Search

Background: Rapid diagnostic tests (RDTs) that rely on the detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) have become key tools for diagnosing P. falciparum infection. The utility of RDTs can be limited by PfHRP2 persistence, however it can be a potential benefit in low transmission settings where detection of persistent PfHRP2 using newer ultra-sensitive PfHRP2 based RDTs can serve as a surveillance tool to identify recent exposure. Better understanding of the dynamics of PfHRP2 over the course of a malaria infection can inform optimal use of RDTs. Methods: A previously published mathematical model was refined to mimic the production and decay of PfHRP2 during a malaria infection. Data from 15 individuals from volunteer infection studies were used to update the original model and estimate key model parameters. The refined model was applied to a cohort of patients from Namibia who received treatment for clinical malaria infection for whom longitudinal PfHRP2 concentrations were measured. Results: The refinement of the PfHRP2 dynamic model indicated that in malaria naïve hosts, P. falciparum parasites of the 3D7 strain produce 33.6 × 10−15 g (95% CI 25.0–42.1 × 10−15 g) of PfHRP2 in vivo per parasite replication cycle, with an elimination half-life of 1.67 days (95% CI 1.11–3.40 days). The refined model included these updated parameters and incorporated individualized body fluid volume calculations, which improved predictive accuracy when compared to the original model. The performance of the model in predicting clearance of PfHRP2 post treatment in clinical samples from six adults with P. falciparum infection in Namibia improved when using a longer elimination half-life of 4.5 days, with 14% to 67% of observations for each individual within the predicted range. Conclusions: The updated mathematical model can predict the growth and clearance of PfHRP2 during the production and decay of a mono-infection with P. falciparum, increasing the understanding of PfHRP2 antigen dynamics. This model can guide the optimal use of PfHRP2-based RDTs for reliable diagnosis of P. falciparum infection and re-infection in endemic settings, but also for malaria surveillance and elimination programmes in low transmission areas. [ABSTRACT FROM AUTHOR]

Hyaluronan (HA) is a structurally simple polysaccharide, but its ability to act as a template for organizing pericellular matrices and its regulated synthesis and degradation are key to initiating repair responses. Importantly, these HA functions are usurped by tumor cells to facilitate progression and metastasis. Recent advances have identified the functional complexities associated with the synthesis and degradation of HA-rich matrices. Three enzymes synthesize large HA polymers while multiple hyaluronidases or tissue free radicals degrade these into smaller bioactive fragments. A family of extracellular and cell-associated HA-binding proteins/receptors translates the bioinformation encrypted in this complex polymer mixture to activate signaling networks required for cell survival, proliferation, and migration in an actively remodeling microenvironment. Changes in HA metabolism within both the peritumor stroma and parenchyma are linked to tumor initiation, progression, and poor clinical outcome. We review evidence that metastatic tumor cells must acquire the capability to autonomously synthesize, assemble, and process their own "portable" HA-rich microenvironments to survive in the circulation, metastasize to ectopic sites, and escape therapeutic intervention. Strategies to disrupt the HA machinery of primary tumor and circulating tumor cells may enhance the effectiveness of current conventional and targeted therapies. Cancer Res; 76(9); 2507-12. [ABSTRACT FROM AUTHOR]

Even as resilience thinking becomes evermore popular as part of strategic programming among development and humanitarian organizations, uncertainty about how to define, operationalize, measure, and evaluate resilience for development goals prevails. As a result, many organizations and institutions have undertaken individual, collective, and simultaneous efforts toward clarification and definition. This has opened up a unique opportunity for a rethinking of development practices. The emergent consensus about what resilience means within development practice will have important consequences both for development practitioners and the communities in which they work. Incorporating resilience thinking into development practice has the potential to radically transform this arena in favor of social and environmental justice, but it could also flounder as a way to dress old ideas in new clothes or, at worst, to further exploit, disempower, and marginalize the world's most vulnerable populations. We seek to make an intervention into the definitional debates surrounding resilience that supports the former and helps prevent the latter. We argue that resilience thinking as it has been developed in social-ecological systems and allied literatures has a lot in common with the concept of food sovereignty and that paying attention to some of the lessons and claims of food sovereignty movements could contribute toward building a consensus around resilience that supports social and environmental justice. In particular, the food sovereignty movement relies on a strategy that elevates rights. We suggest that a rights-based approach to resilience-oriented development practice could contribute to its application in just and equitable ways. [ABSTRACT FROM AUTHOR]

As malaria transmission continues to decrease, an increasing number of countries will enter pre-elimination and elimination. To interrupt transmission, changes in control strategies are likely to require more accurate identification of all carriers of Plasmodium parasites, both symptomatic and asymptomatic, using diagnostic tools that are highly sensitive, high throughput and with fast turnaround times preferably performed in local health service settings. Currently available immunochromatographic lateral low rapid diagnostic tests and field microscopy are unlikely to consistently detect infections at parasite densities less than 100 parasites/µL making them insufficiently sensitive for detecting all carriers. Molecular diagnostic platforms, such as PCR and LAMP, are currently available in reference laboratories, but at a cost both financially and in turnaround time. This review describes the recent progress in developing molecular diagnostic tools in terms of their capacity for high throughput and potential for performance in non-reference laboratories for malaria elimination. [ABSTRACT FROM AUTHOR]

Interventions that lead to reductions in soil-transmitted helminths (STHs) include chemotherapy with anthelmintic drugs and improvements in water, sanitation, and hygiene (WASH). In this opinion article we aim to determine the evidence for optimal approaches for STH control. First we explore the evidence for the above interventions. We then appraise two integration strategies: current chemotherapy-oriented integrated neglected tropical disease (NTD) control and expanded ‘multicomponent integration’, which includes integrated chemotherapy, WASH, and other intervention strategies. While multicomponent integrated control may be an effective approach to sustainably reduce STH transmission, there is a need for evidence to prove the feasibility of this approach. [ABSTRACT FROM AUTHOR]

Discusses an alternative physiology class using a deciduous limb as a `bare bones' tree. Students make ornaments pertaining to any topic covered to date, with an emphasis on the skeletal system. Making the decorations from real bone; Candy bones, bonedeer, and decorated wishbones; Surprise Osteology Party; Rearranged version of `The Twelve Days of Christmas'; More.

Questions Grill and Bartel's article on the existence of bias in the Grammatical Closure subtest of the Illinois Test of Psycholinguistic Abilities against speakers of nonstandard English, published in the April 1977 issue of the 'Journal of Learning Disabilities.' Problems with internal validity; Problems with external validity; Problems with operational definitions.

Highlights a debate among academicians concerning the validity of the research procedures and the psychological tests employed in measuring the components of perceptual ability. Problems related to the selection of subjects; Improper use of the null hypotheses; Arguments refuting the claim that the tests employed for measuring perceptual ability are invalid.

Background: Although there is unprecedented interest in experimental human hookworm infection, details of hookworm manufacture and characterisation have been sparsely reported. In this report, we detail the production and characterisation of Necator americanus larvae for use in a recently published clinical trial. Methods: Faeces was obtained from an experimentally infected donor. Faecal hookworm DNA was determined by quantitative PCR. Paired samples were incubated in either sterile water or sterile water mixed with antimicrobials (amphotericin and gentamicin). Coproculture was performed by modified Harada-Mori method. The harvested larvae were then processed in either sterile water or antiseptic solution. Larval yield was then calculated (larvae per gram), larval viability was determined by thermally induced motility assay and microbial burden was determined at the day of harvest, at 48 h and at 7 days. Results: Twenty-eight faecal cultures were performed over 16 months. The faecal hookworm DNA content was variable over this time. There was no association of larval yield with faecal hookworm DNA content. Pre-treatment of faeces with antimicrobials did not influence larval yield. Larval motility was 85.3% (95% CI 79.3–91.3%). Incubation of larvae in antiseptics did not reduce viability at 14 days with a marginal mean of 68.6% (95% CI 59.1–78.1%) washed in water vs. 63.3% (95% CI 53.8 – 72.9%) when incubated in betadine (p = 0.38). Larvae washed in sterile water did not meet microbial bioburden criteria. Incubation in antiseptic resulted in acceptable microbial bioburden at 48 h but not at 7 days. Although the addition of gentamicin did reduce the microbial bio-burden acceptable levels, it was found to significantly lower larval motility at 7 days compared to incubation in sterile water and motility at 7 days 37.8% (95% CI 4.7–70.9%) vs. 67.3% (95% CI 35.2–99.3%, p < 0.001), respectively. Conclusions: Despite standardised culture methodologies and the use of a single donor, larval yield varied considerably between batches and had no association with faecal hookworm DNA. Larval viability decreases over time and the age of larvae at time of use are likely to be important. Microbial bioburden maybe temporarily reduced by incubation in antiseptics and has little effect on viability. Incubation of larvae in gentamicin is effective at reducing microbial bioburden but is deleterious to larval viability. [ABSTRACT FROM AUTHOR]

Commercial point-of-care tests remain insufficient for accurately detecting and differentiating low-level malaria infections in regions co-endemic with multiple non-falciparum species, including zoonotic Plasmodium knowlesi (Pk). A 5-plex chemiluminescent assay simultaneously measures pan-Plasmodium lactate dehydrogenase (pLDH), P. falciparum (Pf)-LDH, P. vivax (Pv)-LDH, Pf-histidine-rich protein-2 (HRP2), and C-reactive protein. We assessed its diagnostic performance on whole blood (WB) samples from 102 healthy controls and 306 PCR-confirmed clinical cases of Pf, Pv, Pk, P. malariae (Pm) and P. ovale (Po) mono-infections from Southeast-Asia. We confirm its excellent HRP2-based detection of Pf. Cross-reactivity of Pf-LDH with all non-falciparum species tested was observed (specificity 57.3%). Pv-LDH performance was suboptimal for Pv (93.9% sensitivity and 73.9% specificity). Poor specificity was driven by strong Pk cross-reactivity, with Pv-LDH detecting 93.9% of Pk infections. The pan-LDH-to-Pf-LDH ratio was capable of discerning Pv from Pk, and robustly differentiated Pf from Pm or Po infection, useful in regions with hrp2/3 deletions. We tested the platform's performance in plasma for the first time, with WB outperforming plasma for all analytes except Pv-LDH for Pk. The platform is a promising tool for WB malaria diagnosis, although further development is warranted to improve its utility in regions co-endemic for multiple non-falciparum species. [ABSTRACT FROM AUTHOR]

Analyzing meteoric 10 Be in soil profiles along with soil measurements such as pedogenic Fe and clay content permits better understanding of meteoric 10 Be transport in soils, soil formation, and hillslope geomorphology. This study presents meteoric 10 Be depth profiles from saprolite-derived soil catenas sampled in the Gordon Gulch catchment, Colorado Front Range and from nearby c. 130 and 15 ka glacial moraines. We compare meteoric 10 Be data with more classically used soil analyses of clay and extractable iron (Fed) content. Meteoric 10 Be and Fed do not show consistent trends in the hillslope profiles. Meteoric 10 Be and clay concentrations, however, generally decrease with depth and highest concentrations of 10 Be in horizons coincide with highest clay concentrations. Soils at moraine sites are better developed than those on hillslopes, and correlations of 10 Be, Fed, and clay are stronger. In Gordon Gulch, south-facing hillslopes display meteoric 10 Be bulges at depth and lower near-surface concentrations compared to the declining profiles and higher near-surface concentrations of north-facing hillslopes. The aspect differences imply that south-facing hillslopes experience greater vertical mixing than north-facing hillslopes, and that greater lateral transport and erosion has occurred over the last 15–20 ka on south-facing hillslopes relative to north-facing hillslopes. Meteoric 10 Be depth profiles at moraine sites display bulge profiles with highest meteoric 10 Be concentrations in B-horizons, reflecting landform stability and pedogenic processes. Overall, our data demonstrate that signatures of chemical weathering in soils (Fed and clay) may or may not correlate to the meteoric 10 Be added through atmospheric deposition, and that profile shape of meteoric 10 Be can provide insight into the relative contribution of vertical mixing and surface erosion in relation to catena location and aspect during hillslope evolution. [ABSTRACT FROM AUTHOR]

Cerebral malaria is the most serious manifestation of severe falciparum malaria. Sequestration of infected red blood cells and microvascular dysfunction are key contributing processes. Whether these processes occur in early stage disease prior to clinical manifestations is unknown. To help localize and understand these processes during the early stages of infection, we performed 18-F fluorodeoxyglucose positron emission tomography/magnetic resonance imaging in volunteers with Plasmodium falciparum induced blood stage malaria (IBSM) infection, and compared results to individuals with P. vivax infection, in whom coma is rare. Seven healthy, malaria-naïve participants underwent imaging at baseline, and at early symptom onset a median 9 days following inoculation (n = 4 P. falciparum, n = 3 P. vivax). Participants with P. falciparum infection demonstrated marked lability in radiotracer uptake across all regions of the brain, exceeding expected normal variation (within subject coefficient of variation (wCV): 14.4%) compared to the relatively stable uptake in participants with P. vivax infection (wCV: 3.5%). No consistent imaging changes suggestive of microvascular dysfunction were observed in either group. Neuroimaging in early IBSM studies is safe and technically feasible, with preliminary results suggesting that differences in brain tropism between P. falciparum and P. vivax may occur very early in infection. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to establish consensus for the assessment of foot alignment and function in ambulatory children with cerebral palsy, using expert surgeon’s opinion through a modified Delphi technique. Methods: The panel used a five-level Likert-type scale to record agreement or disagreement with 33 statements regarding the assessment of foot alignment and function. Consensus was defined as at least 80% of responses being in the highest or lowest of two of the five Likert-type ratings. General agreement was defined as 60%–79% falling into the highest or lowest two ratings. There was no agreement if neither threshold was reached. Results: Consensus was achieved for 25 (76%) statements, general agreement for 4 (12%) statements, and lack of consensus for 4 (12%) of the statements. There was consensus that the functional anatomy of the foot is best understood by dividing the foot into three segments and two columns. Consensus was achieved concerning descriptors of foot segmental alignment for both static and dynamic assessment. There was consensus that radiographs of the foot should be weight-bearing. There was general agreement that foot deformity in children with cerebral palsy can be classified into three levels based on soft tissue imbalance and skeletal malalignment. Conclusion: The practices identified in this study can be used to establish best care guidelines, and the format used will be a template for future Delphi technique studies on clinical decision-making for the management of specific foot segmental malalignment patterns commonly seen in children with cerebral palsy. Level of Evidence: V [ABSTRACT FROM AUTHOR]

Background: Interventions that effectively target Plasmodium vivax are critical for the future control and elimination of malaria. We conducted a P. vivax volunteer infection study to characterize the antimalarial activity of artefenomel, a new drug candidate.Methods: Eight healthy, malaria-naive participants were intravenously inoculated with blood-stage P. vivax and subsequently received a single oral 200-mg dose of artefenomel. Blood samples were collected to monitor the development and clearance of parasitemia, and plasma artefenomel concentration. Mosquito feeding assays were conducted before artefenomel dosing to investigate parasite transmissibility.Results: Initial parasite clearance occurred in all participants after artefenomel administration (log10 parasite reduction ratio over 48 hours, 1.67; parasite clearance half-life, 8.67 hours). Recrudescence occurred in 7 participants 11-14 days after dosing. A minimum inhibitory concentration of 0.62 ng/mL and minimum parasiticidal concentration that achieves 90% of maximum effect of 0.83 ng/mL were estimated, and a single 300-mg dose was predicted to clear 109 parasites per milliliter with 95% certainty. Gametocytemia developed in all participants and was cleared 4-8 days after dosing. At peak gametocytemia, 75% of participants were infectious to mosquitoes.Conclusions: The in vivo antimalarial activity of artefenomel supports its further clinical development as a treatment for P. vivax malaria.Clinical Trials Registration: NCT02573857. [ABSTRACT FROM AUTHOR]

Background: Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the "parasite clearance curve", has been critical for assessing drug efficacy; yet underlying mechanisms remain partly unresolved. The clearance curve may be shaped both by the rate at which drugs kill parasites, and the rate at which drug-affected parasites are removed from circulation. Methods: In this context, two anti-malarials, SJ733, and an ACT partner drug, pyronaridine were compared against sodium artesunate in mice infected with Plasmodium berghei (strain ANKA). To measure each compound's capacity for pRBC removal in vivo, flow cytometric monitoring of a single cohort of fluorescently-labelled pRBC was employed, and combined with ex vivo parasite culture to assess parasite maturation and replication. Results: These three compounds were found to be similarly efficacious in controlling established infection by reducing overall parasitaemia. While sodium artesunate acted relatively consistently across the life-stages, single-dose SJ733 elicited a biphasic effect, triggering rapid, partly phagocyte-dependent removal of trophozoites and schizonts, followed by arrest of residual ring-stages. In contrast, pyronaridine abrogated maturation of younger parasites, with less pronounced effects on mature parasites, while modestly increasing pRBC removal. Conclusions: Anti-malarials SJ733 and pyronaridine, though similarly efficacious in reducing overall parasitaemia in mice, differed markedly in their capacity to arrest replication and remove pRBC from circulation. Thus, similar parasite clearance curves can result for anti-malarials with distinct capacities to inhibit, kill and clear parasites. [ABSTRACT FROM AUTHOR]

Abstract: Background: Sepsis is a deleterious systemic response to an infection with a high incidence of morbidity and mortality, affecting more than a million patients a year in the US. The purpose of this study was to develop a screening tool for the early identification of sepsis in emergency department patients using readily available information at triage. Materials and methods: This prospective, observational study took place at an academic tertiary referral hospital. Over a period of 10 wk, all patients who were seen at triage were screened for study enrollment. Inclusion criteria were adult (age ≥18 y) nontrauma patients and exclusion criteria were prisoners and pregnant women. Using a Spot Check StO2 device to measure StO2 value, heart rate, respiratory rate, and temperature, these values were used to generate a cumulative screening score indicating whether a patient may have sepsis. Results: A total of 500 patients were screened. The incidence of sepsis in the present study population was 8.4%. The screening tool yielded a sensitivity of 85.7%, a specificity of 78.4%, a positive predictive value of 26.7%, and a negative predictive value of 98.4%. Conclusions: Heart rate, respiratory rate, and temperature have good diagnostic potential for the early identification of sepsis among emergency department triage personnel. Additionally, early evidence suggests StO2 may play a complementary and synergistic role in the early identification of sepsis by triage personnel. [Copyright &y& Elsevier]

This study examines the Object relations of hospitalized children who exhibit nonsuicidal self-injurious behavior (NSSI). A retrospective review of medical records of 87 adolescents in an urban psychiatric hospital was conducted. Thematic Apperception Test responses of NSSI children were scored using the Social Cognition and Object relations Scale and compared to non-NSSI peers. Results of Analysis of Variance showed a significant difference in complexity of representation of others between NSSI and non-NSSI adolescents, and trends in the data showed lower emotional investment in values and moral standards and greater understanding of social causality among NSSI youth. NSSI participants had a greater percentage of nonspecific learning disorders and trend towards a greater percentage of depression. NSSI adolescents were significantly older than non-NSSI adolescents. Clinical implications for psychotherapy are discussed. [ABSTRACT FROM AUTHOR]

Signaling from an actively remodeling extracellular matrix (ECM) has emerged as a critical factor in regulating both the repair of tissue injuries and the progression of diseases such as metastatic cancer. Hyaluronan (HA) is a major component of the ECM that normally functions in tissue injury to sequentially promote then suppress inflammation and fibrosis, a duality in which is featured, and regulated in, wound repair. These essential response-to-injury functions of HA in the microenvironment are hijacked by tumor cells for invasion and avoidance of immune detection. In this review, we first discuss the numerous size-dependent functions of HA and emphasize the multifunctional nature of two of its receptors (CD44 and RHAMM) in regulating the signaling duality of HA in excisional wound healing. This is followed by a discussion of how HA metabolism is de-regulated in malignant progression and how targeting HA might be used to better manage breast cancer progression. [ABSTRACT FROM AUTHOR]

Background: Malaria-associated anaemia, arising from symptomatic, asymptomatic and submicroscopic infections, is a significant cause of morbidity worldwide. Induced blood stage malaria volunteer infection studies (IBSM-VIS) provide a unique opportunity to evaluate the haematological response to early Plasmodium falciparum and Plasmodium vivax infection. Methods: This study was an analysis of the haemoglobin, red cell counts, and parasitaemia data from 315 participants enrolled in IBSM-VIS between 2012 and 2019, including 269 participants inoculated with the 3D7 strain of P. falciparum (Pf3D7), 15 with an artemisinin-resistant P. falciparum strain (PfK13) and 46 with P. vivax. Factors associated with the fractional fall in haemoglobin (Hb-FF) were evaluated, and the malaria-attributable erythrocyte loss after accounting for phlebotomy-related losses was estimated. The relative contribution of parasitized erythrocytes to the malaria-attributable erythrocyte loss was also estimated. Results: The median peak parasitaemia prior to treatment was 10,277 parasites/ml (IQR 3566–27,815), 71,427 parasites/ml [IQR 33,236–180,213], and 34,840 parasites/ml (IQR 13,302–77,064) in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. The median Hb-FF was 10.3% (IQR 7.8–13.3), 14.8% (IQR 11.8–15.9) and 11.7% (IQR 8.9–14.5) in those inoculated with Pf3D7, PfK13 and P. vivax, respectively, with the haemoglobin nadir occurring a median 12 (IQR 5–21), 15 (IQR 7–22), and 8 (IQR 7–15) days following inoculation. In participants inoculated with P. falciparum, recrudescence was associated with a greater Hb-FF, while in those with P. vivax, the Hb-FF was associated with a higher pre-treatment parasitaemia and later day of anti-malarial treatment. After accounting for phlebotomy-related blood losses, the estimated Hb-FF was 4.1% (IQR 3.1–5.3), 7.2% (IQR 5.8–7.8), and 4.9% (IQR 3.7–6.1) in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. Parasitized erythrocytes were estimated to account for 0.015% (IQR 0.006–0.06), 0.128% (IQR 0.068–0.616) and 0.022% (IQR 0.008–0.082) of the malaria-attributable erythrocyte loss in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. Conclusion: Early experimental P. falciparum and P. vivax infection resulted in a small but significant fall in haemoglobin despite parasitaemia only just at the level of microscopic detection. Loss of parasitized erythrocytes accounted for < 0.2% of the total malaria-attributable haemoglobin loss. [ABSTRACT FROM AUTHOR]

In 1896, a serendipitous laboratory accident led to the understanding that hookworms propagate infection by penetrating skin, a theory that was then confirmed with the first experimental human infection, reported in 1901. Experimental human infections undertaken in the 20th century enabled understanding of the natural history of infection and the immune response. More recently, experimental hookworm infection has been performed to investigate the immunomodulatory potential of hookworm infection and for the evaluation of hookworm vaccines and chemotherapeutic interventions. Experimental human hookworm infection has been proven to be safe, with no deaths observed in over 500 participants (although early reports predate systematic adverse event reporting) and no serious adverse events described in over 200 participants enrolled in contemporary clinical trials. While experimental human hookworm infection holds significant promise, as both a challenge model for testing anti-hookworm therapies and for treating various diseases of modernity, there are many challenges that present. These challenges include preparation and storage of larvae, which has not significantly changed since Harada and Mori first described their coproculture method in 1955. In vitro methods of hookworm larval culture, storage, and the development of meaningful potency or release assays are required. Surrogate markers of intestinal infection intensity are required because faecal egg counts or hookworm faecal DNA intensity lack the fidelity required for exploration of hookworm infection as a vaccine/drug testing platform or as a regulated therapy. [ABSTRACT FROM AUTHOR]

Background: Control of human hookworm infection would be greatly aided by the development of an effective vaccine. We aimed to develop a live attenuated human hookworm vaccine.Methods: This was a two-part clinical trial done at Q-Pharm in Brisbane (QLD, Australia) using a live ultraviolet C (UVC)-attenuated Necator americanus larvae vaccine. Part one was an open-label, dose-finding study using 50 L3 larvae suspended in water to a volume of 200 μL, attenuated with UVC exposure of 700 μJ (L3-700) or 1000 μJ (L3-1000). Part two was a randomised, double-blind, placebo-controlled, challenge study, in which participants were randomly assigned 2:1 to the vaccine group or placebo group. Healthy hookworm-naive adults aged 18-65 years with body-mass index 18-35 kg/m2 received two doses of either placebo (Tabasco sauce) or vaccine (50 L3-700) on day 1 and day 42, followed by challenge with 30 unattenuated L3 larvae to both groups. All participants received a single oral dose of 400 mg albendazole 4 weeks after each inoculation and a 3-day course (400 mg orally daily) initiated on day 161 after the challenge phase, to eliminate any remaining infection. The primary outcome of part 1 was the level of larval attenuation the resulted in a grade 2 or 3 dermal adverse event. The primary outcome of part 2 was safety and tolerability, assessed by frequency and severity of adverse events in all randomly assigned participants. Prespecified exploratory outcomes in the challenge study were faecal N americanus DNA concentration, the number of N americanus larvae recovered per g of faeces cultured, hookworm antigen-specific serum IgG antibody responses, and hookworm antigen-specific peripheral blood cytokine responses. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617001007325).Findings: Between Sept 19, 2017, and Oct 24, 2018, seven participants were enrolled into three cohorts in part one (two participants in cohort 1, who received L3-700; two participants in cohort 2, who received L3-700; and three participants in cohort 3, who received L3-1000) and a further 15 were enrolled into part two. There were no serious adverse events in part one or part two. In part one, a greater number of skin penetration sites were observed after administration of L3-700 than L3-1000 (mean 15·75 [95% CI 11·18 to 20·32] with L3-700 vs 4·33 [-1·40 to 10·07] with L3-1000). Similarly, greater erythema (median 225 mm2 [IQR 150 to 325] vs 25 mm2 [12·5 to 80]) and a longer duration of the dermal reaction (median 8·0 days [IQR 3·5 to 11·5] vs 2·0 days [2·0 to 4·5]) were observed after L3-700 than L3-1000. The mean number of adverse events per participant did not differ between the groups (3·25 [95% CI 1·48 to 5·02] vs 3·00 [1·04 to 4·96]). Thus, L3-700 was used for vaccination in part two. In part two, ten participants were randomly assigned to receive L3-700 and five to placebo. Significantly more adverse events occurred after vaccination with attenuated larvae than with placebo (incident rate ratio [IRR] 2·13 [95% CI 2·09 to 5·51]; p=0·0030). There was no difference between groups in the frequency of adverse events after challenge (IRR 1·25 [0·78 to 2·01]; p=0·36). Most adverse events were mild in severity, with only one severe adverse event reported (erythematous and indurated pruritic rash >100 mm in a vaccine group participant after challenge). The eosinophil count increased in all participants after challenge, with a significantly greater increase among vaccinated participants than placebo participants (1·55 × 109 cells per L [IQR 0·92 to 1·81] in the vaccine group vs 0·49 × 109 cells per L [0·43 to 0·63] in the placebo group; p=0·014). Vaccinated participants had an IgG response to larval extract after challenge that was higher than that in placebo participants (increase in IgG titre 0·22 [IQR 0·10 to 0·41] vs 0·03 [-0·40 to 0·06]; p=0·020). Significantly fewer larvae per g of faeces were recovered in the vaccine group than in the placebo group after challenge (median larvae per g 0·8 [IQR 0·00 to 3·91] vs 10·2 [5·1 to 18·1]; p=0·014). The concentration of N americanus DNA in faeces was not significantly different between the vaccinated group and the placebo group (log10 DNA intensity 4·28 [95% CI 3·92 to 4·63] vs 4·88 [4·31 to 5·46]; p=0·14). Peripheral blood mononuclear cells from vaccinated participants exhibited significantly greater cytokine production at day 112 than placebo participants for IFNγ, TNFα, IL-2, IL-4, and IL-5 (p<0·05), but not IL-10.Interpretation: Vaccination with UVC-attenuated N americanus larvae is well tolerated, induces humoral and cellular responses to hookworm antigens, and reduces larval output after challenge with unattenuated larvae. Larger studies are required to confirm protective efficacy.Funding: National Health and Medical Research Council of Australia. [ABSTRACT FROM AUTHOR]

The empirical literature offers evidence that childhood sexual abuse is a predictor of psychopathology in adults. However, the literature examining the relations between thought disorder and psychotic symptoms in children is sparse. Children with a history of childhood sexual abuse are expected to demonstrate more disturbances in thought relative to their peers with no childhood sexual abuse. Using the Thought and Language Index, Thematic Apperception Test (TAT) narratives for four commonly used TAT cards obtained from 39 closed charts of hospitalized children were analyzed. Narratives were assessed on seven dimensions including weakening of goals, perseveration, looseness, peculiar word usage, peculiar sentence construction, non-logical reasoning, and distractibility. Good inter-rater reliability was obtained. Sexually abused children had higher aberrant scores on card number four compared to non-abused children. Sexual abuse history was a predictive factor for non-logical reasoning, with small effect size. Implications and suggestions for future research are discussed. [ABSTRACT FROM AUTHOR]

Abstract: In many transport-limited environments, morphology, pedogenic iron and clay content provide a basis for estimating the exposure age of soils and associated landforms. We measured citrate-buffered dithionite (CBD)-extractable Fe (Fed) and clay concentration in fresh rock, saprolite, morainal and colluvial materials, and soil horizons from stable surfaces and hillslopes in the Colorado Front Range. Fresh igneous and high-grade metamorphic rocks contain <1% Fed and 1 to 5% clay. As bedrock and surficial deposits age, Fed and clay accumulate from weathering and dustfall. Late Holocene regolith at warm, dry sites contains small amounts of Fed and clay, but relatively moist soils developed on early Holocene cirque deposits contain as much as 1.5% Fed and 8% clay. Concentrations and total profile accumulation of Fed and clay increase with age in soils developed on stable surfaces of glacial deposits as old as ~130kyr. On stable sites, Fed and clay accumulation from weathering and dust is ~0.02gcm−2 kyr−1 and ~0.2gcm−2 kyr−1, respectively. We used the Fed and clay inventory in soil profiles at dated, stable Front Range surfaces to calculate accumulation functions, which allowed us to estimate soil age at hillslope sites. Heterogeneous parent material, particularly on hillslopes, and climate-related effects add to variability in measured relations. Mobile regolith in Gordon Gulch, one of the Boulder Creek Critical Zone Observatory (CZO) catchments, yields profile ages from about 0.5 to 5×104 yr, comparable to values measured using other techniques. Calculated profile ages are older on a north- vs. south-facing slope and increase from the drainage divide to the footslope. Ages calculated for stabilized colluvium and well-developed buried profiles at nearby hillslope sites (Lefthand, Ward and Rollinsville) suggest that these soils have stabilized over periods >105 yr. In the absence of radiometric ages, the accumulation of Fed and clay in soils on stable sites and hillslopes provides a useful, local chronofunction for 103 to ~3×105 yr. Local footslope thickening of mobile regolith, buried soils, and areas of Fed- and clay-rich stabilized colluvium suggest that steady-state models of hillslope regolith must be modified to account for observed soil properties. [Copyright &y& Elsevier]

US public awareness of the reality and risks of human-caused climate change remains limited, despite strong evidence presented in the IPCC and other major climate assessments. One contributing factor may be that the immense collective effort to produce periodic climate assessments is typically not well matched with public communication and outreach efforts for these reports, leaving a vacuum to be filled by less authoritative sources. Print and online media coverage provides one metric of the US public reach of selected climate assessments between 2000 and 2010. The number of Lexis-Nexis articles for the search terms ' climate change' or ' global warming' within 14 days of each report's release varied significantly over time with a peak occurring in 2007. When compared to background ' chatter' relating to climate change, each assessment had widely diverse penetration in the US media (~4% for US National Climate Assessment in 2000; ~17% for Arctic Climate Impacts Assessment in 2004; ~19% and ~10% for Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report Working Group I and Working Group II respectively in 2007; ~4% for the US Global Change Research Program (USGCRP) assessment report in 2009; and ~5% for US National Research Council's America's Climate Choices reports in 2010). We propose ways to improve the public reach of climate assessments, focusing in particular on approaches to more effectively characterize and communicate the role of uncertainty in human actions as distinct from other sources of uncertainty across the range of possible climate futures. [ABSTRACT FROM AUTHOR]

The anticipated eradication of poliovirus emphasizes the need to identify other enteroviral causes of severe central nervous system disease. Enterovirus 68 has been implicated only in cases of respiratory illness. We therefore report a case of fatal meningomyeloencephalitis caused by enterovirus 68 in a 5-year-old boy, which required neuropathology, microbiology, and molecular techniques to diagnose. [ABSTRACT FROM AUTHOR]

Chloroplast transformation is a promising approach for the commercial production of recombinant proteins in plants. However, gene containment still remains an issue for the large-scale cultivation of transplastomic plants in the field. Here, we have evaluated the potential of using tobacco transplastomic cell suspensions for the fully contained production of a modified form of the green fluorescent protein (GFP+) and, a vaccine antigen, fragment C of tetanus toxin (TetC). Expression of these proteins in cell suspension cultures (and calli) was much less than in leaves, reaching 0.5%-1.5% of total soluble protein (TSP), but still produced 2.4-7.2 mg/L of liquid culture. Much better expression levels were achieved with a novel protein production platform in which transgenic cell suspension cultures were placed in a temporary immersion bioreactor in the presence of Thidiazuron to initiate shoot formation. GFP+ yield reached 660 mg/L of bioreactor (33% TSP), and TetC accumulated to about 95 mg/L (8% TSP). This new production platform, combining the rapid generation of transplastomic cell suspension cultures and the use of temporary immersion bioreactors, is a promising route for the fully contained low-cost production of recombinant proteins in chloroplasts. [ABSTRACT FROM AUTHOR]

Background: Helminth parasites cause untold morbidity and mortality to billions of people and livestock. Anthelmintic drugs are available but resistance is a problem in livestock parasites, and is a looming threat for human helminths. Testing the efficacy of available anthelmintic drugs and development of new drugs is hindered by the lack of objective high-throughput screening methods. Currently, drug effect is assessed by observing motility or development of parasites using laborious, subjective, low-throughput methods. Methodology/Principal Findings: Here we describe a novel application for a real-time cell monitoring device (xCELLigence) that can simply and objectively assess anthelmintic effects by measuring parasite motility in real time in a fully automated high-throughput fashion. We quantitatively assessed motility and determined real time IC50 values of different anthelmintic drugs against several developmental stages of major helminth pathogens of humans and livestock, including larval Haemonchus contortus and Strongyloides ratti, and adult hookworms and blood flukes. The assay enabled quantification of the onset of egg hatching in real time, and the impact of drugs on hatch rate, as well as discriminating between the effects of drugs on motility of drug-susceptible and –resistant isolates of H. contortus. Conclusions/Significance: Our findings indicate that this technique will be suitable for discovery and development of new anthelmintic drugs as well as for detection of phenotypic resistance to existing drugs for the majority of helminths and other pathogens where motility is a measure of pathogen viability. The method is also amenable to use for other purposes where motility is assessed, such as gene silencing or antibody-mediated killing. Author Summary: Parasitic worms cause untold morbidity and mortality on billions of people and livestock. Drugs are available but resistance is problematic in livestock parasites and is a looming threat for human helminths. Currently, new drug discovery and resistance monitoring is hindered as drug efficacy is assessed by observing motility or development of parasites using laborious, subjective, low-throughput methods evaluated by eye using microscopy. Here we describe a novel application for a cell monitoring device (xCELLigence) that can simply and objectively assess real time anti-parasite efficacy of drugs on eggs, larvae and adults in a fully automated, label-free, high-throughput fashion. This technique overcomes the current low-throughput bottleneck in anthelmintic drug development and resistance detection pipelines. The widespread use of this device to screen for new therapeutics or emerging drug resistance will be an invaluable asset in the fight against human, animal and plant parasitic helminths and other pathogens that plague our planet. [ABSTRACT FROM AUTHOR]

Background: Helminth parasites cause untold morbidity and mortality to billions of people and livestock. Anthelmintic drugs are available but resistance is a problem in livestock parasites, and is a looming threat for human helminths. Testing the efficacy of available anthelmintic drugs and development of new drugs is hindered by the lack of objective highthroughput screening methods. Currently, drug effect is assessed by observing motility or development of parasites using laborious, subjective, low-throughput methods. Methodology/Principal Findings: Here we describe a novel application for a real-time cell monitoring device (xCELLigence) that can simply and objectively assess anthelmintic effects by measuring parasite motility in real time in a fully automated high-throughput fashion. We quantitatively assessed motility and determined real time IC50 values of different anthelmintic drugs against several developmental stages of major helminth pathogens of humans and livestock, including larval Haemonchus contortus and Strongyloides ratti, and adult hookworms and blood flukes. The assay enabled quantification of the onset of egg hatching in real time, and the impact of drugs on hatch rate, as well as discriminating between the effects of drugs on motility of drug-susceptible and -resistant isolates of H. contortus. Conclusions/Significance: Our findings indicate that this technique will be suitable for discovery and development of new anthelmintic drugs as well as for detection of phenotypic resistance to existing drugs for the majority of helminths and other pathogens where motility is a measure of pathogen viability. The method is also amenable to use for other purposes where motility is assessed, such as gene silencing or antibody-mediated killing. [ABSTRACT FROM AUTHOR]

The empirical literature offers evidence that loss of a caregiver in childhood is a significant predictor of psychopathology in adolescents and adults. There is a paucity of empirical research exploring the intrapsychic effects of caregiver loss in an at-risk population of hospitalized children. The Social Cognition and Object Relations Scale: Global Rating Method (SCORS-G) was used to analyze Thematic Apperception Test (TAT) narratives for five commonly used TAT cards. Narratives were assessed on eight dimensions, including complexity of representations of people, affective quality of representations, emotional investment in relationships, understanding of social causality, experience and management of aggressive impulses, self-esteem, and identity and coherence of self. Interrater reliability was obtained by using three independent raters. On average, the participants reported a mean age of 13 years and 35 percent were females. Analyses of variance (ANOVAs), correlations, and regression analyses show that age is a significant predictor of self-esteem in children who have experienced caregiver loss (R2 = 0.34, p < .05). Further exploration revealed that depending on how early the loss occurred, IQ was a significant predictor of children's sense of self-esteem (R2 = 0.84, p < .05) and their emotional investment in relationships (R2 = -0.78, p < .01). Implications for treatment of children are discussed. [ABSTRACT FROM AUTHOR]

Abstract: Helminth infections are an important constraint on the health and development of poor children and adults. Anthelmintic treatment programmes provide a safe and effective response, and increasing numbers of people are benefitting from these public health initiatives. Despite decades of clinical experience with anthelmintics for the treatment of human infections, relatively little is known about their clinical pharmacology. All of the drugs were developed initially in response to the considerable market for veterinary anthelmintics in high- and middle-income countries. In contrast, the greatest burden caused by these infections in humans is in resource-poor settings and as a result there has been insufficient commercial incentive to support studies on how these drugs work in humans, and how they should best be used in control programmes. The advent of mass drug administration programmes for the control of schistosomiasis, lymphatic filariasis, onchocerciasis and soil-transmitted helminthiases in humans increases the urgency to better understand and better monitor drug resistance, and to broaden the currently very narrow range of available anthelmintics. This provides fresh impetus for developing a comprehensive research platform designed to improve our understanding of these important drugs, in order to bring the scientific knowledge base supporting their use to a standard equivalent to that of drugs commonly used in developed countries. Furthermore, a better understanding of their clinical pharmacology will enable improved therapy and could contribute to the discovery of new products. [Copyright &y& Elsevier]

Background: Success of heart transplantation is affected by allograft rejection, which is known as a lymphocyte-mediated process. Recent studies suggest that neutrophils contribute to this process. We hypothesized that the severity of cardiac rejection can be predicted by evaluating an individual''s neutrophil transendothelial migration potential, which can be assessed through artificial stimulation of neutrophils. Methods: Eleven patients were recruited from the active heart transplant list. Pre-operative blood samples were stained with neutrophil adhesion molecule (CD11b, CD62L, and PSGL-1) antibodies before and after in vitro stimulation with phorbol 12-myristate 13-acetate (PMA; 1 ng/ml) and lipopolysaccharide (LPS 1 μg/ml), and assessed using flow cytometry. Stimulated neutrophil responses were correlated with rejection grade of the first endomyocardial biopsy sampled 10 days post-operatively. Results: Neutrophil adhesion molecules are upregulated after artificial stimulation. Pre-operative neutrophil surface CD11b expression after in vitro lipopolysaccharide stimulation correlated with rejection grade detected in the first endomyocardial biopsy sample (R = 0.677; p = 0.022). Conclusion: Pre-operative neutrophil response to in vitro stimuli predicted the rejection grade in the first post-transplant endomyocardial biopsy specimen, suggesting that neutrophils may contribute more to cardiac allograft rejection than previously thought. [Copyright &y& Elsevier]

The article presents a case study of a 59-year-old man with pituitary disease. The patient had a history of renal and pituitary insuffiency with noted abnormalities of brain magnetic resonance imaging. Insuffiency at those sites was deemed to involve immunoglobulin G-related disease (IgG4-RD) causing hypophysitis and interstitial nephritis. The tendency of the IgG4-RD to remain in remission was also mentioned.

The functional complexity of higher organisms is not easily accounted for by the size of their genomes. Rather, complexity appears to be generated by transcriptional, translational, and post-translational mechanisms and tissue organization that produces a context-dependent response of cells to specific stimuli. One property of gene products that likely increases the ability of cells to respond to stimuli with complexity is the multifunctionality of expressed proteins. Receptor for hyaluronan-mediated motility (RHAMM) is an example of a multifunctional protein that controls differential responses of cells in response-to-injury contexts. Here, we trace its evolution into a sensor-transducer of tissue injury signals in higher organisms through the detection of hyaluronan (HA) that accumulates in injured microenvironments. Our goal is to highlight the domain and isoform structures that generate RHAMM's function complexity and model approaches for targeting its key functions to control cancer progression. [ABSTRACT FROM AUTHOR]

Abstract: Resistance of the canine hookworm Ancylostoma caninum to anthelmintic therapy with pyrantel is an emerging problem in canine veterinary practice. Detecting anthelmintic resistance in parasites of pets is problematic because traditional resistance-monitoring techniques used with livestock parasites, such as the faecal egg count reduction test, are often impractical for use in small animals. We used two field-collected isolates of A. caninum in an abbreviated critical trial to test their pyrantel resistance status. The strains showed high-level and low-level resistance, with in vivo pyrantel efficacies of 28% and 71%, respectively. We noted a distinct worm density dependence effect on faecal egg count during the critical trial; egg counts in the dogs containing the low-level resistant isolate were 41% higher 6 days after drug treatment, despite the removal of 71% of the adult worms by the drug treatment. We then assessed four candidate in vitro assays for their ability to detect pyrantel resistance in A. caninum larvae, using these two isolates. The assays included a new format termed the larval arrested morphology assay (LAMA), based on observation of the effects of pyrantel on the body shape adopted by infective stage A. caninum larvae in vitro. Our data suggests that three of these assays, the LAMA, the larval motility assay (LMA), and larval feeding inhibition assay (LFIA) show promise with regards to detection of pyrantel resistance in A. caninum, but the complexity of the LFIA would likely limit its suitability for field studies. In vivo pyrantel efficacies of 28% and 71% in the two A. caninum isolates were associated with a 17-fold shift in the in vitro IC50 values measured using the LAMA. Further testing with isolates of varying degrees of resistance is required to determine which of these assays is suitable as a rapid in vitro laboratory test for pyrantel resistance in A. caninum. The present study also indicates that potential exists for the novel LAMA or the LMA to be of use in detecting pyrantel resistance in the human hookworms, Necator americanus and Ancylostoma duodenale. [Copyright &y& Elsevier]

Green fluorescent proteins (GFPs) are well known for their intensive use in cellular and molecular biology in applications that take advantage of the GFPs self-folding and built-in fluorophore characteristics as biomarker. Occurrence and function of GFPs in nature is less known. For a long time GFPs were described only from some cnidarians, and it is only recently that they were also found in copepod crustaceans. Here we describe the occurrence of a GFP from three species of amphioxus, namely Branchiostoma floridae, B. lanceolatum, and B. belcheri (Chordata: Cephalochordata). This is the first time an endogenous GFP has been found in any representative of the deuterostome branch of the Animal Kingdom. We have isolated and characterized a gene (AmphiGFP) from B. floridae that encodes a GFP protein related to those of cnidarians and copepods in both its amino acid sequence and its predicted higher order structure (an 11-stranded β-barrel enclosing a fluorophore). Bayesian and maximum parsimony phylogenetic analyses demonstrate that the AmphiGFP protein is markedly more closely related to copepod than to cnidarian GFPs. In adults of all three amphioxus species, the green fluorescence is strikingly concentrated anteriorly. The anterior end is the only body part exposed to light in these shallow-water dwellers, suggesting possible photoreceptive or photoprotective functions for the endogenous GFP. [ABSTRACT FROM AUTHOR]

Abstract: While anthelmintic resistance is now a widely recognized issue in the livestock industries, its existence within companion animal medicine has been rarely established conclusively. We undertook a placebo-controlled in vivo trial to measure the efficacy of pyrantel embonate against pooled isolates of the hookworm Ancylostoma caninum from Brisbane, Australia. A statistically significant fall in adult worm burden was observed among dogs in the pyrantel treatment group compared to the control dogs (178.0±24.5 versus 239.7±14.0; p =0.02), equating to an efficacy of just 25.7% (95% CI, 15.0–35.1%), as based upon reduction in mean worm burden. Analysis of faecal egg count trends through the course of the study revealed that egg counts rose in both control and pyrantel-treated dogs, with a greater rise observed in the latter group (11.6±8.3% versus 17.3±7.6%; p =0.04), despite the decrease in adult worm numbers in this group. Our results indicate that high-level anthelmintic resistance does occur in companion animal medicine, and highlight the need for greater vigilance and more judicious use of anthelmintics in small animal practice. They further indicate that the faecal egg count reduction test needs to be used with caution with this parasite. [Copyright &y& Elsevier]

Abstract: Antiretroviral protease inhibitors were assessed in vitro for their activity against Giardia duodenalis and Trichomonas vaginalis. Kaletra® (a co-formulation of ritonavir and lopinavir) was the most effective overall, with 50% effective drug concentrations (EC50) of 1.1–2.7μM (ritonavir concentration) against G. duodenalis and 6.8–8μM against metronidazole-sensitive and clinically metronidazole-resistant T. vaginalis. Minimal inhibitory concentrations were 2–2.5μM and 10–50μM for G. duodenalis and T. vaginalis, respectively. Within the range of human plasma concentrations for ritonavir, only G. duodenalis was inhibited. Lopinavir alone was less inhibitory than ritonavir but was associated with a blockage in cytokinesis of G. duodenalis trophozoites. Saquinavir was not effective. These findings are significant considering the association between human immunodeficiency virus and T. vaginalis, and between G. duodenalis and homosexual behaviour. [Copyright &y& Elsevier]

Abstract: The relationship between the form of cell adhesion, ligand presentation, and cell receptor function was characterized using model Langmuir–Blodgett supported films, containing lipid-conjugated peptide ligands, in which isolated variables of the ligand presentation were systematically altered. First, the conformation of an adhesive Arginine–Glycine–Aspartic acid (RGD) peptide was varied by synthesizing linear and looped RGD peptide-containing amphiphiles and subsequently measuring the impact on the function of human umbilical vein endothelial cells. Secondly, the contribution of non-contiguous ligands to cellular engagement was assessed using multi-component biomimetic films. The peptide amphiphiles were composed of fibronectin-derived headgroups—GRGDSP, and its synergy site Pro–His–Ser–Arg–Asn (PHSRN)—attached to hydrocarbon tails. The peptide amphiphiles were diluted using polyethylene glycol (PEG) amphiphiles, where PEG inhibited non-specific cell adhesion. Cells adhered and spread on GRGDSP/PEG systems in a dose-dependent manner. The presentation of GRGDSP influenced integrin cell surface receptor specificity. Results demonstrated that β 1-containing integrins mediated adhesion to the linear GRGDSP presentation to a greater extent than did the α v β 3 integrin, and looped GRGDSP preferentially engaged α v β 3. GRGDSP/PHSRN/PEG mixtures that closely mimicked the RGD–PHSRN distance in fibronectin, enhanced cell spreading over their two-component analogues. This study demonstrated that controlling the microenvironment of the cell was essential for biomimetics to modulate specific binding and subsequent signaling events. [Copyright &y& Elsevier]

Abstract: The World Health Organization is sponsoring major treatment programs with the aim of controlling helminth infection throughout the tropical world. Prominent among the anthelmintics recommended for use in these programs are drugs in the benzimidazole (BZ) class. Resistance to these drugs has been associated with polymorphisms in the β-tubulin gene. We have cloned and sequenced the β-tubulin genes of Strongyloides stercoralis and Strongyloides ratti and have proceeded to develop a protocol for genotyping single worms for polymorphisms in β-tubulin. Our findings indicate that S. ratti has a single β-tubulin gene, making DNA sequence analysis of a single larva PCR product a feasible means of studying BZ resistance in these species. Our genotyping test allows the identification of polymorphisms at codons 167, 198, and 200 in the Strongyloides β-tubulin gene, thus enabling survey for BZ resistant genotypes. [Copyright &y& Elsevier]

An EST database has been generated for coffee based on sequences from approximately 47,000 cDNA clones derived from five different stages/tissues, with a special focus on developing seeds. When computationally assembled, these sequences correspond to 13,175 unigenes, which were analyzed with respect to functional annotation, expression profile and evolution. Compared with Arabidopsis, the coffee unigenes encode a higher proportion of proteins related to protein modification/turnover and metabolism—an observation that may explain the high diversity of metabolites found in coffee and related species. Several gene families were found to be either expanded or unique to coffee when compared with Arabidopsis. A high proportion of these families encode proteins assigned to functions related to disease resistance. Such families may have expanded and evolved rapidly under the intense pathogen pressure experienced by a tropical, perennial species like coffee. Finally, the coffee gene repertoire was compared with that of Arabidopsis and Solanaceous species (e.g. tomato). Unlike Arabidopsis, tomato has a nearly perfect gene-for-gene match with coffee. These results are consistent with the facts that coffee and tomato have a similar genome size, chromosome karyotype (tomato, n=12; coffee n=11) and chromosome architecture. Moreover, both belong to the Asterid I clade of dicot plant families. Thus, the biology of coffee (family Rubiacaeae) and tomato (family Solanaceae) may be united into one common network of shared discoveries, resources and information. [ABSTRACT FROM AUTHOR]

Mn(II)-oxidizing microbes have an integral role in the biogeochemical cycling of manganese, iron, nitrogen, carbon, sulfur, and several nutrients and trace metals. There is great interest in mechanistically understanding these cycles and defining the importance of Mn(II)-oxidizing bacteria in modern and ancient geochemical environments. Linking Mn(II) oxidation to cellular function, although still enigmatic, continues to drive efforts to characterize manganese biomineralization. Recently, complexed-Mn(III) has been shown to be a transient intermediate in Mn(II) oxidation to Mn(IV), suggesting that the reaction might involve a unique multicopper oxidase system capable of a two-electron oxidation of the substrate. In biogenic and abiotic synthesis experiments, the application of synchrotron-based X-ray scattering and spectroscopic techniques has significantly increased our understanding of the oxidation state and relatively amorphous structure (i.e. δ–MnO2-like) of biogenic oxides, providing a new blueprint for the structural signature of biogenic Mn oxides. [Copyright &y& Elsevier]

Background: The tetraspan protein CD63, originally described as a stage-specific melanoma antigen but also present in a number of normal cells, regulates melanoma cell growth in nude mice, motility in serum containing media, and adhesion to several extracellular matrix proteins. CD63 has been reported to associate with β1 and β2 integrins, but the mechanism of signal transduction by CD63 is not clear. This study examined whether CD63 is associated with protein kinase and can transmit signals in melanoma cells. Methods: Immunoprecipitation and radiolabeling were used to test for association of protein kinase activity with CD63. Adhesion of cells to monoclonal antibodies immobilized to microtiter plates was used to examine the ability of CD63 to transmit signals. Results: CD63 was capable of transmitting a signal in melanoma cells that required extracellular calcium. In the absence of extracellular calcium at the time of binding to the CD63 mAb, the cell was no longer responsive to stimulation by CD63. Immunoprecipitation studies demonstrated protein kinase activity associated with CD63, and phosphoamino acid analysis revealed that most of this protein kinase activity was due to serine kinase activity. Conclusion: The current study suggests that serine protein kinase activity associated with CD63 may play a role in signaling by CD63 in melanoma cells. [ABSTRACT FROM AUTHOR]