and enables determination of the full psychiatric diagnosis of PTSD. Medical and demographic data concerning their child were gathered from physical evaluations three months after discharge. Of 250 eligible families, 144 (57.6%) participated in this study. The questionnaires were completed by 140 mothers and 107 fathers.

Results: More than three‐quarters of the parents experienced persistent symptoms of PTSD. In 21 mothers (15.0%) and 10 fathers (9.3%), the full psychiatric diagnosis of PTSD was determined. In six families, both parents had PTSD. Furthermore, a significant positive correlation was found between symptoms of PTSD of the mothers and the fathers. No obvious medical risk factors could be distinguished.

Conclusion: The unexpected admission of a child to a PICU is a stressful event associated with parental posttraumatic stress. Treatment should not end after discharge. Follow‐up care is warranted and research should be focused on prevention of these symptoms.
Noradrenaline for management of septic shock refractory to fluid loading and dopamine or dobutamine in full‐term newborn infants
Authors: Tourneux Pierre , Rakza Thameur , Abazine Abdel , Krim Gérard , Storme Laurent
Published: January 2008

Aim: To determine the effects of noradrenaline in full‐term newborns with refractory septic shock.

Methods: Newborns of >35 weeks' gestation with persistent septic shock, despite adequate fluid resuscitation and high dose of dopamine/dobutamine were eligible. In this prospective observational study, we recorded respiratory and hemodynamic parameters prior to and 3 h after starting noradrenaline infusion.

Results: Twenty‐two newborns were included (gestational age [GA] 39 ± 1.7 weeks, birth weight (BW) 3110 ± 780 g). Before starting noradrenaline, the infants received a mean volume expansion of 31 ± 15 mL/kg and a mean infusion rate of dopamine of 14 ± 5 μg/kg/min or dobutamine of 12 ± 6 μg/kg/min. Three hours after starting noradrenaline (rate 0.5 ± 0.4 μg/kg/min), the mean arterial blood pressure rose from 36 ± 5 to 51 ± 7 mmHg (p < 0.001). Urine output increased from 1 ± 0.5 to 1.7 ± 0.4 mL/kg/h (p < 0.05). Blood lactate concentration decreased from 4.8 ± 2.3 to 3.3 ± 1.8 mmol/L (p < 0.01). Despite an initial correction of hypotension, four infants died later.

Conclusion: Noradrenaline was effective in increasing systemic blood pressure. An increase in urine output and a decrease in blood lactate concentration suggest that noradrenaline may have improved cardiac function and tissue perfusion.
Persistent neonatal mortality despite improved under‐five survival: a retrospective cohort study in northern Vietnam
Authors: Hoa Dinh P , Nga Nguyen T , Målqvist Mats , Persson Lars Åke
Published: January 2008

Aim: To examine trends in neonatal, infant and under‐five mortality rates in a northern Vietnamese district during 1970–2000, and to analyze socioeconomic differences in child survival over time.

Methods: Retrospective interviews with all women aged 15–54 years in Bavi district in Northern Vietnam (n = 14 329) were conducted. Of these women, 13 943 had been pregnant, giving birth to 26 796 children during 1970–2000.

Results: There was a dramatic reduction in infant and under‐five mortality rate (47%) over time. However, the neonatal mortality rate (NMR) showed a very small reduction, thus causing its proportion of the total child mortality to increase. Mortality trends followed the political and socioeconomic development of Vietnam over war, peace and periods of reforms. There were no differences in under‐five and neonatal mortalities associated with family economy, while differentials related to mothers' education and ethnicity were increasing.

Conclusion: Interventions to reduce child mortality should be focused on improving neonatal care. In settings with a rapid economic growth and consequent social change, like in Vietnam, it is important that such interventions are targeted at vulnerable groups, in this case, families with low level of education and belonging to ethnic minorities.
Neurobehavioural assessment of skin‐to‐skin effects on reaction to pain in preterm infants: a randomized, controlled within‐subject trial
Authors: Ferber Sari Goldstein , Makhoul Imad R
Published: January 2008

Objective: To assess the immediate and sustained effects of Kangaroo Care on reaction to pain of premature infants.

Patients and methods: A controlled, within‐subject randomized study, performed in a large neonatal intensive care unit. Thirty premature infants were observed with blood test stick (BT) or without the blood test stick (W) procedure, either during Kangaroo care (K) or during standard within‐crib care (C). Each of the four conditions (BTK, WK, BTC, WC) was observed in four separate sessions: baseline session – 10 min; intervention (BT or W) – 2 min; posttest – 10 min and follow‐up – 20 min, in crib (starting 1 h after treatment). For neurobehavioural assessment, the naturalistic observation method was adopted from the Newborn Individualized Developmental Care and Assessment Program (NIDCAP).

Results: During the BTK session (blood test stick with K‐care), we observed a decrease in motor disorganization and extension movements and an increase in attention signs, both negative and positive. Significant neurobehavioural changes were sustained in the follow‐up period after K‐care in comparison to the within‐crib‐care intervention sessions.

Conclusions: K‐care, as compared to within‐crib condition, led to a decrease in stressful neurobehavioural signs after BT procedures in premature infants. Painful procedures such as the BT procedure in premature infants should be performed while the infants are being held in K‐care position.
Analysis of an Unconfined Aquifer Subject to Asynchronous Dual‐Tide Propagation
Authors: Rotzoll Kolja , El‐Kadi Aly I. , Gingerich Stephen B.
Published: January 2008

Most published solutions for aquifer responses to ocean tides focus on the one‐sided attenuation of the signal as it propagates inland. However, island aquifers experience periodic forcing from the entire coast, which can lead to integrated effects of different tidal signals, especially on narrow high‐permeability islands. In general, studies disregard a potential time lag as the tidal wave sweeps around the island. We present a one‐dimensional analytical solution to the ground water flow equation subject to asynchronous and asymmetric oscillating head conditions on opposite boundaries and test it on data from an unconfined volcanic aquifer in Maui. The solution considers sediment‐damping effects at the coastline. The response of Maui Aquifers indicate that water table elevations near the center of the aquifer are influenced by a combination of tides from opposite coasts. A better match between the observed ground water head and the theoretical response can be obtained with the proposed dual‐tide solution than with single‐sided solutions. Hydraulic diffusivity was estimated to be 2.3 × 107 m2/d. This translates into a hydraulic conductivity of 500 m/d, assuming a specific yield of 0.04 and an aquifer thickness of 1.8 km. A numerical experiment confirmed the hydraulic diffusivity value and showed that the y‐intercepts of the modal attenuation and phase differences estimated by regression can approximate damping factors caused by low‐permeability units at the boundary.
Conformational Movement of F251 Contributes to the Molecular Mechanism of Constitutive Activation in the C5a Receptor
Authors: Sen Saurabh , Baranski Thomas J. , Nikiforovich Gregory V.
Published: January 2008

The activation mechanism of G‐protein‐coupled receptors triggered upon binding of a ligand represents a very important ‘conformational switch’ in the biological array of signal transduction. However, the molecular and functional details for this activation switch remain unknown. Random saturation mutagenesis data on the complement factor 5a receptor has provided a large data set of mutants including several constitutively active mutants. In the present study, we employed computational modeling to rationalize the constitutive activity for two constitutively active mutants, NQ (I124N/L127Q) and F251A, and we then made predictions for a series of mutants that either promote or constrain constitutive activity. Biological testing of the site‐directed mutants confirmed most of the predictions of the computational modeling. These results support a molecular mechanism of constitutive activity in complement factor 5a receptor mutants that is associated with conformational changes in a network of residues neighboring F251 as the focal point of origin.
Comparison of the prevalence of enteric viruses in healthy dogs and those with acute haemorrhagic diarrhoea by electron microscopy
Authors: Schulz B. S. , Strauch C. , Mueller R. S. , Eichhorn W. , Hartmann K.
Published: January 2008

Objectives:  To evaluate prevalence of enteric viruses in healthy dogs and to compare it with prevalences in dogs with acute haemorrhagic diarrhoea.

Methods:  Faecal samples were collected from 200 healthy dogs and examined by electron microscopy for presence of viral particles. Data were compared with viral prevalences that had been determined retrospectively by electron microscopy for 936 dogs with acute haemorrhagic diarrhoea.

Results:  There were significantly more negative faecal samples among the healthy dogs (82·0 per cent) compared with 55·8 per cent in dogs with acute haemorrhagic diarrhoea (P<0·001). With a prevalence of 17·5 per cent, significantly more healthy dogs were shedding coronavirus compared with 11·6 per cent in dogs with acute haemorrhagic diarrhoea (P=0·034). Parvovirus was only detected in one healthy dog (0·5 per cent), thus with a prevalence that was significantly lower than 16·0 per cent detected in the dogs with acute haemorrhagic diarrhoea (P<0·001). Paramyxovirus was not found in any of the healthy dogs but was found in 9·3 per cent of dogs with acute haemorrhagic diarrhoea (P<0·001).

Clinical Significance:  Results suggest that shedding of parvovirus and paramyxovirus is strongly associated with acute haemorrhagic diarrhoea. However, coronavirus seems to be even more prevalent among healthy dogs, raising the need for further studies to investigate the strain‐associated pathogenicity of this virus.
DNA reassociation kinetics and diversity indices: richness is not rich enough
Authors: Haegeman Bart , Vanpeteghem Dimitri , Godon Jean‐Jacques , Hamelin Jérôme
Published: January 2008

DNA reassociation kinetics, also known as Cot curves, were recently used by Gans and co‐workers to estimate the number of bacterial species present in soil samples. By reanalysing the mathematical model we show that rather than the number of species, Simpson and Shannon diversity indices are encoded in the experimental data. Our main tool to establish this result are the so‐called Rényi diversities, closely related to Hill numbers, illustrating the power of these concepts in interpreting ecological data. We argue that the huge diversity encountered in microbial ecology can be quantified more informatively by diversity indices than by number of species.
Stronger compensatory growth in a permanent‐pond Lestes damselfly relative to temporary‐pond Lestes
Authors: De Block Marjan , McPeek Mark A. , Stoks Robby
Published: January 2008

Compensatory growth where animals compensate for time stress or transient nutritional or thermal stress by accelerating their growth rate is widespread. We know, however, relatively little about the evolution and ecological correlates of compensatory growth. For this we need studies on congeneric species with known phylogenetic relationships that also focus on the associated largely understudied costs. Here we tested for compensatory growth and associated costs in response to time stress (manipulated by photoperiod) and a transient period of starvation or cooling in larvae of the permanent‐pond damselfly Lestes eurinus, and compare the results with former studies on temporary‐pond Lestes. Larvae showed full compensation in body mass at emergence for all combinations of time stress and starvation or cooling. Unexpectedly, compensatory growth to starvation or cooling was not stronger under time stress. Instead, males under time stress delayed emergence after these transient stressors. In line with a stronger compensatory growth response to time stress than to the other stressors, physiological costs in terms of a reduced investment in immune response (measured as phenoloxidase activity) and energy storage (measured as fat content) were detected only under time stress. Compared to temporary‐pond Lestes, L. eurinus showed stronger compensatory growth to time stress. We hypothesize that the stronger compensatory (growth) response in permanent‐pond Lestes co‐evolved with their derived slower lifestyle when they invaded permanent ponds.
Clinical photography and patient rights: the need for orthopraxy
Authors: Berle I
Published: January 2008

The increasing use of digital image recording devices, whether they are digital cameras or mobile phone cameras, has democratised clinical photography in the UK. However, when non-professional clinical photographers take photographs of patients the issues of consent and confidentiality are either ignored or given scant attention.

Whatever the status of the clinician, the taking of clinical photographs must be practised within the context of a professional etiquette. Best practice recognises the need for informed consent and the constraints associated with confidentiality. Against the background of the poverty of the current discourse of these issues, as presented during the Valentine GMC Fitness to Practice1 hearing, the paper considers the need for orthopraxy in the use of clinical photography.
Ulysses arrangements in psychiatry: a matter of good care?
Authors: Gremmen I , Widdershoven G , Beekman A , Zuijderhoudt R , Sevenhuijsen S
Published: January 2008

This article concerns the issue of how an ethic of care perspective may contribute to both normative theory and mental health care policy discussions on so called Ulysses arrangements, a special type of advance directives in psychiatry. The debate on Ulysses arrangements has predominantly been waged in terms of autonomy conceived of as the right to non-intervention. On the basis of our empirical investigations into the experiences of persons directly involved with Ulysses arrangements, we argue that a care ethics perspective may broaden and deepen the debate on Ulysses arrangements, by introducing additional concepts, such as vulnerability, responsibility and mutuality, and by refining familiar concepts, such as autonomy.
Medical education and patients’ responsibilities: back to the future?
Authors: Draper H , Ives J , Parle J , Ross N
Published: January 2008

Medical student learning is dependent on an unwritten agreement between patients and the medical profession, in which students “practise” upon real patients in order that, when they are doctors, those same patients will benefit from the doctors’ skills. Given the increasing propensity for patients to refuse to take part in such learning, there is a danger that doctors will qualify without being truly competent. As patients, we must all ask ourselves, when asked to take part in medical teaching: if this student/trainee doesn’t learn now, on me and under supervision, how will the person be truly competent next time, when this is for real, and the patient might be me or my loved one?

We argue that a new and more explicit agreement is needed, in which the default should be thatallpatients are willing to help in the education of medical students, while we ensure that all such students are already competent in simulation before first practising upon real patients.
The effects of hypoxia on fishes: from ecological relevance to physiological effects
Authors: Pollock M.S. , Clarke L.M.J. , Dubé M.G.
Published: January 2008

Hypoxia is an ever increasing threat to aquatic systems. While fluctuating levels of dissolved oxygen (DO) can be a natural phenomenon, hypoxia caused by eutrophication and organic pollution is now considered to be amongst the most pressing and critical water pollution problems in the world, particularly in densely populated regions. The effects of low DO on fishes are an area of great concern and thriving study. Researchers have examined the effects of low DO on fishes from the cellular to community level. The purpose of the current paper is to review the effects of low DO on complex fish behaviour, community and fish physiology. Our review will also highlight studies in which DO is known to interact with a known contaminant. Throughout the paper we will highlight areas in need of future research such as chronic exposure, interactive effects of DO and contaminants, an increased understanding of how hypoxia affects communities of organisms, and finally a need for an increase in freshwater studies.
The Wetlands of Lakes Pontchartrain and Maurepas: Past, Present and Future
Authors: Keddy P.A. , Campbell D. , McFalls T. , Shaffer G.P. , Moreau R. , Dranguet C. , Heleniak R.
Published: January 2008

One of the largest wetlands along the Gulf Coast of North America (ca. 150 000 ha) occurs around the shorelines of Lake Pontchartrain and Lake Maurepas in southeastern Louisiana, just north and west of New Orleans. We provide an introduction to the environmental history of the marshes and swamps in the upper Lake Pontchartrain basin, a review of the existing vegetation patterns and their possible causes, and a discussion of restoration targets and priorities. The Mississippi River produced the St. Bernard Delta 3000–4000 years ago, trapping fresh water to produce both Lake Maurepas and Lake Pontchartrain (Frazier 1967). The natural vegetation of much of the region remains fresh or brackish marshes, mixed with swamps dominated by bald cypress ( Taxodium distichum ) and tupelo ( Nyssa aquatica ). Yearly flooding by the Mississippi River was once a major factor controlling vegetation patterns, but these processes have been greatly impaired by the construction of artificial levees for flood control. Humans also removed most of the cypress swamps in a pulse of logging between 1876 and 1956. Continued subsidence of the land, slowly rising sea levels, salinity pulses from hurricanes, and canals from the Gulf of Mexico, add further stress to these wetlands. Over the past century there has been a steady loss of wetland area, and a gradual conversion of fresh water to salt water vegetation types. Biotic processes are also important. An exotic species of mammal, nutria ( Myocastor coypus ), consumes both aboveground and belowground parts of wetland plants. Reforestation is strictly limited by the combination of salt pulses, competition, and nutria. Alligators are the top predator in this system, but their potential for reducing the impacts of nutria has received minimal attention from biologists. There are many potential future states for this ecosystem. In the extreme case of rising sea level and warmer climate, the area may become a salt and brackish embayment fringed with mangroves. The state closest to historical conditions would be large areas of bald cypress swamp. Two important priorities are to increase flow of freshwater into the system from multiple pulsed fresh water diversions, and to decrease saltwater intrusions by closing canals such as the Mississippi River Gulf Outlet.
Freshwater acidification research in Atlantic Canada: a review of results and predictions for the future
Authors: Clair Thomas A. , Dennis Ian F. , Scruton David A. , Gilliss Mallory
Published: January 2008

Atlantic Canada receives the lowest acid deposition amounts in eastern North America, but has some of the most acidic surface waters on the continent, due to the low buffering provided by regional bedrock and wetlands that produce natural organic acids. Southwestern and eastern parts of Nova Scotia combine poor buffering, high organic acidity, and higher acid deposition, to produce extremely low surface water pH and acid neutralization capacity (ANC) values. Although sulfate deposition is decreasing, concurrent reductions in dissolved base cations, as well as the acid-base characteristics of natural organic acids, are not allowing the recovery of ANC or surface water pH. Spring-time acid pulses occur in Atlantic Canada, though these have been reduced in severity with decreases in winter acid deposition, while autumnal low pH pulses caused by organic acids are a regular occurence in Nova Scotia and must be separated from mineral acidity pulses. Geochemical modeling using both critical load and dynamic approaches, nevertheless predict improvements in the water chemistry of Nova Scotia lakes within the next 20 years. However, re-establishment of pre-acidification water chemistry in most of its lakes will require greater reductions in S emissions than are currently planned in Canada and the United States.
NONDEGENERATED SPIN STATES OF A TRAPPED SPINOR BOSE GAS BEYOND MEAN FIELD THEORY
Authors: JIA DUOJE , XU YAN , LI ZHAOXIN , HOU FENGCHAO , CHEN ZHAOYANG
Published: January 2008

An effective Hamiltionian with level splitting of the collective spin states is derived for a spinor Bose condensate of trapped atoms with hyperfine spin f = 1 beyond the single-mode approximation. The splitting of these spin states arises from quantum polarization between the mf = +1 and mf = -1 spin channels, and is characterized by small magnetization exhibited by the trapped gas. For big ferromagnetic 87 Rb and antiferromagnetic 23 Na Bose gases, the splitting fraction in total energy increases as -N-1 and decreases as N-2 when the atom number N varies, with typical order of 10-6 and 10-4, respectively. In the case of small condensates, the splitting fraction increases as -N-2, with typical order of 10-5~10-6, both for 87 Rb and 23 Na atoms. In both cases of the big and small condensates, the splitting energy is analogous to the anisotropic energy of a magnet, being proportional to the square of the pseudo-magnetization.
CRYSTALLINE MAGNETOTUNNEL JUNCTIONS: Fe-MgO-Fe, Fe-FeOMgO-Fe and Fe-AuMgOAu-Fe
Authors: STILLING MORTEN
Published: January 2008

We have modeled the electrical properties of three magnetotunnel junctions and find results similar to those in the literature. We have commenced investigations into the effects of perturbations to the exact positions of the atoms in these structures and report on the progress of these investigations.

Note from Publisher: This article contains the abstract only.
A MODIFIED GRAVITY AND ITS CONSEQUENCES FOR THE SOLAR SYSTEM, ASTROPHYSICS AND COSMOLOGY
Authors: MOFFAT J. W.
Published: January 2008

A relativistic modified gravity (MOG) theory leads to a self-consistent, stable gravity theory that can describe the solar system, galaxy and clusters-of-galaxies data, and cosmology.
The Aging Brain
Authors: Yankner Bruce A. , Lu Tao , Loerch Patrick
Published: January 2008

Aging is accompanied by cognitive decline in a major segment of the population and is the primary risk factor for Alzheimer's disease and other prevalent neurodegenerative disorders. Despite this central role in disease pathogenesis and morbidity, the aging of the brain has not been well understood at a molecular level. This review seeks to integrate what is known about age-related cognitive and neuroanatomical changes with recent advances in understanding basic molecular mechanisms that underlie aging. An important issue is how normal brain aging transitions to pathological aging, giving rise to neurodegenerative disorders. Toxic protein aggregates have been identified as potential contributory factors, including amyloid β-protein in Alzheimer's disease, tau in frontotemporal dementia, and α-synuclein in Parkinson's disease. However, current models of pathogenesis do not explain the origin of the common sporadic forms of these diseases or address the critical nexus between aging and disease. This review discusses potential approaches to unifying the systems biology of the aging brain with the pathogenesis of neurodegeneration.
Anti-Inflammatory and Proresolving Lipid Mediators
Authors: Serhan Charles N. , Yacoubian Stephanie , Yang Rong
Published: January 2008

The popular view that all lipid mediators are pro-inflammatory arises largely from the finding that nonsteroidal anti-inflammatory drugs block the biosynthesis of prostaglandins. The resolution of inflammation was widely held as a passive event until recently, with the characterization of novel biochemical pathways and lipid-derived mediators that are actively turned on in resolution and that possess potent anti-inflammatory and proresolving actions. A lipid-mediator informatics approach was employed to systematically identify new families of endogenous local-acting mediators from omega-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) in resolving exudates, which also contain lipoxins and aspirin-triggered lipoxins generated from arachidonic acid. Given their potent bioactions, these new chemical mediator families were termed resolvins and protectins. Here, we review the recent advances in our understanding of the biosynthesis and stereospecific actions of these new proresolving mediators, which have also proven to be organ protective and antifibrotic.
The Inflammatory Response to Cell Death
Authors: Rock Kenneth L. , Kono Hajime
Published: January 2008

When cells die in vivo, they trigger an inflammatory response. The ensuing hyperemia, leak of plasma proteins, and recruitment of leukocytes serve a number of useful functions in host defense and tissue repair. However, this response can also cause tissue damage and contribute to the pathogenesis of a number of diseases. Given the key role of inflammation in these processes, it is important to understand the underlying mechanisms that drive this response. Injured cells release danger signals that alert the host to cell death. Some of these molecules are recognized by cellular receptors that stimulate the generation of proinflammatory mediators. Other molecules released by dead cells stimulate the generation of mediators from extracellular sources. The resulting mediators then orchestrate the inflammatory response, eliciting its various vascular and cellular components. Dead cells also release danger signals that activate dendritic cells and promote the generation of immune responses to antigens. Here we review what is presently known about the sterile inflammatory response and its underlying mechanisms.
The Role of Hypoxia in Vascular Injury and Repair
Authors: Walshe Tony E. , D'Amore Patricia A.
Published: January 2008

Although the terms ischemia and hypoxia are often used interchangeably, they represent distinct processes that result in different modulatory effects at the cellular level. Hypoxia is a reduction in oxygen delivery below tissue demand, whereas ischemia is a lack of perfusion, characterized not only by hypoxia but also by insufficient nutrient supply. Hypoxia can be either acute or chronic, and both are centrally regulated by hypoxia-inducible factor, a transcription factor that governs the expression of key response genes such as vascular endothelial growth factor and erythropoietin. Whereas severe chronic hypoxia can cause cell death, less-severe hypoxia can protect against subsequent damage, a phenomenon known as hypoxic conditioning. Several important processes are characterized by hypoxia, including ischemia-reperfusion, tumor growth and progression, inflammation, myocardial ischemia, and a number of ocular pathologies.
Modeling Morphogenesis and Oncogenesis in Three-Dimensional Breast Epithelial Cultures
Authors: Hebner Christy , Weaver Valerie M. , Debnath Jayanta
Published: January 2008

Three-dimensional (3D) epithelial culture systems recreate the cardinal features of glandular epithelium in vivo and represent a valuable tool for modeling breast cancer initiation and progression in a structurally appropriate context. 3D models have emerged as a powerful method to interrogate the biological activities of cancer genes and oncogenic pathways, and recent studies have poignantly illustrated their utility in dissecting the emerging role of tensional force in regulating epithelial tissue homeostasis. We review how 3D models are being used to investigate fundamental cellular and biophysical mechanisms associated with breast cancer progression that have not been readily amenable to traditional genetic or biochemical analysis.
Molecular Biology and Pathogenesis of Viral Myocarditis
Authors: Esfandiarei Mitra , McManus Bruce M.
Published: January 2008

Myocarditis is a cardiac disease associated with inflammation and injury of the myocardium. Several viruses have been associated with myocarditis in humans. However, coxsackievirus B3 is still considered the dominant etiological agent. The observed pathology in viral myocarditis is a result of cooperation or teamwork between viral processes and host immune responses at various stages of disease. Both innate and adaptive immune responses are crucial determinants of the severity of myocardial damage, and contribute to the development of chronic myocarditis and dilated cardiomyopathy following acute viral myocarditis. Advances in genomics and proteomics, and in the use of informatics and biostatistics, are allowing unbiased initial evaluations that can be the basis for testable hypotheses about virus pathogenesis and new therapies.
Molecular Pathobiology of Gastrointestinal Stromal Sarcomas
Authors: Corless Christopher L. , Heinrich Michael C.
Published: January 2008

Gastrointestinal stromal tumors (GISTs) form an interesting group of sarcomas whose unique pathobiology provides a model of how molecularly targeted therapeutics can have a major impact on patient welfare. Approximately 85% of GISTs are driven by oncogenic mutations in either of two receptor tyrosine kinases: KIT or platelet-derived growth factor receptor α. We review the pivotal relationship between specific mutations in these kinase genes, the origin and pathologic spectrum of GISTs, and the response of these tumors to treatment with kinase inhibitors such as imatinib and sunitinib. Mechanisms of resistance to kinase inhibitor therapy are discussed, and targets for the next generation of therapeutics are considered. The rapid evolution in our understanding of GISTs, which stems directly from the close alliance of basic and clinical researchers in the field, illustrates the growing role of the molecular classification of solid tumors in the development of modern oncological treatments.
Notch Signaling in Leukemia
Authors: Aster Jon C. , Pear Warren S. , Blacklow Stephen C.
Published: January 2008

Recent discoveries indicate that gain-of-function mutations in the Notch1 receptor are very common in human T cell acute lymphoblastic leukemia/lymphoma. This review discusses what these mutations have taught us about normal and pathophysiologic Notch1 signaling, and how these insights may lead to new targeted therapies for patients with this aggressive form of cancer.
Pancreatic Cancer
Authors: Maitra Anirban , Hruban Ralph H.
Published: January 2008

The past two decades have witnessed an explosion in our understanding of pancreatic cancer, and it is now clear that pancreatic cancer is a disease of inherited (germ-line) and somatic gene mutations. The genes mutated in pancreatic cancer include KRAS2, p16/CDKN2A, TP53, and SMAD4/DPC4, and these are accompanied by a substantial compendium of genomic and transcriptomic alterations that facilitate cell cycle deregulation, cell survival, invasion, and metastases. Pancreatic cancers do not arise de novo, and three distinct precursor lesions have been identified. Experimental models of pancreatic cancer have been developed in genetically engineered mice, which recapitulate the multistep progression of the cognate human disease. Although the putative cell of origin for pancreatic cancer remains elusive, minor populations of cells with stem-like properties have been identified that appear responsible for tumor initiation, metastases, and resistance of pancreatic cancer to conventional therapies.
The Pathology of Influenza Virus Infections
Authors: Taubenberger Jeffery K. , Morens David M.
Published: January 2008

Influenza viruses are significant human respiratory pathogens that cause both seasonal, endemic infections and periodic, unpredictable pandemics. The worst pandemic on record, in 1918, killed approximately 50 million people worldwide. Human infections caused by H5N1 highly pathogenic avian influenza viruses have raised concern about the emergence of another pandemic. The histopathology of fatal influenza virus pneumonias as documented over the past 120 years is reviewed here. Strikingly, the spectrum of pathologic changes described in the 1918 influenza pandemic is not significantly different from the histopathology observed in other less lethal pandemics or even in deaths occurring during seasonal influenza outbreaks.
Molecular Mechanisms of Prion Pathogenesis
Authors: Aguzzi Adriano , Sigurdson Christina , Heikenwaelder Mathias
Published: January 2008

Prion diseases are infectious neurodegenerative diseases occurring in humans and animals with an invariably lethal outcome. One fundamental mechanistic event in prion diseases is the aggregation of aberrantly folded prion protein into large amyloid plaques and fibrous structures associated with neurodegeneration. The cellular prion protein (PrPC) is absolutely required for disease development, and prion knockout mice are not susceptible to prion disease. Prions accumulate not only in the central nervous system but also in lymphoid organs, as shown for new variant and sporadic Creutzfeldt-Jakob patients and for some animals. To date it is largely accepted that prions consist primarily of PrPSc, a misfolded and aggregated β-sheet-rich isoform of PrPC. However, PrPSc may or may not be completely congruent with the infectious moiety. Here, we discuss the molecular mechanisms leading to neurodegeneration, the role of the immune system in prion pathogenesis, and the existence of prion strains that appear to have different tropisms and biochemical characteristics.
Diurnal profiles of hypothalamic energy balance gene expression with photoperiod manipulation in the Siberian hamster, Phodopus sungorus
Authors: Ellis Claire , Moar Kim M. , Logie Tracy J. , Ross Alexander W. , Morgan Peter J. , Mercer Julian G.
Published: January 2008

Hypothalamic energy balance genes have been examined in the context of seasonal body weight regulation in the Siberian hamster. Most of these long photoperiod (LD)/short photoperiod (SD) comparisons have been of tissues collected at a single point in the light-dark cycle. We examined the diurnal expression profile of hypothalamic genes in hamsters killed at 3-h intervals throughout the light-dark cycle after housing in LD or SD for 12 wk. Gene expression of neuropeptide Y, agouti-related peptide, proopiomelanocortin, cocaine- and amphetamine-regulated transcript, long-form leptin receptor, suppressor of cytokine signaling-3, melanocortin-3 receptor, melanocortin-4 receptor, and the clock gene Per1 as control were measured by in situ hybridization in hypothalamic nuclei. Effects of photoperiod on gene expression and leptin levels were generally consistent with previous reports. A clear diurnal variation was observed for Per1 in the suprachiasmatic nucleus in both photoperiods. Temporal effects on expression of energy balance genes were restricted to long-form leptin receptor in the arcuate nucleus and ventromedial nucleus, where similar diurnal expression profiles were observed, and melanocortin-4 receptor in the paraventricular nucleus; these effects were only observed in LD hamsters. There was no variation in serum leptin concentration. The 24-h profiles of hypothalamic energy balance gene expression broadly confirm photoperiodic differences that were observed previously, based on single time point comparisons, support the growing consensus that these genes have a limited role in seasonal body weight regulation, and further suggest limited involvement in daily rhythms of food intake.
The trajectory of sensory pathways from the lamina terminalis to the insular and cingulate cortex: a neuroanatomical framework for the generation of thirst
Authors: Hollis Jacob H. , McKinley Michael J. , D'Souza Moyra , Kampe Juliane , Oldfield Brian J.
Published: January 2008

The pathways involved in the emotional aspects of thirst, the arousal and affect associated with the generation of thirst and the motivation to obtain satiation, have been studied but remain poorly understood. Rats were therefore injected with the neurotropic virus pseudorabies in either the insular or cingulate cortex. After 2 days of infection, pseudorabies-positive neurons were identified within the thalamus and lamina terminalis. In a separate group of rats, the retrograde tracer cholera toxin subunit b (CTb) was used in combination with either isotonic (0.15 M NaCl) or hypertonic (0.8 M NaCl) saline (1 ml/100 g body wt ip). Rats injected with CTb in the insular cortex and stimulated with hypertonic saline had increased numbers of Fos/CTb double-positive neurons in the paraventricular, rhomboid, and reuniens thalamic nuclei, whereas those rats injected with CTb in the cingulate cortex and challenged with hypertonic saline had increased numbers of Fos/CTb double-positive neurons in the medial part of the mediodorsal, interanteromedial, anteromedial, and ventrolateral part of the laterodorsal thalamic nuclei. Rats injected with CTb in the dorsal midline of the thalamus and challenged with hypertonic saline had increased numbers of Fos/CTb double-positive neurons within the organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus, and insular cortex but not the subfornical organ. A small proportion of the CTb-positive neurons in the OVLT were immunopositive for transient receptor potential vanilloid 1, a putative osmoresponsive membrane protein. These results identify functional thalamocortical pathways involved in relaying osmotic signals to the insular and cingulate cortex and may provide a neuroanatomical framework for the emotional aspects of thirst.
Spinomuscular Coherence in Monkeys Performing a Precision Grip Task
Authors: Takei Tomohiko , Seki Kazuhiko
Published: January 2008

We recorded local field potentials (LFPs) from cervical spinal cord (C5–C8) in monkeys performing a precision grip task and examined their coherence with electromyographic (EMG) activities (spinomuscular coherence) recorded from hand and arm muscles. Among 164 LFP-EMG pairs, significant coherence was found in 34 pairs (21%). We classified the coherence into two groups based on its frequency range, narrowband coherence, and broadband coherence. The narrowband coherence was restricted to discrete frequencies in the range of 14–55 Hz and was widespread throughout the superficial and deep gray matter. In contrast, the broadband coherence distributed between 10 and 95 Hz and was found only in the ventral half of the spinal cord. The narrowband coherence suggests that oscillations, which have been described in many motor control areas of the brain, could also pass though spinal interneurons to affect motor output and sensorimotor integration. On the other hand, the broadband coherence could be a unique feature of spinal motoneuron-muscle physiology.
Short-Term Plasticity of Spinal Reflex Excitability Induced by Rhythmic Arm Movement
Authors: Javan Bahar , Zehr E. Paul
Published: January 2008

Rhythmic arm movement reduces Hoffmann (H)-reflex amplitudes in leg muscles by modulation of presynaptic inhibition in group Ia transmission. To date only the acute effect occurring during arm movement has been studied. We hypothesized that the excitability of soleus H-reflexes would remain suppressed beyond a period of arm cycling conditioning. Subjects used a customized arm ergometer to perform rhythmic 1-Hz arm cycling for 30 min. H-reflexes were evoked before, during, and after arm cycling via stimulation of the tibial nerve in the popliteal fossa. The most important finding was that the H-reflex amplitudes were significantly suppressed during and ≤20 min after arm cycling had been terminated. Thus remote arm cycling can induce adaptive plasticity in the soleus H-reflex pathway that persists beyond the period of conditioning. In an additional experiment, the prolonged effect of arm cycling combined with cutaneous superficial radial (SR) nerve stimulation was investigated. Cutaneous stimulation cancelled the prolonged suppression of H-reflex amplitude induced by arm cycling. Because SR nerve stimulation facilitates soleus H-reflex via reducing the level of Ia presynaptic inhibition, persistence in presynaptic inhibitory pathways is suggested as the underlying neural mechanism. The simplest explanation of this observation is plateau potential-like behavior of interneurons mediating presynaptic inhibition of Ia afferent transmission.
Genome-wide identification and characterization of transcripts translationally regulated by bacterial lipopolysaccharide in macrophage-like J774.1 cells
Authors: Kitamura Hiroshi , Ito Masatoshi , Yuasa Tomoko , Kikuguchi Chisato , Hijikata Atsushi , Takayama Michiyo , Kimura Yayoi , Yokoyama Ryo , Kaji Tomohiro , Ohara Osamu
Published: January 2008

Although Escherichia coli LPS is known to elicit various proinflammatory responses in macrophages, its effect on the translational states of transcripts has not yet been explored on a genome-wide scale. To address this, we investigated the mRNA profiles in polysomal and free messenger ribonucleoprotein particle (mRNP) fractions of mouse macrophage-like J774.1 cells, using Affymetrix Mouse Genome 430 2.0 GeneChips. Comparison of the mRNA profiles in total cellular, polysomal, and free mRNP fractions enabled us to identify transcripts that were modulated at the translational level by LPS: among 19,791 transcripts, 115 and 418 were up- and downregulated at 1, 2, or 4 h after LPS stimulation (100 ng/ml) in a translation-dependent manner. Interestingly, gene ontology-based analysis suggested that translation-dependent downregulated genes frequently include those encoding proteins in the mitochondrial respiratory chain. In fact, the mRNA levels of some transcripts for complexes I, IV, and V in the mitochondrial respiratory chain were translationally downregulated, eventually contributing to the decline of their protein levels. Moreover, the amount of metabolically labeled cytochrome oxidase subunit Va in complex IV was decreased without any change of its mRNA level in total cellular fraction after LPS stimulation. Consistently, the total amounts and activities of complexes I and IV were attenuated by LPS stimulation, and the attenuation was independent of nitric oxide. These results demonstrated that translational suppression may play a critical role in the LPS-mediated attenuation of mitochondrial oxidative phosphorylation in a nitric oxide-independent manner in J774.1 cells.