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We tested the influence of genetic variation on responses to natural and artificial diets in Varroa-resistant Pol-line and Russian honey bee stocks. Newly emerged workers from six colonies per stock were fed pollen, spirulina (blue-green microalgae), and sucrose-only diets in 144 total cages. Diet type had a strong effect on sugar intake, body weight, fat body lipid content, and vitellogenin (vg) expression. Spirulina consumption was approximately half that of pollen, but led to higher head weights, equivalent thorax weights and vg levels, and marginally reduced fat body lipids. Bee stock and colony had a significant impact on nutritional response. Despite equivalent diet intakes, Pol-line bees accumulated higher lipid levels and consumed less sugar overall than Russian bees. Furthermore, pollen-fed bees sourced from Pol-line colonies had significantly higher vg levels. These differences in nutrient and energy allocation may reflect life history-related physiological tradeoffs. Our results suggest that genotype-dependent nutritional responses are present in honey bees, with promising implications for breeding efforts and tailored approaches to diet and health in a changing global climate.

BackgroundChanging demographics across the UK has led to general practitioners (GPs) managing increasing numbers of older patients with multi-morbidity and resultant polypharmacy. Through government led initiatives within the National Health Service, an increasing number of GP practices employ pharmacist support. The purpose of this study is to evaluate the impact of a medicines optimisation intervention, delivered by GP practice-based pharmacists, to patients at risk of medication-related problems (MRPs), on patient outcomes and healthcare costs.MethodsA multi-centre, randomised (normal care or pharmacist supplemented care) study in four regions of the UK, involving patients (n = 356) from eight GP practices, with a 6-month follow-up period. Participants were adult patients who were at risk of MRPs.ResultsMedian number of MRPs per intervention patient were reduced at the third assessment, i.e. 3 to 0.5 (p p = 0.001). Using the intention-to-treat (ITT) approach, the number of telephone consultations in intervention group patients was reduced and different from the control group (1 [0–3] to 1 [0–2] vs 1 [0–2] to 1 [0–3],p = 0.020). No significant differences between groups were, however, found in unplanned hospital admissions, length of hospital stay, number of A&E attendances or outpatient visits. The mean overall healthcare cost per intervention patient fell from £1041.7 ± 1446.7 to £859.1 ± 1235.2 (p = 0.032). Cost utility analysis showed an incremental cost per patient of − £229.0 (95% CI − 594.6, 128.2) and a mean QALY gained of 0.024 (95% CI − 0.021 to 0.065), i.e. indicative of a health status gain at a reduced cost (2016/2017).ConclusionThe pharmacist service was effective in reducing MRPs, inappropriateness of medications and telephone consultations in general practice in a cost-effective manner.Trial registration:ClinicalTrials.Gov, NCT03241498. Registered 7 August 2017—Retrospectively registered,https://clinicaltrials.gov/ct2/show/NCT03241498

Malnutrition is an increasing threat to honey bees that can be mitigated by feeding artificial pollen substitute diets; however, little is known about the molecular mechanisms underlying their impa...

OBJECTIVES: To survey and explore current approaches to deployment of pharmaceutical care prioritisation tools in acute hospitals in the UK.METHODS: A national online survey was circulated electronically to chief pharmacists of hospitals to determine if they use a prioritisation tool or process. Where such mechanisms exist, respondents were invited to participate in a semistructured telephone interview to explore the development, evaluation and application of their tool and share relevant documentation. Interviews were transcribed and thematically analysed.RESULTS: Seventy hospitals (70/130) used a tool or process to prioritise clinical pharmacy services. Thirty-six interviews were conducted, and two were excluded. The majority of tools had been developed in-house. Few hospitals had undertaken formal evaluations of their prioritisation tool. Pharmacy prioritisation tools ranged in complexity and often included a combination of pharmacy service prioritisation, such as medicines reconciliation, and a section to assign an individual patient prioritisation level. Determining the priority of a patient based on the identification of set indicators instilled confidence in pharmacists by ensuring they were not missing high-risk patients. Electronic prioritisation tools were especially useful at retrieving real-time data to prioritise workload, improving workflow and ensuring continuity in patient care. Drawbacks of using prioritisation tools included lack of tool sensitivity across certain specialties and time spent using the tool if not all information was accessible.CONCLUSIONS: Prioritisation tools were seen to be useful for prioritising workload and ensuring the right patients are seen at the right time. As few hospitals had formally evaluated their tools, it is important to rigorously and systematically develop an evidence-based prioritisation tool that is both useable and acceptable. Further research to evaluate such tools would be needed to ensure it improves patient health outcomes and efficiency in pharmacy services.

Though bulk stool remains the gold standard specimen type for enteropathogen diagnosis, rectal swabs may offer comparable sensitivity with greater ease of collection for select pathogens. This study sought to evaluate the validity and reproducibility of rectal swabs as a sample collection method for the molecular diagnosis of Giardia duodenalis. Paired rectal swab and bulk stool samples were collected from 86 children ages 0-4 years living in southwest Niger, with duplicate samples collected among a subset of 50 children. Infection was detected using a previously validated real-time PCR diagnostic targeting the small subunit ribosomal RNA gene. Giardia duodenalis was detected in 65.5% (55/84) of bulk stool samples and 44.0% (37/84) of swab samples. The kappa evaluating test agreement was 0.81 (95% CI: 0.54-1.00) among duplicate stool samples (N = 49) and 0.75 (95% CI: 0.47-1.00) among duplicate rectal swabs (N = 48). Diagnostic sensitivity was 93% (95% CI: 84-98) by bulk stool and 63% (95% CI: 49-75) by rectal swabs. When restricting to the lowest three quartiles of bulk stool quantitation cycle values (an indication of relatively high parasite load), sensitivity by rectal swabs increased to 78.0% (95% CI: 64-89, P < 0.0001). These findings suggest that rectal swabs provide less sensitive and reproducible results than bulk stool for the real-time PCR diagnosis of G. duodenalis. However, their fair sensitivity for higher parasite loads suggests that swabs may be a useful tool for detecting higher burden infections when stool collection is excessively expensive or logistically challenging.

Parafilaroides decorus, also known as sea lion lungworm, is a metastrongyloid nematode that infects otariid hosts, such as the charismatic California sea lion, Zalophus californianus. P. decorus causes bronchointerstitial pneumonia, respiratory distress, reduced ability to swim, dive and hunt and as a result, increased mortality particularly in young animals. Respiratory disease is a leading cause of stranding and admission to rehabilitation centers on the Pacific coast. Low-coverage genomic sequencing of four P. decorus individuals analyzed through Galaxy's RepeatExplorer identified a novel repeat DNA family we employed to design a sensitive quantitative PCR (qPCR) assay for diagnosing infections from fecal or sputum samples. The assay detects as little as 10 fg of P. decorus DNA and a linear regression model developed using a standard curve can be used to estimate the concentration of P. decorus DNA in a sample, ± 0.015 ng. This knowledge can be leveraged to estimate the level of parasite burden, which can be used to design improved treatments for animals in rehabilitation. Improved treatment of infections will aid in more animals being successfully released back into the wild., Graphical abstract Image 1, Highlights • Developed qPCR assay for P. decorus. • Sensitive to 10 fg. • Applicable for feces or sputum.

A semester-long research project for second-semester organic chemistry lab sections was developed. Student projects were based on preliminary data from faculty research that suggested the natural p...

Surveillance for soil-transmitted helminths, strongyloidiasis, cryptosporidiosis, and giardiasis was conducted in Mississippi, USA. PCR performed on 224 fecal samples for all soil-transmitted helminths and on 370 samples for only Necator americanus and Strongyloides stercoralis identified 1 S. stercoralis infection. Seroprevalences were 8.8% for Toxocara, 27.4% for Cryptosporidium, 5.7% for Giardia, and 0.2% for Strongyloides parasites.

Background Treatment resistant depression is a significant source of morbidity and mortality. For patients having failed or unable to undergo the electroconvulsive therapy procedure few effective alternative treatments exist. Methods A case series is presented where six patients with treatment resistant depression failing both electroconvulsive therapy and oral antidepressants are concomitantly treated with short course intravenous ketamine and longer term selegiline transdermal system. Results All six patients experienced clinical improvement with intravenous ketamine, with resolution of suicidality, increased food intake, and commitment to treatment adherence. Five patients showed sustained improvement with the selegiline transdermal system. One patient discontinued selegiline after developing peripheral edema and palpitations. Limitations This case series included only patients experiencing moderate to severe treatment resistant depression. Availability of long-term follow-up data not available in some cases. Conclusion Intravenous ketamine with simultaneous administration of the selegiline transdermal system is one strategy for treating treatment resistant depression in patients having failed or unable to undergo the electroconvulsive therapy procedure.

Background Hospital pharmacists play an essential role in patient care; however, a lack of resources means pharmacists are unable to review all patients daily. Consequently, there is a demand for reliable screening tools to allocate care to patients with urgent and/or complex pharmaceutical needs. Several tools have been developed, but no broad consensus exists on the design of a screening tool to be used in the adult hospital setting. Objective To obtain expert consensus on the design of a pharmaceutical care complexity screening tool for use on admission to hospital. Methods Two Delphi studies were conducted: the first sought to gain consensus from experts including pharmacists, academics and physicians on the components of a pharmaceutical complexity tool, the second to achieve consensus from UK chief pharmacists and clinical service pharmacy managers on the clinical appropriateness and practicality of the tool. Tool components and Delphi statements were identified and refined from our previous systematic review, UK survey and interview study of prioritisation tools. A valid definition for consensus was used. Results Over 300 components were extracted from the interview data and systematic review and then refined for inclusion in the first Delphi study. Thirty-three experts completed Delphi One and consensus was reached on 92 components. Components were grouped into demographic, clinical and medication components and condensed to 33 items, which were included in the first draft of the Adult Complexity Tool for Pharmaceutical Care (ACTPC). The tool stratified patients into highly, moderately or least complex. Forty expert panellists completed Delphi Two and consensus was reached on review frequency and experience of pharmacy practitioner at each level. These decisions were incorporated into the final version of the ACTPC. Conclusions The ACTPC is the first systematically designed and internationally agreed tool for use on medical admission to hospital. It has potential to enable the delivery of targeted patient-centred pharmaceutical care.

Summary:. The United States’s overdue awakening on systemic and structural racism has triggered global dialogue regarding racial inequities. Historically, discrimination and practitioner bias have resulted in poorer health and health outcomes in minority communities. To address racial and ethnic disparities in healthcare, it is imperative that plastic surgeons, trainees, and staff understand definitions to create a socially conscious environment in the workplace. We explore various measures that can be implemented to develop antiracist practices in the field of plastic surgery and ultimately to provide a foundation to improve diversity within our discipline and beyond.

Background Nucleic acid amplification tests (NAATs) are increasingly being used as diagnostic tools for soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, Necator americanus, Ancylostoma duodenale and A. ceylanicum), Strongyloides stercoralis and Schistosoma in human stool. Currently, there is a large diversity of NAATs being applied, but an external quality assessment scheme (EQAS) for these diagnostics is lacking. An EQAS involves a blinded process where test results reported by a laboratory are compared to those reported by reference or expert laboratories, allowing for an objective assessment of the diagnostic performance of a laboratory. In the current study, we piloted an international EQAS for these helminths (i) to investigate the feasibility of designing and delivering an EQAS; (ii) to assess the diagnostic performance of laboratories; and (iii) to gain insights into the different NAAT protocols used. Methods and principal findings A panel of twelve stool samples and eight DNA samples was validated by six expert laboratories for the presence of six helminths (Ascaris, Trichuris, N. americanus, Ancylostoma, Strongyloides and Schistosoma). Subsequently this panel was sent to 15 globally dispersed laboratories. We found a high degree of diversity among the different DNA extraction and NAAT protocols. Although most laboratories performed well, we could clearly identify the laboratories that were poorly performing. Conclusions/Significance We showed the technical feasibility of an international EQAS for the NAAT of STHs, Strongyloides and Schistosoma. In addition, we documented that there are clear benefits for participating laboratories, as they can confirm and/or improve the diagnostic performance of their NAATs. Further research should aim to identify factors that explain poor performance of NAATs., Author summary Tests that detect parasite DNA in human stool are increasingly being used for the diagnosis of infections with intestinal worms, including schistosomiasis. To ensure the quality in diagnostic testing of these parasitic worms, it is important that laboratories evaluate the diagnostic performance of their DNA-based tests. This can best be achieved by participating in an external quality assessment scheme (EQAS). An EQAS involves a blinded process where test results reported by a laboratory are compared to those reported by reference or expert laboratories, allowing for an objective assessment of the diagnostic performance of a laboratory. Currently, such an EQAS for parasitic worms is lacking. We therefore piloted an international EQAS for the diagnosis of parasitic worms involving 15 laboratories in Africa, Asia, Australia, Europe, and North America. Although most laboratories performed well, we could clearly identify those laboratories that may need to improve their test protocol. We found that laboratories were using many different test protocols, and further research should aim to verify whether this has an impact on the performance of the diagnostic outcomes.

We recently developed a superhydrophobic cone-based method for the collection of mosquito excreta/feces (E/F) for the molecular xenomonitoring of vector-borne parasites showing higher throughput compared to the traditional approach. To test its field applicability, we used this platform to detect the presence of filarial and malaria parasites in two villages of Ghana and compared results to those for detection in mosquito carcasses and human blood. We compared the molecular detection of three parasites (Wuchereria bancrofti, Plasmodium falciparum and Mansonella perstans) in mosquito E/F, mosquito carcasses and human blood collected from the same households in two villages in the Savannah Region of the country. We successfully detected the parasite DNA in mosquito E/F from indoor resting mosquitoes, including W. bancrofti which had a very low community prevalence (2.5–3.8%). Detection in the E/F samples was concordant with detection in insect whole carcasses and human blood, and a parasite not vectored by mosquitoes was detected as well.Our approach to collect and test mosquito E/F successfully detected a variety of parasites at varying prevalence in the human population under field conditions, including a pathogen (M. perstans) which is not transmitted by mosquitoes. The method shows promise for further development and applicability for the early detection and surveillance of a variety of pathogens carried in human blood., Author summary Molecular xenomonitoring of parasites or viruses using mosquitoes as “flying syringes” is a promising and non-invasive tool for early detection and surveillance of various pathogens, particularly in low prevalence settings, but there is a need for cost-effective and higher throughput alternatives. We recently developed a novel approach based on the collection of mosquito excreta/feces (E/F) using a superhydrophobic cone that directs the sample into a tube at the bottom of the collection cup. We tested this method’s ability to detect the presence of filarial and malaria parasite DNA from households in two endemic rural communities of Ghana and compared it to the molecular detection from blood and mosquito carcass samples from corresponding households. The detection of parasite DNA in mosquito E/F was successful for all three pathogens, and it showed good concordance with the detection in the insects’ whole carcasses. Given the successful detection of Mansonella perstans, which is not transmitted by mosquitoes, our tool shows promise for use as an alternative method for the early and non-invasive detection and surveillance of various pathogens in human blood, including those not strictly mosquito-borne, in endemic settings.

Introduction Neck pain among rotary-wing aviators has been established as an important issue in the military community, yet no U.S. Army regulation defines exactly what cervical spine range of motion (CROM) is adequate for flight. This lack of regulation leaves flight surgeons to subjectively determine whether an aviator affected by limited CROM is fit to maintain flight status. The U.S. Army Aeromedical Research Laboratory is conducting a study among AH-64 and UH-60 pilots to define CROM requirements in simulated and actual flight using optical head tracking equipment. Presented here is a preliminary analysis of head position data from a pilot and co-pilot in two AH-64 missions. Methods Maintenance data recorder (MDR) files from two AH-64 missions were provided by the Apache Attack Helicopter Project Management Office. Data were filtered down to three-dimensional pilot and co-pilot head position data and each data point was analyzed to determine neck posture. These neck postures were then categorized as neutral, mild, and severe for flexion/extension, lateral bending, and twist rotation postural categories. Results Twist rotation postures reached 90 degrees, particularly early in the flight; additionally, a few instances of 90-degree lateral bends were observed. Co-pilots spent more time than pilots in mild and severe twist rotation posture for both flights. Co-pilots also spend a high percentage of time in mild flexion and twist rotation. Conclusion This investigation provides a proof of concept for analysis of head tracking data from MDR files as a surrogate measure of neck posture in order to estimate CROM requirements in rotary-wing military flight missions. Future studies will analyze differences in day and night flights, pilot versus co-pilot CROM, and neck movement frequency.

Background: Japan is one of the few countries believed to have eliminated soil-transmitted helminths (STHs). In 1949, the national prevalence of Ascaris lumbricoides was 62.9%, which decreased to 0.6% in 1973 due to improvements in infrastructure, socioeconomic status, and the implementation of national STH control measures. The Parasitosis Prevention Law ended in 1994 and population-level screening ceased in Japan; therefore, current transmission status of STH in Japan is not well characterized. Sporadic cases of STH infections continue to be reported, raising the possibility of a larger-scale recrudescence of STH infections. Given that traditional microscopic detection methods are not sensitive to low-intensity STH infections, we conducted targeted prevalence surveys using sensitive PCR-based assays to evaluate the current STH-transmission status and to describe epidemiological characteristics of areas of Japan believed to have achieved historical elimination of STHs. Methods: Stool samples were collected from 682 preschool- and school-aged children from six localities of Japan with previously high prevalence of STH. Caregivers of participants completed a questionnaire to ascertain access to water, sanitation and hygiene (WASH), and potential exposures to environmental contamination. For fecal testing, multi-parallel real-time PCR assays were used to detect infections of Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale and Trichuris trichiura. Results: Among the 682 children, no positive samples were identified, and participants reported high standards of WASH. Conclusions: To our knowledge, this is the first STH-surveillance study in Japan to use sensitive molecular techniques for STH detection. The results suggest that recrudescence of STH infections has not occurred, and that declines in prevalence have been sustained in the sampled areas. These findings suggest that reductions in prevalence below the elimination thresholds, suggestive of transmission interruption, are possible. Additionally, this study provides circumstantial evidence that multi-parallel real-time PCR methods are applicable for evaluating elimination status in areas where STH prevalence is extremely low.[Figure not available: see fulltext.], Parasites & Vectors, 13(1), art.no.6; 2020

We present early-time ($t < +50$ days) observations of SN 2019muj (= ASASSN-19tr), one of the best-observed members of the peculiar SN Iax class. Ultraviolet and optical photometric and optical and near-infrared spectroscopic follow-up started from $\sim$5 days before maximum light ($t_{max}(B)$ on $58707.8$ MJD) and covers the photospheric phase. The early observations allow us to estimate the physical properties of the ejecta and characterize the possible divergence from a uniform chemical abundance structure. The estimated bolometric light curve peaks at 1.05 $\times$ 10$^{42}$ erg s$^{-1}$ and indicates that only 0.031 $M_\odot$ of $^{56}$Ni was produced, making SN 2019muj a moderate luminosity object in the Iax class with peak absolute magnitude of $M_{V}$ = -16.4 mag. The estimated date of explosion is $t_0 = 58698.2$ MJD and implies a short rise time of $t_{rise}$ = 9.6 days in $B$-band. We fit of the spectroscopic data by synthetic spectra, calculated via the radiative transfer code TARDIS. Adopting the partially stratified abundance template based on brighter SNe Iax provides a good match with SN 2019muj. However, without earlier spectra, the need for stratification cannot be stated in most of the elements, except carbon, which is allowed to appear in the outer layers only. SN 2019muj provides a unique opportunity to link extremely low-luminosity SNe Iax to well-studied, brighter SNe Iax., 24 pages, 17 figures, accepted for publication in MNRAS

BackgroundWe recently developed a superhydrophobic cone-based method for the collection of mosquito excreta/feces (E/F) for the molecular xenomonitoring of vector-borne parasites showing higher throughput compared to the traditional approach. To test its field applicability, we used this platform to detect the presence of filarial and malaria parasites in two villages of Ghana and compared results to those for detection in mosquito carcasses and human blood.Methodology and principal findingsWe compared the molecular detection of three parasites (Wuchereria bancrofti, Plasmodium falciparum and Mansonella perstans) in mosquito E/F, mosquito carcasses and human blood collected from the same households in two villages in the Savannah Region of the country. We successfully detected the parasite DNA in mosquito E/F from indoor resting mosquitoes, including W. bancrofti which had a very low community prevalence (2.5-3.8%). Detection in the E/F samples was concordant with detection in insect whole carcasses and people, and laboratory tests showed that the risk of mosquito carcass cross-contamination with positive excreta when insects are held together in the device is minimal.ConclusionsOur approach to collect and test mosquito E/F successfully detected a variety of parasites at varying prevalence in the human population under field conditions, including a pathogen (M. perstans) which is not transmitted by mosquitoes. The method shows promise for further development and applicability for the early detection and surveillance of a variety of pathogens carried in human blood.Author summaryMolecular xenomonitoring of parasites or viruses using mosquitoes as “flying syringes” is a promising and non-invasive tool for early detection and surveillance of various pathogens, particularly in low prevalence settings, but there is a need for cost-effective and higher throughput alternatives. We recently developed a novel approach based on the collection of mosquito excreta/feces (E/F) using a superhydrophobic cone that directs the sample into a tube at the bottom of the collection cup. We tested this method’s ability to detect the presence of lymphatic filariasis, malaria, and mansonellosis from households in two endemic rural communities of Ghana and compared it to the molecular detection from blood and mosquito carcass samples from corresponding households. The detection of parasite DNA in mosquito E/F was successful for all three pathogens, and it showed good concordance with the detection in the insects’ whole carcasses. Given the successful detection of Mansonella perstans, which is not transmitted by mosquitoes, our tool shows promise for use as an alternative method for the early and non-invasive detection and surveillance of various pathogens in human blood, including those not strictly mosquito-borne, in endemic settings.

Autism spectrum disorders (ASD) and obsessive compulsive disorder (OCD) are often comorbid and are associated with changes in striatal volumes and N-Acetylaspartate (NM) and glutamate levels. Here, we investigated the relation between dorsal striatal volume and NAA and glutamate levels. We additionally compared striatal volume and shape between ASD, OCD and controls. T1-weighted magnetic resonance (MR) images, proton spectra (1H-MRS) in the left striatum, and phenotypic information were collected from 54 children with ASD, 32 with OCD, and 56 controls (aged 8-13 years) in a four-site study. Dorsal striatal volume and shape were determined using the FMRIB integrated registration and segmentation tool (FIRST). Spectra were processed with Linear Combination Model. The relationship of left striatal volume with NAA and glutamate was investigated, and group comparisons were performed for NAA levels and for bilateral striatal volume and shape. NM levels were lower in subjects with ASD compared with controls (t=2.86, p= 0.005) and were associated with striatal volume 03=0.37, t=2.78, p=0.008). Glutamate levels were also associated with volume in the ASD group 03=0.38, t=2.46, p=0.018). No group differences were found for striatal volume or shape, but a post-hoc diagnosis-by-hemisphere interaction (F(2,129)=3.86, p=0.024) revealed greater asymmetry (right> left) in striatal volume for the disorder-groups compared with controls. Our findings show involvement of NM and glutamate in striatal volume in ASD and suggest greater asymmetry in paediatric ASD and OCD compared with controls, pointing to overlapping subcortical abnormalities. The lower NAA in ASD reflects reduced neuronal integrity or impaired neuronal functioning. (C) 2017 Elsevier B.V. All rights reserved.

The lemurs of Madagascar are threatened by human activities. We present the first molecular detection of canine heartworm (Dirofilaria immitis) in a wild non-human primate, the mouse lemur (Microcebus rufus). Zoonotic D. immitis infection has been associated with clinical pathology that includes serious and often fatal cardiac and pulmonary reactions. With human encroachment and associated increases in free-roaming dog populations in Madagascar, we examined lemurs for zoonotic canid pathogens. D. immitis presents a new potential conservation threat to lemurs. We highlight the need for wide-ranging and effective interventions, particularly near protected areas, to address this growing conservation issue. Keywords: Madagascar conservation, Pathogen spillover, Mosquito-borne disease, Blood parasite, Canine vector-borne diseases, brown mouse lemur, Microcebus rufus

In the last decade we have witnessed tremendous advances in our understanding of the landscape of the molecular alterations that underpin many of the most prevalent cancers, in the use of automated high-throughput platforms for high-throughput drug screens in cancer cells, in the creation of more clinically relevant cancer cell models, and lastly in the development of more useful computational approaches in the pursuit of biomarkers of drug response. Separately, each of these improvements will undoubtedly lead to improvements in the treatment of cancer patients but to fulfill the promise of truly personalized cancer medicine, we must bring these disciplines together in a truly multidisciplinary fashion.

SP6 is a salmonella phage closely related to coliphage K1-5. K1-5 is notable in that it encodes two polysaccharide-degrading tailspike proteins, an endosialidase that allows it to infect E. coli K1, and a lyase that enables it to infect K5 strains. SP6 is similar to K1-5 except that it encodes a P22-like endorhamnosidase tailspike, gp46, allowing it to infect group B Salmonella. We show here that SP6 can also infect Salmonella serogroups C2 and C3 and that a mutation in a putative second tailspike, gp47, eliminates this specificity. Gene 47 was fused to the coding region of the N-terminal portion of the Pseudomonas aeruginosa R2 pyocin tail fiber and expressed in trans such that the fusion protein becomes incorporated into pyocin particles. These pyocins, termed AvR2-SP47, killed serogroups C2 and C3 Salmonella. We conclude that SP6 encodes two tail proteins providing it a broad host range among Salmonella enterica.

A shock tube and anthropomorphic headforms were used to investigate eye protection form and fit using eyewear on the Authorized Protective Eyewear List in primary ocular blast trauma experiments. Time pressure recordings were obtained from highly linear pressure sensors mounted at the cornea of instrumented headforms of different sizes. A custom shock tube produced highly reliable shock waves and pressure recordings were collected as a function of shock wave orientation and protective eyewear. Eyewear protection coefficients were calculated as a function of a new metric of eyewear fit. In general, better protection was correlated with smaller gaps between the eyewear and face. For oblique angles, most spectacles actually potentiated the blast wave by creating higher peak pressures at the cornea. Installing foam around the perimeter of the spectacle lens to close the gap between the lens and face resulted in significantly lower pressure at the cornea. In conclusion, current eye protection, which was designed to reduce secondary and tertiary blast injuries, provides insufficient protection against primary blast injury.

Forensic chemists frequently conduct weight analyses of seized drugs to determine criminal trafficking thresholds. Drug weights remain relatively constant from the time of seizure until their analysis; however, the weight of freshly harvested cannabis plants changes over time as a consequence of drying. A decrease in the chemist’s recorded weight is therefore observed. Core samples were taken 0–3 days after seizure from bulk cannabis cases. Weight, date, time, temperature, and relative humidity data were recorded over a period of 0–21 days. The most significant loss in weight occurred in 1–3 days of the drying process and weights plateaued after one week. Cannabis lost between 25 and 77% of its original weight stored at an average of 22.2 °C and 49% relative humidity. Environmental conditions are expected to alter weight loss and time of the drying process. Quantifying the weight difference after a seizure can serve to explain general quantitative differences in recorded weights in a case.

The lymphatic system is a series of vessels that transport cells and excess fluid from tissues to the blood vascular system. Normally quiescent, the lymphatics can grow or remodel in response to developmental, immunological, or cells pathological stimuli. Lymphatic vessels comprise lymphatic endothelial cells (LECs) that can respond to external growth factors by undergoing proliferation, migration, adhesion, and tube and lumen formation into new vessel structures, a process known as lymphangiogenesis. To understand the key gene and signaling pathways necessary for lymphangiogenesis and lymphatic vessel remodeling, we have developed a three-dimensional LEC tube formation assay to explore the role of kinase signaling in these processes. The collagen-overlay-based assay was used with primary human adult dermal LECs to investigate a library of 60 tyrosine kinase (TK) and TK-like genes by siRNA knockdown. Nine candidate genes were identified and characterized for their ability to modify key parameters of lymphatic tube formation, including tube length, area, thickness, branching, and number of blind-ended sacs. Four genes-ZAP70, IRAK4, RIPK1, and RIPK2-were identified as high-confidence hits after tertiary deconvolution screens and demonstrate the utility of the assay to define LEC genes critical for the formation of tube structures. This assay facilitates the identification of potential molecular targets for novel drugs designed to modulate the remodeling of lymphatics that is important for the metastatic spread of cancer and other pathologies.

VEGF-C and VEGF-D are secreted glycoproteins that induce angiogenesis and lymphangiogenesis in cancer, thereby promoting tumor growth and spread. They exhibit structural homology and activate VEGFR-2 and VEGFR-3, receptors on endothelial cells that signal for growth of blood vessels and lymphatics. VEGF-C and VEGF-D were thought to exhibit similar bioactivities, yet recent studies indicated distinct signaling mechanisms (e.g. tumor-derived VEGF-C promoted expression of the prostaglandin biosynthetic enzyme COX-2 in lymphatics, a response thought to facilitate metastasis via the lymphatic vasculature, whereas VEGF-D did not). Here we explore the basis of the distinct bioactivities of VEGF-D using a neutralizing antibody, peptide mapping, and mutagenesis to demonstrate that the N-terminal α-helix of mature VEGF-D (Phe93–Arg108) is critical for binding VEGFR-2 and VEGFR-3. Importantly, the N-terminal part of this α-helix, from Phe93 to Thr98, is required for binding VEGFR-3 but not VEGFR-2. Surprisingly, the corresponding part of the α-helix in mature VEGF-C did not influence binding to either VEGFR-2 or VEGFR-3, indicating distinct determinants of receptor binding by these growth factors. A variant of mature VEGF-D harboring a mutation in the N-terminal α-helix, D103A, exhibited enhanced potency for activating VEGFR-3, was able to promote increased COX-2 mRNA levels in lymphatic endothelial cells, and had enhanced capacity to induce lymphatic sprouting in vivo. This mutant may be useful for developing protein-based therapeutics to drive lymphangiogenesis in clinical settings, such as lymphedema. Our studies shed light on the VEGF-D structure/function relationship and provide a basis for understanding functional differences compared with VEGF-C.

Background Helminth and protozoan infections affect more than 1 billion children globally. Improving water quality, sanitation, handwashing, and nutrition could be more sustainable control strategies for parasite infections than mass drug administration, while providing other quality of life benefits. Methods and findings We enrolled geographic clusters of pregnant women in rural western Kenya into a cluster-randomized controlled trial (ClinicalTrials.gov NCT01704105) that tested 6 interventions: water treatment, improved sanitation, handwashing with soap, combined water treatment, sanitation, and handwashing (WSH), improved nutrition, and combined WSH and nutrition (WSHN). We assessed intervention effects on parasite infections by measuring Ascaris lumbricoides, Trichuris trichiura, hookworm, and Giardia duodenalis among children born to the enrolled pregnant women (index children) and their older siblings. After 2 years of intervention exposure, we collected stool specimens from 9,077 total children aged 2 to 15 years in 622 clusters, including 2,346 children in an active control group (received household visits but no interventions), 1,117 in the water treatment arm, 1,160 in the sanitation arm, 1,141 in the handwashing arm, 1,064 in the WSH arm, 1,072 in the nutrition arm, and 1,177 in the WSHN arm. In the control group, 23% of children were infected with A. lumbricoides, 1% with T. trichiura, 2% with hookworm, and 39% with G. duodenalis. The analysis included 4,928 index children (median age in years: 2) and 4,149 older siblings (median age in years: 5); study households had an average of 5 people, 90% had dirt floors. Compared to the control group, Ascaris infection prevalence was lower in the water treatment arm (prevalence ratio [PR]: 0.82 [95% CI 0.67, 1.00], p = 0.056), the WSH arm (PR: 0.78 [95% CI 0.63, 0.96], p = 0.021), and the WSHN arm (PR: 0.78 [95% CI 0.64, 0.96], p = 0.017). We did not observe differences in Ascaris infection prevalence between the control group and the arms with the individual interventions sanitation (PR: 0.89 [95% CI 0.73, 1.08], p = 0.228), handwashing (PR: 0.89 [95% CI 0.73, 1.09], p = 0.277), or nutrition (PR: 86 [95% CI 0.71, 1.05], p = 0.148). Integrating nutrition with WSH did not provide additional benefit. Trichuris and hookworm were rarely detected, resulting in imprecise effect estimates. No intervention reduced Giardia. Reanalysis of stool samples by quantitative polymerase chain reaction confirmed the reductions in Ascaris infections measured by microscopy in the WSH and WSHN groups. Trial limitations included imperfect uptake of targeted intervention behaviors, limited power to detect effects on rare parasite infections, and that it was not feasible to blind participants and sample collectors to treatment status. However, lab technicians and data analysts were blinded to treatment status. The trial was funded by the Bill & Melinda Gates Foundation and the United States Agency for International Development. Conclusions Integration of improved water quality, sanitation, and handwashing could contribute to sustainable control strategies for Ascaris infections, particularly in similar settings with recent or ongoing deworming programs. Combining nutrition with WSH did not provide further benefits, and water treatment alone was similarly effective to integrated WSH. Our findings provide new evidence that drinking water should be given increased attention as a transmission pathway for Ascaris. Trial registration ClinicalTrials.gov NCT01704105., Interventions for improved water and hygiene in pregnant women in Kenya resulted in fewer Ascaris infections in newborns, Amy Pickering and colleagues reveal., Author summary Why was this study done? Intestinal worm and protozoan infections affect >1 billion children and are associated with growth faltering and impaired cognitive development. High reinfection rates can prevent mass drug administration programs from eliminating transmission. Improved water quality, sanitation, handwashing, and nutrition could interrupt environmental transmission of parasites, but few trials evaluating these interventions have measured parasite infections as an outcome. What did the researchers do and find? The authors conducted a randomized controlled trial among a birth cohort to test if single and combined improved drinking water quality, sanitation, handwashing, and nutrition interventions can reduce intestinal worm and Giardia infections. The authors measured parasite infections after 2 years of intervention exposure. The authors demonstrated that water treatment alone and integrated water, sanitation, and handwashing interventions can sustainably reduce roundworm (Ascaris) infection prevalence among young children in Kenya. Improved nutrition did not enhance the effectiveness of the water, sanitation, and handwashing interventions, and none of the interventions reduced Giardia. What do these findings mean? Improving water quality, sanitation, and handwashing concurrently in the household environment can protect children from infection with Ascaris. The study also provides evidence that water treatment alone may provide a similar level of protection against Ascaris infection, suggesting that combining water, sanitation, and handwashing interventions does not yield greater health benefits than implementing single interventions. Treating drinking water is a relatively unexplored strategy for controlling intestinal worm infections, and drinking water should be given increased attention as an ingestion exposure pathway for Ascaris eggs.

Introduction Malignant mesothelioma (MM) has no biomarker driven therapies in routine clinical use. We used a drug screen of molecularly characterised MM lines to identify novel genomic biomarker driven therapy. This led to the discovery of a subset of MMs, defined by loss of function (LOF) of the nuclear deubiquitinase BRCA associated protein 1 (BAP1), that demonstrate heightened sensitivity to tumour necrosis factor related apoptosis inducing ligand (TRAIL). We then validated this association across in vitro, in vivo and ex vivo models and delineated the underlying mechanism. Methods 15 MM lines were characterised for mutations in five MM tumour driver genes and screened for response to 95 compounds. The identified BAP1-TRAIL association was validated in an extended panel of MM lines with apoptosis and cell viability assays. 25 early passage MM cultures, mouse xenograft and human tumour explant models were used to further validate the association. Knock-in and knock-out models in BAP1 mutant and wild type lines confirmed the effect of loss of BAP1 expression on TRAIL sensitivity. 6 mutant BAP1 constructs were generated and identified which functional BAP1 sites modulate TRAIL sensitivity. The effect of BAP1 function on the downstream death receptor/apoptosis pathway components was determined using microarray and immunoblot analysis. Results BAP1 LOF significantly correlated with TRAIL sensitivity in established MM lines (p=0.015) and primary MM cultures (p Conclusions We identify loss of BAP1 as a novel biomarker for TRAIL sensitivity in MM. BAP1 LOF is observed in up to 67% of MM tumours and BAP1 immunohistochemistry is in use as a diagnostic tool; hence this approach is validated and ready for immediate and actionable clinical use for this disease.

Background.Helminth and protozoan infections affect >1 billion children globally. Improved water, sanitation, handwashing, and nutrition could be more sustainable control strategies for parasite infections than mass drug administration (MDA), while providing other quality of life benefits.Methods and Findings.We enrolled geographic clusters of pregnant women into a cluster-randomized controlled trial that tested six interventions: disinfecting drinking water(W), improved sanitation(S), handwashing with soap(H), combined WSH, improved nutrition(N), and combined WSHN. We assessed intervention effects on parasite infections by measuringAscaris lumbricoides,Trichuris trichiura, hookworm, andGiardia duodenalisamong individual children born to enrolled mothers and their older siblings (ClinicalTrials.govNCT01704105). We collected stool specimens from 9077 total children in 622 clusters, including 2346 children in control, 1117 in water, 1160 in sanitation, 1141 in handwashing, 1064 in WSH, 1072 in nutrition, and 1177 in WSHN. In the control group, 23% of children were infected withAscaris lumbricoides, 1% withTrichuris trichuria, 2% with hookworm and 39% withGiardia duodenalis. After two years of intervention exposure,Ascarisinfection prevalence was 18% lower in the water treatment arm (95% confidence interval (CI) 0%, 33%), 22% lower in the WSH arm (CI 4%, 37%), and 22% lower in the WSHN arm (CI 4%, 36%) compared to control. Individual sanitation, handwashing, and nutrition did not significantly reduceAscarisinfection on their own, and integrating nutrition with WSH did not provide additional benefit.Trichurisand hookworm were rarely detected, resulting in imprecise effect estimates. No intervention reducedGiardia. Reanalysis of stool samples by quantitative polymerase chain reaction (qPCR) confirmed the reductions inAscarisinfections measured by microscopy in the WSH and WSHN groups. Lab technicians and data analysts were blinded to treatment assignment, but participants and sample collectors were not blinded. The trial was funded by the Bill & Melinda Gates Foundation and USAID.Conclusions.Our results suggest integration of improved water quality, sanitation, and handwashing could contribute to sustainable control strategies forAscarisinfections, particularly in similar settings with recent or ongoing deworming programs. Water treatment alone was similarly effective to integrated WSH, providing new evidence that drinking water should be given increased attention as a transmission pathway forAscaris.

Prior work has revealed sex/gender-dependent autistic characteristics across behavioural and neural/biological domains. It remains unclear whether and how neural sex/gender differences are related to behavioural sex/gender differences in autism. Here, we examined whether atypical neural responses during mentalizing and self-representation are sex/gender-dependent in autistic adults and explored whether ‘camouflaging’ (acting as if behaviourally neurotypical) is associated with sex/gender-dependent neural responses. In total, N = 119 adults (33 typically developing males, 29 autistic males, 29 typically developing females and 28 autistic females) participated in a task-related functional magnetic resonance imaging paradigm to assess neural activation within right temporo-parietal junction and ventromedial prefrontal cortex during mentalizing and self-representation. Camouflaging in autism was quantified as the discrepancy between extrinsic behaviour in social–interpersonal contexts and intrinsic status. While autistic men showed hypoactive right temporo-parietal junction mentalizing and ventromedial prefrontal cortex self-representation responses compared to typically developing men, such neural responses in autistic women were not different from typically developing women. In autistic women only, increasing camouflaging was associated with heightened ventromedial prefrontal cortex self-representation response. There is a lack of impaired neural self-representation and mentalizing in autistic women compared to typically developing women. Camouflaging is heightened in autistic women and may relate to neural self-representation response. These results reveal brain-behaviour relations that help explain sex/gender-heterogeneity in social brain function in autism.

Correction to: Scientific Data https://doi.org/10.1038/sdata.2017.139, published online 03 October 2017. The Data Descriptor incorrectly states the formula used to calculate the Bliss additivity score in the Data analysis subsection of the Methods. The correct equation is listed below: Blissadditivity=1–(1–VsiRNA)–(1–Vanchor)+((1–VsiRNA)×(1–Vanchor))

An inversion polymorphism of the filamin and emerin genes at the tip of the long arm of the human X-chromosome serves as the basis of an investigative laboratory in which students learn something new about their own genomes. Long, nearly identical inverted repeats flanking the filamin and emerin genes illustrate how repetitive elements can lead to alterations in genome structure (inversions) through nonallelic homologous recombination. The near identity of the inverted repeats is an example of concerted evolution through gene conversion. While the laboratory in its entirety is designed for college level genetics courses, portions of the laboratory are appropriate for courses at other levels. Because the polymorphism is on the X-chromosome, the laboratory can be used in introductory biology courses to enhance understanding of sex-linkage and to test for Hardy-Weinberg equilibrium in females. More advanced topics, such as chromosome interference, the molecular model for recombination, and inversion heterozygosity suppression of recombination can be explored in upper-level genetics and evolution courses. DNA isolation, restriction digests, ligation, long PCR, and iPCR provide experience with techniques in molecular biology. This investigative laboratory weaves together topics stretching from molecular genetics to cytogenetics and sex-linkage, population genetics and evolutionary genetics.

Eukaryotic parasites are significant contributors to childhood illness in Niger. While helminthiases have received national attention through mass deworming efforts, the epidemiology of intestinal protozoa in Niger remains underexamined. This study employed real-time PCR diagnostics to describe the prevalence of two schistosomes, four soil-transmitted helminths, and one protozoan parasite in Boboye Department, Dosso Region. Prevalence was assessed using bulk stool specimens collected from a population-based sample of 86 children residing in 9 communities. Anthropometric measurements were used to calculate child growth z-scores and stool consistency was graded. Helminths were absent from the study population, with the exception of a single Schistosoma haematobium infection (1/86; 1.2%). Giardia duodenalis was the only protozoa present, detected in 65% (56/86) of children. Prevalence of G. duodenalis peaked in 2-year-olds with 88% (15/17) positivity. The population was generally undernourished, though growth indices did not differ significantly between children with and without G. duodenalis infection.

Background: Results from an increasing number of studies suggest that mosquito excreta/feces (E/F) testing has considerable potential to serve as a supplement for traditional molecular xenomonitoring techniques. However, as the catalogue of possible use-cases for this methodology expands, and the list of amenable pathogens grows, a number of fundamental methods-based questions remain. Answering these questions is critical to maximizing the utility of this approach and to facilitating its successful implementation as an effective tool for molecular xenomonitoring.Methods: Utilizing E/F produced by mosquitoes or tsetse flies experimentally exposed toBrugia malayi,Plasmodium falciparum, orTrypanosoma brucei brucei, factors such as limits of detection, throughput of testing, adaptability to use with competent- and incompetent-vector species, and effects of additional blood feedings post parasite-exposure were evaluated. Two platforms for the detection of pathogen signal (quantitative real-time PCR and digital PCR [dPCR]) were also compared, with strengths and weaknesses examined for each. Results: Experimental results indicated that high throughput testing is possible when evaluating mosquito E/F for the presence of eitherB. malayiorP. falciparumfrom both competent- and incompetent-vector mosquito species. Furthermore, following exposure to pathogen, providing mosquitoes with a second, uninfected bloodmeal did not expand the temporal window for E/F collection during which pathogen detection was possible. However, this collection window did appear longer in E/F collected from tsetse flies following exposure toT. b. brucei. Testing also suggested that dPCR may facilitate detection through its increased sensitivity. Unfortunately, logistical obstacles will likely make the large-scale use of dPCR impractical for this purpose.Conclusions: By examining many E/F testing variables, expansion of this technology to a field-ready platform has become increasingly feasible. However, translation of this methodology from the lab to the field will first require the completion of field-based pilot studies aimed at assessing the efficacy of E/F screening.

Since the emergence of the biopharmaceutical industry in the 1980's, Escherichia coli, has played an important role in the industrial production of recombinant proteins and plasmid DNA for therapeutic use. Currently, advanced biopharmaceutical products, including rationally designed recombinant proteins and viral-vector gene therapies, offer unprecedented promise for the long-term management, and even cure of disease. As such, E. coli remains an important production host for the biopharmaceutical industry. This review provides insight into the industrially relevant strain engineering approaches used to enhance both the quantity and quality of these therapeutic products.

Metastasis via the lymphatic vasculature is an important step in cancer progression. The formation of new lymphatic vessels (lymphangiogenesis), or remodeling of existing lymphatics, is thought to facilitate the entry and transport of tumor cells into lymphatic vessels and on to distant organs. The migration of lymphatic endothelial cells (LEC) toward guidance cues is critical for lymphangiogenesis. While chemokines are known to provide directional navigation for migrating immune cells, their role in mediating LEC migration during tumor-associated lymphangiogenesis is not well defined. Here, we undertook gene profiling studies to identify chemokine–chemokine receptor pairs that are involved in tumor lymphangiogenesis associated with lymph node metastasis. CCL27 and CCL28 were expressed in tumor cells with metastatic potential, while their cognate receptor, CCR10, was expressed by LECs and upregulated by the lymphangiogenic growth factor VEGFD and the proinflammatory cytokine TNFα. Migration assays demonstrated that LECs are attracted to both CCL27 and CCL28 in a CCR10-dependent manner, while abnormal lymphatic vessel patterning in CCR10-deficient mice confirmed the significant role of CCR10 in lymphatic patterning. In vivo analyses showed that LECs are recruited to a CCL27 or CCL28 source, while VEGFD was required in combination with these chemokines to enable formation of coherent lymphatic vessels. Moreover, tumor xenograft experiments demonstrated that even though CCL27 expression by tumors enhanced LEC recruitment, the ability to metastasize was dependent on the expression of VEGFD. These studies demonstrate that CCL27 and CCL28 signaling through CCR10 may cooperate with inflammatory mediators and VEGFD during tumor lymphangiogenesis. Significance: The study shows that the remodeling of lymphatic vessels in cancer is influenced by CCL27 and CCL28 chemokines, which may provide a future target to modulate metastatic spread.

As high-level recombinant protein production (RPP) exerts a massive stress on the production host, an extensive literature on RPP optimization focuses on separating the growth phase from RPP production once sufficient biomass has been obtained. The aim of the current investigation was to optimize the benefits of the relatively neglected alternative strategy to achieve high-level RPP during growth by minimizing stress on the host. High yields of the biopharmaceutical recombinant human tumour necrosis factor alpha (rhTNFα) were obtained by fed-batch fermentation relevant to industrial production based upon parameters that most severely affected RPP in preliminary laboratory scale batch cultures. Decreasing the inducer concentration and growth temperature, but increasing the production period, were far more effective for increasing RPP yields than changing the growth phase at which production was induced. High yields of up to 5 g l−1 of rhTNFα were obtained with minimal plasmid loss, even in synthetic media that lack animal-derived components and are therefore fully compliant with regulatory requirements. Most of the product was soluble and biologically active. In summary, stress minimization was shown to be an effective way to optimize the production of rhTNFα. Data generated in shake-flask experiments allowed the design of intensified bioreactor cultures in which RPP and growth could be balanced, leading to higher yield of both rhTNFα and biomass than with previous fermentations. An additional benefit of this approach is avoidance of lysis during harvesting and downstream processing.

Acute mental status changes in children and adolescents can often be a harbinger of a medical or psychiatric illness that requires an urgent and timely assessment. Acute mental status changes in a child can accompany acute changes in vital signs, which indicate need for an expedited evaluation. This chapter gives examples of presentations of acute mental status changes and their management. The interface between delirium and psychosis can be difficult to delineate, and examples of these conditions are given.

Cerebral small vessel disease (SVD) is a major health challenge. Therapeutic approaches remain limited, hampered by the lack of mechanistic understanding and identification of therapeutic targets. Relevant animal models could provide a cornerstone to basic scientific studies of disease mechanisms and pre-clinical studies of potential therapies, but there is a critical need to improve the current translational gap that exists between pre-clinical research and treatments in patients. The Medical Research Council Dementias Platform UK (MRC DPUK) Vascular Experimental Medicine Theme identified that a comprehensive assessment of the latest developments in animal models and of their contribution to understanding of cerebral microvascular disease would reduce the translational gap. In response to this, a two day workshop took place in late January 2017 at the British Heart Foundation Centre of Research Excellence in Glasgow, Scotland in conjunction with MRC DPUK and brought together experts from several disciplines in cerebrovascular disease, dementia and cardiovascular biology, to highlight current advances in these fields, explore synergies and scope for development. There were presentations from UK and international researchers and a specific focus on animal models of cerebral microvascular disease and dementia, considering vascular biology, neurogliovascular coupling, blood-brain barrier function, neuroinflammation, cerebral drainage pathways, and methodological and translational challenges (see Figure 1 for the general organisation of the meeting including the key topics and themes discussed). This overview provides a summary of the key talks, with a particular focus on mechanisms of cerebral vascular disease (see Figure 2) and improving translation. These talks were followed by related themed discussion groups on the gaps in knowledge and requirements to advance knowledge, the outcomes of which are highlighted in Table 1. Additional related articles are published in the Special Edition of Clinical Science (http://www.portlandpresspublishing.com/cc/small-vessels).

Lymphatic vessels constitute a specialized vasculature that is involved in development, cancer, obesity, and immune regulation. The migration of lymphatic endothelial cells (LECs) is critical for vessel growth (lymphangiogenesis) and vessel remodeling, processes that modify the lymphatic network in response to developmental or pathological demands. Using the publicly accessible results of our genome-wide siRNA screen, we characterized the migratome of primary human LECs and identified individual genes and signaling pathways that regulate LEC migration. We compared our data set with mRNA differential expression data from endothelial and stromal cells derived from two in vivo models of lymphatic vessel remodeling, viral infection and contact hypersensitivity-induced inflammation, which identified genes selectively involved in regulating LEC migration and remodeling. We also characterized the top candidates in the LEC migratome in primary blood vascular endothelial cells to identify genes with functions common to lymphatic and blood vascular endothelium. On the basis of these analyses, we showed that LGALS1, which encodes the glycan-binding protein Galectin-1, promoted lymphatic vascular growth in vitro and in vivo and contributed to maintenance of the lymphatic endothelial phenotype. Our results provide insight into the signaling networks that control lymphangiogenesis and lymphatic remodeling and potentially identify therapeutic targets and biomarkers in disease specific to lymphatic or blood vessels.

Metastatic colorectal cancer is a leading cause of cancer death. However, current therapy options are limited to chemotherapy, with the addition of anti-EGFR antibodies for patients with RAS wild-type tumours. Novel drug targets, or drug combinations that induce a synergistic response, would be of great benefit to patients. The identification of genes that are essential for cell survival can be undertaken using functional genomics screens. Furthermore, performing such screens in the presence of a targeted agent would allow the identification of combinations that result in a synthetic lethal interaction. Here, we present a dataset containing the results of a large scale RNAi screen (815 genes) to detect essential genes as well as synergistic combinations with targeted therapeutic agents using a panel of 27 colorectal cancer cell lines. These data identify genes that are essential for colorectal cancer cell survival as well as synthetic lethal treatment combinations using novel computational approaches. Moreover, this dataset could be utilised in combination with genomic profiling to identify predictive biomarkers of response.