Ecosystem service bundles for analyzing tradeoffs in diverse landscapes.

A key challenge of ecosystem management is determining how to manage multiple ecosystem services across landscapes. Enhancing important provisioning ecosystem services, such as food and timber, often leads to tradeoffs between regulating and cultural ecosystem services, such as nutrient cycling, flood protection, and tourism. We developed a framework for analyzing the provision of multiple ecosystem services across landscapes and present an empirical demonstration of ecosystem service bundles, sets of services that appear together repeatedly. Ecosystem service bundles were identified by analyzing the spatial patterns of 12 ecosystem services in a mixed-use landscape consisting of 137 municipalities in Quebec, Canada. We identified six types of ecosystem service bundles and were able to link these bundles to areas on the landscape characterized by distinct social-ecological dynamics. Our results show landscape-scale tradeoffs between provisioning and almost all regulating and cultural ecosystem services, and they show that a greater diversity of ecosystem services is positively correlated with the provision of regulating ecosystem services. Ecosystem service-bundle analysis can identify areas on a landscape where ecosystem management has produced exceptionally desirable or undesirable sets of ecosystem services.

Nicotinamide adenine dinucleotide based therapeutics.

Nicotinamide adenine dinucleotide (NAD), generally considered a key component involved in redox reactions, has been found to participate in an increasingly diverse range of cellular processes, including signal transduction, DNA repair, and post-translational protein modifications. In recent years, medicinal chemists have become interested in the therapeutic potential of molecules affecting interactions of NAD with NAD-dependent enzymes. Also, enzymes involved in de novo biosynthesis, salvage pathways, and down-stream utilization of NAD have been extensively investigated and implicated in a wide variety of diseases. These studies have bolstered NAD-based therapeutics as a new avenue for the discovery and development of novel treatments for medical conditions ranging from cancer to aging. Industrial and academic groups have produced structurally diverse molecules which target NAD metabolic pathways, with some candidates advancing into clinical trials. However, further intensive structural, biological, and medical studies are needed to facilitate the design and evaluation of new generations of NAD-based therapeutics. At this time, the field of NAD-therapeutics is most likely at a stage similar to that of the early successful development of protein kinase inhibitors, where analogs of ATP (a more widely utilized metabolite than NAD) began to show selectivity against target enzymes. This review focuses on key representative opportunities for research in this area, which extends beyond the scope of this article.

Clathrin hub expression dissociates the actin-binding protein Hip1R from coated pits and disrupts their alignment with the actin cytoskeleton.

The actin cytoskeleton has been implicated in the maintenance of discrete sites for clathrin-coated pit formation during receptor-mediated endocytosis in mammalian cells, and its function is intimately linked to the endocytic pathway in yeast. Here we demonstrate that staining for mammalian endocytic clathrin-coated pits using a monoclonal antibody against the AP2 adaptor complex revealed a linear pattern that correlates with the organization of the actin cytoskeleton. This vesicle organization was disrupted by treatment of cells with cytochalasin D, which disassembles actin, or with 2,3-butanedione monoxime, which prevents myosin association with actin. The linear AP2 staining pattern was also disrupted in HeLa cells that were induced to express the Hub fragment of the clathrin heavy chain, which acts as a dominant-negative inhibitor of receptor-mediated endocytosis by direct interference with clathrin function. Additionally, Hub expression caused the actin-binding protein Hip1R to dissociate from coated pits. These findings indicate that proper function of clathrin is required for coated pit alignment with the actin cytoskeleton and suggest that the clathrin-Hip1R interaction is involved in the cytoskeletal organization of coated pits.

Clathrin hub expression affects early endosome distribution with minimal impact on receptor sorting and recycling.

Clathrin-coated vesicles execute receptor-mediated endocytosis at the plasma membrane. However, a role for clathrin in later endocytic trafficking processes, such as receptor sorting and recycling or maintaining the organization of the endocytic pathway, has not been thoroughly characterized. The existence of clathrin-coated buds on endosomes suggests that clathrin might mediate later endocytic trafficking events. To investigate the function of clathrin-coated buds on endosomal membranes, endosome function and distribution were analyzed in a HeLa cell line that expresses the dominant-negative clathrin inhibitor Hub in an inducible manner. As expected, Hub expression reduced receptor-mediated endocytosis at the plasma membrane. Hub expression also induced a perinuclear aggregation of early endosome antigen 1-positive early endosomes, such that sorting and recycling endosomes were found tightly concentrated in the perinuclear region. Despite the dramatic redistribution of endosomes, Hub expression did not affect the overall kinetics of receptor sorting or recycling. These data show that clathrin function is necessary to maintain proper cellular distribution of early endosomes but does not play a prominent role in sorting and recycling events. Thus, clathrin's role on endosomal membranes is to influence organelle localization and is distinct from its role in trafficking pathways at the plasma membrane and trans-Golgi network.

Paced mating behavior in the naturally cycling and the hormone-treated female rat.

During a sexual encounter with a male rat, a female rat will display both receptive (lordosis) and proceptive (hopping, darting, and ear-wiggling) behaviors. Additionally, if mating occurs in an environment where the female rat may approach and withdraw from the male rat, she will control the timing of the receipt of mounts, intromissions, and ejaculations. This temporal patterning by the female rat is known as paced mating behavior. The present experiment compared paced mating behavior in rats during an intact, proestrous phase and an ovariectomized phase, during which they were treated with estradiol benzoate (10 microg per rat) and progesterone (0.5 mg per rat). Though no differences in sexual receptivity were observed across the two phases, patterns of paced mating behavior were found to differ. Specifically, female rats exhibited significantly longer contact-return latencies when hormone treated than when intact.

Computer-based methods for measuring joint space and estimating erosion volume in the finger and wrist joints of patients with rheumatoid arthritis.

OBJECTIVE: This study was conducted 1) to determine the feasibility of using computer programs to measure radiographic joint space width and estimate erosion volume in the hands of patients with rheumatoid arthritis (RA), and 2) to compare the new computer-based methods with established scoring methods. METHODS: To measure the joint space width in the finger and wrist joints of RA patients, hand and wrist radiographic films were scanned using a tabletop scanner and analyzed with programs written using the "macro" capabilities of NIH Image software. Estimation of erosion volume was determined by utilizing gray-scale intensity to calibrate bone density units per mm3, which made possible comparisons between the erosions and noneroded, anatomically similar sites. RESULTS: In 3 sets of duplicate measurements of joint space width on 79, 48, and 48 finger and wrist joints, the mean absolute deviation from the mean of the 2 measurements was 0.036 mm (SD 0.034), 0.032 mm (SD 0.049), and 0.021 mm (SD 0.016), respectively. Joint space measurements and scoring of joint space narrowing both demonstrated a difference between active treatment and placebo in an old trial set on gold therapy (P = 0.03 and P = 0.01, respectively). Two repeated measurements of bone density units in the bones of 3 different hands differed from the mean of the measurement by 2.29-4.04%. In 2 experiments, estimates of erosion volume showed a greater difference between gold therapy and placebo than did erosion scores in the trial set (P = 0.049 and P = 0.016 versus P = 0.27). CONCLUSION: Computer-based methods for measuring finger and wrist joint spaces and estimating erosion volume in patients with RA agree with the results of radiographic scoring of erosions and joint space narrowing.

Trends in self-reported use of mammograms (1989-1997) and Papanicolaou tests (1991-1997)--Behavioral Risk Factor Surveillance System.

PROBLEM/CONDITION: In 1999, an estimated 175,000 women will be diagnosed with breast cancer, and 43,300 will die from the disease. In the same year, an estimated 12,800 women will be diagnosed with invasive cervical cancer, and 4,800 will die from it. Early detection and timely treatment of breast cancer and cervical dysplasia can alter the progress of and reduce mortality from these diseases. REPORTING PERIOD COVERED: 1989-1997 for breast cancer screening and 1991-1997 for cervical cancer screening. DESCRIPTION OF SYSTEM: The Behavioral Risk Factor Surveillance System is a state-based telephone survey of the civilian, noninstitutionalized adult population (i.e., persons aged > or =18 years). In this report, responses for women aged > or =40 years are included for measures of breast cancer screening, and responses for women aged > or =18 years with an intact uterine cervix are included for measures of cervical cancer screening. RESULTS: The percentage of women aged > or =40 years who reported ever participating in breast cancer screening and the proportion who had participated within the previous 2 years increased during 1989-1997. The percentage of women aged > or =18 years who reported ever participating in cervical cancer screening and the proportion who had participated within the previous 2 years were stable during 1991-1997. For both types of screening, substantially fewer women had received screening within the previous 2 years than had ever been screened. INTERPRETATION: These findings may indicate that some women who participate in initial screening do not seek further screening. ACTIONS TAKEN: Initiatives to encourage women to receive initial screening should continue, but additional initiatives specifically aimed at promoting rescreening should be developed. Continued surveillance of the percentage of women who receive regular screening will help public health officials evaluate breast and cervical cancer prevention programs.

Human pathogen subversion of antigen presentation.

Many pathogens have co-evolved with their human hosts to develop strategies for immune evasion that involve disruption of the intracellular pathways by which antigens are bound by class I and class II molecules of the major histocompatibility complex (MHC) for presentation to T cells. Here the molecular events in these pathways are reviewed and pathogen interference is documented for viruses, extracellular and intracellular bacteria and intracellular parasites. In addition to a general review, data from our studies of adenovirus, Chlamydia trachomatis and Coxiella burnetii are summarized. Adenovirus E19 is the first viral gene product described that affects class I MHC molecule expression by two separate mechanisms, intracellular retention of the class I heavy chain by direct binding and by binding to the TAP transporter involved in class I peptide loading. Coxiella and Chlamydia both affect peptide presentation by class II MHC molecules as a result of their residence in endocytic compartments, although the properties of the parasitophorous vacuoles they form are quite different. These examples of active interference with antigen presentation by viral gene products and passive interference by rickettsiae and bacteria are typical of the strategies used by these different classes of pathogens, which need to evade different types of immune responses. Pathogen-host co-evolution is evident in these subversion tactics for which the pathogen crime seems tailored to fit the immune system punishment.

Cutting edge: adenovirus E19 has two mechanisms for affecting class I MHC expression.

Viral strategies for immune evasion include inhibition of various steps in the class I MHC assembly pathway. Here, we demonstrate that adenovirus produces one gene product with a dual function in this regard. It is well established that adenovirus E19 binds class I molecules and retains them in the endoplasmic reticulum (ER). However, E19 also delays the expression of class I alleles to which it cannot tightly bind. Here, we show that E19 binds TAP and acts as a tapasin inhibitor, preventing class I/TAP association. DeltaE19, an E19 mutant lacking the ER-retention signal, delays maturation of class I molecules, indicating that E19's inhibition of class I/TAP interaction is sufficient to delay class I expression. These data identify tapasin inhibition as a novel mechanism of viral immune evasion and suggest that, through this secondary mechanism, adenovirus can affect Ag presentation by MHC alleles that it can only weakly affect by direct retention.

Paced mating behavior in female rats in response to different hormone priming regimens.

A female rat will display a repertoire of behaviors during a sexual encounter with a male rat including sexually receptive (the lordosis response) and proceptive (hopping, darting) behaviors. In addition, when given the opportunity, a sexually receptive female rat will approach and withdraw from the male rat, controlling the timing of the receipt of mounts, intromissions, and ejaculations, a behavior known as paced mating behavior. The present experiments tested the hypotheses (1) that progesterone regulates paced mating behavior, and (2) that multiple hormone regimens used previously to induce sexual receptivity have the same effect on paced mating behavior. Paced mating behavior was assessed in sexually receptive ovariectomized female rats after treatment with: (1) estradiol benzoate (EB; 30.0 mg/kg) followed by a range of doses of progesterone (P; 1.0-8.0 mg/kg), (2) two pulses of unesterified estradiol (E2; 2.0 microg/rat) followed by 1.0 mg/rat of P, and (3) EB alone (5.0 microg/rat) for 6 days. No differences in sexual receptivity or in paced mating behavior were observed across doses of P (1.0-8.0 mg/kg). In contrast, the number of hops and darts per min increased with the dose of P administered. E2 + P administration resulted in slightly, but significantly, lower levels of sexual receptivity along with significantly longer contact-return latencies following an intromission in relation to the other treatment conditions. In addition, female rats exhibited fewer hops and darts per min in response to E2 + P than in response to EB + 8.0 mg/kg of P. The administration of EB alone for 6 days induced levels of receptivity and paced mating behavior indistinguishable from EB + P, while eliciting significantly fewer hops and darts per min than the EB + 8.0 mg/kg P treatment condition. Hormone priming regimen had no effect on the percentage of exits displayed during the paced mating tests in any experimental phase. Dose of P had no effect on paced mating behavior in sexually receptive rats. In addition, P does not appear to be necessary for the display of paced mating behavior following long-term treatment with EB. In contrast, the pulsatile administration of E2 + P induced a different pattern of paced mating behavior in sexually receptive rats.

Alcohol consumption by pregnant women in the United States during 1988-1995.

OBJECTIVE: To examine trends in alcohol use among pregnant women in the United States and to characterize pregnant women who use alcohol, with an emphasis on frequent use (at least five drinks per occasion or at least seven drinks per week). METHODS: We used the Behavioral Risk Factor Surveillance System data from 1988 through 1995 to obtain the percentage of pregnant women who used alcohol. We used multiple logistic models to identify subgroups of pregnant women who are at increased risk for alcohol use. RESULTS: Overall, 14.6% (869 of 5983) of pregnant women consumed alcohol and 2.1% (133 of 5983) consumed alcohol frequently. Among pregnant women, alcohol use decreased from 22.5% (95% confidence interval [CI] 20.8, 23.9) in 1988 to 9.5% (95% CI 7.9, 11.8) in 1992 and then increased to 15.3% (95% CI 13.1, 17.2) by 1995. Among pregnant women, frequent alcohol use decreased from 3.9% (95% CI 2.4, 5.2) in 1988 to 0.9% (95% CI 0.4, 1.6) in 1991 and then increased to 3.5% (95% CI 2.0, 5.1) by 1995. Pregnant women who were at high risk for alcohol use were college educated, unmarried, employed, or students, had annual household incomes of more than $50,000, or were smokers. Pregnant women who were at high risk for frequent alcohol use were more likely to be unmarried, or smokers. CONCLUSION: The increasing prevalence of alcohol use among pregnant women calls for increased ascertainment of alcohol use among preconceptional and pregnant women. Brief interventions by clinicians, increased referral to alcohol treatment programs, and increased use of contraception by women of reproductive age who are problem drinkers should be considered as means of preventing alcohol-exposed pregnancies.

Stanozolol, oxymetholone, and testosterone cypionate effects on the rat estrous cycle.

Anabolic-androgenic steroid (AAS) effects on the estrous cycle of adult Long-Evans rats were examined in four different experiments. Sexual receptivity, vaginal cytology, and body weight were monitored throughout two-week baseline, AAS treatment, and recovery periods. In Experiments 1-3, rats were administered stanozolol, oxymetholone, or testosterone cypionate within dose ranges selected to mimic the human abuse levels of each compound. In these studies, the highest doses of stanozolol (5 mg/kg), oxymetholone (12 mg/kg), or testosterone cypionate (7.5 mg/kg) disrupted the cyclical display of sexual receptivity and vaginal estrus. To compare effects on estrous cyclicity across AAS compounds, rats in Experiment 4 received a single dose (7.5 mg/kg) of each compound for 2 weeks. At the 7.5 mg/kg dose, all AAS compounds interfered with the cyclical display of vaginal estrus, although effects on sexual receptivity were not uniform. No striking AAS effects on body weight were seen in any experiment. The short-term administration of AAS compounds at high doses disrupts female neuroendocrine function in rats.

Considerations for conducting group intervention with adults who stutter.

With recent changing trends in healthcare delivery and reimbursement, the focus on more efficient and cost-effective intervention has become increasingly important. A summary of desired clinician skills and responsibilities reported in the literature are presented along with information on structuring group intervention. Preliminary findings and a rationale for conducting speech therapy in a group environment with several adults who suffer are presented. In addition, findings and perceptions gleaned from the authors' experience in conducting group treatment with persons who stutter are also discussed.

Is abuse during childhood a risk factor for developing substance abuse problems as an adult?

The purpose of this study was to evaluate the relationship between a history of childhood physical abuse and later substance abuse, controlling for family history of substance abuse. The study was a cross-sectional survey. Subjects were a convenience sample of mothers with children younger than 6 years being seen for routine care in five pediatric clinics. Mothers were given an anonymous, self-administered questionnaire on demographics, substance abuse, history of physical abuse, and family history of substance abuse. Of the 733 respondents, 24% reported having been physically abused, 24% reported a family history of substance abuse, and 36% had a positive screen for substance abuse. A positive screen for substance abuse was more common among those who reported having been abused than those who had not (47% vs 32%, p < .001). After controlling for family history of substance abuse, a history of being abused remained significantly associated with current substance abuse (odds ratio = 1.58, 95% confidence interval 1.1, 2.2). Suffering abuse during childhood is a significant risk factor for later substance abuse, even after controlling for a family history of substance abuse. Clinicians treating victims of abuse may wish to include substance abuse prevention measures.

Weight-loss practices of overweight adults.

Data from the Behavioral Risk Factor Surveillance System, 1985-1988, were used to assess differences in weight-loss practices of overweight adults by sex and race. Data were available for 112,108 respondents from 21 states, aged greater than or equal to 18 y. Overweight was defined as body mass index greater than or equal to 27.3 for women and greater than or equal to 27.8 for men. Weight-loss practices were defined as increasing physical activity only, eating fewer calories only, increasing physical activity and eating fewer calories only, increasing physical activity and eating fewer calories, and not trying to lose weight. The weight-loss practice most frequently reported by overweight women was increasing physical activity and eating fewer calories (blacks, 32%; whites, 33%). Overweight men most frequently reported not trying to lose weight (blacks, 55%; whites, 49%). Although the prevalence of overweight for black women was twice that for white women, weight-loss practices were similar for both groups. Prevalence of overweight was similar for black and white men but weight-loss practices differed slightly.

Identification of two structurally and functionally distinct sites on human platelet membrane glycoprotein IIb-IIIa using monoclonal antibodies.

Platelet membrane glycoprotein IIb-IIIa exists as a calcium-dependent complex of two large peptides (designated IIb and IIIa) in Triton X-100 solutions, but it remains unknown if these peptides are subunits of one glycoprotein or are actually two individual glycoproteins in the intact platelet membrane. We used crossed immunoelectrophoresis to define the epitopes of two monoclonal antibodies to IIb-IIIa, then used these antibodies to study the structural and functional organization of IIb and IIIa in the platelet membrane. Human platelets solubilized in Triton X-100 were electrophoresed through an intermediate gel containing 125I-monoclonal IgG, then into an upper gel containing rabbit anti-human platelet antibodies. Our previously characterized antibody. Tab, and a new monoclonal antibody, T10, both bound to the immunoprecipitate corresponding to the IIb-IIIa complex. When platelets were electrophoresed after solubilization in 5 mM EDTA, 125I-Tab bound to the dissociated IIb polypeptide, but not to IIIa. In contrast, 125-I-T10 did not react with either IIb or IIIa. Thus, Tab recognizes a determinant on IIb, while T10 recognizes a determinant created only after the association of IIb and IIIa. Gel-filtered platelets from six normal donors bound 50,600 +/- 5,600 125I-T10 molecules/platelet and 47,800 +/- 11,200 125I-Tab molecules/platelet, consistent with IIb-IIIa being a heterodimer. 125I-T10 binding was identical in unactivated platelets and platelets stimulated with 10 microM ADP. However, platelets did not aggregate or bind 125I-fibrinogen until ADP was added. T10, but not Tab or nonimmune mouse antibody, inhibited ADP-induced platelet aggregation and 125I-fibrinogen binding. Our findings suggest that IIb and IIIa exist as subunits of a single membrane glycoprotein in unstimulated platelets. Fibrinogen binding appears to require not only the interaction of IIb and IIIa, but also some additional change occurring after platelet activation.