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Sinorhizobium melilotiis a model alpha-proteobacterium for investigating microbe-host interactions, in particular nitrogen-fixing rhizobium-legume symbioses. Successful infection requires complex coordination between compatible host and endosymbiont, including bacterial production of succinoglycan, also known as exopolysaccharide-I (EPS-I). InS. melilotiEPS-I production is controlled by the conserved ExoS-ChvI two-component system. Periplasmic ExoR associates with the ExoS histidine kinase and negatively regulates ChvI-dependent expression ofexogenes, necessary for EPS-I synthesis. We show that two extracytoplasmic proteins, LppA (a lipoprotein) and JspA (a metalloprotease), jointly influence EPS-I synthesis by modulating the ExoR-ExoS-ChvI pathway and expression of genes in the ChvI regulon. Deletions ofjspAandlppAled to lower EPS-I production and competitive disadvantage during host colonization, for bothS. melilotiwithMedicago sativaandS. medicaewithM. truncatula. Overexpression ofjspAreduced steady-state levels of ExoR, suggesting that the JspA protease participates in ExoR degradation. This reduction in ExoR levels is dependent on LppA and can be replicated with ExoR, JspA, and LppA expressed exogenously inCaulobacter crescentusandEscherichia coli. Akin to signaling pathways that sense extracytoplasmic stress in other bacteria, JspA and LppA may monitor periplasmic conditions during interaction with the plant host to adjust accordingly expression of genes that contribute to efficient symbiosis. The molecular mechanisms underlying host colonization in our model system may have parallels in related alpha-proteobacteria.Author summarySymbiotic bacteria that live in the roots of legume plants produce biologically accessible nitrogen compounds, offering a more sustainable and environmentally sound alternative to industrial fertilizers generated from fossil fuels. Understanding the multitude of factors that contribute to successful interaction between such bacteria and their plant hosts can help refine strategies for improving agricultural output. In addition, because disease-causing microbes share many genes with these beneficial bacteria, unraveling the cellular mechanisms that facilitate host invasion can reveal ways to prevent and treat infectious diseases. In this report we show that two genes in the model bacteriumSinorhizobium meliloticontribute to effective symbiosis by helping the cells adapt to living in host plants. This finding furthers knowledge about genetics factors that regulate interactions between microbes and their hosts.

Human and animal malaria parasites increase their host erythrocyte permeability to a broad range of solutes as mediated by parasite-associated ion channels. Molecular and pharmacological studies have implicated an essential role in parasite nutrient acquisition, but inhibitors suitable for development of antimalarial drugs are missing. Here, we generated a potent and specific drug lead using Plasmodium falciparum, a virulent human pathogen, and derivatives of MBX-2366, a nanomolar affinity pyridazinone inhibitor from a high-throughput screen. As this screening hit lacks the bioavailability and stability needed for in vivo efficacy, we synthesized 315 derivatives to optimize drug-like properties, establish target specificity, and retain potent activity against the parasite-induced permeability. Using a robust, iterative pipeline, we generated MBX-4055, a derivative active against divergent human parasite strains. MBX-4055 has improved oral absorption with acceptable in vivo tolerability and pharmacokinetics. It also has no activity against a battery of 35 human channels and receptors and is refractory to acquired resistance during extended in vitro selection. Single-molecule and single-cell patch-clamp indicate direct action on the plasmodial surface anion channel, a channel linked to parasite-encoded RhopH proteins. These studies identify pyridazinones as novel and tractable antimalarial scaffolds with a defined mechanism of action. SIGNIFICANCE STATEMENT: Because antimalarial drugs are prone to evolving resistance in the virulent human P. falciparum pathogen, new therapies are needed. This study has now developed a novel drug-like series of pyridazinones that target an unexploited parasite anion channel on the host cell surface, display excellent in vitro and in vivo ADME properties, are refractory to acquired resistance, and demonstrate a well defined mechanism of action.

Objectives We retrospectively examined the venous thromboembolism (VTE) events diagnosed in the Prophylaxis of High-Risk Ambulatory Cancer Patients Study (PHACS), a multi-center randomized trial, to assess the value of screening vascular imaging for the diagnosis of incidental VTE in high-risk cancer patients. Methods A total of 117 asymptomatic cancer patients with a Khorana score ≥3 starting a new systemic chemotherapy regimen were enrolled in a prospective randomized control trial. Patients underwent baseline venous ultrasound (US) of the lower extremities (LEs) and screening contrast-enhanced chest computed tomography (CT). Those without preexisting VTE were then randomized into observation or dalteparin prophylaxis groups and were screened with serial US every 4 weeks for up to 12 weeks and imaged with contrast-enhanced chest CT at 12 weeks. Any additional imaging performed during the study period was also evaluated for VTE. Results Baseline prevalence of incidental VTE was 9% (n = 10) with 58% percent of VTEs diagnosed by screening US. Incidence of VTE in the randomized phase of the trial was 16% (n = 16) with 21% (n = 10) of patients in the control arm and 12% (n = 6) of patients in the dalteparin arm developing VTE, a non-significant 9% absolute risk reduction (HR = 0.69, 95% CI 0.23-1.89). Sixty-nine percent of these patients were asymptomatic with 31% of patients diagnosed by screening US. Conclusions Adding screening US to routine oncologic surveillance CT in high-risk ambulatory cancer patients with a Khorana score ≥3 can lead to increased VTE detection, with potential for decreased morbidity, mortality, and health care spending.

We investigated the static reactions of highly delithiated Li(Ni1/3Mn1/3Co1/3)O2, Li(Ni0.5Mn0.3Co0.2)O2, Li(Ni0.6Mn0.2Co0.2)O2, and Li(Ni0.8Mn0.1Co0.1)O2 positive electrodes with 2,3-butanedione an...

The trans-translation pathway for rescuing stalled ribosomes is conserved and essential in bacterial pathogens but has no mammalian homolog, making it an ideal target for new antibiotics. We previously reported the discovery of a family of acylaminooxadiazoles that selectively inhibit trans-translation, resulting in broad-spectrum antibiotic activity. Optimization of the pharmacokinetic and antibiotic properties of the acylaminooxadiazoles produced MBX-4132, which cleared multiple-drug resistant Neisseria gonorrhoeae infection in mice after a single oral dose. Cryo-EM studies of non-stop ribosomes showed that acylaminooxadiazoles bind to a unique site near the peptidyl-transfer center and significantly alter the conformation of ribosomal protein L27, suggesting a novel mechanism for specific inhibition of trans-translation by these molecules.One Sentence SummaryRibosome rescue inhibitors reveal a new conformation of the ribosome and kill drug-resistant Neisseria gonorrhoeae in vivo.

Food-borne illness occurs through the consumption of food that has been tainted at some point in the food supply chain. While most contamination is accidental, there is some evidence of intentional food adulteration. This study explores the relationship between food safety practices and consumer behavior in a two-stage food supply chain. We use a vector-borne model to represent the spread of contaminated food through the supply chain. Based on our computational study,we determine the number of consumers that become ill as a result of a contamination event, describe the effect of consumer consumption and purchase behavior on the spread of food-borne illness, and evaluate the effects of various intervention strategies on consumer illness.

Does society benefit from encouraging or discouraging private infectious disease-risk mitigation? Private individuals routinely mitigate infectious disease risks through the adoption of a range of precautions, from vaccination to changes in their contact with others. Such precautions have epidemiological consequences. Private disease-risk mitigation generally reduces both peak prevalence of symptomatic infection and the number of people who fall ill. At the same time, however, it can prolong an epidemic. A reduction in prevalence is socially beneficial. Prolongation of an epidemic is not. We find that for a large class of infectious diseases, private risk mitigation is socially suboptimal—either too low or too high. The social optimum requires either more or less private mitigation. Since private mitigation effort depends on the cost of mitigation and the cost of illness, interventions that change either of these costs may be used to alter mitigation decisions. We model the potential for instruments that affect the cost of illness to yield net social benefits. We find that where a disease is not very infectious or the duration of illness is short, it may be socially optimal to promote private mitigation effort by increasing the cost of illness. By contrast, where a disease is highly infectious or long lasting, it may be optimal to discourage private mitigation by reducing the cost of disease. Society would prefer a shorter, more intense, epidemic to a longer, less intense epidemic. There is, however, a region in parameter space where the relationship is more complicated. For moderately infectious diseases with medium infectious periods, the social optimum depends on interactions between prevalence and duration. Basic reproduction numbers are not sufficient to predict the social optimum.

Since the September 11th terrorist attacks, there has been increased concern about the vulnerability of the food supply chain due to food outbreaks and recalls. This concern, as well as recurring instances of foodborne illness has made food safety and food defense an important public health priority in the United States. An understanding of the contamination process serves as a foundation for action by CDC, regulatory agencies, and industry. This study focuses on a mathematical model of a food contamination event that leads to consumer illness. We specifically consider how the consumer’s purchasing and consumption behavior impact their risk of food borne illness. We characterize the relationship between consumer behavior and consumer risk by product shelf life. We also show that consumer illness is more sensitive to changes in purchasing behavior rather than consumption behavior.

In the course of preparing the treatment of Nemacladus (Campanulaceae, Nemacladoideae) for Volume 18 of Flora of North America north of Mexico, it has become apparent that several new taxa must be described and others recircumscribed. These are: two new species of uncertain affinities from the White Mountains and Inyo Mountains; in the N. longiflorus A.Gray group, a new species and a variety elevated to species; four new species in the N. sigmoideus/N. secundiflorus complex; and a new variety of Nemacladus twisselmannii J.T.Howell.

The personal choices affecting the transmission of infectious diseases include the number of contacts an individual makes, and the risk-characteristics of those contacts. We consider whether these different choices have distinct implications for the course of an epidemic. We also consider whether choosing contact mitigation (how much to mix) and affinity mitigation (with whom to mix) strategies together has different epidemiological effects than choosing each separately. We use a set of differential equation compartmental models of the spread of disease, coupled with a model of selective mixing. We assess the consequences of varying contact or affinity mitigation as a response to disease risk. We do this by comparing disease incidence and dynamics under varying contact volume, contact type, and both combined across several different disease models. Specifically, we construct a change of variables that allows one to transition from contact mitigation to affinity mitigation, and vice versa. In the absence of asymptomatic infection we find no difference in the epidemiological impacts of the two forms of disease risk mitigation. Furthermore, since models that include both mitigation strategies are under-determined, varying both results in no outcome that could not be reached by choosing either separately. Which strategy is actually chosen then depends not on their epidemiological consequences, but on the relative cost of reducing contact volume versus altering contact type. Although there is no fundamental epidemiological difference between the two forms of mitigation, the social cost of alternative strategies can be very different. From a social perspective, therefore, whether one strategy should be promoted over another depends on economic not epidemiological factors.

The susceptible-infected-recovered (SIR) model has greatly evidenced epidemiology despite its apparent simplicity. Most applications of the SIR framework use a form of nonlinear incidence to describe the number of new cases per instant. We adapt theorems to analyze the stability of SIR models with a generalized nonlinear incidence structure. These theorems are then applied to the case of standard incidence and incidence resulting from adaptive behavioral response based on epidemiological-economic theory. When adaptive behavior is included in the SIR model multiple equilibria and oscillatory epidemiological dynamics can occur over a greater parameter space. Our analysis, based on the epidemiological-economic incidence, provides new insights into epidemics as complex adaptive systems, highlights important nonlinearities that lead to complex behavior, and provides mechanistic motivation for a shift away from standard incidence, and outlines important areas of research related to the complex-adaptive dynamics of epidemics.

The aging characteristics and the life expectancy of stator bar insulating systems are examined under load cycling conditions in a three-phase model stator, such as can arise with frequent start/stops of generators in service. It is demonstrated that the rate of stator bar insulation deterioration, when subjected simultaneously to electrical, mechanical, and thermal stresses, is influenced by the number of load cycles and magnitude of the temperature swings between the full- and zero-load conditions.

The science and management of infectious disease are entering a new stage. Increasingly public policy to manage epidemics focuses on motivating people, through social distancing policies, to alter their behavior to reduce contacts and reduce public disease risk. Person-to-person contacts drive human disease dynamics. People value such contacts and are willing to accept some disease risk to gain contact-related benefits. The cost–benefit trade-offs that shape contact behavior, and hence the course of epidemics, are often only implicitly incorporated in epidemiological models. This approach creates difficulty in parsing out the effects of adaptive behavior. We use an epidemiological–economic model of disease dynamics to explicitly model the trade-offs that drive person-to-person contact decisions. Results indicate that including adaptive human behavior significantly changes the predicted course of epidemics and that this inclusion has implications for parameter estimation and interpretation and for the development of social distancing policies. Acknowledging adaptive behavior requires a shift in thinking about epidemiological processes and parameters.

An SIS/SAS model of gonorrhea transmission in a population of highly active men-having-sex-with-men (MSM) is presented in this paper to study the impact of safe behavior on the dynamics of gonorrhea prevalence. Safe behaviors may fall into two categories-prevention and self-awareness. Prevention will be modeled via consistent condom use and self-awareness via STD testing frequency. Stability conditions for the disease free equilibrium and endemic equilibrium are determined along with a complete analysis of global dynamics. The control reproductive number is used as a means for measuring the effect of changes to model parameters on the prevalence of the disease. We also find that appropriate intervention would be in the form of a multifaceted approach at overall risk reduction rather than tackling one specific control individually.

Structure-activity relationships of a 4-aminoquinoline MCH1R antagonist lead series were explored by synthesis of analogs with modifications at the 2-, 4-, and 6-positions of the original HTS hit. Improvements to the original screening lead included lipophilic groups at the 2-position and biphenyl, cyclohexyl phenyl, and hydrocinnamyl carboxamides at the 6-position. Modifications of the 4-amino group were not well tolerated.

In July 1981, two of three skywalks in the atrium of the Hyatt Hotel located in Kansas City, Mo., collapsed, resulting in 113 deaths and 186 injuries. This catastrophic loss has been the subject of numerous investigative reports, news specials, and engineering reviews. This paper briefly reviews the facts and circumstances leading up to the failure so that readers will better appreciate the problems that arose from the complex interactions between design, specifications, construction, and quality control. Finally, the question of “Do we really learn from our mistakes?” is explored.

The aging characteristics of stator bars, which have been subjected to accelerated aging tests in a three-phase model stator under simultaneously applied electrical, mechanical, and thermal stresses, have been evaluated using diagnostic test procedures. The ac breakdown test has been found to be the most effective means for assessing the extent of aging undergone by the stator bars. The results indicate that under multistress conditions relatively small increases in the magnitudes of the stress acceleration factors are sufficient to lead to significant increases in the aging rate of the insulating systems of stator bars.

Un inventaire de l'occupation du sol pour chaque terrain agricole peut être produit par le croisement (automatisé) entre une image satellitaire classifiée et une image des terrains, provenant du cadastre numérisé. Trois sources d'erreur sont examinées. L'erreur planimétrique, créée par la « rasteurisation » des polygones-terrain, Terreur dans les proportions des classes d'occupation du sol due à la résolution spatiale, et l'erreur de la classification elle-même. Les résultats démontrent que chacune de ces erreurs varie en fonction des terrains, donnant des inventaires de qualité inégale. Il est difficile de le corréler avec les dimensions des terrains, et de fixer ainsi des dimensions minimales nécessaires au succès de l'inventaire agricole dans un milieu péri-urbain., An inventory of the land cover per individual agricultural plot can be produced by the cross-tabulation of a classified satellite image and an image of plots provided by the digitized land survey of the region. Three sources of error are examined. The planimetric error, created by the rasterization of the ground polygons, the proportional error in the land cover classes due to the spatial resolution and lastly, the classification error itself. The results show that each of these errors varies in relation to the land parcels which produces inventories of unequal quality. It is difficult to correlate them with the plot dimensions, and thus to set the minimal dimensions required to insure the success of the agricultural inventory in a suburban area.

Accelerated aging tests have been carried on stator bars under simultaneous electrical, thermal and mechanical multi-stress conditions, using a simulated three-phase model stator. Over each thermal load cycle, the partial discharge activity has been found to be a strong function of temperature. Tests at twice rated electrical stress did not result in any bar specimen failures up to a total of 1500 load cycles. However, when the three phase load current was increased above its rated value, current-limited type failures were observed to occur below 1000 load cycles, thereby indicating a marked influence of thermal and mechanical stresses associated with the elevated three phase load current.

The present study was designed to explore serial position and suffix effects in the short-term retention of nonverbal sounds. In contrast with previous studies of these effects, a probe recognition paradigm was used to minimize the possibility that participants would use a verbal labelling strategy. On each trial, participants heard a memory set consisting of three pure tones, followed five seconds later by a probe tone. Participants were required to indicate whether or not the probe tone had been a member of the memory set. On most trials, a suffix sound was presented 1 second following the third sound in the memory set. Results revealed that tones presented in the first and last positions of the memory set were recognized more accurately than were tones presented in the middle position. Furthermore, recognition of sounds presented in the last position was compromised when the memory set was followed by a postlist suffix of similar pitch, spectral composition, and spatial location.

Background and Purpose. The purpose of this case report is to describe an occupational rehabilitation program for a person whose work-related inguinal hernia was surgically repaired. Case Description. A 35-year-old baggage service attendant acquired an inguinal hernia while lifting at work. Postoperatively, the patient had discomfort in the groin, weakness of the lower extremities and trunk, limited ability to walk, and a decreased ability to work due to impaired tolerance.Outcomes. Following postoperative rehabilitation, the patient was able to return to full-time, full-duty work. Discussion. This case report describes occupational rehabilitation as a method to treat patients with work-related inguinal hernias following surgical repair.

The Flora of North America north of Mexico treats all native and naturalized vascular plants and bryophytes in Canada, Greenland, St. Pierre et Miquelon, and the continental United States including the Florida Keys and Aleutian Islands (approximately 18 million square kilometers). It provides accepted names, literature citations, basionyms, synonyms, morphological descriptions, habitat, geographical distribution, conservation or weed status, and a discussion of taxonomic issues for approximately 20,000 species. Of the total 30 volumes anticipated, 18 have been published and one is in press, treating 2021 genera and 12,393 species. For the remaining volumes, 763 genera and 5,008 species have been submitted, and 82 of the 144 families have been submitted in full. Completion is anticipated by the end of 2017. The project is managed by the Flora of North America Association. Content from published volumes is available through eFloras and JSTOR and has been provided to the World Flora informatics team. Resumo A Flora da América do Norte ao Norte do México trata todas as espécies de plantas vasculares e briófitas ocorrente sno Canadá, Groenlândia, St. Pierre et Miquelon e na parte continental dos Estados Unidos, incluindo as Florida Keys e as Aleutian Islands (aproximadametne 18 milhões de kilômetros quadrados). Informações como nomes aceitos, citações bibliográficas, basiônimos, sinonímia, descrições morfológicas, habitat, distribuição geográfica, estado de conservação e informação sobre invasoras, bem como discussões relativas à taxonomia de aproximadamente 20.000 espécies. A previsão final é de 30 volumes, sendo que, nos 18 já publicados e naquele que está no prelo, foram tratados 2021 gêneros e 12,393 espécies. Os restantes volumes contam com a submissão de 763 gêneros e 5.008 espécies, sendo que 82 das 144 famílias estão completas. A finalização da flora está prevista para 2017. O projeto é gerenciado pela Flora of North America Association. O conteúdo dos volumes publicados está disponibilizado através de e-Floras e do JSTOR, e foi repassado para o time de informática do projeto World Flora.

Presently marketed vaginal barrier methods are cytotoxic and damaging to the vaginal epithelium and natural vaginal flora when used frequently. Novel noncytotoxic agents are needed to protect men and women from sexually transmitted diseases. One novel candidate is a mandelic acid condensation polymer, designated SAMMA. The spectrum and mechanism of antiviral activity were explored using clinical isolates and laboratory-adapted strains of human immunodeficiency virus (HIV) and herpes simplex virus (HSV). SAMMA is highly effective against all CCR5 and CXCR4 isolates of HIV in primary human macrophages and peripheral blood mononuclear cells. SAMMA also inhibits infection of cervical epithelial cells by HSV. Moreover, it exhibits little or no cytotoxicity and has an excellent selectivity index. SAMMA, although not a sulfonated or sulfated polymer, blocks the binding of HIV and HSV to cells by targeting the envelope glycoproteins gp120 and gB-2, respectively, and also inhibits HSV entry postattachment. SAMMA is an excellent, structurally novel candidate microbicide that warrants further preclinical evaluation.

Neuropeptide Y (NPY) is a polypeptide found in the peripheral and central nervous system and is involved in the regulation of feeding. Antagonists of NPY receptor activation could therefore have potential for development as antiobesity drugs. Fermentation of an isolate of Xylaria persicaria yielded two novel eremophilane sesquiterpenoids xylarenals A (1) and B (2). These compounds are selective for the NPY Y5 receptor but have only modest affinity. The isolation, structure elucidation, and biological activities of these compounds are described.

The susceptible-infected-recovered (SIR) model has greatly evidenced epidemiology despite its apparent simplicity. Most applications of the SIR framework use a form of nonlinear incidence to describe the number of new cases per instant. We adapt theorems to analyze the stability of SIR models with a generalized nonlinear incidence structure. These theorems are then applied to the case of standard incidence and incidence resulting from adaptive behavioral response based on epidemiological-economic theory. When adaptive behavior is included in the SIR model multiple equilibria and oscillatory epidemiological dynamics can occur over a greater parameter space. Our analysis, based on the epidemiological-economic incidence, provides new insights into epidemics as complex adaptive systems, highlights important nonlinearities that lead to complex behavior, and provides mechanistic motivation for a shift away from standard incidence, and outlines important areas of research related to the complex-adaptive dynamics of epidemics.

Human melanin-concentrating hormone (hMCH) is a potent but nonselective agonist at human melanin-concentrating hormone receptors 1 and 2 (hMCH-1R and hMCH-2R, respectively). To determine the structural features of this neuropeptide which are necessary for efficient binding to and activation of the receptors, Ala-substituted, open-chain, and truncated analogues were synthesized and tested in the binding assays in CHO cells expressing hMCH-1R and hMCH-2R, and in functional assays measuring the level of intracellular calcium mobilization in human HEK-293 cells expressing these receptors. A compound consisting merely of the cyclic core of hMCH with the Arg attached to the N-terminus of the disulfide ring was found to activate both hMCH-1R and hMCH-2R about as effectively as full-length hMCH. Thus, the sequence Arg-cyclo(S-S)(Cys-Met-Leu-Gly-Arg-Val-Tyr-Arg-Pro-Cys) appears to constitute the "active core" that is necessary for agonist potency at hMCH-1R and hMCH-2R. A potent and approximately 4-fold more selective agonist at hMCH-1R than at hMCH-2R is also reported.

Melanin-concentrating hormone (MCH) is a 19-aa cyclic neuropeptide originally isolated from chum salmon pituitaries. Besides its effects on the aggregation of melanophores in fish several lines of evidence suggest that in mammals MCH functions as a regulator of energy homeostasis. Recently, several groups reported the identification of an orphan G protein-coupled receptor as a receptor for MCH (MCH-1R). We hereby report the identification of a second human MCH receptor termed MCH-2R, which shares about 38% amino acid identity with MCH-1R. MCH-2R displayed high-affinity MCH binding, resulting in inositol phosphate turnover and release of intracellular calcium in mammalian cells. In contrast to MCH-1R, MCH-2R signaling is not sensitive to pertussis toxin and MCH-2R cannot reduce forskolin-stimulated cAMP production, suggesting an exclusive G α q coupling of the MCH-2R in cell-based systems. Northern blot and in situ hybridization analysis of human and monkey tissue shows that expression of MCH-2R mRNA is restricted to several regions of the brain, including the arcuate nucleus and the ventral medial hypothalamus, areas implicated in regulation of body weight. In addition, the human MCH-2R gene was mapped to the long arm of chromosome 6 at band 6q16.2–16.3, a region reported to be associated with cytogenetic abnormalities of obese patients. The characterization of a second mammalian G protein-coupled receptor for MCH potentially indicates that the control of energy homeostasis in mammals by the MCH neuropeptide system may be more complex than initially anticipated.

A full scale three-phase multi-stress accelerated electrical aging test facility for stator bars is described. Electrical aging characteristics may be determined under simultaneous electrical, mechanical and electrical stress at either 60 Hz or an accelerated frequency of 400 Hz. Typical initial aging data are presented and discussed.

Neuropeptide Y (NPY) increases food intake through the action of hypothalamic NPY receptors. At least six subtypes of NPY, peptide YY (PYY), and pancreatic polypeptide (PP) receptors have been identified in mice. Although the involvement of Y1 and Y5 receptors in feeding regulation has been suggested, the relative importance of each of these NPY receptors and the participation of a novel feeding receptor are still unclear. To address this issue, we generated a Y1 receptor-deficient (Y1-/-) and a Y5 receptor-deficient (Y5-/-) mouse line in which we directly compared the orexigenic effects of NPY and its analogs after intracerebroventricular (icv) administration. The icv NPY-induced food intake was remarkably reduced in Y1-/- mice, but was not significantly altered by inactivation of the Y5 receptor. The Y1 receptor therefore plays a dominant role in NPY-induced feeding. Stimulation of feeding by moderately selective Y5 agonists [PYY-(3-36), human PP, and bovine PP] was reduced in Y5-/- mice, although food intake did not decrease to vehicle control levels. These results indicate that the Y5 receptor functions as one of the feeding receptors. In addition, the finding that Y5-preferring agonists still induce food intake in Y5-/- mice suggests a role for another NPY receptor(s), including the possibility of novel NPY receptors. Surprisingly, despite the limited efficacy of PYY-(3-36) and PPs at the Y1 receptor, food consumption induced by these agonists was significantly diminished in Y1-/- mice compared with that in wild-type controls. These observations suggest that the feeding stimulation induced by NPY and its analogs may be directly or indirectly modulated by the action of the Y1 receptor. We conclude that multiple NPY receptors, possibly including the novel feeding receptor, are involved in the feeding response evoked by NPY and its analogs. Among them, the Y1 receptor plays a key role in NPY-induced feeding in mice.

We compared habitat associations of southern Gulf of St. Lawrence Atlantic cod (Gadus morhua) and American plaice (Hippoglossoides platessoides) between the summer feeding season on the Magdalen Shallows and the overwintering period in the Cabot Strait. Data were from bottom trawl surveys conducted in September 1993, 1994, and 1995 and January 1994, 1995, and 1996. Both species occupied much deeper, warmer water in winter than in summer. The effect of cod age on temperature distribution reversed between the two seasons, with younger cod occupying warmer water than older cod in summer and colder water in winter. Selection of both depth and temperature by cod tended to be more significant in September than in January. The reduced statistical significance of habitat selection by cod in winter was associated with a more aggregated distribution in this season. The contrast between seasons in habitat associations was particularly strong for plaice. The median habitats occupied by plaice were 58-67 m and -0.1 to 0.3°C in September and 374-426 m and 5.2-5.4°C in January. Habitat selection by plaice was significant in both seasons, but significance tended to be greater in January. Degree of aggregation in plaice distribution was similar between the two seasons. Female plaice occupied significantly warmer water than males in September but not in January. The ecological and practical implications of this striking seasonal variation in habitat associations are discussed.

Retraction is a major rate-limiting step in cell motility, particularly in slow moving cell types that form large stable adhesions. Myosin II dependent contractile forces are thought to facilitate detachment by physically pulling up the rear edge. However, retraction can occur in the absence of myosin II activity in cell types that form small labile adhesions. To investigate the role of contractile force generation in retraction, we performed traction force microscopy during the movement of fish epithelial keratocytes. By correlating changes in local traction stress at the rear with the area retracted, we identified four distinct modes of retraction. “Recoil” retractions are preceded by a rise in local traction stress, while rear edge is temporarily stuck, followed by a sharp drop in traction stress upon detachment. This retraction type was most common in cells generating high average traction stress. In “pull” type retractions local traction stress and area retracted increase concomitantly. This was the predominant type of retraction in keratocytes and was observed mostly in cells generating low average traction stress. “Continuous” type retractions occur without any detectable change in traction stress, and are seen in cells generating low average traction stress. In contrast, to many other cell types, “release” type retractions occur in keratocytes following a decrease in local traction stress. Our identification of distinct modes of retraction suggests that contractile forces may play different roles in detachment that are related to rear adhesion strength. To determine how the regulation of contractility via MLCK or Rho kinase contributes to the mechanics of detachment, inhibitors were used to block or augment these pathways. Modulation of MLCK activity led to the most rapid change in local traction stress suggesting its importance in regulating attachment strength. Surprisingly, Rho kinase was not required for detachment, but was essential for localizing retraction to the rear. We suggest that in keratocytes MLCK and Rho kinase play distinct, complementary roles in the respective temporal and spatial control of rear detachment that is essential for maintaining rapid motility.

© 2014, The Author(s). Mathematical epidemiology, one of the oldest and richest areas in mathematical biology, has significantly enhanced our understanding of how pathogens emerge, evolve, and spread. Classical epidemiological models, the standard for predicting and managing the spread of infectious disease, assume that contacts between susceptible and infectious individuals depend on their relative frequency in the population. The behavioral factors that underpin contact rates are not generally addressed. There is, however, an emerging a class of models that addresses the feedbacks between infectious disease dynamics and the behavioral decisions driving host contact. Referred to as “economic epidemiology” or “epidemiological economics,” the approach explores the determinants of decisions about the number and type of contacts made by individuals, using insights and methods from economics. We show how the approach has the potential both to improve predictions of the course of infectious disease, and to support development of novel approaches to infectious disease management.

O NE of the most urgent global issues is preservation of biodiversity. Establishing a baseline for such an effort should include: determining what species exist, how they are related to other species, where they live, how their distributions are expanding or receding, and which are endangered. For the plant species of the United States and Canada, the most up-to-date compilation of such information will be provided by the Flora of North America North of Mexico (FNA), the official name of the project. The plant life of this continent is remarkably rich and diverse, with about 20,000 species of plants in the area north of Mexico alone. Of the native genera, 3817o are found only in North America, and an additional 18% are found only in the Western Hemisphere. The Flora of North America is the first comprehensive description of all plants growing spontaneously in this area. The project, a collaborative, bi-national effort of more than 30 major botanical institutions in the United States and Canada, draws on the expertise of botanists around the world to write and review treatments. The Missouri Botanical Garden in St. Louis serves as the organizational center for the project. The 30 volumes of the Flora of North America are to be published over about 15 years, with the first two volumes published in 1993. The Flora of North America is the first project compiled on a database as well as books, making it easier to compile the information as well as making it available electronically. (See the section on the On-Line Resources.) For the only other Floras of similar scope, Flora Europaea and Flora USSR, the publications were compiled with no equivalent database. (The capitalized word "Flora" is used when referring to a publication; the lowercase "flora" refers to the plants in an area.)

The reliability of substation connectors is a constant concern for electrical utilities and represents one of the weak links of Hydro-Quebec's 735 kV power system. This paper describes some of the early findings of current-cycling tests on 4000 kcmil aluminum cable connectors and defines the need for more stringent qualification test specifications. Use of the ANSI C119.4 light-duty (125 cycles) test specification revealed a strong dependency on basic parameters such as surface roughness, dimension, type and surface finish of hardware, surface preparation, mounting techniques, etc. The first batch of test samples failed dramatically at an early stage in the current and load cycling tests. Some recommendations are formulated.