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Adaptation to Plant Defence in an Agricultural Insect Pest: Integrating Genome Scans and Gene Expression in the Soybean Aphid Reveals Multi-Genic Pathways.

In agroecosystems, intense selection pressures cause species to adapt and spread, often leading to the evolution and persistence of pests. Understanding how pests rapidly adapt can help develop sustainable strategies for their management and improve agroecosystem health. Pest adaptation involves stable variations in DNA sequence, as well as dynamic shifts in gene expression, often mediated by non-coding regulatory elements. We examined adaptation to plant defences in the soybean aphid, Aphis glycines, in which virulent aphids have overcome plant defences and avirulent aphids have not. Previous data with laboratory colonies suggested that virulent aphids have higher overall gene expression, including transposable elements, some of which influence gene regulation. However, we lack information on how genetic variation in natural populations impacts adaptation and potentially gene regulation. We integrated population genome scans of field-collected, soybean aphid populations with gene expression profiles of virulent and avirulent laboratory colonies to uncover connections between genetic differentiation and gene regulation for virulence. Genome scan methods found 2144 single nucleotide polymorphisms (SNPs) with significant genetic differentiation (i.e., outliers) in field-collected populations. These SNPs were near 1004 genes, representing 5.16% of the effective number of genes. Based on previous RNA-Seq data with laboratory colonies, we found 3160 genes and 147 long non-coding RNAs (lncRNAs) with differential expression among virulent and avirulent biotypes. By integrating both data sets, we identified 16 genes and 5 long non-coding RNAs with differential expression and that were associated with an outlier SNP (within 10 kbp). We validated SNPs with additional field collected aphids and found an aphid clone with stronger virulence than our laboratory virulent colony, surviving on 2 different aphid-resistant soybean varieties. This new virulent clone had fixed allele differences at 9 SNPs compared to our avirulent and other virulent colony. Field collected soybean aphids matching the phenotype of this new virulent clone had significant genetic differentiation with 3 outlier SNPs near genes related to zinc transport and lachesin compared to field collected avirulent aphids. Our entire data reinforced the importance of a potential multi-genetic response to overcome plant defence and generates new insights into complex genetic and regulatory mechanisms involved in insect-plant interactions.

Animals↗

Relaxing and metabolic inhibitory action of X537A (Lasalocid) on the taenia of the guinea-pig caecum.

1. In the isolated guinea-pig taenia, application of X537A to the muscle caused a relaxation, while A23187 caused a sustained contraction. 2. Treatment with adrenergic blocking agents and tetrodotoxin had no effect on the relaxing response to X537A. 3. In the presence of a low concentration (10(-6) M) of X537A or under hypoxic conditions (bubbled with 95% N2: 5% CO2), the taenia lost the ability to respond to a high concentration (40 mM) of potassium with a sustained tonic contraction, although the rapid phasic contraction was still present. 4. When a low concentration of X537A was applied the shape of the contractile response to A23187 was changed from a sustained development of tension to an oscillatory tension which was also observed under hypoxia. 5. In tissues treated with glycerol for 3 weeks, neither X537A nor A23187 had any effect on the contractile response induced by elevation of calcium concentration (pCa = 4) in the presence of magnesium and ATP. 6. Exposure to a low concentration (10(-6) M) of X537A, or hypoxia, slightly yet significantly decreased the ATP content of the muscle. A high concentration (10(-5) M) of X537A markedly decreased the ATP content to about half normal. A23187 did not alter the ATP content. 7. Application of X537A did not alter the calcium content of the muscle and inhibited the A23187-induced increase in content. Under hypoxia, A23187 failed to increase the calcium content of the muscle. 8. The results indicate that, in contrast to A23187, X537A has a relaxing and metabolic inhibitory action on the guinea-pig taenia. The action of low concentrations of X537A resembled that of the hypoxia, indicating that X537A might exert its relaxing action, at least in part, by inhibition of aerobic energy metabolism of the muscle.

Adenosine Triphosphate↗

Neuroeffector characteristics of sweat glands in the human hand activated by regular neural stimuli.

1. Intraneural electrical stimuli (0.3-1.2 mA, 0.2 ms) were delivered via a tungsten microelectrode inserted into a cutaneous fascicle in the median nerve at the wrist in twenty-eight normal subjects. The effects on sweat glands within the innervation zone were monitored as changes of skin resistance and water vapour partial pressure (WVPP). Regional anaesthesia of the brachial plexus in the axilla eliminated spontaneous sympathetic activity and reflex effects. 2. At stimulation frequencies of 0.1 Hz each stimulus evoked a transient skin resistance reduction, the amplitude of which varied initially but reached a steady state of less than 10 k omega after, on average, nine responses. If preceded by stimulation-free intervals of 5 min or more, up to fifteen stimuli were required before the first response occurred. With higher frequencies individual responses started to merge, skin resistance levels decreased successively and levelled off around 10 Hz. The total change of resistance (0-10 Hz) was 101 +/- 46 (n = 9) k omega and the higher the pre-stimulus level, the larger the reduction (r = 0.68, P less than 0.05). 3. Stimulus-response latencies to the onset of a skin resistance reduction (single stimuli or trains of six impulses/20 Hz given at 0.1 Hz) shortened initially but reached steady-state values after on average nine to twelve impulses. Average conduction velocity between stimulating electrode and skin resistance recording site was 0.78 m/s and average time for electrical neuroeffector transfer in sweat glands was estimated to be 348 ms. 4. In addition to direct stimulation-induced resistance responses there were also small spontaneous reductions of resistance. They were seen in all subjects and at all frequencies but were more common in some subjects and occurred predominantly at the beginning of stimulation or at changes of frequency. They occurred independently at two skin sites in the same subject and disappeared during stimulation-free periods and after atropine. 5. With train stimulation (six impulses/20 Hz) at 0.1 Hz, each train evoked transient increases of WVPP of 1 mmHg or less in some subjects (latency around 1.6 s). After averaging weak increases were seen also after single stimuli in two subjects. Increases of stimulation current or frequency led to slowly developing sustained increases of WVPP concomitant with decreases in skin resistance. 6. Responses in skin resistance and WVPP to train stimulation at 0.1 Hz were suppressed in a dose-dependent way by I.V. injections of atropine.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Prevention of scrapie pathogenesis by transgenic expression of anti-prion protein antibodies.

Variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy are initiated by extracerebral exposure to prions. Although prion transmission from extracerebral sites to the brain represents a potential target for prophylaxis, attempts at vaccination have been limited by the poor immunogenicity of prion proteins. To circumvent this, we expressed an anti-prion protein (anti-PrP) mu chain in Prnp(o/o) mice. Transgenic mice developed sustained anti-PrP titers, which were not suppressed by introduction of Prnp+ alleles. Transgene expression prevented pathogenesis of prions introduced by intraperitoneal injection in the spleen and brain. Expression of endogenous PrP (PrP(C)) in the spleen and brain was unaffected, suggesting that immunity was responsible for protection. This indicates the feasibility of immunological inhibition of prion disease in vivo.

Amyloid↗

Abnormal vascular function and hypertension in mice deficient in estrogen receptor beta.

Blood vessels express estrogen receptors, but their role in cardiovascular physiology is not well understood. We show that vascular smooth muscle cells and blood vessels from estrogen receptor beta (ERbeta)-deficient mice exhibit multiple functional abnormalities. In wild-type mouse blood vessels, estrogen attenuates vasoconstriction by an ERbeta-mediated increase in inducible nitric oxide synthase expression. In contrast, estrogen augments vasoconstriction in blood vessels from ERbeta-deficient mice. Vascular smooth muscle cells isolated from ERbeta-deficient mice show multiple abnormalities of ion channel function. Furthermore, ERbeta-deficient mice develop sustained systolic and diastolic hypertension as they age. These data support an essential role for ERbeta in the regulation of vascular function and blood pressure.

Adrenergic alpha-Agonists↗

Economic reasons for conserving wild nature.

On the eve of the World Summit on Sustainable Development, it is timely to assess progress over the 10 years since its predecessor in Rio de Janeiro. Loss and degradation of remaining natural habitats has continued largely unabated. However, evidence has been accumulating that such systems generate marked economic benefits, which the available data suggest exceed those obtained from continued habitat conversion. We estimate that the overall benefit:cost ratio of an effective global program for the conservation of remaining wild nature is at least 100:1.

Agriculture↗

Spontaneous hypertension ion cross-suckled rats.

Genetically normotensive Sprague-Dawley rats nursed by spontaneously hypertensive foster mothers develop sustained high blood pressure. Some factor related to the genetically programmed hypertension of the foster mother is probably transmitted to the infant rats through her milk. Alternatively, the hyperkinetic behavior of the mother may activate a hypertensinogen in young having the proper constellation of genes.

Animal Population Groups↗

Isoprenaline as an aid to the induction of catecholamine dependent supraventricular tachycardias during programmed stimulation.

The effects of isoprenaline on the induction of supraventricular tachycardia by programmed stimulation were studied in 67 patients to see whether they correlated with spontaneous catecholamine mediated symptoms during exercise testing and Holter monitoring. Thirty seven control patients (group 1) did not have spontaneous arrhythmias either during exercise testing or Holter monitoring. Thirty patients (group 2) had documented exercise or stress related supraventricular tachycardias--that is paroxysmal junctional tachycardia (24) or atrial arrhythmia (6). Programmed electrical stimulation was performed before and during the infusion of isoprenaline. No group 1 patient developed sustained supraventricular tachycardia during isoprenaline infusion. In 21 patients with paroxysmal junctional tachycardia and all the patients with atrial arrhythmias electrical stimulation during isoprenaline infusion produced the same tachycardia that had been seen during exercise testing and Holter monitoring. Changes in electrophysiological variables and the concentrations of serum potassium were not associated with the induction of supraventricular tachycardia by isoprenaline. Infusion of isoprenaline safely facilitated the induction of supraventricular tachycardia by programmed stimulation in patients who had spontaneously occurring catecholamine mediated symptoms.

Adolescent↗

Early complications of permanent pacemaker implantation: no difference between dual and single chamber systems.

OBJECTIVE: To evaluate the incidence of intraoperative and early postoperative complications (up to two months after implant) of endocardial permanent pacemaker insertion in all patients under-going a first implant at a referral centre. METHODS: Prospective evaluation of all endocardial pacemaker implantation procedures performed from April 1992 to January 1994 carried out by completion of standard audit form at implant. Patients' demographic data, medical history, details of pacemaker hardware used, and any complications were noted. Follow up information was also collected prospectively onto standard forms at pacemaker outpatient clinic. SETTING: United Kingdom tertiary referral cardiothoracic centre. PATIENTS: 1088 consecutive patients underwent implantation of their first endocardial permanent pacemaker from April 1992 to January 1994. Implant and follow up data were available for 1059 (97.3%) patients at analysis. The median (range) age was 77 years (16-99); 51.2 % were male. RESULTS: Dual chamber units were implanted in 54.1% of patients, single chamber atrial in 5.2%, and ventricular in 40.7%. A temporary pacing lead was present at implant in 22.9% of patients. Most (93.6%) implants were performed via the subclavian vein. Immediate complications were rare: eight (0.8%) patients developed pneumothorax requiring medical treatment and 11 (1.0%) an insignificant pneumothorax. There was no significant difference in the pneumothorax rate for dual chamber (DDD) compared with single chamber systems. Arterial puncture without sequelae was documented in 2.7% of attempts at subclavian vein cannulation. A total of 35 patients (3.3%) required reoperation; the reoperation rate for dual chamber (3.5%) was similar to that for single chamber (3.1%) systems. Electrode displacement (n = 15, 1.4%) was the most common reason for reoperation. Atrial lead displacement (n = 10, 1.6% of atrial leads) was significantly more common than ventricular lead displacement (n = 5, 0.5% of ventricular leads, P = 0.047). There was no difference in electrode displacement rates for dual (1.6%) compared with single (1.2%) chamber systems. Pacemaker pocket infection led to reoperation in 10 patients (six dual, four single chamber, P = not significant) and was significantly more common in patients who had a temporary pacing lead in place at implant (2.9%) than in those who did not (0.4%, P = 0.0014). Five patients (0.5%) required reoperation for generator erosion (two dual, three single chamber, P = not significant). and a further five for drainage of haematoma or a serous fluid collection (three dual, two single chamber, P = not significant). Complications that did not require reoperation were also rare. Undersensing occurred in 10 patients (0.9%). Atrial undersensing (n = 8) was significantly more common than ventricular undersensing (n = 2, P = 0.017). All patients were successfully treated by reprogramming of sensitivity. Superficial wound infection was treated successfully with antibiotics in nine patients (six dual, three single chamber, P = not significant). Three patients with DDD generators developed sustained atrial fibrillation: two required reprogramming to VVI mode and one required cardioversion. CONCLUSIONS: Permanent pacing in a large tertiary referral centre with experienced operators carries a low risk. Infection rates are low, < 1% overall but significantly higher in patients who undergo temporary pacing before implantation. Lead displacement and undersensing are more likely to occur with atrial than ventricular leads. The overall complication rate for dual chamber pacing, however, is no higher than for single chamber pacing.

Adolescent↗

Achieving the Framework Convention on Tobacco Control's potential by investing in national capacity.

May 2003 marked a critical achievement in efforts to stem the global tobacco epidemic, as the member states of the World Health Organization unanimously endorsed the Framework Convention on Tobacco Control (FCTC). However, the adoption of the FCTC signifies only the end of the beginning of effective global action to control tobacco. Over the next several years the utility of the FCTC process and the treaty itself will be tested as individual countries seek to ratify and implement the treaty's obligations. Significant barriers to the treaty's long term success exist in many countries. It is crucial that the international tobacco control community now refocuses its efforts on national capacity building and ensures that individual countries have the knowledge, tools, data, people, and organisations needed to implement the convention and develop sustained tobacco control programmes. This paper provides a model of national tobacco control capacity and offers a prioritised agenda for action.

Cost of Illness↗

Alcohol and pregnancy: a clinical perspective.

Exposure of the fetus at any gestational stage to high concentrations of alcohol can adversely affect growth, morphology, and neurophysiologic development. Sustained heavy drinking can result in the fetal alcohol syndrome. Cessation of heavy drinking during pregnancy will benefit both mother and child. Primary health care providers can effectively identify and treat women at risk.

Alcoholism↗

Tospovirus-thrips interactions.

The complex and specific interplay between thrips, tospoviruses, and their shared plant hosts leads to outbreaks of crop disease epidemics of economic and social importance. The precise details of the processes underpinning the vector-virus-host interaction and their coordinated evolution increase our understanding of the general principles underlying pathogen transmission by insects, which in turn can be exploited to develop sustainable strategies for controlling the spread of the virus through plant populations. In this review, we focus primarily on recent progress toward understanding the biological processes and molecular interactions involved in the acquisition and transmission of Tospoviruses by their thrips vectors.

Animals↗

Telemedicine: a new health care delivery system.

The resurgence of telemedicine can be attributed to its potential for addressing intransigent problems in health care, including limited accessibility, cost inflation, and uneven quality. After discussing definitions and the genesis of telemedicine, this review focuses on conceptual issues and an assessment of past research. The scope and methodological rigor necessary for sustained development and policy making have been limited in this area of research, owing to the nature of extant telemedicine projects and the lack of a comprehensive research strategy that specifies the objectives of telemedicine research regarding accessibility, cost, and quality. Research strategies and a framework for analysis are discussed. Without a commitment to the types of research objectives, framework, and strategy presented here, the considerable promise of telemedicine, as an innovative system of care, may not be fully realized.

Cost Control↗

cAMP- but not Ca(2+)-regulated Cl- conductance in the oviduct is defective in mouse model of cystic fibrosis.

Defective adenosine 3',5'-cyclic monophosphate (cAMP)-mediated Cl- transport in cystic fibrosis (CF) reflects defects in the cystic fibrosis transmembrane conductance regulator (CFTR). A moderate level of CFTR mRNA expression has been found in rodent and human oviductal epithelium, but unlike other CFTR-expressing tissues, the oviduct in CF patients is apparently normal. The present study was carried out to investigate the relative magnitude of the cAMP- and intracellular Ca2+ (Cai2+)-regulated Cl- secretion in primary cultures of the oviduct from normal and CF mice generated by targeted disruption of the murine CF gene. Normal oviductal epithelium exhibited a basal equivalent short-circuit current (Ieq) of 20.3 +/- 1.7 muA/cm2. CF oviduct exhibited a lower basal Ieq of 4.5 +/- 1.9 muA/cm2. In normal mice, forskolin (10(-5) M, apical) elicited a slowly developing sustained rise in Ieq, whereas ionomycin (5 x 10(-6) M, apical) and ATP (10(-4) M, apical) induced larger increases in Ieq consisting of a prompt, transient response followed by a slowly decreasing component. The Ieq response to forskolin was totally abolished in CF mouse oviducts, but the magnitudes of the peak Ieq responses to ionomycin and ATP were not different from normal. The time courses of the ionomycin- and ATP-evoked responses, however, were significantly more transient in CF than in normal oviducts. These results demonstrate that CF mouse oviduct exhibits defective cAMP- but not Cai(2+)-mediated Cl- secretion. The relatively high level of functional expression of the alternative Cai(2+)-activated Cl- secretory pathway in the mouse oviduct may contribute to the absence of major pathology in the CF oviduct.

Adenosine Triphosphate↗

Endothelium-derived contracting and relaxing factors contribute to hypoxic responses of pulmonary arteries.

The response of porcine pulmonary arteries to hypoxia depended on their location in the vasculature and the degree and duration of the hypoxic challenge. In rings of pulmonary artery suspended for isometric tension recording (37 degrees C, 16% O2 and 5% CO2), moderate hypoxia (10% and 4% O2) caused endothelium-dependent relaxation in distal arteries but transient endothelium-dependent contraction in proximal arteries. In both proximal and distal arteries, the initial response to anoxia (0% O2) was a transient endothelium-dependent contraction. This was followed by a slowly developing, sustained endothelium-dependent contraction in proximal arteries, or by an endothelium-independent relaxation in distal arteries. The endothelium-dependent relaxation to moderate hypoxia in distal arteries was inhibited only by combined inhibition of endothelium-derived relaxing factor (EDRF)-nitric oxide (NO) synthase [N omega-nitro-L-arginine methyl ester (L-NAME)] and cyclooxygenase (indomethacin), suggesting mediation by EDRF-NO and prostacyclin. Transient endothelium-dependent contractions to moderate hypoxia (proximal arteries) or anoxia (all arteries) were abolished by L-NAME, but the late endothelium-dependent anoxic contraction observed in proximal arteries was not reduced by L-NAME and/or indomethacin. Therefore, hypoxia/anoxia may initiate contraction of pulmonary arteries by decreasing the activity of EDRF-NO, but the contractions appear to be maintained by an increased activity of an endothelium-derived contracting factor.

Acetylcholine↗

Evidence for the role of p38 MAP kinase in hypoxia-induced pulmonary vasoconstriction.

Mitogen-activated protein (MAP) kinases regulate smooth muscle cell contraction. Hypoxia contracts pulmonary arteries by mechanisms that are incompletely understood. We hypothesized that hypoxic contraction of pulmonary arteries involves activation of the MAP kinases. To test this hypothesis, we studied the effects of SB-202190, a p38 MAP kinase inhibitor, PD-98059 and UO-126, two structurally different MEKK inhibitors, and anisomycin, a stimulator of p38 MAP kinase on acute hypoxia-induced contraction in rat conduit pulmonary artery rings precontracted with phenylephrine or KCl. Hypoxia induced a transient contraction, followed by a relaxation, and then a slowly developing sustained contraction. Hypoxia also significantly increased phosphorylation of p38 MAP kinase. SB-202190 did not affect the transient phase but abrogated the sustained phase of hypoxic contraction, whereas anisomycin enhanced both phases of contraction. SB-202190 also attenuated and anisomycin enhanced the phenylephrine-induced contraction. In contrast, PD-98059 and UO-126 had minimal effects on either hypoxic or phenylephrine-induced contraction. None of the treatments modified KCl-induced contraction. We conclude that p38, but not the ERK1/ERK2 MAP kinase pathway, mediates the sustained phase of hypoxic contraction in isolated rat pulmonary arteries.

Acute Disease↗

Calcium-dependent regulation of Cl secretion in tracheal epithelium.

In primary cultures of dog tracheal epithelium, isoproterenol produced a transient increase in short-circuit current (Isc) (duration 30 s; maximal increase, 32 +/- 5 microA/cm2). This was followed by a more slowly developing sustained increase (9 +/- 3 microA/cm2), which mimicked the response to N6, 2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP). The transient and sustained responses had dissociation constants for isoproterenol of 2 x 10(-8) and 2 x 10(-9) M, respectively. Bradykinin (in the presence of indomethacin), substance P, histamine, and thrombin produced only transient increases in Isc. The time courses of these transients closely paralleled changes in concentration of intracellular Ca ([Ca2+]i) as measured with fura 2. For different mediators, there was a significant correlation between the maximal transient increase in Isc and the maximal increase in [Ca2+]i. The transients in Isc were not associated with elevation of adenosine 3',5'-cyclic monophosphate (cAMP) and were unaffected by pretreatment with DBcAMP, which abolishes the steady-state increase in response to isoproterenol. Both the transient increases in Isc and [Ca2+]i were inhibited by pretreatment with the Ca chelator 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid. The phorbol ester 12-O-tetradecanoylphorbol 13-acetate abolished the transient increases in [Ca2+]i and Isc in response to isoproterenol but not to bradykinin. These results provide evidence that 1) isoproterenol and bradykinin elevate [Ca2+]i by different mechanisms, and 2) Ca elevation is associated with a transient increase in Isc, whereas increased cAMP is associated with a smaller sustained increase.

Animals↗

Reduction of the edema of acute hyperoxic lung injury by granulocyte depletion.

Increased numbers of granulocytes are found in lungs acutely injured by hyperoxia, but their contribution to lung injury remains unknown. We found that circulating granulocytes markedly increased (P less than 0.01) in rabbits exposed to hyperoxia for 72 h and that the numbers of granulocytes in lung lavages also increased and were correlated (r = 0.72, P less than 0.01) with the degree of edematous lung injury. Furthermore, when rabbits were treated with nitrogen mustard (1.75 mg/kg) and developed sustained granulocytopenia, exposure to hyperoxia for 72 h resulted in fewer granulocytes in lung lavages and less edematous lung injury. In contrast, when rabbits were similarly treated with nitrogen mustard but did not maintain sustained granulocytopenia throughout the exposure to hyperoxia, increased numbers of granulocytes were found in lung lavages and the degree of edematous lung injury increased to levels not different from those observed in oxygen-exposed rabbits that had not been treated with nitrogen mustard. These findings suggest that granulocytes may contribute to production of edema in acute oxygen toxicity.

Animals↗