Cellular mechanisms of epiboly in leech embryos

Gastrulation in leech embryos is dominated by the epibolic movements of two tissues: germinal bands, composed of segmental precursor cells, and an overlying epithelium that is part of a provisional integument. During gastrulation, the germinal bands move over the surface of the embryo and coalesce along the prospective ventral midline. Concurrently, the epithelium spreads to cover the embryo. We have begun to analyze the mechanisms involved in gastrulation in the leech by assessing the independent contributions of the epithelium and the germinal bands to these cell movements. Here we describe cellular events during epiboly in normal embryos and in embryos perturbed by either reducing the number of cells in the epithelium, or by preventing the formation of the germinal bands, or both. These experiments indicate that both the germinal bands and the epithelium are able to undergo epibolic movements independently, although each is required for the other to behave as in control embryos.     

Homeobox genes in the ribbonworm Lineus sanguineus: evolutionary implications

From our current understanding of the genetic basis of development and pattern formation in Drosophila and vertebrates it is commonly thought that clusters of Hox genes sculpt the morphology of animals in specific body regions. Based on Hox gene conservation throughout the animal kingdom it is proposed that these genes and their role in pattern formation evolved early during the evolution of metazoans. Knowledge of the history of Hox genes will lead to a better understanding of the role of Hox genes in the evolution of animal body plans. To infer Hox gene evolution, reliable data on lower chordates and invertebrates are crucial. Among the lower triploblasts, the body plan of the ribbonworm Lineus (nemertini) appears to be close to the common ancestral condition of protostomes and deuterostomes. In this paper we present the isolation and identification of Hox genes in Lineus sanguineus. We find that the Lineus genome contains a single cluster of at least six Hox genes: two anterior-class genes, three middle-class genes, and one posterior-class gene. Each of the genes can be definitely assigned to an ortholog group on the basis of its homeobox and its flanking sequences. The most closely related homeodomain sequences are invariably found among the mouse or Amphioxus orthologs, rather than Drosophila and other invertebrates. This suggests that the ribbonworms have diverged relatively little from the last common ancestors of protostomes and deuterostomes, the urbilateria.     

Self-regulation of response patterning: implications for psychophysiological research and therapy

This paper develops the basic premise that learning to self-regulate a pattern of responses can have different consequences from those observed when controlling individual functions alone. It is suggested that the self-regulation of patterns of responses can be a particularly sensitive and effective procedure for (a) uncovering biological linkages and constraints between responses in the intact human, (b) investigating how multiphysiological systems combine to produce unique subjective experiences and effects on performance, and (c) enhancing the clinical effectiveness of biofeedback procedures by training patients to integrate and coordinate voluntarily specific patterns of cognitive, autonomic, and motor responses. These hypotheses are illustrated by basic research involving biofeedback training for patterns of blood pressure, heart rate and EEG activity, related experiments on the cognitive self-regulation of patterns of physiological responses using affective imagery and meditation procedures, and case studies of patients treated with biofeedback. The concept of electronic biofeedback as an "unnatural act" is presented with the goal of placing self-regulation within a more biobehavioral perspective emphasizing the natural patterning of physiological processes.     

Neuromodulation of hypoglossal motoneurons: cellular and developmental mechanisms

Hypoglossal motoneurons (HMs) in the caudal brainstem have a respiratory-related activity pattern and contribute to control of upper airway resistance. In this review, we focus primarily on signalling mechanisms utilized by neurotransmitters to enhance HM excitability. In particular, we consider: (1) the membrane depolarization induced by a number of different putative transmitters [thyrotropin-releasing hormone (TRH), serotonin (5-HT), norepinephrine (NE)]; and (2) the inhibition of a calcium-dependent spike after hyperpolarization (AHP) by 5-HT and its effect on firing behavior. Potential functional consequences on HM behavior of these different neurotransmitter effects is discussed. In addition, we describe postnatal changes in transmitter effects and suggest potential cellular mechanisms to explain those developmental changes. Most of the data discussed are derived from in vitro electrophysiological recordings performed in preparations from neonatal and adult rats.     

Binuclear Drosophila oocytes: consequences and implications for dorsal-ventral patterning in oogenesis and embryogenesis

The position of the nucleus along the anterior rim of stage 8 Drosophila oocytes presages the dorsal side of the egg and the developing embryo. In this paper, we address the question of whether the oocyte has a previously determined dorsal side to which the nucleus is drawn, or whether nuclear position randomly determines the dorsal side. To do so, we have taken advantage of a genetic system in which Drosophila oocytes occasionally become binuclear. We find that (i) the two nuclei migrate independently to their respective positions on the anterior rim, sometimes selecting the same site, sometimes not, (ii) the two nuclei are equivalent in their ability to induce a dorsal-ventral pattern in the overlying follicular epithelium, and (iii) at any position around the anterior circumference of the egg chamber the follicle cell sheet is equally responsive to the Gurken signal associated with the oocyte nuclei. These results argue that the dorsal-ventral axis is determined arbitrarily by the randomly selected position of the nucleus on the anterior rim of the oocyte. Some of the binuclear eggs support embryonic development. However, despite the duplication of dorsal chorion structures, the majority of such embryos show normal dorsal-ventral patterning. Thus, processes exist in the ventral follicular epithelium or in the perivitelline space that compensate for the expansion of dorsal follicle cell fates and consequently allow the formation of a normal embryonic axis.     

Hyperthermia in the chick embryo: HSP and possible mechanisms of developmental defects

PURPOSE: To report a case of isolated inferior rectus palsy secondary to a metastasis to the oculomotor nucleus. METHODS: Case report. A 41-year-old woman with a history of breast cancer presented with acute onset of left hypotropia and exotropia. RESULTS: Forced generation testing confirmed weakness of the right inferior rectus muscle that was not reversed by intravenous edrophonium infusion. Magnetic resonance imaging disclosed numerous metastatic lesions to the cerebral hemispheres and brainstem. One lesion in the right midbrain was adjacent to the cerebral aqueduct in the right oculomotor nucleus. CONCLUSION: Metastasis to the oculomotor nucleus is a rare cause of isolated inferior rectus palsy; however, this entity should be considered in the differential diagnosis of an isolated inferior rectus palsy because of the life-threatening consequences of a brainstem lesion.     

Understanding developmental psychopathology: how useful are evolutionary accounts?

OBJECTIVE: To consider the power of principles derived from evolutionary biology to explain the causes and determinants of some forms of child and adolescent mental disorders. METHOD: The authors reviewed the scientific literature for evolutionary mechanisms proposed to contribute to the pathogenesis of early-onset disorders. RESULTS: A diverse set of evolutionary mechanisms has been proposed. With the exception of certain genetically determined conditions, many of the proposed mechanisms have little empirical data to support them. One mechanism focuses on the vulnerabilities associated with conserved behavior patterns, such as separation anxiety and other alarm responses. These behavioral patterns are adaptive if they appear in some situations, but not in others. Other attractive theories include a co-optation of underlying neurobiology systems (substance abuse), environmental shifts (transformation of present day environments away from primeval environments), and evolutionary arms races as may occur in putative autoimmune disorders with neuropsychiatric sequelae. CONCLUSIONS: Evolutionary biology provides a potentially powerful framework for understanding disease pathogenesis in child psychiatry and should permit the integration of new knowledge from a broad range of scientific disciplines. Evolutionary explanations are typically population-based and fail to account for why a particular individual is disciplines. Evolutionary explanations are typically population-based and fail to account for why a particular individual is affected. Consequently, any adequate account of disease pathogenesis requires that environmental events that impinge on CNS development be considered. Finally, the empirical testing of specific theories may prove to be difficult if not impossible.     

The origins of primitive blood in Xenopus: implications for axial patterning

The marginal zone in Xenopus laevis is proposed to be patterned with dorsal mesoderm situated near the upper blastoporal lip and ventral mesoderm near the lower blastoporal lip. We determined the origins of the ventralmost mesoderm, primitive blood, and show it arises from all vegetal blastomeres at the 32-cell stage, including blastomere C1, a progenitor of Spemann's organizer. This demonstrates that cells located at the upper blastoporal lip become ventral mesoderm, not solely dorsal mesoderm as previously believed. Reassessment of extant fate maps shows dorsal mesoderm and dorsal endoderm descend from the animal region of the marginal zone, whereas ventral mesoderm descends from the vegetal region of the marginal zone, and ventral endoderm descends from cells located vegetal of the bottle cells. Thus, the orientation of the dorsal-ventral axis of the mesoderm and endoderm is rotated 90( degrees) from its current portrayal in fate maps. This reassessment leads us to propose revisions in the nomenclature of the marginal zone and the orientation of the axes in pre-gastrula Xenopus embryos.     

Social justice in practicum training: Competencies and developmental implications.

This article addresses the challenge in the predoctoral education of professional psychologists of providing practicum training experiences with a strong social justice focus while also ensuring that students are acquiring the full range of foundational competencies expected of practicing psychologists. The theory-based distinction between interactional, procedural, and distributive justice will be discussed as a framework for considering a developmental progression in practicum training, moving from individually focused skills to more advanced competencies emphasizing social/institutional change. The article concludes with aspirational recommendations for any academic program seriously committed to the pursuit of social justice as part of its training mission. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

S-adenosylmethionine synthesis: molecular mechanisms and clinical implications

Methionine adenosyltransferase (MAT) is an ubiquitous enzyme that catalyzes the synthesis of S-adenosylmethionine from methionine and ATP. In mammals, there are two genes coding for MAT, one expressed exclusively in the liver and a second enzyme present in all tissues. Molecular studies indicate that liver MAT exists in two forms: as a homodimer and as a homotetramer of the same oligomeric subunit. The liver-specific isoenzymes are inhibited in human liver cirrhosis, and this is the cause of the abnormal metabolism of methionine in these subjects.     

Spontaneous platelet aggregation in arterial insufficiency: mechanisms and implications

To investigate the clinical implications and mechanisms of spontaneous platelet aggregation (SPA) in man, 150 normal subjects, 22 patient controls and 130 patients with vascular insufficiency were studied. SPA was negative in normal subjects and patient controls whereas it was positive in 36 of 66 (54%) patients with transient ischemic attacks, 6 of 32 (19%) patients with stable angina, 7 of 10 (70%) patients with acute myocardial infarction and 11 of 14 (80%) patients with acute peripheral arterial insufficiency. The SPA was inhibited with aspirin in vivo, and inhibited competitively in vitro by low concentrations of aspirin, 2-chloroadenosine, prostaglandin E1 or apyrase but only by high concentrations of heparin or hirudin. Addition of platelet-poor plasma from patients with positive SPA did not cause normal platelets to aggregate. Treatment of patients who had acute peripheral arterial insufficiency with aspirin and dipyridamole prevented SPA with notable clinical improvement of the ischemic changes.     

A mixed disulfide bond in bacterial glutathione transferase: functional and evolutionary implications

BACKGROUND: Glutathione S-transferases (GSTs) are a multifunctional group of enzymes, widely distributed in aerobic organisms, that have a critical role in the cellular detoxification process. Unlike their mammalian counterparts, bacterial GSTs often catalyze quite specific reactions, suggesting that their roles in bacteria might be different. The GST from Proteus mirabilis (PmGST B1-1) is known to bind certain antibiotics tightly and reduce the antimicrobial activity of beta-lactam drugs. Hence, bacterial GSTs may play a part in bacterial resistance towards antibiotics and are the subject of intense interest. RESULTS: Here we present the structure of a bacterial GST, PmGST B1-1, which has been determined from two different crystal forms. The enzyme adopts the canonical GST fold although it shares less than 20% sequence identity with GSTs from higher organisms. The most surprising aspect of the structure is the observation that the substrate, glutathione, is covalently bound to Cys 10 of the enzyme. In addition, the highly structurally conserved N-terminal domain is found to have an additional beta strand. CONCLUSIONS: The crystal structure of PmGST B1-1 has highlighted the importance of a cysteine residue in the catalytic cycle. Sequence analyses suggest that a number of other GSTs share this property, leading us to propose a new class of GSTs - the beta class. The data suggest that the in vivo role of the beta class GSTs could be as metabolic or redox enzymes rather than conjugating enzymes. Compelling evidence is presented that the theta class of GSTs evolved from an ancestral member of the thioredoxin superfamily.     

Inflammatory mechanisms in Alzheimer's disease: implications for therapy

OBJECTIVE: The purpose of this article is to review evidence that inflammatory and immune mechanisms are important in the pathophysiology of Alzheimer's disease and to suggest new treatment strategies. METHOD: The authors review the English-language literature of the last 10 years pertaining to the pathophysiology of Alzheimer's disease. RESULTS: There is ample evidence supporting the hypothesis that inflammatory and immune mechanisms are involved in tissue destruction in Alzheimer's disease. Acute phase proteins are elevated in the serum and are deposited in amyloid plaques, activated microglial cells that stain for inflammatory cytokines accumulate around senile plaques, and complement components including the membrane attack complex are present around dystrophic neurites and neurofibrillary tangles. CONCLUSIONS: Clinical trials of anti-inflammatory/immunosuppressive drugs are necessary to determine whether alteration of these inflammatory mechanisms can slow the progression of Alzheimer's disease.     

The evolutionary scrambling and developmental unscrambling of germline genes in hypotrichous ciliates

Genes in the germline (micronuclear) genome of hypotrichous ciliates are interrupted by multiple, short, non-coding, AT-rich sequences called internal eliminated segments, or IESs. During conversion of a micronucleus to a somatic nucleus (macronucleus) after cell mating, all IESs are excised from the germline genes and the gene segments, called macronuclear-destined segments, or MDSs, are spliced. Excision of the approximately 150 000 IESs from a haploid germline genome in Oxytricha nova requires approximately 150 000 recombinant events. In three of 10 genes the MDSs are scrambled. During macronuclear development the MDSs are unscrambled, possibly by folding of the DNA to allow MDSs to ligate in the correct order. The nine MDSs in the actin I gene of O.nova are scrambled in the random order, 3-4-6-5-7-9-2-1-8, and MDS 2 is inverted. The 14 MDSs in the alphaTP gene of O.nova and Stylonychia mytilus are scrambled in the non-random order, 1-3-5-7-9-11-2-4-6-8-10-12-13-14. The 45 MDSs in the DNA pol alpha gene are non-randomly scrambled into an odd/even series, with an inversion of one-third of the gene. Additional IESs have been inserted into these three genes during evolution of Oxytricha trifallax, slightly modifying scrambling patterns. The non-random scrambled patterns in the alphaTP and DNA pol alpha genes are explained by multiple, simultaneous IES insertions. The randomly scrambled pattern in the actin I gene may arise from an initially non-randomly scrambled pattern by recombination among multiple IESs. Alternatively, IESs inserted sporadically (individually) in a non-scrambled configuration might subsequently recombine, converting a non-scrambled gene into a randomly scrambled one. IESs shift along a DNA molecule, most likely as a result of mutations at MDS/IES junctions. Shifting of IESs has the effect of 'transferring' nucleotides from one MDS to another, but does not change the overall sequence of nucleotides in the combined MDSs. In addition to shifting in position, IESs accumulate mutations at a high rate and increase and decrease in length within a species and during speciation. The phenomena of IESs and of MDS scrambling represent remarkable flexibility of the hypotrich genome, possibly reflecting a process of MDS shuffling that facilitates the evolution of genes.     

Functional and evolutionary implications of natural variation in clock genes

Stomach cancer remains the second leading cancer in incidence in Shanghai, China, despite its decline over the past 2 decades. To clarify risk factors for this common malignancy, we conducted a population-based case-control study in Shanghai, China. Included in the study were 1,124 stomach cancer patients (age 20-69) newly diagnosed in 1988-1989 and 1,451 controls randomly selected among Shanghai residents. Usual adult dietary intake was assessed using a comprehensive food frequency questionnaire. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. Risks of stomach cancer were inversely associated with high consumption of several food groups, including fresh vegetables and fruits, poultry, eggs, plant oil, and some nutrients, such as protein, fat, fiber and antioxidant vitamins. By contrast, risks increased with increasing consumption of dietary carbohydrates, with odds ratios (ORs) of 1.5 (95% confidence interval [CI] 1.1-2.1) and 1.9 (95% CI 1.3-2.9) in the highest quartile of intake among men (p for trend=0.02) and women (p=0.0007), respectively. Similar increases in risk were associated with frequent intake of noodles and bread in both men (p=0.07) and women (p=0.05) after further adjustment for fiber consumption. In addition, elevated risks were associated with frequent consumption of preserved, salty or fried foods, and hot soup/porridge, and with irregular meals, speed eating and binge eating. No major differences in risk were seen according to subsite (cardia vs. non-cardia). Our findings add to the evidence that diet plays a major role in stomach cancer risk and suggest the need for further evaluation of risks associated with carbohydrates and starchy foods as well as the mechanisms involved.     

Small cell lung cancer: pathophysiologic mechanisms and nursing implications

PURPOSE/OBJECTIVES: To review current incidence and treatment perspectives for small cell lung cancer (SCLC). DATA SOURCES: Published articles, book chapters, American Cancer Society materials. DATA SYNTHESIS: SCLC constitutes 20%-30% of lung cancer cases and accounts for 40,000 deaths annually. Characterized by rapid cell division, SCLC is very sensitive to radiation and chemotherapy; however, long-term survival rates are very low. A number of paraneoplastic syndromes are associated with this disease, thereby increasing the medical and nursing management challenges. CONCLUSIONS: Because SCLC usually is diagnosed late in the disease process and survival rates are poor, quality of life and palliation of metastatic symptoms (e.g., pain, breathing difficulties) are important focuses of care. Smoking deterrence and cessation programs, as well as early detection of lesions, are key to reducing incidence and mortality. IMPLICATIONS FOR NURSING PRACTICE: Nursing care focuses on promoting comfort and preventing and managing disease and treatment complications. Nursing diagnoses include ineffective airway clearance, impaired gas exchange, pain, altered nutrition, activity intolerance, and ineffective coping. A patient care standard is presented.