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Alluvial rivers are conveyor belts of fluid and sediment that provide a record of upstream climate and erosion on Earth, Titan, and Mars. However, many of Earth's rivers remain unsurveyed, Titan's rivers are not well resolved by current spacecraft data, and Mars' rivers are no longer active, hindering reconstructions of planetary surface conditions. To overcome these problems, we use dimensionless hydraulic geometry relations-scaling laws that relate river channel dimensions to flow and sediment transport rates-to calculate in-channel conditions using only remote sensing measurements of channel width and slope. On Earth, this offers a way to predict flow and sediment flux in rivers that lack field measurements and shows that the distinct dynamics of bedload-dominated, suspended load-dominated, and bedrock rivers give rise to distinct channel characteristics. On Mars, this approach not only predicts grain sizes at Gale Crater and Jezero Crater that overlap with those measured by the Curiosity and Perseverance rovers, it enables reconstructions of past flow conditions that are consistent with proposed long-lived hydrologic activity at both craters. On Titan, our predicted sediment fluxes to the coast of Ontario Lacus could build the lake's river delta in as little as ~1,000 y, and our scaling relationships suggest that Titan's rivers may be wider, slope more gently, and transport sediment at lower flows than rivers on Earth or Mars. Our approach provides a template for predicting channel properties remotely for alluvial rivers across Earth, along with interpreting spacecraft observations of rivers on Titan and Mars.
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Physical laws-such as the laws of motion, gravity, electromagnetism, and thermodynamics-codify the general behavior of varied macroscopic natural systems across space and time. We propose that an additional, hitherto-unarticulated law is required to characterize familiar macroscopic phenomena of our complex, evolving universe. An important feature of the classical laws of physics is the conceptual equivalence of specific characteristics shared by an extensive, seemingly diverse body of natural phenomena. Identifying potential equivalencies among disparate phenomena-for example, falling apples and orbiting moons or hot objects and compressed springs-has been instrumental in advancing the scientific understanding of our world through the articulation of laws of nature. A pervasive wonder of the natural world is the evolution of varied systems, including stars, minerals, atmospheres, and life. These evolving systems appear to be conceptually equivalent in that they display three notable attributes: 1) They form from numerous components that have the potential to adopt combinatorially vast numbers of different configurations; 2) processes exist that generate numerous different configurations; and 3) configurations are preferentially selected based on function. We identify universal concepts of selection-static persistence, dynamic persistence, and novelty generation-that underpin function and drive systems to evolve through the exchange of information between the environment and the system. Accordingly, we propose a "law of increasing functional information": The functional information of a system will increase (i.e., the system will evolve) if many different configurations of the system undergo selection for one or more functions.
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The gas-phase reaction between the ethyl cation (C2H5+) and ethyne (C2H2) is re-investigated by measuring absolute reactive cross sections (CSs) and branching ratios (BRs) as a function of collision energy, in the thermal and hyperthermal energy range, via tandem-guided ion beam mass spectrometry under single collision conditions. Dissociative photoionization of C2H5Br using tuneable VUV radiation in the range 10.5-14.0 eV is employed to generate C2H5+, which has also allowed us to explore the impact of increasing (vibrational) excitation on the reactivity. Reactivity experiments are complemented by theoretical calculations, at the G4 level of theory, of the relative energies and structures of the most relevant stationary points on the reactive potential energy hypersurface (PES) and by mass-analyzed ion kinetic energy (MIKE) spectrometry experiments to probe the metastable decomposition from the [C4H7]+ PES and elucidate the underlying reaction mechanisms. Two main product channels have been identified at a centre-of-mass collision energy of â¼0.1 eV: (a) C3H3++CH4, with BR = 0.76±0.05 and (b) C4H5++H2, with BR = 0.22±0.02. A third channel giving C2H3+ in association with C2H4 is shown to emerge at both high internal excitation of C2H5+ and high collision energies. From CS measurements, energy-dependent total rate constants in the range 4.3×10-11-5.2×10-10 cm3·molecule-1·s-1 have been obtained. Theoretical calculations indicate that both channels stem from a common covalently bound intermediate, CH3CH2CHCH+, from which barrierless and exothermic pathways exist for the production of both cyclic c-C3H3+ and linear H2CCCH+ isomers of the main product channel. For the minor C4H5+ product, two isomers are energetically accessible: the three-member cyclic isomer c-C3H2(CH3)+ and the higher energy linear structure CH2CHCCH2+, but their formation requires multiple isomerization steps and passages via transition states lying only 0.11 eV below the reagents' energy, thus explaining the smaller BR. Results have implications for the modeling of hydrocarbon chemistry in the interstellar medium and the atmospheres of planets and satellites as well as in laboratory plasmas (e.g., plasma-enhanced chemical vapor deposition of carbon nanotubes and diamond-like carbon films).
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INTRODUCTION: Modular femoral components allow for patient-specific restoration of hip joint geometry and the reconstruction of extensive bone defects in revision total hip arthroplasty (THA); however, potential problems of modular implants such as taper corrosion and the risk of implant fracture continue to be of concern. The aim of the present study was to evaluate the clinical and radiological results of a cementless modular revision stem following revision surgery due to aseptic loosening and periprosthetic fracture and to assess patient-reported outcome measures (PROMs) in these patients at mid-term follow-up. MATERIALS AND METHODS: In this study, a consecutive cohort of 75 patients who underwent primary revision THA at our institution using a modular cementless stem design (MRP-TITAN stem) was retrospectively evaluated at a mean follow-up of 7.7 years. Kaplan-Meier survivorship analyses were performed with revision of the femoral component for any reason as the end point. The Harris-Hip Score, the UCLA Activity Score, the Forgotten Joint Score and the SF-12 Score were used for clinical assessment. We used the Wilcoxon signed rank test to compare pre- and postoperative clinical scores. RESULTS: Overall stem survival with the endpoint stem re-revision for any reason was 85.4% at a mean follow-up of 7.7 years (range 2.4-14 years). Stem survival was 89.5% in the aseptic loosening group and 78.3% in the periprosthetic fracture group with no statistically significant difference between both groups (p = 0.107). One patient had to be revised due to taper fracture. PROMs improved significantly up to the latest follow-up, and radiographic evaluation showed full osseointegration of all stems in this cohort. CONCLUSIONS: Revision THA using a modular cementless titanium revision stem demonstrated adequate clinical and radiological results at mid- to long-term follow-up in this cohort. Cementless revision stems are a useful treatment option to restore the anatomy, especially in deformed hips and in complex revision hip arthroplasty. However, there are some significant disadvantages related to an increased risk of mechanical failure such as corrosion/fretting damage and implant fracture. Future high-quality prospective studies with longer follow-up are necessary to confirm the supposed advantages.
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Artroplastia de Quadril , Prótese de Quadril , Fraturas Periprotéticas , Humanos , Artroplastia de Quadril/efeitos adversos , Seguimentos , Fraturas Periprotéticas/diagnóstico por imagem , Fraturas Periprotéticas/cirurgia , Fraturas Periprotéticas/etiologia , Estudos Retrospectivos , Estudos Prospectivos , Desenho de Prótese , Reoperação , Falha de Prótese , Resultado do TratamentoRESUMO
Metastatic chest lesion is rare in patients with soft palate tumors. We present a 52-year-old patient with metastatic lesion of the left ribs III-V and lung in 13 years after resection of cylindroma of the soft palate. The patient underwent successful chest reconstruction and atypical resection of the left lung. Isolation of the pleural cavity by xenopericardial patches and preoperative 3D CT modeled titanium implants meet all the requirements for maintaining the chest function. This approach also positively affects postoperative period and recovery. The above-described method of replacing chest defects is highly effective.
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Carcinoma Adenoide Cístico , Procedimentos de Cirurgia Plástica , Parede Torácica , Humanos , Pessoa de Meia-Idade , Parede Torácica/cirurgia , Costelas/cirurgia , Pulmão/cirurgia , Palato Mole/cirurgiaRESUMO
Cryptococcosis therapy is often limited by toxicity problems, antifungal tolerance, and high costs. Studies approaching chalcogen compounds, especially those containing selenium, have shown promising antifungal activity against pathogenic species. This work aimed to evaluate the in vitro and in vivo antifungal potential of organoselenium compounds against Cryptococcus neoformans. The lead compound LQA_78 had an inhibitory effect on C. neoformans planktonic cells and dispersed cells from mature biofilms at similar concentrations. The fungal growth inhibition led to an increase in budding cells arrested in the G2/M phase, but the compound did not significantly affect structural cell wall components or chitinase activity, an enzyme that regulates the dynamics of the cell wall. The compound also inhibited titan cell (Tc) and enlarged capsule yeast (NcC) growth and reduced the body diameter and capsule thickness associated with increased capsular permeability of both virulent morphotypes. LQA_78 also reduced fungal melanization through laccase activity inhibition. The fungicidal activity was observed at higher concentrations (16 to 64 µg/mL) and may be associated with augmented plasma membrane permeability, ROS production, and loss of mitochondrial membrane potential. While LQA_78 is a nonhemolytic compound, its cytotoxic effects were cell type dependent, exhibiting no toxicity on Galleria mellonella larvae at a dose ≤46.5 mg/kg. LQA_78 treatment of larvae infected with C. neoformans effectively reduced the fungal burden and inhibited virulent morphotype formation. To conclude, LQA_78 displays fungicidal action and inhibits virulence factors of C. neoformans. Our results highlight the potential use of LQA_78 as a lead molecule for developing novel pharmaceuticals for treating cryptococcosis.
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Antifúngicos , Cryptococcus neoformans , Animais , Antifúngicos/uso terapêutico , Cryptococcus neoformans/efeitos dos fármacos , Larva/efeitos dos fármacos , Larva/microbiologia , Mariposas/efeitos dos fármacos , Mariposas/microbiologia , Fatores de Virulência/metabolismoRESUMO
Many successful pathogens cause latent infections, remaining dormant within the host for years but retaining the ability to reactivate to cause symptomatic disease. The human opportunistic fungal pathogen Cryptococcus neoformans establishes latent pulmonary infections in immunocompetent individuals upon inhalation from the environment. These latent infections are frequently characterized by granulomas, or foci of chronic inflammation, that contain dormant and persistent cryptococcal cells. Immunosuppression can cause these granulomas to break down and release fungal cells that proliferate, disseminate, and eventually cause lethal cryptococcosis. This course of fungal latency and reactivation is understudied due to limited models, as chronic pulmonary granulomas do not typically form in mouse cryptococcal infections. A loss-of-function mutation in the Cryptococcus-specific MAR1 gene was previously described to alter cell surface remodeling in response to host signals. Here, we demonstrate that the mar1Δ mutant strain persists long term in a murine inhalation model of cryptococcosis, inducing a chronic pulmonary granulomatous response. We find that murine infections with the mar1Δ mutant strain are characterized by reduced fungal burden, likely due to the low growth rate of the mar1Δ mutant strain at physiological temperature, and an altered host immune response, likely due to inability of the mar1Δ mutant strain to properly employ virulence factors. We propose that this combination of features in the mar1Δ mutant strain collectively promotes the induction of a more chronic inflammatory response and enables long-term fungal persistence within these granulomatous regions.
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Criptococose , Cryptococcus neoformans , Infecção Latente , Animais , Criptococose/microbiologia , Modelos Animais de Doenças , Inflamação , Pulmão , CamundongosRESUMO
Nitrogen (N) emissions and atmospheric deposition have increased significantly during the last century and become a stressor for many N-sensitive plant species. Understanding individual and community herbaceous plant species thresholds to atmospheric N deposition can inform emissions reduction policy. Here, we present results using Threshold Indicator Taxa Analysis (TITAN) applied to more than 1200 unique plant species and 24 vegetation communities (i.e., alliances) across the United States (US) to assess vulnerability to N deposition. Alliance-level thresholds (change points) for species decreasing in abundance along the gradient ranged from 1.8 to 14.3 kg N haâ1 yearâ1 and tended to be lower in the west than the east, which suggests that eastern communities, where N deposition has been historically higher, may have already lost many sensitive species. For the species that were present in more than one alliance, over half had a variable response to the N deposition gradient, suggesting that local factors affect vulnerability. Significant progress has been made during the past 30 years to reduce N emissions, which has reduced the percentage of plots at risk to N deposition from 72% to 35%. Nevertheless, over a third of plots remain at risk, and an average reduction of N deposition of 20% would protect half of the plots where N deposition exceeds community thresholds. Furthermore, the alliance- and species-level change points determined in this study may be used to inform N critical loads.
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Nitrogênio , Plantas , Nitrogênio/análise , Estados UnidosRESUMO
Titan is a sedimentary world, with lakes, rivers, canyons, fans, dissected plateaux, and sand dunes. Sediments on Saturn's moon are thought to largely consist of mechanically weak organic grains, prone to rapid abrasion into dust. Yet, Titan's equatorial dunes have likely been active for 10s-100s kyr. Sustaining Titan's dunes over geologic timescales requires a mechanism that produces sand-sized particles at equatorial latitudes. We explore the hypothesis that a combination of abrasion, when grains are transported by winds or methane rivers, and sintering, when they are at rest, could produce sand grains that maintain an equilibrium size. Our model demonstrates that seasonal sediment transport may produce sand under Titan's surface conditions and could explain the latitudinal zonation of Titan's landscapes. Our findings support the hypothesis of global, source-to-sink sedimentary pathways on Titan, driven by seasons, and mediated by episodic abrasion and sintering of organic sand by rivers and winds.
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Healthy aquatic ecosystems can offer basic ecological services for the sustainable development of humans and society. Water quality greatly influences the macroinvertebrate community in aquatic ecosystems and can alter the aquatic ecosystem's health status. However, the quantitative relationship between macroinvertebrate community and water quality factors in rivers remains unclear, particularly in urban rivers, which are strongly affected by human activities. Therefore, a new framework for the quantitative analysis between macroinvertebrate community and key water quality driving factors was developed in the study, meanwhile, the aquatic ecosystem health conditions were evaluated and validated by different methods. The framework was applied to a typical urban river, the North Canal River, which is regarded as the "mother river" of Beijing. Combined with the redundancy analysis (RDA) and the threshold indicator taxa analysis (TITAN), the water quality driving factors and their indicator species were identified and the corresponding response threshold was determined. Based on the benthic index of biotic integrity (B-IBI), the multi-metric rapid bioassessment method, and the biological monitoring working party (BMWP) score, the aquatic ecosystem health condition in the basin was comprehensively evaluated. The results show that fluoride, biochemical oxygen demand, ammonia-nitrogen and total phosphorus were the key water quality driving factors influencing the community structure of macroinvertebrates. Four indicator species of ammonia-nitrogen were identified by the TITAN method with a threshold range of 1.09-6.94 mg L-1, and three indicator species of total phosphorus were identified with a threshold range of 0.48-1.27 mg L-1. According to the results of the aquatic ecosystem health assessment, the river ecosystem was generally unhealthy and the upstream was better than downstream; the health condition in the mountainous areas of Changping district was the best, while that in Chaoyang district and the central city area was the worst. The framework could provide a strong basis for ecological restoration and pollution control of the urban rivers and become an important tool for the rehabilitation of aquatic ecosystems.
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Ecossistema , Qualidade da Água , Amônia , Animais , Pequim , China , Monitoramento Ambiental/métodos , Humanos , Invertebrados , Nitrogênio , FósforoRESUMO
A study targeting the etiology of severe anaemia that sporadically occurred in laboratory-bred cyprinid hybrids resulted in a diagnosis of a Mycoplasma-like organism selectively invading the cytoplasm of erythrocytes. Despite the fact that there was a concurrent yeast infection in moribund anaemic hybrids, the primary role in the development of anaemia was assigned to the Mycoplasma-like organism due to its regular occurrence in erythrocytes of both the moribund hybrids and hybrids that were free of yeast infection yet showed early to advanced symptoms of the disease. Novel data on the Mycoplasma-like organism's cytoskeleton were obtained from ultrathin sections of affected erythrocytes. An ultrastructural study of the concurrent yeast infection in moribund hybrids manifesting the most advanced anaemia revealed the presence of Titan cells in ascitic fluid. The original findings presented in this study underline the diagnostic relevance of transmission electron microscopy in the research of similar infections.
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Anemia , Infecções por Mycoplasma , Mycoplasma , Animais , Infecções por Mycoplasma/diagnóstico , Infecções por Mycoplasma/veterinária , Saccharomyces cerevisiae , Anemia/veterinária , Mycoplasma/ultraestrutura , Eritrócitos/ultraestruturaRESUMO
According to the World Health Organization report, the increasing antibiotic resistance of microorganisms is one of the biggest global health problems. The percentage of bacterial strains showing multidrug resistance (MDR) to commonly used antibiotics is growing rapidly. Therefore, the search for alternative solutions to antibiotic therapy has become critical to combat this phenomenon. It is especially important as frequent and recurring infections can cause cancer. One example of this phenomenon is urinary tract infections that can contribute to the development of human urinary bladder carcinoma. This tumor is one of the most common malignant neoplasms in humans. It occurs almost three times more often in men than in women, and in terms of the number of cases, it is the fifth malignant neoplasm after prostate, lung, colon, and stomach cancer. The risk of developing the disease increases with age. Despite the improvement of its treatment methods, the current outcome in the advanced stages of this tumor is not satisfactory. Hence, there is an urgent need to introduce innovative solutions that will prove effective even in the advanced stage of the disease. In our study, a nanosystem based on ionic silver (Ag+) bound to a carrier-Titan yellow (TY) was analyzed. The possibility of binding the thus formed TY-Ag system to Congo red (CR) and albumin (BSA) was determined. TY-Ag binding to CR provides for better nanosystem solubility and enables its targeted intracellular transport and binding to immune complexes. The binding of TY-Ag or CR-TY-Ag to albumin also protects the system against the uncontrolled release of silver ions. It will also allow the delivery of silver in a targeted manner directly to the desired site in the case of intravenous administration of such a system. In this study, the MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values of the TY-Ag or BSA-TY-Ag systems were determined in two reference strains (Escherichia coli and Staphylococcus aureus). The paper presents nanosystems with a size of about 40-50 nm, with an intense antibacterial effect obtained at concentrations of 0.019 mM. We have also discovered that TY-Ag free or complexed with BSA (with a minimal Ag+ dose of 15-20 µM) inhibited cancer cells proliferation. TY-Ag complex diminished migration and effectively inhibited the T24 cell viability and induced apoptosis. On the basis of the obtained results, it has been shown that the presented systems may have anti-inflammatory and antitumor properties at the same time. TY-Ag or BSA-TY-Ag are new potential drugs and may become in future important therapeutic compounds in human urinary bladder carcinoma treatment and/or potent antimicrobial factors as an alternative to antibiotics.
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Albuminas/farmacologia , Antibacterianos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Vermelho Congo/farmacologia , Íons/farmacologia , Prata/farmacologia , Triazenos/farmacologia , Neoplasias da Bexiga Urinária/microbiologia , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Escherichia coli/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana/métodos , Staphylococcus aureus/efeitos dos fármacos , Neoplasias da Bexiga Urinária/tratamento farmacológicoRESUMO
Human studies have shown associations between cryptococcal meningitis and reduced IgM memory B cell levels, and studies in IgM- and/or B cell-deficient mice have demonstrated increased Cryptococcus neoformans dissemination from lungs to brain. Since immunoglobulins are part of the immune milieu that C. neoformans confronts in a human host, and its ability to form titan cells is an important virulence mechanism, we determined the effect of human immunoglobulins on C. neoformans titan cell formation in vitro (i) Fluorescence microscopy showed normal human IgG and IgM bind C. neoformans (ii) C. neoformans grown in titan cell-inducing medium with IgM, not IgG, inhibited titan-like cell formation. (iii) Absorption of IgM with laminarin or curdlan (branched and linear 1-3-beta-d-glucans, respectively) decreased this effect. (iv) Transmission electron microscopy revealed that cells grown with IgM had small capsules and unique features not seen with cells grown with IgG. (v) Comparative transcriptional analysis of cell wall, capsule, and stress response genes showed that C. neoformans grown with IgM, not IgG or phosphate-buffered saline (PBS), had decreased expression of chitin synthetase, CHS1, CHS2, and CHS8, and genes encoding cell wall carbohydrate synthetases α-1-3-glucan (AGS1) and ß-1,3-glucan (FKS1). IgM also decreased expression of RIM101 and HOG1, genes encoding central regulators of C. neoformans stress response pathways and cell morphogenesis. Our data show human IgM affects C. neoformans morphology in vitro and suggest that the hypothesis that human immunoglobulins may affect C. neoformans virulence in vivo warrants further investigation.
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Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/crescimento & desenvolvimento , Interações Hospedeiro-Patógeno , Imunoglobulina M/metabolismo , Fatores Imunológicos/metabolismo , Cryptococcus neoformans/citologia , Humanos , Imunoglobulina G/metabolismo , Virulência/efeitos dos fármacosRESUMO
We present here a versatile computational code named "elecTric fIeld generaTion And maNipulation (TITAN)," capable of generating various types of external electric fields, as well as quantifying the local (or intrinsic) electric fields present in proteins and other biological systems according to Coulomb's Law. The generated electric fields can be coupled with quantum mechanics (QM), molecular mechanics (MM), QM/MM, and molecular dynamics calculations in most available software packages. The capabilities of the TITAN code are illustrated throughout the text with the help of examples. We end by presenting an application, in which the effects of the local electric field on the hydrogen transfer reaction in cytochrome P450 OleTJE enzyme and the modifications induced by the application of an oriented external electric field are examined. We find that the protein matrix in P450 OleTJE acts as a moderate catalyst and that orienting an external electric field along the FeâO bond of compound I has the biggest impact on the reaction barrier. The induced catalysis/inhibition correlates with the calculated spin density on the O-atom. © 2019 Wiley Periodicals, Inc.
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Sistema Enzimático do Citocromo P-450/metabolismo , Simulação de Dinâmica Molecular , Software , Sistema Enzimático do Citocromo P-450/química , Eletricidade , Teoria QuânticaRESUMO
The structure and thermal expansion of the astronomical molecule propionitrile have been determined from 100 to 150â K using synchrotron powder X-ray diffraction. This temperature range correlates with the conditions of Titan's lower stratosphere, and near surface, where propionitrile is thought to accumulate and condense into pure and mixed-nitrile phases. Propionitrile was determined to crystallize in space group, Pnma (No.â 62), with unit cell a = 7.56183â (16)â Å, b = 6.59134â (14)â Å, c = 7.23629â (14), volume = 360.675â (13)â Å3 at 100â K. The thermal expansion was found to be highly anisotropic with an eightfold increase in expansion between the c and b axes. These data will prove crucial in the computational modelling of propionitrile-ice systems in outer Solar System environments, allowing us to simulate and assign vibrational peaks in the infrared spectra for future use in planetary astronomy.
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Cryptococcus neoformans is a human pathogenic yeast that causes hundreds of thousands of deaths worldwide among susceptible individuals, in particular, HIV+ patients. This yeast has developed several adaptation mechanisms that allow replication within the host. During decades, this yeast has been well known for a very peculiar and unique structure that contributes to virulence, a complex polysaccharide capsule that surrounds the cell wall. In contrast to other fungal pathogens, such as Candida albicans or Aspergillus fumigatus, the role of morphological transitions has not been studied in the virulence of Cryptococcus neoformans since this yeast does not form hyphae during infection. However, in the last years, different groups have described the ability of this fungus to change its size during infection. In particular, Cryptococcus can form "titan cells," which are blastoconidia of an abnormal large size. Since their discovery, there is increasing evidence that these cells contribute, not only to long-term persistence in the host, but they can also actively participate in the development of the disease. Recently, several groups have simultaneously described different media that induce the appearance of titan cells in laboratory conditions. Using these conditions, new inducing factors and signaling pathways involved in this transition have been described. In this article, we will review the main phenotypic features of these cells, factors, and transduction pathways that induce cell growth, and how titan cells contribute to the disease caused by this pathogen.
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Criptococose/microbiologia , Cryptococcus neoformans/citologia , Cryptococcus neoformans/patogenicidade , Parede Celular/metabolismo , Cryptococcus neoformans/crescimento & desenvolvimento , Cryptococcus neoformans/metabolismo , Interações Hospedeiro-Patógeno , Humanos , VirulênciaRESUMO
Prostate cancer is the fifth leading cause of cancer-related death among men with the majority of deaths linked to metastatic disease. Accumulating clinical data have confirmed the substantial survival benefit of the addition of docetaxel or androgen signaling inhibitors to androgen deprivation therapy for the treatment of metastatic castration-sensitive prostate cancer (mCSPC). Apalutamide, a next-generation androgen receptor inhibitor, has recently been shown to provide an added survival benefit in the treatment of mCSPC and consequently approved for this indication. This review summarizes the body of evidence with regards to the preclinical activity and clinical efficacy of apalutamide with a specific focus on its efficacy in the treatment of mCSPC.
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Antagonistas de Receptores de Andrógenos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Tioidantoínas/uso terapêutico , Androgênios/biossíntese , Ensaios Clínicos como Assunto , Humanos , Masculino , Metástase Neoplásica , Medidas de Resultados Relatados pelo Paciente , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Qualidade de Vida , Tioidantoínas/efeitos adversosRESUMO
The chemistry of hydrogen cyanide (HCN) is believed to be central to the origin of life question. Contradictions between Cassini-Huygens mission measurements of the atmosphere and the surface of Saturn's moon Titan suggest that HCN-based polymers may have formed on the surface from products of atmospheric chemistry. This makes Titan a valuable "natural laboratory" for exploring potential nonterrestrial forms of prebiotic chemistry. We have used theoretical calculations to investigate the chain conformations of polyimine (pI), a polymer identified as one major component of polymerized HCN in laboratory experiments. Thanks to its flexible backbone, the polymer can exist in several different polymorphs, which are relatively close in energy. The electronic and structural variability among them is extraordinary. The band gap changes over a 3-eV range when moving from a planar sheet-like structure to increasingly coiled conformations. The primary photon absorption is predicted to occur in a window of relative transparency in Titan's atmosphere, indicating that pI could be photochemically active and drive chemistry on the surface. The thermodynamics for adding and removing HCN from pI under Titan conditions suggests that such dynamics is plausible, provided that catalysis or photochemistry is available to sufficiently lower reaction barriers. We speculate that the directionality of pI's intermolecular and intramolecular =N-H( )N hydrogen bonds may drive the formation of partially ordered structures, some of which may synergize with photon absorption and act catalytically. Future detailed studies on proposed mechanisms and the solubility and density of the polymers will aid in the design of future missions to Titan.
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Cianeto de Hidrogênio/química , Polímeros/química , Meio Ambiente Extraterreno , Estrutura Molecular , Polimerização , SaturnoRESUMO
NASA is designing an unmanned submarine to explore the depths of the hydrocarbon-rich seas on Saturn's moon Titan. Data from Cassini indicates that the Titan north polar environment sustains stable seas of variable concentrations of ethane, methane, and nitrogen, with a surface temperature near 93 K. The submarine must operate autonomously, study atmosphere/sea exchange, interact with the seabed, hover at the surface or any depth within the sea, and be capable of tolerating variable hydrocarbon compositions. Currently, the main thermal design concern is the effect of effervescence on submarine operation, which affects the ballast system, science instruments, and propellers. Twelve effervescence measurements on various liquid methane-ethane compositions with dissolved gaseous nitrogen are thus presented from 1.5 bar to 4.5 bar at temperatures from 92 K to 96 K to simulate the conditions of the seas. After conducting effervescence measurements, two freezing point depression measurements were conducted. The freezing liquid line was depressed more than 15 K below the triple point temperatures of pure ethane (90.4 K) and pure methane (90.7 K). Experimental effervescence measurements will be used to compare directly with effervescence modeling to determine if changes are required in the design of the thermal management system as well as the propellers.
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Literature review is devoted to the main implants used in hernia surgery and their disadvantages. Advisability of titanium mesh implants in surgery of anterior abdominal wall hernias is shown.