Search

Abstract Malaria, caused by Plasmodium parasites, imposes a significant health burden and live-attenuated parasites are being pursued as vaccines. Here, we report on the creation of a genetically attenuated parasite by the deletion of Plasmodium LINUP, encoding a liver stage nuclear protein. In the rodent parasite Plasmodium yoelii, LINUP expression was restricted to liver stage nuclei after the onset of liver stage schizogony. Compared to wildtype P. yoelii, P. yoelii LINUP gene deletion parasites (linup —) exhibited no phenotype in blood stages and mosquito stages but suffered developmental arrest late in liver stage schizogony with a pronounced defect in exo-erythrocytic merozoite formation. This defect caused severe attenuation of the liver stage-to-blood stage transition and immunization of mice with linup — parasites conferred robust protection against infectious sporozoite challenge. LINUP gene deletion in the human parasite Plasmodium falciparum also caused a severe defect in late liver stage differentiation. Importantly, P. falciparum linup — liver stages completely failed to transition from the liver stage to a viable blood stage infection in a humanized mouse model. These results suggest that P. falciparum LINUP is an ideal target for late liver stage attenuation that can be incorporated into a late liver stage-arresting replication competent whole parasite vaccine.

A 2022 canine gastroenteritis outbreak in the United Kingdom was associated with circulation of a new canine enteric coronavirus closely related to a 2020 variant with an additional spike gene recombination. The variants are unrelated to canine enteric coronavirus–like viruses associated with human disease but represent a model for coronavirus population adaptation.

Summary: Mir483 is a conserved and highly expressed microRNA in placental mammals, embedded within the Igf2 gene. Its expression is dysregulated in a number of human diseases, including metabolic disorders and certain cancers. Here, we investigate the developmental regulation and function of Mir483 in vivo. We find that Mir483 expression is dependent on Igf2 transcription and the regulation of the Igf2/H19 imprinting control region. Transgenic Mir483 overexpression in utero causes fetal, but not placental, growth restriction through insulin-like growth factor 1 (IGF1) and IGF2 and also causes cardiovascular defects leading to fetal death. Overexpression of Mir483 post-natally results in growth stunting through IGF1 repression, increased hepatic lipid production, and excessive adiposity. IGF1 infusion rescues the post-natal growth restriction. Our findings provide insights into the function of Mir483 as a growth suppressor and metabolic regulator and suggest that it evolved within the INS-IGF2-H19 transcriptional region to limit excessive tissue growth through repression of IGF signaling.

Abstract Advanced epithelial ovarian cancer (EOC) survival rates are dishearteningly low, with ~25% surviving beyond 5 years. Evidence suggests that cancer stem cells contribute to acquired chemoresistance and tumor recurrence. Here, we show that IRAK1 is upregulated in EOC tissues, and enhanced expression correlates with poorer overall survival. Moreover, low molecular weight hyaluronic acid, which is abundant in malignant ascites from patients with advanced EOC, induced IRAK1 phosphorylation leading to STAT3 activation and enhanced spheroid formation. Knockdown of IRAK1 impaired tumor growth in peritoneal disease models, and impaired HA-induced spheroid growth and STAT3 phosphorylation. Finally, we determined that TCS2210, a known inducer of neuronal differentiation in mesenchymal stem cells, is a selective inhibitor of IRAK1. TCS2210 significantly inhibited EOC growth in vitro and in vivo both as monotherapy, and in combination with cisplatin. Collectively, these data demonstrate IRAK1 as a druggable target for EOC.

Abstract The CoLab score was developed and externally validated to rule out COVID-19 among suspected patients presenting at the emergency department. We hypothesized a within-patient decrease in the CoLab score over time in an intensive care unit (ICU) cohort. Such a decrease would create the opportunity to potentially rule out the need for isolation when the infection is overcome. Using linear mixed-effects models, data from the Maastricht Intensive Care COVID (MaastrICCht) cohort were used to investigate the association between time and the CoLab score. Models were adjusted for sex, APACHE II score, ICU mortality, and daily SOFA score. The CoLab score decreased by 0.30 points per day (95% CI − 0.33 to − 0.27), independent of sex, APACHE II, and Mortality. With increasing SOFA score over time, the CoLab score decreased more strongly (− 0.01 (95% CI − 0.01 to − 0.01) additional decrease per one-point increase in SOFA score.) The CoLab score decreased in ICU patients on mechanical ventilation for COVID-19, with a one-point reduction per three days, independent of sex, APACHE II, and ICU mortality, and somewhat stronger with increasing multi-organ failure over time. This suggests that the CoLab score would decrease below a threshold where COVID-19 can be excluded.

Abstract RfaH, a paralog of the universally conserved NusG, binds to RNA polymerases (RNAP) and ribosomes to activate expression of virulence genes. In free, autoinhibited RfaH, an α-helical KOW domain sequesters the RNAP-binding site. Upon recruitment to RNAP paused at an ops site, KOW is released and refolds into a β-barrel, which binds the ribosome. Here, we report structures of ops-paused transcription elongation complexes alone and bound to the autoinhibited and activated RfaH, which reveal swiveled, pre-translocated pause states stabilized by an ops hairpin in the non-template DNA. Autoinhibited RfaH binds and twists the ops hairpin, expanding the RNA:DNA hybrid to 11 base pairs and triggering the KOW release. Once activated, RfaH hyper-stabilizes the pause, which thus requires anti-backtracking factors for escape. Our results suggest that the entire RfaH cycle is solely determined by the ops and RfaH sequences and provide insights into mechanisms of recruitment and metamorphosis of NusG homologs across all life.

Abstract Malaria-causing Plasmodium parasites first replicate as liver stages (LS), which then seed symptomatic blood stage (BS) infection. Emerging evidence suggests that these stages impact each other via perturbation of host responses, and this influences the outcome of natural infection. We sought to understand whether the parasite stage interplay would affect live-attenuated whole parasite vaccination, since the efficacy of whole parasite vaccines strongly correlates with their extend of development in the liver. We thus investigated the impact of BS infection on LS development of genetically attenuated and wildtype parasites in female rodent malaria models and observed that for both, LS infection suffered severe suppression during concurrent BS infection. Strikingly and in contrast to previously published studies, we find that the BS-induced iron-regulating hormone hepcidin is not mediating suppression of LS development. Instead, we demonstrate that BS-induced host interferons are the main mediators of LS developmental suppression. The type of interferon involved depended on the BS-causing parasite species. Our study provides important mechanistic insights into the BS-mediated suppression of LS development. This has direct implications for understanding the outcomes of live-attenuated Plasmodium parasite vaccination in malaria-endemic areas and might impact the epidemiology of natural malaria infection.

Abstract Background Lung cancer is associated with the greatest cancer mortality as it typically presents with incurable distributed disease. Biomarkers relevant to risk assessment for the detection of lung cancer continue to be a challenge because they are often not detectable during the asymptomatic curable stage of the disease. A solution to population-scale testing for lung cancer will require a combination of performance, scalability, cost-effectiveness, and simplicity. Methods One solution is to measure the activity of serum available enzymes that contribute to the transformation process rather than counting biomarkers. Protease enzymes modify the environment during tumor growth and present an attractive target for detection. An activity based sensor platform sensitive to active protease enzymes is presented. A panel of 18 sensors was used to measure 750 sera samples from participants at increased risk for lung cancer with or without the disease. Results A machine learning approach is applied to generate algorithms that detect 90% of cancer patients overall with a specificity of 82% including 90% sensitivity in Stage I when disease intervention is most effective and detection more challenging. Conclusion This approach is promising as a scalable, clinically useful platform to help detect patients who have lung cancer using a simple blood sample. The performance and cost profile is being pursued in studies as a platform for population wide screening.

Exact three-dimensional (3D) structural information of developing organoids is key for optimising organoid generation and for studying experimental outcomes in organoid models. We set up a 3D imaging technique and studied complexly arranged native and experimentally challenged cardioids of two stages of remodelling. The imaging technique we employed is S-HREM (Scanning High Resolution Episcopic Microscopy), a variant of HREM, which captures multiple images of subsequently exposed surfaces of resin blocks and automatically combines them to large sized digital volume data of voxels sizes below 1 μm3. We provide precise volumetric information of the examined specimens and their single components and comparisons between stages in terms of volume and micro- and macroanatomic structure. We describe the 3D arrangement and lining of different types of cavities and their changes between day 10 and day 14 and map the various cell types to their precise spatial and structural environment. Exemplarily, we conducted semiautomatic counts of nuclei. In cryo-injured cardioids, we examined the extension and composition of the injured areas. Our results demonstrate the high quality and the great potential of digital volume data produced with S-HREM. It also provides sound metric and structural information, which assists production of native and experimentally challenged left ventricle cardioids and interpretation of their structural remodelling.

ABSTRACT Piperaquine (PPQ) is widely used in combination with dihydroartemisinin as a first-line treatment against malaria. Multiple genetic drivers of PPQ resistance have been reported, including mutations in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and increased copies of plasmepsin II/III (pm2/3). We generated a cross between a Cambodia-derived multidrug-resistant KEL1/PLA1 lineage isolate (KH004) and a drug-susceptible Malawian parasite (Mal31). Mal31 harbors a wild-type (3D7-like) pfcrt allele and a single copy of pm2/3, while KH004 has a chloroquine-resistant (Dd2-like) pfcrt allele with an additional G367C substitution and multiple copies of pm2/3. We recovered 104 unique recombinant parasites and examined a targeted set of progeny representing all possible combinations of variants at pfcrt and pm2/3. We performed a detailed analysis of competitive fitness and a range of PPQ susceptibility phenotypes with these progenies, including PPQ survival assay, area under the dose response curve, and a limited point IC50. We find that inheritance of the KH004 pfcrt allele is required for reduced PPQ sensitivity, whereas copy number variation in pm2/3 further decreases susceptibility but does not confer resistance in the absence of additional mutations in pfcrt. A deep investigation of genotype-phenotype relationships demonstrates that progeny clones from experimental crosses can be used to understand the relative contributions of pfcrt, pm2/3, and parasite genetic background to a range of PPQ-related traits. Additionally, we find that the resistance phenotype associated with parasites inheriting the G367C substitution in pfcrt is consistent with previously validated PPQ resistance mutations in this transporter.IMPORTANCEResistance to piperaquine, used in combination with dihydroartemisinin, has emerged in Cambodia and threatens to spread to other malaria-endemic regions. Understanding the causal mutations of drug resistance and their impact on parasite fitness is critical for surveillance and intervention and can also reveal new avenues to limiting the evolution and spread of drug resistance. An experimental genetic cross is a powerful tool for pinpointing the genetic determinants of key drug resistance and fitness phenotypes and has the distinct advantage of quantifying the effects of naturally evolved genetic variation. Our study was strengthened since the full range of copies of KH004 pm2/3 was inherited among the progeny clones, allowing us to directly test the role of the pm2/3 copy number on resistance-related phenotypes in the context of a unique pfcrt allele. Our multigene model suggests an important role for both loci in the evolution of this multidrug-resistant parasite lineage.

Combinatorial optimization is a challenging problem applicable in a wide range of fields from logistics to finance. Recently, quantum computing has been used to attempt to solve these problems using a range of algorithms, including parameterized quantum circuits, adiabatic protocols, and quantum annealing. These solutions typically have several challenges: 1) there is little to no performance gain over classical methods; 2) not all constraints and objectives may be efficiently encoded in the quantum ansatz; and 3) the solution domain of the objective function may not be the same as the bit strings of measurement outcomes. This work presents “nonnative hybrid algorithms”: a framework to overcome these challenges by integrating quantum and classical resources with a hybrid approach. By designing nonnative quantum variational anosatzes that inherit some but not all problem structure, measurement outcomes from the quantum computer can act as a resource to be used by classical routines to indirectly compute optimal solutions, partially overcoming the challenges of contemporary quantum optimization approaches. These methods are demonstrated using a publicly available neutral-atom quantum computer on two simple problems of Max $k$-Cut and maximum independent set. We find improvements in solution quality when comparing the hybrid algorithm to its “no quantum” version, a demonstration of a “comparative advantage.”

Notes on four Festucula species are provided. One species, F. botswana sp. nov., is described as new to science (♀, Botswana). The name F. monticola is revalidated and the male of this species is assigned. The female of F. lawrencei is described for the first time. A new record of F. leroyae is provided.

Goats are natural hosts of Mycobacterium (M.) bovis, and affected herds can be the cause of significant economic losses. Similarites in disease course and lesions of M. bovis infections in goats and M. tuberculosis in humans make goats good models for human tuberculosis. The aim of this investigation was to characterize M. bovis challenge models in goats. For this, goats were endobronchially inoculated with three doses of M. bovis or culture medium. Clinical signs, shedding, and immune responses were monitored until 146 days post inoculation (dpi). At necropsy, lesions were examined by computed tomography, histology, and bacteriological culture. Infected goats did not develop clinical signs. M. bovis was cultured from feces, but never from nasal swabs. IGRAs were positive from 28 dpi onwards, antibodies at 140 dpi, and SICCT at 146 dpi. The increase in CD25+, IFN-γ+, and IFN-γ-releasing T-cell subpopulations was time-related, but not dose-dependent. All infected goats developed paucibacillary granulomas in the lungs and regional lymph nodes. M. bovis was regularly cultured. Dose-dependent effects included the size of pulmonary lesions, caverns, intestinal lesions, and early generalization in the high-dose group. In summary, reproducible challenge models with dose-dependent differences in lesions were established, which may serve for testing vaccines for veterinary or medical use.

Abstract Most animal cell types are classified as non‐excitable because they do not generate action potentials observed in excitable cells, such as neurons and muscle cells. Thus, resolving voltage signals in non‐excitable cells demands sensors with exceptionally high voltage sensitivity. In this study, the ultrabright, ultrasensitive, and calibratable genetically encoded voltage sensor rEstus is developed using structure‐guided engineering. rEstus is most sensitive in the resting voltage range of non‐excitable cells and offers a 3.6‐fold improvement in brightness change for fast voltage spikes over its precursor ASAP3. Using rEstus, it is uncovered that the membrane voltage in several non‐excitable cell lines (A375, HEK293T, MCF7) undergoes spontaneous endogenous alterations on a second to millisecond timescale. Correlation analysis of these optically recorded voltage alterations provides a direct, real‐time readout of electrical cell–cell coupling, showing that visually connected A375 and HEK293T cells are also largely electrically connected, while MCF7 cells are only weakly coupled. The presented work provides enhanced tools and methods for non‐invasive voltage imaging in living cells and demonstrates that spontaneous endogenous membrane voltage alterations are not limited to excitable cells but also occur in a variety of non‐excitable cell types.

ABSTRACT Activin A strongly influences immune responses; yet, few studies have examined its role in infectious diseases. We measured serum activin A levels in two independent tuberculosis (TB) patient cohorts and in patients with pneumonia and sarcoidosis. Serum activin A levels were increased in TB patients compared to healthy controls, including those with positive tuberculin skin tests, and paralleled severity of disease, assessed by X-ray scores. In pneumonia patients, serum activin A levels were also raised, but in sarcoidosis patients, levels were lower. To determine whether blockade of the activin A signaling axis could play a functional role in TB, we harnessed a soluble activin type IIB receptor fused to human IgG1 Fc, ActRIIB-Fc, as a ligand trap in a murine TB model. The administration of ActRIIB-Fc to Mycobacterium tuberculosis-infected mice resulted in decreased bacterial loads and increased numbers of CD4 effector T cells and tissue-resident memory T cells in the lung. Increased frequencies of tissue-resident memory T cells corresponded with downregulated T-bet expression in lung CD4 and CD8 T cells. Altogether, the results suggest a disease-exacerbating role of ActRIIB signaling pathways. Serum activin A may be useful as a biomarker for diagnostic triage of active TB or monitoring of anti-tuberculosis therapy.IMPORTANCETuberculosis remains the leading cause of death by a bacterial pathogen. The etiologic agent of tuberculosis, Mycobacterium tuberculosis, can remain dormant in the infected host for years before causing disease. Significant effort has been made to identify biomarkers that can discriminate between latently infected and actively diseased individuals. We found that serum levels of the cytokine activin A were associated with increased lung pathology and could discriminate between active tuberculosis and tuberculin skin-test-positive healthy controls. Activin A signals through the ActRIIB receptor, which can be blocked by administration of the ligand trap ActRIIB-Fc, a soluble activin type IIB receptor fused to human IgG1 Fc. In a murine model of tuberculosis, we found that ActRIIB-Fc treatment reduced mycobacterial loads. Strikingly, ActRIIB-Fc treatment significantly increased the number of tissue-resident memory T cells. These results suggest a role for ActRIIB signaling pathways in host responses to Mycobacterium tuberculosis and activin A as a biomarker of ongoing disease.

BackgroundSeborrheic dermatitis (SD) affects 18.6%-59% of persons with Parkinson disease (PD), and recent studies provide evidence that oral cannabidiol (CBD) therapy could reduce sebum production in addition to improving motor and psychiatric symptoms in PD. Therefore, oral CBD could be useful for improving symptoms of both commonly co-occurring conditions. ObjectiveThis study investigates whether oral CBD therapy is associated with a decrease in SD severity in PD. MethodsFacial photographs were collected as a component of a randomized (1:1 CBD vs placebo), parallel, double-blind, placebo-controlled trial assessing the efficacy of a short-term 2.5 mg per kg per day oral sesame solution CBD-rich cannabis extract (formulated to 100 mg/mL CBD and 3.3 mg/mL THC) for reducing motor symptoms in PD. Participants took 1.25 mg per kg per day each morning for 4 ±1 days and then twice daily for 10 ±4 days. Reviewers analyzed the photographs independently and provided a severity ranking based on the Seborrheic Dermatitis Area and Severity Index (SEDASI) scale. Baseline demographic and disease characteristics, as well as posttreatment SEDASI averages and the presence of SD, were analyzed with 2-tailed t tests and Pearson χ2 tests. SEDASI was analyzed with longitudinal regression, and SD was analyzed with generalized estimating equations. ResultsA total of 27 participants received a placebo and 26 received CBD for 16 days. SD severity was low in both groups at baseline, and there was no treatment effect. The risk ratio for patients receiving CBD, post versus pre, was 0.69 (95% CI 0.41-1.18; P=.15), compared to 1.20 (95% CI 0.88-1.65; P=.26) for the patients receiving the placebo. The within-group pre-post change was not statistically significant for either group, but they differed from each other (P=.07) because there was an estimated improvement for the CBD group and an estimated worsening for the placebo group. ConclusionsThis study does not provide solid evidence that oral CBD therapy reduces the presence of SD among patients with PD. While this study was sufficiently powered to detect the primary outcome (efficacy of CBD on PD motor symptoms), it was underpowered for the secondary outcomes of detecting changes in the presence and severity of SD. Multiple mechanisms exist through which CBD can exert beneficial effects on SD pathogenesis. Larger studies, including participants with increased disease severity and longer treatment periods, may better elucidate treatment effects and are needed to determine CBD’s true efficacy for affecting SD severity. Trial RegistrationClinicalTrials.gov NCT03582137; https://clinicaltrials.gov/ct2/show/NCT03582137

A checklist of 2265 spider species and subspecies, 495 genera and 71 families is provided. Data were extracted from the South African National Survey of Arachnida database and over 200 taxonomic revisions, ending December 2022. Global distributions, endemicity and conservation assessment using IUCN Criteria are provided for each species. A total of 1325 spp. are endemic to South Africa (58.5%), 126 spp. (5.6%) are of special concern and 693 spp. (30.6%) are Data Deficient (DD), while 15 species were described without exact locality data. Most species (1444 spp., 63.8%) are widely distributed with no known threats and are of Least Concern. A total of 1316 spp. (57.6%) are known from both sexes and 23 spp. (1.0%) were described from juveniles. Salticidae is the most species-rich family (354 spp.), followed by Gnaphosidae (195 spp.), Thomisidae (143 spp.) and Araneidae (100 spp.) and ten families are represented by a single species.

The mononuclear phagocyte system includes monocytes, macrophages, some dendritic cells, and multinuclear giant cells. These cell populations display marked heterogeneity depending on their differentiation from embryonic and bone marrow hematopoietic progenitors, tissue location, and activation. They contribute to tissue homeostasis by interacting with local and systemic immune and non-immune cells through trophic, clearance, and cytocidal functions. During evolution, they contributed to the innate host defense before effector mechanisms of specific adaptive immunity emerged. Mouse macrophages appear at mid-gestation and are distributed throughout the embryo to facilitate organogenesis and clear cells undergoing programmed cell death. Yolk sac, AGM, and fetal liver-derived tissue-resident macrophages persist throughout postnatal and adult life, supplemented by bone marrow-derived blood monocytes, as required after injury and infection. Nobel awards to Elie Metchnikoff and Paul Ehrlich in 1908 drew attention to cellular phagocytic and humoral immunity, respectively. In 2011, prizes were awarded to Jules Hoffmann and Bruce Beutler for contributions to innate immunity and to Ralph Steinman for the discovery of dendritic cells and their role in antigen presentation to T lymphocytes. We trace milestones in the history of mononuclear phagocyte research from the perspective of Nobel awards bearing directly and indirectly on their role in cellular immunity.

This research was aimed at comparing the fire characteristics of different types of pepper in the context of explosion prevention. The following characteristics were studied: explosion pressure Pmax and Kst at selected concentrations, ignition temperature of the deposited dust layer from the hot surface, and minimum ignition energy. The comparison of the chemical properties of the used types of pepper was performed using TG/DSC. The results of the measurements suggest that different types of peppers exhibit different explosion characteristics. Each sample reached the maximum value of the explosion pressure and rate of pressure rise at different concentrations. The volume of the explosion chamber used also influenced the explosion characteristics. It is a consequence of the fact that the explosion characteristics strongly depend on the mechanism of action of a particular igniter. The minimum effect on the safety characteristics was observed when measuring the minimum ignition energy and the minimum ignition temperature of the dust layer from the hot surface. The results of the measurements suggest that different types of peppers exhibit different explosion characteristics. This information should then be considered in explosion prevention.

Safety characteristics are used to keep processes, including flammable gases, vapors, and combustible dusts, safe. In the standards for the determination of safety characteristics of gases and vapors, the induction spark is commonly used. However, classic transformers are hard to obtain, and replacement with new electronic transformers is not explicitly allowed in the standards. This article presents the investigation of five gases that are normally used to calibrate devices for the determination of safety characteristics, the maximum experimental safe gap (MESG), with an electronic transformer, and the values are compared to the ones that are obtained with the standard transformer. Additionally, calorimetric measurements on the net energy of both ignition sources were performed as well as open-circuit voltage measurements. It is concluded that the classic type of transformer can be replaced by the new type obtaining the same results for the MESG and introducing the same amount of energy into the system.

Abstract Objective To evaluate the concept and efficacy of an adjustable implant (Prototype SH30: porcine implant and APrevent® VOIS: human concept) for treatment of unilateral vocal fold paralysis (UVFP) via in vivo mini‐pig studies, human computed tomographic (CT) and magnetic resonance (MR) image analysis, ex‐vivo aerodynamic and acoustic analysis. Methods Feasibility testing and prototype implantation were performed using in‐vivo UVFP porcine model (n = 8), followed by a dimensional finding study using CT and MR scans of larynges (n = 75) for modification of the implant prototypes. Acoustic and aerodynamic measurements were recorded on excised canine (n = 7) larynges with simulated UVFP before and after medialization with VOIS‐Implant. Results The prototype showed in the in‐vivo UVFP porcine model an improved glottic closure from grade 6 incomplete closure to complete closure (n = 5), to grade 2 incomplete closure (n = 2) and grade 3 incomplete closure (n = 1). On human CT/MR scans the identification of the correct size was successful in 97.3% using the thyroid cartilage alar “distance S” as the only parameter, which is an important step towards procedure standardization and implant design. Results were confirmed with implantation in human laryngeal cadavers (n = 44). Measurements of the acoustic and aerodynamic effects after implantation showed a significant decreased phonation threshold pressure (p = .0187), phonation threshold flow (p = .0001) and phonation threshold power (p = .0046) on excised canine larynges with simulated UVFP. Percent jitter and percent shimmer decreased (p = .2976; p = .1771) but not significant. Conclusions Based on the preclinical results four sizes, differing in medial length, implant width and expansion direction of silicone cushions, seem to be enough to satisfy laryngeal size variations. This concept is significantly effective in medializing UVFP and improving the aerodynamic and acoustic qualities of phonation as reported in a preliminary clinical outcome study with long‐term implantation. Level of Evidence N/A

Summary: This study investigates the potential use of circulating extracellular vesicles’ (EVs) DNA and protein content as biomarkers for traumatic brain injury (TBI) in a mouse model. Despite an overall decrease in EVs count during the acute phase, there was an increased presence of exosomes (CD63+ EVs) during acute and an increase in microvesicles derived from microglia/macrophages (CD11b+ EVs) and astrocytes (ACSA-2+ EVs) in post-acute TBI phases, respectively. Notably, mtDNA exhibited an immediate elevation post-injury. Neuronal (NFL) and microglial (Iba1) markers increased in the acute, while the astrocyte marker (GFAP) increased in post-acute TBI phases. Novel protein biomarkers (SAA, Hp, VWF, CFD, CBG) specific to different TBI phases were also identified. Biostatistical modeling and machine learning identified mtDNA and SAA as decisive markers for TBI detection. These findings emphasize the importance of profiling EVs’ content and their dynamic release as an innovative diagnostic approach for TBI in liquid biopsies.

In order to contribute to spider diversity distribution records within Zimbabwe, spiders were sampled at a mixed wildlife and cattle ranch using pitfall traps and sweep-netting. Sampling was conducted from June 2017 to April 2018. A total of 2328 spiders representing 25 families, 94 genera, and 166 species were recorded. The most species-rich families were Salticidae (33 spp.), followed by the Gnaphosidae (28 spp.) and Lycosidae (20 spp.), while eight families were represented by a single species. Pitfall traps accounted for 1857 individuals overall, with the ground-dwelling fauna dominated by Stenaelurillus guttiger (37.86% of the total abundance). Sweep-nets accounted for 471 individuals overall, with the grass-dwelling fauna dominated by Thyene thyenioides (15.29% of the total abundance). The most abundant functional group was the free-living ground-dwellers (n = 1809, 77.71%), followed by free-living plant-dwellers (n = 266, 11.43%) and orb-web builders (n = 186, 7.98%). The current study contributes to the knowledge of a megadiverse group of predatory arthropods in the region. Conservation implications: Sampling and monitoring of rangelands is essential, as the former aids in the identification of new species not previously recorded, as well as increasing knowledge on the distribution of spider species, which if not adequately conserved could face significant threats to their survival even before their documentation.

Explosions of benzene, toluene and xylenes were carried out in a 16.7 L chamber in the presence of O2 at different fuel-rich molar ratios such that an aerosol of elemental carbon was produced. The product was a powder at higher precursor oxygen content and an aerosol gel at lower oxygen where the carbon yield was larger. The explosion temperature was measured by a spectrometer that detected black body, Planck radiation from the incandescent carbon, the analysis of which indicated temperatures in the range 2000–2500 K. The product collected was characterized by Raman, X-ray diffraction, Brunauer, Emmett and Teller (BET) specific surface area, high-resolution transmission electron microscopy (HRTEM), etc. HRTEM and Raman showed two product types: amorphous soot at a lower explosion temperature and few-layer graphene at a higher explosion temperature. BET showed that the graphene sample is highly porous and has a specific surface area of 388 m2/g. We conclude that chamber explosion of aromatic hydrocarbons can produce graphene, and the high explosion temperature during the reaction is the primary reason graphene is formed rather than soot.

Introduction Malaria, a devastating febrile illness caused by protozoan parasites, sickened 247,000,000 people in 2021 and killed 619,000, mostly children and pregnant women in sub-Saharan Africa. A highly effective vaccine is urgently needed, especially for Plasmodium falciparum (Pf), the deadliest human malaria parasite. Areas covered Sporozoites (SPZ), the parasite stage transmitted by Anopheles mosquitoes to humans, are the only vaccine immunogen achieving > 90% efficacy against Pf infection. This review describes > 30 clinical trials of PfSPZ vaccines in the U.S.A., Europe, Africa, and Asia, based on first-hand knowledge of the trials and PubMed searches of ‘sporozoites,’ ‘malaria,’ and ‘vaccines.’ Expert opinion First generation (radiation-attenuated) PfSPZ vaccines are safe, well tolerated, 80-100% efficacious against homologous controlled human malaria infection (CHMI) and provide 18-19 months protection without boosting in Africa. Second generation chemo-attenuated PfSPZ are more potent, 100% efficacious against stringent heterologous (variant strain) CHMI, but require a co-administered drug, raising safety concerns. Third generation, late liver stage-arresting, replication competent (LARC), genetically-attenuated PfSPZ are expected to be both safe and highly efficacious. Overall, PfSPZ vaccines meet safety, tolerability, and efficacy requirements for protecting pregnant women and travelers, with licensure for these populations possible within five years. Protecting children and mass vaccination programs to block transmission and eliminate malaria are long-term objectives.

Quantum computers are increasing in size and quality but are still very noisy. Error mitigation extends the size of the quantum circuits that noisy devices can meaningfully execute. However, state-of-the-art error mitigation methods are hard to implement and the limited qubit connectivity in superconducting qubit devices restricts most applications to the hardware's native topology. Here we show a quantum approximate optimization algorithm (QAOA) on nonplanar random regular graphs with up to 40 nodes enabled by a machine learning-based error mitigation. We use a swap network with careful decision-variable-to-qubit mapping and a feed-forward neural network to optimize a depth-two QAOA on up to 40 qubits. We observe a meaningful parameter optimization for the largest graph which requires running quantum circuits with 958 two-qubit gates. Our paper emphasizes the need to mitigate samples, and not only expectation values, in quantum approximate optimization. These results are a step towards executing quantum approximate optimization at a scale that is not classically simulable. Reaching such system sizes is key to properly understanding the true potential of heuristic algorithms like QAOA.

Coronavirus disease (Covid-19) has not only shaped awareness of the impact of infectious diseases on global health. It has also provided instructive lessons for better prevention strategies against new and current infectious diseases of major importance. Tuberculosis (TB) is a major current health threat caused by Mycobacterium tuberculosis (Mtb) which has claimed more lives than any other pathogen over the last few centuries. Hence, better intervention measures, notably novel vaccines, are urgently needed to accomplish the goal of the World Health Organization to end TB by 2030. This article describes how the research and development of TB vaccines can benefit from recent developments in the Covid-19 vaccine pipeline from research to clinical development and outlines how the field of TB research can pursue its own approaches. It begins with a brief discussion of major vaccine platforms in general terms followed by a short description of the most widely applied Covid-19 vaccines. Next, different vaccination regimes and particular hurdles for TB vaccine research and development are described. This specifically considers the complex immune mechanisms underlying protection and pathology in TB which involve innate as well as acquired immune mechanisms and strongly depend on fine tuning the response. A brief description of the TB vaccine candidates that have entered clinical trials follows. Finally, it discusses how experiences from Covid-19 vaccine research, development, and rollout can and have been applied to the TB vaccine pipeline, emphasizing similarities and dissimilarities.

Safety characteristics are widely used in industrial processes to avoid explosive atmospheres (primary explosion protection) or to mitigate the consequences of an explosion (constructive explosion protection). Several laboratory parameters influence the determined values when performing the test series such as the beginning pressure and the pre-ignition pressure rise, the ignition source, the ignition energy, the burning duration and volume or the concentration of the combustible substance. In the different standards for the determination of safety characteristics of dusts there is no statement about the scattering or the deviation when parameters are chosen or occur on the borders of their allowed range. Thus, two laboratories might determine values that are hardly comparable for the same given substance. This article summarizes some of the influential factors that cause a deviation and shows the inherent scattering of dust tests when all other parameters are kept constant. It also provides some advice how to minimize the deviation and the scattering with little effort.

Tick serine protease inhibitors (serpins) play crucial roles in tick feeding and pathogen transmission. We demonstrate that Ixodes scapularis (Ixs) nymph tick saliva serpin (S) 41 (IxsS41), secreted by Borrelia burgdorferi (Bb)-infected ticks at high abundance, is involved in regulating tick evasion of host innate immunity and promoting host colonization by Bb. Recombinant (r) proteins were expressed in Pichia pastoris, and substrate hydrolysis assays were used to determine. Ex vivo (complement and hemostasis function related) and in vivo (paw edema and effect on Bb colonization of C3H/HeN mice organs) assays were conducted to validate function. We demonstrate that rIxsS41 inhibits chymase and cathepsin G, pro-inflammatory proteases that are released by mast cells and neutrophils, the first immune cells at the tick feeding site. Importantly, stoichiometry of inhibition analysis revealed that 2.2 and 2.8 molecules of rIxsS41 are needed to 100% inhibit 1 molecule of chymase and cathepsin G, respectively, suggesting that findings here are likely events at the tick feeding site. Furthermore, chymase-mediated paw edema, induced by the mast cell degranulator, compound 48/80 (C48/80), was blocked by rIxsS41. Likewise, rIxsS41 reduced membrane attack complex (MAC) deposition via the alternative and lectin complement activation pathways and dose-dependently protected Bb from complement killing. Additionally, co-inoculating C3H/HeN mice with Bb together with rIxsS41 or with a mixture (rIxsS41 and C48/80). Findings in this study suggest that IxsS41 markedly contributes to tick feeding and host colonization by Bb. Therefore, we conclude that IxsS41 is a potential candidate for an anti-tick vaccine to prevent transmission of the Lyme disease agent.

Abstract Soil moisture deficits and water table dynamics are major biophysical controls on peat and non-peat fires in Indonesia. Development of modern fire forecasting models in Indonesia is hampered by the lack of scalable hydrologic datasets or scalable hydrology models that can inform the fire forecasting models on soil hydrologic behaviour. Existing fire forecasting models in Indonesia use weather data-derived fire probability indices, which often do not adequately proxy the sub-surface hydrologic dynamics. Here we demonstrate that soil moisture and water table dynamics can be simulated successfully across tropical peatlands and non-peatland areas by using a process-based eco-hydrology model (ecosys) and publicly available data for weather, soil, and management. Inclusion of these modelled water table depth and soil moisture contents significantly improves the accuracy of a neural network model in predicting active fires at two-weekly time scale. This constitutes an important step towards devising an operational fire early warning system for Indonesia.

Purpose Bio-effects following thermal treatments are a function of the achieved temperature profile in tissue, which can be estimated across tumor volumes with real-time MRI thermometry (MRIT). Here, we report on expansion of a previously developed small-animal microwave hyperthermia system integrated with MRIT for delivering thermal ablation to subcutaneously implanted tumors in mice.Methods Computational models were employed to assess suitability of the 2.45 GHz microwave applicators for delivering ablation to subcutaneous tumor targets in mice. Phantoms and ex-vivo tissues were heated to temperatures in the range 47–67 °C with custom-made microwave applicators for validating MRIT with the proton resonance frequency shift method against fiberoptic thermometry. HAC15 tumors implanted in nude mice (n = 6) were ablated in vivo and monitored with MRIT in multiple planes. One day post ablation, animals were euthanized, and excised tumors were processed for viability assessment.Results Average absolute error between temperatures from fiberoptic sensors and MRIT was 0.6 °C across all ex-vivo ablations. During in-vivo experiments, tumors with volumes ranging between 5.4–35.9 mm3 (mean 14.2 mm3) were ablated (duration: 103–150 s) to achieve 55 °C at the tumor boundary. Thermal doses ≥240 CEM43 were achieved across 90.7–98.0% of tumor volumes for four cases. Ablations were incomplete for remaining cases, attributed to motion-affected thermometry. Thermal dose-based ablative tumor coverage agreed with viability assessment of excised tumors.Conclusions We have developed a system for delivering microwave ablation to subcutaneous tumors in small animals under MRIT guidance and demonstrated its performance in-vivo.

Introduction: Complex integrated information on disease mechanisms and in-hospital outcomes in mild to moderate acute kidney injury (AKI) is scarce. Methods: The Stockholm Prospective AKI Cohort Study (SAKIS) included all patients (≥18 years, n = 1,519) with community-acquired AKI (KDIGO criteria) admitted to the nephrology ward at Danderyd University Hospital, Stockholm, Sweden, between 2009 and 2018. Detailed laboratory measures were registered. Odds ratio for hypo- and hyperkalemia, recovery of kidney function by 30% and 50%, and in-hospital mortality were assessed by logistic regression analysis. Results: Factors independently associated with the presence of hyperkalemia at admission were high age, high serum creatinine (sCr), and low C-reactive protein (CRP). Signs of malnutrition, inflammation, and acidosis were seen in 31% of patients. Kidney recovery, defined as a reduction of sCr by 30% in-hospital (63% of all patients), was associated with higher age, female sex, lower body mass index (BMI), higher hemoglobin, and higher CRP. Factors independently associated with mortality (4.4% of patients) were high age, high BMI, and low albumin. Conclusion: This study provides a detailed description of community-acquired AKI and comprehensive analyses of integrated clinical and laboratory data associated with kidney recovery. Features related to anemia, albuminuria, malnutrition, inflammation, and acidosis associate with partial or moderate short-term recovery of kidney function, with disturbances in potassium homeostasis, and with in-hospital mortality. Future studies are warranted to analyze the long-term consequences of AKI in terms of risk of kidney failure, cardiovascular morbidity, and mortality.

We present the first records of the butterfly theridiid Episinus marignaci (Lessert, 1933) beyond its type locality, resulting in an extension of its geographic range from Angola to South Africa. Images of live specimens and a dis-tribution map are provided. Episinus marignaci is rare locally but has a relatively large geographical distribution in South Africa.

Abstract Background Chronic kidney disease (CKD) is a recognized risk factor for severe complications in COVID-19. Our objective was to analyze the association between kidney function / T and B lymphocyte modulatory factors and risk of mortality in COVID-19 patients. Methods In-hospital and 30‐day mortality were analyzed in COVID‐19 patients (n = 110). Plasma levels of selected T and B cell modulators were analyzed and correlated to mortality risk. A subgroup of sex- and eGFR-matched COVID-19 patients was compared to CKD patients without infection and healthy subjects. Results COVID-19 patients who died in hospital and within 30 days had significantly higher BAFF and sCD25 plasma levels than survivors. In logistic regression models patients with high BAFF, sCD25 and sPD-L1 levels had significantly higher risk of both in-hospital and 30-day mortality while there was no association to eGFR. In the subgroup analysis, a higher level of BAFF, IFN-α, sCD25, sPD-L1 and a lower level of sCD40L was observed in COVID-19 patients compared to the CKD group with corresponding kidney function. Conclusions We demonstrate that kidney function and concentrations of BAFF, sCD25 and PD-L1, independent of previously recognized risk factors; age, male gender, and leukocytosis are associated with risk of in-hospital and 30-day mortality in patients with COVID-19. These data indicate the significance of adaptive immune system modulators in COVID-19 and motivate further analysis to identify new potential prognostic and therapeutic approaches.

ABSTRACT Sexual reproduction of the malaria parasites is critical for their transmission to a mosquito vector. Several signaling molecules, such as kinases and phosphatases, are known to regulate this process. We previously demonstrated that Plasmodium falciparum (Pf) Ca2+-dependent protein kinase 4 (CDPK4) and serine/arginine-rich protein kinase 1 (SRPK1) are critical for axoneme formation during male gametogenesis, with genetic deletion of either gene causing a complete block in parasite transmission to the mosquito. A comparative phospho-proteome analysis of Pfcdpk4− and RNA-seq analysis of Pfsrpk1− gametocytes showed that these kinases regulate similar biological processes linked to both microtubule (MT) dynamics and cell motility. One of these proteins was a nuclear MT-associated End Binding protein 1 (EB1), which was hypophosphorylated in Pfcdpk4− gametocytes. To study the functional relevance of EB1, we created gene deletion parasites for EB1. We further demonstrate that Pfeb1− parasites like WT NF54 parasites proliferate normally as asexuals and undergo gametocytogenesis and gametogenesis. Strikingly, these parasites suffer a severe defect in nuclear segregation and partitioning of nuclei into emerging microgametes. Further genetic crosses utilizing male- and female-sterile parasites revealed that Pfeb1− parasites only suffer a male fertility defect. Overall, our study reveals an essential function for PfEB1 in male gamete nuclear segregation and suggests a potential therapeutic avenue in the design of transmission-blocking drugs to prevent malaria transmission from humans to mosquito. IMPORTANCE Gametogenesis and subsequent gamete fusion are central to successful transmission of the malaria parasites to a female Anopheles mosquito vector and completion of the sexual phase of the parasite life cycle. Male gametogenesis involves the formation of axonemes inside male gametes from male gametocytes via active cytoskeleton remodeling. The tubulin and tubulin-binding proteins are, thus, attractive anti-malarial drug targets. In the present study, we demonstrate that a microtubule-binding protein PfEB1 is essential for male gamete fertility, specifically for the inheritance of nuclei from activated male gametocytes. Targeting PfEB1 function may provide new avenues into designing interventions to prevent malaria transmission and disease spread.

The water repellent behaviour of soils is a widely studied phenomenon given its implications for infiltration, runoff, erosion and preferential flow. However, the principles underlying the eventual penetration of water into affected soils remain poorly understood. Theoretical considerations of the energetics and kinetics involved as a water drop makes contact with a water repellent soil surface and eventually penetrates into the soil suggest three distinct stages in the overall process. These stages are 1) adhesional wetting as soil and water first make contact, followed by 2) a kinetic barrier transitional stage in which molecular reorganisation of organics on soil reduces the water-soil contact angle to allow the water drop to sit deeper over soil particles of initial contact such that there is contact with particles in directly underlying soil layers, and finally 3) branching interstitial wetting as water penetrates into the bulk soil. Studies presented here of optical microscopy, mass of soil initially wetted, penetration time through layers of soil of different thicknesses, and time-dependent measurements of contact angle, volume of water penetrated, and mass of soil wetted, all give results consistent with this model. However, only for highly water repellent soils can distinct stages in wetting be clearly resolved experimentally, presumably because only these soils have a high enough kinetic barrier in the transitional stage for good separation between stages. For less water repellent soils, while the general time dependent behaviour remains consistent with the model, the distinction between the three stages is not so easy to resolve experimentally. The roles of contact angle, particle size distribution and drop size in determining the rates of these stages is considered, and the implications of the model for understanding soil water repellency are discussed.

Magnetic resonance imaging (MRI) is a highly significant imaging platform for a variety of medical and research applications. However, the low spatiotemporal resolution of conventional MRI limits its applicability toward rapid acquisition of ultrahigh-resolution scans. Current aims at high-resolution MRI focus on increasing the accuracy of tissue delineation, assessments of structural integrity, and early identification of malignancies. Unfortunately, high-resolution imaging often leads to decreased signal/noise (SNR) and contrast/noise (CNR) ratios and increased time cost, which are unfeasible in many clinical and academic settings, offsetting any potential benefits. In this study, we apply and assess the efficacy of super-resolution reconstruction (SRR) through iterative back-projection utilizing through-plane voxel offsets. SRR allows for high-resolution imaging in condensed time frames. Rat skulls and archerfish samples, typical models in academic settings, were used to demonstrate the impact of SRR on varying sample sizes and applicability for translational and comparative neuroscience. The SNR and CNR increased in samples that did not fully occupy the imaging probe and in instances where the low-resolution data were acquired in three dimensions, while the CNR was found to increase with both 3D and 2D low-resolution data reconstructions when compared with directly acquired high-resolution images. Limitations to the applied SRR algorithm were investigated to determine the maximum ratios between low-resolution inputs and high-resolution reconstructions and the overall cost effectivity of the strategy. Overall, the study revealed that SRR could be used to decrease image acquisition time, increase the CNR in nearly all instances, and increase the SNR in small samples.

Climate and insect pests are vital variables that affect crop production. Climate change will alter the magnitude and timing of precipitation, but how rainfall and temperature interact to affect insect pest damage in agriculture is poorly understood. Here, we explore the interacting effects of elevation and contrasting weather conditions (a wet vs. dry year) on macadamia nut quality, which is strongly affected by insect pests. For two years, we sampled macadamia nuts at 40 plots, stratified across ten farms along an elevational gradient in subtropical Limpopo province of South Africa. As measures of nut quality, we related total kernel recovery, nut immaturity, and kernel insect damage to precipitation and elevation. Higher rainfall reduced nut quality in all three response variables, while colder temperatures at higher elevations mitigated this effect. Our findings suggest that future warmer temperatures, more intense and wetter rainy seasons could lead to lowered macadamia nut quality even at higher elevations and economic losses to the industry.

Temperature is the most influential condition affecting insect development and population dynamics. Understanding its impact and other important factors, such as diet, could provide fine-scale predictions of species abundance and distribution in space and time. The two-spotted stink bug, Bathycoelia distincta Distant (Hemiptera: Pentatomidae), is a significant pest of macadamia in South Africa for which limited information on developmental biology exists. Here, for the first time, variations in key developmental parameters of the B. distincta biology were studied systematically. The developmental duration, survival rate, development rate, lower developmental threshold (Tmin), optimum developmental threshold (Topt), upper developmental threshold (Tmax), and thermal constant were quantified for each developmental stage of B. distincta. In addition, the effect of diet (macadamia nut and sweetcorn) on the developmental duration and survival rate were quantified. This study was conducted at five constant temperatures (18, 21, 22, 25, and 29 °C) with relative humidity (RH) variations. The developmental duration from egg to adult decreased significantly with increased temperature: 21 °C (±60 days) to 29 °C (±32 days). The survival rate was significantly different for instar 2 between temperatures. Nymphs (instars 2 and 4) developed faster on the sweetcorn diet than on a macadamia diet, but the total developmental time did not differ significantly between the diets. Development from egg to adult required 783 degree days (DD), with a Tmin of 13.5 °C, Topt of 29.5 °C, and Tmax of 38 °C. Ongoing global warming will increase the population growth of B. distincta through increased development rate, resulting in more damage to macadamia nuts. Understanding the developmental biology and thresholds for the DD model of B. distincta is fundamental for predicting its phenology and outbreaks in macadamia orchards.

Abstract Heme, an iron-protoporphyrin IX complex, is a cofactor bound to various hemoproteins and supports a broad range of functions, such as electron transfer, oxygen transport, signal transduction, and drug metabolism. In recent years, there has been a growing recognition of heme as a non-genomic modulator of ion channel functions. Here, we show that intracellular free heme and hemin modulate human ether à go-go (hEAG1, Kv10.1) voltage-gated potassium channels. Application of hemin to the intracellular side potently inhibits Kv10.1 channels with an IC 50 of about 4 nM under ambient and 63 nM under reducing conditions in a weakly voltage-dependent manner, favoring inhibition at resting potential. Functional studies on channel mutants and biochemical analysis of synthetic and recombinant channel fragments identified a heme-binding motif CxHx8H in the C-linker region of the Kv10.1 C terminus, with cysteine 541 and histidines 543 and 552 being important for hemin binding. Binding of hemin to the C linker may induce a conformational constraint that interferes with channel gating. Our results demonstrate that heme and hemin are endogenous modulators of Kv10.1 channels and could be exploited to modulate Kv10.1-mediated cellular functions.

Abstract A study of the detonation synthesis method to make graphene and the properties of the resulting graphene is presented. The gaseous precursors are mixtures of oxygen and acetylene with oxygen/carbon molar ratios of O/C = 0.25 to 0.75. Chamber pressure and temperature data indicate pressures ≤ 300 psi and temperatures of 2550 ± 100K after initiation of the reaction mixture. The graphene material collected from the chamber after the detonation was characterized by Raman, XRD (X‐ray diffraction), BET, SEM (scanning electron microscopy), TEM (transmission electron microscopy), and so on. The material properties divide into two groups: low O/C (≤ 0.45) and high O/C (≥ 0.5). Low O/C graphene appears as a low density, aerosol gel with ∼8 weakly associated, disordered turbostratic layers with a lateral extent of 20 to 30 nm. High O/C graphene appears as a denser powder with ∼30 weakly associated turbostratic layers, with a lateral extent of 100 to 200 nm. We conclude, as we have previously, that the high detonation temperature during the reaction is the primary reason that graphene is formed rather than soot. Differentiation into two types of graphene products is hypothesized to be a result of aggregation kinetics to form a static gel that pre‐empts layering (stacking) when O/C is low.

Abstract Vaccine-induced sterilizing protection from infection by Plasmodium parasites, the pathogens that cause malaria, will be essential in the fight against malaria as it would prevent both malaria-related disease and transmission. Stopping the relatively small number of parasites injected by the mosquito before they can migrate from the skin to the liver is an attractive means to this goal. Antibody-eliciting vaccines have been used to pursue this objective by targeting the major parasite surface protein present during this stage, the circumsporozoite protein (CSP). While CSP-based vaccines have recently had encouraging success in disease reduction, this was only achieved with extremely high antibody titers and appeared less effective for a complete block of infection (i.e., sterile protection). While such disease reduction is important, these and other results indicate that strategies focusing on CSP alone may not achieve the high levels of sterile protection needed for malaria eradication. Here, we show that monoclonal antibodies (mAbs) recognizing another sporozoite protein, TRAP/SSP2, exhibit a range of inhibitory activity and that these mAbs may augment CSP-based protection despite conferring no sterile protection on their own. Therefore, pursuing a multivalent subunit vaccine immunization is a promising strategy for improving infection-blocking malaria vaccines.

Tropical peatlands in Southeast Asia are a significant carbon sink, but are under major threat of fire resulting in significant carbon emissions. This study focused on the residual ash method, which has not been applied before for a tropical peatland, to determine the amount of carbon lost due to fire along two transects. To evaluate the method in a tropical peatland, we sampled peat cores to a depth of 150 cm along two transects in a drainage-affected peatland in Brunei Darussalam and analysed Landsat images to determine burn count at individual sampling locations between 1988 and 2020. The ash residue method indicated that the carbon release from the two transects was 3.61 ± 1.08 kg m-2 and 3.77 ± 0.80 kg m-2 respectively due to peat decomposition and fire. However, our results show that although some locations burned up to five times, the expected ash content (of at least 4 %) was not found in the surface peat. Therefore, the majority of the resulting ash from these fires must have been transported out of the peatland, possibly in smoke or washed away via ground and surface water transport. We conclude that the residual ash method to determine carbon loss is not a reliable method to determine carbon loss in degraded tropical peatlands.

The pathogen Mycobacterium abscessus can switch from a smooth colony form (S) into a highly inflammatory, rough colony form (R) during infection. Here, Kam et al. use an adult zebrafish model of M. abscessus chronic infection to illustrate differences in the immunopathogenesis induced by R and S variants.

Objective: Pancreatic cancer (PC) is a silent killer, because its detection is difficult and to date no effective treatment has been developed. In the US, the current 5-year survival rate of 11%. Therefore, PC has to be detected as early as possible. Methods and procedures: In this work, we have combined the use of ultrasensitive nanobiosensors for protease/arginase detection with information fusion based hierarchical decision structure to detect PC at the localized stage by means of a simple Liquid Biopsy. The problem of early-stage detection of pancreatic cancer is modelled as a multi-class classification problem. We propose a Hard Hierarchical Decision Structure (HDS) along with appropriate feature engineering steps to improve the performance of conventional multi-class classification approaches. Further, a Soft Hierarchical Decision Structure (SDS) is developed to additionally provide confidences of predicted labels in the form of class probability values. These frameworks overcome the limitations of existing research studies that employ simple biostatistical tools and do not effectively exploit the information provided by ultrasensitive protease/arginase analyses. Results: The experimental results demonstrate that an overall mean classification accuracy of around 92% is obtained using the proposed approach, as opposed to 75% with conventional multi-class classification approaches. This illustrates that the proposed HDS framework outperforms traditional classification techniques for early-stage PC detection. Conclusion: Although this study is only based on 31 pancreatic cancer patients and a healthy control group of 48 human subjects, it has enabled combining Liquid Biopsies and Machine Learning methodologies to reach the goal of earliest PC detection. The provision of both decision labels (via HDS) as well as class probabilities (via SDS) helps clinicians identify instances where statistical model-based predictions lack confidence. This further aids in determining if more tests are required for better diagnosis. Such a strategy makes the output of our decision model more interpretable and can assist with the diagnostic procedure. Clinical impact: With further validation, the proposed framework can be employed as a decision support tool for the clinicians to help in detection of pancreatic cancer at early stages.