Search

Objectives: Skeletal malocclusions are common, and severe malocclusions are treated by invasive surgeries. Recently, jaw bone length has been shown to be developmentally controlled by osteoclasts. Our objective was to determine the effect of inhibiting osteoclast‐secreted proteolytic enzymes on lower jaw bone length of avian embryos by pharmacologically inhibiting matrix metalloproteinase‐9 (MMP9) or cathepsin K (CTSK). Methods: Quail (Coturnix coturnix japonica) embryos were given a single dose of an inhibitor of MMP9 (iMMP9), an inhibitor CTSK (iCTSK), or vehicle at a developmental stage when bone deposition is beginning to occur. At a developmental stage when the viscerocranium is largely calcified, the heads were scanned via micro‐computed tomography and reproducible landmarks were placed on 3D‐reconstructed skulls; the landmark coordinates were used to quantify facial bone dimensions. Results: Approximately half of the quail given either iMMP9 or iCTSK demonstrated an overt lower jaw phenotype, characterized by longer lower jaw bones and a greater lower to upper jaw ratio than control embryos. Additionally, iMMP9‐treated embryos exhibited a significant change in midface length and iCTSK‐treated embryos had significant change in nasal bone length. Conclusion: MMP9 and CTSK play a role in osteoclast‐mediated determination of lower jaw bone length. Pharmacological inhibition of MMP9 or CTSK may be a promising therapeutic alternative to surgery for treating skeletal jaw malocclusions, but more preclinical research is needed prior to clinical translation. [ABSTRACT FROM AUTHOR]

This study compared the performance of near-infrared spectroscopy (NIRS) and mid-infrared spectroscopy (MIRS) for the prediction of moisture, protein, total phenolic content (TPC), ferric reducing antioxidant potential (FRAP) and total monomeric anthocyanin (TMA) content in 65 samples of Australian wheat flour. Models were constructed on 50 of the wheat samples, with the 15 remaining samples used as a dependent test set. NIRS showed excellent results for the prediction of protein content (R2test = 0.991; RMSEP = 0.22% w/v) and acceptable to good results for TPC (R2test = 0.83; RMSEP = 3.9 mg GAE/100 g), FRAP (R2test = 0.92; RMSEP = 5.4 mg TE/100 g) and moisture content (R2test = 0.76, RMSEP = 0.62% w/v). Similarly, MIRS showed the best results for protein prediction (R2test = 0.93, RMSEP = 0.62% w/v) and acceptable results for moisture content (R2test = 0.83, RMSEP = 0.65% w/v), FRAP (R2test = 0.83, RMSEP = 7.0 mg TE/100 g) and TPC (R2test = 0.73, RMSEP = 5.6 mg GAE/100 g). However, the TMA content could not be predicted. Finally, moving window analysis was conducted to determine the optimum wavelength ranges for predicting selected analytes. On average, this improved RMSECV values by an average of 18–20% compared to the corresponding full wavelength models, when using the same component selection method. The results confirm that infrared spectroscopy may be useful for the real-time quantitation and/or screening of key quality parameters in wheat, such as protein, TPC and antioxidant capacity. [ABSTRACT FROM AUTHOR]

Modern infectious disease outbreaks often involve changes in host tropism, the preferential adaptation of pathogens to specific hosts. The Lyme disease- causing bacterium Borrelia burgdorferi (Bb) is an ideal model to investigate the molecular mechanisms of host tropism, because different variants of these tick- transmitted bacteria are distinctly maintained in rodents or bird reservoir hosts. To survive in hosts and escape complement- mediated immune clearance, Bb produces the outer surface protein CspZ that binds the complement inhibitor factor H (FH) to facilitate bacterial dissemination in vertebrates. Despite high sequence conservation, CspZ variants differ in human FH- binding ability. Together with the FH polymorphisms between vertebrate hosts, these findings suggest that minor sequence variation in this bacterial outer surface protein may confer dramatic differences in host- specific, FH- binding- mediated infectivity. We tested this hypothesis by determining the crystal structure of the CspZ--human FH complex, and identifying minor variation localized in the FH- binding interface yielding bird and rodent FH- specific binding activity that impacts infectivity. Swapping the divergent region in the FH- binding interface between rodent- and bird- associated CspZ variants alters the ability to promote rodent- and bird- specific early- onset dissemination. We further linked these loops and respective host- specific, complement- dependent phenotypes with distinct CspZ phylogenetic lineages, elucidating evolutionary mechanisms driving host tropism emergence. Our multidisciplinary work provides a novel molecular basis for how a single, short protein motif could greatly modulate pathogen host tropism. [ABSTRACT FROM AUTHOR]

The synthesis and characterisation (IR, NMR, HR-MS, and X-ray crystallography) of six oxazoline Zn complexes, containing enolate ligands derived from a series of (Z)-1-R-2-(4′,4′-dimethyl-2′-oxazolin-2′-yl)-eth-1-en-1-ols (R = C6H5, C6H4-p-NO2, C6H4-p-OCH3, CF3, CH3, or CMe3) is detailed. All derivatives are air-stable solids of formula Zn(Ln)2 and are formed in the presence of the title ligands and NEt3. Reasonable yields (53%–82%) are obtained with the exception of R = CMe3 (9%); in this case, by-product formation and high solubility affected complex isolation. Crystallographic characterisation reveals that in all cases the ligands are bound in a κ2-N,O-bonding motif. Little structural diversity is noted within the series; these complexes are further placed into structural context with related Zn materials containing oxazoline, phenolate, and (or) Schiff base ligands. [ABSTRACT FROM AUTHOR]

Introduction: Promoting healthy ageing is increasingly important to maintain functional ability and wellbeing in older age. However, there is a lack of consolidated evidence-based information to support the selection of non-drug interventions to support healthy ageing outcomes for individuals. Methods: A narrative review of the evidence-based literature on non-drug interventions to support healthy ageing was performed. Evidence for intervention benefits was evaluated and mapped into the Systematic Wellness Intervention Pathway framework and aligned to relevant goals, needs and outcomes relating to physical fitness and function, emotional wellbeing, cognitive health, sleep and diet and nutrition. Comments from a modified Delphi survey of 75 expert peer reviewers were analysed to inform the development of the next Pathway iteration. Results: The narrative review identified key healthy ageing interventions, including physical activity, social interaction, interventions for emotional wellbeing, creative and cognitively stimulating activities and diet and nutrition. Peer review survey results indicated majority agreement with all domains and non-drug interventions for healthy ageing in the Pathway, and suggested interventions and outcome revisions informed Pathway iteration. Conclusion: The Pathway could be a step forward in operationalising the delivery of non-drug interventions in an accessible and scalable way, supplementing conventional health and social care, to enable older people to live well for longer. [ABSTRACT FROM AUTHOR]

Gliomas, the most prevalent primary brain tumors, pose considerable challenges due to their heterogeneity, intricate tumor microenvironment (TME), and blood-brain barrier (BBB), which restrict the effectiveness of traditional treatments like surgery and chemotherapy. This review provides an overview of engineered cell membrane technologies in glioma therapy, with a specific emphasis on targeted drug delivery and modulation of the immune microenvironment. This study investigates the progress in engineered cell membranes, encompassing physical, chemical, and genetic alterations, to improve drug delivery across the BBB and effectively target gliomas. The examination focuses on the interaction of engineered cell membrane-coated nanoparticles (ECM-NPs) with the TME in gliomas, emphasizing their potential to modulate glioma cell behavior and TME to enhance therapeutic efficacy. The review further explores the involvement of ECM-NPs in immunomodulation techniques, highlighting their impact on immune reactions. While facing obstacles related to membrane stability and manufacturing scalability, the review outlines forthcoming research directions focused on enhancing membrane performance. This review underscores the promise of ECM-NPs in surpassing conventional therapeutic constraints, proposing novel approaches for efficacious glioma treatment., (© 2024 Wiley‐VCH GmbH.)

Trypanosoma brucei is the causal agent of African Trypanosomiasis in humans and other animals. It maintains a long-term infection through an antigenic variation based population survival strategy. To proliferate in a mammal, T. brucei acquires iron and haem through the receptor mediated uptake of host transferrin and haptoglobin-hemoglobin respectively. The receptors are exposed to host antibodies but this does not lead to clearance of the infection. Here we discuss how the trypanosome avoids this fate in the context of recent findings on the structure and cell biology of the receptors., (© 2024 The Authors. BioEssays published by Wiley Periodicals LLC.)

Continuing education for dementia has been shown to be beneficial by improving informal caregiver knowledge, dementia care, management, and caregiver physical and mental health. Technology-based dementia education has been noted to have equivalent effects as in-person education, but with the added benefit of asynchronous and/or remote delivery, which increases accessibility. Using Cochrane review methodology, this study systematically reviewed the literature on technology-based dementia education and its impacts on caregivers. Technology-based delivery included dementia education delivered via the Internet, telephone, telehealth, videophone, computer, or digital video device (DVD). In the review, twenty-eight studies were identified with fourteen included in a meta-analysis, and these data revealed a significant small effect of technologically based dementia education on reducing caregiver depression, and a medium effect on reducing caregiver distress in response to caregivers' observations of behavioral problems displayed by persons with dementia. No evidence was found for a significant effect of the educational intervention on caregiver burden or self-efficacy, which are known to be gendered aspects of caregiving. None of the studies included in the meta-analysis reported separate outcomes for male and female care providers, which has implications for gendered caregiving norms and aspects of care. Registration number: PROSPERO 2018 CRD42018092599. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the potential of handheld near-infrared (NIR) and benchtop mid-infrared (MIR) spectroscopy for the rapid prediction of antioxidant capacity, dry matter, and total phenolic contents in cayenne pepper (Capsicum annuum 'Cayenne'). Using NIR spectroscopy, the best-performing model for dry matter had an R2pred = 0.74, RMSEP = 0.38%, and RPD of 2.02, exceeding the best results previously reported in the literature. This was also the first study to predict dry matter content from the mid-infrared spectra, although with lower accuracy (R2pred = 0.54; RMSEP = 0.51%, RPD 1.51). The models for antioxidant capacity and total phenolic content did not perform well using NIR or MIR spectroscopy (RPD values < 1.5), indicating that further optimization is required in this area. Application of support vector regression (SVR) generally gave poorer results compared to partial least squares regression (PLSR). NIR spectroscopy may be useful for in-field measurement of dry matter in the chili crop as a proxy measure for fruit maturity. However, the lower accuracy of MIR spectroscopy is likely to limit its use in this crop. [ABSTRACT FROM AUTHOR]

Abnormal heart rate variability (HRV) is commonly observed in cancer patients who have undergone targeted therapy and/or surgery, yet the effects of cancer itself on cardiac function remain underexplored. Specifically, there is limited knowledge about sex‐specific manifestations of HRV in cancer patients. Transgenic mouse models are widely used to study different types of cancer. Here, we aimed to investigate the sex‐specific effects of cancer on cardiac function using transgenic mouse models of pancreatic and liver cancers. This study used male and female transgenic mice with cancer and wild‐type controls. Cardiac function was assessed by recording electrocardiograms in conscious mice. RR intervals were detected to determine HRV using time and frequency domain analyses. Histological analysis with Masson's trichrome staining was performed to determine structural changes. In females, increased HRV was observed in both pancreatic and liver cancer‐bearing mice. In contrast, in males, increased HRV was observed only in the liver cancer group. Male pancreatic cancer mice demonstrated autonomic balance shift showing an increase in parasympathetic to sympathetic tone. The heart rate (HR) was higher in control and liver cancer male mice groups than in females. Histological analysis did not show significant sex differences but suggested a higher degree of remodeling in liver cancer mice than in control, specifically in the right atrium and left ventricle. This study revealed sex differences in cancer's HR modulation. Specifically, female cancer mice had lower median HR and higher HRV. These findings indicate that sex must be considered when using HRV as a cancer biomarker. [ABSTRACT FROM AUTHOR]

Habanero chillies (Capsicum chinense cv Habanero) are a popular species of hot chilli in Australia, with production steadily increasing. However, there is limited research on this crop due to its relatively low levels of production at present. Rapid methods of assessing fruit quality could be greatly beneficial both for quality assurance purposes and for use in breeding programs or experimental growing trials. This work investigated the potential of using infrared spectroscopy for the quality assessment of 20 Australian Habanero chilli samples, including the prediction of dry matter content, total phenolic content, ferric reducing antioxidant potential and capsaicin/dihydrocapsaicin content. Near-infrared spectra (908–1676 nm) taken from the fresh fruit showed strong potential for the estimation of dry matter content, with a root mean standard error of cross-validation (RMSECV) of 0.50% FW. A moving-window partial least squares regression model was applied to optimise the spectral window used for dry matter content prediction, with the best-performing window being between 1224 and 1422 nm. However, the near-infrared spectra of fresh fruit could not be used to estimate the total phenolic content or capsaicin/dihydrocapsaicin content of the samples. Mid-infrared spectra (4000 − 400 cm− 1) collected from the dried, powdered material showed slightly more promise for the prediction of total phenolics and the ratio of capsaicin:dihydrocapsaicin, with a R2cv of 0.45 and RMSECV of 0.32 for the latter parameter. Although further refinement is required, this method may be able to detect samples with high/low contents of total phenolics or for the estimation of the capsaicin:dihydrocapsaicin ratio. [ABSTRACT FROM AUTHOR]

Plants recognize the direction of a light source and exhibit phototropic responses. Physiological studies have predicted that differences in the light intensity received by the cells on the irradiated and shaded sides of a coleoptile or hypocotyl cause differences in the amounts of photoproduct. This hypothetical photoproduct appears to regulate a signaling pathway that controls cell elongation in which cells under lower light intensity elongate more than those under higher light intensity. This results in a bending growth toward a light source and has been proposed as the photoproduct-gradient model of phototropism. In this review, we summarize recent findings on the photosensory adaptation mechanisms involving a blue-light photoreceptor, phototropin1 (phot1), ROOT PHOTOTROPISM2, NONPHOTOTROPIC HYPOCOTYL3 (NPH3), and another photoreceptor family, the phytochromes. The current evidence demonstrates that, in addition to the transition of the phot1–NPH3 photoreceptor complexes to their active state, the presence of a certain population of the phot1–NPH3 complexes showing a steady state, even in a light environment, is essential for recognition of the light source direction in phototropism. This is consistent with the photoproduct-gradient model, and a dissociation state of the phot1–NPH3 complex would be considered an entity of the hypothetical photoproduct in this model. [ABSTRACT FROM AUTHOR]

Simple Summary: New types of pesticides are increasingly found in surface waters around the world. Little is known about how they interact in mixtures, and how these mixtures might then affect aquatic organisms at risk of exposure. We looked at how two new pesticides, chlorantraniliprole (CHL) and imidacloprid (IMI), affected a sensitive aquatic organism, Daphnia magna. We exposed Daphnia to surface waters known to be contaminated by agricultural runoff at two time points: during an extended dry period and after the first seasonal storm event. In surface waters, the concentrations of CHL, IMI, and other pesticides of concern increased after the storm event. Exposure to these waters caused Daphnia to be hypoactive, and their response to light varied with the concentration of surface water. We then exposed Daphnia to each chemical individually and then to mixtures of the two chemicals, at concentrations that occur in polluted waterways. Daphnia exposed to CHL and IMI mixtures were more active in response to light stimuli than the control group. Daphnia swimming behavior is a sensitive way to measure the biological effects of CHL, IMI, and surface waters. Pesticides with novel modes of action including neonicotinoids and anthranilic diamides are increasingly detected in global surface waters. Little is known about how these pesticides of concern interact in mixtures at environmentally relevant concentrations, a common exposure scenario in waterways impacted by pesticide pollution. We examined effects of chlorantraniliprole (CHL) and imidacloprid (IMI) on the sensitive invertebrate, Daphnia magna. Exposures were first performed using surface waters known to be contaminated by agricultural runoff. To evaluate the seasonal variation in chemical concentration and composition of surface waters, we tested surface water samples taken at two time points: during an extended dry period and after a first flush storm event. In surface waters, the concentrations of CHL, IMI, and other pesticides of concern increased after first flush, resulting in hypoactivity and dose-dependent photomotor responses. We then examined mortality and behavior following single and binary chemical mixtures of CHL and IMI. We detected inverse photomotor responses and some evidence of synergistic effects in binary mixture exposures. Taken together, this research demonstrates that CHL, IMI, and contaminated surface waters all cause abnormal swimming behavior in D. magna. Invertebrate swimming behavior is a sensitive endpoint for measuring the biological effects of environmental pesticides of concern. [ABSTRACT FROM AUTHOR]

Three experiments were conducted to assess the effect of different doses of gamma radiation on various seedling traits; determine the optimum doses of gamma radiation for different faba bean genotypes; find out the variation in optimum doses with respect to the different times of sowings after irradiation and methods of irradiation. Five faba bean genotypes viz., L-2013-060, L-2013-092, Anandnagar Local, Gazipur Local and Bangla Gangachar were used in these experiments. In Experiment I, seeds of five experimental genotypes were exposed to different doses (100 Gy 200 Gy, 300 Gy, 400 Gy, 500 Gy, 600 Gy, 700 Gy and 800 Gy) of gamma radiation and were sown immediately after irradiation. In Experiment II, seeds of Bangla Gangachar and L-2013-060 were exposed to varying doses (100–800 Gy) of gamma radiation and were sown at seven sowings starting from 0 h to 24 h at 4-h intervals after irradiation. In Experiment III, L-2013-092 genotypes was exposed to different doses (100 –800 Gy) of gamma radiation with two different methods of irradiation. In Experiment I, the lethal dose 50 (LD50) values have arrived at 140 Gy, 669 Gy, 575 Gy, 386 Gy and 158 Gy for L-2013-060, L-2013-092, Anandnagar Local, Gazipur Local and Bangla Gangachar, respectively. The growth reduction 50 (GR50) doses for different seedling traits ranged from 130 Gy to 320 Gy for L-2013-060, 250 Gy to 480 Gy for L-2013-092, 130 Gy to 370 Gy for Anandnagar Local, 200 Gy to 350 Gy for Gazipur Local and 250 Gy to 400 Gy for Bangla Gangachar. In Experiment II, the values for LD50 of the genotypes Bangla Gangachar and L-2013-060 were significantly singular for different time intervals of sowing. The values of GR50 for most of the seedling traits were found to increase with the delay in sowing after irradiation from 4 to 24 h when compared with the immediately sown seed lots. In Experiment III, LD50 for L-2013-092 was 337 Gy with Method 1 and 669 Gy with Method 2. In Method 1, most of the growth parameters attained GR50 doses lower than Method 2. The first method was found to increase the radiosensitivity of L-2013-092. Every experimental genotype used in these three experiments showed dose-dependent retardation of different seedling traits. These optimized doses may be employed to establish mutant populations for exploiting the novel traits of faba bean. The time of sowing after irradiation and method of irradiation was found to be essential for confirming optimum doses. [ABSTRACT FROM AUTHOR]

The increasing importance of identifying lesbian, gay, bisexual and transgender (LGBT+) populations is a key driver in changes to demographic data collection in representative surveys of youth. While such population-based data are rare, Growing Up in Ireland (GUI), an Irish, government-funded, longitudinal survey, includes sexual orientation and gender identity (SOGI) measurements. This qualitative study responds to a query from the GUI study team and aims to identify how best to collect SOGI data in future waves of GUI. A university Human Research Ethics Committee granted approval for online consultations with LGBT+ youth (n = 6) with experiential expertise in policy making. The research is underpinned by rights-based public patient involvement (PPI) with recorded discussions, which were transcribed and imported into NVivo 12, generating the theme "recognition in research, policy and society". This co-created article, with the LGBT+ young PPI Panel members, commends the inclusion of SOGI data in GUI and recommends changes in question placement and phrasing. Aligning with best practice, the PPI members provide a template for wording on consecutive sex and gender questions, expanded sexual orientation identity categories and maintaining the existing well-phrased transgender question from GUI. This offers potential to improve the quality of the SOGI data collected and the experience of those completing the questionnaire. These findings extend beyond GUI, with relevance for surveys with youth populations. This paper underscores the potential and benefits of participatory approaches to research with youth and views their role beyond simply as sources of data. [ABSTRACT FROM AUTHOR]

The Central Queensland region of Australia is a large producer of horticultural produce; however, there are limited studies on the phytochemical composition of the produce from this region. Additionally, some crops or cultivars are poorly known in domestic markets; hence are currently only grown for niche markets. There is opportunity to expand production of these crops if they contain higher levels of health-benefiting compounds compared to existing cultivars. Hence this work aimed to elucidate the phytochemical composition of such under-marketed and/or under-utilised crops, including their phenolic acid and flavonoid profiles. The samples included nine cucurbits, two citrus fruits, dragonfruit and Brazilian cherry. The vitamin C (ascorbic acid) content was quantified using high-performance liquid chromatography with diode array detection, while the phenolic profiles were gathered using targeted liquid chromatograph tandem mass spectrometry analysis. Antioxidant activity was quantified using the FRAP and CUPRAC assays, while total phenolic content was measured using the Folin-Ciocalteu assay. The results revealed extensive variation in the levels of health-benefiting compounds between the samples. The phenolic profiles of several species/cultivars are reported for the first time. The highest ascorbic acid content was found in blood orange skin (817 mg/100 g DW), while the highest total phenolic content was found in blood orange skin (1988 mg GAE/100 g). Samples showing high antioxidant capacity included blood orange skin, Brazilian cherry and spaghetti squash. These results may support the prospect of marketing several of the crops/cultivars as functional food crops in domestic or export markets. [ABSTRACT FROM AUTHOR]

A series of laboratory experiments was performed to investigate the transport and retention of viable C. parvum oocysts in soil columns homogeneously packed with loamy sand soils (Lewiston and Greenson series) and sandy loam soils (Sparta and Gilford series), and under hydrologic conditions involving the presence of an anionic surfactant—Aerosol 22 in artificial rainfall. To characterize the effect of surfactant on the mobility of C. parvum oocysts in the soils used in this study, these results were compared with previous laboratory‐scale column experiments of a previous study using soils contaminated with oocysts, under conditions identical to those described here except for the absence of the surfactant in the percolating water. Quantitative polymerase chain reaction was used for the detection and quantification of C. parvum oocysts in soil leachates to assess their breakthrough and in soil matrices to characterize their spatial distribution. Alterations in the rate and extent of transport of C. parvum oocysts were discerned per the physicochemical parameters analyzed—soil types, soil chemistry, and surfactant—and resulted in either the enhancement or hinderance of C. parvum oocysts adsorption to surfaces, and their movement in soils. In the case of loamy sand soils, the transport of C. parvum oocysts through the soil matrices increased with the application of surfactant for Sparta series and remained at a similar level for Gilford series. Regarding sandy loam soils, the movement of C. parvum oocysts through the soil matrices increased for Greenson series and decreased for Lewiston series with the application of surfactant. Core Ideas: Mechanisms governing transport of C. parvum oocysts in soils are influenced by soil types and soil water chemistry.Surfactant affected the transport and retention behaviors of C. parvum oocysts in soils.qPCR was used for the detection and enumeration of C. parvum oocysts in natural soil and water samples. [ABSTRACT FROM AUTHOR]

Bacteria, filamentous fungi, and plants synthesize thousands of secondary metabolites with important biological and pharmacological activities. The biosynthesis of these metabolites is performed by networks of complex enzymes such as non-ribosomal peptide synthetases, polyketide synthases, and terpenoid biosynthetic enzymes. The efficient production of these metabolites is dependent upon the supply of precursors that arise from primary metabolism. In the last decades, an impressive array of biosynthetic enzymes that provide specific precursors and intermediates leading to secondary metabolites biosynthesis has been reported. Suitable knowledge of the elaborated pathways that synthesize these precursors or intermediates is essential for advancing chemical biology and the production of natural or semisynthetic biological products. Two of the more prolific routes that provide key precursors in the biosynthesis of antitumor, immunosuppressant, antifungal, or antibacterial compounds are the lysine and ornithine pathways, which are involved in the biosynthesis of β-lactams and other non-ribosomal peptides, and bacterial and fungal siderophores. Detailed analysis of the molecular genetics and biochemistry of the enzyme system shows that they are formed by closely related components. Particularly the focus of this study is on molecular genetics and the enzymatic steps that lead to the formation of intermediates of the lysine pathway, such as α-aminoadipic acid, saccharopine, pipecolic acid, and related compounds, and of ornithine-derived molecules, such as N5-Acetyl-N5-Hydroxyornithine and N5-anhydromevalonyl-N5-hydroxyornithine, which are precursors of siderophores. We provide evidence that shows interesting functional relationships between the genes encoding the enzymes that synthesize these products. This information will contribute to a better understanding of the possibilities of advancing the industrial applications of synthetic biology. [ABSTRACT FROM AUTHOR]

Fermented juice from the noni tree (Morinda citrifolia) is a traditional medicinal product used by South Pacific Islanders to treat a wide range of ailments, including cancer, inflammation and obesity, as well as improving overall wellbeing. Many of its bioactive properties have been suggested to arise from the high antioxidant capacity and phenolic content found in the juice. However, there have been limited investigations into the phenolic profiles of noni juice produced locally in the Pacific. This study aimed to investigate the chemical composition and bioactive properties of noni juice. The first phase of this study used liquid chromatography with tandem mass spectrometry (LC-MS/MS) to characterise the phenolic composition of five brands of commercial noni juice produced in the South Pacific region. A total of 21 phenolic compounds were putatively identified, with the most abundant generally being rutin, 4-hydroxybenzoic acid and gentisic acid. Vastly differing phenolic profiles were found between the noni juice brands. Significant differences were also found in their antioxidant capacities and total phenolic contents. Of the three major phenolic compounds identified, gentisic acid showed the highest antioxidant activity (640% higher than Trolox). Additionally, the noni juice showed no significant anti-acetylcholinesterase activity and no to moderate cytotoxicity against two cancer cell lines (HeLa and HT29). These results indicate that the phytochemical profiles—and hence, the expected bioactive properties—are likely to vary significantly between different noni juice brands. Furthermore, the anti-cancer activity of non-concentrated noni juice appears to be relatively low. [ABSTRACT FROM AUTHOR]

The use of extracellular vesicle (EV)-based vaccines is a strategically promising way to prevent cancer metastasis. The effective roles of immune cell-derived EVs have been well understood in the literature. In the present paper, we focus on cancer cell-derived EVs to enforce, more thoroughly, the use of EV-based vaccines against unexpected malignant cells that might appear in poor prognostic patients. As a model of such a cancer cell with high malignancy, Nanog-overexpressing melanoma cell lines were developed. As expected, Nanog overexpression enhanced the metastatic potential of melanomas. Against our expectations, a fantastic finding was obtained that determined that EVs derived from Nanog-overexpressing melanomas exhibited a metastasis-suppressive effect. This is considered to be a novel role for Nanog in regulating the property of cancer cell-derived EVs. Stimulated by this result, the review of Nanog's roles in various cancer cells and their EVs has been updated once again. Although there was no other case presenting a similar contribution by Nanog, only one case suggested that NANOG and SOX might be better prognosis markers in head and neck squamous cell carcinomas. This review clarifies the varieties of Nanog-dependent phenomena and the relevant signaling factors. The information summarized in this study is, thus, suggestive enough to generate novel ideas for the construction of an EV-based versatile vaccine platform against cancer metastasis. [ABSTRACT FROM AUTHOR]

Genetic tools for targeted modification of the mycobacterial genome contribute to the understanding of the physiology and virulence mechanisms of mycobacteria. Human and animal pathogens, such as the Mycobacterium tuberculosis complex, which causes tuberculosis, and M. leprae, which causes leprosy, are of particular importance. Genetic research opens up novel opportunities to identify and validate new targets for antibacterial drugs and to develop improved vaccines. Although mycobacteria are difficult to work with due to their slow growth rate and a limited possibility to transfer genetic information, significant progress has been made in developing genetic engineering methods for mycobacteria. The review considers the main approaches to changing the mycobacterial genome in a targeted manner, including homologous and site-specific recombination and use of the CRISPR/Cas system. [ABSTRACT FROM AUTHOR]

Background and Purpose: Endoplasmic reticulum (ER) stress triggers an adaptive response in tumours which fosters cell survival and resilience to stress. Activation of the ER stress response, through its PERK branch, promotes phosphorylation of the α‐subunit of the translation initiation factor eIF2, thereby repressing general protein translation and augmenting the translation of ATF4 with the downstream CHOP transcription factor and the protein disulfide oxidase, ERO1‐alpha Experimental Approach: Here, we show that ISRIB, a small molecule that inhibits the action of phosphorylated eIF2alpha, activating protein translation, synergistically interacts with the genetic deficiency of protein disulfide oxidase ERO1‐alpha, enfeebling breast tumour growth and spread. Key Results: ISRIB represses the CHOP signal, but does not inhibit ERO1. Mechanistically, ISRIB increases the ER protein load with a marked perturbing effect on ERO1‐deficient triple‐negative breast cancer cells, which display impaired proteostasis and have adapted to a low client protein load in hypoxia, and ERO1 deficiency impairs VEGF‐dependent angiogenesis. ERO1‐deficient triple‐negative breast cancer xenografts have an augmented ER stress response and its PERK branch. ISRIB acts synergistically with ERO1 deficiency, inhibiting the growth of triple‐negative breast cancer xenografts by impairing proliferation and angiogenesis. Conclusion and Implications: These results demonstrate that ISRIB together with ERO1 deficiency synergistically shatter the PERK‐dependent adaptive ER stress response, by restarting protein synthesis in the setting of impaired proteostasis, finally promoting tumour cytotoxicity. Our findings suggest two surprising features in breast tumours: ERO1 is not regulated via CHOP under hypoxic conditions, and ISRIB offers a therapeutic option to efficiently inhibit tumour progression in conditions of impaired proteostasis. [ABSTRACT FROM AUTHOR]

Reflecting the neglect of childhood disability in social stratification research, there is a notable dearth of research on the mechanisms underpinning disability differentials in educational outcomes. Drawing on rich longitudinal data collected at 9, 13 and 17 years as part of Ireland's 'Growing Up in Ireland' study, we look at the impact of special educational needs (SEN) identification in primary school on upper secondary outcomes. A bioecological framework and the Process–Person–Context–Time model allow us to understand how interactions with family, teachers, friends and school—as proximal processes—relate to early school leaving and post‐school planned pathways after accounting for personal and context characteristics. Overall, young people identified at age 9 as having SEN are at increased risk of early school leaving and are more likely to plan to attend further education and training, rather than higher education. However, after accounting for proximal processes and personal and context variables, students identified at age 9 as having SEN are no longer distinct in terms of secondary attainment and post‐school planning. Instead, these young people are more likely to experience forms of vulnerability that are important in shaping these outcomes. These key educational outcomes are strongly shaped by family and school‐related factors—both proximal processes and context characteristics—suggesting that efforts to support retention and pathway planning should be underpinned by an ecological understanding of young people's trajectories and the cumulative disadvantages they face. [ABSTRACT FROM AUTHOR]

Antidepressants can cause sexual dysfunction side effects, necessitating the co-administration of phosphodiesterase type 5 inhibitors. The simultaneous determination of these drugs in biological fluids is critical for therapeutic drug monitoring. For the first time, two binary mixtures containing duloxetine with either avanafil or tadalafil were estimated utilizing simple green spectrofluorimetric methods without the need for a previous separation step. The study was based on first derivative synchronous spectrofluorimetry in ethanol using a change in wavelength difference (∆λ) of 20 and 25 nm for the first and second combinations, respectively. Duloxetine and avanafil were estimated at 297.7 and 331 nm in their binary mixture, while duloxetine and tadalafil were determined at 290.3 and 297.7 nm, respectively. The linearity was achieved over the ranges of 0.1-1.5 μg mL -1 for both duloxetine and avanafil and 0.01-0.40 μg mL -1 for tadalafil, with limits of detection of 0.013, 0.022, and 0.004 μg mL -1 for duloxetine, avanafil, and tadalafil, respectively. Successful application of the developed approaches was accomplished for the estimation of the two mixtures in dosage forms as well as human plasma with excellent percentage recoveries (96-103.75% in plasma), which supports their suitability for use in quality control laboratories and pharmacokinetic studies. Moreover, the adopted approaches' greenness was evidenced by applying three tools., (© 2024 John Wiley & Sons Ltd.)

Somatotroph adenomas are the leading cause of acromegaly, with the nearly sparsely granulated somatotroph subtype belonging to high-risk adenomas, and they are less responsive to medical treatment. The integrated stress response (ISR) is an essential stress-support pathway increasingly recognized as a determinant of tumorigenesis. In this study, we identified the characteristic profiling of the integrated stress response in translocation and translation initiation factor activity in somatotroph adenomas, normal pituitary, or other adenoma subtypes through proteomics. Immunohistochemistry exhibited the differential significance and the priority of eukaryotic translation initiation factor 2β (EIF2β) in somatotroph adenomas compared with gonadotroph and corticotroph adenomas. Differentially expressed genes based on the level of EIF2β in somatotroph adenomas were revealed. MetaSape pathways showed that EIF2β was involved in regulating growth and cell activation, immune system, and extracellular matrix organization processes. The correlation analysis showed Spearman correlation coefficients of r = 0.611 (p < 0.001) for EIF2β and eukaryotic translation initiation factor 2 alpha kinase 1 (HRI), r = 0.765 (p < 0.001) for eukaryotic translation initiation factor 2 alpha kinase 2 (PKR), r = 0.813 (p < 0.001) for eukaryotic translation initiation factor 2 alpha kinase 3 (PERK), r = 0.728 (p < 0.001) for GCN2, and r = 0.732 (p < 0.001) for signal transducer and activator of transcription 3 (STAT3). Furthermore, the invasive potential in patients with a high EIF2β was greater than that in patients with a low EIF2β (7/10 vs. 4/18, p = 0.038), with a lower immune-cell infiltration probability (p < 0.05). The ESTIMATE algorithm showed that the levels of activation of the EIF2 pathway were negatively correlated with the immune score in somatotroph adenomas (p < 0.001). In in vitro experiments, the knockdown of EIF2β changed the phenotype of somatotroph adenomas, including cell proliferation, migration, and the secretion ability of growth hormone/insulin-like growth factor-1. In this study, we demonstrate that the ISR is pivotal in somatotroph adenomas and provide a rationale for implementing ISR-based regimens in future treatment strategies. [ABSTRACT FROM AUTHOR]

This paper examines multidimensional poverty for three waves of a cohort of Irish children ranging from ages 9 to 17. Poverty is measured over the dimensions of health, education and family resources and both unidimensional and multidimensional poverty is examined. Both show a clear gradient with respect to maternal education. The dynamics of both unidimensional and multidimensional poverty are also analysed. The greatest degree of mobility is observed with respect to family resources. Mobility also is higher for children whose mothers have lower levels of education, with net movements into rather than out of poverty. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain metastases are the most common brain tumor in adults and are associated with poor prognosis. The propensity of different solid tumors to metastasize varies greatly, with lung, breast, and melanoma primary tumors commonly leading to brain metastases, while other primaries such as prostate rarely metastasize to the brain. The molecular mechanisms that predispose and facilitate brain metastasis development are poorly understood. In this review, we present the current data on the genomic landscape of brain metastases that arise from various primary cancers and also outline potential molecular mechanisms that drive the formation of distant metastases in the brain. Targeted therapies for cancers have improved primary tumor response rates, but concomitantly, brain metastases (BM) have become the most common brain tumors in adults and are associated with a dismal prognosis of generally less than 6 months, irrespective of the primary cancer type. They most commonly occur in patients with primary breast, lung, or melanoma histologies; however, they also appear in patients with other primary cancers including, but not limited to, prostate cancer, colorectal cancer, and renal cell carcinoma. Historically, molecular biomarkers have normally been identified from primary tumor resections. However, clinically informative genomic alterations can occur during BM development and these potentially actionable alterations are not always detected in the primary tumor leading to missed opportunities for effective targeted therapy. The molecular mechanisms that facilitate and drive metastasis to the brain are poorly understood. Identifying the differences between the brain and other extracranial sties of metastasis, and between primary tumors and BM, is essential to improving our understanding of BM development and ultimately patient management and survival. In this review, we present the current data on the genomic landscape of BM from various primary cancers which metastasize to the brain and outline potential mechanisms which may play a role in promoting the formation of the distant metastases in the brain. [ABSTRACT FROM AUTHOR]

There is a well‐established socio‐economic gradient in child cognitive test scores. This gradient emerges at early ages, with some evidence that it can widen as children age. We investigate this phenomenon with two longitudinal cohorts of Irish children who take such tests at ages ranging from 9 months to 17 years, using maternal education and equivalised income as our measure of socio‐economic resources. The gradient is observed from the age of 3 with tentative evidence that it widens as children get older. We have evidence on a wide range of tests and there is some evidence that the gradient is slightly stronger for tests involving crystalised as opposed to fluid intelligence. Exploiting the longitudinal nature of the data, we also investigate mobility across the distribution of test scores, with some evidence that such mobility is less among poorer children, which raises the disturbing possibility that such children could become trapped in low achievement. [ABSTRACT FROM AUTHOR]

Nutrients in quail eggs can be affected by egg product processing technologies. However, freeze-drying would be the most suitable, but it is very costly and difficult to transfer to the quail egg production actors. This study is aimed at comparing the physicochemical and microbiological qualities of liquid, pasteurized, hot air-dried, and freeze-dried quail eggs. Liquid quail eggs were used as controls. The physicochemical and microbiological qualities were evaluated by conventional methods. The results showed that freeze-dried and hot air-dried quail eggs differed (p < 0.05) from liquid and pasteurized quail eggs for all the evaluated parameters. On the other hand, pasteurized quail eggs were more concentrated (p < 0.05) in dry matter (45.2 ± 0.06 %) and fat (25.8 ± 1.33 %) with a more basic pH (7.9 ± 0.20) than liquid eggs. As for microbiological parameters, only total mesophilic aerobic germs were present with a significant difference (p < 0.05) between liquid (2.0 ± 1.4 log10 CFU/g), hot air-dried (2.1 ± 1.5 log10 CFU/g), and freeze-dried (1.8 ± 1.0 log10 CFU/g) quail eggs, but the load was much lower than the standard (5.7 log10 CFU/g). Total coliforms (0 CFU/g), Enterobacteriaceae (0 CFU/g), yeasts (0 CFU/g), molds (0 CFU/g), Salmonella, and Staphylococcus aureus were absent in all the egg products, while the standards provided 2.0 log10 CFU/g for total coliforms, 1.0 log10 CFU/g for Enterobacteriaceae, Salmonella absent in 25 g, Staphylococcus aureus absent in 1 g, and 2.0 log10 CFU/g for yeasts and molds. In conclusion, hot air-drying and pasteurization are transferable and suitable for the processing of quail eggs. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) is still a huge danger to human health. Sensitive markers are necessary for the prediction of the risk of AMI and would be beneficial for managing the incidence rate. N6-methyladenosine (m6A) RNA methylation regulators have been confirmed to be involved in the development of various diseases. However, their function in AMI has not been fully elucidated. The purpose of this study was to determine the expression of m6A RNA methylation regulators in AMI as well as their possible functions and prognostic values. The GEO database was used to get the gene expression profiles of patients with and without AMI, and bioinformatics assays of genes with differently expressed expression were performed. We establish two separate m6A subtypes, and relationships between subtypes and immunity were studied. In this study, we identified IGF2BP1, FTO, RBM15, METTL3, YTHDC2, FMR1, and HNRNPA2B1 as the seven major m6A regulators. A nomogram model was developed and confirmed. The consensus clustering algorithm was conducted to categorize AMI patients into two m6A subtypes from the identified m6A regulators. Patients who have activated T-cell activities were found to be in clusterA; they may have a better prognosis as a result. Importantly, we found that patients with high METTL3 expressions had an increased level of Activated.CD4.T.cell and Type.2.T.helper.cell, while having a decreased level of CD56bright.natural.killer.cell, Macrophage, Monocyte, Natural.killer.cell, and Type.17.T.helper.cell. Overall, a diagnostic model of AMI was established based on the genes of IGF2BP1, FTO, RBM15, METTL3, YTHDC2, FMR1, and HNRNPA2B1. Our investigation of m6A subtypes may prove useful in the developments of therapy approaches for AMI. [ABSTRACT FROM AUTHOR]

Simple Summary: Quail has become a popular poultry species, and it is usually used for egg production in Asia and for meat production in Europe and America. In laying quails, aging negatively affects productive performance, egg parameters, and reproductive hormones, just as it affects their bones and digestive systems. Farmers who raise quails suffer great losses due to this fact. There are several nutrients and bioactive substances in Maca with positive effects on hormones and digestive health, which makes it an excellent option for reducing the effects of aging. This study specifies the benefits of Maca powder on aging quails' diet. The experimental data indicate that adding 1 g/kg Maca powder to a quail's diet significantly improved eggshell, ileum, and bone traits that deteriorate with age, without affecting performance. Adding 2 g/kg Maca powder to a quail's diet also significantly reduced serum cholesterol levels. Incorporating Maca powder into the diet of aged birds could reduce the negative effects of aging. Using additives can reduce the negative effects of aging on factors affecting profitability, such as the availability of nutrients, production, and egg quality. Maca is an herbaceous plant rich in protein, crude oil, essential acids, and pharmacological compounds. Maca has positive effects on different health parameters. In this study, the effect of adding Maca powder to the diets of young and old laying quails at the end of the 10-week trial was investigated. In total, 150 laying Japanese quails (Coturnix japonica) (209.1 ± 10.0 g) were randomly distributed to a 2 × 3 factorial arrangement with two ages (10 weeks and 30 weeks) and three Maca powder levels (0, 1, or 2 g/kg), with five subgroups per treatment. According to the study, eggshell quality, total cholesterol, triglyceride, progesterone, and testosterone concentrations of serum were lower in old quail than in young quail, while egg weight, feed intake, and follicle-stimulating hormone increased significantly as quail aged. (p < 0.05). Furthermore, aging negatively affected the histomorphology of the ileum and cortical bone thickness (p < 0.05). Additional findings show that adding 1 g/kg Maca powder to the diet of quail significantly improved eggshell, ileum, and bone traits that deteriorate with age, without affecting performance, and adding 2 g/kg Maca powder to the diet significantly reduced serum total cholesterol levels (p < 0.05). Incorporating Maca powder into the diet of aged birds could reduce the negative effects of aging. [ABSTRACT FROM AUTHOR]

Non-canonical nuclear factor kappa B (NF-κB) signaling pathway regulates many physiological and pathological processes, including liver homeostasis and diseases. Recent studies demonstrate that non-canonical NF-κB signaling pathway plays an essential role in hyperglycemia, non-alcoholic fatty liver disease, alcoholic liver disease, liver regeneration, liver injury, autoimmune liver disease, viral hepatitis, and hepatocellular carcinoma. Small-molecule inhibitors targeting to non-canonical NF-κB signaling pathway have been developed and shown promising results in the treatment of liver injuries. Here, the recent advances and future prospects in understanding the roles of the non-canonical NF-κB signaling pathways in the regulation of liver diseases are discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer stem cells (CSCs) in breast cancer have been identified for almost two decades. Many outstanding discoveries have established the important functions of CSCs in breast cancer progression, metastasis, and resistance to therapy. As the defining feature of CSCs, stemness is induced and maintained by several important signaling pathways. Targeting these pathways is inevitably challenging because they are also critically involved in normal stem cells. Here, we will summarize the literature on breast cancer stem cells, including major signaling pathways, cellular interactions within the tumor microenvironment (TME), and potential therapeutic implications. Breast cancer stem cells (BCSCs) constitute a small population of cells within breast cancer and are characterized by their ability to self-renew, differentiate, and recapitulate the heterogeneity of the tumor. Clinically, BCSCs have been correlated with cancer progression, metastasis, relapse, and drug resistance. The tumorigenic roles of BCSCs have been extensively reviewed and will not be the major focus of the current review. Here, we aim to highlight how the crucial intrinsic signaling pathways regulate the fate of BCSCs, including the Wnt, Notch, Hedgehog, and NF-κB signaling pathways, as well as how different cell populations crosstalk with BCSCs within the TME, including adipocytes, endothelial cells, fibroblasts, and immune cells. Based on the molecular and cellular activities of BCSCs, we will also summarize the targeting strategies for BCSCs and related clinical trials. This review will highlight that BCSC development in breast cancer is impacted by both BCSC endogenous signaling and external factors in the TME, which provides an insight into how to establish a comprehensively therapeutic strategy to target BCSCs for breast cancer treatments. [ABSTRACT FROM AUTHOR]

Using data from Ireland's national longitudinal study of children, this paper employs a capabilities approach to disability to understand how individual characteristics as well as home and school environmental factors at age 9 relate to academic and socio-emotional outcomes of students with special educational needs (SEN) at age 17. Results suggest that young people with SEN register both lower average scores and make less academic progress between the age of 9 and their national lower secondary examination, with the exception of young people with a physical SEN. Both home and school environmental factors at 9 years have long-term associations with the academic outcomes of young people with SEN, after controlling for individual characteristics and prior academic achievement. Home and school environmental factors had less consistent associations with the socio-emotional outcomes of young people with SEN. By using rigorous nationally representative longitudinal data, this paper offers a more holistic understanding of the development of young people with SEN. The paper also provides important evidence that a more inclusive approach for supporting students with additional needs, their parents, and their schools is needed. [ABSTRACT FROM AUTHOR]

Catholic worship prioritises in-person ritual contact, but due to COVID-19, most Australian places of worship closed during 2020. An online survey of 1173 Australian churchgoing Catholics using the Spiritual Well Being Scale found no significant difference in Existential and Religious Wellbeing scores between groups who were still experiencing church closures and those who could attend church again. In those still experiencing church closures, standard multiple regression revealed significant and positive relationships between age and virtual worship engagement and both Existential and Religious Wellbeing scores. However, in those who could attend church once more, pre- and post-closure Mass attendance rate, and both virtual and real-life worship during church closures were all predictive of higher Existential and Religious Wellbeing scores. These results support the provision of access to both virtual and real-life worship during church closures, and their positive effects on both existential and religious wellbeing in a churchgoing Catholic population. [ABSTRACT FROM AUTHOR]

One hundred fifty 1-d-old quail chicks (Coturnix coturnix japonica) were divided into 2 groups. The 2 groups were designated as controls (CX) and fumonisin-fed birds (FX) with each containing 50 and 100 chicks, respectively. The birds in group CX were maintained on quail mash alone, whereas the birds in group FX were maintained on diets supplemented with 300 ppm of fumonisin B1 from Fusarium verticillioides (formerly Fusarium moniliforme) culture material from 1 d. Quail chicks in both groups were examined daily for clinical signs and mortality. Five randomly selected quail from each group were individually weighed on 0, 7, 14, 21, and 28 d post-feeding (DPF). After weighing, blood was collected from these birds at 7, 14, 21, and 28 DPF for hematological studies and at 14, 21, and 28 DPF for biochemical studies. Fumonisin B1-fed birds (FX) had ruffled feathers, reduced feed and water intake, poor body growth, and greenish mucus diarrhea with 59% mortality. Nearly 30% of the fumonisin B1-fed birds showed nervous signs during the 4-wk experimental period. From 7 DPF onward, BW in group FX were significantly lower than those in group CX. Fumonisin feeding significantly increased hemoglobin, packed cell volume, total erythrocyte count, and total leukocyte count. There was also a significant increase in aspartate transaminase and alanine transaminase in the fumonisin-fed group. Fumonisins significantly increased concentrations of total serum protein and albumin on 14 and 21 DPF, serum calcium and cholesterol levels from 14 DPF onward, and creatinine from 21 DPF onward. This study revealed that the addition of F. verticillioides culture material supplying a level of 300 ppm of FB1/kg of diet is highly toxic to quail chicks, resulting in heavy mortality, decreased growth rate, and significant alterations in hemato-biochemical parameters. [ABSTRACT FROM AUTHOR]

Background: A positive association has been known to exist between social activity engagements and fewer insomnia symptoms in later life. However, little is known about which social activities are associated with insomnia symptoms. Investigating mediating factors in this relationship may contribute to developing effective strategies for the reduction of sleep complaints in older adults. This study aimed to examine the mediating role of loneliness on the relationship between engagement in different social activities and insomnia symptoms. Methods: We used secondary data from the 2018 Health and Retirement Study. The study sample included 3236 older adults who responded to a survey on social activity engagement, insomnia symptoms, and loneliness. After adjusting for covariates, simple mediation analyses were performed with bootstrapping to identify the mediating role. Results: Among the several types of social activities, higher levels of engagement in educational courses and community arts group had a significant and direct relationship with fewer insomnia symptoms in older adults. Mediation analyses confirmed the mediating role of loneliness in the relationship between these specific social activity engagements and insomnia symptoms. Conclusion: These findings provide new evidence for associations among social activity, loneliness, and insomnia symptoms in older adults. [ABSTRACT FROM AUTHOR]

Prevention of neosporosis is advantageous for cattle health and productivity. Previously, several vaccine candidates were nominated for vaccination against Neospora caninum. This study was premised on in silico evaluation of N. caninum IMP-1 in order to determine its physicochemical features and immunogenic epitopes. We employed a wide array of network-based tools for the prediction of antigenicity, allergenicity, solubility, posttranslational modification (PTM) sites, physicochemical properties, transmembrane domains and signal peptide, secondary and tertiary structures, and intrinsically disordered regions. Also, prediction and screening of potential continuous B cell peptides and those epitopes having stringent affinity to couple with mouse major histocompatibility complex (MHC) and cytotoxic T lymphocyte (CTL) receptors were accomplished. The protein had 393 residues with a molecular weight of 42.71 kDa, representing aliphatic index of 85.83 (thermotolerant) and GRAVY score of -0.447 (hydrophilic). There were 47 PTM sites without a signal peptide in the sequence. Secondary structure comprised mostly of extended strand and helices, followed by coils. The Ramachandran plot of the refined model showed 90.1%, 9.9%, 0.0%, and 0.0% residues in the favored, additional allowed, generously allowed, and disallowed regions, correspondingly. Additionally, various potential B cell (linear and conformational), CTL, and MHC binding epitopes were predicted for N. caninum IMP-1. The findings of the present study could be further directed for next-generation vaccine design against neosporosis. [ABSTRACT FROM AUTHOR]

Sweet potatoes are experiencing increased popularity across many parts of the world due to their high levels of functionally beneficial compounds, including vitamin C, anthocyanins and carotenoids. However, limited work has been performed on Australian-grown sweet potatoes. This work investigated the key phytochemical composition of the root tissue of five Australian sweet potato cultivars that are grown commercially. The cultivar WSPF (White Skin, Purple Flesh) displayed the highest total phenolic content, total antioxidant capacity and total anthocyanin content. However, the cultivar Bellevue contained the highest β-carotene content (48.2 mg 100 g−1 on a dry weight basis), followed by New Orleans and Beauregard (43.0 and 34.0 mg 100 g−1, respectively). White and purple-fleshed cultivars contained virtually no β-carotene (0.1–0.2 mg 100 g−1). The New Orleans cultivar had the highest ascorbic acid content on a dry weight basis (51.9 mg 100 g−1) and the WSPF cultivar the lowest (17.8 mg 100 g−1). [ABSTRACT FROM AUTHOR]

Fluctuations in environmental conditions greatly influence life on earth. Plants, as sessile organisms, have developed molecular mechanisms to adapt their development to changes in daylength, or photoperiod. One of the first plant features that comes to mind as affected by the duration of the day is flowering time; we all bring up a clear image of spring blossom. However, for many plants flowering happens at other times of the year, and many other developmental aspects are also affected by changes in daylength, which range from hypocotyl elongation in Arabidopsis thaliana to tuberization in potato or autumn growth cessation in trees. Strikingly, many of the processes affected by photoperiod employ similar gene networks to respond to changes in the length of light/dark cycles. In this review, we have focused on developmental processes affected by photoperiod that share similar genes and gene regulatory networks. [ABSTRACT FROM AUTHOR]

Recombination is a major force that shapes genetic diversity. Determination of recombination rate is important and can theoretically be improved by increasing the sample size. However, it is nearly impossible to estimate recombination rates using traditional population genetics methods when the sample size is large because these methods are highly computationally demanding. In this study, we used a refined machine learning approach to estimate the recombination rate of the human genome using the UK10K human genomic dataset with 7,562 genomic sequences and its three subsets with 200, 400 and 2,000 genomic sequences. The estimation was performed under the human Out-of-Africa demographic model. We not only obtained an accurate human genetic map, but also found that the fluctuation of estimated recombination rate is reduced along the human genome when the sample size increases. The estimated UK10K recombination rate heterogeneity is less than that estimated from its subsets. Our results demonstrate how the sample size affects the estimated recombination rate, and analyses of a larger number of genomes result in a more precise estimation of recombination rate. The accurate genetic map based on UK10K data set is also expected to benefit other human biology researches. [ABSTRACT FROM AUTHOR]

A microplate-based assay was developed for the measurement of total phenolic content in polar ginger extracts, using the Folin-Ciocalteu method. The method optimisation process included investigating the effects of wavelength, incubation time and incubation temperature. The method was relatively robust, with most of these parameters having minimal impact on the results obtained. The optimised method could be conducted at room temperature and required only 20 min of combined incubation time. The repeatability of the microplate reader was 0.57%, with the gallic acid standards curve showing good linearity (R2 > 0.999). The mean intra- and inter-day reproducibility of the entire assay, which included operator error, was 4.4% and 7.8%, respectively. The optimised method was applied to analyse the total phenolic content of 200 ginger extracts in triplicate within approximately 8 h of labour time, finding a mean total phenolic content of 1713 ± 235 mg GAE 100 g−1 in the dried ginger powder samples. The total phenolic contents of the ginger samples showed a moderate positive correlation (R2 = 0.46) with the sum of gingerol and 6-shogaol contents, as measured by high-performance liquid chromatography (HPLC). This method could be useful to aid in screening large numbers of samples for total phenolic content in order to identify high-phenolic genotypes or for use in quality assurance settings. [ABSTRACT FROM AUTHOR]

Lower-grade glioma (LGG) is a common type of central nervous system tumor. Due to its complicated pathogenesis, the choice and timing of adjuvant therapy after tumor treatment are controversial. This study explored and identified potential therapeutic targets for lower-grade. The bioinformatics method was employed to identify potential biomarkers and LGG molecular mechanisms. Firstly, we selected and downloaded GSE15824, GSE50161, and GSE86574 from the GEO database, which included 40 LGG tissue and 28 normal brain tissue samples. GEO and VENN software identified of 206 codifference expressed genes (DEGs). Secondly, we applied the DAVID online software to investigate the DEG biological function and KEGG pathway enrichment, as well as to build the protein interaction visualization network through Cytoscape and STRING website. Then, the MCODE plug is used in the analysis of 22 core genes. Thirdly, the 22 core genes were analyzed with UNCLA software, of which 18 genes were associated with a worse prognosis. Fourthly, GEPIA was used to analyze the 18 selected genes, and 14 genes were found to be a significantly different expression between LGGs and normal brain tumor samples. Fifthly, hierarchical gene clustering was used to examine the 14 important gene expression differences in different histologies, as well as analysis of the KEGG pathway. Five of these genes were shown to be abundant in the natural killer cell-mediated cytokines (NKCC) and phagosome pathways. The five key genes that may be affected by the immune microenvironment play a crucial role in LGG development. [ABSTRACT FROM AUTHOR]

Featured Application: Full-length cathepsin B is sorted to endo-lysosomes of colorectal carcinoma cells, while N-terminally truncated cathepsin B accumulates in aggresomes. Cathepsin B is an endo-lysosomal cysteine protease. However, its increased expression and altered localization to the extracellular space, to mitochondria, or to the nucleus has been linked to tumor progression. In the present study, we show enhanced levels of cathepsin B in adenocarcinoma tissue in comparison to adjacent normal colon. Additionally, cathepsin B was observed in the nuclear compartment of mucosal cells in adenocarcinoma tissue samples and in the nuclei of the colorectal carcinoma cell line HCT116. Accordingly, a distinct 40-kDa form of cathepsin B was detected in HCT116 cells, which is proposed to represent a specific form lacking the signal peptide and parts of the propeptide. Trafficking studies with an EGFP-tagged N-terminally truncated form, mimicking the 40-kDa form, demonstrated accumulation in aggresome-like inclusion bodies, while EGFP-tagged full-length cathepsin B revealed regular sorting to endo-lysosomes. We conclude that the identity of nuclear cathepsin B in colorectal adenocarcinoma (in situ) and in carcinoma cells (in vitro) cannot be attributed to either full-length or 40-kDa N-terminally truncated cathepsin B forms. Hence, future studies are needed to demonstrate which form/s of cathepsin B may be sorted to the nuclei of colorectal carcinoma cells, and whether redundant regulation of related cathepsin expression occurs. [ABSTRACT FROM AUTHOR]

Protein synthesis is one of the most essential processes in every kingdom of life, and its dysregulation is a known driving force in cancer development. Multiple signaling pathways converge on the translation initiation machinery, and this plays a crucial role in regulating differential gene expression. In colorectal cancer, dysregulation of initiation results in translational reprogramming, which promotes the selective translation of mRNAs required for many oncogenic processes. The majority of upstream mutations found in colorectal cancer, including alterations in the WNT, MAPK, and PI3K\AKT pathways, have been demonstrated to play a significant role in translational reprogramming. Many translation initiation factors are also known to be dysregulated, resulting in translational reprogramming during tumor initiation and/or maintenance. In this review, we outline the role of translational reprogramming that occurs during colorectal cancer development and progression and highlight some of the most critical factors affecting the etiology of this disease. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the second leading cause of cancer death in women worldwide, and settings of specific prognostic factors and efficacious therapies are made difficult by phenotypic heterogeneity of BC subtypes. Therefore, there is a current urgent need to define novel predictive genetic predictors that may be useful for stratifying patients with distinct prognostic outcomes. Here, we looked for novel molecular signatures for triple negative breast cancers (TNBCs). By a bioinformatic approach, we identified a panel of genes, whose expression was positively correlated with disease-free survival in TNBC patients, namely IL18R1, CD53, TRIM, Jaw1, LTB, and PTPRCAP, showing specific immune expression profiles linked to survival prediction; most of these genes are indeed expressed in immune cells and are required for productive lymphocyte activation. According to our hypothesis, these genes were not, or poorly, expressed in different TNBC cell lines, derived from either primary breast tumours or metastatic pleural effusions. This conclusion was further supported in vivo, as immuno-histochemical analysis on biopsies of TNBC invasive ductal carcinomas highlighted differential expression of these six genes in cancer cells, as well as in intra- and peri-tumoral infiltrating lymphocytes. Our data open to the possibility that inter-tumour heterogeneity of immune markers might have predictive value; further investigations are recommended in order to establish the real power of cancer-related immune profiles as prognostic factors. [ABSTRACT FROM AUTHOR]