Search Results (32)

This paper suggests a method of private internalization of externalities via the bundling of new fossil fuel automobile purchases. The bundle encourages and pursues a new quality of life entailing planting trees, a healthy body and mind, and efficient use of new energy usages for the joining of a grassroots environmental club. The work was motivated by the classic economics article by Ronald Coase, The Problem of Social Cost (1960). Marketing plays an important role in this internalization endeavor. Indeed, modern behavioral economics and psychology help inform how creative bundles of a new automobile purchase with sustainable lifestyle elements can effectively formulate some promotional propositions. The pragmatism we are demonstrating in this piece is to show the linkage between theories and marketable directions that can be experimented with via trial-and-error, as in many bundling exercises. Full article

Background/objectives: Amino acids (AAs) play a critical role in diseases such as cystic fibrosis where Pseudomonas aeruginosa PAO1 adapts its metabolism in response to host-derived nutrients. The adaptation influences virulence and complicates antibiotic treatment mainly for the antimicrobial resistance context. D- and L-AAs have been analyzed for their impact on quorum sensing (QS), a mechanism that regulates virulence factors. This research aimed to reconstruct the genome-scale metabolic model (GEM) of P. aeruginosa PAO1 to investigate the metabolic roles of D- and L-AAs in QS-related pathways. Methods: The updated GEM, iJD1249, was reconstructed by using protocols to integrate data from previous models and refined with well-standardized in silico media (LB, M9, and SCFM) to improve flux balance analysis accuracy. The model was used to explore the metabolic impact of D-Met, D-Ala, D-Glu, D-Ser, L-His, L-Glu, L-Arg, and L-Ornithine (L-Orn) at 5 and 50 mM in QS-related pathways, focusing on the effects on bacterial growth and carbon flux distributions. Results: Among the tested AAs, D-Met was the only one that did not enhance the growth rate of P. aeruginosa PAO1, while L-Arg and L-Orn increased fluxes in the L-methionine biosynthesis pathway, influencing the metH gene. These findings suggest a differential metabolic role for D-and L-AAs in QS-related pathways. Conclusions: Our results shed some light on the metabolic impact of AAs on QS-related pathways and their potential role in P. aeruginosa virulence. Future studies should assess D-Met as a potential adjuvant in antimicrobial strategies, optimizing the concentration in combination with antibiotics to maximize its therapeutic effectiveness. Full article

Background/Objectives: Rehabilitation helps reduce disability in dementia. The Australian National Dementia Action Plan identifies a gap in clear treatment pathways post-diagnosis, affecting the quality of life for those with dementia. This study assessed the impact of a one-day dementia training course and follow-up on GPs’ and practice nurses’ knowledge, attitudes, and confidence regarding dementia rehabilitation. Methods: The training, led by two experienced GPs and an academic physiotherapist, covered dementia diagnosis, allied health roles, care planning, and referrals. The follow-up involved applying the learnt material and completing a reflective task. Three longitudinal surveys (Dementia Knowledge Assessment Scale—DKAS, General Practitioners’ Attitudes and Confidence towards Dementia Survey—GPACS-D, and Dementia Rehabilitation Scale) and Likert-scale statements were conducted pre-course, post-course, and at four-month follow-up, alongside a focus group. Descriptive and regression analyses were applied to survey data, and content analysis was used for focus group data. Results: Seventeen participants (14 GPs, 3 nurses) completed the pre–post-course survey, with eight (6 GPs, 2 nurses) participating in follow-up and focus group discussions. Post-course, DKAS scores increased by 12.1%, GPACS-D by 10.1%, and the dementia rehabilitation scale by 9.4%. Likert-scale statements improved by 8–79%. At the four-month follow-up, there was a slight, non-significant decline in most measures. Focus groups highlighted the training’s impacts, useful components, barriers, and suggestions for improvement. Conclusion: Training GPs and practice nurses in dementia rehabilitation enhances knowledge, awareness, and confidence. Ongoing efforts are needed to sustain benefits and address referral barriers for better access to dementia rehabilitation services. Full article

This essay is based on a case study of international medical graduates (IMGs) in Canada who migrated from sub-Saharan Africa. The chapter examines how narratives of race are situated and deployed in the field of medicine and can produce some aversive social–psychological landscapes in the credentialing and the professional-entry process as it relates to persons of African descent. It will show that, often without predetermination or intent, professionals of African descent in Canada are highly susceptible to implicit racial associations and implicit racial stereotyping in relation to evaluations of character, credentials, and culture. The article exposes some of the critical intersections of common experience, such as: (a) cultural deficit bias—Whiteness as an institutionalized cultural capital attribute; (b) confirmation bias—reaching a negative conclusion and working backwards to find evidence to support it; (c) repurposed sub-Saharan Blackness stereotypes—binary forms of techno-scamming and fraud; and (d) biased deception judgement—where the accuracy of deception judgements deteriorates when made across cultures. These social psychological phenomena result in significantly disproportionate returns on their foreign education and labour market experience for Black medical professionals that require decisive efforts in changing the narratives. Full article

Over the past few decades, Canadian courts have exerted strong influence over the meaning and operation of parliamentary privileges. Starting with a television producer’s Charter rights claim to access a provincial legislature’s public gallery and followed by an employment law claim made by the chauffeur to the Speaker of the House of Commons, the Supreme Court of Canada has articulated an approach under which judges closely scrutinise privileges invoked by legislatures when defending themselves against litigated claims. By applying the doctrine of necessity, Canadian courts make authoritative rulings on what counts as a valid legislative function and the processes and activities needed to fulfil those functions. Canadian courts also require the scope of parliamentary privileges to be pleaded in narrow terms that correspond to the details of a plaintiff’s claim, which has resulted in a hollowed-out conception of privilege over time. In scrutinising the necessity and scope of privilege, Canadian courts have chipped away at the separation of powers. Further, the Canadian approach unjustifiably prioritises the judicial vindication of private rights over the institutional needs of the legislature. Courts in other jurisdictions should reject the Canadian approach and avoid scrutinising the propriety of the exercise of privilege through a necessity test. Instead, courts should engage in a more limited jurisdictional test to confirm the availability of a relevant category of parliamentary privilege in law or historical practice. Judicialising parliamentary privileges weakens the autonomy and vitality of legislative institutions, with the Canadian approach serving as a cautionary tale. Ultimately, the legislature is accountable to the electorate for the exercise of its privileges. To promote fairness and reduce the risk of court interference, parliaments should strengthen the accountability and transparency associated with the exercise of their privileges, including by developing guidelines for their appropriate use. Full article

Label-free electrochemical biosensors have many desirable characteristics in terms of miniaturization, scalability, digitization, and other attributes associated with point-of-care (POC) applications. In the era of COVID-19 and pandemic preparedness, further development of such biosensors will be immensely beneficial for rapid testing and disease management. Label-free electrochemical biosensors often employ [Fe(CN)₆]^−3/4 redox probes to detect low-concentration target analytes as they dramatically enhance sensitivity. However, such Faradaic-based sensors are reported to experience baseline signal drift, which compromises the performance of these devices. Here, we describe the use of a mecaptohexanoic (MHA) self-assembled monolayer (SAM) modified Au-interdigitated electrode arrays (IDA) to investigate the origin of the baseline signal drift, developed a protocol to resolve the issue, and presented insights into the underlying mechanism on the working of label-free electrochemical biosensors. Using this protocol, we demonstrate the application of MHA SAM-modified Au-IDA for POC analysis of human serum samples. We describe the use of a label-free electrochemical biosensor based on covalently conjugated SARS-CoV-2 spike protein for POC detection of COVID-19 antibodies. The test requires a short incubation time (10 min), and has a sensitivity of 35.4/decade (35.4%/10 ng mL⁻¹) and LOD of 21 ng/mL. Negligible cross reactivity to seasonal human coronavirus or other endogenous antibodies was observed. Our studies also show that Faradaic biosensors are ~17 times more sensitive than non-Faradaic biosensors. We believe the work presented here contributes to the fundamental understanding of the underlying mechanisms of baseline signal drift and will be applicable to future development of electrochemical biosensors for POC applications. Full article

Treatment of hyperpigmented skin disorders by novel drug candidates without side effects remains an ongoing area of research. Chemically modified tetracyclines (CMTs) are a group of nonantimicrobial tetracycline drugs that have been shown to possess multiple pharmacological activities. We have previously documented the anti-melanogenic effects of CMT-3 and its 9-amino derivative, CMT-308. Herein, we have extended our analysis to evaluate other CMT analogs, namely CMT-1, CMT-4, CMT-5, CMT-6, and CMT-8, for their impact on melanogenesis using primary human epidermal melanocytes (HEMn-DP cells). CMT analogs were screened using a tetrazolium-based assay to identify nontoxic concentration ranges that were further used to analyze the effects of CMTs on cellular melanin content and morphology (via quantitation of dendricity). Cellular tyrosinase (TYR) activity and levels of melanogenesis proteins, TYR, and microphthalmia transcription factor (MITF) were also evaluated to elucidate the mechanisms underlying their effects on melanogenesis. The findings demonstrated that exposure to CMT-8 resulted in notable cytotoxic effects at concentrations >10 µM; hence, all five analogs were further evaluated and compared at 10 µM. None of the five CMT analogs exhibited any impact on intracellular melanin in HEMn-DP cells at the concentration of 10 µM. However, CMT-1, CMT-4, and CMT-8 robustly suppressed dendricity parameters in HEMn-DP cells, while CMT-5 and CMT-6 showed no effect, suggesting that only a subset of CMT analogs can attenuate melanocyte dendricity. Moreover, the analog CMT-5, which has β-diketone blocked, was ineffective, thus confirming the role of this moiety in suppressing dendrite formation. CMT-1 and CMT-8 did not affect cellular tyrosinase activity, while CMT-4 suppressed TYR activity at 10 µM. The capacity of CMT-4 and CMT-8 to suppress dendricity was partly associated with their ability to downregulate MITF protein levels, while CMT-1 had no effect on MITF but suppressed TYR protein levels. The results of this study indicate that CMT-1, CMT-4, and CMT-8 merit further investigation using in vivo studies as potential drug candidates for the treatment of hyperpigmentation disorders. Full article

The drive for net-zero emission and global decarbonization spurred the need for a worldwide transition towards cleaner energy options. The fossil-fuel-dominated global transportation system is a target for these initiatives, accounting for 37% of recent carbon emissions. This has accelerated the adoption of electric vehicles (EVs) into the global market to cut down carbon emissions and improve efficiency in the transportation sector. In the face of this growth, limitations in EV charging infrastructure still loom large amongst EV consumers. Resolving this bottleneck requires systematic approaches to ensure seamless operation and integration into the existing transport systems. This study examines the critical role of IoT in addressing the challenges of EV public charging through reviewing the literature to understand the inter-relation and highlighting its attendant impact on consumer experience. Findings show that while IoT serves as a strong tool to foster public interest through favorable public policy, its novel and innovative nature faces developmental challenges based on existing government policies that could hinder the interest of potential investors. Therefore, governments should consider evaluating existing policies and practices to ascertain their suitability for IoT adoption in EVs, ensuring that they do not constitute unintentional barriers. Full article

Geological lineaments are linear or curvilinear surfaces that are considered a superficial expression of discontinuities on the earth’s surface. The extraction of lineaments from remotely sensed satellite data is one of the most frequently used applications of remote sensing in geology. This study focuses on the semi-automatic extraction of lineaments in the Girón–Santa Isabel basin using a Topographic Position Index (TPI). The lineaments were extracted in the PCI Geomatics 2016 software and analyzed in the ArcGIS and Rockworks software. Statistical and density map analyses of the lineaments were performed; then, these results were interpreted to obtain the geological lineaments. Finally, a bibliographic verification was carried out, and structures such as faults and folds were defined. The total number of geological lineaments was 76, and 71 of them were defined as faults, the longest with a length of 33 km. It was determined that the preferential orientation of the lineaments is NE–SW, which is consistent with the axis of the Girón–Santa Isabel basin. This methodology can be useful to optimize time and reduce costs when gathering the structural information of the study area in the first stage of geological and mining prospecting or the educational field. Full article

Synthetic nucleic acid interactors represent an exciting research field due to their biotechnological and potential therapeutic applications. The translation of these molecules into drugs is a long and difficult process that justifies the continuous research of new chemotypes endowed with favorable binding, pharmacokinetic and pharmacodynamic properties. In this scenario, we describe the synthesis of two sets of homo-thymine nucleopeptides, in which nucleobases are inserted in a peptide structure, to investigate the role of the underivatized amino acid residue and the distance of the nucleobase from the peptide backbone on the nucleic acid recognition process. It is worth noting that the CD spectroscopy investigation showed that two of the reported nucleopeptides, consisting of alternation of thymine functionalized L-Orn and L-Dab and L-Arg as underivatized amino acids, were able to efficiently bind DNA and RNA targets and cross both cell and nuclear membranes. Full article

The Clinical Proteomic Tumor Analysis Consortium (CPTAC) has provided some of the most in-depth analyses of the phenotypes of human tumors ever constructed. Today, the majority of proteomic data analysis is still performed using software housed on desktop computers which limits the number of sequence variants and post-translational modifications that can be considered. The original CPTAC studies limited the search for PTMs to only samples that were chemically enriched for those modified peptides. Similarly, the only sequence variants considered were those with strong evidence at the exon or transcript level. In this multi-institutional collaborative reanalysis, we utilized unbiased protein databases containing millions of human sequence variants in conjunction with hundreds of common post-translational modifications. Using these tools, we identified tens of thousands of high-confidence PTMs and sequence variants. We identified 4132 phosphorylated peptides in nonenriched samples, 93% of which were confirmed in the samples which were chemically enriched for phosphopeptides. In addition, our results also cover 90% of the high-confidence variants reported by the original proteogenomics study, without the need for sample specific next-generation sequencing. Finally, we report fivefold more somatic and germline variants that have an independent evidence at the peptide level, including mutations in ERRB2 and BCAS1. In this reanalysis of CPTAC proteomic data with cloud computing, we present an openly available and searchable web resource of the highest-coverage proteomic profiling of human tumors described to date. Full article

Quantitative real-time PCR was used to monitor the expression of 15 Verticillium dahliae’s genes, putatively involved in pathogenicity, highly (HAV) and weakly aggressive (WAV) V. dahliae isolates after either (i) elicitation with potato leaf, stem, or root extracts, or (ii) inoculation of potato detached petioles. These genes, i.e., coding for Ras-GAP-like protein, serine/threonine protein kinase, Ubiquitin-conjugating enzyme variant-MMS2, NADH-ubiquinone oxidoreductase, Thioredoxin, Pyruvate dehydrogenase E1 VdPDHB, myo-inositol 2-dehydrogenase, and HAD-superfamily hydrolase, showed differential upregulation in the HAV versus WAV isolate in response to plant extracts or after inoculation of potato leaf petioles. This suggests their potential involvement in the observed differential aggressiveness between isolates. However, other genes like glucan endo-1,3-alpha-glucosidase and nuc-1 negative regulatory protein VdPREG showed higher activity in the WAV than in the HAV in response to potato extracts and/or during infection. This, in contrast, may suggest a role in their lower aggressiveness. These findings, along with future functional analysis of selected genes, will contribute to improving our understanding of V. dahliae’s pathogenesis. For example, expression of VdPREG negatively regulates phosphorus-acquisition enzymes, which may indicate a lower phosphorus acquisition activity in the WAV. Therefore, integrating the knowledge about the activity of both genes enhancing pathogenicity and those restraining it will provide a guild line for further functional characterization of the most critical genes, thus driving new ideas towards better Verticillium wilt management. Full article

Lipids play essential roles in numerous cellular processes, including membrane remodeling, signal transduction, the modulation of hormone activity, and steroidogenesis. We chose steroidogenic MA-10 mouse tumor Leydig cells to investigate subcellular lipid localization during steroidogenesis. Electron microscopy showed that cAMP stimulation increased associations between the plasma membrane (PM) and the endoplasmic reticulum (ER) and between the ER and mitochondria. cAMP stimulation also increased the movement of cholesterol from the PM compared to untreated cells, which was partially inhibited when ATPase family AAA-domain containing protein 3 A (ATAD3A), which functions in ER and mitochondria interactions, was knocked down. Mitochondria, ER, cytoplasm, PM, PM-associated membranes (PAMs), and mitochondria-associated membranes (MAMs) were isolated from control and hormone-stimulated cells. Lipidomic analyses revealed that each isolated compartment had a unique lipid composition, and the induction of steroidogenesis caused the significant remodeling of its lipidome. cAMP-induced changes in lipid composition included an increase in phosphatidylserine and cardiolipin levels in PAM and PM compartments, respectively; an increase in phosphatidylinositol in the ER, mitochondria, and MAMs; and a reorganization of phosphatidic acid, cholesterol ester, ceramide, and phosphatidylethanolamine. Abundant lipids, such as phosphatidylcholine, were not affected by hormone treatment. Our data suggested that PM–ER–mitochondria tethering may be involved in lipid trafficking between organelles and indicated that hormone-induced acute steroid production involves extensive organelle remodeling. Full article

An estimated two billion people worldwide have been infected with hepatitis B virus (HBV). Despite the high infectivity of HBV in vivo, a lack of easily infectable in vitro culture systems hinders studies of HBV. Overexpression of the sodium taurocholate co-transporting polypeptide (NTCP) bile acid transporter in hepatoma cells improved infection efficiency. We report here a hepatoma cell culture system that does not require dimethyl sulfoxide (DMSO) for HBV infection. We overexpressed NTCP in Huh7.5 cells and allowed these cells to differentiate in a medium supplemented with human serum (HS) instead of fetal bovine serum (FBS). We show that human serum culture enhanced HBV infection in Huh7.5-NTCP cells, e.g., in HS cultures, HBV pgRNA levels were increased by as much as 200-fold in comparison with FBS cultures and 19-fold in comparison with FBS+DMSO cultures. Human serum culture increased levels of hepatocyte differentiation markers, such as albumin secretion, in Huh7.5-NTCP cells to similar levels found in primary human hepatocytes. N-glycosylation of NTCP induced by culture in human serum may contribute to viral entry. Our study demonstrates an in vitro HBV infection of Huh7.5-NTCP cells without the use of potentially toxic DMSO. Full article

Dental implants are widely utilized for the replacement of missing teeth and are increasingly being placed in patients with systemic diseases, as well as in those who are medically healthy. Furthermore, it is recognized that peri-implant mucositis and peri-implantitis are highly prevalent, affecting large numbers of patients with implants, and it is pertinent to consider whether there may be any systemic impact of these conditions, given that there are known links between periodontitis and a number of chronic inflammatory diseases. In this article, we propose that the potential systemic complications of peri-implant diseases should be investigated in future clinical research, together with studies to identify whether systemically-administered host modulation therapies (HMTs) may be of benefit in the treatment of peri-implant diseases. These “HMTs” may prove a useful adjunct to routinely employed debridement and disinfection protocols, as well as potentially being of benefit in reducing risks of systemic complications. We also consider the use of chair-side diagnostic tests for active matrix metalloproteinase-8 (aMMP-8) in the detection of peri-implant disease given the ability of such tests to detect active tissue breakdown associated with peri-implantitis and periodontitis before conventional clinical and radiographic measurements indicate pathologic changes. These novel diagnostic and therapeutic strategies are relevant to consider as they may improve the management of peri-implant disease (beyond local debridement procedures), especially in those patients in whom systemic inflammation might be of concern. Full article