Showing papers in "The Scientific World Journal in 2006"

Human empathy through the lens of social neuroscience.

Abstract: Empathy is the ability to experience and understand what others feel without confusion between oneself and others. Knowing what someone else is feeling plays a fundamental role in interpersonal interactions. In this paper, we articulate evidence from social psychology and cognitive neuroscience, and argue that empathy involves both emotion sharing (bottom-up information processing) and executive control to regulate and modulate this experience (top-down information processing), underpinned by specific and interacting neural systems. Furthermore, awareness of a distinction between the experiences of the self and others constitutes a crucial aspect of empathy. We discuss data from recent behavioral and functional neuroimaging studies with an emphasis on the perception of pain in others, and highlight the role of different neural mechanisms that underpin the experience of empathy, including emotion sharing, perspective taking, and emotion regulation.

Aspects of growth hormone and insulin-like growth factor-I related to neuroprotection, regeneration, and functional plasticity in the adult brain.

Abstract: Apart from regulating somatic growth and metabolic processes, accumulating evidence suggests that the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis is involved in the regulation of brain growth, development, and myelination. In addition, both GH and IGF-I affect cognition and biochemistry in the adult brain. Some of the effects of GH are attributable to circulating IGF-I, while others may be due to IGF-I produced locally within the brain. Some of the shared effects in common to GH and IGF-I may also be explained by cross-talk between the GH and IGF-I transduction pathways, as indicated by recent data from other cell systems. Otherwise, it also seems that GH may act directly without involving IGF-I (either circulating or locally). Plasticity in the central nervous system (CNS) may be viewed as changes in the functional interplay between the major cell types, neurons, astrocytes, and oligodendrocytes. GH and IGF-I affect all three of these cell types in several ways. Apart from the neuroprotective effects of GH and IGF-I posited in different experimental models of CNS injury, IGF-I has been found to increase progenitor cell proliferation and new neurons, oligodendrocytes, and blood vessels in the dentate gyrus of the hippocampus. It appears that the MAPK signaling pathway is required for IGF-I-stimulated proliferation in vitro, whereas the PI3K/Akt or MAPK/Erk signaling pathway appears to mediate antiapoptotic effects. The increase of IGF-I on endothelial cell phenotype may explain the increase in cerebral arteriole density observed after GH treatment. The functional role of GH and IGF-I in the adult brain will be reviewed with reference to neurotransmitters, glucose metabolism, cerebral blood flow, gap junctional communication, dendritic arborization, exercise, enriched environment, depression, learning, memory, and aging. Briefly, these findings suggest that IGF-I functions as a putative regenerative agent in the adult CNS. Hitherto less studied regarding in these aspects, GH may have similar effects, especially as it is the main regulator of IGF-I in vivo. Some of the positive cognitive features of GH treatment are likely attributable to the mechanisms reviewed here.

The bacterial microflora of fish, revised.

Abstract: The results of numerous studies indicate that fish possess bacterial populations on or in their skin, gills, digestive tract, and light-emitting organs. In addition, the internal organs (kidney, liver, and spleen) of healthy fish may contain bacteria, but there is debate about whether or not muscle is actually sterile. Using traditional culture-dependent techniques, the numbers and taxonomic composition of the bacterial populations generally reflect those of the surrounding water. More modern culture-independent approaches have permitted the recognition of previously uncultured bacteria. The role of the organisms includes the ability to degrade complex molecules (therefore exercising a potential benefit in nutrition), to produce vitamins and polymers, and to be responsible for the emission of light by the light-emitting organs of deep-sea fish. Taxa, including Pseudomonas, may contribute to spoilage by the production of histamines in fish tissue.

Anticholinesterase toxicity and oxidative stress.

Abstract: Anticholinesterase compounds, organophosphates (OPs) and carbamates (CMs) are commonly used for a variety of purposes in agriculture and in human and veterinary medicine. They exert their toxicity in mammalian system primarily by virtue of acetylcholinesterase (AChE) inhibition at the synapses and neuromuscular junctions, leading into the signs of hypercholinergic preponderance. However, the mechanism(s) involved in brain/muscle damage appear to be linked with alteration in antioxidant and the scavenging system leading to free radical-mediated injury. OPs and CMs cause excessive formation of F2-isoprostanes and F4-neuroprostanes, in vivo biomarkers of lipid peroxidation and generation of reactive oxygen species (ROS), and of citrulline, a marker of NO/NOS and reactive nitrogen species (RNS) generation. In addition, during the course of these excitatory processes and inhibition of AChE, a high rate of ATP consumption, coupled with the inhibition of oxidative phosphorylation, compromise the cell's ability to maintain its energy levels and excessive amounts of ROS and RNS may be generated. Pretreatment with N-methyl D-aspartate (NMDA) receptor antagonist memantine, in combination with atropine sulfate, provides significant protection against inhibition of AChE, increases of ROS/RNS, and depletion of high-energy phosphates induced by DFP/carbofuran. Similar antioxidative effects are observed with a spin trapping agent, phenyl-N-tert-butylnitrone (PBN) or chain breaking antioxidant vitamin E. This review describes the mechanisms involved in anticholinesterase-induced oxidative/nitrosative injury in target organs of OPs/CMs, and protection by various agents.

Fmr1 KO Mice as a Possible Model of Autistic Features

Abstract: Autism is a pervasive developmental disorder appearing before the age of 3, where communication and social interactions are impaired. It also entails stereotypic behavior or restricted interests. Although this disorder was first described in 1943, little is still known about its etiology and that of related developmental disorders. Work with human patients has provided many data on neuropathological and cognitive symptoms, but our understanding of the functional defects at the cellular level and how they come about remains sketchy. To improve this situation, autism research is in need of valid animal models. However, despite a strong hereditary component, attempts to identify genes have generally failed, suggesting that many different genes are involved. As a high proportion of patients suffering from the Fragile X Syndrome show many autistic symptoms, a mouse model of this disorder could potentially also serve as a model for autism. The Fmr1 KO mouse is a valid model of the Fragile X Syndrome and many data on behavioral and sensory-motor characteristics of this model have been gathered. We present here an assessment of autistic features in this candidate model. We conclude that Fmr1 KO mice display several autistic-like features, but more work is needed to validate this model.

Effects of hyperbaric oxygen on inflammatory response to wound and trauma: possible mechanism of action.

Abstract: There is growing interest in expanding the clinical applications for HBO2 (hyperbaric oxygen therapy) into new medical and surgical fields. The pathophysiology of response towards wounds, infection, trauma, or surgery involves various chemical mediators that include cytokines, prostaglandins (PGs), and nitric oxide (NO). The beneficial role played by HBO2 in wound healing, carbon monoxide poisoning, decompression sickness, and other indications is well documented. However, the exact mechanism of action is still poorly understood. This review addresses the effects of HBO2 on PGs, NO, and cytokines involved in wound pathophysiology and inflammation in particular. The results of this review indicate that HBO2 has important effects on the biology of cytokines and other mediators of inflammation. HBO2 causes cytokine down-regulation and growth factor up-regulation. HBO2 transiently suppresses stimulus-induced proinflammatory cytokine production and affects the liberation of TNFa (tumor necrosis factor alpha) and endothelins. VEGF (vascular endothelial growth factor) levels are significantly increased with HBO2, whereas the value of PGE2 and COX-2 mRNA are markedly reduced. The effect of HBO2 on NO production is not well established and more studies are required. In conclusion, cytokines, PGs, and NO may play a major role in the mechanism of action of HBO2 and further research could pave the way for new clinical applications for HBO2 to be established. It could be proposed that chronic wounds persist due to an uncontrolled pathological inflammatory response in the wound bed and that HBO2 enhances wound healing by damping pathological inflammation (anti-inflammatory effects); this hypothetical proposal remains to be substantiated with experimental results.

Transcriptional profiling of caudal fin regeneration in zebrafish.

Abstract: Regeneration of severed limbs in adult animals is restricted to urodele amphibians. Mammals, including humans, have very limited regenerative capabilities and even with proper treatment, only the tips of our digits can grow back. Teleost fish can regenerate amputated fins, the evolutionary ancestors of limbs. To elucidate the principles of limb-fin regeneration, we performed an Affymetrix microarray screen on regenerating caudal fins 12, 24, 48, and 72 h post amputation. Approximately 15,000 zebrafish transcripts were analyzed, identifying 829 transcripts as differentially expressed during regeneration. Of those, 563 were up-regulated and 266 were down-regulated. We constructed a comprehensive database containing expression data, functional assignment, and background information from the literature for each differentially expressed transcript. In order to validate our findings, we employed three approaches: (1) microarray expression analysis of genes previously implicated in fin regeneration, (2) RT-PCR analysis of genes newly identified as differentially expressed during regeneration, and (3) in situ hybridization of the up-regulated genes bambi, dlx5A, and her6. Moreover, we show that Smad 1/5/8 proteins, effector molecules of Bmp signaling, are phosphorylated during fin regeneration. Taken together, we provide a comprehensive database of fin regeneration that will serve as an important tool for understanding the molecular mechanisms of regeneration.

Diabetes, Inflammation, Proinflammatory Cytokines, and Diabetic Nephropathy

Abstract: Diabetes and its complications have become a public health problem. Diabetic nephropathy is the main cause of renal failure. In spite of our higher knowledge on this complication, the intimate mechanisms leading to the development and progression of renal injury are not yet fully known. Activated innate immunity and inflammation are relevant factors in the pathogenesis of diabetes. Moreover, inflammation, and more specifically proinflammatory cytokines and other molecules with a relevant role within the inflammatory process, may be critical factors in the development of microvascular diabetic complications, including nephropathy. This new pathogenic perspective may lead to important new therapeutic considerations and new therapeutic goals for the treatment of diabetic nephropathy.

Vitamin D as a neuroactive substance: review.

Abstract: The objectives of this paper were (1) to review recent research on the actions of vitamin D as a steroid derivative with neuroactive properties and (2) to highlight clinical relevance and need for more research. Our methods included review of research from current journals, Medline, and Cochrane Reviews; theoretical discussion. Scientific research has had a justifiably strong emphasis on how vitamin D affects calcium metabolism and bone. This appears to have eclipsed its fundamental actions on several other important systems, including the central nervous system. Vitamin D as a neuroactive compound, a prohormone, is highly active in regulating cell differentiation, proliferation, and peroxidation in a variety of structures, including the brain. Vitamin D insufficiency is not rare. Historically, focus has been on bone metabolism, which appears to have caused research bias and evidence bias, distorting physiological importance. The central nervous system is increasingly recognized as a target organ for vitamin D via its wide-ranging hormonal effects, including the induction of proteins such as nerve growth factor. We need more research on this important neuroactive substance because it may play a role as a relatively safe and inexpensive pharmaceutical in the prevention and treatment of a number of common neuropsychiatric conditions.

Prevalence of overweight misperception and weight control behaviors among normal weight adolescents in the United States.

Abstract: Weight perceptions and weight control behaviors have been documented with underweight and overweight adolescents, yet limited information is available on normal weight adolescents. This study investigates the prevalence of overweight misperceptions and weight control behaviors among normal weight adolescents in the U.S. by sociodemographic and geographic characteristics. We examined data from the 2003 Youth Risk Behavior Survey (YRBS). A total of 9,714 normal weight U.S. high school students were included in this study. Outcome measures included self-reported height and weight measurements, overweight misperceptions, and weight control behaviors. Weighted prevalence estimates and odds ratios were computed. There were 16.2% of normal weight students who perceived themselves as overweight. Females (25.3%) were more likely to perceive themselves as overweight than males (6.7%) (p < 0.05). Misperceptions of overweight were highest among white (18.3%) and Hispanic students (15.2%) and lowest among black students (5.8%). Females (16.8%) outnumbered males (6.8%) in practicing at least one unhealthy weight control behavior (use of diet pills, laxatives, and fasting) in the past 30 days. The percentage of students who practiced at least one weight control behavior was similar by ethnicity. There were no significant differences in overweight misperception and weight control behaviors by grade level, geographic region, or metropolitan status. A significant portion of normal weight adolescents misperceive themselves as overweight and are engaging in unhealthy weight control behaviors. These data suggest that obesity prevention programs should address weight misperceptions and the harmful effects of unhealthy weight control methods even among normal weight adolescents.

COX-2: a pivotal enzyme in mucosal protection and resolution of inflammation

Abstract: The discovery of a second form of cyclooxygenase, COX-2, led to a burst of research aimed at the development of nonsteroidal anti-inflammatory drugs that would not damage the gastrointestinal tract. In the years since, this promise has only been partially fulfilled. Selective COX-2 inhibitors cause less gastric damage than conventional, nonselective COX inhibitors, but their use is still associated with significant gastrointestinal injury, and with toxicity in the renal and cardiovascular systems. COX-2 is now recognized as a source of mediators that produce many beneficial and detrimental effects in the digestive system. In this review, the roles of COX-2 in mucosal defense and injury are discussed. Furthermore, contributions of COX-2-derived products to the long-term consequences of intestinal inflammation, including cancer, are reviewed.

Limb regeneration in Xenopus laevis froglet.

Abstract: Limb regeneration in amphibians is a representative process of epimorphosis. This type of organ regeneration, in which a mass of undifferentiated cells referred to as the “blastema” proliferate to restore the lost part of the amputated organ, is distinct from morphallaxis as observed, for instance, in Hydra, in which rearrangement of pre-existing cells and tissues mainly contribute to regeneration. In contrast to complete limb regeneration in urodele amphibians, limb regeneration in Xenopus, an anuran amphibian, is restricted. In this review of some aspects regarding adult limb regeneration in Xenopus laevis, we suggest that limb regeneration in adult Xenopus, which is pattern/tissue deficient, also represents epimorphosis.

Limb regeneration in amphibians: immunological considerations.

Abstract: We review key aspects of what is known about limb regeneration in urodele and anuran amphibians, with a focus on the early events of the process that lead to formation of the regeneration blastema. This includes the role of the nerves and wound epithelium, but also covers the inflammatory effects of the amputation trauma and their importance for regenerative growth. We propose that immunotolerance is important for limb regeneration and changes in its regulation may underlie the loss of regenerative capacity during anuran metamorphosis.

Neuroregulation of the hypothalamus-pituitary-adrenal (HPA) axis in humans: effects of GABA-, mineralocorticoid-, and GH-Secretagogue-receptor modulation.

Abstract: The hypothalamus-pituitary-adrenal (HPA) axis exerts a variety of effects at both the central and peripheral level. Its activity is mainly regulated by CRH, AVP, and the glucocorticoid-mediated feedback action. Moreover, many neurotransmitters and neuropeptides influence HPA axis activity by acting at the hypothalamic and/or suprahypothalamic level. Among them, GABA and Growth Hormone Secretagogues (GHS)/GHS-receptor systems have been shown to exert a clear inhibitory and stimulatory effect, respectively, on corticotroph secretion. Alprazolam (ALP), a GABA-A receptor agonist, shows the most marked inhibitory effect on both spontaneous and stimulated HPA axis activity, in agreement with its peculiar efficacy in panic disorders and depression where an HPA axis hyperactivation is generally present. Ghrelin and synthetic GHS possess a marked ACTH/cortisol-releasing effect in humans and the ghrelin/GHS-R system is probably involved in the modulation of the HPA response to stress and nutritional/metabolic variations. The glucocorticoid-mediated negative feedback action is mediated by both glucocorticoid (GR) and mineralocorticoid (MR) receptors activation at the central level, mainly in the hippocampus. In agreement with animal studies, MRs seem to play a crucial role in the maintenance of the circadian ACTH and cortisol rhythm, through the modulation of CRH and AVP release. GABA agonists (mainly ALP), ghrelin, as well as MR agonists/antagonists, may represent good tools to explore the activity of the HPA axis in both physiological conditions and pathological states characterized by an impaired control of the corticotroph function.

Natural history, recurrence, and progression in superficial bladder cancer

Abstract: Superficial bladder cancer encompasses patients with stage Ta T1 tumors and patients with carcinoma in situ (CIS). The natural history or treatment-related prognosis of these patients varies considerably from one patient to the next based on the patient's clinical and the tumor's pathological characteristics. Based on a review of the literature, the most important prognostic factors for recurrence are the prior recurrence rate, number of tumors, and tumor size; whereas for progression, the most important prognostic factors are the T category, grade, and presence of CIS. Treatment with intravesical bacillus Calmette-Guerin reduces both the risk of recurrence and the risk of progression, and is the treatment of choice in high-risk papillary tumors and in patients with CIS. Assessment of a patient's prognostic factors and his or her risk of recurrence and progression is a prerequisite for determining the most appropriate treatment and frequency of follow-up for a given patient.

DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A): a gene with dosage effect during development and neurogenesis.

Abstract: DYRKs (dual-specificity tyrosine-regulated kinases) are an emerging family of evolutionarily conserved dual-specificity kinases that play key roles in cell proliferation, survival, and development. The research in the last years suggests a relevant conserved function during neuronal development, related to proliferation and/or differentiation for DYRK1A. It is expressed in neural progenitor cells and has been proposed to participate in the signaling mechanisms that regulate dendrite differentiation. In Drosophila, disruption of the homolog minibrain gene results in flies with reduced neuroblast proliferation, decreased numbers of central brain neurons, and learning/memory deficits. Knockout DYRK1A mice are embryonic lethal, and heterozygotes show decreased viability and region-specific reductions in brain size. In humans, DYRK1A has been proposed to be involved in the neurodevelopmental alterations associated with Down syndrome. The large number of protein interaction and putative substrates described for DYRK1A suggest multiple pathways and functions to be involved in its developmental function. This review focuses on the functional role that DYRK1A plays in brain development.

Anterograde and retrograde effects of benzodiazepines on memory.

Abstract: Benzodiazepines are known as “acquisition-impairing” molecules, and their effects on anterograde memory processes are well described. In contrast, the impact of benzodiazepines on retrograde memory and, more particularly, on retrieval processes, is only marginally studied. This mini-review provides an overlook of the main studies evidencing an effect of benzodiazepines on retrograde memory, both in humans and animals, with special emphasis on retrieval processes. The conditions for the emergence of the benzodiazepine-induced retrieval impairments are also discussed.

Function and Diversification of MADS-Box Genes in Rice

Abstract: MADS-box genes play critical roles in a number of developmental processes in flowering plants, such as specification of floral organ identity, control of flowering time, and regulation of fruit development. Because of their crucial functions in flower development, diversification of the MADS-box gene family has been suggested to be a major factor responsible for floral diversity during radiation of the flowering plants. Inflorescences and flowers in the grass species have unique structures that are distinct from those in eudicots. Thus, it is plausible that the diversification of the function of MADS-box genes may have been a key driving force in the morphological divergence of the flowers and inflorescences in the grasses. Indeed, recent progress in genetic studies has shown that MADS-box genes function in flower development in Oryza sativa (rice), in support of the idea that functional diversification of the MADS-box genes was involved in evolution of the angiosperms. In this review, we summarize the functions of the major subfamilies of the MADS-box genes in rice and discuss their role in the development and evolution of rice flowers and inflorescences.

Signal transduction of sphingosine-1-phosphate G protein-coupled receptors.

Abstract: Sphingosine-1-phosphate (S1P) is a bioactive lipid capable of eliciting dramatic effects in a variety of cell types. Signaling by this molecule is by a family of five G protein-coupled receptors named S1P1-5 that signal through a variety of pathways to regulate cell proliferation, migration, cytoskeletal organization, and differentiation. These receptors are expressed in a wide variety of tissues and cell types, and their cellular effects contribute to important biological and pathological functions of S1P in many processes, including angiogenesis, vascular development, lymphocyte trafficking, and cancer. This review will focus on the current progress in the field of S1P receptor signaling and biology.

Integrated confocal and scanning probe microscopy for biomedical research.

Abstract: Atomic force microscopy (AFM) continues to be developed, not only in design, but also in application. The new focus of using AFM is changing from pure material to biomedical studies. More frequently, it is being used in combination with other optical imaging methods, such as confocal laser scanning microscopy (CLSM) and fluorescent imaging, to provide a more comprehensive understanding of biological systems. To date, AFM has been used increasingly as a precise micromanipulator, probing and altering the mechanobiological characteristics of living cells and tissues, in order to examine specific, receptor-ligand interactions, material properties, and cell behavior. In this review, we discuss the development of this new hybrid AFM, current research, and potential applications in diagnosis and the detection of disease.

Alcohol and Suicide: Neurobiological and Clinical Aspects

Abstract: Alcohol, primarily in the form of ethyl alcohol (ethanol), has occupied an important place in the history of humankind for at least 8,000 years. In most Western societies, at least 90% of people consume alcohol at some time during their lives, and 30% or more of drinkers develop alcohol-related problems. Severe alcohol-related life impairment, alcohol dependence (alcoholism), is observed at some time during their lives in about 10% of men and 3-5% of women. An additional 5-10% of each sex develops persistent, but less intense, problems that are diagnosed as alcohol abuse. It this review, neurobiological aspects of suicidal behavior in alcoholism is discussed. In individuals with comorbid depression and alcoholism, greater serotonergic impairment may be associated with higher risk of completed suicide. Dopaminergic dysfunction may play an important role in the pathophysiology of suicidal behavior in alcoholism. Brain damage and neurobehavioral deficits are associated with alcohol use disorders and may contribute to suicidal behavior in persons with alcohol dependence or abuse. Aggression/impulsivity and alcoholism severity affect risk for suicide among individuals with alcoholism. Major depressive episodes and stressful life events particularly, partner-relationship disruptions, may precipitate suicidal behavior in individuals with alcohol use disorders. Alcohol misuse and psychosocial adversity can combine to increase stress on the person, and, thereby, potentially, increase the risk for suicidal behavior. The management of suicidal patients with alcohol use disorders is also discussed. It is to be hoped that the efforts of clinicians will reduce morbidity and mortality associated with alcohol misuse.

Benign mixed epithelial and stromal tumor of the kidney.

Abstract: A 51-year-old, perimenopausal, female patient with 1-month history of right flank pain who was diagnosed with a renal mass and underwent nephron-sparing partial nephrectomy is presented. The renal mass was found to be a benign, biphasic tumor composed of an epithelial component, consisting of ducts of variable size scattered within a mesenchymal component, composed of spindle cells arranged in sheets and fascicles. No atypia, mitosis, or necrosis was found. The spindle component shows desmin, smooth muscle actin, and estrogen and progesterone receptor positivity immunohistochemically. The diagnosis of benign mixed epithelial and stromal tumor of the kidney is rendered. No recurrent disease has been detected during 2 years of follow up.

Limb regeneration in axolotl: is it superhealing?

Abstract: The ability of axolotls to regenerate their limbs is almost legendary. In fact, urodeles such as the axolotl are the only vertebrates that can regenerate multiple structures like their limbs, jaws, tail, spinal cord, and skin (the list goes on) throughout their lives. It is therefore surprising to realize, although we have known of their regenerative potential for over 200 years, how little we understand the mechanisms behind this achievement of adult tissue morphogenesis. Many observations can be drawn between regeneration and other disciplines such as development and wound healing. In this review, we present new developments in functional analysis that will help to address the role of specific genes during the process of regeneration. We also present an analysis of the resemblance between wound healing and regeneration, and discuss whether axolotls are superhealers. A better understanding of these animals' regenerative capacity could lead to major benefits by providing regenerative medicine with directions on how to develop therapeutic approaches leading to regeneration in humans.

Developmental defects in trisomy 21 and mouse models.

Abstract: Aneuploidies have diverse phenotypic consequences, ranging from mental retardation and developmental abnormalities to susceptibility to common phenotypes and various neoplasms. This review focuses on the developmental defects of murine models of a prototype human aneuploidy: trisomy 21 (Down syndrome, DS, T21). Murine models are clearly the best tool for dissecting the phenotypic consequences of imbalances that affect single genes or chromosome segments. Embryos can be studied freely in mice, making murine models particularly useful for the characterization of developmental abnormalities. This review describes the main phenotypic alterations occurring during the development of patients with T21 and the developmental abnormalities observed in mouse models, and investigates phenotypes common to both species.

Targeted Anticancer Immunotoxins and Cytotoxic Agents with Direct Killing Moieties

Abstract: Despite the progress of the bioinformatics approach to characterize cell-surface antigens and receptors on tumor cells, it remains difficult to generate novel cancer vaccines or neutralizing monoclonal antibody therapeutics. Among targeted cancer therapeutics, biologicals with targetable antibodies or ligands conjugated or fused to toxins or chemicals for direct cell-killing ability have been developed over the last 2 decades. These conjugated or fused chimeric proteins are termed immunotoxins or cytotoxic agents. Two agents, DAB389IL-2 (ONTAKTM) targeting the interleukin-2 receptor and CD33-calicheamicin (Mylotarg), have been approved by the FDA for cutaneous T-cell lymphoma (CTCL) and relapsed acute myeloid leukemia (AML), respectively. Such targetable agents, including RFB4(dsFv)-PE38 (BL22), IL13-PE38QQR, and Tf-CRM107, are being tested in clinical trials. Several agents using unique technology such as a cleavable adapter or immunoliposomes with antibodies are also in the preclinical stage. This review summarizes the generation, mechanism, and development of these agents. In addition, possible future directions of this therapeutic approach are discussed.

Pharmaceutical Compounds in Wastewater: Wetland Treatment as a Potential Solution

Abstract: Pharmaceutical compounds are being released into the aquatic environment through wastewater discharge around the globe. While there is limited removal of these compounds within wastewater treatment plants, wetland treatment might prove to be an effective means to reduce the discharge of the compounds into the environment. Wetlands can promote removal of these pharmaceutical compounds through a number of mechanisms including photolysis, plant uptake, microbial degradation, and sorption to the soil. We review relevant laboratory research on these various mechanisms and provide data on the few studies that have examined wetland removal. There is a need to document the degree to which various pharmaceutical compounds are removed in full-scale treatment wetlands, as there is a paucity of data on overall pharmaceutical removal rates.

Two different transgenes to study gene silencing and re-expression during zebrafish caudal fin and retinal regeneration.

Abstract: We used the 500-bp Xenopus ef1-alpha promoter and the 2-kb zebrafish histone 2A.F/Z promoter to generate several independent transgenic zebrafish lines expressing EGFP. While both promoters drive ubiquitous EGFP expression in early zebrafish development, they are systematically silenced in several adult tissues, including the retina and caudal fin. However, EGFP expression is temporarily renewed in the adult during either caudal fin or retinal regeneration. In the Tg(H2A.F/Z:EGFP)nt line, EGFP is moderately expressed in both the wound epithelium and blastema of the regenerating caudal fin. In the Tg(ef1-alpha:EGFP)nt line, EGFP expression is reinitiated and restricted to the blastema of the regenerating caudal fin and colabels with BrdU, PCNA, and msxc-positive cells. Thus, these two ubiquitous promoters drive EGFP transgene expression in different cell populations during caudal fin regeneration. We further analyzed the ability of the ef1-alpha:EGFP transgene to label nonterminally differentiated cells during adult tissue regeneration. First, we demonstrated that the transgene is highly methylated in adult zebrafish caudal fin tissue, but not during fin regeneration, implicating methylation as a potential means of transgene silencing in this line. Next, we determined that the ef1-alpha:EGFP transgene is also re-expressed during adult retinal regeneration. Specifically, the ef1-alpha:EGFP transgene colabels with PCNA in the Muller glia, a specialized cell that is the source of neuronal progenitors during zebrafish retinal regeneration. Thus, we concluded that Tg(ef1-alpha:EGFP)nt line visually marks nonterminally differentiated cells in multiple adult regeneration environments and may prove to be a useful marker in tissue regeneration studies in zebrafish.

Risk and Protective Factors for Suicide in Patients with Alcoholism

Abstract: Alcoholism is associated with a high risk for suicidal behavior. Up to 40% of persons with alcoholism attempt suicide at some time and 7% end their lives by committing suicide. Risk factors include being male, older than 50 years of age, living alone, being unemployed, poor social support, interpersonal losses, continued drinking, consumption of a greater amount of alcohol when drinking, a recent alcohol binge, previous alcohol treatment, a family history of alcoholism, a history of comorbid substance abuse (especially cocaine), a major depressive episode, serious medical illness, suicidal communication, and prior suicidal behavior. Suicidal behavior is especially frequent in patients with comorbid alcoholism and major depression. However, all patients with alcoholism should be evaluated for suicide risk. Understanding of risk and vulnerability to suicidal behavior in alcoholism still outweighs our knowledge of protective factors and resilience. Knowledge of protective factors for suicide may help to prevent and/or predict suicidal behavior. Protective factors for suicide in alcoholism are quite varied and include an individual's biological and behavioral characteristics, as well as attributes of the environment and culture. Protective factors include effective clinical care for psychiatric (including alcoholism and drug abuse) and physical disorders, easy access to a variety of clinical interventions and support for seeking help, restricted access to highly lethal means of suicide, strong connections to family and community support, skills in problem solving and conflict resolution, cultural and religious beliefs that discourage suicide and support self-preservation. Future studies are necessary to determine which interventions may reduce suicidal behavior in alcoholism.

Formation of the Ventricles

Abstract: The formation of the ventricles of the heart involves numerous carefully regulated temporal events, including the initial specification and deployment of ventricular progenitors, subsequent growth and maturation of the ventricles through “ballooning” of chamber myocardium, the emergence of trabeculations, the generation of the compact myocardium, and the formation of the interventricular septum. Several genes have been identified through studies on mouse knockout and transgenic models, which have contributed to our understanding of the molecular events governing these developmental processes. Interpretation of these studies highlights the fact that even the smallest perturbation at any stage of ventricular development may lead to cardiac malformations that result in either early embryonic mortality or a manifestation of congenital heart disease.

Effectiveness of the Tier 1 Program of the Project P.A.T.H.S.: preliminary objective and subjective outcome evaluation findings.

Abstract: There are two tiers of programs in the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes). In the Tier 1 Program, teaching units based on different positive youth development constructs are covered. Pre- and post-test data utilizing the Chinese Positive Youth Development Scale (CPYDS) and post-test subjective outcome evaluation data were collected from 546 students who participated in the 20h Tier 1 Program of the P.A.T.H.S. Project. Results showed that high proportions of the respondents had positive perceptions of the program and the instructors, with 85.3% of the respondents regarding the program as helpful to them. Positive changes in the program participants in many measures of positive youth development were also observed. Although there were some increases in problem behavior in some areas, adolescent problem behavior was generally stable. The present study provides preliminary support for the effectiveness of the Tier 1 Program of the Project P.A.T.H.S. in Hong Kong.