bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain Mechanisms for Social Perception
Authors: Pelphrey Kevin A. , Carter Elizabeth J.
Published: August 2009

In this review, we summarize our research program, which has as its goal charting the typical and atypical development of the social brain in children, adolescents, and adults with and without autism. We highlight recent work using virtual reality stimuli, eye tracking, and functional magnetic resonance imaging that has implicated the superior temporal sulcus (STS) region as an important component of the network of brain regions that support various aspects of social cognition and social perception. Our work in typically developing adults has led to the conclusion that the STS region is involved in social perception via its role in the visual analysis of others' actions and intentions from biological‐motion cues. Our work in high‐functioning adolescents and adults with autism has implicated the STS region as a mechanism underlying social perception dysfunction in this neurodevelopmental disorder. We also report novel findings from a study of biological‐motion perception in young children with and without autism.
Structural Correlates of Implicit Learning Deficits in Subjects with Developmental Dyslexia
Authors: Menghini Deny , Hagberg Gisela E. , Petrosini Laura , Bozzali Marco , Macaluso Emiliano , Caltagirone Carlo , Vicari Stefano
Published: August 2009

Several neuroimaging studies in developmental dyslexia (DD) have mainly focused on brain regions subserving phonological processes. However, additional deficits characterize subjects with DD, such as an impairment of visual and rapid stimuli processing and deficits in implicit learning (IL). Little is known about structural abnormalities in brain regions not directly related to phonology and reading processes. The aim of this study was to investigate, using voxel‐based morphometry, whether subjects with DD exhibit any structural grey matter (GM) abnormalities in regions that have previously shown abnormal functional magnetic resonance imaging (fMRI) activation during an IL task. Significantly smaller GM volumes were found in the right posterior superior parietal lobule and precuneus and in the right supplementary motor area (SMA) of subjects with DD compared to controls. Moreover, a larger GM volume in parietal cortex was associated with an increase of IL effect in controls but not in subjects with DD. These structural abnormalities are consistent with functional changes and reinforce the hypothesis that an impairment of IL might play a relevant role in learning to read.
Morphosyntax and Phonological Awareness in Children with Speech Sound Disorders
Authors: Mortimer Jennifer , Rvachew Susan
Published: August 2009

The goals of the current study were to examine concurrent and longitudinal relationships of expressive morphosyntax and phonological awareness in a group of children with speech sound disorders. Tests of phonological awareness were administered to 38 children at the end of their prekindergarten and kindergarten years. Speech samples were elicited and analyzed to obtain a set of expressive morphosyntax variables. Finite verb morphology and inflectional suffix use by prekindergarten children were found to predict significant unique variance in change in phonological awareness a year later. These results are consistent with previous research showing finite verb morphology to be a sensitive indicator of language impairment in English.
From Loci to Networks and Back Again
Authors: Müller Ralph‐Axel
Published: August 2009

Recent developments in functional imaging as well as the emergence of new anatomical imaging techniques suited for the study of white matter have shifted investigational paradigms from a localized to a more holistic network approach. Aside from detecting local activity, functional MRI can be applied to the study of connectivity. However, the concept of “functional connectivity” remains broad, and specific designs and analyses may affect the results. In addition, connectivity cannot be viewed in isolation. Rather, from a developmental perspective, connectivity and local cortical architecture are intimately related. Therefore, combined approaches examining local organization and connectivity are the most promising avenues for elucidating disturbances of neurofunctional organization in developmental disorders. Here this approach is illustrated via data obtained from autism research that suggest impaired local cortical architecture and reduced long‐range connectivity between cerebral regions.
ADHD and Developmental Dyslexia
Authors: Eden Guinevere F. , Vaidya Chandan J.
Published: August 2009

Academic success and occupational outcome rely on a person's ability to attend to and learn from their surroundings. The cognitive mechanisms underlying these respective skills are impaired in individuals with attention deficit hyperactivity disorder (ADHD) and learning disability (LD). The high co‐occurrence between ADHD and the learning disability developmental dyslexia has raised the possibility of a common etiology. We propose that studying the functional anatomy of disordered executive control and reading‐related skills using carefully selected paradigms, coupled with rigorous studies of intervention efficacy, provide the most promising avenue for ameliorating these two commonly encountered impediments to learning.
Signed Language and Human Action Processing
Authors: Corina David P. , Knapp Heather Patterson
Published: August 2009

In the quest to further understand the neural underpinning of human communication, researchers have turned to studies of naturally occurring signed languages used in Deaf communities. The comparison of the commonalities and differences between spoken and signed languages provides an opportunity to determine core neural systems responsible for linguistic communication independent of the modality in which a language is expressed. The present article examines such studies, and in addition asks what we can learn about human languages by contrasting formal visual‐gestural linguistic systems (signed languages) with more general human action perception. To understand visual language perception, it is important to distinguish the demands of general human motion processing from the highly task‐dependent demands associated with extracting linguistic meaning from arbitrary, conventionalized gestures. This endeavor is particularly important because theorists have suggested close homologies between perception and production of actions and functions of human language and social communication. We review recent behavioral, functional imaging, and neuropsychological studies that explore dissociations between the processing of human actions and signed languages. These data suggest incomplete overlap between the mirror‐neuron systems proposed to mediate human action and language.
A Meta‐analysis of Functional Neuroimaging Studies of Dyslexia
Authors: Maisog José M. , Einbinder Erin R. , Flowers D. Lynn , Turkeltaub Peter E. , Eden Guinevere F.
Published: August 2009

Reading and phonological processing deficits have been the primary focus of neuroimaging studies addressing the neurologic basis of developmental dyslexia, but to date there has been no objective assessment of the consistency of these findings. To address this issue, spatial coordinates reported in the literature were submitted to two parallel activation likelihood estimate (ALE) meta‐analyses. First, a meta‐analysis including 96 foci from nine publications identified regions where typical readers are likely to show greater activation than dyslexics: two left extrastriate areas within BA 37, precuneus, inferior parietal cortex, superior temporal gyrus, thalamus, and left inferior frontal gyrus. Right hemisphere ALE foci representing hypoactivity in dyslexia were found in the fusiform, postcentral, and superior temporal gyri. To identify regions in which dyslexic subjects reliably show greater activation than controls, 75 foci from six papers were entered into a second meta‐analysis. Here ALE results revealed hyperactivity associated with dyslexia in right thalamus and anterior insula. These findings suggest that during the performance of a variety of reading tasks, normal readers activate left‐sided brain areas more than dyslexic readers do, whereas dyslexia is associated with greater right‐sided brain activity. The most robust result was in left extrastriate cortex, where hypoactivity associated with dyslexia was found. However, the ALE maps provided no support for cerebellar dysfunction, nor for hyperactivity in left frontal cortex in dyslexia, suggesting that these findings, unlike those described above, are likely to be more varied in terms of their reproducibility or spatial location.
Phonological Awareness and Short‐Term Memory in Hearing and Deaf Individuals of Different Communication Backgrounds
Authors: Koo Daniel , Crain Kelly , LaSasso Carol , Eden Guinevere F.
Published: August 2009

Previous work in deaf populations on phonological coding and working memory, two skills thought to play an important role in the acquisition of written language skills, have focused primarily on signers or did not clearly identify the subjects' native language and communication mode. In the present study, we examined the effect of sensory experience, early language experience, and communication mode on the phonological awareness skills and serial recall of linguistic items in deaf and hearing individuals of different communicative and linguistic backgrounds: hearing nonsigning controls, hearing users of ASL, deaf users of ASL, deaf oral users of English, and deaf users of cued speech. Since many current measures of phonological awareness skills are inappropriate for deaf populations on account of the verbal demands in the stimuli or response, we devised a nonverbal phonological measure that addresses this limitation. The Phoneme Detection Test revealed that deaf cuers and oral users, but not deaf signers, performed as well as their hearing peers when detecting phonemes not transparent in the orthography. The second focus of the study examined short‐term memory skills and found that in response to the traditional digit span as well as an experimental visual version, digit‐span performance was similar across the three deaf groups, yet deaf subjects' retrieval was lower than that of hearing subjects. Our results support the claim (Bavelier et al., 2006) that lexical items processed in the visual‐spatial modality are not as well retained as information processed in the auditory channel. Together these findings show that the relationship between working memory, phonological coding, and reading may not be as tightly interwoven in deaf students as would have been predicted from work conducted in hearing students.
Development of Ventral Stream Representations for Single Letters
Authors: Turkeltaub Peter E. , Flowers D. Lynn , Lyon Lynn G. , Eden Guinevere F.
Published: August 2009

Visual form recognition is mediated by the ventral extrastriate processing stream. Some regions of ventral stream cortex show preferential activity for specific stimulus categories, but little is known about how this regional specialization develops. Acquisition of letter‐naming skill is of particular interest because letter recognition serves as the gateway to visual processing of words, and fluent letter naming predicts children's reading success. For this reason, we examined the school‐age development of visual letter processing using fMRI. In a 2 × 2 design, we compared ventral stream BOLD activity in two groups, children (n= 22, age 6–11) and adults (n= 15, age 20–22), during two tasks: naming of single letters and naming of simple line drawings of objects. We hypothesized that, based on adults' greater experience with letters, the posterior left fusiform gyrus would be activated more in adults for letter naming than it would be in children. We found that bilateral areas of ventral stream cortex during letter naming were activated in both children and adults and that the midposterior areas of the fusiform gyrus in both hemispheres were activated to a greater degree in adults than in children. There were no areas within the ventral stream in either hemisphere that were activated preferentially for letters over line drawings, nor were there any significant differences in the developmental changes observed for letter naming compared to object naming. These findings indicate that visual processing of single letters continues to develop in both hemispheres during grade school. However, we found no evidence for development of areas specialized for single letter processing. Rather, our findings suggest that letter recognition is performed using the same general form recognition systems as are used to process other visually similar stimuli.
Informed Development of Drugs Acting at Family B G Protein–Coupled Receptors
Authors: Miller Laurence J.
Published: August 2009

Rational refinement and development of receptor‐active ligands can come from high‐resolution insights into the structures of these potential drug targets. Structural insights for Family A G protein–coupled receptors (GPCRs) have been advanced substantially with the recently reported crystal structure of the intact β2‐adrenergic receptor. While high‐resolution structural insights for Family B GPCRs are also advancing, this is currently limited to the functionally important extracellular amino‐terminal tail domain of those receptors. The current report describes how these structures can provide leads for the development of small‐molecule agonist drugs acting at Family B GPCRs. Endogenous agonist activity within the amino terminus of these receptors could be key for the development of such drugs.
Monitoring the State of Cholecystokinin Receptor Oligomerization after Ligand Binding Using Decay of Time‐Resolved Fluorescence Anisotropy
Authors: Harikumar Kaleeckal G. , Miller Laurence J.
Published: August 2009

Oligomeric complexes of G protein–coupled receptors (GPCRs) are now commonly recognized and can provide a mechanism for regulation of signaling systems. Receptor oligomerization has been most extensively studied using coimmunoprecipitation and bioluminescence or fluorescence resonance energy‐transfer techniques. Here, we have utilized decay of time‐resolved fluorescence anisotropy of yellow fluorescent protein‐labeled cholecystokinin receptor constructs to examine the state of oligomerization of this receptor in living cells. The rotational correlation times established that the cholecystokinin receptor is constitutively present in an oligomeric state that is dissociated in response to agonist occupation. In contrast, antagonist occupation failed to modify this signal, leaving the oligomeric structure intact. This dynamic technique complements the other biochemical and steady‐state fluorescence techniques to establish the presence of oligomeric receptor complexes in living cells.
Glutamate and Neurotrophic Factors in Neuronal Plasticity and Disease
Authors: Mattson Mark P.
Published: August 2009

Glutamate's role as a neurotransmitter at synapses has been known for 40 years, but glutamate has since been shown to regulate neurogenesis, neurite outgrowth, synaptogenesis, and neuron survival in the developing and adult mammalian nervous system. Cell‐surface glutamate receptors are coupled to Ca2+ influx and release from endoplasmic reticulum stores, which causes rapid (kinase‐ and protease‐mediated) and delayed (transcription‐dependent) responses that change the structure and function of neurons. Neurotrophic factors and glutamate interact to regulate developmental and adult neuroplasticity. For example, glutamate stimulates the production of brain‐derived neurotrophic factor (BDNF), which, in turn, modifies neuronal glutamate sensitivity, Ca2+ homeostasis, and plasticity. Neurotrophic factors may modify glutamate signaling directly, by changing the expression of glutamate receptor subunits and Ca2+‐regulating proteins, and also indirectly by inducing the production of antioxidant enzymes, energy‐regulating proteins, and antiapoptotic Bcl‐2 family members. Excessive activation of glutamate receptors, under conditions of oxidative and metabolic stress, may contribute to neuronal dysfunction and degeneration in diseases ranging from stroke and Alzheimer's disease to psychiatric disorders. By enhancing neurotrophic factor signaling, environmental factors such as exercise and dietary energy restriction, and chemicals such as antidepressants may optimize glutamatergic signaling and protect against neurological disorders.
Parathyroid Hormone‐Related Protein Regulates Glioma‐Associated Oncogene Transcriptional Activation
Authors: Alman Benjamin A. , Wunder Jay S.
Published: August 2009

Hedgehog and parathyroid hormone‐related protein (PTHrP) signaling play important roles regulating the differentiation of chondrocytes, which form the template for growing bone. By studying the interaction of the pathways in normal and neoplastic growth‐plate chondrocytes (from enchondromas, a benign cartilage tumor), an unexpected direct regulation of  hedgehog‐mediated transcriptional activation by parathyroid hormone‐related protein was uncovered. This regulation acts through the processing of the hedgehog‐activated transcription factor, glioma‐associated oncogene–three (Gli3). When PTHrP activates its receptor, Gli3 is processed to its repressor form though a protein kinase A (PKA) –dependent mechanism. Thus, activation of a G protein–coupled receptor can negatively regulate hedgehog‐mediated transcription independent of hedgehog ligand activity, raising intriguing therapeutic possibilities.
Diverse Mechanisms and Consequences of Immunoadoption of Neuromediator Systems
Authors: Goetzl Edward J. , Chan Robert C. , Yadav Mahesh
Published: August 2009

Modern investigations of the mechanisms of both neuroregulation of immunity and neural effects of immune reactions have focused on identification of the mediators, their receptors, and signal transduction pathways in both systems. Less attention has been directed to delineation of the tissue context of neuroregulation of immunity that determines the principal sources of neuromediators, the physiological consequences of integration of neural and immune activities, and possible approaches to pharmacological manipulation. To illustrate these points, we describe here the corticotropin‐releasing hormone (CRH) and vasoactive intestinal peptide (VIP) axes. When generated by the hypothalamus in response to inflammation or other stresses, CRH is immunosuppressive through its ability to increase levels of glucocorticoids and catecholamines. In contrast, CRH from peripheral nerves and immune accessory cells is immunostimulatory in tissue immune responses through direct effects on macrophages and lymphocytes. VIP released from several sets of nerves is immunosuppressive as a result of actions on macrophages and T cells in lymphoid organs, whereas VIP from immune cells in local tissue responses to antigen enhances development of some types of memory T cells and effector Th17 cells. Better understanding of how tissue context establishes the nature of neuroregulation of immunity will improve neuropharmacological and other neurotherapeutic approaches to immune diseases.
Neuropeptides, Mesenteric Fat, and Intestinal Inflammation
Authors: Karagiannides Iordanes , Pothoulakis Charalabos
Published: August 2009

The ability of fat tissue cells to produce proinflammatory cytokines and the concept that obesity represents a low‐grade inflammatory response have been well documented during the past decade. The effects of fat‐mediated inflammation on metabolic pathologies have also been drawing increasing interest. However, very little is known on the potential effects of adipose tissue in the pathophysiology of gastrointestinal diseases with an inflammatory component, such as inflammatory bowel disease (IBD). The development of large fat masses around the inflamed intestine during Crohn's disease makes this tissue a candidate for more intense investigation in studies aiming to gain insights into the pathogenesis and progress of the disease. Furthermore, neuropeptides act in many cases in a proinflammatory manner and are shown to participate in the pathogenesis of intestinal inflammation in animal models of IBD. However, the potential of these molecules to interact with fat cells in the context of IBD has not been investigated. In this review the authors' most recent data related to the effects of neuropeptides on noninflammatory fat tissue components are described. In addition, a discussion to associate neuropeptide‐induced, adipose tissue–mediated responses with the generation of intestinal inflammatory conditions such as Crohn's disease is included.
Inhibitory Effects of a Neurokinin‐1 Receptor Antagonist on Postoperative Peritoneal Adhesion Formation
Authors: Reed Karen L. , Stucchi Arthur F. , Leeman Susan E. , Becker James M.
Published: August 2009

Intra‐abdominal adhesions are a costly, long‐term sequela of abdominal surgeries. They occur in up to 94% of patients following abdominal operation and cause significant postoperative morbidity including difficult reoperative surgeries, small bowel obstructions, and infertility. The pathophysiology of adhesion formation remains poorly defined, and a uniformly effective method of adhesion prevention does not exist. Research focused on understanding the mechanisms underlying adhesion formation is essential for the development of safe and effective therapeutic approaches to adhesion prevention. The proinflammatory peptide substance P (SP), known to participate in inflammatory and wound‐healing events, may contribute to the early processes of adhesion formation. SP is the most widely studied ligand of the neurokinin‐1 receptor (NK‐1R), and we have determined in a rat model that intraoperative administration of an NK‐1R antagonist, CJ‐12–255 (Pfizer), that blocks ligand binding to the NK‐1R, significantly reduces adhesion formation. It also has been determined that animals administered the NK‐1R antagonist intraperitoneally have increased peritoneal fibrinolytic and matrix metalloproteinase activities, and reduced levels of oxidative stress postoperatively, all of which may contribute to the observed reduction in adhesion formation. Studies suggest that intra‐abdominal adhesion formation begins within hours of surgery and that the regulation of fibrin deposition, and degradation is of key importance. A pharmacologic agent, such as an NK‐1R antagonist, administered at the time of surgery that could augment postoperative peritoneal fibrinolytic activity without compromising wound healing, would be a beneficial tool in the prevention of postoperative adhesions.
Experimental Therapeutic Strategies for Severe Sepsis
Authors: Parrish William R. , Gallowitsch‐Puerta Margot , Czura Christopher J. , Tracey Kevin J.
Published: August 2009

Severe sepsis is the leading cause of mortality in intensive care units. The limited ability of current therapies to reduce sepsis mortality rates has fueled research efforts for the development of novel treatment strategies. Through the close collaboration between clinicians and scientists, progress can be seen in the struggle to develop effective therapeutic approaches for the treatment of sepsis and other immune and inflammatory disorders. Indeed, significant advances in intensive care, such as lung protective mechanical ventilation, improved antibiotics, and superior monitoring of systemic perfusion, are improving patient survival. Nonetheless, specific strategies that target the pathophysiological disorders in sepsis patients are essential to further improve clinical outcomes. This article reviews current clinical management approaches and experimental interventions that target pleiotropic or late‐acting inflammatory mediators like caspases, C5a, MIF, and HMGB1, or the body's endogenous inflammatory control mechanisms such as the cholinergic anti‐inflammatory pathway. These inflammatory mediators and anti‐inflammatory mechanisms, respectively, show significant potential for the development of new experimental therapies for the treatment of severe sepsis and other infectious and inflammatory disorders.
Activation of the Proopiomelanocortin Gene with Ketoconazole as a Treatment for Parkinson's Disease
Authors: Bucay Alberto Halabe
Published: August 2009

Parkinson's disease is a neurodegenerative process characterized by progressive degeneration of the substantia nigra and concurrent loss of neuromelanin in these structures. The present hypothesis suggests that progression of Parkinson's disease may be reduced by enhancing the regional levels of neuroprotective factors derived from proopiomelanocortin (POMC). One practical means to accomplish this goal may be administration of ketoconazole or other inhibitors of corticosteroid synthesis at doses sufficient to stimulate hypophyseal secretion of  POMC. The POMC constituents adrenocorticotropic hormone (ACTH) and melanocycle‐stimulating hormone (MSH), which mobilize neuromelanin generation and lipotropins, those motivating lipid components of neuromelanin and endorphin, which then together stimulate and protect neural components of the substantia nigra.
Prenatal Alcohol Exposure Increases Vulnerability to Stress and Anxiety‐Like Disorders in Adulthood
Authors: Hellemans Kim G.C. , Verma Pamela , Yoon Esther , Yu Wayne , Weinberg Joanne
Published: August 2009

Children and adults with fetal alcohol spectrum disorder (FASD) have elevated rates of depression and anxiety disorders compared to control populations. The effects of prenatal alcohol exposure (PAE) on anxiety, locomotor activity, and hormonal reactivity in male and female rats tested on the elevated plus maze (EPM), a task commonly used to assess anxiety‐like behaviors in rodents, were examined. Pregnant dams were assigned to PAE, pair‐fed (PF), or ad libitum‐fed control (C) groups. At adulthood, half of all male (N= 60) and female (N= 60) PAE, PF, and C offspring were exposed to 10 days of chronic mild stress (CMS); the other half remained undisturbed. Animals were then tested on the EPM, and blood collected 30 min posttest for analysis of corticosterone (CORT), testosterone, estradiol, and progesterone. Overall, CMS exposure produced a significant anxiogenic profile. Moreover, CMS increased anxiety‐like behavior in PAE males and females compared to controls and eliminated the locomotor hyperactivity observed in nonstressed PAE females. CMS also increased post‐EPM CORT, testosterone, and progesterone levels in all groups, with CORT and progesterone levels significantly higher in PAE than in C females. By contrast, CMS selectively lowered estradiol levels in PAE and PF, but not C, females. CMS exposure reveals sexually dimorphic behavioral and endocrine alterations in PAE compared to C animals. Together, these data suggest the possibility that fetal reprogramming of hypothalamic–pituitary–adrenal (HPA) and –gonadal (HPG) systems by alcohol may underlie, at least partly, an enhanced susceptibility of fetal alcohol‐exposed offspring to depression/anxiety‐like disorders in adulthood.
Substance P in Stress and Anxiety
Authors: Ebner Karl , Muigg Patrik , Singewald Georg , Singewald Nicolas
Published: August 2009

In a previous work it was demonstrated that emotional stressors trigger thein vivorelease of the neuropeptide substance P (SP) in brain areas known to be implicated in stress and anxiety mechanisms, such as the amygdala, lateral septum, nucleus accumbens, and locus coeruleus. However, the specific role of SP within the hypothalamic paraventricular nucleus (PVN), the critical site of the neuroendocrine stress axis, is unclear. Studies performed in neurokinin‐1‐receptor (NK‐1R) knockout mice have provided conflicting results. Therefore, the aim of the present study was to use a pharmacological approach and examine whether intracerebroventricular NK‐1R‐antagonist treatment modulates stress‐induced neuronal activity in key brain areas of the stress circuitry, including the PVN. The elevated plus maze test was used as a mild stressor known to stimulate stress hormone secretion and c‐Fos‐expression in the PVN and simultaneously to obtain behavioral readout for anxiety‐like behavior. Results demonstrate an anxiolytic‐like effect of intracerebral NK‐1R antagonism that is associated with an attenuation of the stress‐induced c‐Fos expression in the PVN and lateral septum. In the amygdala and the bed nucleus of stria terminalis, c‐Fos induction by elevated plus maze exposure was much lower and was not influenced by NK‐1R‐antagonist treatment. Thus, our findings provide clear evidence that central NK‐1R‐blockade reduces neuronal activity in key brain areas of the stress circuitry, which is thought to be associated with attenuation of the neuroendocrine stress response. These findings support the idea that a stress‐sensitive subset of the human psychiatric patients may particularly benefit from a pharmacological approach that interfers with SP transmission.
Gastrin‐Releasing Peptide, Immune Responses, and Lung Disease
Authors: Degan Simone , Lopez Giselle Y. , Kevill Katharine , Sunday Mary E.
Published: August 2009

Gastrin‐releasing peptide (GRP) is produced by pulmonary neuroendocrine cells (PNECs), with highest numbers of GRP‐positive cells present in fetal lung. Normally GRP‐positive PNECs are relatively infrequent after birth, but PNEC hyperplasia is frequently associated with chronic lung diseases. To address the hypothesis that GRP mediates chronic lung injury, we present the cumulative evidence implicating GRP in bronchopulmonary dysplasia (BPD), the chronic lung disease of premature infants who survive acute respiratory distress syndrome. The availability of well‐characterized animal models of BPD was a critical tool for demonstrating that GRP plays a direct role in the early pathogenesis of this disease. Potential mechanisms by which GRP contributes to injury are analyzed, with the main focus on innate immunity. Autoreactive T cells may contribute to lung injury late in the course of disease. A working model is proposed with GRP triggering multiple cell types in both the innate and adaptive immune systems, promoting cascades culminating in chronic lung disease. These observations represent a paradigm shift in the understanding of the early pathogenesis of BPD, and suggest that GRP blockade could be a novel treatment to prevent this lung disease in premature infants.
Opportunities and Challenges in the Discovery of New Central Nervous System Drugs
Authors: Krause James E. , Chenard Bertrand L.
Published: August 2009

There have been relatively few new mechanism‐based approvals for nervous system relevant drugs over the past 5 years, despite the increasing budgets of pharmaceutical and biotechnology companies. The genomic revolution has provided scientists with many molecular targets for drug discovery and research advances in chemistry, drug metabolism, pharmacology, and toxicology have provided much insight into understanding the pitfalls of the drug discovery and development process. Herein is provided a perspective on both the opportunities and challenges in the discovery and development of novel medicines for the treatment of human CNS disorders.
Diseases of Backyard Turkeys in the Mexican Tropics
Authors: Camacho‐Escobar Marco A. , Arroyo‐Ledezma Jaime , Ramirez‐Cancino Laura
Published: August 2009

With the purpose of identifying the causes of disease and death in backyard turkeys, 768 interviews with growers were carried out in communities of the coastal region of Oaxaca, Mexico. Later, a clinical sanitary evaluation was performed on five randomly selected turkeys of different age and sex. The laboratory tests included: necropsy for clinical diagnosis of diseases and for a histopathological examination of tissues with macroscopic lesions to identify microscopic lesions; hemagglutination inhibition tests to diagnose Newcastle disease and avian influenza; agglutination test to identify Mycoplasma gallisepticum, M. synoviae, and Salmonella pullorum; and enzyme‐linked immunosorbent assay to identify infectious bronchitis and infectious bursal disease. Both internal and external parasites were identified. The data obtained by the interviews showed that sudden death, avian pox, respiratory disease, and diarrhea were the most important manifestations in backyard turkeys. The laboratory tests found avian pox, avian influenza, and infectious bronchitis; sensitivity to M. synoviae and M. gallisepticum; protozoal infections by Eimeria meleagridis and E. dispersa; internal parasite infestation by Heterakis gallinae and Ascaridia gallinae; and mycotoxicoses.
Virulence of Metarhizium anisopliae to Eggs and Immature Stages of Stomoxys calcitrans
Authors: Moraes Ana Paula R. , Angelo Isabele da C. , Fernandes Éverton K. K. , Bittencourt Vânia R. E. P. , Bittencourt Avelino J.
Published: August 2009

Stomoxys calcitrans control is primarily based on the use of chemical products; however, new methods for control have been investigated. Biological control has been proposed as a promising alternative to traditional chemicals. The current study evaluated three methods in vitro to treat S. calcitrans eggs with the fungus Metarhizium anisopliae and assessed the virulence of this fungus to immature stages of this fly. In the first method of egg exposure, eggs were immersed in conidial suspensions and transferred to Petri plates with high humidity. A high mortality was observed in both treated and control groups. In the second method, the eggs were transferred to rearing medium right after immersion in conidial suspensions; the suspensions with highest conidial concentrations, 107 and 108 conidia mL−1, caused 96.25% and 100% mortality, respectively. In the third method, the eggs were sprayed with conidial suspensions on the rearing medium. A high mortality was observed at 107 and 108 conidia mL−1, 78.3% and 100%, respectively. The second method had the lowest mortality in the control group and was considered the most useful method for evaluating the effect of entomopathogenic fungi on S. calcitrans eggs. While eggs were very susceptible to M. anisopliae infection, larvae and pupae were not.
Virulence of Metarhizium anisopliae and Beauveria bassiana to Ctenocephalides felis felis
Authors: De Melo Denise R. , Fernandes Éverton K. K. , Da Costa Gisela L. , Scott Fabio B. , Bittencourt Vânia R. E. P.
Published: August 2009

Ctenocephalides felis felis is a flea species that parasitizes dogs and cats. The current study verified the in vitro virulence of the entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana to eggs and adults of C. felis felis. The fungal isolates were cultivated on rice grains in plastic bags. Conidial suspensions were then prepared by immersing the grains in Tween 80 aqueous solution (0.01%). Eggs and adults of C. felis felis were obtained from a laboratory colony. Experiments were composed of one control and four treatment groups (105, 106, 107, and 108 conidia mL−1). Both insect pathogens inhibited egg hatchability and caused adult mortality. Among isolates used in this study, M. anisopliae (isolate E9) was the most successful at inhibiting hatching, while B. bassiana (isolate 986) was the most powerful for causing mortality in adults. The results indicate that these entomopathogenic fungi have promising potential for use in controlling both C. felis felis egg and adult stages.
Milk Production Increase in a Dairy Farm under a Six‐Year Brucellosis Control Program
Authors: Herrera Enrique , Palomares Gabriela , Díaz‐Aparicio Efrén
Published: August 2009

The present work aims to quantify milk production in a bovine dairy herd during a 6‐year brucellosis control program in Hidalgo, Mexico, where bovine brucellosis is endemic. This 6‐year longitudinal pilot study comprised 74 monthly samplings to determine the incidence of brucellosis and to quantify daily milk production. To determine the monthly incidence of brucellosis, an average of 346 Holstein cows was examined each month with the card and Rivanol tests. These animals had been vaccinated as calves with the normal dose of Brucella abortus RB51 and were revaccinated annually with a reduced dose. Brucellosis is endemic in Mexico, where the control programs include vaccination and diagnosis; nevertheless, it is uncommon to carry out other essential control practices, such as separation and elimination of positive cows. In this herd, the cows positive to the card and rivanol tests were separated in specific units, especially at the moment of delivery. These cows were placed at the end of the line for milking and were eliminated from the herd at the end of their productive cycle. In this dairy herd, cows were milked three times a day and there was a monthly average of 300 cows in production. At the beginning of this study the prevalence of brucellosis was 8.43%; from days 180–330 the incidence was from 0.51% to 0.90%. Between days 360–570, the incidence diminished to 0%; between days 600 to 1140, it increased to 4.46%; and from days 1440 to 2220 the incidence was kept beneath 1%. The average of dairy milk production for each cow per day started with 24 L, increasing in direct proportion to the decrease in the presence of new cases of brucellosis: in the subsequent years, the production increased successively to 25, 27, 28, 29, and 30 L. The daily average per year of milk production in the herd was also quantified: at the beginning of the study it was 7220 L and in subsequent years was 7470, 7710, 8340, 8790, 8970, and 9150 L, respectively. We conclude that a direct relation existed between the application of a program of brucellosis control and the increase in milk production.
Prevalence of Pathogens Associated with Bovine Mastitis in Bulk Tank Milk in Mexico
Authors: Miranda‐Morales Rosa E. , Rojas‐Trejo Verónica , Segura‐Candelas Raúl , Carrillo‐Casas Erika M. , Sánchez‐Gonzalez Ma Guadalupe , Castor Rafael S. , Trigo‐Tavera Francisco J.
Published: August 2009

Mastitis as cause of low milk production coupled with the use of medication to control it cause dairy farms to register large economic losses. Microorganisms' prevalence, and somatic cell counts (SCCs) were determined in 112 Holstein bovine herds in two bulk tank milk‐screening assays. Detection ofStaphylococcus aureus,Streptococcus agalactiae, andMycoplasmaspp. as microorganisms primarily responsible for clinical and subclinical mastitis and their relationship with SCCs was evaluated by Student'st‐test and the kappa test. Prevalence ofMycoplasmawas 55%; ofS. aureus,30%; ofStreptococcus uberis,37.5%; and ofStaphylococcuscoagulase‐negative, 38.3%. The geometric mean of the SCC was 465,000 cells/mL. No significant differences were observed in the SCCs between the positive and negative samples of pathogens isolated (P> 0.5). There was a low kappa value ofMycoplasmacorrelation between samplings (kappa value = 0.10). This work aimed to understand the relationship between the prevalence of mastitis pathogens in bulk tank milk and SCCs in bovine herds in the central part of Mexico.
Prevention of Blackleg by an Immunogen ofClostridium chauvoei
Authors: Corpus Ma. de Lourdes Ontiveros , Andrade Laura Hernández , Mendez Jaime López , Gutierrez Victor Tenorio
Published: August 2009

Diseases in livestock caused byClostridiumspp. are of concern in Mexico. There are no good‐quality vaccines against these infections, and for this reason several outbreaks have occurred in recent years. The objective of this work was to study the immunogenic capacity of a 156‐kDa recombinant protein ofClostridium chauvoeithat has shown 80% protection against this disease in guinea pigs. This immunogenic protein was cloned in the expression vector pBluescript and was used to immunizeC. chauvoei–free bovine animals that were kept in an endemic area. Three experimental groups were studied. In group 1, 30 bovines were vaccinated by subcutaneous route with one dose of 350 μg/animal of the recombinant protein of 156 kDa. In group 2, 30 bovines were vaccinated with the same concentration of this protein plus aluminium hydroxide as adjuvant. Group 3 was vaccinated with a commercial bacterin by intramuscular route with a dose of 5 mL/animal. In each group, five animals were inoculated with saline solution and remained as controls without vaccination. Blood samples were obtained each month during a 6‐month period. Serum samples were analyzed by agglutination test and Western blotting. The recombinant protein of 156 kDa was recognized by serum samples from all the animals in groups 1 and 2. Only two animals from group 3 recognized this protein. During the time of the experiment any cases of this disease were observed. However, other studies with a longer time or greater stress conditions that would favor occurrence of the disease would be required to confirm whether this immunogen is also protective in bovines.
Human Brucellosis in Urban and Peri‐Urban Areas of Kampala, Uganda
Authors: Makita Kohei , Fèvre Eric Maurice , Waiswa Charles , Kaboyo Winyi , De Clare Bronsvoort Barend Mark , Eisler Mark Charles , Welburn Susan Christina
Published: August 2009

A retrospective case–control study of human brucellosis in urban, peri‐urban, and rural areas in Kampala, Uganda was undertaken to find the risks associated with the disease using the medical records of Mulago National Referral Hospital (Mulago Hospital). From the Brucella agglutination test (BAT) records between June 2004 and May 2006, 652 positive results were found. The case–control study showed that living in urban areas was a risk factor for brucellosis. The numbers of improved and cross‐breed cattle per 1000 households were calculated on the basis of data obtained from interviews of 75 randomly selected local councils (LCls) in an area between 5 and 20 km radii from the city center of Kampala. Cattle‐keeping activities were, however, unpopular in urban areas compared to peri‐urban and rural areas. Poor correlation between the distribution of human brucellosis cases and the distribution of cattle suggested that most of the brucellosis cases resulted from consumption of raw milk transported from peri‐urban and rural areas of Kampala and/or dairy production areas outside Kampala.
Existence of Splicing Variants in Homologues of Theileria lestoquardi Clone‐5 Gene's Transcripts in Theileria annulata and Theileria parva
Authors: Bakheit Mohammed A. , Ahmed Jabbar S. , Seitzer Ulrike
Published: August 2009

Clone 5 has been described as an immunogenic protein and was used to establish an ELISA for malignant theileriosis. Molecular characterization of the gene product revealed alternative splicing at the single intron resulting in two mRNA transcripts, translating into a long and a short protein form. Homologues of clone 5 exist in Theileria annulata and T. parva according to the available annotated GenBank sequences, showing however only the long protein forms in these parasites (GenBank accession numbers CAI73679, EAN33624). The present study aimed to determine whether two splice variants of homologues of clone 5 occur in T. annulata and T. parva.
Small‐scale Expressed Sequence Tag Analysis of Theileria uilenbergi: Identification of a Gene Family Encoding Potential Antigenic Proteins
Authors: Liu Zhijie , Dang Zhisheng , Luo Jianxun , Yin Hong , Ahmed Jabbar S. , Seitzer Ulrike
Published: August 2009

Recently, Theileria sp. (China) has been designated as T. luwenshuni[formerly Theileria sp. (China 1)] and T. uilenbergi[formerly Theileria sp. (China 2)]. A cDNA library of T. uilenbergi merozoites was constructed and subjected to random sequencing. Among the obtained sequences were three highly identical cDNA clones, indicating a gene family. Bioinformatic analyses indicated these genes contain signal peptides and encode potential immunogenic proteins. The presence of tandemly arranged and additional variants of these genes was shown. Analysis of one recombinantly expressed clone revealed immunoreactivity for serum from Theileria‐infected animals. No cross‐reaction with serum of T. lestoquardi‐, Babesia motasi‐, or Anaplasma ovis‐infected animals was observed, indicating a potential antigen for development of serological diagnostic tools.
Cutaneous Basophilia in the Resistance of Goats to Amblyomma cajennense Nymphs after Repeated Infestations
Authors: Monteiro Gaby E. R. , Bechara Gervásio H.
Published: August 2009

The acquisition of resistance in goats against Amblyomma cajennense after repeated infestations and the role of inflammatory cells in this mechanism were investigated. Ten naive goats aged 6 months were distributed into two groups: test (n= 5), infested thrice at 30‐day intervals; and control (n= 5), infested once. Nymphs (n= 115 per animal per infestation) were released inside alimentary chambers glued to the animal's dorsum and the following biological parameters were evaluated: yielding rate, nymphal engorgement weight, engorgement period, ecdise rate, and ecdise period. Skin fragments of tick bite sites were collected at 24, 48, 72, and 120 h post attachment for histopathology and inflammatory cells counts. The engorgement weight decreased significantly (P < 0.05) from the first infestation onward; nymphs weighed 41.7% and 37.1% less after the second and third infestations, respectively, as compared to those collected after the first infestation (12.55 mg ± 3.21). Furthermore, the ecdise period increased significantly (P < 0.05) in the third infestation (18 days ± 2.83) in comparison with the first infestation (15 days ± 0.82) and the ecdise rate was significantly lower after the second infestation (71.91%± 17.38) in comparison with the first infestation (96.89%± 3.38). There were no significant differences with regard to both the engorgement period and yielding rate. A cutaneous basophilia was evidenced between 48 and 72 h (P < 0.05) after both the second and third infestations. We conclude that goats develop resistance against nymphs of A. cajennense and that basophils may play an important role in such a mechanism.
Guinea Pigs Develop Cutaneous Basophilia after Repeated Infestations by Nymphs of the Tick Amblyomma triste
Authors: Otávio Flávio S. , Bechara Gervásio H.
Published: August 2009

This study investigated the development of resistance in guinea pigs to nymphs of Amblyomma triste ticks after repeated infestations. Guinea pigs were infested thrice, at 30‐day intervals, with 30 nymphs of A. triste per animal per infestation. Acquisition of resistance was evaluated by determining: nymph yielding rate, engorgement period, and weight. Skin biopsies of tick bite sites were collected at 24, 48, and 96 h after tick attachment for inflammatory cell counts. Engorged nymphs weighed 5.53 mg ± 1.9 in re‐infested hosts (56.6% less than in primary infestation) and took 6.9 days ± 2.16 to feed in the third infestation (14.5% more than in the first infestation). Guinea pigs yielded 78%± 7.2 of nymphs in the re‐infestation (11.6% less than in the primary infestation). In addition, a marked increase in basophil influx was observed from the first infestation onward; 69% of infiltrated cells were basophils in re‐infested hosts 24 h after tick attachment. No basophils were seen at this time in primary infested animals. That number increased to 84.7% 48 h post attachment in re‐infested hosts (73.2% more than in the primary infested ones) and decreased markedly 96 h post attachment in both groups (2.6% and 1% of basophils in the third and first infestation, respectively). We conclude that guinea pigs acquire resistance against nymphs of A. triste ticks after repeated infestations and that a cutaneous basophilia must play a crucial role in such a mechanism.