Vascularized tumor-on-chip microplatforms for the studies of neovasculature as hope for more effective cancer treatments.

Angiogenesis is the development of new blood vessels from pre-existing vasculature. Multiple factors control its course. Disorders of the distribution of angiogenic agents are responsible for development of solid tumors and its metastases. Understanding of the molecular interactions regulating pathological angiogenesis will allow for development of more effective, even personalized treatment. A simulation of angiogenesis under microflow conditions is a promising alternative to previous studies conducted on animals and on 2D cell cultures. In this review, we summarize what has been discovered so far in the field of vascularized tumor-on-a-chip platforms. For this purpose, we describe different vascularization techniques used in microfluidics, present various attempts to induce angiogenesis-on-a-chip and report some approaches to recapitulate vascularized tumor microenvironment under microflow conditions.

Neurogenetic identification of mosquito sensory neurons.

Anopheles mosquitoes, as vectors for the malaria parasite, are a global threat to human health. To find and bite a human, they utilize neurons within their sensory appendages. However, the identity and quantification of sensory appendage neurons are lacking. Here we use a neurogenetic approach to label all neurons in Anopheles coluzzii mosquitoes. We utilize the homology assisted CRISPR knock-in (HACK) approach to generate a T2A-QF2w knock-in of the synaptic gene bruchpilot. We use a membrane-targeted GFP reporter to visualize the neurons in the brain and to quantify neurons in all major chemosensory appendages (antenna, maxillary palp, labella, tarsi, and ovipositor). By comparing labeling of brp>GFP and Orco>GFP mosquitoes, we predict the extent of neurons expressing ionotropic receptors (IRs) or other chemosensory receptors. This work introduces a valuable genetic tool for the functional analysis of Anopheles mosquito neurobiology and initiates characterization of the sensory neurons that guide mosquito behavior.

A spatial map of antennal-expressed ionotropic receptors in the malaria mosquito.

The mosquito's antenna represents its main olfactory appendage for detecting volatile chemical cues from the environment. Whole-mount fluorescence in situ hybridization of ionotropic receptors (IRs) expressed in the antennae reveals that the antenna might be divisible into proximal and distal functional domains. The number of IR-positive cells appear stereotyped within each antennal segment (flagellomere). Highly expressed odor-tuning IRs exhibit distinct co-localization patterns with the IR coreceptors Ir8a, Ir25a, and Ir76b that might predict their functional properties. Genetic knockin and in vivo functional imaging of IR41c-expressing neurons indicate both odor-induced activation and inhibition in response to select amine compounds. Targeted mutagenesis of IR41c does not abolish behavioral responses to the amine compounds. Our study provides a comprehensive map of IR-expressing neurons in the main olfactory appendage of mosquitoes. These findings show organizing principles of Anopheles IR-expressing neurons, which might underlie their functional contribution to the detection of behaviorally relevant odors.

Exploring Endothelial Expansion on a Chip.

Angiogenesis is the development of new blood vessels from the existing vasculature. Its malfunction leads to the development of cancers and cardiovascular diseases qualified by the WHO as a leading cause of death worldwide. A better understanding of mechanisms regulating physiological and pathological angiogenesis will potentially contribute to developing more effective treatments for those urgent issues. Therefore, the main goal of the following study was to design and manufacture an angiogenesis-on-a-chip microplatform, including cylindrical microvessels created by Viscous Finger Patterning (VFP) technique and seeded with HUVECs. While optimizing the VFP procedure, we have observed that lumen's diameter decreases with a diminution of the droplet's volume. The influence of Vascular Endothelial Growth Factor (VEGF) with a concentration of 5, 25, 50, and 100 ng/mL on the migration of HUVECs was assessed. VEGF's solution with concentrations varying from 5 to 50 ng/mL reveals high angiogenic potential. The spatial arrangement of cells and their morphology were visualized by fluorescence and confocal microscopy. Migration of HUVECs toward loaded angiogenic stimuli has been initiated after overnight incubation. This research is the basis for developing more complex vascularized multi-organ-on-a-chip microsystems that could potentially be used for drug screening.

Environmental impacts of mass drug administration programs: exposures, risks, and mitigation of antimicrobial resistance.

Mass drug administration (MDA) of antimicrobials has shown promise in the reduction and potential elimination of a variety of neglected tropical diseases (NTDs). However, with antimicrobial resistance (AMR) becoming a global crisis, the risks posed by widespread antimicrobial use need to be evaluated. As the role of the environment in AMR emergence and dissemination has become increasingly recognized, it is likewise crucial to establish the role of MDA in environmental AMR pollution, along with the potential impacts of such pollution. This review presents the current state of knowledge on the antimicrobial compounds, resistant organisms, and antimicrobial resistance genes in MDA trials, routes of these determinants into the environment, and their persistence and ecological impacts, particularly in low and middle-income countries where these trials are most common. From the few studies directly evaluating AMR outcomes in azithromycin MDA trials, it is becoming apparent that MDA efforts can increase carriage and excretion of resistant pathogens in a lasting way. However, research on these outcomes for other antimicrobials used in MDA trials is sorely needed. Furthermore, while paths of AMR determinants from human waste to the environment and their persistence thereafter are supported by the literature, quantitative information on the scope and likelihood of this is largely absent. We recommend some mitigative approaches that would be valuable to consider in future MDA efforts. This review stands to be a valuable resource for researchers and policymakers seeking to evaluate the impacts of MDA.

Olfaction in Anopheles mosquitoes.

As vectors of disease, mosquitoes are a global threat to human health. The Anopheles mosquito is the deadliest mosquito species as the insect vector of the malaria-causing parasite, which kills hundreds of thousands every year. These mosquitoes are reliant on their sense of smell (olfaction) to guide most of their behaviors, and a better understanding of Anopheles olfaction identifies opportunities for reducing the spread of malaria. This review takes a detailed look at Anopheles olfaction. We explore a range of topics from chemosensory receptors, olfactory neurons, and sensory appendages to behaviors guided by olfaction (including host-seeking, foraging, oviposition, and mating), to vector management strategies that target mosquito olfaction. We identify many research areas that remain to be addressed.

Current iodine nutrition status in Poland (2017): is the Polish model of obligatory iodine prophylaxis able to eliminate iodine deficiency in the population?

OBJECTIVE: The monitoring of the populations' iodine status is an essential part of successful programmes of iodine deficiency elimination. The current study aimed at the evaluation of current iodine nutrition in school children, pregnant and lactating women as a marker of the effectiveness and sustainability of mandatory iodine prophylaxis in Poland. DESIGN: The following iodine nutrition indicators were used: urinary iodine concentration (UIC) (all participants) and serum thyroglobulin (pregnant and lactating women). SETTING: The study was conducted in 2017 within the National Health Programme in five regions of Poland. PARTICIPANTS: The research included 300 pregnant women, 100 lactating women and 1000 school children (aged 6-12 years). RESULTS: In pregnant women, median UIC was 111·6 µg/l; there was no significant difference in median UIC according to the region of residence. In 8 % of pregnant women, thyroglobulin level was >40 ng/ml (median thyroglobulin 13·3 ng/ml). In lactating women, median UIC was 68·0 µg/l. A significant inter-regional difference was noted (P = 0·0143). In 18 % of breastfeeding women, thyroglobulin level was >40 ng/ml (median thyroglobulin 18·5 ng/ml). According to the WHO criteria, the investigated sample of pregnant and lactating women was iodine-deficient. Median UIC in school children was 119·8 µg/l (with significant inter-regional variation; P = 0·0000), which is consistent with iodine sufficiency. Ninety-four children (9·4 %) had UIC < 50 µg/l. CONCLUSIONS: Mandatory iodisation of household salt in Poland has led to a sustainable optimisation of iodine status in the general population. However, it has failed to assure adequate iodine nutrition during pregnancy and lactation.

A modified DNA barcode approach to define trophic interactions between native and exotic pentatomids and their parasitoids.

The establishment of invasive Halyomorpha halys (Stål) outside of its native range may impact native species assemblages, including other pentatomids and their scelionid parasitoids. This has generated interest in defining species diversity and host-parasitoid associations in this system to better understand the impact of invasive alien species on trophic interactions in invaded regions. Information on scelionid-pentatomid associations in natural habitats is lacking, and species-level identification of these associations can be tenuous using rearing and dissection techniques. Naturally occurring pentatomid eggs were collected in areas where H. halys has established in Canada and were analysed using a modified DNA barcoding approach to define species-level trophic interactions. Identification was possible for >90% of egg masses. Eleven pentatomid and five scelionid species were identified, and trophic links were established. Approximately 70% of egg masses were parasitized; parasitism and parasitoid species composition were described for each species. Telenomus podisi Ashmead was the dominant parasitoid and was detected in all host species. Trissolcus euschisti Ashmead was detected in several host species, but was significantly more prevalent in Chinavia hilaris (Say) and Brochymena quadripustulata (Fabricius). Trissolcus brochymenae Ashmead and Tr. thyantae Ashmead were recorded sporadically. Parasitism of H. halys was 55%, and this species was significantly less likely to be parasitized than native pentatomids. The scelionid species composition of H. halys consisted of Te. podisi, Tr. euschisti and Tr. thyantae. Although these species cannot develop in fresh H. halys eggs, we demonstrate that parasitoids attempt to exploit this host under field conditions.

Understanding the mismatch between behaviour and development in a novel host-parasitoid association.

Foraging parasitoid females should preferentially oviposit on hosts most suitable for progeny development to maximize their fitness. However, the introduction of a new host species may disrupt the link between the reliability of the cues and the expected adaptive outcome of female choice, leading to an evolutionary trap. This mismatch between behavioural acceptance and lack of development exists for North American and European egg parasitoids (Scelionidae) that encounter invasive Halyomorpha halys in areas where this exotic host has recently established. To explain this mismatch, we utilized an L9 orthogonal array design to assess and rank the influence of several critical factors characterizing host resource (host species, egg age, egg status, and surface wash) on behaviour (acceptance, patch residence and patch exploitation) and development of North American native Trissolcus euschisti egg parasitoid. Our results indicate that the host egg age is most important for behaviour, but is least influential for development of the progeny. This study suggests that the maladaptive decision to oviposit in an unsuitable host is due to a mismatch between the cues that females use, and the subsequent expected outcome of this choice. Therefore, it is the relative importance of individual factors when assessed simultaneously that influences the decision-making of female parasitoids.

Day-night temperature differential, rather than mean temperature, determines age of sexual maturation in Straicosta albicosta (Noctuidae).

While pheromone traps have been effectively used to monitor the recent range expansion of the western bean cutworm (WBC), very little is known about the pheromone mediated reproductive biology of this species. The age at which females initiated calling (the behaviour associated with the release of the sex pheromone), and the pattern of calling on the first three nights following sexual maturation were determined for virgin females held under four temperature regimes (25:20; 25:15; 20:15; 20:10 °C L:D and 16L:8D photoperiod), and two RH (60 and 80%). Regardless of the rearing conditions the pre-calling period (PCP) was always several days post emergence, supporting the hypothesis that WCB is a migrant species. However, surprisingly the length of the PCP was not directly related to mean temperature but rather to the temperature differential between the photophase and the scotophase. The duration of calling increased with female age, but unlike in other moths was not affected by the abiotic factors tested. The relative insensitivity to temperature and humidity, when compared with many other moth species, may be related to the WBC being a univoltine species with a mid-summer flight period. Consequently, there would not be strong selection pressure for plasticity in calling behavior when compared with the case of multivoltine species that experience a wide range of environmental conditions during different seasonal flight periods.

An exotic parasitoid provides an invasional lifeline for native parasitoids.

The introduction of an exotic species may alter food webs within the ecosystem and significantly affect the biodiversity of indigenous species at different trophic levels. It has been postulated that recent introduction of the brown marmorated stinkbug (Halyomorpha halys (Stål)) represents an evolutionary trap for native parasitoids, as they accept H. halys egg masses as a host but produce no viable progeny. Interspecific interactions between European egg parasitoid, Trissolcus cultratus (Mayr), and an Asian parasitoid, Trissolcus japonicus (Ashmead), were assessed by providing egg masses to T. cultratus at various time intervals following the initial parasitization by T. japonicus. The suitability of the host for the parasitoid development was re-assessed by providing T. cultratus with fresh and frozen egg masses of various ages. The likelihood of T. cultratus being able to attack previously parasitized egg masses was determined by assessing the duration of egg mass guarding behavior by T. japonicus following parasitization. The results of experiments examining the interspecific interactions between a native European egg parasitoid, T. cultratus, and an Asian parasitoid, T. japonicus (a candidate for the biological control of H. halys), showed that the native species can act as facultative hyperparasitoid of the exotic one. Although this is only possible during certain stages of T. japonicus development, the presence of the introduced parasitoid may reduce the impact of the evolutionary trap for indigenous parasitoid species. There is a possibility that the occurrence of facultative hyperparasitism between scelionid parasitoids associated with stinkbugs is common. This resulting intraguild predation could promote conservation and stabilization of natural communities by impacting the diversity and population dynamics of native stinkbugs and their parasitoids (e.g., by allowing native parasitoids to avoid wasting reproductive effort on unsuitable hosts), or reduce success of biological control programs (e.g., by reducing the population size of the exotic parasitoids).

Does the response of insect herbivores to cadmium depend on their feeding strategy?

Phytoremediation has been proposed for the elimination of toxic metals in soil, yet little attention has been given to the performance of insects that feed on contaminant-tolerant plants. We tested the performance of two herbivores with different feeding behaviors, the cabbage looper, Trichoplusia ni, and the green peach aphid, Myzus persicae, reared on cadmium-tolerant Brassica juncea plants that contained different concentrations of cadmium. We also tested the performance of the aphid parasitoid Aphidius colemani developing in aphids reared on plants with different levels of cadmium. The hypothesis tested was that the chewing insect would be more negatively affected than the sucking insect, because of the localization of cadmium within the host plant, and that the aphid parasitoid would not be affected. We also compared the performance of T. ni on artificial diet with different levels of cadmium. Neither the phloem-feeding aphid nor its parasitoid was affected by cadmium in the host plant. The effects of cadmium on the foliage-feeding cabbage looper varied, with negative effects on development observed in experiments with artificial diet but not in those using natural host plants. These data, together with information available in the literature, support the idea that the effects of toxic metals present in a host plant may be influenced by a herbivore's feeding strategy. However, a wide range of chewing and sucking species needs to be tested to confirm this hypothesis.

Costs of insecticide resistance in Cydia pomonella (Lepidoptera: Tortricidae).

The obvious benefits associated with insecticide resistance for pest species may come at a cost to other life-history traits. In this study, we compared the larval and pupal developmental times, pupal mass wing surface area and wing fluctuating asymmetry (FA) in insecticide resistant and control strains of codling moth, Cydia pomonella (L.) (Lepidoptera: Tortricidae), collected from apple (Malus spp.) orchards in central Canada. Resistant strains had significantly longer larval developmental times and lower pupal masses compared with the susceptible strain. Although the forewings of resistant moths were smaller in resistant than control strain, no difference in wing FA was detected. Longer developmental times could increase exposure time to natural enemies, and reduced adult size could affect longevity and total reproductive output.