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This project examined the effectiveness of the three-lecture-per-week method of teaching general education biology as compared with six alternative approaches involving various reductions in weekly class attendance. In three of the experimental groups lectures were reduced in number and supplemented by readings, quiz sessions or study guides; in the other three attendance at lectures was not required, students were assigned readings, met in seminars, or were tutored by other students. Tape recordings of lectures and review sessions were available to all students. Students in all groups were administrated a pre-course examination, two midterm achievement examinations, and final tests of content, attitude to science and scientists, and attitude to the course. No significant differences were found on the attitude measures. On the final content test all experimental groups achieved significantly higher than the control section. It was noted that the students' expressed approval of an instructional method was not always supported by their use of the method when available. (EB)

Hemophilia A is an X-linked hereditary disorder that results from deficient coagulation factor VIII (FVIII) activity, leading to spontaneous bleeding episodes, particularly in joints and muscles. FVIII deficiency has been associated with altered bone remodeling, dysregulated macrophage polarization, and inflammatory processes that are associated with the neoformation of abnormal blood vessels. Treatment based on FVIII replacement can lead to the development of inhibitors that render FVIII concentrate infusion ineffective. In this context, hemophilia has entered a new therapeutic era with the development of new drugs, such as emicizumab, that seek to restore the hemostatic balance by bypassing pathologically acquired antibodies. We discuss the potential extrahemostatic functions of FVIII that may be crucial for defining future therapies in hemophilia.

Triazole resistance in Aspergillus fumigatus is an increasing worldwide problem that causes major challenges in the management of aspergillosis. New antifungal drugs are needed, with novel targets, that are effective in triazole-resistant infection., Triazole resistance in Aspergillus fumigatus is an increasing worldwide problem that causes major challenges in the management of aspergillosis. New antifungal drugs are needed, with novel targets, that are effective in triazole-resistant infection. In this study, we retrospectively evaluated the potency of the novel drug olorofim compared to contemporary antifungal agents against 111 clinical A. fumigatus isolates collected from Huashan Hospital, Shanghai, China, using EUCAST methodology, and we reviewed the literature on triazole-resistant A. fumigatus (TRAF) published between 1966 and 2020 in China. Olorofim was active in vitro against all tested A. fumigatus isolates, with a MIC90 of 0.031 mg/liter (range, 0.008 to 0.062 mg/liter). For 4 triazole-resistant A. fumigatus isolates, the olorofim MIC ranged between 0.016 and 0.062 mg/liter. The reported rates of TRAF in China are 2.5 to 5.56% for clinical isolates and 0 to 1.4% for environmental isolates. TR34/L98H/S297T/F495I is the predominant resistance mechanism, followed by TR34/L98H. Non-TR-mediated TRAF isolates, mostly harboring a cyp51A single point mutation, showed greater genetic diversity than TR-mediated resistant isolates. Resistance due to TR34/L98H and TR34/L98H/S297T/F495I mutations among TRAF isolates might have evolved from separate local isolates in China. Continuous isolation of TRAF in China underscores the need for systematic resistance surveillance as well as the need for novel drug targets, such as olorofim.

The Mediterranean fruit fly Ceratitis capitata (Wiedemann) (Diptera: Tephritidae) is one of the most destructive agricultural pests in the world. New attractants are needed as a key strategy for detecting and suppressing insect pest densities. The aim of this study was to evaluate the attractiveness of essential oils isolated from the aerial parts of three Pulicaria species collected from the Al-kharj province of Saudi Arabia, targeting sterile medfly males. The volatile constituents of the aerial parts of P. arabica, P. crispa, and P. somalensis were characterized using gas chromatography-flame ionization detection and gas chromatography-mass spectrometry. tau-Cadinol was found to be the major compound in the essential oils of P. arabica (38.6 %) and P. crispa (53.5 %), and intermedeol (15.9 %), α-cadinol (9.7 %), α-, β- (5.2 % each), and γ-eudesmol (9.1 %) were the most abundant components in the essential oil of P. somalensis. Carvotanacetone (10.3 %) was detected only in P. arabica. The essential oils from each of the three Pulicaria species were subjected to short-range attraction bioassays against the sterile male medfly C. capitata. The results were compared with the response to a known strong attractant, tea tree oil (Melaleuca alternifolia); P. arabica exhibited mild attractancy, whereas neither P. crispa nor P. somalensis showed attractant activity.

Spiders are key predators in many agroecosystems, including orchards. Despite the importance of spiders in biological control, pesticide nontarget effects on this group are poorly described. This is especially true for herbicides, which spiders frequently encounter as they move between the ground cover and tree canopy. We sought to determine the nontarget effects of seven herbicides used in orchards on three species of spiders that are commonly found in Washington state (USA) orchards: Pelegrina aeneola (Curtis) (Araneae: Salticidae), Philodromus cespitum (Walckenaer) (Araneae: Philodromidae), and Phanias watonus (Chamberlin & Ivie) (Araneae: Salticidae). Immature spiders were collected from orchards and used in laboratory assays. Single spiders were placed in vials with dried herbicide residues and mortality was evaluated after 1, 2, and 5 d. We also evaluated herbicide impacts on prey consumption rates and on spider movement using motion-tracking software. Only oxyfluorfen caused significant spider mortality. P. cespitum seemed to be less acutely sensitive to oxyfluorfen than the two salticid species. Several herbicide treatments significantly increased locomotion in P. cespitum, whereas rimsulfuron numerically decreased movement of P. aeneola. Sulfonylurea herbicides (rimsulfuron, halosulfuron) decreased prey consumption of P. aeneola. Our work indicates that although spiders may be less acutely sensitive to some pesticides than beneficial insects, they can be affected by sublethal effects of herbicides. Future work should determine if herbicide applications impact spider abundance in the field and reduce biological control services. In general, more work is needed on the impacts of herbicides on natural enemies.

Women with hormone receptor positive breast cancer may receive 5 years of treatment with aromatase inhibitors but the magnitude of benefit was relatively small. Our goal was to develop a tool for identification of women with limited treatment benefit. Regression analyses were applied to women treated by placebo in CCTG MA.17R trial (NCT00754845) to identify important prognostic factors associated with distant recurrence and develop a nomogram for predicting 5-year likelihood of distant recurrence, which was internally validated using bootstrap resampling method. Differential treatment effects between risk categories derived from the nomogram were evaluated among all women enrolled through interaction test between treatment and risk category. A total of 1735 women were included and the final model from 866 women treated by placebo identified the following three factors associate with distant recurrence: tumor size, nodal status, and presence of cardiovascular disease. The nomogram derived from the final model exhibited good discrimination power with a bootstrap-corrected concordance index of 0.71 and, importantly, identified 64% of low risk patients in whom extended treatment has limited benefit. Interaction between treatment and risk category derived from the nomogram was significant (p = 0.04). A nomogram with good performance may be used to accurately predict distant recurrence risk and also benefits with extended treatment after 5 years of aromatase inhibitors. Future independent validation of the proposed nomogram is warranted. NCT00754845

Enzymes have in vivo life spans. Analysis of life spans, i.e., lifetime totals of catalytic turnovers, suggests that nonsurvivable collateral chemical damage from the very reactions that enzymes catalyze is a common but underdiagnosed cause of enzyme death. Analysis also implies that many enzymes are moderately deficient in that their active-site regions are not naturally as hardened against such collateral damage as they could be, leaving room for improvement by rational design or directed evolution. Enzyme life span might also be improved by engineering systems that repair otherwise fatal active-site damage, of which a handful are known and more are inferred to exist. Unfortunately, the data needed to design and execute such improvements are lacking: there are too few measurements of in vivo life span, and existing information about the extent, nature, and mechanisms of active-site damage and repair during normal enzyme operation is too scarce, anecdotal, and speculative to act on. Fortunately, advances in proteomics, metabolomics, cheminformatics, comparative genomics, and structural biochemistry now empower a systematic, data-driven approach for identifying, predicting, and validating instances of active-site damage and its repair. These capabilities would be practically useful in enzyme redesign and improvement of in-use stability and could change our thinking about which enzymes die young in vivo, and why.

Cryptococcus gattii is a fungal pathogen that primarily affects the respiratory and nervous systems of humans and other animals. C. gattii emerged in temperate North America in 1999 as a multispecies outbreak of cryptococcosis in British Columbia (Canada) and Washington State and Oregon (USA), affecting humans, domestic animals, and wildlife. Here we describe the C. gattii epizootic in odontocetes. Cases of C. gattii were identified in 42 odontocetes in Washington and British Columbia between 1997 and 2016. Species affected included harbor porpoises Phocoena phocoena (n = 26), Dall’s porpoises Phocoenoides dalli (n = 14), and Pacific white-sided dolphins Lagenorhynchus obliquidens (n = 2). The probable index case was identified in an adult male Dall’s porpoise in 1997, 2 yr prior to the initial terrestrial outbreak. The spatiotemporal extent of the C. gattii epizootic was defined, and cases in odontocetes were found to be clustered around terrestrial C. gattii hotspots. Case-control analyses with stranded, uninfected odontocetes revealed that risk factors for infection were species (Dall’s porpoises), age class (adult animals), and season (winter). This study suggests that mycoses are an emerging source of mortality for odontocetes, and that outbreaks may be associated with anthropogenic environmental disturbance.

Ethyl formate (EF) was evaluated as a potential alternative to methyl bromide (MB) for phytosanitary treatment of imported citrus fruit in the Republic of Korea. Planococcus citri (Risso) (Hemiptera: Pseudococcidae), a mealybug with known tolerance against EF and MB, was used as a representative pest to test efficacy of the two fumigants against eggs. In nine commercial-scale refrigerated container (67.5 m3) trials using imported orange, lemon and grapefruit, EF applied at the currently approved dose for citrus (70 g·m-3 at 5°C for 4 h, developed for Aspidiotus excisus Green (Hemiptera: Diaspididae), a species less EF tolerant than P. citri) resulted in 76.9–98.3% mortality of P. citri eggs. The EF treatment did not affect the sugar content or the color of peel and pulp of the treated fruit. When oranges were treated according to the current MB (64 g·m-3 at >5°C for 2 h) or EF treatment guidelines, the concentration of fumigant around the fruit fluctuated between 9.4 and 185.1 ppm for EF and 9.5–203.0 ppm for MB during the 72-h post-fumigation processes (venting [0–2 h], transportation to storage [2–24 h], and storage periods [24–72 h]) with both EF and MB maintained between 10 and 100 ppm during the storage period. Considering the efficacy of EF, its apparent lack of phytotoxicity, and its more manageable threshold limit value for humans (100 ppm EF compared to 1 ppm MB for an 8-h time weighted average exposure), our results suggest that EF may be a promising alternative to MB for the phytosanitary treatment of imported citrus in Korea.

Nutrient input from estuarine producers underpins coastal fisheries production and knowing which producers are the most responsible for fish diet helps effectively protect and restore coastal ecosystems. Focussing on the Richmond River in Australia as a case study, we sampled the main estuarine producers and estimated their proportional contributions of nutritional input to seven commercially important fisheries species using Bayesian isotope mixing models. We valued the dietary input of estuarine producers to the commercial fisheries by combining dietary contribution estimates with total annual catch data from commercial fishers. A conservative estimate is that estuarine producers in the Richmond River Estuary contribute at least 82 725 kg (78%) of the total annual catch of the seven commercially important fish with an estimated annual value of $AU 450 117. Sea mullet and Mud crab contributed 95% of the total catch, and 93% of the total value assigned to estuarine producers. The two highest valued estuarine producers were tidal marsh (Juncus kraussii) $AU 82 432 and seagrass (Zostera capricorni) $AU 65 423. This study demonstrates the substantial role of estuarine producers to commercial fisheries production and the fisheries economy more broadly. With large areas of estuarine producers under threat globally from land clearing for agriculture, aquaculture and urbanisation, the results presented here provide evidence to support the value of coastal habitats and benefits of their preservation and restoration. GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13280-021-01600-3.

Monoclonal antibodies are the leading class of biopharmaceuticals in terms of numbers approved for therapeutic purposes. Antigen-binding fragments (Fab) are also used as biotherapeutics and used widely in research applications. The dominant expression systems for full-length antibodies are mammalian cell-based, whereas for Fab molecules the preference has been an expression in bacterial systems. However, advances in CHO and downstream technologies make mammalian systems an equally viable option for small- and large-scale Fab production. Using a panel of full-length IgG antibodies and their corresponding Fab pair with different antigen specificities, we investigated the impact of the IgG and Fab molecule format on production from Chinese hamster ovary (CHO) cells and assessed the cellular capability to process and produce these formats. The full-length antibody format resulted in the recovery of fewer mini-pools posttransfection when compared to the corresponding Fab fragment format that could be interpreted as indicative of a greater overall burden on cells. Antibody-producing cell pools that did recover were subsequently able to achieve higher volumetric protein yields (mg/L) and specific productivity than the corresponding Fab pools. Importantly, when the actual molecules produced per cell of a given format was considered (as opposed to mass), CHO cells produced a greater number of Fab molecules per cell than obtained with the corresponding IgG, suggesting that cells were more efficient at making the smaller Fab molecule. Analysis of cell pools showed that gene copy number was not correlated to the subsequent protein production. The amount of mRNA correlated with secreted Fab production but not IgG, whereby posttranscriptional processes act to limit antibody production. In summary, we provide the first comparative description of how full-length IgG and Fab antibody formats impact on the outcomes of a cell line construction process and identify potential limitations in their production that could be targeted for engineering increases in the efficiency in the manufacture of these recombinant antibody formats.

Summary Background A large, double-blind, randomised, placebo-controlled trial of repeat BCG found 49% efficacy against leprosy but no protection against tuberculosis after 6–9 years’ follow-up in 1995. We report here additional follow-up, which resulted in greatly increased tuberculosis case numbers, and allowed subgroup analysis. Methods Nearly 47 000 individuals of all ages living in northern Malawi with a BCG vaccine scar were randomly assigned (1:1) between 1986 and 1989 to receive a second BCG or placebo. The investigators and project staff remained masked to all interventions. Enhanced passive surveillance ensured ascertainment of tuberculosis and leprosy to the end of 2018. Tuberculosis case definitions included rigorous microbiological or histological confirmation. Prespecified subgroup analyses were by tuberculosis type, age at vaccination, time since vaccination, previous tuberculin reactivity, HIV status and Mycobacterium tuberculosis lineage. The original trial is registered with ISRCTN registry, ISRCTN11311670. Findings In follow-up until Dec 31, 2018, 824 participants had developed tuberculosis, including 786 with pulmonary disease, of whom 383 (63%) of 607 with known HIV status were HIV positive. There was no effect of a second BCG overall (odds ratio [OR] 0·92; 95% CI 0·80–1·05), or for pulmonary (0·93; 0·81–1·07), or lymph node tuberculosis (0·60; 0·31–1·17). The OR was lower for those with known HIV-negative tuberculosis (0·77; 0·59–1·00), for those vaccinated as children (aged

Social behaviors, including reproductive behaviors, often display sexual dimorphism. Lordosis, the measure of female sexual receptivity, is one of the most apparent sexually dimorphic reproductive behaviors. Lordosis is regulated by estrogen and progesterone (P4) acting within a hypothalamic-limbic circuit, consisting of the arcuate, medial preoptic, and ventromedial nuclei of the hypothalamus. Social cues are integrated into the circuit through the amygdala. The posterodorsal part of the medial amygdala (MeApd) is involved in sexually dimorphic social and reproductive behaviors, and sends projections to hypothalamic neuroendocrine regions. GABA from the MeApd appears to facilitate social behaviors, while glutamate may play the opposite role. To test these hypotheses, adult female vesicular GABA transporter (VGAT)-Cre and vesicular glutamate transporter 2 (VGluT2)-Cre mice were transfected with halorhodopsin (eNpHR)-expressing or channelrhodopsin-expressing adeno-associated viruses (AAVs), respectively, in the MeApd. The lordosis quotient (LQ) was measured following either photoinhibition of VGAT or photoexcitation of VGluT2 neurons, and brains were assessed for c-Fos immunohistochemistry (IHC). Photoinhibition of VGAT neurons in the MeApd decreased LQ, and decreased c-Fos expression within VGAT neurons, within the MeApd as a whole, and within the ventrolateral part of the ventromedial nucleus (VMHvl). Photoexcitation of VGluT2 neurons did not affect LQ, but did increase time spent self-grooming, and increased c-Fos expression within VGluT2 neurons in the MeApd. Neither condition altered c-Fos expression in the medial preoptic nucleus (MPN) or the arcuate nucleus (ARH). These data support a role for MeApd GABA in the facilitation of lordosis. Glutamate from the MeApd does not appear to be directly involved in the lordosis circuit, but appears to direct behavior away from social interactions.SIGNIFICANCE STATEMENTLordosis, the measure of female sexual receptivity, is a sexually dimorphic behavior regulated within a hypothalamic-limbic circuit. Social cues are integrated through the amygdala, and the posterodorsal part of the medial amygdala (MeApd) is involved in sexually dimorphic social and reproductive behaviors. Photoinhibition of GABAergic neurons in the MeApd inhibited lordosis, while photoactivation of glutamate neurons had no effect on lordosis, but increased self-grooming. These data support a role for MeApd GABA in the facilitation of social behaviors and MeApd glutamate projections in anti-social interactions.

Includes phenological and climate data used for analysis of article titled 'Bird populations most exposed to climate change are less sensitive to climatic variation' (Nature Communications). Each data file is described below, with a description of all columns. - baileyetal_phenology_data.csv: Primary data used as the basis for all analysis. Column name Description Pop_ID Unique population ID. Species Species ID. Can be either GT (great tit/Parus major) or BT (blue tit/Cyanistes caeruleus). Sample_year Calendar year in which laying date was recorded. Mean Mean laying date (April days). SE Standard error of mean laying date (April days). Min Minimum observed laying date (April days). Count Total number of first nests laying date records for this population/species/year combination. Date Starting date used sliding window analysis (dd/mm/yyyy). SE_calc Inverse of standard error (1/SE), used to weight statistical models. Temp Mean temperature (oC) within population specific temperaturewindow - Pop_info.csv:Information about each study location where data were collected. Column name Description Site_Name Full name of study site Pop_ID Unique population ID Habitat_Type Either deciduous dominant (DEC), evergreen dominant (EVE), or mixed (MIX). Latitude Latitudinal coordinates of study site Longitude Longitudinal coordinates of study site Latitude_new_temp Latitudinal coordinates used to extract data from ECA&D gridded dataset. In most cases this will be identical to column Latitude; however, in 4 cases (Sagunto, Cardiff, Barcelona, Askainen) latitude is shifted slightly to overlap with the gridded dataset. Longitude_new_temp Longitudinal coordinates used to extract data from ECA&D gridded dataset. In most cases this will be identical to column Longitude; however, in 4 cases (Sagunto, Cardiff, Barcelona, Askainen) longitude is shifted slightly to overlap with the gridded dataset. -Sicily_temp_data.csv:Temperature data from study population in Sicily used to fit temperature window. Column name Description Year Year of temperature data collection Month Month of temperature data collection Day Day of temperature data collection Temperature Mean daily temperature (oC) -Vlieland_temp_data_old.csv: Temperature data used to determine temperature windows for Vlieland, Netherlands (1954 - 2016). Column name Description STN KNMI station number Date Date of weather data (dd/mm/yyyy) Mean Daily mean temperature (oC) Min Daily minimum temperature (oC) Max Daily maximum temperature (oC) -Vlieland_temp_data_new.csv: Temperature data used to determine temperature windows for Vlieland, Netherlands (1996 - 2017). Column name Description Station_no KNMI station number Date Date of weather data (yyyymmdd) Mean Daily mean temperature (oC) Min Daily minimum temperature (oC) Max Daily maximum temperature (oC) -slidingwin_results.rar:Compressed file containing results of sliding time window analysis for all population/species combinations. Each population/species combination has three corresponding files: - PopID_Sp.RDS: Results of sliding time window analysis. - PopID_Sp_rand.RDS: Results of randomization procedure to deal with issues of multiple testing. - PopID_Sp_SEM.RDS: Results of structural equation model used to apply detrending to analysis.

OBJECTIVES: With implementation of mass immunization and improvements in sanitation, China is moving rapidly from high to low endemicity of hepatitis A (HA). To prevent a resurgence after intense vaccination, a comprehensive and systematic assessment of long-term protection against HA conferred by vaccine was thus performed. METHODS: In 1996, 3,515 susceptible children aged one to 12 years were recruited in a randomized, open trial to assess the efficacy of a live-attenuated HA vaccine. During a 17-year follow-up period, children were tested for antibody persistence and long-term protection against both hepatitis A virus (HAV) disease and infection. Case finding was conducted using the China National Notifiable Infectious Disease Reporting System. Serum anti-HAV antibody levels were evaluated by the ELISA method to ascertain antibody persistence and protection against infection. RESULTS: During the 17-year follow-up, 2,132 (61%) children from the initial cohort were available for analysis. After calibrating the sensitivity of assay, excluding natural infection and vaccine booster, the sero-positive rate and the geometric mean concentrations declined from 94.9% and 131.3 mIU/mL (91.5-188.4mIU/mL) at the peak to 55.6% and 41.1 mIU/mL (95% CI: 27.8-61.0 mIU/mL) respectively, with a similar natural infection rate in both groups. CONCLUSIONS: This study demonstrates that long-term protection against hepatitis A persists at least for 17 years after administration of a single dose of a live-attenuated HA vaccine and suggests that a booster dose is currently not necessary. FUNDING STATEMENT: This work was supported by grants from National Natural Science Foundation (China) (81072346), National Science and Technology Project of Major Infectious Diseases (2008ZX10002-003, 2012ZX10002002004) DECLARATION OF INTERESTS: The authors declare that they have no competing interests. ETHICS APPROVAL STATEMENT: This study was reviewed and approved by the Institutional Review Board of the Institutes of Biomedical Sciences, Fudan University. Written inform consent was obtained from each participant.

The molecular link between amyloid-β plaques and neurofibrillary tangles, the two pathological hallmarks of Alzheimer’s disease, is still unclear. Increasing evidence suggests that amyloid-β peptide activates multiple regulators of cell cycle pathways, including transcription factors CDKs and E2F1, leading to hyperphosphorylation of tau protein. However, the exact pathways downstream of amyloid-β-induced cell cycle imbalance are unknown. Here, we show that PAX6, a transcription factor essential for eye and brain development which is quiescent in adults, is increased in the brains of patients with Alzheimer’s disease and in APP transgenic mice, and plays a key role between amyloid-β and tau hyperphosphorylation. Downregulation of PAX6 protects against amyloid-β peptide-induced neuronal death, suggesting that PAX6 is a key executor of the amyloid-β toxicity pathway. Mechanistically, amyloid-β upregulates E2F1, followed by the induction of PAX6 and c-Myb, while Pax6 is a direct target for both E2F1 and its downstream target c-Myb. Furthermore, PAX6 directly regulates transcription of GSK-3β, a kinase involved in tau hyperphosphorylation and neurofibrillary tangles formation, and its phosphorylation of tau at Ser356, Ser396 and Ser404. In conclusion, we show that signalling pathways that include CDK/pRB/E2F1 modulate neuronal death signals by activating downstream transcription factors c-Myb and PAX6, leading to GSK-3β activation and tau pathology, providing novel potential targets for pharmaceutical intervention.

Bacillus cytotoxicus is a member of the Bacillus cereus group with the ability to grow at high temperatures (up to 52℃) and to synthesize cytotoxin K-1, a diarrhoeagenic cytotoxin, which appears to be unique to this species and more cytotoxic than the cytotoxin K-2 produced by other members of this group. Only a few isolates of this species have been characterized with regard to their cytotoxic effects, and the role of cytotoxin K-1 as a causative agent of food poisoning remains largely unclear. Bacillus cytotoxicus was initially isolated from a food-borne outbreak, which led to three deaths, and the organism has since been linked to other outbreaks all involving plant-based food matrices. Other studies, as well as food-borne incidents reported to the UK Food Standards Agency, detected B. cytotoxicus in insect-related products and in dried food products. With insect-related food becoming increasingly popular, the association with this pathogen is concerning, requiring further investigation and evidence to protect public health. This review summarizes the current knowledge around B. cytotoxicus and highlights gaps in the literature from a food safety perspective.

Social networks research using non-human animals has grown over the past decade, utilizing a wide range of species to answer an array of pure and applied questions. Network approaches have relevance to conservation, evaluating social influences on fecundity, health, fitness and longevity. While the application of network approaches to in situ populations with conservation concern appears in published literature, the degree to which ex situ and zoo-housed populations are the focus of "social networks for conservation research" is limited. Captive environments provide scientists with an ability to understand the social behavior of species that may be hard to observe consistently in the wild. This paper evaluates the scope of network research involving ex situ populations, analyzing output from 2010 to 2019 to determine trends in questions and subjects using ex situ populations. We show that only 8.2% of ex situ social network analysis (SNA) implications are of conservation-focus, apparent in papers relating to birds, carnivores, bats, primates, reptiles, and ungulates. Husbandry and welfare questions predominate in ex situ network research, but over half of these papers have nonpractical application (basic science). The chance of a citation for a basic science paper was 95.4% more than for a conservation-based paper. For taxonomic groups, primate-focused papers had the most citations. The focus of ex situ conservation-based networks research may be driven by the needs of conservation programs (e.g., population recovery outcomes) or by a need to evaluate the efficacy of ex situ conservation goals. We evaluate our findings considering the IUCN's One Plan Approach to conservation to show how in situ and ex situ network research is applicable to global conservation efforts. We have identified that there is a lack of application and evaluation of SNA to wildlife conservation. We highlight future areas of research in zoos and hope to stimulate discussion and collaboration between relevant parties.

Global patterns of plant biomass drive the distribution of much of the marine and terrestrial life on Earth. This is because their biomass and physical structure have important consequences for the communities they support by providing food and habitat. In terrestrial ecosystems, temperature is one of the major determinants of plant biomass and can influence plant and leaf morphology. In temperate marine systems, macroalgae are major habitat‐formers and commonly display highly variable morphology in response to local environmental conditions. Variation in their morphology, and thus habitat structure on temperate reefs, however, is poorly understood across large scales. In this study, we used a trait‐based approach to quantify morphological variability in subtidal rocky reefs dominated by the algal genus Sargassum along a latitudinal gradient, in southeastern Australia (~900 km). We tested whether large‐scale variation in sea surface temperature (SST), site exposure, and nutrient availability can predict algal biomass and individual morphology. We found Sargassum biomass declined with increasing maximum SST. We also found that individual morphology varied with abiotic ocean variables. Frond size and intraindividual variability in frond size decreased with increasing with distance from the equator, as SST decreased and nitrate concentration increased. The shape of fronds displayed no clear relationship with any of the abiotic variables measured. These results suggest climate change will cause significant changes to the structure of Sargassum habitats along the southeastern coast of Australia, resulting in an overall reduction in biomass and increase in the prevalence of thalli with large, highly variable fronds. Using a space‐for‐time approach means shifts in morphological trait values can be used as early warning signs of impending species declines and regime shifts. Consequently, by studying traits and how they change across large scales we can potentially predict and anticipate the impacts of environmental change on these communities., Using a trait‐based approach, we tested predictions about how the biomass and morphological traits of macroalgae from the genus Sargassum varied across six degrees of latitude on the southeastern coast of Australia. Our results suggest climate change will cause significantly changes to Sargassum habitat along the southeastern coast of Australia, resulting in an overall reduction in biomass and increasing the prevalence of thalli with large, highly variable fronds.

The fossa is a specialized Malagasy carnivore housed in ex situ facilities since the late 19th century. Moderate breeding success has occurred since the 1970s, and welfare issues (notably stereotypic pacing behaviour) are commonly documented. To understand challenges relating to fossa housing and husbandry (H&H) across global facilities and to identify areas of good practice that dovetail with available husbandry standards, a survey was distributed to ZIMS-registered zoos in 2017. Results showed that outdoor housing area and volume varied greatly across facilities, the majority of fossa expressed unnatural behaviours, with pacing behaviour the most frequently observed. All fossa received enrichment, and most had public access restricted to one or two sides of the enclosure. The majority of fossa were locked in/out as part of their daily management and forty-one percent of the fossa surveyed as breeding individuals bred at the zoo. Dense cover within an enclosure, restricted public viewing areas, a variable feeding schedule and limited view of another species from the fossa exhibit appear to reduce the risk of unnatural behavior being performed. The achievement of best practice fossa husbandry may be a challenge due to its specialized ecology, the limited wild information guiding captive care, and the range of housing dimensions and exhibit features provided by zoos that makes identification of standardized practices difficult. We recommended that holders evaluate how and when enrichment is provided and assess what they are providing for environmental complexity as well as consider how the public views their fossa.

The Mesonychia is a group of archaic carnivorous mammals of uncertain phylogenetic affinities with a Holarctic distribution during the Paleogene. Intensive fossil collecting efforts in the Bighorn Basin, Wyoming, have resulted in recovery of the largest sample and most complete specimens yet known of the mesonychid Dissacus praenuntius from the second biozone of the Wasatchian North American Land Mammal Age (Wa-0). The Wa-0 biozone corresponds to the body of the Paleocene-Eocene Thermal Maximum (PETM), a brief but intense global warming event that occurred ~56 myr ago that significantly impacted terrestrial mammal faunas, including dwarfing in many mammal lineages. To evaluate the potential response of this lineage to climate change, we compared the PETM sample of D. praenuntius with those recovered from just before the PETM in the last biozone of the Clarkforkian North American Land Mammal Age (Cf-3) and just after the PETM in the Wa-1 biozone. While the sample size is still too small to say with certainty, tooth size (as a proxy for body weight) of D. praenuntius appears to be smaller during the late PETM than during either the pre-PETM Cf-3, or post-PETM Wa-1 biozones, suggesting the possibility of a muted dwarfing response to the PETM. However, the pattern observed for D. praenuntius differs from that of many other PETM mammals, as the shift to smaller body size is less pronounced and may have only occurred in late Wa-0.

Coral growth anomalies (GAs) are tumor-like protrusions that are detrimental to coral health, affecting both the coral skeleton and soft tissues. These lesions are increasingly found throughout the tropics and are commonly associated with high human population density, yet little is known about the molecular pathology of the disease. Here, we investigate the metabolic impacts of GAs through 1H nuclear magnetic resonance (NMR) metabolomics in Porites compressa tissues from a site of high disease prevalence (Coconut Island, Hawaii). We putatively identified 18 metabolites (8.1% of total annotated features) through complementary 1H and 1H–13C heteronuclear single quantum correlation NMR data that increase confidence in pathway analyses and may bolster future coral metabolite annotation efforts. Extract yield was elevated in both GA and unaffected (normal tissue from a diseased colony) compared to reference (normal tissue from GA-free colony) samples, potentially indicating elevated metabolic activity in GA-impacted colonies. Relatively high variation in metabolomic profiles among coral samples of the same treatment (i.e., inter-colony variation) confounded data interpretation, however, analyses of paired GA and unaffected samples identified 73 features that differed between these respective metabolome types. These features were largely annotated as unknowns, but 1-methylnicotinamide and trigonelline were found to be elevated in GA samples, while betaine, glycine, and histamine were lower in GA samples. Pathway analyses indicate decreased choline oxidation in GA samples, making this a pathway of interest for future targeted studies. Collectively, our results provide unique insights into GA pathophysiology by showing these lesions alter both the absolute and relative metabolism of affected colonies and by identifying features (metabolites and unknowns) and metabolic pathways of interest in GA pathophysiology going forward.

Lineage-ambiguous leukemias are high-risk malignancies of poorly understood genetic basis. Here, we describe a distinct subgroup of acute leukemia with expression of myeloid, T lymphoid, and stem cell markers driven by aberrant allele-specific deregulation of BCL11B, a master transcription factor responsible for thymic T-lineage commitment and specification. Mechanistically, this deregulation was driven by chromosomal rearrangements that juxtapose BCL11B to superenhancers active in hematopoietic progenitors, or focal amplifications that generate a superenhancer from a noncoding element distal to BCL11B. Chromatin conformation analyses demonstrated long-range interactions of rearranged enhancers with the expressed BCL11B allele and association of BCL11B with activated hematopoietic progenitor cell cis-regulatory elements, suggesting BCL11B is aberrantly co-opted into a gene regulatory network that drives transformation by maintaining a progenitor state. These data support a role for ectopic BCL11B expression in primitive hematopoietic cells mediated by enhancer hijacking as an oncogenic driver of human lineage-ambiguous leukemia. Significance: Lineage-ambiguous leukemias pose significant diagnostic and therapeutic challenges due to a poorly understood molecular and cellular basis. We identify oncogenic deregulation of BCL11B driven by diverse structural alterations, including de novo superenhancer generation, as the driving feature of a subset of lineage-ambiguous leukemias that transcend current diagnostic boundaries. This article is highlighted in the In This Issue feature, p. 2659

A transient heat stress occurring during early seed development in rice (Oryza sativa) reduces seed size by altering endosperm development. However, the relationship between the timing of the stress and specific developmental stage on heat sensitivity is not well-understood. To address this, we imposed a series of non-overlapping heat stress treatments and found that young seeds are most sensitive during the first two days after flowering. Temporal transcriptome analysis of developing, heat stressed (35°C) seeds during this window shows that Inositol-requiring enzyme 1 (IRE1)-mediated endoplasmic reticulum (ER) stress response and jasmonic acid (JA) pathways are the early (1-3 h) drivers of heat stress response. We propose that increased JA levels under heat stress may precede ER stress response as JA application promotes the spliced form of OsbZIP50, an ER response marker gene linked to IRE1-specific pathway. This study presents temporal and mechanistic insights into the role of JA and ER stress signalling during early heat stress response of rice seeds that impact both grain size and quality. Modulating the heat sensitivity of the early sensing pathways and downstream endosperm development genes can enhance rice resilience to transient heat stress events.

A range of first-line similarly effective medications ranging in price are recommended for treating uncomplicated hypertension. Considering drug costs alone, thiazides and thiazide-like diuretics are the most cost-efficient option. We determined incident prescribing of thiazides for newly diagnosed hypertension as first-line treatment in Alberta, factors that predicted receiving thiazides vs more costly medications, and how much could be saved if more patients were prescribed thiazides.Using a retrospective cohort design, factors predicting receiving thiazides vs other agents were determined using mixed effects logistic regression. Cost savings were simulated by shifting patients from other antihypertensive medications to thiazides and calculating the difference.Within our cohort of 89,548 adults, only 12% received thiazides as first-line treatment whereas 44% received angiotensin converting enzyme inhibitors, 17% received angiotensin receptor blockers, 16% received calcium channel blockers, and 10% received β-blockers. Antihypertensive medications were typically prescribed by office-based, general practitioners (88%). Being male and receiving a prescription from a physician with ≥ 20 years of practice and a high clinical workload were associated with increased odds of receiving nonthiazides. In the extreme case that all patients received thiazides as their first prescription, spending would have been reduced by a maximum of 95% (CAD$1.8 million).Only 12% of Albertan adults with incident, uncomplicated hypertension were prescribed thiazides as first-line treatment. With the opportunity for drug cost savings, future research should evaluate the risk of adverse events and side effects across the drug classes and whether the costs associated with managing those risks could offset the savings achieved through increased thiazide use.De nombreux médicaments tous aussi efficaces les uns que les autres, mais de prix variable, sont recommandés pour le traitement de première intention de l’hypertension non compliquée. Si l’on tient compte du coût du médicament seulement, les thiazides et les diurétiques apparentés aux thiazides sont les options les plus économiques. Nous avons évalué le taux de prescription d’un thiazide pour le traitement de première intention de l’hypertension nouvellement diagnostiquée en Alberta, les facteurs de prédiction de la prescription d’un thiazide plutôt que d’un autre médicament plus coûteux, ainsi que les économies qui pourraient être réalisées si on prescrivait un thiazide à un plus grand nombre de patients.Dans le cadre de notre étude de cohorte rétrospective, nous avons déterminé les facteurs de prédiction de la prescription d’un thiazide plutôt que d’un autre agent à l’aide d’une régression logistique à effets mixtes. Nous avons simulé les économies qui pourraient être réalisées en faisant passer à un thiazide les patients à qui un autre médicament antihypertenseur a été prescrit et en calculant la différence.Dans notre cohorte de 89 548 adultes, seulement 12 % des patients ont reçu un thiazide en première intention; 44 % ont reçu un inhibiteur de l’enzyme de conversion de l’angiotensine; 17 %, un antagoniste des récepteurs de l’angiotensine; 16 %, un inhibiteur calcique; et 10 %, des bêtabloquants. Les agents antihypertenseurs sont généralement prescrits par des omnipraticiens en cabinet (88 %). Le fait d’être un homme et le fait d’obtenir une prescription auprès d’un médecin exerçant depuis au moins 20 ans et ayant une lourde charge de travail clinique étaient associés à une probabilité supérieure de recevoir un agent autre qu’un thiazide. Dans le cas extrême où tous les patients se verraient prescrire un thiazide en première intention, la réduction des dépenses pourrait atteindre 95 % (soit 1,8 million de dollars canadiens).En Alberta, un thiazide a été prescrit en première intention à seulement 12 % des adultes venant de recevoir un diagnostic d’hypertension non compliquée. Compte tenu des économies qui pourraient être réalisées si un thiazide était prescrit dans ce contexte, il conviendrait d’effectuer des recherches plus poussées pour évaluer le risque de manifestations indésirables et d’effets secondaires associé aux différentes classes de médicaments, et pour déterminer si les coûts liés à la prise en charge de ce risque annuleraient les économies réalisées en augmentant le recours aux thiazides.

Objectives Histoplasmosis and cryptococcosis are important public health problems in people living with HIV (PLHIV) in Central America. Conventional laboratory assays, based on microscopy and culture, are not optimal for the diagnosis of either disease. However, antigen (Ag) assays are rapid and highly accurate for the diagnosis of these infections. Methods Laboratory surveillance of PLHIV was carried out in four hospitals in Panama, Honduras and Nicaragua, between 2015 and 2019. Detection of Histoplasma antigens in urine was performed by enzyme immunoassay (EIA), and Cryptococcus antigen detection in sera and cerebrospinal fluid specimens was performed by lateral flow assay (LFA). Results A total of 4,453 PLHIV with clinical suspicion of histoplasmosis (n = 1,343) or cryptococcosis (n = 3,110; 2,721 sera and 389 CSF) were tested. Of 1,343 patients suspected of having histoplasmosis, 269 (20%) were Histoplasma Ag positive. Of 3,110 patients tested using the Cryptococcus Ag assay, 329 (11%) were positive. Honduras reported the highest positivity rates (32% for Histoplasma Ag, and 16% for Cryptococcus Ag); Panama reported the largest number of patients testing positive using the Histoplasma Ag assay (n = 201); and Nicaragua reported the largest number of patients testing positive using the Cryptococcus Ag assay (n = 170). Conclusion Here, we show how the implementation of rapid diagnostics assays impacted case detection and was useful for the care of people with advanced HIV. Rapid and accurate diagnosis could reduce mortality associated with histoplasmosis and cryptococcosis in PLHIV.

The sound environment of a zoo animal is a complex milieu of animal and human-generated sounds; coming from the species itself, other species, visitors, keepers and other zoo-users. Research determining how different components of the sound environment affect animal behaviour is surprisingly lacking but could have real-world impacts for animal welfare and zoo enclosure design. The current study investigated the effects of the sound environment on two flocks of flamingos housed in open-air enclosures at British zoos. Measures of how each flock used its enclosure (as a response variable) and environmental variables (Inband Power and Peak Frequency were recorded as characteristics of the sound environment, as well as temperature, humidity and cloud cover, and finally visitor presence-all as potential predictor variables) were made over a 2-month period. Assessment of space use by zoo animals is often used as a measure of the appropriateness of an exhibit and to understand welfare. Given that flamingo activity is influenced by weather and that the sound environment of the zoo is likely to be influenced by the number and the presence of visitors, it was assumed that these predictor variables would influence where the flamingos were located at different times of the day. As expected, there was a complicated relationship between enclosure use and Inband Power (average spectral density, a measure of sound energy) in both flocks; visitors generated salient sound but other visitor characteristics such as their physical presence may have impacted the movement of the birds around their enclosures. Results show a complex picture where environmental conditions influence flamingo enclosure usage as well as visitor presence and sounds around/in the enclosure. Findings are not consistent between the two flocks, with one flock demonstrating distinct temporal change to enclosure zone occupancy and the other responsive to humidity and cloud cover variation. We believe enclosure use can provide a valuable indication of how birds react to their soundscape; however, our findings suggest more work is needed to unpick the components of captive sound environments, and their relative effects on how animals use their space.

Fungus farming ambrosia beetles carry their nutritional mutualistic fungi in specialized structures called mycetangia. Fungal propagules are also dispersed phoretically on the beetle’s exoskeleton. We determined the phoretic presence and abundance of Raffaelea lauricola, the causal agent of the laurel wilt disease in avocado, on five ambrosia beetle species: Xyleborus bispinatus, Xyleborus volvulus, Xyleborus affinis, Xyleborinus saxesenii and Xylosandrus crassiusculus. Beetles were captured while in flight, excavated from logs, and from logs placed in emergence chambers. Beetles collected by the three methods were assayed for the presence of internal (gut and mycetangium) and external (attached to the exoskeleton) colony forming units (CFUs) of R. lauricola. The pathogen was recovered from the exoskeleton of all beetle species. The collection method significantly influenced the frequency of pathogen recovery, and the abundance of both internal and phoretic R. lauricola was species-specific. Internal CFUs recovery was greater than phoretic recovery. Besides R. lauricola, other cycloheximide tolerant fungi, including mutualistic and entomopathogenic fungi, were isolated from the beetle’s exoskeleton. However, phoretic CFUs of R. lauricola were more prevalent and abundant than any other mutualistic phoretic fungi across the beetle species. Our results suggest that phoresy is a common mechanism of transportation of wood-inhabiting fungi and that phoretic transmission of R. lauricola may potentially contribute to the infection in avocado.

Tetranychus urticae Koch (Acari: Tetranychidae), twospotted spider mite, is a major secondary pest of strawberry and can cause significant yield loss. Tetranychus urticae is typically controlled using miticides, which has led to rapid resistance development. In South Carolina (USA), extension agents and growers have reported field failures of miticides (inadequate pest suppression), but resistance has not been quantitatively determined. In 2018, we determined the level of miticide resistance of six T. urticae populations found on strawberry across South Carolina. We examined efficacy of all miticides registered for use on US strawberry by conducting an initial diagnostic bioassay at 20% of the maximum labeled field rate. Any population × active ingredient combination resulting in

Kelp forests provide many important ecosystem services to people, including mitigating storm damage, cycling nutrients, and providing commercially-harvestable resources. However, kelp forests’ ability to sequester carbon dioxide, and therefore help regulate the climate, has until recently, been overlooked in assessments of the beneficial services they provide. In this study we incorporate updated knowledge on the potential of kelp to sequester ‘blue carbon’, and use the extensive kelp forests of the Falkland Islands as a case study to assess the value of kelp forest to society through multiple associated ecosystem services. Our analysis shows kelp forests provide a highly valuable range of direct and indirect services, which if managed correctly, will continue to benefit people, both now and in the future. The total estimated value of the Falkland Islands’ kelp system is currently equivalent to ~ £2.69 billion per year (or £3.24 million km-2 year-1). However, the true value of the kelp forest surrounding the Falkland Islands is likely to be higher still, given that our estimate does not account for elements such as associated scientific research, tourism, and cultural services, due to the necessary data currently being unavailable. Similarly, the full value of these highly biodiverse ecosystems in supplying habitat and food to a large range of associated species is crucial, yet extremely difficult to fully quantify. This study illustrates the importance of maintaining kelp ecosystems in a healthy state to ensure they continue to supply valuable ecological processes, functional roles, and ecosystem services, including their overlooked role as significant long-term carbon sinks.

Mesozooplankton research in high latitude ecosystems tends to focus on different life stages of Calanus spp. due to its biomass dominance and trophic roles. However, a complex seasonal succession of abundant smaller mesozooplankton taxa suggests that the ecological functioning of the mesozooplankton communities is more complicated. We studied the year‐round taxon‐specific biomass measurements and size distributions of mesozooplankton on a sub‐Arctic continental shelf based on formalin preserved samples. Our results confirm that Calanus spp. dominate the mesozooplankton biomass (81%). We show that commonly used length–weight relationships underestimate Calanus biomass in autumn and winter, and accordingly, a strong seasonal bias was introduced in our understanding of sub‐Arctic plankton communities. We observed two periods with considerable contribution of meroplankton, the planktonic larvae of benthic invertebrates, to the mesozooplankton biomass: (a) Cirripedia nauplii accounted for 17% of total biomass close to the coast in early April and (b) meroplankton comprised up to 12.7% of total biomass in late July. Based on these results, we suggest that meroplankton may play an ecologically important role in addition to their role in dispersal of benthic species. We conclude that the seasonal succession of the biomass of small‐sized holoplankton and meroplankton, often obscured by patterns in the Calanus biomass, should receive more attention as these smaller individuals are likely an important functional component of the pelagic food web., Mesozooplankton play a key role as the major trophic link between the pelagic primary producers and higher trophic levels. Here, we show that meroplankton, the planktonic larvae of benthic invertebrates, contribute considerably to the biomass of the smallest mesozooplankton size fraction (

Here, we perform structural, thermodynamic, and kinetics tests of the Kirkwood-Buff-derived force field, KBFF20, for peptides and proteins developed in the previous article. The physical/structural tests measure the ability of KBFF20 to capture the experimental J-couplings for small peptides, to keep globular monomeric and oligomeric proteins folded, and to produce the experimentally relevant expanded conformational ensembles of intrinsically disordered proteins. The thermodynamic-based tests probe KBFF20's ability to quantify the preferential interactions of sodium chloride around native β-lactoglobulin and urea around native lysozyme, to reproduce the melting curves for small helix- and sheet-based peptides, and to fold the small proteins Trp-cage and Villin. The kinetics-based tests quantify how well KBFF20 can match the experimental contact formation rates of small, repeat-sequence peptides of variable lengths and the rotational diffusion coefficients of globular proteins. The results suggest that KBFF20 is naturally able to reproduce properties of both folded and disordered proteins, which we attribute to the use of the Kirkwood-Buff theory as the foundation of the force field's development. However, we show that KBFF20 tends to lose some well-defined secondary structural elements and increases the percentage of coil regions, indicating that the perfect balance of all interactions remains elusive. Nevertheless, we argue that KBFF20 is an improvement over recently modified force fields that require ad hoc interventions to prevent the collapse of intrinsically disordered proteins.

Millipedes in the family Xystodesmidae (Polydesmida) are often referred to as “colorful, flat-backed millipedes” for their bright aposematic coloration and tendency to form Müllerian mimicry rings in the Appalachian region. However, there are many species of Xystodesmidae that do not display colorful warning patterns, and instead have more cryptic appearances. Perhaps for this reason, groups such as the genus Nannaria have remained understudied, despite containing a large number of undescribed species. Before his death in 2012, R. L. Hoffman worked on a revision of the genus Nannaria, and synthesized material and drawings since 1949. Here the work is continued, inferring a molecular phylogeny of the Nannariini (Nannaria + Oenomaea pulchella), and revealing two clades within the genus. One clade is named the minor species group, and the second is the wilsoni species group. This revision, using a molecular phylogenetic framework, is the basis for descriptions of 35 new species in the minor species group. A multi-gene molecular phylogeny is used to make taxonomic changes in the taxon. Eleven putative species of Nannaria are also illustrated and discussed. Additionally, detailed collection, natural history and habitat notes, distribution maps, and a key to species of the Nannaria minor species group are provided. These items are synthesized as a basis for a revision of the genus, which hopefully will aid conservation and evolutionary investigations of this cryptic and understudied group.

BACKGROUND Pseudocercospora fijiensis is the causal agent of the black leaf streak disease (BLSD) of banana. Bananas are important global export commodities and a major staple food. Their susceptibility to BLSD pushes disease management towards excessive fungicide use, largely relying on multisite inhibitors and sterol demethylation inhibitors (DMIs). These fungicides are ubiquitous in plant disease control, targeting the CYP51 enzyme. We examined sensitivity to DMIs in P. fijiensis field isolates collected from various major banana production zones in Colombia, Costa Rica, Dominican Republic, Ecuador, the Philippines, Guadalupe, Martinique and Cameroon and determined the underlying genetic reasons for the observed phenotypes. RESULTS We observed a continuous range of sensitivity towards the DMI fungicides difenoconazole, epoxiconazole and propiconazole with clear cross‐sensitivity. Sequence analyses of PfCYP51 in 266 isolates showed 28 independent amino acid substitutions, nine of which correlated with reduced sensitivity to DMIs. In addition to the mutations, we observed up to six insertions in the Pfcyp51 promoter. Such promoter insertions contain repeated elements with a palindromic core and correlate with the enhanced expression of Pfcyp51 and hence with reduced DMI sensitivity. Wild‐type isolates from unsprayed bananas fields did not contain any promoter insertions. CONCLUSION The presented data significantly contribute to understanding of the evolution and global distribution of DMI resistance mechanisms in P. fijiensis field populations and facilitate the prediction of different DMI efficacy. The overall reduced DMI sensitivity calls for the deployment of a wider range of solutions for sustainable control of this major banana disease. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., Studies on Pseudocercospora fijiensis demethylation inhibitor (DMI) sensitivity shows that Pfcyp51 modulations correlated with fungicide resistance. The importance of amino acid substitutions at positions 137, 311, 378, 379 and 458–461 is strengthened by mathematical modelling. Changes in these positions compromise the three‐dimensional structure of the protein resulting in an affinity change. The presence of repeated elements and insertions in the promotor region of Pfcyp51 was also positively correlated with resistance to DMIs. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Alzheimer’s disease (AD) is associated with memory impairment and altered peripheral metabolism. Mounting evidence indicates that abnormal signaling in a brain-periphery metabolic axis plays a role in AD pathophysiology. The activation of pro-inflammatory pathways in the brain, including the interleukin-6 (IL-6) pathway, comprises a potential point of convergence between memory dysfunction and metabolic alterations in AD that remains to be better explored. Using T2-weighted magnetic resonance imaging (MRI), we observed signs of probable inflammation in the hypothalamus and in the hippocampus of AD patients when compared to cognitively healthy control subjects. Pathological examination of post-mortem AD hypothalamus revealed the presence of hyperphosphorylated tau and tangle-like structures, as well as parenchymal and vascular amyloid deposits surrounded by astrocytes. T2 hyperintensities on MRI positively correlated with plasma IL-6, and both correlated inversely with cognitive performance and hypothalamic/hippocampal volumes in AD patients. Increased IL-6 and suppressor of cytokine signaling 3 (SOCS3) were observed in post-mortem AD brains. Moreover, activation of the IL-6 pathway was observed in the hypothalamus and hippocampus of AD mice. Neutralization of IL-6 and inhibition of the signal transducer and activator of transcription 3 (STAT3) signaling in the brains of AD mouse models alleviated memory impairment and peripheral glucose intolerance, and normalized plasma IL-6 levels. Collectively, these results point to IL-6 as a link between cognitive impairment and peripheral metabolic alterations in AD. Targeting pro-inflammatory IL-6 signaling may be a strategy to alleviate memory impairment and metabolic alterations in the disease.

Spotted wing drosophila, Drosophila suzukii (Diptera: Drosophilidae), is a serious invasive pest of berries and cherries in the U.S. and Europe and has become a major phytosanitary trade barrier. In this pilot study, we explored the potential of using stand-alone ethyl formate (EF) treatment and a combinatory treatment of EF and cold temperature as postharvest control options for D. suzukii in imported blueberries. Stand-alone EF fumigations were effective against D. suzukii with LCt99% of 207.7 and 168.5 g·h·m−3 for eggs, the most tolerant life stage, at 5 and 21 °C, respectively. In a scale-up (10 m3) trial conducted at 5 °C, complete control of D. suzukii eggs placed inside and outside of blueberry boxes was achieved using 70 g·m−3 EF for 4 h with 5% blueberry loading ratio without deleterious impact on blueberry appearance such as soft spot or berry shrivel. In small scale pilot studies, 9-d stand-alone cold treatment at 5 °C was sufficient for complete control of D. suzukii eggs and larvae tested, but not pupae. The efficacy of this cold treatment appeared to be improved when D. suzukii eggs were first treated with low-dose EF (LCt50% level) prior to the cold treatment. The combination treatment resulted in complete mortality of D. suzukii eggs, larvae, and pupae tested after 7, 5, and 9 d of cold treatment, respectively. Together, these results suggest that stand-alone EF treatment, or the combination treatment of low-dose EF and cold as a systems approach may have a potential as postharvest treatments for D. suzukii in blueberries.