bluuebunny/crossref_metadata_2025 huggingface dataset:
Escaping real (non-benign) competency traps: linking the dynamics of organizational structure to the dynamics of search
Authors: Siggelkow Nicolaj , Levinthal Daniel A.
Published: January 2005

Focusing on the effect that organizational structure exerts on organizational search, we show under which conditions a change in structure increases performance even in stable environments. We model five different organizational structures (centralized, decentralized, ambidextrous, hybrid and team-based) and study with the help of an agent-based simulation whether transitions among these structures are beneficial. We find that sequences of structures can achieve higher performance than fixed structures. Alternative structures differ in their competency traps or sets of sticking points, that is the sets of points at which a search process in a given structure will terminate. As a result, a shift in structure may dislodge an organization from its current configuration of choices and provoke further search. Changes in organizational structure effectively differentiate between settings in which remaining at a competency trap is in fact a trap and settings in which remaining at a competency trap indicates competence. In particular, a shift in organizational structure differentially sorts among more or less favorable sticking points, as sticking points that are common to two structures tend to be higher-performing. Thus, behavior that remains inert when structures change will tend to be associated with particularly high-performing sticking points. Moreover, behavior should be dislodged from the prior sticking point, this provides a favorable starting point for subsequent search. Consequently, a shift in organizational structure need not be a response to new environmental contingency, but a mechanism to overcome the challenge of competency traps as well.
Emotional Intelligence and Emotion Work: Examining Constructs From an Interdisciplinary Framework
Authors: Opengart Rose
Published: January 2005

Emotional intelligence and emotion work are two research areas traditionally presented as distinct. This article reviews their definitions, examines their intersections, and illustrates the advantage of approaching emotion research from an interdisciplinary framework. Conclusions address the following: (a) An employee’s emotional intelligence or cognitive abilities cannot be assessed or developed without an understanding of the context or emotion work rules; (b) an employee’s emotional intelligence provides the foundational ability to perceive the display rules within a given job context or situation; (c) emotion work cannot be performed well without possessing a foundation of emotional intelligence. Those responsible for employee development must help the employee develop cognitive abilities and knowledge about contextual emotional expression rules. Implications for human resource development address ways professionals can utilize this interdisciplinary perspective in research and practice and the importance of developing both cognitive abilities and contextual knowledge about emotions to help employees develop emotional intelligence and perform emotion work.
The Structure and Function of Attitudes Toward Organizational Change
Authors: Lines Rune
Published: January 2005

In this article, an attitudinal perspective on organizational members’ reactions to change is proposed and developed. By viewing change as an attitude object in this sense, a richer conceptualization of perceptions of change and reactions to change in terms of emotions, cognitions, and behaviors is achieved. The perspective also frames organizational changes in terms of aspects that are relevant for change recipients because of their relationships with important values that are held by organizational members. To identify classes of beliefs underlying the formation of attitudes toward change, constructs are integrated from theories of job characteristics and organizational justice with the overarching attitude perspective. Research implications of the framework as well as implications for managing change are discussed.
Market-Based Information for Decision Support in Human Resource Development
Authors: Passmore David L. , Cebeci Evin D. , Baker Rose M.
Published: January 2005

Common methods for obtaining and organizing information for evaluating human resource development (HRD) decisions, such as surveys, focus groups, Delphi processes, and discussion at business meetings, can be relatively costly, ad hoc, and difficult to apply. In this article, a review is presented of relatively inexpensive, continuous, and easy-to-apply innovations in information aggregation for examining futures of ideas that are drawn from principles and mechanisms of commodity futures markets. A description is given of how futures markets for ideas have strong applicability to strategic, tactical, and operational decisions about the development, diffusion, and implementation of HRD products and services. Examples are offered for how idea futures markets could support HRD decisions about sales forecasting, product efficacy, project management, environmental scanning, and identification of expertise.
The Spread of Contingent Work in the Knowledge-Based Economy
Authors: Szabó Katalin , Négyesi Áron
Published: January 2005

Permanent employment, typical of industrial societies and bolstered by numerous social guaranties, has been declining in the past 2 decades. There has been a steady expansion of various forms of contingent work. The decomposition of traditional work is a logical consequence of the characteristic patterns of the knowledge-based economy. According to the logic of information technology, changeable modules are key characteristics of production processes and economic organizations. Each module leads a life of its own, with infinite combinatory possibilities. As a consequence, static and “safe” economic arrangements are replaced by dynamic and uncertain institutions. Employees (except for key personnel) become interchangeable, disposable, recallable, and transferable. Consequently, the portfolio of workers’ capabilities and knowledge should be adjusted to the requirements of changing workplaces. For companies, the return on investments in employees’ knowledge is uncertain; thus, contingent workers have to undertake, at least partly, the responsibility and costs of their own training.
Efficient decoding algorithms for generalized hidden Markov model gene finders
Authors: Majoros William H , Pertea Mihaela , Delcher Arthur L , Salzberg Steven L
Published: January 2005

Background

The Generalized Hidden Markov Model (GHMM) has proven a useful framework for the task of computational gene prediction in eukaryotic genomes, due to its flexibility and probabilistic underpinnings. As the focus of the gene finding community shifts toward the use of homology information to improve prediction accuracy, extensions to the basic GHMM model are being explored as possible ways to integrate this homology information into the prediction process. Particularly prominent among these extensions are those techniques which call for the simultaneous prediction of genes in two or more genomes at once, thereby increasing significantly the computational cost of prediction and highlighting the importance of speed and memory efficiency in the implementation of the underlying GHMM algorithms. Unfortunately, the task of implementing an efficient GHMM-based gene finder is already a nontrivial one, and it can be expected that this task will only grow more onerous as our models increase in complexity.

Results

As a first step toward addressing the implementation challenges of these next-generation systems, we describe in detail two software architectures for GHMM-based gene finders, one comprising the common array-based approach, and the other a highly optimized algorithm which requires significantly less memory while achieving virtually identical speed. We then show how both of these architectures can be accelerated by a factor of two by optimizing their content sensors. We finish with a brief illustration of the impact these optimizations have had on the feasibility of our new homology-based gene finder, TWAIN.

Conclusions

In describing a number of optimizations for GHMM-based gene finders and making available two complete open-source software systems embodying these methods, it is our hope that others will be more enabled to explore promising extensions to the GHMM framework, thereby improving the state-of-the-art in gene prediction techniques.
Induction of chondro-, osteo- and adipogenesis in embryonic stem cells by bone morphogenetic protein-2: Effect of cofactors on differentiating lineages
Authors: zur Nieden Nicole I , Kempka Grazyna , Rancourt Derrick E , Ahr Hans-Jürgen
Published: January 2005

Background

Recently, tissue engineering has merged with stem cell technology with interest to develop new sources of transplantable material for injury or disease treatment. Eminently interesting, are bone and joint injuries/disorders because of the low self-regenerating capacity of the matrix secreting cells, particularly chondrocytes. ES cells have the unlimited capacity to self-renew and maintain their pluripotency in culture. Upon induction of various signals they will then differentiate into distinctive cell types such as neurons, cardiomyocytes and osteoblasts.

Results

We present here that BMP-2 can drive ES cells to the cartilage, osteoblast or adipogenic fate depending on supplementary co-factors. TGFβ1, insulin and ascorbic acid were identified as signals that together with BMP-2 induce a chondrocytic phenotype that is characterized by increased expression of cartilage marker genes in a timely co-ordinated fashion. Expression of collagen type IIB and aggrecan, indicative of a fully mature state, continuously ascend until reaching a peak at day 32 of culture to approximately 80-fold over control values. Sox9 and scleraxis, cartilage specific transcription factors, are highly expressed at very early stages and show decreased expression over the time course of EB differentiation. Some smaller proteoglycans, such as decorin and biglycan, are expressed at earlier stages. Overall, proteoglycan biosynthesis is up-regulated 7-fold in response to the supplements added. BMP-2 induced chondrocytes undergo hypertrophy and begin to alter their expression profile towards osteoblasts. Supplying mineralization factors such as β-glycerophosphate and vitamin D3 with the culture medium can facilitate this process. Moreover, gene expression studies show that adipocytes can also differentiate from BMP-2 treated ES cells.

Conclusions

Ultimately, we have found that ES cells can be successfully triggered to differentiate into chondrocyte-like cells, which can further alter their fate to become hypertrophic, and adipocytes. Compared with previous reports using a brief BMP-2 supplementation early in differentiation, prolonged exposure increased chondrogenic output, while supplementation with insulin and ascorbic acid prevented dedifferentiation. These results provide a foundation for the use of ES cells as a potential therapy in joint injury and disease.
PCR cloning of a histone H1 gene from Anopheles stephensi mosquito cells: comparison of the protein sequence with histone H1-like, C-terminal extensions on mosquito ribosomal protein S6
Authors: Zhai Yongjiao , Fallon Ann M
Published: January 2005

Background

In Aedes and Anopheles mosquitoes, ribosomal protein RPS6 has an unusual C-terminal extension that resembles histone H1 proteins. To explore homology between a mosquito H1 histone and the RPS6 tail, we took advantage of the Anopheles gambiae genome database to clone a histone H1 gene from an Anopheles stephensi mosquito cell line.

Results

We designed specific primers based on RPS6 and histone H1 alignments to recover an Anopheles stephensi histone H1 corresponding to a conceptual An. gambiae protein, with 92% identity. Southern blots suggested that Anopheles stephensi histone H1 gene has multiple variants, as is also the case for histone H1 proteins in Chironomid flies.

Conclusions

Histone H1 proteins from Anopheles stephensi and Anopheles gambiae mosquitoes share 92% identity to each other, but only 50% identity to a Drosophila homolog. In a phylogenetic analysis, Anopheles, Chironomus and Drosophila histone H1 proteins cluster separately from the histone H1-like, C-terminal tails on RPS6 in Aedes and Anopheles mosquitoes. These observations suggest that the resemblance between histone H1 and the C-terminal extensions on mosquito RPS6 has been maintained by convergent evolution.
Steroid-refractory ulcerative colitis treated with corticosteroids, metronidazole and vancomycin: a case report
Authors: Miner Jonathan , Gillan M Monem , Alex Philip , Centola Michael
Published: January 2005

Background

Increasing evidence elucidating the pathogenic mechanisms of ulcerative colitis (UC) has accumulated and the disease is widely assumed to be the consequence of genetic susceptibility and an abnormal immune response to commensal bacteria. However evidence regarding an infectious etiology in UC remains elusive.

Case presentation

We report a provocative case of UC with profound rheumatologic involvement directly preceded by Clostridium difficile infection and accompanying fever, vomiting, bloody diarrhea, and arthritis. Colonic biopsy revealed a histopathology suggestive of UC. Antibiotic treatment eliminated detectable levels of enteric pathogens but did not abate symptoms. Resolution of symptoms was procurable with oral prednisone, but tapering of corticosteroids was only achievable in combination therapy with vancomycin and metronidazole.

Conclusions

An infectious pathogen may have both precipitated and exacerbated autoimmune disease attributes in UC, symptoms of which could be resolved only with a combination of corticosteroids, vancomycin and metronidazole. This may warrant the need for more perceptive scrutiny of C. difficile and the like in patients with UC.
Suppression of MMP-9 by doxycycline in brain arteriovenous malformations
Authors: Hashimoto Tomoki , Matsumoto Melissa M , Li Jenny F , Lawton Michael T , Young William L ,   the University of California, San Francisco, BAVM Study Group
Published: January 2005

Background

The primary aim of this study is to demonstrate the feasibility of utilizing doxycycline to suppress matrix metalloproteinase-9 (MMP-9) in brain arteriovenous malformations (AVMs).

Methods

Ex-vivo treatment of AVM tissues: Intact AVM tissues were treated with doxycycline for 48 hours. Active and total MMP-9 in the medium were measured. Pilot trial: AVM patients received either doxycycline (100 mg) or placebo twice a day for one week prior to AVM resection. Active and total MMP-9 in BVM tissues were measured.

Results

Ex-vivo treatment of AVM tissues: Doxycycline at 10 and 100 μg/ml significantly decreased MMP-9 levels in AVM tissues ex-vivo (total: control vs 10 vs 100 μg/ml = 100 ± 6 vs 60 ± 16 vs 61 ± 9%; active: 100 ± 8 vs 48 ± 16 vs 59 ± 10%). Pilot trial: 10 patients received doxycycline, and 4 patients received placebo. There was a trend for both MMP-9 levels to be lower in the doxycycline group than in the placebo group (total: 2.18 ± 1.94 vs 3.26 ± 3.58, P = .50; active: 0.48 ± 0.48 vs 0.95 ± 1.01 ng/100 μg protein, P = .25).

Conclusions

A clinically relevant concentration of doxycycline decreased MMP-9 in ex-vivo AVM tissues. Furthermore, there was a trend that oral doxycycline for as short as one week resulted in a decrease in MMP-9 in AVM tissues. Further studies are warranted to justify a clinical trial to test effects of doxycycline on MMP-9 expression in AVM tissues.
Results of paclitaxel (day 1 and 8) and carboplatin given on every three weeks in advanced (stage III-IV) non-small cell lung cancer
Authors: Yumuk Perran F , Turhal Nazim S , Gumus Mahmut , Hatabay Nilgun F , Turken Orhan , Ozkan Alper , Salepci Taflan , Aliustaoglu Mehmet , Ahiskali Rengin
Published: January 2005

Background

Both paclitaxel (P) and carboplatin (C) have significant activity in non-small cell lung cancer (NSCLC). The weekly administration of P is active, dose intense, and has a favorable toxicity profile. We retrospectively reviewed the data of 51 consecutive patients receiving C and day 1 and 8 P chemotherapy (CT) regimen in advanced stage NSCLC to evaluate the efficacy and toxicity.

Methods

Patients treated in our institutions having pathologically proven NSCLC, no CNS metastases, adequate organ function and performance status (PS) ECOG 0–2 were given P 112.5 mg/m2 intravenously (IV) over 1 hour on day 1 and 8, followed by C AUC 5 IV over 1 hour, repeated in every three weeks. PC was given for maximum of 6 cycles.

Results

Median age was 58 (age range 39–77) and 41 patients (80%) were male. PS was 0/1/2 in 29/17/5 patients and stage was IIIA/IIIB/IV in 3/14/34 patients respectively. The median number of cycles administered was 3 (1–6). Seven patients (14%) did not complete the first 3 cycles either due to death, progression, grade 3 hypersensitivity reactions to P or lost to follow up. Best evaluable response was partial response (PR) in 45% and stable disease (SD) in 18%. Twelve patients (24%) received local RT. Thirteen patients (25%) received 2nd line CT at progression. At a median follow-up of 7 months (range, 1–20), 25 (49%) patients died and 35 patients (69%) progressed. Median overall survival (OS) was 11 ± 2 months (95% CI; 6 to 16), 1-year OS ratio was 44%. Median time to progression (TTP) was 6 ± 1 months (95% CI; 4 to 8), 1-year progression free survival (PFS) ratio was 20%. We observed following grade 3 toxicities: asthenia (10%), neuropathy (4%), anorexia (4%), anemia (4%), hypersensitivity to P (2%), nausea/vomiting (2%), diarrhea (2%) and neutropenia (2%). Two patients (4%) died of febrile neutropenia. Doses of CT were reduced or delayed in 12 patients (24%).

Conclusions

P on day 1 and 8 and C every three weeks is practical and fairly well tolerated outpatient regimen. This regimen seems to be comparably active to regimens given once in every three weeks.
Tissue classification for the epidemiological assessment of surgical transmission of sporadic Creutzfeldt-Jakob disease. A proposal on hypothetical risk levels
Authors: Rábano Alberto , de Pedro-Cuesta Jesús , Mølbak Kåre , Siden Åke , Calero Miguel , Laursen Henning ,   the EUROSURGYCJD Research Group
Published: January 2005

Background

Epidemiological studies on the potential role of surgery in Creutzfeldt-Jakob Disease transmission have disclosed associations with history of specific surgical interventions or reported negative results.

Methods

Within the context of a case-control study designed to address surgical risk of sporadic Creutzfeldt-Jakob Disease in Nordic European countries (EUROSURGYCJD Project), a strategy was adopted to categorise reported surgical procedures in terms of potential risk of Creutzfeldt-Jakob Disease acquisition. We took into account elements of biological plausibility, either clinically or experimentally demonstrated, such as tissue infectivity, PrP expression content or successful route of infection.

Results

We propose a classification of exposed tissues and anatomic structures, drawn up on the basis of their specific putative role as entry site for prion transmission through contact with surgical instruments that are not fully decontaminated.

Conclusions

This classification can serve as a reference, both in our study and in further epidemiological research, for categorisation of surgical procedures in terms of risk level of Creutzfeldt-Jakob Disease acquisition.
Generation of human antibody fragments against Streptococcus mutansusing a phage display chain shuffling approach
Authors: Kupper Michael B , Huhn Michael , Spiegel Holger , Ma Julian KC , Barth Stefan , Fischer Rainer , Finnern Ricarda
Published: January 2005

Background

Common oral diseases and dental caries can be prevented effectively by passive immunization. In humans, passive immunotherapy may require the use of humanized or human antibodies to prevent adverse immune responses against murine epitopes. Therefore we generated human single chain and diabody antibody derivatives based on the binding characteristics of the murine monoclonal antibody Guy's 13. The murine form of this antibody has been used successfully to prevent Streptococcus mutans colonization and the development of dental caries in non-human primates, and to prevent bacterial colonization in human clinical trials.

Results

The antibody derivatives were generated using a chain-shuffling approach based on human antibody variable gene phage-display libraries. Like the parent antibody, these derivatives bound specifically to SAI/II, the surface adhesin of the oral pathogen S. mutans.

Conclusions

Humanization of murine antibodies can be easily achieved using phage display libraries. The human antibody fragments bind the antigen as well as the causative agent of dental caries. In addition the human diabody derivative is capable of aggregating S. mutans in vitro, making it a useful candidate passive immunotherapeutic agent for oral diseases.
Variation in tissue-specific gene expression among natural populations
Authors: Whitehead Andrew , Crawford Douglas L
Published: January 2005

Background

Variation in gene expression is extensive among tissues, individuals, strains, populations and species. The interactions among these sources of variation are relevant for physiological studies such as disease or toxic stress; for example, it is common for pathologies such as cancer, heart failure and metabolic disease to be associated with changes in tissue-specific gene expression or changes in metabolic gene expression. But how conserved these differences are among outbred individuals and among populations has not been well documented. To address this we examined the expression of a selected suite of 192 metabolic genes in brain, heart and liver in three populations of the teleost fish Fundulus heteroclitus using a highly replicated experimental design.

Results

Half of the genes (48%) were differentially expressed among individuals within a population-tissue group and 76% were differentially expressed among tissues. Differences among tissues reflected well established tissue-specific metabolic requirements, suggesting that these measures of gene expression accurately reflect changes in proteins and their phenotypic effects. Remarkably, only a small subset (31%) of tissue-specific differences was consistent in all three populations.

Conclusions

These data indicate that many tissue-specific differences in gene expression are unique to one population and thus are unlikely to contribute to fundamental differences between tissue types. We suggest that those subsets of treatment-specific gene expression patterns that are conserved between taxa are most likely to be functionally related to the physiological state in question.
Vγ9Vδ2 T cells use a combination of mechanisms to limit the spread of the pathogenic bacteria Brucella
Authors: Oliaro Jane , Dudal Sherri , Liautard Janny , Andrault Jean-Baptiste , Liautard Jean-Pierre , Lafont Virginie
Published: January 2005

Human Vγ9Vδ2 T cells pay a crucial role in early immune response to intracellular pathogens. In brucellosis infection, this population of cells is drastically increased in the peripheral blood of patients during the acute phase of infection. In vitro, Vγ9Vδ2 T cells exhibit strong cytolytic activity against Brucella-infected cells and are able to impair intracellular growth of Brucella suis in autologous macrophages. In this study, we have investigated the relative importance of contact-dependent mechanisms versus soluble factors in the intracellular growth and viability of B. suis. We show that Vγ9Vδ2 T cells use contact-dependent mechanisms, such as the release of lytic granules and Fas-mediated signals, to decrease intracellular B. suis through lysis of infected macrophages, but these mechanisms have little impact on Brucella survival. Moreover, we demonstrate that soluble factors secreted by Vγ9Vδ2 T cells can directly affect B. suis survival through their potent bactericidal effects. From these results, we conclude that Vγ9Vδ2 T cells are able to use a combination of mechanisms that reduce the total numbers of B. suis and thus, may benefit the host by limiting the spread of this intracellular pathogen.
A Psychobiological Perspective on Genetic Determinants of Hypothalamus‐Pituitary‐Adrenal Axis Activity
Authors: WÜST STEFAN , FEDERENKO ILONA S. , van ROSSUM ELISABETH F.C. , KOPER JAN W. , KUMSTA ROBERT , ENTRINGER SONJA , HELLHAMMER DIRK H.
Published: January 2005

Abstract: From the perspective of psychobiological stress research we present a brief overview of findings documenting a significant impact of genetic factors on the activity of the hypothalamus‐pituitary‐adrenal (HPA) axis. Quantitative genetic studies in twins as well as association studies, primarily on polymorphisms in the glucocorticoid receptor gene, are depicted. Recent findings suggest that the collaboration of psychobiology and molecular genetics is a promising interdisciplinary approach that will significantly contribute to the understanding of the mechanisms underlying the link between stress, the HPA axis, and HPA‐related clinical states.
Maternal Programming of Individual Differences in Defensive Responses in the Rat
Authors: ZHANG TIE‐YUAN , PARENT CARINE , WEAVER IAN , MEANEY MICHAEL J.
Published: January 2005

Abstract:This paper describes the results of a series of studies showing that variations in mother‐pup interactions program the development of individual differences in behavioral and endocrine stress responses in the rat. These effects are associated with altered expression of genes in brain regions, such as the amygdala, hippocampus, and hypothalamus, that regulate the expression of stress responses. Studies from evolutionary biology suggest that such “maternal effects” are common and often associated with variations in the quality of the maternal environment. Together these findings suggest an epigenetic process whereby the experience of the mother alters the nature of the parent‐offspring interactions and thus the phenotype of the offspring.
Effects of Hormones and Sex Chromosomes on Stress‐Influenced Regions of the Developing Pediatric Brain
Authors: ROSE A BLYTHE , MERKE DEBORAH P. , CLASEN LIV S. , ROSENTHAL MICHAEL A. , WALLACE GREGORY L. , VAITUZIS A CATHERINE , FIELDS JEREMY D. , GIEDD JAY N.
Published: January 2005

Abstract: Recently discovered sexual dimorphism within developing brain structures such as the amygdala and hippocampus suggests that biological factors may account for many of the sex differences in stress reactivity. In this study, we have relied on studies of naturally occurring anomalous processes, such as congenital adrenal hyperplasia (CAH) and Klinefelter's syndrome (XXY), to observe the effects of hormones and sex chromosomes on brain structures thought to influence an individual's vulnerability to stress. Brain magnetic resonance imaging (MRI) scans were obtained both from 16 boys with classic CAH and 34 age‐ and sex‐matched controls and from 20 XXY children and 40 age‐matched controls. Smaller amygdala volumes were observed in boys with CAH than in matched controls, and in XXY patients than in matched controls. XXY patients were also found to have smaller hippocampus volumes when compared with matched controls. Acknowledging that hormone and sex chromosome effects upon the developing human brain are widespread and complex, it is difficult to conclude, with any certainty, the etiology of the differences found in this study. Future studies that examine longitudinal data and/or other diagnostic groups, however, may help to better elucidate specific hormone and sex chromosome effects upon stress‐related structures in the brain.
Evidence for Altered Monoamine Activity and Emotional and Cognitive Disturbance in Marmoset Monkeys Exposed to Early Life Stress
Authors: PRYCE CHRISTOPHER R. , DETTLING ANDREA , SPENGLER MARIANNE , SPAETE CORINNE , FELDON JORAM
Published: January 2005

Abstract: In common marmoset monkeys (Callithrix jacchus, order Primates), infants aged 2‐28 days were deprived of parental care for 30‐120 min/day in order to investigate the long‐term effects of this neglect‐stress model on affect and cognition in a primate species. Basal morning levels of urinary cortisol across the first year of life were unaffected in early deprived marmosets relative to their sibling controls. Basal morning levels of urinary dopamine were chronically increased. This peripheral increase in dopamine activity could represent a marker for central dopamine hyperactivity. Certainly, subadult early deprived marmosets exhibited performance deficits in two dopamine‐regulated neuropsychological tasks. They demonstrated: (1) impaired behavioral inhibition in an object reaching with detour task, exhibiting significantly more nonreinforced forward reaches to a reward visible inside a cube that could only be retrieved through an opening to the side of the cube; and (2) impaired reversal learning in a two‐way discrimination task based on visual icons presented on a touch‐sensitive computer screen. These findings provide further evidence for the relevance of this novel primate model of parent‐infant neglect to the environmental causes and mechanisms of human developmental psychopathology.
Effects of Chronic Stress on Methamphetamine‐Induced Dopamine Depletions in the Striatum
Authors: MATUSZEWICH LESLIE , YAMAMOTO BRYAN K.
Published: January 2005

Abstract: Research has shown that exposure to repeated stress alters acute behavioral and neurochemical responses to drugs of abuse. However, few studies have characterized the longer‐term detrimental effects of psychostimulant drugs such as methamphetamine (METH) after exposure to chronic stress. The current study tested whether 10 days of unpredictable stress produced greater striatal dopamine depletions after neurotoxic injections of METH and whether monoamine reuptake blockers protected against stress/METH‐induced DA depletion. Male rats were exposed to 10 d of unpredictable stress or weighed daily but not stressed. On day 11, all rats were given 4 injections of 0, 7.5, or 10 mg/kg METH, 1 injection every 2 h, and tissue collected 7 d later. Male rats exposed to unpredictable stress had greater depletions of striatal dopamine tissue content than nonstressed controls injected with METH. In a separate study, rats were treated with vehicle, desipramine (10 mg/kg), or fluoxetine (5 mg/kg) daily during the 10‐d stress regimen. These antidepressants did not attenuate the stress‐potentiated depletion of striatal dopamine. These findings suggest that chronic unpredictable stress enhances vulnerability of the brain to neurotoxic effects of psychostimulants, but this vulnerability is mediated through mechanisms other than the norepinephrine or serotonin uptake systems.
Regulation of Chronic Stress‐Induced Changes in Hypothalamic‐Pituitary‐Adrenal Activity by the Basolateral Amygdala
Authors: BHATNAGAR SEEMA , VINING COURTENAY , DENSKI KAI
Published: January 2005

Abstract: Little is known about the role of the basolateral amygdala (BLA) in regulating hypothalamic‐pituitary‐adrenal (HPA) activity, particularly chronic stress‐induced HPA activity. In the current studies, we examined the effects of manipulations of the BLA on HPA responses to the eighth restraint, to novel restraint after repeated cold, or to acute novel restraint alone. Excitotoxic lesions of the BLA, in general, inhibited HPA activity in both acute and chronically stressed animals.To examine the role of the BLA in chronic stress without affecting the response to the first stress, we injected the GABA agonist muscimol to temporarily inactivate the BLA prior to restraint in the same three groups of animals. In contrast to the lesion data, muscimol enhanced the HPA response to acute restraint and to novel restraint after repeated cold, but it did not affect responses to the eighth restraint. These data suggest that the BLA inhibits HPA responses to novel stress but is not important in animals repeatedly exposed to the same stressor. Future studies will focus on the neuro‐anatomical substrates of BLA's effects on HPA activity including whether inputs from the pPVTh are important.
A CRH1 Antagonist into the Amygdala of Mice Prevents Defeat‐Induced Defensive Behavior
Authors: ROBISON C L. , MEYERHOFF J L. , SAVIOLAKIS G A. , CHEN W K. , RICE K C. , LUMLEY L A.
Published: January 2005

Abstract: Corticotropin‐releasing hormone (CRH) is believed to play an important role in the regulation of behavioral responses to stress. CRH1 receptor antagonists may reduce stress responsivity. Stress increases CRH in the amygdala, important in memory consolidation. We hypothesized that infusion of a CRH1 antagonist into the amygdala following social defeat would prevent the development of generalized fear responses. Acute social defeat in mice increases defense towards intruders, even nonaggressive intruders, placed within their home cage. We infused the CRH1 antagonist antalarmin (0.25 μg/125 nl) bilaterally into the amygdala of mice immediately after defeat and measured their response to a nonaggressive intruder stimulus mouse placed within their home cage 24 h after defeat. Defeated mice that received vehicle displayed high levels of crouch defensive posture and numerous flights from intruders, relative to nondefeated mice that received vehicle. Defeated mice that received antalarmin into the amygdala exhibited significantly less defensive posture than did vehicle‐treated defeated mice. Display of defensive posture in antalarmin‐treated mice approached that of vehicle‐treated nondefeated mice. These findings support a role for CRH in the amygdala to promote consolidation of emotional memory and indicate that antagonism of CRH1 receptors in the amygdala may prevent the development of exaggerated fear responses in stressed mice.
Clinical Activity of Rituximab in Gastric Marginal Zone Non-Hodgkin's Lymphoma Resistant to or Not Eligible for Anti–Helicobacter Pylori Therapy
Authors: Martinelli Giovanni , Laszlo Daniele , Ferreri Andrés J.M. , Pruneri Giancarlo , Ponzoni Maurilio , Conconi Annarita , Crosta Cristiano , Pedrinis Ennio , Bertoni Francesco , Calabrese Liliana , Zucca Emanuele
Published: January 2005

Purpose

Preliminary results using rituximab in extranodal marginal zone (MALT) non-Hodgkin's lymphoma (NHL) patients seem to indicate a relevant clinical activity. Aim of the present study is to investigate the efficacy of conventional weekly treatment using rituximab in gastric MALT NHL patients resistant/refractory or not suitable for eradication treatment, and to evaluate the relevance of the t(11; 18)(q21; q21) translocation and its possible role as a predictive criteria of response.

Patients and Methods

Twenty-seven patients presenting with gastric MALT NHL at any stage, relapsed/refractory to initial treatment or not suitable for eradication were treated with rituximab in a weekly conventional schedule and evaluated for response and relapse. Flourescence in situ hybridization (FISH) analysis for the presence of 18q21 translocation was performed in 21 patients and was evaluated with clinical outcome.

Results

Among the 26 evaluated patients, 20 (77%) achieved an objective response. Twelve patients (46%) had a pathological and clinical complete remission, and eight (31%) had a partial response. With a median follow-up of 33 months, only two patients relapsed at 26 and 14 months, respectively. No correlation was founded between FISH analysis and response or relapse.

Conclusion

Our experience seems to confirm the clinical activity of rituximab in gastric MALT NHL patients resistant/refractory to antibiotics treatment or not presenting with clinical evidence of Helicobacter pylori infection. The t(11; 18)(q21; q21) translocation seems not to be a predictive marker to response or to subsequent relapse.
The mechanism of cell adhesion by classical cadherins: the role of domain 1
Authors: Harrison Oliver J. , Corps Elaine M. , Berge Torunn , Kilshaw Peter J.
Published: January 2005

The mechanism by which classical cadherins mediate cell adhesion and, in particular, the roles played by calcium and Trp2, the second amino acid in the N-terminal domain, have long been controversial. We have used antibodies to investigate the respective contributions of Trp2 and calcium to the stability of the N-terminal domain of N-cadherin. Using a peptide antibody to the βB strand in domain 1, which detects a disordered structure, we show that both Trp2 and calcium play crucial parts in regulating stability of the domain. The epitope for another antibody, mAb GC4, has been mapped to the base of domain 1. Binding of GC4 to this epitope was shown to depend on intramolecular `docking' of Trp2 into the domain 1 structure. Using this property, we provide evidence that calcium regulates a dynamic equilibrium between docked and undocked Trp2. Finally, a novel technique has been developed to test whether Trp2 cross-intercalation between cadherin molecules from adjacent cells (strand exchange) is central to cadherin-mediated cell adhesion. Guided by crystal structures showing strand exchange, we have introduced single cysteine point mutations into N-cadherin domain 1 in such a way that a disulphide bond will form between opposing N-cadherin molecules during cell adhesion if strand exchange occurs. The bond requires complementary cysteines to be precisely juxtaposed according to the strand exchange model. Our results demonstrate that the disulphide bond forms as predicted. This provides compelling evidence that strand exchange is indeed a primary event in cell adhesion by classical cadherins.
Variation in morphology and performance of predator-sensing system in wild cricket populations
Authors: Dangles Olivier , Magal Christelle , Pierre Dominique , Olivier Aurélie , Casas Jérôme
Published: January 2005

Even though variation in morphology is known to translate into variation in performance, studies looking at structural variability of a sensor to predict its consequences on the performance of animals are exceedingly rare. We investigated the morphological variability of air-flow-sensing receptors in wild populations of wood crickets (Nemobius sylvestris) sampled in a wide variety of habitats differing in latitude, litter structure, vegetation and predator communities. These hair receptors act as predator sensors. The observed levels of hair morphological variation were then incorporated into a biomechanical model of the hair canopy response to air flow to predict their influence on cricket predator perception. Cricket populations differ from each other, often strongly so, in the total number of hairs and in the number of hairs longer than 1 mm, which are the hairs most sensitive for the perception of approaching predators. The hair canopy response, the output of the biomechanical model, sums up over the entire canopy the angles of deflection at which a neurophysiological response is triggered and represents the sensitivity of the cercal system. It is 35% higher in the most sensitive population, compared with the least sensitive population. These large differences in perception sensitivity for a given predator signal translate into larger distances at which predators could be perceived. Thus, differences in morphology at the sensor level seem to be translated both at the perception level and subsequently at the performance level of crickets.
Optimal swim speeds for traversing velocity barriers: an analysis of volitional high-speed swimming behavior of migratory fishes
Authors: Castro-Santos Theodore
Published: January 2005

Migrating fish traversing velocity barriers are often forced to swim at speeds greater than their maximum sustained speed (Ums). Failure to select an appropriate swim speed under these conditions can prevent fish from successfully negotiating otherwise passable barriers. I propose a new model of a distance-maximizing strategy for fishes traversing velocity barriers, derived from the relationships between swim speed and fatigue time in both prolonged and sprint modes. The model predicts that fish will maximize traversed distance by swimming at a constant groundspeed against a range of flow velocities, and this groundspeed is equal to the negative inverse of the slope of the swim speed–fatigue time relationship for each mode. At a predictable flow velocity, they should switch from the optimal groundspeed for prolonged mode to that for sprint mode. Data from six migratory fish species(anadromous clupeids: American shad Alosa sapidissima, alewife A. pseudoharengus and blueback herring A. aestivalis; amphidromous:striped bass Morone saxatilis; and potomodromous species: walleye(previously known as Stizostedion vitrium) and white sucker Catostomus commersonii) were used to explore the ability of fish to approximate the predicted distance-maximizing behaviors, as well as the consequences of deviating from the optima. Fish volitionally sprinted up an open-channel flume against fixed flow velocities of 1.5–4.5 m s-1, providing data on swim speeds and fatigue times, as well as their groundspeeds. Only anadromous clupeids selected the appropriate distance-maximizing groundspeed at both prolonged and sprint modes. The other three species maintained groundspeeds appropriate to the prolonged mode, even when they should have switched to the sprint optima. Because of this, these species failed to maximize distance of ascent. The observed behavioral variability has important implications both for distributional limits and fishway design.
Factors reducing the expected deflection in initial orientation in clock-shifted homing pigeons
Authors: Gagliardo Anna , Odetti Francesca , Ioalè Paolo
Published: January 2005

To orient from familiar sites, homing pigeons can rely on both an olfactory map and visual familiar landmarks. The latter can in principle be used in two different ways: either within a topographical map exploited for piloting or in a so-called mosaic map associated with a compass bearing. One way to investigate the matter is to put the compass and the topographical information in conflict by releasing clock-shifted pigeons from familiar locations. Although the compass orientation is in general dominant over a piloting strategy, a stronger or weaker tendency to correct towards the home direction by clock-shifted pigeons released from very familiar sites has often been observed. To investigate which factors are involved in the reduction of the deviation due to clock-shift, we performed a series of releases with intact and anosmic pigeons from familiar sites in unshifted and clock-shifted conditions and a series of releases from the same sites with naive clock-shifted birds. Our data suggest that the following factors have a role in reducing deviation due to the clock-shift: familiarity with the release site, the lack of olfactory information and some unknown site-dependent features.
Mechanics and energetics of swinging the human leg
Authors: Doke Jiro , Donelan J. Maxwell , Kuo Arthur D.
Published: January 2005

We measured how much metabolic energy is expended to swing a human leg. A previous dynamical model of walking predicted that increasing metabolic costs for walking with step length and step frequency trade-off against each other to determine the optimum step combination at a given speed. Simple pendulum dynamics indicate that the cost of walking at high step frequencies could be associated with driving the legs back and forth relative to the body, at a rate increasing approximately with the fourth power of frequency, possibly due to the low economy of producing muscle force for short durations. A similar cost would be expected for isolated swinging of a leg at faster than its natural frequency. We constructed an apparatus to measure work performed on the leg, and measured metabolic cost as human subjects (N=12) swung one leg at frequencies 0.5-1.1 Hz and fixed amplitude. Rate of mechanical work ranged from 0.02-0.27 W kg-1 over these frequencies. Net metabolic rate for leg swinging (subtracting that for quiet standing) increased from 0.41-2.10 W kg-1, approximately with the fourth power of frequency(R2=0.92) and in proportion to a hypothesized cost of force production for short durations. The costs of producing force and work could account for the increase. In a crude comparison, moving the legs back and forth at a typical stride frequency of 0.9 Hz, might consume about one-third of the net energy (2.8±0.8 W kg-1) needed for walking at 1.3 m s-1.
Sodium and anion transport across the avian uterine (shell gland)epithelium
Authors: Vetter Alisen E. , O'Grady Scott M.
Published: January 2005

The uterine (shell gland) epithelium from the domestic chicken was mounted in Ussing chambers, bathed in symmetric avian saline solution on both apical and basolateral aspects and voltage clamped at 0 mV. The epithelium exhibited a basal short circuit current (Isc) that was partially inhibited by the epithelial Na+ channel (ENaC) blockers, amiloride and benzamil (IC50 values of 0.8 and 0.12 μmol l-1,respectively). Inhibition of basal Na+ absorption by 10 μmol l-1 amiloride was confirmed by measurements of transepithelial Na+ and Cl- fluxes, where inhibition of the apical-to-basolateral and net Na+ flux occurred, but no significant effects on Cl- fluxes were detected. The amiloride-insensitive portion of the basal Isc was both Cl- and HCO3- dependent and was inhibited by the Cl-channel blocker, diphenyl-2-carboxylate (DPC; 100 μmol l-1). Stimulation with 8-(4-chlorophenylthio)-cyclic 3′-5′, adenosine monophosphate (8-cpt cAMP) produced a sustained increase in Isc that was dependent on both Cl- and HCO3-. The magnitude of the amiloride-sensitive Isc was approximately twofold greater in birds where shell formation was complete, but oviposition had not yet occurred. In addition, the amiloride-sensitive Isc was greater in hens over the age of 55 weeks and in molting birds. The anion-dependent component of the basal Isc was reduced in older birds, and electrogenic HCO3- transport was nearly absent in molting birds. These results demonstrated that electrogenic Na+ transport in avian shell gland was similar to the mammalian uterine epithelium and increased with age and during molting. Electrogenic Cl- and HCO3- transport were coupled under basal and cAMP stimulated conditions and basal anion transport decreased with age and during molting.