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An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

The advent of coronavirus disease 2019, or COVID-19, continues to trigger several important disruptions/innovations in practically every sector around the world. Additionally, the impacts are predominant in certain educational systems and in creating opportunities. Previous studies had addressed possible effective methods in handling distant learning and student interactions. This qualitative study explored lecturers' information literacy experience during online classes as a result of the pandemic. Semi-structured interview techniques were applied among participants, made up of 15 lecturers in the Humanities Faculty, Diponegoro University, Indonesia, and thematic analysis was used to analyze the data obtained. The results showed the focus of lecturers' information literacy experience was primarily on student interactions and knowledge of various online learning platforms. However, information repackaging was a significant initial consideration during virtual classes, after identifying salient student characteristics. In summary, the present study have contributed to the theoretical understanding of information literacy and may be of benefit to the teaching faculties for enhancing teaching and learning activities, as well as providing student support. [ABSTRACT FROM AUTHOR]

Background: Effective malaria surveillance requires detailed assessments of mosquitoes biting indoors, where interventions such as insecticide-treated nets work best, and outdoors, where other interventions may be required. Such assessments often involve volunteers exposing their legs to attract mosquitoes [i.e., human landing catches (HLC)], a procedure with significant safety and ethical concerns. Here, an exposure-free, miniaturized, double-net trap (DN-Mini) is used to assess relationships between indoor–outdoor biting preferences of malaria vectors, Anopheles arabiensis and Anopheles funestus, and their physiological ages (approximated by parity and insemination states). Methods: The DN-Mini is made of UV-resistant netting on a wooden frame and PVC base. At 100 cm × 60 cm × 180 cm, it fits indoors and outdoors. It has a protective inner chamber where a volunteer sits and collects host-seeking mosquitoes entrapped in an outer chamber. Experiments were conducted in eight Tanzanian villages using DN-Mini to: (a) estimate nightly biting and hourly biting proportions of mosquitoes indoors and outdoors; (b) compare these proportions to previous estimates by HLC in same villages; and, (c) compare distribution of parous (proxy for potentially infectious) and inseminated mosquitoes indoors and outdoors. Results: More than twice as many An. arabiensis were caught outdoors as indoors (p < 0.001), while An. funestus catches were marginally higher indoors than outdoors (p = 0.201). Anopheles arabiensis caught outdoors also had higher parity and insemination proportions than those indoors (p < 0.001), while An. funestus indoors had higher parity and insemination than those outdoors (p = 0.04). Observations of indoor-biting and outdoor-biting proportions, hourly biting patterns and overall species diversities as measured by DN-Mini, matched previous HLC estimates. Conclusions: Malaria vectors that are behaviourally adapted to bite humans outdoors also have their older, potentially infectious sub-populations concentrated outdoors, while those adapted to bite indoors have their older sub-populations concentrated indoors. Here, potentially infectious An. arabiensis more likely bite outdoors than indoors, while potentially infectious An. funestus more likely bite indoors. These observations validate previous evidence that even outdoor-biting mosquitoes regularly enter houses when young. They also demonstrate efficacy of DN-Mini for measuring indoor–outdoor biting behaviours of mosquitoes, their hourly biting patterns and epidemiologically relevant parameters, e.g., parity and insemination status, without exposure to volunteers. The trap is easy-to-use, easy-to-manufacture and affordable (prototypes cost ~ 100 US$/unit). [ABSTRACT FROM AUTHOR]

Background: Push–pull strategies have been proposed as options to complement primary malaria prevention tools, indoor residual spraying (IRS) and long-lasting insecticide-treated nets (LLINs), by targeting particularly early-night biting and outdoor-biting mosquitoes. This study evaluated different configurations of a push–pull system consisting of spatial repellents [transfluthrin-treated eave ribbons (0.25 g/m2 ai)] and odour-baited traps (CO2-baited BG-Malaria traps), against indoor-biting and outdoor-biting malaria vectors inside large semi-field systems. Methods: Two experimental huts were used to evaluate protective efficacy of the spatial repellents (push-only), traps (pull-only) or their combinations (push–pull), relative to controls. Adult volunteers sat outdoors (1830 h–2200 h) catching mosquitoes attempting to bite them (outdoor-biting risk), and then went indoors (2200 h–0630 h) to sleep under bed nets beside which CDC-light traps caught host-seeking mosquitoes (indoor-biting risk). Number of traps and their distance from huts were varied to optimize protection, and 500 laboratory-reared Anopheles arabiensis released nightly inside the semi-field chambers over 122 experimentation nights. Results: Push-pull offered higher protection than traps alone against indoor-biting (83.4% vs. 35.0%) and outdoor-biting (79% vs. 31%), but its advantage over repellents alone was non-existent against indoor-biting (83.4% vs. 81%) and modest for outdoor-biting (79% vs. 63%). Using two traps (1 per hut) offered higher protection than either one trap (0.5 per hut) or four traps (2 per hut). Compared to original distance (5 m from huts), efficacy of push–pull against indoor-biting peaked when traps were 15 m away, while efficacy against outdoor-biting peaked when traps were 30 m away. Conclusion: The best configuration of push–pull comprised transfluthrin-treated eave ribbons plus two traps, each at least 15 m from huts. Efficacy of push–pull was mainly due to the spatial repellent component. Adding odour-baited traps slightly improved personal protection indoors, but excessive trap densities increased exposure near users outdoors. Given the marginal efficacy gains over spatial repellents alone and complexity of push–pull, it may be prudent to promote just spatial repellents alongside existing interventions, e.g. LLINs or non-pyrethroid IRS. However, since both transfluthrin and traps also kill mosquitoes, and because transfluthrin can inhibit blood-feeding, field studies should be done to assess potential community-level benefits that push–pull or its components may offer to users and non-users. [ABSTRACT FROM AUTHOR]

Background: Anopheles funestus is a leading vector of malaria in most parts of East and Southern Africa, yet its ecology and responses to vector control remain poorly understood compared with other vectors such as Anopheles gambiae and Anopheles arabiensis. This study presents the first large-scale survey of the genetic and phenotypic expression of insecticide resistance in An. funestus populations in Tanzania. Methods: We performed insecticide susceptibility bioassays on An. funestus mosquitoes in nine regions with moderate-to-high malaria prevalence in Tanzania, followed by genotyping for resistance-associated mutations (CYP6P9a, CYP6P9b, L119F-GSTe2) and structural variants (SV4.3 kb, SV6.5 kb). Generalized linear models were used to assess relationships between genetic markers and phenotypic resistance. An interactive R Shiny tool was created to visualize the data and support evidence-based interventions. Results: Pyrethroid resistance was universal but reversible by piperonyl-butoxide (PBO). However, carbamate resistance was observed in only five of the nine districts, and dichloro-diphenyl-trichloroethane (DDT) resistance was found only in the Kilombero valley, south-eastern Tanzania. Conversely, there was universal susceptibility to the organophosphate pirimiphos-methyl in all sites. Genetic markers of resistance had distinct geographical patterns, with CYP6P9a-R and CYP6P9b-R alleles, and the SV6.5 kb structural variant absent or undetectable in the north-west but prevalent in all other sites, while SV4.3 kb was prevalent in the north-western and western regions but absent elsewhere. Emergent L119F-GSTe2, associated with deltamethrin resistance, was detected in heterozygous form in districts bordering Mozambique, Malawi and the Democratic Republic of Congo. The resistance landscape was most complex in western Tanzania, in Tanganyika district, where all five genetic markers were detected. There was a notable south-to-north spread of resistance genes, especially CYP6P9a-R, though this appears to be interrupted, possibly by the Rift Valley. Conclusions: This study underscores the need to expand resistance monitoring to include An. funestus alongside other vector species, and to screen for both the genetic and phenotypic signatures of resistance. The findings can be visualized online via an interactive user interface and could inform data-driven decision-making for resistance management and vector control. Since this was the first large-scale survey of resistance in Tanzania's An. funestus, we recommend regular updates with greater geographical and temporal coverage. [ABSTRACT FROM AUTHOR]

This service was carried out with the aim of developing the public speaking skills of teachers at SMP Negeri 11 Prabumulih. This ability is considered important so that the information conveyed by the teacher can be well received by the public. The methods applied in this training are lectures and discussions. this activity In the end, it can provide deeper knowledge and insight to the teachers of SMP Negeri 11 Prabumulih which can be used as provisions to build better communication interaction patterns in front of the audience.

Background: Attractive targeted sugar baits (ATSBs) control sugar-feeding mosquitoes with oral toxicants, and may effectively complement core malaria interventions, such as insecticide-treated nets even where pyrethroid-resistance is widespread. The technology is particularly efficacious in arid and semi-arid areas. However, their performance remains poorly-understood in tropical areas with year-round malaria transmission, and where the abundant vegetation constitutes competitive sugar sources for mosquitoes. This study compared the efficacies of ATSBs (active ingredient: 2% boric acid) in controlled settings with different vegetation densities. Methods: Potted mosquito-friendly plants were introduced inside semi-field chambers (9.6 m by 9.6 m) to simulate densely-vegetated, sparsely-vegetated, and bare sites without any vegetation (two chambers/category). All chambers had volunteer-occupied huts. Laboratory-reared Anopheles arabiensis were released nightly (200/chamber) and host-seeking females recaptured using human landing catches outdoors (8.00 p.m.–9.00 p.m.) and CDC-light traps indoors (9.00 p.m.–6.00 a.m.). Additionally, resting mosquitoes were collected indoors and outdoors each morning using Prokopack aspirators. The experiments included a "before-and-after" set-up (with pre-ATSBs, ATSBs and post-ATSBs phases per chamber), and a "treatment vs. control" set-up (where similar chambers had ATSBs or no ATSBs). The experiments lasted 84 trap-nights. Results: In the initial tests when all chambers had no vegetation, the ATSBs reduced outdoor-biting by 69.7%, indoor-biting by 79.8% and resting mosquitoes by 92.8%. In tests evaluating impact of vegetation, the efficacy of ATSBs against host-seeking mosquitoes was high in bare chambers (outdoors: 64.1% reduction; indoors: 46.8%) but modest or low in sparsely-vegetated (outdoors: 34.5%; indoors: 26.2%) and densely-vegetated chambers (outdoors: 25.4%; indoors: 16.1%). Against resting mosquitoes, the ATSBs performed modestly across settings (non-vegetated chambers: 37.5% outdoors and 38.7% indoors; sparsely-vegetated: 42.9% outdoors and 37.5% indoors; densely-vegetated: 45.5% outdoors and 37.5% indoors). Vegetation significantly reduced the ATSBs efficacies against outdoor-biting and indoor-biting mosquitoes but not resting mosquitoes. Conclusion: While vegetation can influence the performance of ATSBs, the devices remain modestly efficacious in both sparsely-vegetated and densely-vegetated settings. Higher efficacies may occur in places with minimal or completely no vegetation, but such environments are naturally unlikely to sustain Anopheles populations or malaria transmission in the first place. Field studies therefore remain necessary to validate the efficacies of ATSBs in the tropics. [ABSTRACT FROM AUTHOR]

Cyclooxygenase 2 (COX-2) is a key enzyme in the conversion of arachidonic acid to prostaglandins, and COX-2 overexpression plays an important role in carcinogenesis. Exposure to UVB strongly increased COX-2 protein expression in mouse 308 keratinocytes, and this induction was inhibited by apigenin, a nonmutagenic bioflavonoid that has been shown to prevent mouse skin carcinogenesis induced by both chemical carcinogens and UV exposure. Our previous study suggested that one pathway by which apigenin inhibits UV-induced and basal COX-2 expression is through modulation of USF transcriptional activity in the 5′ upstream region of the COX-2 gene. Here, we found that apigenin treatment also increased COX-2 mRNA stability, and the inhibitory effect of apigenin on UVB-induced luciferase reporter gene activity was dependent on the AU-rich element of the COX-2 3′-untranslated region. Furthermore, we identified two RNA-binding proteins, HuR and the T-cell-restricted intracellular antigen 1-related protein (TIAR), which were associated with endogenous COX-2 mRNA in 308 keratinocytes, and apigenin treatment increased their localization to cell cytoplasm. More importantly, reduction of HuR levels by small interfering RNA inhibited apigenin-mediated stabilization of COX-2 mRNA. Cells expressing reduced TIAR showed marked resistance to apigenin's ability to inhibit UVB-induced COX-2 expression. Taken together, these results indicate that in addition to transcriptional regulation, another mechanism by which apigenin prevents COX-2 expression is through mediating TIAR suppression of translation. [ABSTRACT FROM AUTHOR]

Kesantunan berbahasa pada hakikatnya adalah etika kita dalam bersosialisasi di masyarakat. Kaidah kesantunan umumnya dipakai dalam setiap tindak berbahasa. Secara teoretis, pada dasarnya semua orang harus berbicara secara santun. Setiap orang wajib menjaga etika dalam berkomunikasi agar tujuan berkomunikasi dapat tercapai. Berkaitan dengan bahasan latar belakang kesantunan berbahasa maka perlu menganalisis novel Seputih Hati yang Tercabik. Pengisahan tokoh dan penokohan di dalam novel ini lebih kompleks serta dialog-dialognya lebih sering terjadi sehingga maksim-maksim dalam prinsip kesantunan lebih mungkin untuk muncul. Prinsip-prinsip kesantunan dalam bertutur yaitu: (1) maksim kearifan, (2) maksim kedermawanan, (3) maksim pujian, (4) maksim kerendahan hati, (5) maksim kesepakatan, dan (6) maksim kesimpatian. Penelitian ini merupakan studi pustaka dengan menggunakan metode deskriptif kualitatif. Data primer adalah novel Seputih Hati yang Tercabik karya Ratu Wardarita. Data primer di ini dianalisis dengan menggunakan data sekunder sebagai data dukung untuk menganalisis novel Seputih Hati yang Tercabik sesuai ranah penelitian penggunaan kesantunan berbahasa yang diisyaratkan melalui referensi pendukung penelitian ini.

Penelitian ini difokuskan pada kajian penelitian nilai-nilai pendidikan dalam sastra lisan pisaan masyarakat Komering di Kabupaten OKU Timur. Metode penelitian yang digunakan adalah metode deskriptif kualitatif. Objek/informan mengenai penelitian ini adalah ditujukan kepada orang yang benar-benar memahami sastra lisan pisaan pada masyarakat Kabupaten OKU Timur sebagai sumber data, yaitu Bapak H. Leo Budi Rachmadi, SE bin H. Syahrin Nasir Adok Batin Temunggung dari Martapura dan Hamidin Mangkudermawan dari Sabalio,Bunga Mayang OKU Timur. Teknik pengumpulan data penelitian: (1) observasi; (2) wawancara; (3) dokumentasi. Teknik analisis data: (1) mempersiapkan data; (2) membaca keseluruhan data; (3) menganalisis data. Hasil penelitian ini menyimpulkan bahwa: (1) Pisaan dalam sastra lisan masyarakat Komering di Kabupaten OKU Timur, memiliki nilai-nilai pendidikan yang berupa memberikan pemahaman akan kehidupan bagi masyarakat Kabupaten OKU Timur dari generasi ke generasi.

Background: Malaria disproportionately affects low-income households in rural communities where poor housing is common. Despite evidence that well-constructed and mosquito-proofed houses can reduce malaria risk, housing improvement is rarely included in malaria control toolboxes. This study assessed the need, magnitude, and opportunities for housing improvement to control malaria in rural Tanzania. Methods: A mixed-methods study was conducted in 19 villages across four district councils in southern Tanzania. A structured survey was administered to 1292 community members to assess need, perceptions, and opportunities for housing improvement for malaria control. Direct observations of 802 houses and surrounding environments were done to identify the actual needs and opportunities, and to validate the survey findings. A market survey was done to assess availability and cost of resources and services necessary for mosquito-proofing homes. Focus group discussions were conducted with key stakeholders to explore insights on the potential and challenges of housing improvement as a malaria intervention. Results: Compared to other methods for malaria control, housing improvement was among the best understood and most preferred by community members. Of the 735 survey respondents who needed housing improvements, a majority needed window screening (91.1%), repairs of holes in walls (79.4%), door covers (41.6%), closing of eave spaces (31.2%) and better roofs (19.0%). Community members invested significant efforts to improve their own homes against malaria and other dangers, but these efforts were often slow and delayed due to high costs and limited household incomes. Study participants suggested several mechanisms of support to improve their homes, including government loans and subsidies. Conclusion: Addressing the need for housing improvement is a critical component of malaria control efforts in southern Tanzania. In this study, a majority of the community members surveyed needed modest modifications and had plans to work on those modifications. Without additional support, their efforts were however generally slow; households would take years to sufficiently mosquito-proof their houses. It is, therefore, crucial to bring together the key players across sectors to reduce barriers in malaria-proofing housing in endemic settings. These may include government subsidies or partnerships with businesses to make housing improvement more accessible and affordable to residents. [ABSTRACT FROM AUTHOR]

Background: Early-evening and outdoor-biting mosquitoes may compromise the effectiveness of frontline malaria interventions, notably insecticide-treated nets (ITNs). This study aimed to evaluate the efficacy of low-cost insecticide-treated eave ribbons and sandals as supplementary interventions against indoor-biting and outdoor-biting mosquitoes in south-eastern Tanzania, where ITNs are already widely used. Methods: This study was conducted in three villages, with 72 households participating (24 households per village). The households were divided into four study arms and assigned: transfluthrin-treated sandals (TS), transfluthrin-treated eave ribbons (TER), a combination of TER and TS, or experimental controls. Each arm had 18 households, and all households received new ITNs. Mosquitoes were collected using double net traps (to assess outdoor biting), CDC light traps (to assess indoor biting), and Prokopack aspirators (to assess indoor resting). Protection provided by the interventions was evaluated by comparing mosquito densities between the treatment and control arms. Additional tests were done in experimental huts to assess the mortality of wild mosquitoes exposed to the treatments or controls. Results: TERs reduced indoor-biting, indoor-resting and outdoor-biting Anopheles arabiensis by 60%, 73% and 41%, respectively, while TS reduced the densities by 18%, 40% and 42%, respectively. When used together, TER & TS reduced indoor-biting, indoor-resting and outdoor-biting An. arabiensis by 53%, 67% and 57%, respectively. Protection against Anopheles funestus ranged from 42 to 69% with TER and from 57 to 74% with TER & TS combined. Mortality of field-collected mosquitoes exposed to TER, TS or both interventions was 56–78% for An. arabiensis and 47–74% for An. funestus. Conclusion: Transfluthrin-treated eave ribbons and sandals or their combination can offer significant household-level protection against malaria vectors. Their efficacy is magnified by the transfluthrin-induced mortality, which was observed despite the prevailing pyrethroid resistance in the study area. These results suggest that TER and TS could be useful supplementary tools against residual malaria transmission in areas where ITN coverage is high but additional protection is needed against early-evening and outdoor-biting mosquitoes. Further research is needed to validate the performance of these tools in different settings, and assess their long-term effectiveness and feasibility for malaria control. [ABSTRACT FROM AUTHOR]

Background: Malaria transmission can be highly heterogeneous between and within localities, and is influenced by factors such as survival and biting frequencies of Anopheles mosquitoes. This study investigated the relationships between the biological age, distance from aquatic habitats and pyrethroid resistance status of Anopheles funestus mosquitoes, which currently dominate malaria transmission in south-east Tanzania. The study also examined how such relationships may influence malaria transmission and control. Methods: Female An. funestus were collected in houses located 50–100 m, 150–200 m or over 200 m from the nearest known aquatic habitats. The mosquitoes were exposed to 1×, 5× and 10× the diagnostic doses of deltamethrin or permethrin, or to the synergist, piperonyl butoxide (PBO) followed by the pyrethroids, then monitored for 24 h-mortality. Ovaries of exposed and non-exposed mosquitoes were dissected to assess parity as a proxy for biological age. Adults emerging from larval collections in the same villages were tested against the same insecticides at 3–5, 8–11 or 17–20 days old. Findings: Mosquitoes collected nearest to the aquatic habitats (50-100 m) had the lowest mortalities compared to other distances, with a maximum of 51% mortality at 10× permethrin. For the age-synchronized mosquitoes collected as larvae, the insecticide-induced mortality assessed at both the diagnostic and multiplicative doses (1×, 5× and 10×) increased with mosquito age. The highest mortalities at 1× doses were observed among the oldest mosquitoes (17–20 days). At 10× doses, mortalities were 99% (permethrin) and 76% (deltamethrin) among 8–11 day-olds compared to 80% (permethrin) and 58% (deltamethrin) among 3–5 day-olds. Pre-exposure to PBO increased the potency of both pyrethroids. The proportion of parous females was highest among mosquitoes collected farthest from the habitats. Conclusion: In this specific setting, older An. funestus and those collected farthest from the aquatic habitats (near the centre of the village) were more susceptible to pyrethroids than the younger ones and those caught nearest to the habitats. These findings suggest that pyrethroid-based interventions may remain at least moderately effective despite widespread pyrethroid-resistance, by killing the older, less-resistant and potentially-infective mosquitoes. Further studies should investigate how and whether these observations could be exploited to optimize malaria control in different settings. [ABSTRACT FROM AUTHOR]

Tujuan penelitian ini adalah untuk menguji dan mendeskripsikan pengaruh model pembelajaran Diskursus Multy Reprecentacy berbatuan Sparkol videoscribe terhadap kemampuan representasi matematis peserta didik. Metode yang digunakan adalah kuasi eksperimen menggunakan 3 kelompok yaitu kelas eksperimen 1 menggunakan model pembelajaran Diskursus Multy Representasi berbantuan sparkol videoscribe, kelas eksperimen 2 yang menggunakan model pembelajaran Diskursus Multy Representasi, dan kelas eksperimen 3 sebagai kelas kontrol menggunakan model pembelajaran konvensional yang masing-masing dipilih secara acak. Instrumen yang digunakan dalam penelitian ini adalah tes kemampuan representasi matematis yang meliputi 3 aspek, yaitu representasi visual, simbolik, dan verbal. Teknik analisis data menggunakan komparasi secara statistik. Hasil dari penelitian ini menunjukkan bahwa model pembelajaran DMR berbantuan sparkol videoscribe sama baiknya dengan model pembelajaran DMR terhadap kemampuan representasi matematis. Model pembelajaran DMR lebih baik dari model pembelajaran konvenional terhadap kemampuan representasi matematis.

Masalah dalam penelitian ini adalah bagaimanakah tingkat keefektifan penggunaan teknik Prep Technique dalam pemahaman cerpen siswa kelas IX SMP Negeri 3 Babat Toman Kabupaten Musi Banyuasin. Tujuan penelitian ini untuk mengetahui dan mendeskripsikan tingkat keefektifan penggunaan teknik Prep Technique dalam pemahaman cerpen siswa IX SMP Negeri 3 Babat Toman Kabupaten Musi Banyuasin. Data penelitian ini diperoleh melalui teknik tes yaitu tes objektif. Teknik analisis data yang digunakan meliputi uji validitas dan uji raliabilitas. Berdasarkan hasil analisis data tes siswa diperoleh bahwa “thitung” lebih besar dari “ttabel” jika thitung ≥ maka Ho ditolak dan Ha diterima jika thitung ≥ ttabel maka Ha diterima Ho ditolak berdasarkan perhitungan thitung diatas ternyata thitung = 0,953 ≥ ttabel = 0,268 pada taraf signitifikan 99% berarti keefektifan penggunaan teknik Prep Technique dalam pemahaman cerpen siswa IX SMP Negeri 3 Babat Toman Kabupaten Musi Banyuasin lebih efektif. Kata kunci: pemahaman cerpen, teknik Prep Technique Abstract The problem in this study is how the effectiveness of the use of the Prep Technique technique in understanding short stories of class IX students of SMP Negeri 3 Babat Toman, Musi Banyuasin Regency. The purpose of this study was to determine and describe the effectiveness of the use of the Prep Technique technique in understanding the short stories of IX students of SMP Negeri 3 Babat Toman, Musi Banyuasin Regency. The research data was obtained through a test technique that is an objective test. Data analysis techniques used include validity and reliability testing. Based on the results of analysis of student test data obtained that "tcount" is greater than "ttable" if tcount ≥ then Ho is rejected and Ha is accepted if tcount ≥ ttable then Ha is accepted Ho is rejected based on the above tcount calculation turns out tcount = 0.953 ≥ ttable = 0.268 at the significance level 99% means the effectiveness of the use of the Prep Technique technique in understanding the short stories of IX students of SMP Negeri 3 Babat Toman, Musi Banyuasin Regency is more effective. Keywords: understanding short stories, Prep Technique techniques

Background: Wild populations of Anopheles mosquitoes are generally thought to mate outdoors in swarms, although once colonized, they also mate readily inside laboratory cages. This study investigated whether the malaria vectors Anopheles funestus and Anopheles arabiensis can also naturally mate inside human dwellings. Method: Mosquitoes were sampled from three volunteer-occupied experimental huts in a rural Tanzanian village at 6:00 p.m. each evening, after which the huts were completely sealed and sampling was repeated at 11:00 p.m and 6 a.m. the next morning to compare the proportions of inseminated females. Similarly timed collections were done inside local unsealed village houses. Lastly, wild-caught larvae and pupae were introduced inside or outside experimental huts constructed inside two semi-field screened chambers. The huts were then sealed and fitted with exit traps, allowing mosquito egress but not entry. Mating was assessed in subsequent days by sampling and dissecting emergent adults caught indoors, outdoors and in exit traps. Results: Proportions of inseminated females inside the experimental huts in the village increased from approximately 60% at 6 p.m. to approximately 90% the following morning despite no new mosquitoes entering the huts after 6 p.m. Insemination in the local homes increased from approximately 78% to approximately 93% over the same time points. In the semi-field observations of wild-caught captive mosquitoes, the proportions of inseminated An. funestus were 20.9% (95% confidence interval [CI]: ± 2.8) outdoors, 25.2% (95% CI: ± 3.4) indoors and 16.8% (± 8.3) in exit traps, while the proportions of inseminated An. arabiensis were 42.3% (95% CI: ± 5.5) outdoors, 47.4% (95% CI: ± 4.7) indoors and 37.1% (CI: ± 6.8) in exit traps. Conclusion: Wild populations of An. funestus and An. arabiensis in these study villages can mate both inside and outside human dwellings. Most of the mating clearly happens before the mosquitoes enter houses, but additional mating happens indoors. The ecological significance of such indoor mating remains to be determined. The observed insemination inside the experimental huts fitted with exit traps and in the unsealed village houses suggests that the indoor mating happens voluntarily even under unrestricted egress. These findings may inspire improved vector control, such as by targeting males indoors, and potentially inform alternative methods for colonizing strongly eurygamic Anopheles species (e.g. An. funestus) inside laboratories or semi-field chambers. [ABSTRACT FROM AUTHOR]

Background: Different forms of mosquito modifications are being considered as potential high-impact and low-cost tools for future malaria control in Africa. Although still under evaluation, the eventual success of these technologies will require high-level public acceptance. Understanding prevailing community perceptions of mosquito modification is, therefore, crucial for effective design and implementation of these interventions. This study investigated community perceptions regarding genetically-modified mosquitoes (GMMs) and their potential for malaria control in Tanzanian villages where no research or campaign for such technologies has yet been undertaken. Methods: A mixed-methods design was used, involving: (i) focus group discussions (FGD) with community leaders to get insights on how they frame and would respond to GMMs, and (ii) structured questionnaires administered to 490 community members to assess awareness, perceptions and support for GMMs for malaria control. Descriptive statistics were used to summarize the findings and thematic content analysis was used to identify key concepts and interpret the findings. Results: Nearly all survey respondents were unaware of mosquito modification technologies for malaria control (94.3%), and reported no knowledge of their specific characteristics (97.3%). However, community leaders participating in FGDs offered a set of distinctive interpretive frames to conceptualize interventions relying on GMMs for malaria control. The participants commonly referenced their experiences of cross-breeding for selecting preferred traits in domestic plants and animals. Preferred GMMs attributes included the expected reductions in insecticide use and human labour. Population suppression approaches, requiring as few releases as possible, were favoured. Common concerns included whether the GMMs would look or behave differently than wild mosquitoes, and how the technology would be integrated into current malaria control policies. The participants emphasised the importance and the challenge of educating and engaging communities during the technology development. Conclusions: Understanding how communities perceive and interpret novel technologies is crucial to the design and effective implementation of new vector control programmes. This study offers vital clues on how communities with no prior experience of modified mosquitoes might conceptualize or respond to such technologies when deployed in the context of malaria control programmes. Drawing upon existing interpretive frames and locally-resonant analogies when deploying such technologies may provide a basis for more durable public support in the future. [ABSTRACT FROM AUTHOR]

• MWCNT induces chronic pulmonary granulomatous inflammation. • MWCNT reduces mitochondrial fatty acid oxidation in alveolar macrophages. • MWCNT induces pulmonary oxidative stress and apoptosis. • MWCNT increases miR-27b expression in alveolar macrophages. Human exposure to carbon nanotubes (CNT) has been associated with the development of pulmonary sarcoid-like granulomatous disease. Our previous studies demonstrated that multi-walled carbon nanotubes (MWCNT) induced chronic pulmonary granulomatous inflammation in mice. Granuloma formation was accompanied by decreased peroxisome proliferator-activated receptor gamma (PPARγ) and disrupted intracellular lipid homeostasis in alveolar macrophages. Others have shown that PPARγ activation increases mitochondrial fatty acid oxidation (FAO) to reduce free fatty acid accumulation. Hence, we hypothesized that the disrupted lipid metabolism suppresses mitochondrial FAO. To test our hypothesis, C57BL/6 J mice were instilled by an oropharyngeal route with 100 μg MWCNT freshly suspended in 35 % Infasurf. Control sham mice received vehicle alone. Sixty days following instillation, mitochondrial FAO was measured in permeabilized bronchoalveolar lavage (BAL) cells. MWCNT instillation reduced the mitochondrial oxygen consumption rate of BAL cells in the presence of palmitoyl-carnitine as mitochondrial fuel. MWCNT also reduced mRNA expression of mitochondrial genes regulating FAO, carnitine palmitoyl transferase-1 (CPT1), carnitine palmitoyl transferase-2 (CPT2), hydroxyacyl-CoA dehydrogenase subunit beta (HADHB), and PPARγ coactivator 1 alpha (PPARGC1A). Importantly, both oxidative stress and apoptosis in alveolar macrophages and lung tissues of MWCNT-instilled mice were increased. Because macrophage PPARγ expression has been reported to be controlled by miR-27b which is known to induce oxidative stress and apoptosis, we measured the expression of miR-27b. Results indicated elevated levels in alveolar macrophages from MWCNT-instilled mice compared to controls. Given that inhibition of FAO and apoptosis are linked to M1 and M2 macrophage activation, respectively, the expression of both M1 and M2 key indicator genes were measured. Interestingly, results showed that both M1 and M2 phenotypes of alveolar macrophages were activated in MWCNT-instilled mice. In conclusion, alveolar macrophages of MWCNT-instilled mice had increased miR-27b expression, which may reduce the expression of PPARγ resulting in attenuation of FAO. This reduction in FAO may lead to activation of M1 macrophages. The upregulation of miR-27b may also induce apoptosis, which in turn can cause M2 activation of alveolar macrophages. These observations indicate a possible role of miR-27b in impaired mitochondrial function in the chronic activation of alveolar macrophages by MWCNT and the development of chronic pulmonary granulomatous inflammation. [ABSTRACT FROM AUTHOR]

Agents that stimulate the endoplasmic reticulum (ER) stress pathway are being exploited pharmacologically to induce cancer cell death. Cytotoxic ER stress is typically regulated by the transcription factor, C/EBP homologous protein 10 (CHOP10). Products of CHOP10 transcription include the pro-apoptotic proteins: ER oxidoreductase 1α (ERO1α), death receptor-5 (DR5), and tribbles-related protein 3 (TRB3). Our previous findings showed cell death induced by 15-deoxy- Δ12,14 prostamide J 2 (15d-PMJ 2 ) occurred in an ER stress-dependent manner. However, the pathway by which 15d-PMJ 2 regulates ER stress-mediated death downstream of CHOP10 has not been identified. Our results demonstrate 5 µM 15d-PMJ 2 increased CHOP10 expression and apoptosis in HCT116 colon cancer cells. In cells treated with pharmacological inhibitors of ER stress, 15d-PMJ 2 -induced apoptosis was reliant upon the ER stress pathway. To investigate the role of CHOP10 and its transcriptional products in apoptosis, genetic deletion of CHOP10 (CHOP10-KO) was performed using the CRISPR/Cas9 system. The apoptotic action of 15d-PMJ 2 was blunted in cells lacking CHOP10 expression. The deletion of CHOP10 reduced the expression of DR5, ERO1α, and TRB3 although only the expression of TRB3 was significantly reduced. Therefore, we overexpressed TRB3 in CHOP10-KO cells and observed that the activation of Akt was inhibited and 15d-PMJ2-induced apoptosis was restored. Thus, a mechanism of apoptosis elicited by 15d-PMJ 2 includes the stimulation of CHOP10/TRB3/Akt inhibition. Given the important role these signaling molecules play in cancer cell fate, 15d-PMJ 2 may be an effective inducer of apoptosis in cancer cells., Competing Interests: RV-A, CB, and DL have ownership interest (including awarded and pending patents) in 15d-PMJ2. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Albassam, Ladin, Elhassanny, Burns and Van Dross-Anderson.)

Melanoma is the deadliest form of skin cancer in the US. Although immunotherapeutic checkpoint inhibitors and small-molecule kinase inhibitors have dramatically increased the survival of patients with melanoma, new or optimized therapeutic approaches are still needed to improve outcomes. 15-deoxy-Δ 12,14 -prostamide J 2 (15d-PMJ 2 ) is an investigational small-molecule that induces ER stress-mediated apoptosis selectively in tumor cells. Additionally, 15d-PMJ2 reduces melanoma growth in vivo . To assess the chemotherapeutic potential of 15d-PMJ 2 , the current study sought to uncover molecular pathways by which 15d-PMJ 2 exerts its antitumor activity. B16F10 melanoma and JWF2 squamous cell carcinoma cell lines were cultured in the presence of pharmacological agents that prevent ER or oxidative stress as well as Ca 2+ channel blockers to identify mechanisms of 15d-PMJ 2 cell death. Our data demonstrated the ER stress protein, PERK, was required for 15d-PMJ 2 -induced death. PERK activation triggered the release of ER-resident Ca 2+ through an IP 3 R sensitive pathway. Increased calcium mobilization led to mitochondrial Ca 2+ overload followed by mitochondrial permeability transition pore (mPTP) opening and the deterioration of mitochondrial respiration. Finally, we show the electrophilic double bond located within the cyclopentenone ring of 15d-PMJ 2 was required for its activity. The present study identifies PERK/IP3R/mPTP signaling as a mechanism of 15d-PMJ 2 antitumor activity.

The endoplasmic reticulum (ER) is a key organelle involved in homeostatic functions including protein synthesis and transport, and the storage of free calcium. ER stress potentiates neuroinflammation and neurodegeneration and is a key contributor to the pathogenesis of neurogenic hypertension. Recently, we showed that kinin B1 receptor (B1R) activation plays a vital role in modulating neuroinflammation and hypertension. However, whether B1R activation results in the progression and enhancement of ER stress has not yet been studied. In this brief research report, we tested the hypothesis that B1R activation in neurons contributes to unfolded protein response (UPR) and the development of ER stress. To test this hypothesis, we treated primary hypothalamic neuronal cultures with B1R specific agonist Lys-Des-Arg 9 -Bradykinin (LDABK) and measured the components of UPR and ER stress. Our data show that B1R stimulation via LDABK, induced the upregulation of GRP78, a molecular chaperone of ER stress. B1R stimulation was associated with an increased expression and activation of transmembrane ER stress sensors, ATF6, IRE1α, and PERK, the critical components of UPR. In the presence of overwhelming ER stress, activated ER stress sensors can lead to oxidative stress, autophagy, or apoptosis. To determine whether B1R activation induces apoptosis we measured intracellular Ca 2+ and extracellular ATP levels, caspases 3/7 activity, and cell viability. Our data show that LDABK treatment does increase Ca 2+ and ATP levels but does not alter caspase activity or cell viability. These findings suggest that B1R activation initiates the UPR and is a key factor in the ER stress pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 White, Parekh, Theobald, Pakala, Myers, Van Dross and Sriramula.)

Metastatic melanoma is the most deadly skin neoplasm in the United States. Outcomes for this lethal disease have improved dramatically due to the use of both targeted and immunostimulatory drugs. Immunogenic cell death (ICD) has emerged as another approach for initiating antitumor immunity. ICD is triggered by tumor cells that display damage-associated molecular patterns (DAMPs). These DAMP molecules recruit and activate dendritic cells (DCs) that present tumor-specific antigens to T cells which eliminate neoplastic cells. Interestingly, the expression of DAMP molecules occurs in an endoplasmic reticulum (ER) stress-dependent manner. We have previously shown that ER stress was required for the cytotoxic activity of the endocannabinoid metabolite, 15-deoxy, Δ 12,14 prostamide J 2 (15dPMJ 2 ). As such, the current study investigates whether 15dPMJ 2 induces DAMP signaling in melanoma. In B16F10 cells, 15dPMJ 2 caused a significant increase in the cell surface expression of calreticulin (CRT), the release of ATP and the secretion of high-mobility group box 1 (HMGB1), three molecules that serve as surrogate markers of ICD. 15dPMJ 2 also stimulated the cell surface expression of the DAMP molecules, heat shock protein 70 (Hsp70) and Hsp90. In addition, the display of CRT and ATP was increased by 15dPMJ 2 to a greater extent in tumorigenic compared to non-tumorigenic melanocytes. Consistent with this finding, the activation of bone marrow-derived DCs was upregulated in co-cultures with 15dPMJ 2 -treated tumor compared to non-tumor melanocytes. Moreover, 15dPMJ 2 -mediated DAMP exposure and DC activation required the electrophilic cyclopentenone double bond within the structure of 15dPMJ 2 and the ER stress pathway. These results demonstrate that 15dPMJ 2 is a tumor-selective inducer of DAMP signaling in melanoma., Competing Interests: CONFLICTS OF INTEREST RVD, DL, RE and CB have ownership interest (including awarded and pending patents) in 15dPMJ2. The remaining authors have no conflicts of interest to declare., (Copyright: © 2020 Elhassanny et al.)

15-deoxy, Δ 12,14 -prostaglandin J 2 -ethanolamide, also known as 15-deoxy, Δ 12,14 -prostamide J 2 (15d-PMJ 2 ) is a novel product of the metabolism of arachidonoyl ethanolamide (AEA) by COX-2. 15d-PMJ 2 preferentially induced cell death and apoptosis in tumorigenic A431 keratinocytes and B16F10 melanoma cells compared with nontumorigenic HaCaT keratinocytes and Melan-A melanocytes. Activation of the ER stress execution proteins, PERK and CHOP10, was evaluated to determine whether this process was involved in 15d-PMJ 2 cell death. 15d-PMJ 2 increased the phosphorylation of PERK and expression of CHOP10 in tumorigenic but not nontumorigenic cells. The known ER stress inhibitors, salubrinal and 4-phenylbutaric acid, significantly inhibited 15d-PMJ 2 -mediated apoptosis, suggesting ER stress as a primary apoptotic mediator. Furthermore, the reactive double bond present within the cyclopentenone structure of 15d-PMJ 2 was identified as a required moiety for the induction of ER stress apoptosis. The effect of 15d-PMJ 2 on B16F10 melanoma growth was also evaluated by dosing C57BL/6 mice with 0.5 mg/kg 15d-PMJ 2 Tumors of animals treated with 15d-PMJ 2 exhibited significantly reduced growth and mean weights compared with vehicle and untreated animals. TUNEL and IHC analysis of tumor tissues showed significant cell death and ER stress in tumors of 15d-PMJ 2 -treated compared with control group animals. Taken together, these findings suggest that the novel prostamide, 15d-PMJ 2 , possesses potent antitumor activity in vitro and in vivo Mol Cancer Ther; 16(5); 838-49. ©2017 AACR ., (©2017 American Association for Cancer Research.)