A Public Policy Toward the Management of Feral Cats

[Excerpt] “This paper examines the current wildlife laws, both federal and state, to determine what laws may apply to managing the feral cat population. It begins with a determination of how domestic cats are classified under these laws. Since many laws are vague, the intent of the legislatures is investigated to determine if domestic cats were meant to be defined as a nonindigenous species. The focus then shifts to indicate ways to control the feral domestic cat population. Current trends in the control of other nonindigenous species appear to revolve around public nuisance claims; however, due to the unique nature of domestic cats, these laws are poor candidates for managing the unwanted domestic cat population. On the other hand, given the recent increase in the enactment of leash laws, courts may be more inclined to apply public nuisance laws to cats.

The rise and fall of self-esteem: a critical review, reconceptualization, and recommendations

Self-esteem, viewed for decades as psychology’s Holy Grail, has proved to be an elusive and surprisingly barren destination. One of the oldest concepts in psychology, self-esteem likely ranks among the top three covariates occurring in personality and social psychology research. Propelled by the self-esteem movement of the 1970s, it was popularly believed that self-esteem played a significant causal role in determining a wide range of both positive and negative social behaviors. However, the results of a 2003 large-scale literature review showed that it is actually not a major predictor of almost anything, with the exception of positive feelings (happiness) and possibly greater initiative. With over a decade passing since that publication, the current investigation sought to review, synthesize and critically analyze the more recent literature. Results confirmed a similar dearth of meaningful relationships connected to self-esteem, the only exceptions being some modest correlates to happiness, narcissism, and self-perceived attractiveness and intelligence. However, the literature continues to be plagued with myriad conceptual and methodological problems. This study utilizes specific critical thinking principles to advance understanding in this area, to address why the self-esteem obsession still persists, and to propose a new theoretical model, one that accounts for the construct’s heterogeneous and multidimensional nature. Self-esteem is defined as the appraisal of one’s own personal value, including both emotional components (self-worth) and cognitive components (self-efficacy). The multiple forms of self-esteem are a function of how accurately or closely it matches an individual’s measureable reality, composed of the objective outcome of one’s behavior (actual achievements, measurable capabilities) as well as one’s interpersonal interactions (i.e., the level of congruence between how one thinks he or she is perceived and how he or she is actually perceived). Self-esteem also varies in terms of its level of stability, or the degree to which it is influenced by evaluative events or the need to match external standards across time and situation. The permutations of these sorting variables yield eight types of self-esteem: Optimal High, Fragile High, Accurate Low, Fragile Low, Non-compensatory Narcissism, Compensatory Narcissism, Pessimal, and Disorganized. Specific recommendations for clinicians and researchers are provided

Kcne4 deletion sex- and age-specifically impairs cardiac repolarization in mice.

Myocardial repolarization capacity varies with sex, age, and pathology; the molecular basis for this variation is incompletely understood. Here, we show that the transcript for KCNE4, a voltage-gated potassium (Kv) channel β subunit associated with human atrial fibrillation, was 8-fold more highly expressed in the male left ventricle compared with females in young adult C57BL/6 mice (P < 0.05). Similarly, Kv current density was 25% greater in ventricular myocytes from young adult males (P < 0.05). Germ-line Kcne4 deletion eliminated the sex-specific Kv current disparity by diminishing ventricular fast transient outward current (Ito,f) and slowly activating K(+) current (IK,slow1). Kcne4 deletion also reduced Kv currents in male mouse atrial myocytes, by >45% (P < 0.001). As we previously found for Kv4.2 (which generates mouse Ito,f), heterologously expressed KCNE4 functionally regulated Kv1.5 (the Kv α subunit that generates IKslow1 in mice). Of note, in postmenopausal female mice, ventricular repolarization was impaired by Kcne4 deletion, and ventricular Kcne4 expression increased to match that of males. Moreover, castration diminished male ventricular Kcne4 expression 2.8-fold, whereas 5α-dihydrotestosterone (DHT) implants in castrated mice increased Kcne4 expression >3-fold (P = 0.01) to match noncastrated levels. KCNE4 is thereby shown to be a DHT-regulated determinant of cardiac excitability and a molecular substrate for sex- and age-dependent cardiac arrhythmogenesis

Microarray analysis of genes affected by salt stress in tomato

Large-scale gene expression affected by salt stress was analyzed with tomato seedlings (Lycoperson esculentum Mill cv. Money Maker) by a cDNA microarray (Tom1). The significantly differentially expressed genes (5% Benjamini-Hochberg false discovery rate) consisted of 1757 sequences in the analyzed tissues (cotyledons + shoot tip). Genes with over 2 fold difference were selected from the list and further categorized into different function and cellular processes. Tomato homologous genes for the chaperone proteins, antioxidant enzymes (catalase and peroxidase), and ion transporters (Na+- driven multidrug efflux pump, vacuolar ATPase, and others) were induced. The ACC oxidase and ethylene-responsive gene tomato homologs had higher transcript level after salt treatment. Multiple members with different expression patterns were identified for the bZIP, WRKY, and MADS-box transcription regulator. Different genes in the signal transduction pathway, such as the protein kinases (Shaggy kinase, mitogen-activated protein kinase, ethylene receptor neverripe, and others), protein phosphatases, calmodulin, G-protein, and the N- myristoyltransferase were regulated by salt stress. Most of the protease and the inhibitor homologs were suppressed by salt stress. In addition, different isoforms of cytochrome P450, genes for polyamine biosynthesis (putrescine and proline) and detoxification compounds (glutathione and thioredoxin), several key enzyme genes in the metabolic pathways of carbohydrates, amino acids, and fatty acids, were also affected by salt treatment. This study has provided a set of candidate genes, especially those in the regulatory machinery that can be further investigated to define salt stress in tomato and other plant species.Keywords: Antioxidants, cellular metabolism, cell wall, chaperonine, ethylene, protein kinase, tomato, transcription regulator, translation regulator, salt stres

Influence of acute and chronic glutathione manipulations on coronary vascular resistance and endothelium dependent dilation in isolated perfused rat hearts

Glutathione (GSH), a 3-amino acid compound is ubiquitously expressed in eukaryotic cells and is the most abundant low molecular weight thiol. The importance of GSH is highlighted by its multitude of effects. Within the vascular wall GSH plays a crucial role as an intracellular antioxidant and it possess the ability to act as a signalling intermediate and store for nitric oxide (NO). The importance of NO and its role in vascular wall homeostasis is well recognized. Within the coronary circulation, NO is the primary dilator of many of the large arteries and the smaller arterioles. In addition to controlling coronary vascular tone, the importance of NO is highlighted by its antithrombotic, antihypertrophic, and antriproliferative effects. During instances of cardiovascular disease and normal aging, increases in the production of reactive oxygen species occur. A portion of the deleterious vascular effects of reactive oxygen species are believed to be due to reduction in NO bioavailability as a result of increased ROS-mediated destruction of NO. Altered GSH production in humans has been demonstrated to reduce endothelial function. Conversely, supplementation with GSH augments endothelium-dependent dilation. The mechanisms by which these alterations in GSH influence vasomotor function have not been resolved. The purpose of the studies within this thesis was to examine the impact of chronic and acute GSH modulations on coronary vascular resistance (CVR) and endothelium dependent dilation. In all experiments vascular reactivity was assessed in the isolated perfused rat heart. The advantage of this technique is that it allows the global coronary vasomotor functioning to be examined. Hearts were allowed to stabilize for 30 minutes to allow for the development of spontaneous coronary vascular resistance, followed by a bradykinin (BK) dose-response curve to assess endothelium-dependent dilation. The coronary circulation was then maximally dilated using an endothelium-independent agonist. In all cases BK-mediated dilation is expressed as a percentage of the endothelium-independent dilation. Chapter 2 of this document examines the chronic nature of GSH depletion and examines whether GSH depletion augments the influence of natural aging. Animals (mean age 33 and 65 weeks) were randomized to receive L-Buthionine-(S,R)-sulphoximine (BSO) in the tap water in order to inhibit GSH synthesis, or regular tap water (normal controls). Following 10 days of BSO treatment, ventricular GSH content was reduced in the BSO group compared to the control (0.182±0.021 vs 2.022±0.084 nmol/mg wet weight, p<0.05) and there was increased ventricular H2O2 content (1.345±0.176 vs 0.877±0.123 pmol/µg PRO, p<0.05). Baseline CVR was significantly reduced in the older animals compared to the adult animals (3.92±0.34 vs 4.76±0.20 and 3.67±0.24 vs 5.12±0.37 mmHg/ml×min-1 in the control and BSO treated groups, p<0.05). Conversely, in the presence of LNAME there was a significant increase in CVR in the adult BSO group (14.15±0.99, p<0.05) compared to all other groups. In the absence of LNAME, maximal dilation (percent endothelium-independent response) was reduced in the older animals compared to the adult animals (77±10.3% vs 95.0±1.0% for older and adult control and 92.7±4.5% vs 98.6±0.6% for the older and adult BSO, main effect of age). In the presence of LNAME the adult BSO group had a significantly reduced sensitivity (EC50) compared to all other groups (-7.39±0.09 Log M, p<0.05). Additionally, adult BSO treated animals had an increase in eNOS protein content. These results demonstrate that chronic thiol depletion resulted in an increased reliance on NO in the adult BSO group only. In chapter 3 the beneficial effects of GSH supplementation on BK mediated dilation were examined. Acute GSH was administered in the perfusate at either 0 (control) or with 10 µM for 2 reasons, 1) this concentration does not reduce basal coronary vascular resistance, allowing for a similar baseline CVR across conditions and 2) the 10 µM concentration is a physiologically relevant concentration of plasma/extracellular fluid GSH. The sensitivity to the endothelial agonist bradykinin was enhanced in the presence of GSH (-8.70±0.16 vs -7.94±0.06 LogM, p0.05) and area under the curve (182.33±12.70 vs 170±13.86, p>0.05) between GSH and CON. Thus, it was concluded that the effects of GSH administration requires the presence of ROS and exerts its effect in the microvasculature. The study presented in chapter 4 examined the effects of acute thiol modulation (depletion) on CVR and endothelium-dependent dilation. Previous reports have suggested that a reduction in intracellular GSH causes impaired NO production, and functional data support this contention. However, a majority of the data regarding the effects of thiol manipulation are from endothelial-removed vessels. The following agents were used to reduce GSH: the glutathione reductase inhibitor, BCNU; the thiol oxidizing agent, diamide; the thiol conjugating agent, ethacrynic acid (EA); and a thioredoxin inhibitor (CDNB). Preliminary data revealed that only CDNB (11.46±0.71 mmHg/ml×min-1) and EA (8.61±0.36 mmHg/ml×min-1) caused an elevation in CVR compared to the control (6.73±0.24 mmHg/ml×min-1). Conversely, Diamide and BCNU did not significantly affect baseline CVR, or the BK mediated responses. In the presence of EA, there was an overall blunting of the BK-response curve as observed by reduced EC50 (-7.85±0.07 Log M) and maximal dilation (90.8±1.8 %, percent endothelium-independent dilation) compared to the control group (-8.42±0.08 Log M and 97.7±1.6%). In the presence of CDNB the maximal dilation was 74.4±1.9% and the EC50 was -8.83±0.28 Log M. In addition to altering BK mediated responses, acute thiol depletion with all agents resulted in an increased minimal CVR with significant increases observed in the presence of CDNB and EA. There was a significant correlation with GSH:GSSG ratio and baseline (-0.547, p<0.05) and minimal CVR (r=-0.581, p<0.05). This study demonstrates that modulation of the GSH:GSSG ratio using a variety of agents with diverse mechanisms elicits differential responses within the vasculature. Specifically conjugation of GSH and inhibition of thioredoxin significantly alters BK mediated response, where as BCNU and dimaide did not. These results suggest that a modulation in the GSH:GSSG ratio impairs endothelium-dependent dilation and alters total dilatory capacity (baseline-minimal CVR) and thus may have implications for adequate tissue perfusion. Across all studies there was significant correlation between GSH and GSSG with both baseline and minimal CVR. Therefore it is likely that changes in overall glutathione content plays a role in determining baseline and minimal coronary vascular resistance. These results demonstrate the complexity that manipulations of GSH have on both CVR and endothelium-dependent dilation, and provide mechanistic insight into how changes in GSH alter coronary vascular resistance and endothelium-dependent dilation

Comprehensive Evaluation of Right Heart Performance and Pulmonary Hemodynamics in Neonatal Pulmonary Hypertension: Evaluation of cardiopulmonary performance in neonatal pulmonary hypertension

Purpose of review: Pulmonary hypertension is characterized by an elevation of pulmonary artery pressures and prolonged exposure of the right ventricle to high afterload that collectively contribute to morbidity and mortality in both the term and preterm infants. This review summarizes the pathogenesis, etiologies, and hemodynamic profiles of the conditions that result in pulmonary hypertension in neonates. We explore the application of echocardiographic techniques for the assessment of right ventricular performance and pulmonary hemodynamics that enhance and guide the diagnosis and management strategies in neonates. Recent findings: Clinical assessments based on the determinants of mean pulmonary artery pressures (pulmonary vascular resistance, pulmonary blood flow, and pulmonary capillary wedge pressure) provide a physiologic approach in determining the acute and chronic etiologies of pulmonary hypertension in neonates. In addition, advances in neonatal echocardiography now afford the capability to obtain quantitative information that often precedes the qualitative information acquired by conventional methods and also provide sensitive markers of right ventricle performance for prognostic information based on the determinants of mean pulmonary artery pressures. Summary: Neonatal pulmonary hypertension represents a physiologic spectrum that accounts for the variance in clinical presentation and response to therapies. Physiology-based approaches to etiological identification, coupled with the emerging echocardiographic methods for the assessment of pulmonary hypertension in neonates will likely help to identify cardiovascular compromise earlier, guide therapeutic intervention, monitor therapeutic effectiveness, and improve overall outcome

Towards a development of a Social Engineering eXposure Index (SEXI) using publicly available personal information

Millions of people willingly expose their lives via Internet technologies every day, and even those who stay off the Internet find themselves exposed through data breaches. Trillions of private information records flow through the Internet. Marketers gather personal preferences to coerce shopping behavior, while providers gather personal information to provide enhanced services. Few users have considered where their information is going or who has access to it. Even fewer are aware of how decisions made in their own lives expose significant pieces of information, which can be used to harm the very organizations they are affiliated with by cyber attackers. While this threat can affect everyone, upper management provides a significantly higher risk due to their level of access to critical data and finances targeted by cybercrime. Thus, the goal of this work-in-progress research is to develop and validate a means to measure exposure to social engineering of 100 executives from Fortune 500 companies. This work-in-progress study will include a mixed methods approach combining an expert panel using the Delphi method, developmental research, and a quantitative data collection. The expert panel will provide a weighted evaluation instrument, subsequently used to develop an algorithm that will form the basis for a Social Engineering eXposure Index (SEXI) using publicly available personal information found on the Internet on these executives, which will help quantify the exposure of each executive. The collected data will be quantitatively evaluated, analyzed, and presented

Age-dependent human beta cell proliferation induced by glucagon-like peptide 1 and calcineurin signaling

Inadequate pancreatic beta cell function underlies type 1 and type 2 diabetes mellitus. Strategies to expand functional cells have focused on discovering and controlling mechanisms that limit the proliferation of human beta cells. Here, we developed an engraftment strategy to examine age-associated human islet cell replication competence and reveal mechanisms underlying age-dependent decline of beta cell proliferation in human islets. We found that exendin-4 (Ex-4), an agonist of the glucagon-like peptide 1 receptor (GLP-1R), stimulates human beta cell proliferation in juvenile but not adult islets. This age-dependent responsiveness does not reflect loss of GLP-1R signaling in adult islets, since Ex-4 treatment stimulated insulin secretion by both juvenile and adult human beta cells. We show that the mitogenic effect of Ex-4 requires calcineurin/nuclear factor of activated T cells (NFAT) signaling. In juvenile islets, Ex-4 induced expression of calcineurin/NFAT signaling components as well as target genes for proliferation-promoting factors, including NFATC1, FOXM1, and CCNA1. By contrast, expression of these factors in adult islet beta cells was not affected by Ex-4 exposure. These studies reveal age-dependent signaling mechanisms regulating human beta cell proliferation, and identify elements that could be adapted for therapeutic expansion of human beta cells