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Periodontitis is induced by periodontal dysbiosis characterized by the predominance of anaerobic species. TLRs constitute the classical pathway for cell activation by infection. Interestingly, the Toll/IL-1 receptor homology domain adapters initiate signaling events, leading to the activation of the expression of the genes involved in the host immune response. The aim of this study was to evaluate the effects of Porphyromonas gingivalis on the expression and protein-protein interactions among five TIR adapters (MAL, MyD88, TRIF, TRAM and SARM) in gingival epithelial cells and endothelial cells. It was observed that P. gingivalis is able to modulate the signaling cascades activated through its recognition by TLR4/2 in gingival epithelial cells and endothelial cells. Indeed, MAL-MyD88 protein-protein interactions associated with TLR4 was the main pathway activated by P. gingivalis infection. When transient siRNA inhibition was performed, cell viability, inflammation, and cell death induced by infection decreased and such deleterious effects were almost absent when MAL or TRAM were targeted. This study emphasizes the role of such TIR adapter proteins in P. gingivalis elicited inflammation and the precise evaluation of TIR adapter protein interactions may pave the way for future therapeutics in both periodontitis and systemic disease with a P. gingivalis involvement, such as atherothrombosis.

Neutrophils are the primary responders to infection, rapidly migrating to sites of inflammation and clearing pathogens through a variety of antimicrobial functions. This response is controlled by a complex network of signals produced by vascular cells, tissue resident cells, other immune cells, and the pathogen itself. Despite significant efforts to understand how these signals are integrated into the neutrophil response, we still do not have a complete picture of the mechanisms regulating this process. This is in part due to the inherent disadvantages of the most-used experimental systems: in vitro systems lack the complexity of the tissue microenvironment and animal models do not accurately capture the human immune response. Advanced microfluidic devices incorporating relevant tissue architectures, cell-cell interactions, and live pathogen sources have been developed to overcome these challenges. In this review, we will discuss the in vitro models currently being used to study the neutrophil response to infection, specifically in the context of cell-cell interactions, and provide an overview of their findings. We will also provide recommendations for the future direction of the field and what important aspects of the infectious microenvironment are missing from the current models.

Planarians are flatworms and can perform whole-body regeneration. This ability involves a mechanism to distinguish between anterior-facing wounds that require head regeneration and posterior-facing wounds that require tail regeneration. How this head-tail regeneration polarity decision is made is studied to identify principles underlying tissue-identity specification in regeneration. We report that inhibition of activin-2, which encodes an Activin-like signaling ligand, resulted in the regeneration of ectopic posterior-facing heads following amputation. During tissue turnover in uninjured planarians, positional information is constitutively expressed in muscle to maintain proper patterning. Positional information includes Wnts expressed in the posterior and Wnt antagonists expressed in the anterior. Upon amputation, several wound-induced genes promote re-establishment of positional information. The head-versus-tail regeneration decision involves preferential wound induction of the Wnt antagonist notum at anterior-facing over posterior-facing wounds. Asymmetric activation of notum represents the earliest known molecular distinction between head and tail regeneration, yet how it occurs is unknown. activin-2 RNAi animals displayed symmetric wound-induced activation of notum at anterior- and posterior-facing wounds, providing a molecular explanation for their ectopic posterior-head phenotype. activin-2 RNAi animals also displayed anterior-posterior (AP) axis splitting, with two heads appearing in anterior blastemas, and various combinations of heads and tails appearing in posterior blastemas. This was associated with ectopic nucleation of anterior poles, which are head-tip muscle cells that facilitate AP and medial-lateral (ML) pattern at posterior-facing wounds. These findings reveal a role for Activin signaling in determining the outcome of AP-axis-patterning events that are specific to regeneration.

Objective: Progressive myelopathy causes severe handicap in men with adrenomyeloneuropathy (AMN), an X-linked disorder due to ABCD1 pathogenic variants. At present, treatments are symptomatic but disease-modifying therapies are under evaluation. Given the small effect size of clinical scales in AMN, biomarkers with higher effect size are needed. Here we used high-resolution magnetic resonance techniques to identify non-invasive in vivo biomarkers of the brain and spine with high effect sizes. Methods: We performed a multiparametric imaging and spectroscopy study in 23 male patients with AMN (age: 44 ± 11) and 23 male controls (age: 43 ± 11) of similar age and body-mass index. We combined (i) macrostructural analyses of the spine, using cross-sectional area (CSA) and magnetization transfer ratio (MTR), (ii) microstructural analyses of the spine and the brain, using diffusion tensor and the newly developed fixel-based analysis, and (iii) advanced metabolic analyses of the spine using metabolite cycling coupled to a semi-LASER sequences. Results: Macrostructural alterations (decrease in CSA and MTR) were observed in patients at all spinal cord levels studied (C1-T2 for CSA and C1-C5 for MTR) (p

Nociceptor sensory neurons innervate barrier tissues that are constantly exposed to microbial stimuli. During infection, pathogenic microorganisms can breach barrier surfaces and produce pain by directly activating nociceptors. Microorganisms that live in symbiotic relationships with their hosts, commensals and mutualists, have also been associated with pain, but the molecular mechanisms of how symbionts act on nociceptor neurons to modulate pain remain largely unknown. In this review, we will discuss the known molecular mechanisms of how microbes directly interact with sensory afferent neurons affecting nociception in the gut, skin and lungs. We will touch on how bacterial, viral and fungal pathogens signal to the host to inflict or suppress pain. We will also discuss recent studies examining how gut symbionts affect pain. Specifically, we will discuss how gut symbionts may interact with sensory afferent neurons either directly, through secretion of metabolites or neurotransmitters, or indirectly,through first signaling to epithelial cells or immune cells, to regulate visceral, neuropathic and inflammatory pain. While this area of research is still in its infancy, more mechanistic studies to examine microbial-sensory neuron crosstalk in nociception may allow us to develop new therapies for the treatment of acute and chronic pain.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) with CCR5– donor cells is the only treatment known to cure HIV-1 in patients with underlying malignancy. This is likely due to a donor cell–mediated graft-versus-host effect targeting HIV reservoirs. Allo-HSCT would not be an acceptable therapy for most people living with HIV due to the transplant-related side effects. Chimeric antigen receptor (CAR) immunotherapies specifically traffic to malignant lymphoid tissues (lymphomas) and, in some settings, are able to replace allo-HSCT. Here, we quantified the engraftment of HSC-derived, virus-directed CAR T cells within HIV reservoirs in a macaque model of HIV infection, using potentially novel IHC assays. HSC-derived CAR cells trafficked to and displayed multilineage engraftment within tissue-associated viral reservoirs, persisting for nearly 2 years in lymphoid germinal centers, the brain, and the gastrointestinal tract. Our findings demonstrate that HSC-derived CAR+ cells reside long-term and proliferate in numerous tissues relevant for HIV infection and cancer.

[Aim/Background] Victim age polymorphism occurs when someone offends against victims that span multiple age groups (e.g., child and adult victims). There is a need to better understand the correlates of age polymorphism, as clinicians are often asked about risk of offending against victims who may differ from the index offence victim as part of their risk formulation. The present study examines several potential correlates of age polymorphism: psychopathy, sexual preoccupation, multiple paraphilias, psychosis, and substance use disorders. [Materials/Method] Analyses were conducted using secondary clinical assessment data from a provincial forensic sexual behaviour program. The sample included 387 men with two or more contact sexual offence victims. The assessment data in the archival database included comprehensive information about victim age, as well as standardized assessment measures and diagnostic/clinical impressions. [Results] There were no significant associations between age polymorphism and psychopathy, multiple paraphilias, sexual preoccupation, psychosis, and substance use disorders. The only significant difference that emerged was that men who offended against victims 16 or older had a higher mean score on a measure of drug misuse than those who offended against victims 6 to 11. Most of the analyses produced small effects. [Conclusion] Our findings did not identify significant correlates of age polymorphism when restricting analyses to those men who offended against two or more victims. We consider key methodological differences that may have impacted our findings, as well as the need for rigorously designed research to develop a comprehensive model of age polymorphism.

Chronic HIV infection causes systemic immune activation and dysregulation, resulting in the impairment of most T-cell subsets including MAIT cells. Multiple human cohort studies demonstrate MAIT cells are selectively depleted in the peripheral blood and lymphoid tissues during HIV infection, with incomplete restoration during suppressive antiretroviral therapy. Because MAIT cells play an important role in mucosal defense against a wide array of pathogens, fully reconstituting the MAIT cell compartment in ART-treated populations could improve immunity against co-infections. Non-human primates (NHPs) are a valuable, well-described animal model for HIV infection in humans. NHPs also maintain MAIT cell frequencies more comparable to humans, compared to other common animal models, and provide a unique opportunity to study MAIT cells in the circulation and mucosal tissues in a longitudinal manner. Only recently, however, have NHP MAIT cells been thoroughly characterized using macaque-specific MR1 tetramer reagents. Here we review the similarities and differences between MAIT cells in humans and NHPs as well as the impact of SIV/SHIV infection on MAIT cells and the potential implications for future research.

Development of imaging biomarkers for rare neurodegenerative diseases such as spinocerebellar ataxia (SCA) is important to non-invasively track progression of disease pathology and monitor response to interventions. Diffusion MRI (dMRI) has been shown to identify cross-sectional degeneration of white matter (WM) microstructure and connectivity between healthy controls and patients with SCAs, using various analysis methods. In this paper, we present dMRI data in SCAs type 1, 2, 3, and 6 and matched controls, including longitudinal acquisitions at 12–24-month intervals in a subset of the cohort, with up to 5 visits. The SCA1 cohort also contained 3 premanifest patients at baseline, with 2 showing ataxia symptoms at the time of the follow-up scans. We focused on two aspects: first, multimodal evaluation of the dMRI data in a cross-sectional approach, and second, longitudinal trends in dMRI data in SCAs. Three different pipelines were used to perform cross-sectional analyses in WM: region of interest (ROI), tract-based spatial statistics (TBSS), and fixel-based analysis (FBA). We further analyzed longitudinal changes in dMRI metrics throughout the brain using ROI-based analysis. Both ROI and TBSS analyses identified higher mean (MD), axial (AD), and radial (RD) diffusivity and lower fractional anisotropy (FA) in the cerebellum for all SCAs compared to controls, as well as some cerebral alterations in SCA1, 2, and 3. FBA showed lower fiber density (FD) and fiber crossing (FC) regions similar to those identified by ROI and TBSS analyses. FBA also highlighted corticospinal tract (CST) abnormalities, which was not detected by the other two pipelines. Longitudinal ROI-based analysis showed significant increase in AD in the middle cerebellar peduncle (MCP) for patients with SCA1, suggesting that the MCP may be a good candidate region to monitor disease progression. The patient who remained symptom-free throughout the study displayed no microstructural abnormalities. On the other hand, the two patients who were at the premanifest stage at baseline, and showed ataxia symptoms in their follow-up visits, displayed AD values in the MCP that were already in the range of symptomatic patients with SCA1 at their baseline visit, demonstrating that microstructural abnormalities are detectable prior to the onset of ataxia.

Heat Shock Protein 70s (HSP70s) are key molecular chaperones that are overexpressed in many cancers and often associated with metastasis and poor prognosis. It has proven difficult to develop ATP-competitive, drug-like small molecule inhibitors of HSP70s due to the flexible and hydrophilic nature of the HSP70 ATP-binding site and its high affinity for endogenous nucleotides. The aim of this study was to explore the potential for the inhibition of HSP70 through alternative binding sites using fragment-based approaches. A surface plasmon resonance (SPR) fragment screen designed to detect secondary binding sites in HSP70 led to the identification by X-ray crystallography of a cryptic binding site in the nucleotide-binding domain (NBD) of HSP70 adjacent to the ATP-binding site. Fragment binding was confirmed and characterized as ATP-competitive using SPR and ligand-observed NMR methods. Molecular dynamics simulations were applied to understand the interactions with the protein upon ligand binding, and local secondary structure changes consistent with interconversion between the observed crystal structures with and without the cryptic pocket were detected. A virtual high-throughput screen (vHTS) against the cryptic pocket was conducted, and five compounds with diverse chemical scaffolds were confirmed to bind to HSP70 with micromolar affinity by SPR. These results identified and characterized a new targetable site on HSP70. While targeting HSP70 remains challenging, the new site may provide opportunities to develop allosteric ATP-competitive inhibitors with differentiated physicochemical properties from current series.

Abstract Background We recently upgraded our [18F]fludeoxyglucose (FDG) production capabilities with the goal of futureproofing our FDG clinical supply, expanding the number of batches of FDG we can manufacture each day, and improving patient throughput in our nuclear medicine clinic. In this paper we report upgrade of the synthesis modules to the GE FASTLab 2 platform (Phase 1) and cyclotron updates (Phase 2) from both practical and regulatory perspectives. We summarize our experience manufacturing FDG on the FASTLab 2 module with a high-yielding self-shielded niobium (Nb) fluorine-18 target. Results Following installation of Nb targets for production of fluorine-18, a 55 μA beam for 22 min generated 1330 ± 153 mCi of [18F]fluoride. Using these cyclotron beam parameters in combination with the FASTLab 2, activity yields (AY) of FDG were 957 ± 102 mCi at EOS, corresponding to 72% non-corrected AY (n = 235). Our workflow, inventory management and regulatory compliance have been greatly simplified following the synthesis module and cyclotron upgrades, and patient wait times for FDG PET have been cut in half at our nuclear medicine clinic. Conclusions The combination of FASTlab 2 and self-shielded Nb fluorine-18 targets have improved our yield of FDG, and enabled reliable and repeatable manufacture of the radiotracer for clinical use.

Summary: Perturbations in the transcriptional programs specifying epidermal differentiation cause diverse skin pathologies ranging from impaired barrier function to inflammatory skin disease. However, the global scope and organization of this complex cellular program remain undefined. Here we report single-cell RNA sequencing profiles of 92,889 human epidermal cells from 9 normal and 3 inflamed skin samples. Transcriptomics-derived keratinocyte subpopulations reflect classic epidermal strata but also sharply compartmentalize epithelial functions such as cell-cell communication, inflammation, and WNT pathway modulation. In keratinocytes, ∼12% of assessed transcript expression varies in coordinate patterns, revealing undescribed gene expression programs governing epidermal homeostasis. We also identify molecular fingerprints of inflammatory skin states, including S100 activation in the interfollicular epidermis of normal scalp, enrichment of a CD1C+CD301A+ myeloid dendritic cell population in psoriatic epidermis, and IL1βhiCCL3hiCD14+ monocyte-derived macrophages enriched in foreskin. This compendium of RNA profiles provides a critical step toward elucidating epidermal diseases of development, differentiation, and inflammation. : Cheng et al. report single-cell RNA sequencing of normal and inflamed human epidermis, revealing a discrete set of specialized keratinocytes that exhibit a distinct composition at different anatomic sites. Myeloid dendritic cells and macrophages also vary sharply with epidermal anatomic site and inflammation, indicating dynamic programming of antigen-presenting cells. Keywords: epidermis, single-cell RNA-seq, keratinocyte, skin

Abstract Using a nonhydrostatic model based on a version of Geophysical Fluid Dynamics Laboratory's FV3 dynamical core at a cloud‐resolving resolution in radiative‐convective equilibrium (RCE) configuration, the sensitivity of the mean RCE climate to the magnitude and scale‐selectivity of the divergence damping is explored. Divergence damping is used to reduce small‐scale noise in more realistic configurations of this model. This sensitivity is tied to the strength (and width) of the convective updrafts, which decreases (increases) with increased damping and acts to organize the convection, dramatically drying out the troposphere and increasing the outgoing longwave radiation. Increased damping also results in a much‐broadened precipitation probability distribution and larger extreme values, as well as reduction in cloud fraction, which correspondingly decreases the magnitude of shortwave and longwave cloud radiative effects. Solutions exhibit a monotonic dependence on the strength of the damping and asymptotically converge to the inviscid limit. While the potential dependence of RCE simulations on resolution and microphysical assumptions are generally appreciated, these results highlight the potential significance of the choice of subgrid numerical diffusion in the dynamical core.

Introduction: Very little is known about how waterpipe tobacco smokers and nonsmokers compare on harm beliefs about waterpipe tobacco smoking (WTS) and how these beliefs are related to risk appraisals and intentions to engage in WTS. We investigated these issues among young adult waterpipe tobacco smokers, susceptible nonsmokers, and non-susceptible nonsmokers. Methods: Young adults ages 18 to 30 who smoked waterpipe tobacco during the last 30 days or never used waterpipe tobacco were recruited online through Turkprime. Nonsmokers were grouped as susceptible or not. Participants completed measures of harm beliefs, risk appraisals (i.e., perceived risks and worry), and desire to quit among smokers or willingness/curiosity to try waterpipe among nonsmokers. Results: Analyses were based on 247 smokers and 418 nonsmokers. Smokers endorsed most strongly harm beliefs that portrayed WTS as safe, followed by susceptible and then non-susceptible nonsmokers. Most harm beliefs were significantly related to risk appraisals, yet weakly associated with desire to quit or willingness/curiosity to try waterpipe tobacco, except among susceptible nonsmokers. Conclusions: Greater efforts are needed to correct maladaptive beliefs about WTS harms, especially among smokers. Among susceptible nonsmokers, harm beliefs may be more influential in predicting willingness to try WTS than risk appraisals. Keywords: Hookah, Risk appraisals, Health beliefs, Intentions

Bacterial infection can cause pain but the underlying mechanism is unclear. This study shows pain induced in mice by methicillin-resistant Staphylococcus aureus infection is mediated by bacterial pore-forming toxins, and a sodium channel blocker QX-314 can alleviate infection-associated pain.

Objective: As gene-based therapies may soon arise for patients with spinocerebellar ataxia (SCA), there is a critical need to identify biomarkers of disease progression with effect sizes greater than clinical scores, enabling trials with smaller sample sizes. Methods: We enrolled a unique cohort of patients with SCA1 (n = 15), SCA2 (n = 12), SCA3 (n = 20) and SCA7 (n = 10) and 24 healthy controls of similar age, sex and body mass index. We collected longitudinal clinical and imaging data at baseline and follow-up (mean interval of 24 months). We performed both manual and automated volumetric analyses. Diffusion tensor imaging (DTI) and a novel tractography method, called fixel-based analysis (FBA), were assessed at follow-up. Effect sizes were calculated for clinical scores and imaging parameters. Results: Clinical scores worsened as atrophy increased over time (p 1.2) compared to clinical scores (

In Sub-Saharan Africa, Nile tilapia (Oreochromis niloticus L.) make up over 80% of aquaculture production. However, the local aquaculture farmers are restricted by the unavailability and expensive cost of formulated rations. To reduce reliance on the scarce and expensive fishmeal used in fish feeds, alternative insect protein has been successfully utilized in many aquafeeds. However, data on the influence of insect-based feed on the growth and economic benefit of feeding tilapia with the emerging insect-based diet are scanty. This study investigated the effect of partially and completely substituting fishmeal with black soldier fly larval meal (BM) on growth and economic parameters of tilapia. The O. niloticus was fed a standard commercial diet as a control (100% FM; 0% BM), BM33 (67% FM; 33% BM), BM67 (33% FM; 67% BM) and BM100 (0% FM; 100% BM) for 20 weeks in randomly assigned cages mounted in an 800 m2 earthen pond. Results from this study showed that diet type significantly (p < 0.05) affected the feed intake of the fish as well as weight gain. The feed conversion ratio and survival rate of O. niloticus did not vary across the different diets. Fish fed Diet1 had a 15% increase in weight when compared to fish fed the control diet. Return on investment and the cost–benefit ratio was similar across the diets, suggesting that BM is a suitable and cost-equivalent dietary supplement of FM up to 100% in aquafeed for growing tilapia fish in earthen ponds for the market.

This study characterized the health risks due to the consumption of mycotoxin-contaminated foods and assessed the consumer awareness level of mycotoxins in households in two north-central Nigerian states during the harvest and storage seasons of 2018. Twenty-six mycotoxins and 121 other microbial and plant metabolites were quantified by LC-MS/MS in 250 samples of cereals, nuts and legumes. Aflatoxins were detected in all food types (cowpea, maize, peanut and sorghum) except in millet. Aflatoxin B1 was the most prevalent mycotoxin in peanut (64%) and rice (57%), while fumonisin B1 occurred most in maize (93%) and beauvericin in sorghum (71%). The total aflatoxin concentration was highest in peanut (max: 8422 µg/kg; mean: 1281 µg/kg) and rice (max: 955 µg/kg; mean: 94 µg/kg), whereas the totals of the B-type fumonisins and citrinin were highest in maize (max: 68,204 µg/kg; mean: 2988 µg/kg) and sorghum (max: 1335 µg/kg; mean: 186 µg/kg), respectively. Citrinin levels also reached 51,195 µg/kg (mean: 2343 µg/kg) in maize. Aflatoxin and citrinin concentrations in maize were significantly (p < 0.05) higher during storage than at harvest. The estimated chronic exposures to aflatoxins, citrinin and fumonisins were high, resulting in as much as 247 new liver cancer cases/year/100,000 population and risks of nephrotoxicity and esophageal cancer, respectively. Children who consumed the foods were the most vulnerable. Mycotoxin co-occurrence was evident, which could increase the health risk of the outcomes. Awareness of mycotoxin issues was generally low among the households.

Autophagy, lipophagy, and mitophagy are considered to be the major recycling processes for protein aggregates, excess fat, and damaged mitochondria in adipose tissues in response to nutrient status-associated stress, oxidative stress, and genotoxic stress in the human body. Obesity with increased body weight is often associated with white adipose tissue (WAT) hypertrophy and hyperplasia and/or beige/brown adipose tissue atrophy and aplasia, which significantly contribute to the imbalance in lipid metabolism, adipocytokine secretion, free fatty acid release, and mitochondria function. In recent studies, hyperactive autophagy in WAT was observed in obese and diabetic patients, and inhibition of adipose autophagy through targeted deletion of autophagy genes in mice improved anti-obesity phenotypes. In addition, active mitochondria clearance through activation of autophagy was required for beige/brown fat whitening – that is, conversion to white fat. However, inhibition of autophagy seemed detrimental in hypermetabolic conditions such as hepatic steatosis, atherosclerosis, thermal injury, sepsis, and cachexia through an increase in free fatty acid and glycerol release from WAT. The emerging concept of white fat browning–conversion to beige/brown fat–has been controversial in its anti-obesity effect through facilitation of weight loss and improving metabolic health. Thus, proper regulation of autophagy activity fit to an individual metabolic profile is necessary to ensure balance in adipose tissue metabolism and function, and to further prevent metabolic disorders such as obesity and diabetes. In this review, we summarize the effect of autophagy in adipose tissue browning in the context of obesity prevention and its potential as a promising target for the development of anti-obesity drugs.

Moiré superlattices formed by twisting trilayers of graphene are a useful model for studying correlated electron behaviour and offer several advantages over their formative bilayer analogues, including a more diverse collection of correlated phases and more robust superconductivity. Spontaneous structural relaxation alters the behaviour of moiré superlattices considerably and has been suggested to play an important role in the relative stability of superconductivity in trilayers. Here we use an interferometric four-dimensional scanning transmission electron microscopy approach to directly probe the local graphene layer alignment over a wide range of trilayer graphene structures. Our results inform a thorough understanding of how reconstruction modulates the local lattice symmetries crucial for establishing correlated phases in twisted graphene trilayers, evincing a relaxed structure that is markedly different from that proposed previously.

Micorrhizals fungi contribute to growth and development of different plant species, increasing crop productivity. The aim of this research was to evaluate the interaction between micorrhizals fungi obtained in the experimental farm from the University of Magdalena. Massification of the arbuscular mycorrhizal was done according the method of plant trap. An experimental random design of six treatments and three witnesses was proposed; from mixtures of soil with peat, adding 10 g of soil inoculated with selected fungi (morphotypes fungi 1 and fungi 2). The evaluated variables corresponded to development parameters of pepper plants (number of leaves, height, length radicular and dry weight) and type of fungi, for four months. Three genders were identified: Glomus, Acaulospora and Gigaspora; being the two first most abundant and selected for tests of micorrhization. The mixtures soil-peat in proportion 70:30 added of Glomus registered better growth and development compared with the rest of treatments. The variables evaluated in pepper plants inoculated with Glomus and Acaulospora showed major significant yield compared with the witness, number of leaves (8,0 - 8,5), plant height (8,5 - 13,2 cm), length radicular (6,0 - 7,2 cm) and dry weight (0,26 - 0,28 g). It was found that adding of fungi micorrhizals represents a feasible strategy in crop production.

Engineering drawing is valuable in capturing geometric features, conveying engineering ideas, and creating a blueprint of the intended product. Engineering students usually perform orthographic projections, imagining a 3D situation and sketching its 2D representation. That requires imagination and mental visualization, determined by the learner's spatial ability. This study proposes the infusion of an AR stereogram mobile application into an engineering drawing course to establish how it influences learning outcomes among students with different spatial abilities. The quantitative experimental study involved two mechanical engineering classes in northern Taiwan, N = 69 first-year vocational high schoolers. Statistical analysis revealed that the experimental group with high spatial ability recorded better results and excellent drawing skills. Bloom's taxonomy categorization reported that spatial ability influenced "understanding" and "applying" levels, with the strongest effect on "understanding." Although no significant interaction existed, learning outcomes were highly affected by spatial ability in "understanding" and "applying" levels and AR in the overall performance. The findings and discussions show AR holds great potential to enhance students' spatial ability for real-time visualization and enables better concept comprehension by improving their understanding of engineering topics. Future studies should consider these implications in creating effective and immersive learning environments for different courses in engineering education.

Selective autolysosomal degradation of damaged mitochondria, also called mitophagy, is an indispensable process for maintaining integrity and homeostasis of mitochondria. One well-established mechanism mediating selective removal of mitochondria under relatively mild mitochondria-depolarizing stress is PINK1-Parkin-mediated or ubiquitin-dependent mitophagy. However, additional mechanisms such as LC3-mediated or ubiquitin-independent mitophagy induction by heavy environmental stress exist and remain poorly understood. The present study unravels a novel role of stress-inducible protein Sestrin2 in degradation of mitochondria damaged by transition metal stress. By utilizing proteomic methods and studies in cell culture and rodent models, we identify autophagy kinase ULK1-mediated phosphorylation sites of Sestrin2 and demonstrate Sestrin2 association with mitochondria adaptor proteins in HEK293 cells. We show that Ser-73 and Ser-254 residues of Sestrin2 are phosphorylated by ULK1, and a pool of Sestrin2 is strongly associated with mitochondrial ATP5A in response to Cu-induced oxidative stress. Subsequently, this interaction promotes association with LC3-coated autolysosomes to induce degradation of mitochondria damaged by Cu-induced ROS. Treatment of cells with antioxidants or a Cu chelator significantly reduces Sestrin2 association with mitochondria. These results highlight the ULK1-Sestrin2 pathway as a novel stress-sensing mechanism that can rapidly induce autophagic degradation of mitochondria under severe heavy metal stress.

Background In recent years, there has been a rapidly growing demand for readily accessible substrates for mass production of Black Soldier Fly, Hermetia illucens Linnaeus. Beer production results in various by-products that typically end up in uncontrolled dumpsites constituting pollution problems, which merits urgent attention. The present study investigated whether the 12 formulated diets composed of brewers’ spent grains (BSGs), brewers’ yeast and cane molasses can serve as substrate for H. illucens production. Methods Four different BSGs were selected and formulated into 12 diets, aiming at varying protein and net energy levels. The diets were offered to newly hatched (∼1 h old) H. illucens larvae and the influence on developmental duration, survival, wet weight, pre-oviposition time, fecundity, and longevity were compared. Results Developmental duration of the larvae (16–21 days) and pre-pupae (8–11 days) differed significantly across the different diets. The developmental duration of the pupae (8.7–9.1 days) was not affected by diet. The larval (86–99.2%), pre-pupal (71–95%), and pupal (65–91%) survival rates varied significantly between flies reared on the different diets. The pre-oviposition time was similar for flies provided with water (7–11 days) and 10% sugar solution (8–14 days) or across the different diets. The mean fecundity per female ranged from 324–787 eggs and did not differ between females provided with water or sugar solution. However, the number of eggs laid per female varied significantly across the different diets when provided with water. The longevity of starved H. illucens adults was significantly lower (5 days) compared to those provided with water (11–14 days) or sugar solution (14–15 days). Discussion The implications of these findings as part of a quality control procedure for commercial production of high-quality H. illucens larvae as an alternative protein ingredient in livestock and aquaculture feed are discussed.

This paper explores the literature on gender and development. Achieving women development requires the considerations of various aspects. Education is an important factor of development but it must be tailored to meet the needs of the target group. In developing countries one of the main barriers to women development is early marriage, which prevents further education, physical growth and power of decision; thus leads to more disparities between men and women. The interpretation of religious beliefs is another factor that legitimates inequalities; organizations have to understand its meaning and find ways to implement development programs in faith-based environments. They also have to advocate change in institutions that sustain disparities for the creation of unbiased policies.

Tumors are complex tissues that consist of stromal cells, such as fibroblasts, immune cells and mesenchymal stem cells, as well as non-cellular components, in addition to neoplastic cells. Increasingly, there is evidence to suggest that these non-neoplastic cell components support cancer initiation, progression and metastasis and that their ablation or reprogramming can inhibit tumor growth. Our understanding of the activities of different parts of the tumor stroma in advancing cancer has been improved by the use of scaffold and matrix-based 3D systems originally developed for regenerative medicine. Additionally, drug delivery systems made from synthetic and natural biomaterials deliver drugs to kill stromal cells or reprogram the microenvironment for tumor inhibition. In this article, we review the impact of 3D tumor models in increasing our understanding of tumorigenesis. We also discuss how different drug delivery systems aid in the reprogramming of tumor stroma for cancer treatment.

Somatic mutations in cancer are more frequent in heterochromatic and late-replicating regions of the genome. We report that regional disparities in mutation density are virtually abolished within transcriptionally silent genomic regions of cutaneous squamous cell carcinomas (cSCCs) arising in an XPC−/− background. XPC−/− cells lack global genome nucleotide excision repair (GG-NER), thus establishing differential access of DNA repair machinery within chromatin-rich regions of the genome as the primary cause for the regional disparity. Strikingly, we find that increasing levels of transcription reduce mutation prevalence on both strands of gene bodies embedded within H3K9me3-dense regions, and only to those levels observed in H3K9me3-sparse regions, also in an XPC-dependent manner. Therefore, transcription appears to reduce mutation prevalence specifically by relieving the constraints imposed by chromatin structure on DNA repair. We model this relationship among transcription, chromatin state, and DNA repair, revealing a new, personalized determinant of cancer risk.

This study presents the potential of combining anaerobic grey water sludge treatment with black water in an up-flow anaerobic sludge blanket (UASB) reactor to improve energy recovery within source-separated sanitation concepts. Black water and the mixture of black water and grey water sludge were compared in terms of biochemical methane potential (BMP), UASB reactor performance, chemical oxygen demand (COD) mass balance and methanization. Grey water sludge treatment with black water increased the energy recovery by 23% in the UASB reactor compared to black water treatment. The increase in the energy recovery can cover the increased heat demand of the UASB reactor and the electricity demand of the grey water bioflocculation system with a surplus of 0.7 kWh/cap/y electricity and 14 MJ/cap/y heat. However, grey water sludge introduced more heavy metals in the excess sludge of the UASB reactor and might therefore hinder its soil application.

Pig production is one of the fastest growing livestock sectors. Development of this sector is hampered by rapidly increasing costs of fishmeal (FM), which is a common protein source in animal feeds. Here, we explored the potential of substituting FM with black soldier fly larval meal (BSFLM) on growth and blood parameters of pigs as well as economic aspects. At weaning, 40 hybrid pigs, i.e., crossbreeds of purebred Large White and Landrace were randomly assigned to five iso-nitrogenous and iso-energetic dietary treatments: Control (0% BSFLM and 100% FM (T0)), and FM replaced at 25% (T25), 50% (T50), 75% (T75) and 100% (T100) with BSFLM. Average daily feed intake (ADFI), average daily gain (ADG), body weight gain (BWG) and feed conversion ratio (FCR) were calculated for the whole trial. Hematological and serum biochemical parameters, the cost−benefit ratio (CBR) and return on investment (RoI) were evaluated. No significant effect of diet type was observed on feed intake and daily weight gain. Red or white blood cell indices did not differ among diets. Pigs fed T25, T75 and T100, had lower platelet counts compared to T0 and T50. Dietary inclusion of BSFLM did not affect blood total cholesterol, triglycerides, low-density lipoprotein and high-density lipoprotein. CBR and RoI were similar for the various diets. In conclusion, BSFLM is a suitable and cost-effective alternative to fishmeal in feed for growing pigs.

Microglia are resident immune cells of the CNS that are activated by infection, neuronal injury, and inflammation. Here, we utilize flow cytometry and deep RNA sequencing of acutely isolated spinal cord microglia to define their activation in vivo. Analysis of resting microglia identified 29 genes that distinguish microglia from other CNS cells and peripheral macrophages/monocytes. We then analyzed molecular changes in microglia during neurodegenerative disease activation using the SOD1G93A mouse model of amyotrophic lateral sclerosis (ALS). We found that SOD1G93A microglia are not derived from infiltrating monocytes, and that both potentially neuroprotective and toxic factors, including Alzheimer’s disease genes, are concurrently upregulated. Mutant microglia differed from SOD1WT, lipopolysaccharide-activated microglia, and M1/M2 macrophages, defining an ALS-specific phenotype. Concurrent messenger RNA/fluorescence-activated cell sorting analysis revealed posttranscriptional regulation of microglia surface receptors and T cell-associated changes in the transcriptome. These results provide insights into microglia biology and establish a resource for future studies of neuroinflammation.

Recently, there has been multi-agency promotion of entomophagy as an environmentally-friendly source of food for the ever increasing human population especially in the developing countries. However, food quality and safety concerns must first be addressed in this context. We addressed these concerns in the present study using the edible stink bug Encosternum delegorguei, which is widely consumed in southern Africa. We analysed for mycotoxins, and health beneficials including antioxidants, amino acids and essential fatty acids using liquid chromatography coupled to quadrupole time of flight mass spectrometry (LC-Qtof-MS) and coupled gas chromatography (GC)-MS. We also performed proximate analysis to determine nutritional components. We identified the human carcinogen mycotoxin (aflatoxin B1) at low levels in edible stink bugs that were stored in traditonally woven wooden dung smeared baskets and gunny bags previously used to store cereals. However, it was absent in insects stored in clean zip lock bags. On the other hand, we identified 10 fatty acids, of which 7 are considered essential fatty acids for human nutrition and health; 4 flavonoids and 12 amino acids of which two are considered the most limiting amino acids in cereal based diets. The edible stink bug also contained high crude protein and fats but was a poor source of minerals, except for phosphorus which was found in relatively high levels. Our results show that the edible stink bug is a nutrient- and antioxidant-rich source of food and health benefits for human consumption. As such, use of better handling and storage methods can help eliminate contamination of the edible stink bug with the carcinogen aflatoxin and ensure its safety as human food.