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Molecules (Basel, Switzerland) Sep 2011Replicating cells undergo DNA synthesis in the highly regulated, S-phase of the cell cycle. Analogues of the pyrimidine deoxynucleoside thymidine may be inserted into... (Review)
Review
Replicating cells undergo DNA synthesis in the highly regulated, S-phase of the cell cycle. Analogues of the pyrimidine deoxynucleoside thymidine may be inserted into replicating DNA, effectively tagging dividing cells allowing their characterisation. Tritiated thymidine, targeted using autoradiography was technically demanding and superseded by 5-bromo-2-deoxyuridine (BrdU) and related halogenated analogues, detected using antibodies. Their detection required the denaturation of DNA, often constraining the outcome of investigations. Despite these limitations BrdU alone has been used to target newly synthesised DNA in over 20,000 reviewed biomedical studies. A recent breakthrough in "tagging DNA synthesis" is the thymidine analogue 5-ethynyl-2'-deoxyuridine (EdU). The alkyne group in EdU is readily detected using a fluorescent azide probe and copper catalysis using 'Huisgen's reaction' (1,3-dipolar cycloaddition or 'click chemistry'). This rapid, two-step biolabelling approach allows the tagging and imaging of DNA within cells whilst preserving the structural and molecular integrity of the cells. The bio-orthogonal detection of EdU allows its application in more experimental assays than previously possible with other "unnatural bases". These include physiological, anatomical and molecular biological experimentation in multiple fields including, stem cell research, cancer biology, and parasitology. The full potential of EdU and related molecules in biomedical research remains to be explored.
Topics: Animals; Bromodeoxyuridine; Cell Proliferation; Cells, Cultured; Click Chemistry; DNA; Deoxyuridine; Fluorescent Dyes; Humans; Staining and Labeling; Stem Cell Niche; Thymidine
PubMed: 21921870
DOI: 10.3390/molecules16097980 -
Frontiers in Pharmacology 2021Sepsis is a continuing problem in modern healthcare, with a relatively high prevalence, and a significant mortality rate worldwide. Currently, no specific anti-sepsis... (Review)
Review
Sepsis is a continuing problem in modern healthcare, with a relatively high prevalence, and a significant mortality rate worldwide. Currently, no specific anti-sepsis treatment exists despite decades of research on developing potential therapies. Annexins are molecules that show efficacy in preclinical models of sepsis but have not been investigated as a potential therapy in patients with sepsis. Human annexins play important roles in cell membrane dynamics, as well as mediation of systemic effects. Most notably, annexins are highly involved in anti-inflammatory processes, adaptive immunity, modulation of coagulation and fibrinolysis, as well as protective shielding of cells from phagocytosis. These discoveries led to the development of analogous peptides which mimic their physiological function, and investigation into the potential of using the annexins and their analogous peptides as therapeutic agents in conditions where inflammation and coagulation play a large role in the pathophysiology. In numerous studies, treatment with recombinant human annexins and annexin analogue peptides have consistently found positive outcomes in animal models of sepsis, myocardial infarction, and ischemia reperfusion injury. Annexins A1 and A5 improve organ function and reduce mortality in animal sepsis models, inhibit inflammatory processes, reduce inflammatory mediator release, and protect against ischemic injury. The mechanisms of action and demonstrated efficacy of annexins in animal models support development of annexins and their analogues for the treatment of sepsis. The effects of annexin A5 on inflammation and platelet activation may be particularly beneficial in disease caused by SARS-CoV-2 infection. Safety and efficacy of recombinant human annexin A5 are currently being studied in clinical trials in sepsis and severe COVID-19 patients.
PubMed: 34566657
DOI: 10.3389/fphar.2021.735472 -
Frontiers in Behavioral Neuroscience 2014Analogies may arise from the conscious detection of similarities between a present and a past situation. In this functional magnetic resonance imaging study, we tested...
Analogies may arise from the conscious detection of similarities between a present and a past situation. In this functional magnetic resonance imaging study, we tested whether young volunteers would detect analogies unconsciously between a current supraliminal (visible) and a past subliminal (invisible) situation. The subliminal encoding of the past situation precludes awareness of analogy detection in the current situation. First, participants encoded subliminal pairs of unrelated words in either one or nine encoding trials. Later, they judged the semantic fit of supraliminally presented new words that either retained a previously encoded semantic relation ("analog") or not ("broken analog"). Words in analogs versus broken analogs were judged closer semantically, which indicates unconscious analogy detection. Hippocampal activity associated with subliminal encoding correlated with the behavioral measure of unconscious analogy detection. Analogs versus broken analogs were processed with reduced prefrontal but enhanced medial temporal activity. We conclude that analogous episodes can be detected even unconsciously drawing on the episodic memory network.
PubMed: 24478656
DOI: 10.3389/fnbeh.2014.00009 -
BioRxiv : the Preprint Server For... Jun 2023Microfluidics have enabled significant advances in molecular biology , synthetic chemistry , diagnostics , and tissue engineering . However, there has long been a...
Microfluidics have enabled significant advances in molecular biology , synthetic chemistry , diagnostics , and tissue engineering . However, there has long been a critical need in the field to manipulate fluids and suspended matter with the precision, modularity, and scalability of electronic circuits . Just as the electronic transistor enabled unprecedented advances in the control of electricity on an electronic chip, a microfluidic analogue to the transistor could enable improvements in the complex, scalable control of reagents, droplets, and single cells on an autonomous microfluidic chip. Prior works on creating a microfluidic analogue to the electronic transistor could not replicate the transistor's saturation behavior, which is crucial to perform analog amplification and is fundamental to modern circuit design . Here we exploit the fluidic phenomenon of to develop a microfluidic element with flow-pressure characteristics completely analogous to the current-voltage characteristics of the electronic transistor. As this microfluidic transistor successfully replicates all of the key operating regimes of the electronic transistor (linear, cut-off and saturation), we are able to directly translate a variety of fundamental electronic circuit designs into the fluidic domain, including the amplifier, regulator, level shifter, logic gate, and latch. Finally, we demonstrate a "smart" particle dispenser that senses single suspended particles, performs liquid signal processing, and accordingly controls the movement of said particles in a purely fluidic system without electronics. By leveraging the vast repertoire of electronic circuit design, microfluidic transistor-based circuits are easy to integrate at scale, eliminate the need for external flow control, and enable uniquely complex liquid signal processing and single-particle manipulation for the next generation of chemical, biological, and clinical platforms.
PubMed: 37398240
DOI: 10.1101/2023.05.31.543146 -
Journal of the American Chemical Society Jun 2022Since the advent of organotransuranium chemistry six decades ago, structurally verified complexes remain restricted to π-bonded carbocycle and σ-bonded hydrocarbyl...
Since the advent of organotransuranium chemistry six decades ago, structurally verified complexes remain restricted to π-bonded carbocycle and σ-bonded hydrocarbyl derivatives. Thus, transuranium-carbon multiple or dative bonds are yet to be reported. Here, utilizing diphosphoniomethanide precursors we report the synthesis and characterization of transuranium-carbene derivatives, namely, diphosphonio-alkylidene- and -heterocyclic carbene-neptunium(III) complexes that exhibit polarized-covalent σπ multiple and dative σ single transuranium-carbon bond interactions, respectively. The reaction of [NpI(THF)] with [Rb(BIPMH)] (BIPMH = {HC(PPhNSiMe)}) affords [(BIPMH)Np(I)(THF)] () in situ, and subsequent treatment with the -heterocyclic carbene {C(NMeCMe)} (I) allows isolation of [(BIPMH)Np(I)(I)] (). Separate treatment of in situ prepared with benzyl potassium in 1,2-dimethoxyethane (DME) affords [(BIPM)Np(I)(DME)] (, BIPM = {C(PPhNSiMe)}). Analogously, addition of benzyl potassium and I to gives [(BIPM)Np(I)(I)] (). The synthesis of - was facilitated by adopting a scaled-down prechoreographed approach using cerium synthetic surrogates. The thorium(III) and uranium(III) analogues of these neptunium(III) complexes are currently unavailable, meaning that the synthesis of - provides an example of experimental grounding of 5f- vs 5f- and 5f- vs 4f-element bonding and reactivity comparisons being led by nonaqueous transuranium chemistry rather than thorium and uranium congeners. Computational analysis suggests that these Np═C bonds are more covalent than U═C, Ce═C, and Pm═C congeners but comparable to analogous U═C bonds in terms of bond orders and total metal contributions to the M═C bonds. A preliminary assessment of Np═C reactivity has introduced multiple bond metathesis to transuranium chemistry, extending the range of known metallo-Wittig reactions to encompass actinide oxidation states III-VI.
PubMed: 35609882
DOI: 10.1021/jacs.2c02152 -
Brazilian Journal of Otorhinolaryngology 2019Tinnitus is a subjective auditory symptom usually associated with a sound, even in the absence of external sound sources. Its diagnosis is complex, and some of the forms...
INTRODUCTION
Tinnitus is a subjective auditory symptom usually associated with a sound, even in the absence of external sound sources. Its diagnosis is complex, and some of the forms of measurement alone or in combination, include self-assessment questionnaires, such as the tinnitus handicap inventory, the visual analog scale and/or pitch and loudness matching.
OBJECTIVE
To analyze the correlation among three tinnitus measurement methods: tinnitus handicap inventory, visual analog scale and pitch and loudness matching.
METHODS
The study consisted of 148 patients complaining of chronic tinnitus. An otorhinolaryngological evaluation, anamnesis directed to tinnitus, audiometry (pure tone and speech), imitanciometry, tinnitus handicap inventory, visual analog scale, and pitch and loudness matching were performed. The study was registered in the Ethics Committee of the Institution with no. 0129/12.
RESULTS
Regarding the frequency of tinnitus handicap inventory responses, a higher occurrence of the mild degree was observed. An average of 6 points was observed on the visual analog scale. The mean loudness matching in the right ear was 20dBNS, and in the left ear was 17dBNS. As for the type of stimulus, the most found was continuous pure tone. The frequency of the pitch sensation was 6000Hz in the largest number of cases. Regarding the measures of tinnitus handicap inventory and the visual analogical scale, a significant correlation was observed, and as one value increases the other also increases. Pitch and loudness matching and the visual analogical scale results are also significant.
CONCLUSION
There was a significant correlation between the values measured by the tinnitus handicap inventory, visual analogical scale (annoyance) and loudness matching in the evaluation of tinnitus. The selection of any one of the three evaluative methods for tinnitus investigation provides different dimensions of the tinnitus and complements the others.
Topics: Adolescent; Adult; Audiometry, Pure-Tone; Female; Humans; Male; Middle Aged; Sound Localization; Surveys and Questionnaires; Tinnitus; Visual Analog Scale; Young Adult
PubMed: 29983341
DOI: 10.1016/j.bjorl.2018.05.006 -
Frontiers in Pharmacology 2022Glaucoma is the main cause of irreversible visual loss worldwide, and comprises a group of progressive, age-related, and chronic optic neuropathies. Prostaglandin... (Review)
Review
Glaucoma is the main cause of irreversible visual loss worldwide, and comprises a group of progressive, age-related, and chronic optic neuropathies. Prostaglandin analogs are considered a first-line treatment in the management of glaucoma and have the best efficacy in reducing intraocular pressure. When comparing these therapeutic agents between them, long-term therapy with 0.03% bimatoprost is the most effective followed by treatment with 0.005% latanoprost and 0.004% travoprost. The prevalence of adverse events is lower for latanoprost than for other prostaglandin analogs. However, some patients do not respond to the treatment with prostaglandin analogs (non-responders). Intraocular pressure-lowering efficacy differs significantly between individuals partly owing to genetic factors. Rs1045642 in , rs4241366 in , rs9503012 in , rs10306114 in , rs11568658 in , rs10786455 and rs6686438 in were reported to be positive with the response to prostaglandin analogs in patients with glaucoma. A negative association was found between single nucleotide polymorphisms of (rs11578155 and rs6672484) and the response to prostaglandin analogs in patients with glaucoma. The current review is an analysis of the information relevant to prostaglandin analog treatments based on previous literatures. It describes in detail the clinical pharmacology and pharmacogenetics of drugs belonging to this therapeutical class to provide a sound pharmacological basis for their proper use in ophthalmological clinical practice.
PubMed: 36313286
DOI: 10.3389/fphar.2022.1015338 -
International Journal of Molecular... Jul 2018The most active metabolite of vitamin D is 1α,25-dihydroxyvitamin D₃, which is a central regulator of mineral homeostasis: excessive administration leads to... (Review)
Review
The most active metabolite of vitamin D is 1α,25-dihydroxyvitamin D₃, which is a central regulator of mineral homeostasis: excessive administration leads to hypercalcemia. Additionally, 1α,25-dihydroxyvitamin D₃ is important to decision-making by cells, driving many cell types to growth arrest, differentiate and undergo apoptosis. 1α,25-Dihydroxyvitamin D₃ regulates gene transcription by binding to a single known receptor, the vitamin D receptor. Rapid intracellular signals are also elicited in vitro by 1α,25-dihydroxyvitamin D₃ that are independent of transcription. There are many aspects of the multiple actions of 1α,25-dihydroxyvitamin D₃ that we do not fully understand. These include how a single receptor and provoked rapid events relate to the different actions of 1α,25-dihydroxyvitamin D₃, its calcemic action per se, and whether a large number of genes are activated directly, via the vitamin D receptor, or indirectly. A strategy to resolving these issues has been to generate synthetic analogues of 1α,25-dihydroxyvitamin D₃: Some of these separate the anti-proliferative and calcemic actions of the parent hormone. Crystallography is important to understanding how differences between 1α,25-dihydroxyvitamin D₃- and analogue-provoked structural changes to the vitamin D receptor may underlie their different activity profiles. Current crystallographic resolution has not revealed such information. Studies of our new analogues have revealed the importance of the A-ring adopting the chair β-conformation upon interaction with the vitamin D receptor to receptor-affinity and biological activity. Vitamin D analogues are useful probes to providing a better understanding of the physiology of vitamin D.
Topics: Animals; Cell Differentiation; Humans; Receptors, Calcitriol; Structure-Activity Relationship; Vitamin D
PubMed: 30037036
DOI: 10.3390/ijms19072119 -
Nanomaterials (Basel, Switzerland) Dec 2022The electromagnetic induced transparency (EIT) effect originates from the destructive interference in an atomic system, which contributes to the transparency window in...
The electromagnetic induced transparency (EIT) effect originates from the destructive interference in an atomic system, which contributes to the transparency window in its response spectrum. The implementation of EIT requires highly demanding laboratory conditions, which greatly limits its acceptance and application. In this paper, an improved harmonic spring oscillation (HSO) model with four oscillators is proposed as a classical analog for the tunable triple-band EIT effect. A more general HSO model including more oscillators is also given, and the analyses of the power absorption in the HSO model conclude a formula, which is more innovative and useful for the study of the multiple-band EIT effect. To further inspect the analogizing ability of the HSO model, a hybrid unit cell containing an electric dipole and toroidal dipoles in the metamaterials is proposed. The highly comparable transmission spectra based on the HSO model and metamaterials indicate the validity of the classical analog in illustrating the formation process of the multiple-band EIT effect in metamaterials. Hence, the HSO model, as a classical analog, is a valid and powerful theoretical tool that can mimic the multiple-band EIT effect in metamaterials.
PubMed: 36558255
DOI: 10.3390/nano12244405 -
European Journal of Nuclear Medicine... Feb 2012Radiolabelled receptor-binding peptides targeting receptors (over)expressed on tumour cells are widely under investigation for tumour diagnosis and therapy. The concept... (Review)
Review
Radiolabelled receptor-binding peptides targeting receptors (over)expressed on tumour cells are widely under investigation for tumour diagnosis and therapy. The concept of using radiolabelled receptor-binding peptides to target receptor-expressing tissues in vivo has stimulated a large body of research in nuclear medicine. The (111)In-labelled somatostatin analogue octreotide (OctreoScan) is the most successful radiopeptide for tumour imaging, and was the first to be approved for diagnostic use. Based on the success of these studies, other receptor-targeting peptides such as cholecystokinin/gastrin analogues, glucagon-like peptide-1, bombesin (BN), chemokine receptor CXCR4 targeting peptides, and RGD peptides are currently under development or undergoing clinical trials. In this review, we discuss some of these peptides and their analogues, with regard to their potential for radionuclide imaging of tumours.
Topics: Animals; Bombesin; Cholecystokinin; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Ligands; Neoplasms; Octreotide; Pentetic Acid; Peptides; Radionuclide Imaging; Radiopharmaceuticals; Receptor, Cholecystokinin B; Receptors, Bombesin; Receptors, CXCR4; Receptors, Cholecystokinin; Receptors, Glucagon
PubMed: 22388627
DOI: 10.1007/s00259-011-2014-7