Fatty alcohols, a minor component of the tree tobacco surface wax, are associated with defence against caterpillar herbivory.

Despite decades of research resulting in a comprehensive understanding of epicuticular wax metabolism, the function of these almost ubiquitous metabolites in plant-herbivore interactions remains unresolved. In this study, we examined the effects of CRISPR-induced knockout mutations in four Nicotiana glauca (tree tobacco) wax metabolism genes. These mutations cause a wide range of changes in epicuticular wax composition, leading to altered interactions with insects and snails. Three interaction classes were examined: chewing herbivory by seven caterpillars and one snail species, phloem feeding by Myzus persicae (green peach aphid) and oviposition by Bemisia tabaci (whitefly). Although total wax load and alkane abundance did not affect caterpillar growth, a correlation across species, showed that fatty alcohols, a minor component of N. glauca surface waxes, negatively affected the growth of both a generalist caterpillar (Spodoptera littoralis) and a tobacco-feeding specialist (Manduca sexta). This negative correlation was overshadowed by the stronger effect of anabasine, a nicotine isomer, and was apparent when fatty alcohols were added to an artificial lepidopteran diet. By contrast, snails fed more on waxy leaves. Aphid reproduction and feeding activity were unaffected by wax composition but were potentially affected by altered cutin composition. Wax crystal morphology could explain the preference of B. tabaci to lay eggs on waxy wild-type plants relative to both alkane and fatty alcohol-deficient mutants. Together, our results suggest that the varied responses among herbivore classes and species are likely to be a consequence of the co-evolution that shaped the specific effects of different surface wax components in plant-herbivore interactions.

Biology of BCG response in non-muscle invasive bladder cancer - 2021 IBCN Updates Part III.

Bacillus Calmette-Guerin (BCG) remains the only FDA-approved first-line therapy in patients with high-risk non-muscle invasive bladder cancer. Recurrences, even after adequate BCG therapy, are common and the efficacy of second-line therapies remains modest. Therefore, early identification of patients likely to recur and treatment after recurrence remain critical unmet needs in the clinical care of bladder cancer patients. To address these deficits, a better understanding of the mechanisms of resistance to BCG-therapy is needed. The virtual update of the International Bladder Cancer Network (IBCN) on the biology of response to BCG focused on potential mechanisms and markers of resistance to intravesical BCG therapy. The insights from this meeting will be highlighted and put into context of previously reported mechanisms of resistance to BCG in this review.

Long-Distance Caregivers' Use Of Supportive Services.

While long-distance caregiving has received increased attention as a unique care experience, prior research has not explored the supportive services used by long-distance caregivers (LDCs) and the factors that predict their supportive service utilization. Using the Andersen Model of Health Care Utilization, the current study sought to: 1) describe the types of supportive services LDCs used and the frequency of usage and 2) identify predisposing, enabling, and need-related factors associated with supportive service use in a sample of LDCs. Participants were recruited from aging services organizations, a national participant registry, professional networks, participant referrals, and an existing pool of research participants. The sample included 304 LDCs who reported on the use of nine supportive services and completed measures assessing depression, caregiver burden, self-rated health, sociodemographic characteristics, and the condition of the care recipient (CR). Fifty percent of LDCs reported no service use. Multiple hierarchical regression analyses demonstrated that younger age, higher caregiver burden, greater depressive symptoms, more time spent helping the CR, and worse CR functional status were significantly related to greater total supportive service use by LDCs. The current study contributes to our understanding of the factors associated with LDCs' supportive service utilization, highlighting the importance of need-related factors.

Sediment source fingerprinting as an aid to catchment management: A review of the current state of knowledge and a methodological decision-tree for end-users.

The growing awareness of the environmental significance of fine-grained sediment fluxes through catchment systems continues to underscore the need for reliable information on the principal sources of this material. Source estimates are difficult to obtain using traditional monitoring techniques, but sediment source fingerprinting or tracing procedures, have emerged as a potentially valuable alternative. Despite the rapidly increasing numbers of studies reporting the use of sediment source fingerprinting, several key challenges and uncertainties continue to hamper consensus among the international scientific community on key components of the existing methodological procedures. Accordingly, this contribution reviews and presents recent developments for several key aspects of fingerprinting, namely: sediment source classification, catchment source and target sediment sampling, tracer selection, grain size issues, tracer conservatism, source apportionment modelling, and assessment of source predictions using artificial mixtures. Finally, a decision-tree representing the current state of knowledge is presented, to guide end-users in applying the fingerprinting approach.

Dynamics of the endosymbiont Rickettsia in an insect pest.

A new heritable bacterial association can bring a fresh set of molecular capabilities, providing an insect host with an almost instantaneous genome extension. Increasingly acknowledged as agents of rapid evolution, inherited microbes remain underappreciated players in pest management programs. A Rickettsia bacterium was tracked sweeping through populations of an invasive whitefly provisionally described as the "B" or "MEAM1" of the Bemisia tabaci species complex, in the southwestern USA. In this population, Rickettsia provides strong fitness benefits and distorts whitefly sex ratios under laboratory conditions. In contrast, whiteflies in Israel show few apparent fitness benefits from Rickettsia under laboratory conditions, only slightly decreasing development time. A survey of B. tabaci B samples revealed the distribution of Rickettsia across the cotton-growing regions of Israel and the USA. Thirteen sites from Israel and 22 sites from the USA were sampled. Across the USA, Rickettsia frequencies were heterogeneous among regions, but were generally very high, whereas in Israel, the infection rates were lower and declining. The distinct outcomes of Rickettsia infection in these two countries conform to previously reported phenotypic differences. Intermediate frequencies in some areas in both countries may indicate a cost to infection in certain environments or that the frequencies are in flux. This suggests underlying geographic differences in the interactions between bacterial symbionts and this serious agricultural pest.

Selective activation of angiotensin AT2 receptors attenuates progression of pulmonary hypertension and inhibits cardiopulmonary fibrosis.

BACKGROUND AND PURPOSE: Pulmonary hypertension (PH) is a devastating disease characterized by increased pulmonary arterial pressure, which progressively leads to right-heart failure and death. A dys-regulated renin angiotensin system (RAS) has been implicated in the development and progression of PH. However, the role of the angiotensin AT2 receptor in PH has not been fully elucidated. We have taken advantage of a recently identified non-peptide AT2 receptor agonist, Compound 21 (C21), to investigate its effects on the well-established monocrotaline (MCT) rat model of PH. EXPERIMENTAL APPROACH: A single s.c. injection of MCT (50 mg·kg(-1) ) was used to induce PH in 8-week-old male Sprague Dawley rats. After 2 weeks of MCT administration, a subset of animals began receiving either 0.03 mg·kg(-1) C21, 3 mg·kg(-1) PD-123319 or 0.5 mg·kg(-1) A779 for an additional 2 weeks, after which right ventricular haemodynamic parameters were measured and tissues were collected for gene expression and histological analyses. KEY RESULTS: Initiation of C21 treatment significantly attenuated much of the pathophysiology associated with MCT-induced PH. Most notably, C21 reversed pulmonary fibrosis and prevented right ventricular fibrosis. These beneficial effects were associated with improvement in right heart function, decreased pulmonary vessel wall thickness, reduced pro-inflammatory cytokines and favourable modulation of the lung RAS. Conversely, co-administration of the AT2 receptor antagonist, PD-123319, or the Mas antagonist, A779, abolished the protective actions of C21. CONCLUSIONS AND IMPLICATIONS: Taken together, our results suggest that the AT2 receptor agonist, C21, may hold promise for patients with PH.

Hematologic biomarkers in childhood cataracts.

PURPOSE: To date, more than thirty nine genetic loci have been associated with congenital cataracts. Despite this progress, current diagnostic techniques are insufficient for unraveling the underlying genetic defect in sporadic patients and small families. In the present manuscript we demonstrate the contribution of routine laboratory tests in the search for genetic defects of childhood cataracts. METHODS: Two families with congenital cataracts and hematologic findings that included hyperferritinemia and the "ii" blood type underwent detailed ophthalmologic and clinical examinations. Mutation analysis of the ferritin light chain (FTL) and glucosaminyl (N-acetyl) transferase 2, I-branching enzyme (GCNT2) genes was performed in the two families, respectively. RESULTS: In the family with the "ii" blood group we found a novel GCNT2 mutation c.G935A (p.G312D) in the cataract patients, while in the family with hyperferritinemia cataract syndrome we identified a G→C heterozygous mutation at position +32 of FTL. CONCLUSIONS: Hematologic biomarkers may simplify the search for the underlying molecular defect in families with congenital cataract.

Thermoluminescence solid-state nanodosimetry--the peak 5A/5 dosemeter.

The shape of composite peak 5 in the glow curve of LiF:Mg,Ti (TLD-100) following (90)Sr/(90)Y beta irradiation, previously demonstrated to be dependent on the cooling rate used in the 400°C pre-irradiation anneal, is shown to be dependent on ionisation density in both naturally cooled and slow-cooled samples. Following heavy-charged particle high-ionisation density (HID) irradiation, the temperature of composite peak 5 decreases by ∼5°C and the peak becomes broader. This behaviour is attributed to an increase in the relative intensity of peak 5a (a low-temperature satellite of peak 5). The relative intensity of peak 5a is estimated using a computerised glow curve deconvolution code based on first-order kinetics. The analysis uses kinetic parameters for peaks 4 and 5 determined from ancillary measurements resulting in nearly 'single-glow peak' curves for both the peaks. In the slow-cooled samples, owing to the increased relative intensity of peak 5a compared with the naturally cooled samples, the precision of the measurement of the 5a/5 intensity ratio is found to be ∼15% (1 SD) compared with ∼25% for the naturally cooled samples. The ratio of peak 5a/5 in the slow-cooled samples is found to increase systematically and gradually through a variety of radiation fields from a minimum value of 0.13±0.02 for (90)Sr/(90)Y low-ionisation density irradiations to a maximum value of ∼0.8 for 20 MeV Cu and I ion HID irradiations. Irradiation by low-energy electrons of energy 0.1-1.5 keV results in values between 1.27 and 0.95, respectively. The increasing values of the ratio of peak 5a/5 with increasing ionisation density demonstrate the viability of the concept of the peak 5a/5 nanodosemeter and its potential in the measurement of average ionisation density in a 'nanoscopic' mass containing the trapping centre/luminescent centre spatially correlated molecule giving rise to composite peak 5.

Mating behaviour, life history and adaptation to insecticides determine species exclusion between whiteflies.

1. Negative interspecific interactions, such as resource competition or reproductive interference, can lead to the displacement of species (species exclusion). 2. Here, we investigated the effect of life history, mating behaviour and adaptation to insecticides on species exclusion between cryptic whitefly species that make up the Bemisia tabaci species complex. We conducted population cage experiments independently in China, Australia, the United States and Israel to observe patterns of species exclusion between an invasive species commonly referred to as the B biotype and three other species commonly known as biotypes ZHJ1, AN and Q. 3. Although experimental conditions and species varied between regions, we were able to predict the observed patterns of exclusion in each region using a stochastic model that incorporated data on development time, mating behaviour and resistance to insecticides. 4. Between-species variation in mating behaviour was a more significant factor affecting species exclusion than variation in development time. Specifically, the ability of B to copulate more effectively than other species resulted in a faster rate of population increase for B, as well as a reduced rate of population growth for other species, leading to species exclusion. The greater ability of B to evolve resistance to insecticides also contributed to exclusion of other species in some cases. 5. Results indicate that an integrative analysis of the consequences of variation in life-history traits, mating behaviours and adaption to insecticides could provide a robust framework for predicting species exclusion following whitefly invasions.

Experimental investigation of the 100 keV X-ray dose response of the high-temperature thermoluminescence in LiF:Mg,Ti (TLD-100): theoretical interpretation using the unified interaction model.

The dose response of LiF:Mg,Ti (TLD-100) chips was measured from 1 to 50,000 Gy using 100 keV X rays at the European Synchroton Radiation Facility. Glow curves were deconvoluted into component glow peaks using a computerised glow curve deconvolution (CGCD) code based on first-order kinetics. The normalised dose response, f(D), of glow peaks 4 and 5 and 5b (the major components of composite peak 5), as well as peaks 7 and 8 (two of the major components of the high-temperature thermoluminescence (HTTL) at high levels of dose) was separately determined and theoretically interpreted using the unified interaction model (UNIM). The UNIM is a nine-parameter model encompassing both the irradiation/absorption stage and the thermally induced relaxation/recombination stage with an admixture of both localised and delocalised recombination mechanisms. The effects of radiation damage are included in the present modelling via the exponential removal of luminescent centres (LCs) at high dose levels. The main features of the experimentally measured dose response are: (i) increase in f(D)(max) with glow peak temperature, (ii) increase in D(max) (the dose level at which f(D)(max) occurs) with increasing glow peak temperature, and (iii) decreased effects of radiation damage with increasing glow peak temperature. The UNIM interpretation of this behaviour requires both strongly decreasing values of ks (the relative contribution of localised recombination) as a function of glow peak temperature and, as well, significantly different values of the dose-filling constants of the trapping centre (TC) and LC for peaks 7 and 8 than those used for peaks 4 and 5. This suggests that different TC/LC configurations are responsible for HTTL. The relative intensity of peak 5a (a low-temperature satellite of peak 5 arising from localised recombination) was found to significantly increase at higher dose levels due to preferential electron and hole population of the trapping/recombination complex giving rise to composite glow peak 5. It is also demonstrated that possible changes in the trapping cross section of the LC and the competitive centres due to increasing sample/glow peak temperature do not significantly influence these observations/conclusions.

Transgenic organisms expressing genes from Bacillus thuringiensis to combat insect pests.

Various subspecies (ssp.) of Bacillus thuringiensis (Bt) are considered the best agents known so far to control insects, being highly specific and safe, easily mass produced and with long shelf life.1 The para-crystalline body that is produced during sporulation in the exosporium includes polypeptides named δ-endotoxins, each killing a specific set of insects. The different entomopathogenic toxins of various Bt ssp. can be manipulated genetically in an educated way to construct more efficient transgenic bacteria or plants that express combinations of toxin genes to control pests.2 Joint research projects in our respective laboratories during the last decade demonstrate what can be done by implementing certain ideas using molecular biology with Bt ssp. israelensis (Bti) as a model system. Here, we describe our progress achieved with Gram-negative bacterial species, including cyanobacteria, and some preliminary experiments to form transgenic plants, mainly to control mosquitoes (Diptera), but also a particular Lepidopteran and Coleopteran pest species. In addition, a system is described by which environment-damaging genes can be removed from the recombinants thus alleviating procedures for obtaining permits to release them in nature.

Use of immobilized HLA-A2:Ig dimeric proteins to determine the level of epitope-specific, HLA-restricted CD8(+) T-cell response.

A novel assay to assess antigen-specific cytokine release from stimulated CD8(+) T cells derived from the mucosal and peripheral blood compartments has been developed and standardized using the influenza A virus matrix protein (MP) peptide, GILGFVFTL. This technology is based on the capacity for the human leucocyte antigen (HLA)-A2:Ig dimeric protein to stimulate CD8(+) T cells in a major histocompatibility complex (MHC) class I-restricted fashion without the necessity for antigen presenting cells (APC). This assay has been optimized utilizing a 9-amino acid residue (9mer) peptide, the optimal peptide length for presenting an epitope to CD8(+) T cells. Compared to existing assays, this more sensitive and specific methodology requires fewer cells, enabling easier and more accurate monitoring of the CD8(+) T-cell response in biological compartments, such as the mucosa during the course of viral infection and may be utilized to assess epitope-specific CD8(+) T-cell responses in vaccine trials.

Photolysis of CH3COCH3 at 248 and 266 nm: pressure and temperature dependent overall quantum yields.

The overall quantum yield of photolysis of acetone (CH(3)C(O)CH(3)) at 248 and 266 nm was measured using the pulsed laser photolysis technique. The organic photo-fragment radicals CH(3) and CH(3)CO were detected indirectly as Br atoms using time-resolved resonance fluorescence following their reaction with Br(2). Quantum yields for acetone photolysis were derived relative to COCl(2) (at 248 nm) or Cl(2) (at 266 nm) in back-to-back experiments in which Cl atoms were scavenged by Br(2) to form Br. At 248 nm, experiments were carried out at pressures between 60 and 760 Torr of N(2) and at three temperatures: 224, 234 and 298 K. At this wavelength, the overall quantum yield was 0.98 +/- 0.10 and, within experimental uncertainty, was independent of pressure and temperature in the ranges covered. At 266 nm, experiments were restricted to 298 K, where the quantum yield was also close to unity, but with a weak dependence on bath gas pressure. These results confirm our previous room temperature, 266 nm dataset obtained using a different experimental approach in which the yield of CH(3) was measured directly.

Analyzing haplodiploid inheritance of insecticide resistance in whitefly biotypes.

We developed new methods for analyzing inheritance of insecticide resistance in haplodiploid arthropods and applied them to elucidate resistance of the whitefly Bemisia tabaci (Gennadius) to an insect growth regulator, pyriproxyfen. Two invasive biotypes of this devastating crop pest, the B biotype in Arizona and the Q biotype in Israel, have evolved resistance to pyriproxyfen. Here, we incorporated data from laboratory bioassays and crossing procedures exploiting haplodiploidy into statistical and analytical models to estimate the number of loci affecting pyriproxyfen resistance in strains of both biotypes. In tests with models of one to ten loci, the best fit between expected and observed mortality occurred with a two-locus model for the B biotype strain (QC-02) and for one- and two-locus models for the Q biotype strain (Pyri-R). The estimated minimum number of loci affecting resistance was 1.6 for the B biotype strain and 1.0 for the Q biotype strain. The methods used here can be applied to insecticide resistance and other traits in haplodiploid arthropods.

Investigation of the ionisation density dependence of the glow curve characteristics of LIF:MG,TI (TLD-100).

The dependence of the shape of the glow curve of LiF:Mg,Ti (TLD-100) on ionisation density was investigated using irradiation with (90)Sr/(90)Y beta rays, 60 and 250 kVp X rays, various heavy-charged particles and 0.2 and 14 MeV neutrons. Special attention is focused on the properties of high-temperature thermoluminescence; specifically, the behaviour of the high-temperature ratio (HTR) of Peaks 7 and 8 as a function of batch and annealing protocol. The correlation of Peaks 7 and 8 with average linear-energy-transfer (LET) is also investigated. The HTR of Peak 7 is found to be independent of LET for values of LET approximately >30 keV microm(-1). The behaviour of the HTR of Peak 8 with LET is observed to be erratic, which suggests that applications using the HTR should separate the contributions of Peaks 7 and 8 using computerised glow curve deconvolution. The behaviour of the HTR following neutron irradiation is complex and not fully understood. The shape of composite Peak 5 is observed to be broader following high ionisation alpha particle irradiation, suggesting that the combined use of the HTR and the shape of Peak 5 could lead to improved ionisation density discrimination for particles of high LET.

Larvicidal activities against agricultural pests of transgenic Escherichia coli expressing combinations of four genes from Bacillus thuringiensis.

The genes cry1Ac and cry1Ca from Bacillus thuringiensis subsps. kurstaki HD-73 and aizawai 4J4, respectively, encoding delta-endotoxins against lepidopteran larvae were isolated, cloned and expressed in Escherichia coli, with and without cyt1Aa (encoding cytolytic protein) and p20 (accessory protein) from subsp. israelensis. Nine combinations of the genes under control of an early T7, P A1 inducible promoter, produced the encoding proteins. Toxicities were examined against larvae of three major agricultural pests: Pectinophora gossypiella, Helicoverpa armigera and Spodoptera littoralis. The clones expressing cyt1Aa, with or without p20, were not toxic. The clone expressing cry1Ac (pBt-1A) was the most toxic to P. gossypiella (LC50 of 0.27 x 10(8) cells g(-1)). Clone pBt-1CA expressing cry1Ca and cry1Ac displayed the highest toxicity (LC50 of 0.12 x 10(8) cells ml(-1)) against S. littoralis. Clone pBt-1CARCy expressing all four genes (cry1Ca, cry1Ac, p20, cyt1Aa) in tandem exhibited the highest toxicity to H. armigera (LC50 of 0.16 x 10(8) cells ml(-1)). Cyt1Aa failed to raise the toxicity of these Cry toxins against P. gossypiella and S. littoralis but significantly enhanced toxicity against H. armigera. Two additional clones expressing either cry1Ac or cry1Ca under tandem promoters, P A1 and P psbA (constitutive), displayed significantly higher toxicities (7.5- to 140-fold) than their counterparts with P A1 alone, reducing the LC50 values to below 10(7) cells ml(-1).