Monitoring the concentration of antibiotics rapidly and cost-effectively is crucial for accurate clinical medication and timely identification of drug-induced illnesses. Here, we constructed a novel fluorescent assay kit to monitor Zavicefta, an effective antibiotic composed of avibactam (AVI) and ceftazidime (CFZ) to treat carbapenem-resistant gram-negative bacteria infections. AVI can emit fluorescence, but CFZ cannot.
View Article and Find Full Text PDFIntroduction: The loose-patch clamp technique was first developed and used in native amphibian skeletal muscle (SkM), offering useful features complementing conventional sharp micro-electrode, gap, or conventional patch voltage clamping. It demonstrated the feedback effects of pharmacological modification of ryanodine receptor (RyR)-mediated Ca release on the Na channel (Nav1.4) currents, initiating excitation-contraction coupling in native murine SkM.
View Article and Find Full Text PDFHippocampal pyramidal neuronal activity has been previously studied using conventional patch clamp in isolated cells and brain slices. We here introduce the loose patch clamping study of voltage-activated currents from in situ pyramidal neurons in murine cornus ammonis 1 hippocampal coronal slices. Depolarizing pulses of 15-ms duration elicited early transient inward, followed by transient and prolonged outward currents in the readily identifiable junctional region between the stratum pyramidalis (SP) and oriens (SO) containing pyramidal cell somas and initial segments.
View Article and Find Full Text PDFMetabolic reaction rates (fluxes) play a crucial role in comprehending cellular phenotypes and are essential in areas such as metabolic engineering, biotechnology, and biomedical research. The state-of-the-art technique for estimating fluxes is metabolic flux analysis using isotopic labelling (C-MFA), which uses a dataset-model combination to determine the fluxes. Bayesian statistical methods are gaining popularity in the field of life sciences, but the use of C-MFA is still dominated by conventional best-fit approaches.
View Article and Find Full Text PDFThe quest to comprehend the nature of consciousness has spurred the development of many theories that seek to explain its underlying mechanisms and account for its neural correlates. In this paper, I compare my own conscious electromagnetic information field (cemi field) theory with integrated information theory (IIT) and global workspace theory (GWT) for their ability to 'carve nature at its joints' in the sense of predicting the entities, structures, states and dynamics that are conventionally recognized as being conscious or nonconscious. I go on to argue that, though the cemi field theory shares features of both integrated information theory and global workspace theory, it is more successful at carving nature at its conventionally accepted joints between conscious and nonconscious systems, and is thereby a more successful theory of consciousness.
View Article and Find Full Text PDFOccam's razor-the principle of simplicity-has recently been attacked as a cultural bias without rational foundation. Increasingly, belief in pseudoscience and mysticism is growing. I argue that inclusion of Occam's razor is an essential factor that distinguishes science from superstition and pseudoscience.
View Article and Find Full Text PDFAntibiotic persistence is a phenomenon observed when genetically susceptible cells survive long-term exposure to antibiotics. These 'persisters' are an intrinsic component of bacterial populations and stem from phenotypic heterogeneity. Persistence to antibiotics is a concern for public health globally, as it increases treatment duration and can contribute to treatment failure.
View Article and Find Full Text PDFRapid, reliable, sensitive, portable, and accurate diagnostics are required to control disease outbreaks such as COVID-19 that pose an immense burden on human health and the global economy. Here we developed a loop-mediated isothermal amplification (LAMP)-based electrochemical test for the detection of SARS-CoV-2 that causes COVID-19. The test is based on the oxidation-reduction reaction between pyrophosphates (generated from positive LAMP reaction) and molybdate that is detected by cyclic voltammetry using inexpensive and disposable carbon screen printed electrodes.
View Article and Find Full Text PDFIntroduction: Antibiotic persistence (subpopulation tolerance) occurs when a subpopulation of antibiotic sensitive cells survives prolonged exposure to a bactericidal concentration of an antibiotic, and is capable of regrowth once the antibiotic is removed. This phenomenon has been shown to contribute to prolonged treatment duration, infection recurrence, and accelerated development of genetic resistance. Currently, there are no biomarkers which would allow for segregation of these antibiotic-tolerant cells from the bulk population prior to antibiotic exposure, limiting research on this phenomenon to retrograde analyses.
View Article and Find Full Text PDFConventional theories of consciousness (ToCs) that assume that the substrate of consciousness is the brain's neuronal matter fail to account for fundamental features of consciousness, such as the binding problem. Field ToC's propose that the substrate of consciousness is the brain's best accounted by some kind of field in the brain. Electromagnetic (EM) ToCs propose that the conscious field is the brain's well-known EM field.
View Article and Find Full Text PDFMetabolic flux is the final output of cellular regulation and has been extensively studied for carbon but much less is known about nitrogen, which is another important building block for living organisms. For the tuberculosis pathogen, this is particularly important in informing the development of effective drugs targeting the pathogen's metabolism. Here we performed C N dual isotopic labeling of Mycobacterium bovis BCG steady state cultures, quantified intracellular carbon and nitrogen fluxes and inferred reaction bidirectionalities.
View Article and Find Full Text PDFLeptospirosis is a neglected disease of man and animals that affects nearly half a million people annually and causes considerable economic losses. Current human vaccines are inactivated whole-cell preparations (bacterins) of spp. that provide strong homologous protection yet fail to induce a cross-protective immune response.
View Article and Find Full Text PDFBiological effects of electromagnetic fields (EMFs) have previously been identified for cellular proliferation and changes in expression and conduction of diverse types of ion channels. The major effect elicited by EMFs seems to be directed toward Ca homeostasis. This is particularly remarkable since Ca acts as a central modulator in various signaling pathways, including, but not limited to, cell differentiation and survival.
View Article and Find Full Text PDFis an important pathogenic bacterium commonly associated with human healthcare and community-acquired infections. In recent years, has become a significant threat to global public and veterinary health, because of its high rates of antimicrobial resistance (AMR). Early diagnosis of infection and detection of any associated AMR would help to accelerate directed therapy and reduce the risk of the emergence of multidrug-resistant isolates.
View Article and Find Full Text PDFFront Immunol
February 2022
Tuberculosis (TB) is a devastating infectious disease that kills over a million people every year. There is an increasing burden of multi drug resistance (MDR) and extensively drug resistance (XDR) TB. New and improved therapies are urgently needed to overcome the limitations of current treatment.
View Article and Find Full Text PDFNeisseria meningitidis is the etiologic agent of meningococcal meningitis and sepsis. Initial colonization of meningococci in the upper respiratory tract epithelium is crucial for disease development. The colonization occurs in several steps and expression of type IV pili (Tfp) is essential for both attachment and microcolony formation of encapsulated bacteria.
View Article and Find Full Text PDFMany aspects of chemistry and biology are mediated by electromagnetic field (EMF) interactions. The central nervous system (CNS) is particularly sensitive to EMF stimuli. Studies have explored the direct effect of different EMFs on the electrical properties of neurons in the last two decades, particularly focusing on the role of voltage-gated ion channels (VGCs).
View Article and Find Full Text PDFThe co-catabolism of multiple host-derived carbon substrates is required by Mycobacterium tuberculosis (Mtb) to successfully sustain a tuberculosis infection. However, the metabolic plasticity of this pathogen and the complexity of the metabolic networks present a major obstacle in identifying those nodes most amenable to therapeutic interventions. It is therefore critical that we define the metabolic phenotypes of Mtb in different conditions.
View Article and Find Full Text PDFAn amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDFNeurosci Conscious
September 2020
A key aspect of consciousness is that it represents bound or integrated information, prompting an increasing conviction that the physical substrate of consciousness must be capable of encoding integrated information in the brain. However, as Ralph Landauer insisted, 'information is physical' so integrated information must be physically integrated. I argue here that nearly all examples of so-called 'integrated information', including neuronal information processing and conventional computing, are only temporally integrated in the sense that outputs are correlated with multiple inputs: the information integration is implemented in time, rather than space, and thereby cannot correspond to physically integrated information.
View Article and Find Full Text PDFBovine tuberculosis is an important animal health problem and the predominant cause of zoonotic tuberculosis worldwide. It results in serious economic burden due to losses in productivity and the cost of control programmes. Control could be greatly improved by the introduction of an efficacious cattle vaccine but the most likely candidate, BCG, has several limitations including variable efficacy.
View Article and Find Full Text PDFLeprosy, caused by Mycobacterium leprae, has plagued humanity for thousands of years and continues to cause morbidity, disability and stigmatization in two to three million people today. Although effective treatment is available, the disease incidence has remained approximately constant for decades so new approaches, such as vaccine or new drugs, are urgently needed for control. Research is however hampered by the pathogen's obligate intracellular lifestyle and the fact that it has never been grown in vitro.
View Article and Find Full Text PDFWhenever a genetically homogenous population of bacterial cells is exposed to antibiotics, a tiny fraction of cells survives the treatment, the phenomenon known as bacterial persistence [G.L. Hobby , 50, 281-285 (1942); J.
View Article and Find Full Text PDFNew approaches are needed to control leprosy, but understanding of the biology of the causative agent remains rudimentary, principally because the pathogen cannot be grown in axenic culture. Here, we applied C isotopomer analysis to measure carbon metabolism of in its primary host cell, the Schwann cell. We compared the results of this analysis with those of a related pathogen, , growing in its primary host cell, the macrophage.
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