Anaemia at admission is associated with poor clinical outcome in cerebral venous thrombosis.

BACKGROUND AND PURPOSE: Anaemia is associated with poor clinical outcome after ischaemic and haemorrhagic stroke. The association between anaemia and outcome in patients with cerebral venous thrombosis (CVT) was examined. METHODS: Consecutive adult patients with CVT were included from seven centres. Anaemia at admission was scored according to World Health Organization definitions. Poor clinical outcome was defined as a modified Rankin Scale score 3-6 at last follow-up. A multiple imputation procedure was applied for handling missing data in the multivariable analysis. Using binary logistic regression analysis, adjustments were made for age, sex, cancer and centre of recruitment (model 1). In a secondary analysis, adjustments were additionally made for coma, intracerebral haemorrhage, non-haemorrhagic lesion and deep venous system thrombosis (model 2). In a sensitivity analysis, patients with cancer were excluded. RESULTS: Data for 952 patients with CVT were included, 22% of whom had anaemia at admission. Patients with anaemia more often had a history of cancer (17% vs. 7%, P < 0.001) than patients without anaemia. Poor clinical outcome (21% vs. 11%, P < 0.001) and mortality (11% vs. 6%, P = 0.07) were more common amongst patients with anaemia. After adjustment, anaemia at admission increased the risk of poor outcome [adjusted odds ratio (aOR) 2.4, 95% confidence interval (CI) 1.5-3.7, model 1]. Model 2 revealed comparable results (aOR 1.9, 95% CI 1.2-3.2), as did the sensitivity analysis excluding patients with cancer (aOR 2.3, 95% CI 1.3-3.8, model 1). CONCLUSION: The risk of poor clinical outcome is doubled in CVT patients presenting with anaemia at admission.

HLA- and genotype-based risk assessment model to identify infantile onset pompe disease patients at high-risk of developing significant anti-drug antibodies (ADA).

In Pompe disease, anti-drug antibodies (ADA) to acid alpha-glucosidase (GAA) enzyme replacement therapy contribute to early mortality. Assessing individual risk for ADA development is notoriously difficult in (CRIM-positive) patients expressing endogenous GAA. The individualized T cell epitope measure (iTEM) scoring method predicts patient-specific risk of developing ADA against therapeutic recombinant human GAA (rhGAA) using individualized HLA-binding predictions and GAA genotype. CRIM-negative patients were six times more likely to develop high ADA titers than CRIM-positive patients in this retrospective study, whereas patients with high GAA-iTEM scores were 50 times more likely to develop high ADA titers than patients with low GAA-iTEM scores. This approach identifies high-risk IOPD patients requiring immune tolerance induction therapy to prevent significant ADA response to rhGAA leading to a poor clinical outcome and can assess ADA risk in patients receiving replacement therapy for other enzyme or blood factor deficiency disorders.

Higher ER load is not associated with better outcome in stage 1-3 breast cancer: a descriptive overview of quantitative HR analysis in operable breast cancer.

PURPOSE: In breast cancer, hormone receptor (HR) status is generally a qualitative measure; positive or negative. Quantitatively measured oestrogen and progesterone receptors (ER and PR) are frequently proposed prognostic and predictive markers, some guidelines even provide different treatment options for patients with strong versus weak expression. AIM: To evaluate quantitative HR load assessed by immunohistochemistry as a prognostic and predictive measure in stage 1-3 breast cancer. METHODS: We reviewed all the available literature on quantitatively measured HRs using immunohistochemistry. RESULTS: All included studies (n = 19) comprised a cohort of 30,754 patients. Only 2 out of 17 studies found a clear correlation between higher quantitative ER and better disease outcome. Only one trial examined quantitative ER both as prognostic and predictive marker and found no association between ER% and survival. Ten studies examined quantitative PR load, only two of those found a significant correlation between higher PR load and better disease outcome. Two trials examined quantitative PR both as prognostic and predictive marker, neither found any association between PR% and disease outcome. CONCLUSIONS: There is no clear evidence for using quantitatively assessed ER and PR as prognostic nor predictive marker in patients with stage 1-3 breast cancer. We recommend only using a qualitative HR status in future guidelines and treatment considerations.

Strong CD8+ lymphocyte infiltration in combination with expression of HLA class I is associated with better tumor control in breast cancer patients treated with neoadjuvant chemotherapy.

PURPOSE: Tumor-infiltrating lymphocytes (TILs) are associated with pathological complete response (pCR) and survival after neoadjuvant chemotherapy (NAC) in patients with early breast cancer. We investigated the prognostic and predictive role of TILs, macrophages, and HLA class 1 expression after NAC with or without the potentially immune modulating compound zoledronic acid (ZA). METHODS: Baseline tumor biopsies from 196 patients in the NEOZOTAC trial were analyzed for CD8 (cytotoxic T-cells), FoxP3 (regulatory T-cells), CD68 (macrophages), and HLA class I (HCA2/HC10) expression by immunohistochemistry and subsequently related to pCR and disease-free survival (DFS). RESULTS: A strong intratumoral CD8+ infiltration or expression of HLA class 1 by cancer cells was associated with a higher pCR rate (p < 0.05). Clinical benefit of high CD8+ T-cell infiltration was found when cancer cells expressed HLA class 1 (pCR: 21.8% vs. 6.7%, p = 0.04) but not when HLA class 1 expression was lost or downregulated (pCR: 5.9% vs. 0%, p = 0.38). Interaction analyses revealed survival benefit between HLA class 1 expression and strong CD8+ T-cell infiltration, whereas in the absence or downregulation of HLA class 1 expression, high levels of CD8+ T-cells were associated with survival disadvantage (p for interaction 0.01; hazard ratio 0.41, 95% CI 0.15-1.10, p = 0.08 and hazard ratio 7.67, 95% CI 0.88-66.4, p = 0.07, respectively). Baseline immune markers were not related to ZA treatment. CONCLUSIONS: Strong baseline tumor infiltration with CD8+ T-cells in the presence of tumoral HLA class 1 expression in patients with HER2-negative breast cancer is related to a higher pCR rate and a better DFS after NAC.

Cathelicidins Inhibit Escherichia coli-Induced TLR2 and TLR4 Activation in a Viability-Dependent Manner.

Activation of the immune system needs to be tightly regulated to provide protection against infections and, at the same time, to prevent excessive inflammation to limit collateral damage to the host. This tight regulation includes regulating the activation of TLRs, which are key players in the recognition of invading microbes. A group of short cationic antimicrobial peptides, called cathelicidins, have previously been shown to modulate TLR activation by synthetic or purified TLR ligands and may play an important role in the regulation of inflammation during infections. However, little is known about how these cathelicidins affect TLR activation in the context of complete and viable bacteria. In this article, we show that chicken cathelicidin-2 kills Escherichia coli in an immunogenically silent fashion. Our results show that chicken cathelicidin-2 kills E. coli by permeabilizing the bacterial inner membrane and subsequently binds the outer membrane-derived lipoproteins and LPS to inhibit TLR2 and TLR4 activation, respectively. In addition, other cathelicidins, including human, mouse, pig, and dog cathelicidins, which lack antimicrobial activity under cell culture conditions, only inhibit macrophage activation by nonviable E. coli In total, this study shows that cathelicidins do not affect immune activation by viable bacteria and only inhibit inflammation when bacterial viability is lost. Therefore, cathelicidins provide a novel mechanism by which the immune system can discriminate between viable and nonviable Gram-negative bacteria to tune the immune response, thereby limiting collateral damage to the host and the risk for sepsis.

Quantum Enhancement of the Index of Refraction in a Bose-Einstein Condensate.

We study the index of refraction of an ultracold bosonic gas in the dilute regime. Using phase-contrast imaging with light detuned from resonance by several tens of linewidths, we image a single cloud of ultracold atoms for 100 consecutive shots, which enables the study of the scattering rate as a function of temperature and density using only a single cloud. We observe that the scattering rate is increased below the critical temperature for Bose-Einstein condensation by a factor of 3 compared to the single-atom scattering rate. We show that current atom-light interaction models to second order of the density show a similar increase, where the magnitude of the effect depends on the model that is used to calculate the pair-correlation function. This confirms that the effect of quantum statistics on the index of refraction is dominant in this regime.

Context-dependent alarm signalling in an insect.

Animals often respond to danger by raising alarm to inform others. Alarm signals come in many different forms, such as visual or mechanical display, sound or odour. Some animals produce vocal alarm signals that vary with the level of danger. For chemical alarm signals, virtually nothing is known about such context-dependent signalling due to a general notion that alarm pheromones have fixed compositions. Here, we show that larvae of the Western Flower Thrips (Frankliniella occidentalis) produce an alarm pheromone whose composition varies with the level of danger they face: the presence of a relatively harmless predator or a very dangerous predator, that is either actually attacking or not. The frequency of alarm pheromone excretion increases with the level of danger. Moreover, the composition of excreted alarm pheromone varies in the relationship between total and relative amount of the putative two components, decyl acetate (DAc) and dodecyl acetate (DDAc). When pheromone is excreted with a predator present but not attacking, the percentage DDAc increases with the total amount of pheromone. When a predator does attack, however, the relationship between percentage DDAc and total amount of pheromone is reversed. Taken together, the alarm signal of thrips larvae appears to be context dependent, which to our knowledge is the first report of context-dependent composition of an alarm pheromone.

The extent of the raphe in bicuspid aortic valves is associated with aortic regurgitation and aortic root dilatation.

BACKGROUND: The clinical course of bicuspid aortic valves (BAVs) is variable. Data on predictors of aortopathy and valvular dysfunction mainly focus on valve morphology. AIM: To determine whether the presence and extent of the raphe (fusion site of valve leaflets) is associated with the degree of aortopathy and valvular dysfunction in patients with isolated BAV and associated aortic coarctation (CoA). METHODS: Valve morphology and aortic dimensions of 255 BAV patients were evaluated retrospectively by echocardiography. RESULTS: BAVs with a complete raphe had a significantly higher prevalence of valve dysfunction (especially aortic regurgitation) than BAVs with incomplete raphes (82.9 vs. 66.7 %, p = 0.01). Type 1A BAVs (fusion of right and left coronary leaflets) and complete raphe had larger aortic sinus diameters compared with the rest of the population (37.74 vs. 36.01, p = 0.031). Patients with CoA and type 1A BAV had significantly less valve regurgitation (13.6 vs. 55.8 %, p < 0.001) and smaller diameters of the ascending aorta (33.7 vs. 37.8 mm, p < 0.001) and aortic arch (25.8 vs. 30.2 mm, p < 0.001) than patients with isolated BAV. CONCLUSIONS: Type 1A BAV with complete raphe is associated with more aortic regurgitation and root dilatation. The majority of CoA patients have incomplete raphes, associated with smaller aortic root diameters and less valve regurgitation.

Effects of immune challenge on the oviposition strategy of a noctuid moth.

Infections can have detrimental effects on the fitness of an animal. Reproducing females may therefore be sensitive to cues of infection and be able to adaptively change their oviposition strategy in the face of infection. As one possibility, females could make a terminal investment and shift reproductive effort from future to current reproduction as life expectancy decreases. We hypothesized that females of the noctuid moth Heliothis virescens make a terminal investment and adapt their oviposition timing as well as their oviposition site selectivity in response to an immune challenge. We indeed found that females that were challenged with the bacterial entomopathogen Serratia entomophila laid more eggs than control females one night after the challenge. Additionally, bacteria-challenged females were less discriminating between oviposition sites than control females. Whereas control females preferred undamaged over damaged plants, immune-challenged females did not differentiate between the two. These results indicate that terminal investment is part of the life history of H. virescens females. Moreover, our results suggest that the strategy of terminal investment in H. virescens oviposition represents a fitness trade-off for females: in the face of infection, an increase in oviposition rate enhances female fitness, whereas low oviposition site selectivity reduces female fitness.

Development of major aorto-pulmonary collateral arteries in vegf120/120 isoform mouse embryos with tetralogy of fallot.

The degree of right ventricular outflow tract obstruction, pulmonary stenosis (PS) and the development of major aorto-pulmonary collateral arteries (MAPCAs) in patients with tetralogy of Fallot (TOF) is related to clinical outcome. Vegf120/120 mutant mouse embryos develop TOF with various degrees of PS, comparable to humans. We aimed to study the ontogeny of the development of MAPCAs in this mouse model. The development of the right ventricular outflow tract, pulmonary arteries, and ductus arteriosus (DA) and formation of MAPCAs were studied in both wild type as well as Vegf120/120 mice from embryonic day 10.5 until day 19.5. Of the 49 Vegf120/120 embryos, 35 embryos (71%) had ventral displacement of the outflow tract and a subaortic ventricular septal defect. A time-related development in severity of PS to pulmonary atresia (PA) was observed. From embryonic day 12.5, hypoplasia of the DA was seen in 13 (37%) and absent DA in 12 (37%) of these embryos. The 3 (6%) embryos with PA and absent DA developed MAPCAs, after day 15.5. In all, the MAPCAs arose from both subclavian arteries, running posterior in the thoracic cavity, along the vagal nerve. The MAPCAs connected the pulmonary arteries at the site of the hilus. A time-related development of PS to PA can lead, in combination with absent DA, to the development of MAPCAs later in embryonic life as an alternative route for pulmonary perfusion in this mouse model. This finding contributes to a better understanding of the consecutive morphological changes in the development toward MAPCAs in humans.

Regulation of alternative VEGF-A mRNA splicing is a therapeutic target for analgesia.

Vascular endothelial growth factor-A (VEGF-A) is best known as a key regulator of the formation of new blood vessels. Neutralization of VEGF-A with anti-VEGF therapy e.g. bevacizumab, can be painful, and this is hypothesized to result from a loss of VEGF-A-mediated neuroprotection. The multiple vegf-a gene products consist of two alternatively spliced families, typified by VEGF-A165a and VEGF-A165b (both contain 165 amino acids), both of which are neuroprotective. Under pathological conditions, such as in inflammation and cancer, the pro-angiogenic VEGF-A165a is upregulated and predominates over the VEGF-A165b isoform. We show here that in rats and mice VEGF-A165a and VEGF-A165b have opposing effects on pain, and that blocking the proximal splicing event - leading to the preferential expression of VEGF-A165b over VEGF165a - prevents pain in vivo. VEGF-A165a sensitizes peripheral nociceptive neurons through actions on VEGFR2 and a TRPV1-dependent mechanism, thus enhancing nociceptive signaling. VEGF-A165b blocks the effect of VEGF-A165a. After nerve injury, the endogenous balance of VEGF-A isoforms switches to greater expression of VEGF-Axxxa compared to VEGF-Axxxb, through an SRPK1-dependent pre-mRNA splicing mechanism. Pharmacological inhibition of SRPK1 after traumatic nerve injury selectively reduced VEGF-Axxxa expression and reversed associated neuropathic pain. Exogenous VEGF-A165b also ameliorated neuropathic pain. We conclude that the relative levels of alternatively spliced VEGF-A isoforms are critical for pain modulation under both normal conditions and in sensory neuropathy. Altering VEGF-Axxxa/VEGF-Axxxb balance by targeting alternative RNA splicing may be a new analgesic strategy.

Differential and linear insertion of atrioventricular valves: a useful tool?

OBJECTIVE: The differential insertion of the atrioventricular valves is the ultrasonographic representation of the more apical attachment of the tricuspid valve to the septum with respect to the mitral valve. A linear insertion is present when both valves form a linear continuum and has been suggested as a marker for atrioventricular septal defects (AVSDs). The objective of this study was to evaluate the anatomical substratum of differential and linear insertions of the atrioventricular valves in normal fetal hearts and fetal hearts with an AVSD. METHODS: The extent and position of the fibrous skeleton and attachment of the atrioventricular valves to the septum were studied in histological sections of 17 normal hearts and four hearts with an AVSD from 10 + 0 weeks' gestation to 3 days postpartum with various immunohistochemical tissue markers. In addition, spatiotemporal image correlation (STIC) volumes of 10 normal hearts and STIC volumes of eight hearts with an AVSD at 13 + 6 to 35 + 5 weeks' gestation were examined. RESULTS: The differential insertion of the atrioventricular valves was visible in normal hearts in the four-chamber plane immediately beneath the aorta, but nearer the diaphragm a linear insertion was found. In hearts with an AVSD, a linear appearance was observed in the four-chamber plane immediately beneath the aorta. Towards the diaphragm, however, first a differential insertion and, more caudally, a linear insertion was found. CONCLUSIONS: Both differential and linear insertions can be found in normal fetal hearts and fetal hearts with AVSD, depending on the plane in which the four-chamber view is visualized. Therefore, measurement of the differential insertion is likely to be useful only in experienced hands.

Normal and abnormal development of the aortic wall and valve: correlation with clinical entities.

Dilation of the wall of the thoracic aorta can be found in patients with a tricuspid (TAV) as well as a bicuspid aortic valve (BAV) with and without a syndromic component. BAV is the most common congenital cardiovascular malformation, with a population prevalence of 0.5-2 %. The clinical course is often characterised by aneurysm formation and in some cases dissection. The non-dilated aortic wall is less well differentiated in all BAV as compared with TAV, thereby conferring inherent developmental susceptibility. Furthermore, a turbulent flow, caused by the inappropriate opening of the bicuspid valve, could accelerate the degenerative process in the aortic wall. However, not all patients with bicuspidy develop clinical complications during their life. We postulate that the increased vulnerability for aortic complications in a subset of patients with BAV is caused by a defect in the early development of the aorta and aortic valve. This review discusses histological and molecular genetic aspects of the normal and abnormal development of the aortic wall and semilunar valves. Aortopathy associated with BAV could be the result of a shared developmental defect during embryogenesis.

Specific chaperones for the type VII protein secretion pathway.

Mycobacteria use the dedicated type VII protein secretion systems ESX-1 and ESX-5 to secrete virulence factors across their highly hydrophobic cell envelope. The substrates of these systems include the large mycobacterial PE and PPE protein families, which are named after their characteristic Pro-Glu and Pro-Pro-Glu motifs. Pathogenic mycobacteria secrete large numbers of PE/PPE proteins via the major export pathway, ESX-5. In addition, a few PE/PPE proteins have been shown to be exported by ESX-1. It is not known how ESX-1 and ESX-5 recognize their cognate PE/PPE substrates. In this work, we investigated the function of the cytosolic protein EspG(5), which is essential for ESX-5-mediated secretion in Mycobacterium marinum, but for which the role in secretion is not known. By performing protein co-purifications, we show that EspG(5) interacts with several PPE proteins and a PE/PPE complex that is secreted by ESX-5, but not with the unrelated ESX-5 substrate EsxN or with PE/PPE proteins secreted by ESX-1. Conversely, the ESX-1 paralogue EspG(1) interacted with a PE/PPE couple secreted by ESX-1, but not with PE/PPE substrates of ESX-5. Furthermore, structural analysis of the complex formed by EspG(5) and PE/PPE indicates that these proteins interact in a 1:1:1 ratio. In conclusion, our study shows that EspG(5) and EspG(1) interact specifically with PE/PPE proteins that are secreted via their own ESX systems and suggests that EspG proteins are specific chaperones for the type VII pathway.

One quantitative trait locus for intra- and interspecific variation in a sex pheromone.

Even though premating isolation is hypothesized to be a major driving force in speciation, its genetic basis is poorly known. In the noctuid moth Heliothis subflexa, one group of sex pheromone components, the acetates, emitted by the female, plays a crucial isolating role in preventing interspecific matings to males of the closely related Heliothis virescens, in which females do not produce acetates and males are repelled by them. We previously found intraspecific variation in acetates in H. subflexa: females in eastern North America contain significantly more acetates than females in Western Mexico. Here we describe the persistence of this intraspecific variation in laboratory-reared strains and the identification of one major quantitative trait locus (QTL), explaining 40% of the variance in acetate amounts. We homologized this intraspecific QTL to our previously identified interspecific QTL using restriction-associated DNA (RAD) tags. We found that a major intraspecific QTL overlaps with one of the two major interspecific QTL. To identify candidate genes underlying the acetate variation, we investigated a number of gene families with known or suspected acetyl- or acyltransferase activity. The most likely candidate genes did not map to our QTL, so that we currently hypothesize that a transcription factor underlies this QTL. Finding a single, large QTL that impacts variation in pheromone blends between and within species is, to our knowledge, the first such example for traits that have been demonstrated to affect premating isolation.

[Hidden care needs in elderly people: a descriptive study of an outpatient geriatric consultation practice in the Netherlands]. / Verborgen zorgbehoeften bij ouderen : Ambulante geriatrische consultatie in de praktijk, een dossieronderzoek.

In general older adults, even the oldest old are community dwelling and vital. However, vulnerability can silently or suddenly exist. Multidisciplinary assessment of health problems and disabilities is necessary to compose a comprehensive intervention program. In the Netherlands, a team specialised in elderly care accomplishes home-based assessments. In 2009 we conducted a case study aiming to describe the characteristics of the patients and the reasons for consultation. A total of 84 records were analysed. 60% of the clients were 85 years or older, 32% were living independently and 61% were residents in homes for elderly people. The majority of clients was female and living alone (widowed). Most clients had multiple issues and were referred for cognitive evaluation. During the process of assessment many underlying behavioural, emotional and social problems became manifest. These findings support that symptoms and complaints of frail elderly are complex. A systematic multidisciplinary approach enhances the dialogue with patients and caregivers to discuss their needs and their attitude towards care. More research, however, is necessary to evaluate the effectiveness of this intervention.

Expression of Id2 in the second heart field and cardiac defects in Id2 knock-out mice.

The inhibitor of differentiation Id2 is expressed in mesoderm of the second heart field, which contributes myocardial and mesenchymal cells to the primary heart tube. The role of Id2 in cardiac development is insufficiently known. Heart development was studied in sequential developmental stages in Id2 wildtype and knockout mouse embryos. Expression patterns of Id2, MLC-2a, Nkx2.5, HCN4, and WT-1 were analyzed. Id2 is expressed in myocardial progenitor cells at the inflow and outflow tract, in the endocardial and epicardial lineage, and in neural crest cells. Id2 knockout embryos show severe cardiac defects including abnormal orientation of systemic and pulmonary drainage, abnormal myocardialization of systemic and pulmonary veins, hypoplasia of the sinoatrial node, large interatrial communications, ventricular septal defects, double outlet right ventricle, and myocardial hypoplasia. Our results indicate a role for Id2 in the second heart field contribution at both the arterial and the venous poles of the heart.

Detection of Coxiella burnetii in complex matrices by using multiplex quantitative PCR during a major Q fever outbreak in The Netherlands.

Q fever, caused by Coxiella burnetii, is a zoonosis with a worldwide distribution. A large rural area in the southeast of the Netherlands was heavily affected by Q fever between 2007 and 2009. This initiated the development of a robust and internally controlled multiplex quantitative PCR (qPCR) assay for the detection of C. burnetii DNA in veterinary and environmental matrices on suspected Q fever-affected farms. The qPCR detects three C. burnetii targets (icd, com1, and IS1111) and one Bacillus thuringiensis internal control target (cry1b). Bacillus thuringiensis spores were added to samples to control both DNA extraction and PCR amplification. The performance of the qPCR assay was investigated and showed a high efficiency; a limit of detection of 13.0, 10.6, and 10.4 copies per reaction for the targets icd, com1, and IS1111, respectively; and no cross-reactivity with the nontarget organisms tested. Screening for C. burnetii DNA on 29 suspected Q fever-affected farms during the Q fever epidemic in 2008 showed that swabs from dust-accumulating surfaces contained higher levels of C. burnetii DNA than vaginal swabs from goats or sheep. PCR inhibition by coextracted substances was observed in some environmental samples, and 10- or 100-fold dilutions of samples were sufficient to obtain interpretable signals for both the C. burnetii targets and the internal control. The inclusion of an internal control target and three C. burnetii targets in one multiplex qPCR assay showed that complex veterinary and environmental matrices can be screened reliably for the presence of C. burnetii DNA during an outbreak.

Genetic differentiation across North America in the generalist moth Heliothis virescens and the specialist H. subflexa.

The two moth species Heliothis virescens (Hv) and H. subflexa (Hs) are closely related, but have vastly different feeding habits. Hv is a generalist and an important pest in many crops in the USA, while Hs is a specialist feeding only on plants in the genus Physalis. In this study, we conducted a comparative population genetic analysis to assess whether and how generalist and specialist life styles are reflected in differences in population structures. In Hv 98% of the total variation occurred within populations. The overall differentiation (F(ST) ) between regions was 0.006 and even lower between years (0.0039) and hosts (0.0028). Analyses of population structure suggest that all individuals form one genetically homogeneous population, except for at most 12 individuals (6%) that diverged from this cluster. Population homogeneity likely results from the high mobility of Hv and its generalist feeding behaviour. Hs exhibited substantially more population structure. Even though 96% of the total variation was attributable to within-population variability, F(ST) -values between Hs populations were 10 times higher than between Hv populations. Hs populations showed significant isolation by distance. Analyses of Hs population structure suggest at least two subpopulations and thus some degree of metapopulation structure. We speculate that the patchy distribution of Physalis- the exclusive food source of Hs - contributes to differences in population structure between these closely related species. The finding that the specialist shows more population differentiation than the generalist corroborates the notion that host specialization is not an evolutionary dead end but a dynamic trait.

Complex inheritance of larval adaptation in Plutella xylostella to a novel host plant.

Studying the genetics of host shifts and range expansions in phytophagous insects contributes to our understanding of the evolution of host plant adaptation. We investigated the recent host range expansion to pea, in the pea-adapted strain (P-strain) of the crucifer-specialist diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae). Larval survivorship on the novel host plant pea and a typical crucifer host (kale) was measured in reciprocal F(1), F(2) and backcrosses between the P-strain and a strain reared only on crucifers (C-strain). Reciprocal F(1) hybrids differed: offspring from P-strain mothers survived better on pea, indicating a maternal effect. However, no evidence for sex-linkage was found. Backcrosses to the P-strain produced higher survivorship on pea than C-strain backcrosses, suggesting recessive inheritance. In a linkage analysis with amplified fragment length polymorphism markers using P-strain backcrosses, two, four and five linkage groups contributing to survival on pea were identified in three different families respectively, indicating oligogenic inheritance. Thus, the newly evolved ability to survive on pea has a complex genetic basis, and the P-strain is still genetically heterogeneous and not yet fixed for all the alleles enabling it to survive on pea. Survivorship on kale was variable, but not related to survivorship on pea. This pattern may characterize the genetic inheritance of early host plant adaptation in oligophagous insect species.