RESUMEN
Improved food security and nutrition remain a notable global challenge. Yet, food security and nutrition are areas of strategic importance regarding the United Nations' Sustainable Development Goals. The increasingly weakening global food production systems pose a threat to sustainable improved food security and nutrition. Consequently, a significant population remains chronically hungry and severely malnourished. As a remedy, farm production diversity (FPD) remains a viable pathway through which household nutrition can be improved. However, evidence is mixed, or unavailable on how FPD is associated with key nutrition indicators like household dietary diversity, energy, iron, zinc, and vitamin A (micronutrients). We use the Uganda National Panel Survey (UNPS) data for rural households to analyze differential associations of sub-components of FPD on dietary diversity, energy, and micronutrient intake. Panel data models reveal that indeed crop species count, and animal species count (sub-components of FPD) are differently associated with household dietary diversity score (HDDS), energy, and vitamin A sourced from markets. Moreover, when volumes of these nutrition outcomes were disaggregated by source (own farm vs. markets), the animal species count was only positively significantly associated with nutrition outcomes sourced from consumption of produce from own farm. Associations were insignificant for nutrition indicators sourced from markets except vitamin A. The crop species count, however, consistently showed a strong positive and significant association with energy, and all studied micronutrients sourced from own farm produce consumption, as well as those sourced from markets except Vitamin A, which was negative but insignificant. Therefore, inclusive, pro-poor, and pro-nutrition rural policy initiatives in the context of rural Uganda and similar ones, could more widely improve household nutrition through prioritizing crop species diversification on own farms because crops fetch wider nutrition gains.
Asunto(s)
Abastecimiento de Alimentos , Vitamina A , Humanos , Granjas , Uganda , Dieta , Micronutrientes , Población RuralRESUMEN
In Frongoch Mine (UK), it is unclear the distribution of metals on indigenous algae and whether these species of algae can accumulate metals. This study aimed to investigate the role of indigenous algae for metal removal from acid mine drainage and understand if metals can be adsorbed on the surface of algae or/and bioaccumulated in algae. A sequential extraction procedure was applied for algae samples collected from acid mine drainage (AMD) water to identify the forms in which metals are found in algae. Concentrations of Fe, Pb, Zn, Cu and Cd were evaluated in the algae and AMD samples were collected in June and October 2019. AMDs samples had a pH value ranging between 3.5 and 6.9 and high concentrations of Zn (351 mg/L) and Pb (4.22 mg/L) that exceeded the water quality standards (Water Framework Directive, 2015). Algae Ulothrix sp. and Oedogonium sp. were the two main species in the Frongoch AMDs. The concentrations of metals in algae ranged from 0.007 to 51 mg/g, and the bioconcentration factor of metals decreased in the following order: Fe > > Pb > > Cu > Cd > Zn. It was found that Zn, Cu and Cd were adsorbed onto the surface of and bioaccumulated in the algae, while Pb and Fe were mainly bioaccumulated in the algae. Indigenous algae can be considered as a biogeochemical barrier where metals are accumulating and can be used in bioremediation methods. Also, indigenous algae could be used as a bioindicator to assess water pollution at Frongoch Mine and other similar metal mines.
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Metales Pesados , Contaminantes Químicos del Agua , Ácidos , Bioacumulación , Cadmio , Monitoreo del Ambiente/métodos , Plomo , Metales Pesados/análisis , Plantas , Reino Unido , Contaminantes Químicos del Agua/análisisRESUMEN
Spatially resolved emission inventories were used with an atmospheric dispersion model to predict ambient concentrations of methane, ethane, and propane in the Eagle Ford oil and gas production region in south central Texas; predicted concentrations were compared to ground level observations. Using a base case inventory, predicted median propane/ethane concentration ratios were 106% higher (95% CI: 83% higher-226% higher) than observations, while median ethane/methane concentration ratios were 112% higher (95% CI: 17% higher-228% higher) than observations. Predicted median propane and ethane concentrations were factors of 6.9 (95% CI: 3-15.2) and 3.4 (95% CI: 1.4-9) larger than observations, respectively. Predicted median methane concentrations were 7% higher (95% CI: 39% lower-37% higher) than observations. These comparisons indicate that sources of emissions with high propane/ethane ratios (condensate tank flashing) were likely overestimated in the inventories. Because sources of propane and ethane emissions are also sources of methane emissions, the results also suggest that sources of emissions with low ethane/methane ratios (midstream sources) were underestimated. This analysis demonstrates the value of using multiple light alkanes in attributing sources of methane emissions and evaluating the performance of methane emission inventories for oil and natural gas production regions.
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Contaminantes Atmosféricos , Alcanos , Etano , Metano , Gas Natural , TexasRESUMEN
Laryngeal cryptococcosis is a rare clinical entity. There have been a limited number of case reports in the literature with no consensus regarding optimal management. This review contributes two additional case reports of immunocompetent patients with cryptococcal infection of the larynx in whom exposure to high doses of inhaled corticosteroids is proposed as a significant risk factor. Twenty cases were identified from review of the literature. All patients presented with hoarseness and a spectrum of microlaryngoscopic features, often mimicking laryngeal malignancy. The majority of cases were treated with systemic antifungal therapy, three cases had surgical excision alone, and another three had a combination of medical and surgical management. Risk factor modification, in the form of a reduction in inhaled corticosteroid was employed in the two new cases, and in some previously published cases. Risk factor modification, such as reduction of inhaled corticosteroid dose, in addition to oral antifungal agents can be effective in managing cryptococcal laryngitis.
RESUMEN
Recent studies suggest that cells make stochastic choices with respect to differentiation or division. However, the molecular mechanism underlying such stochasticity is unknown. We previously proposed that the timing of vertebrate neuronal differentiation is regulated by molecular oscillations of a transcriptional repressor, HES1, tuned by a post-transcriptional repressor, miR-9. Here, we computationally model the effects of intrinsic noise on the Hes1/miR-9 oscillator as a consequence of low molecular numbers of interacting species, determined experimentally. We report that increased stochasticity spreads the timing of differentiation in a population, such that initially equivalent cells differentiate over a period of time. Surprisingly, inherent stochasticity also increases the robustness of the progenitor state and lessens the impact of unequal, random distribution of molecules at cell division on the temporal spread of differentiation at the population level. This advantageous use of biological noise contrasts with the view that noise needs to be counteracted.
Asunto(s)
Diferenciación Celular , Proliferación Celular , Regulación de la Expresión Génica , MicroARNs/metabolismo , Neuronas/fisiología , Células Madre/fisiología , Factor de Transcripción HES-1/metabolismo , Simulación por Computador , HumanosAsunto(s)
Prótesis de la Rodilla/efectos adversos , Infecciones por Mycoplasma , Mycoplasma hominis , Infecciones Relacionadas con Prótesis , Adulto , Femenino , Humanos , Infecciones por Mycoplasma/diagnóstico , Infecciones por Mycoplasma/microbiología , Infecciones Relacionadas con Prótesis/diagnóstico , Infecciones Relacionadas con Prótesis/microbiologíaRESUMEN
During the development of the nervous system, apicobasally polarized stem cells are characterized by a shorter cell cycle than nonpolar progenitors, leading to a lower differentiation potential of these cells. However, how polarization might be directly linked to the kinetics of the cell cycle is not understood. Here, we report that apicobasally polarized neuroepithelial cells in Xenopus laevis have a shorter cell cycle than nonpolar progenitors, consistent with mammalian systems. We show that the apically localized serine/threonine kinase aPKC directly phosphorylates an N-terminal site of the cell-cycle inhibitor p27Xic1 and reduces its ability to inhibit the cyclin-dependent kinase 2 (Cdk2), leading to shortening of G1 and S phases. Overexpression of activated aPKC blocks the neuronal differentiation-promoting activity of p27Xic1. These findings provide a direct mechanistic link between apicobasal polarity and the cell cycle, which may explain how proliferation is favored over differentiation in polarized neural stem cells.
Asunto(s)
Puntos de Control del Ciclo Celular/fisiología , Polaridad Celular/fisiología , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Proteína Quinasa C/metabolismo , Proteínas de Xenopus/metabolismo , Animales , Diferenciación Celular/fisiología , División Celular/fisiología , Quinasa 2 Dependiente de la Ciclina/metabolismo , Fosforilación , Proteínas Serina-Treonina Quinasas/metabolismo , Xenopus laevisRESUMEN
SUMMARY: Postoperative pyoderma gangrenosum is a rare neutrophilic dermatosis that may be confused for necrotizing fasciitis. The inflammatory response is triggered by the trauma of surgery and thus must be managed nonsurgically. Clinical and pathological findings in the 2 diseases can be identical, leading to misdiagnosis and massive surgical defects from the ensuing surgery. This report documents a severe case of postsurgical pyoderma following an elective rotator cuff repair presenting with myositis and myonecrosis. The patient was initially treated as having an infection, which resulted in multiple aggressive surgical debridements. Despite this, the patient continued to deteriorate and was in a critical and hemodynamically unstable condition. Following administration of high-dose intravenous corticosteroids, the patient made a dramatic recovery and went on to have internal fixation of the shoulder and closure of the wound with a combination of a free flap and a rotational flap. Extensive myositis, as seen in this case, has not been previously reported in postoperative pyoderma gangrenosum variants. Clinicians should be aware that the presence of myositis and myonecrosis should not preclude this diagnosis.
RESUMEN
Short-period (ultradian) oscillations of Hes1, a Notch signaling effector, are essential for maintaining neural progenitors in a proliferative state, while constitutive downregulation of Hes1 leads to neuronal differentiation. Hes1 oscillations are driven by autorepression, coupled with high instability of the protein and mRNA. It is unknown how Hes1 mRNA stability is controlled and furthermore, how cells exit oscillations in order to differentiate. Here, we identify a microRNA, miR-9, as a component of ultradian oscillations. We show that miR-9 controls the stability of Hes1 mRNA and that both miR-9 overexpression and lack of miR-9 dampens Hes1 oscillations. Reciprocally, Hes1 represses the transcription of miR-9, resulting in out-of-phase oscillations. However, unlike the primary transcript, mature miR-9 is very stable and thus accumulates over time. Given that raising miR-9 levels leads to dampening of oscillations, these findings provide support for a self-limiting mechanism whereby cells might terminate Hes1 oscillations and differentiate.
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Ciclos de Actividad/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Relojes Biológicos/genética , Proteínas de Homeodominio/genética , MicroARNs/fisiología , Ciclos de Actividad/fisiología , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Células Cultivadas , Retroalimentación Fisiológica/fisiología , Regulación de la Expresión Génica , Proteínas de Homeodominio/metabolismo , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Modelos Biológicos , Interferencia de ARN/fisiología , ARN Mensajero/metabolismo , Factor de Transcripción HES-1 , Transcripción Genética/genéticaRESUMEN
The capacity of neurons to develop a long axon and multiple dendrites defines neuron connectivity in the CNS. The highly conserved microRNA-9 (miR-9) is expressed in both neuronal precursors and some post-mitotic neurons, and we detected miR-9 expression in the axons of primary cortical neurons. We found that miR-9 controlled axonal extension and branching by regulating the levels of Map1b, an important protein for microtubule stability. Following microfluidic separation of the axon and the soma, we found that miR-9 repressed Map1b translation and was a functional target for the BDNF-dependent control of axon extension and branching. We propose that miR-9 links regulatory signaling processes with dynamic translation mechanisms, controlling Map1b protein levels and axon development.
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Filariasis Linfática/diagnóstico , Adulto , Australia , Dietilcarbamazina/uso terapéutico , Doxiciclina/administración & dosificación , Doxiciclina/uso terapéutico , Quimioterapia Combinada , Filariasis Linfática/tratamiento farmacológico , Filariasis Linfática/patología , Filaricidas/administración & dosificación , Filaricidas/uso terapéutico , Humanos , Masculino , Cordón Espermático/parasitología , Cordón Espermático/patologíaRESUMEN
Proteolytic release from the cell surface is an essential activation event for many growth factors and cytokines. TNF-α converting enzyme (TACE) is a membrane-bound metalloprotease responsible for solubilizing many pathologically significant membrane substrates and is an attractive therapeutic target for the treatment of cancer and arthritis. Prior attempts to antagonize cell-surface TACE activity have focused on small-molecule inhibition of the metalloprotease active site. Given the highly conserved nature of metalloprotease active sites, this paradigm has failed to produce a truly specific TACE inhibitor and continues to obstruct the clinical investigation of TACE activity. We report the bespoke development of a specific TACE inhibitory human antibody using "two-step" phage display. This approach combines calculated selection conditions with antibody variable-domain exchange to direct individual antibody variable domains to desired epitopes. The resulting "cross-domain" human antibody is a previously undescribed selective TACE antagonist and provides a unique alternative to small-molecule metalloprotease inhibition.
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Proteínas ADAM/antagonistas & inhibidores , Anticuerpos/farmacología , Diseño de Fármacos , Región Variable de Inmunoglobulina/metabolismo , Modelos Moleculares , Proteínas ADAM/metabolismo , Proteína ADAM17 , Animales , Ensayo de Inmunoadsorción Enzimática , Humanos , Región Variable de Inmunoglobulina/genética , Ratones , Mutagénesis , Biblioteca de Péptidos , Estructura Terciaria de Proteína/genética , Resonancia por Plasmón de SuperficieRESUMEN
Blood pressure is critically controlled by angiotensins, which are vasopressor peptides specifically released by the enzyme renin from the tail of angiotensinogen-a non-inhibitory member of the serpin family of protease inhibitors. Although angiotensinogen has long been regarded as a passive substrate, the crystal structures solved here to 2.1 Å resolution show that the angiotensin cleavage site is inaccessibly buried in its amino-terminal tail. The conformational rearrangement that makes this site accessible for proteolysis is revealed in our 4.4 Å structure of the complex of human angiotensinogen with renin. The co-ordinated changes involved are seen to be critically linked by a conserved but labile disulphide bridge. Here we show that the reduced unbridged form of angiotensinogen is present in the circulation in a near 40:60 ratio with the oxidized sulphydryl-bridged form, which preferentially interacts with receptor-bound renin. We propose that this redox-responsive transition of angiotensinogen to a form that will more effectively release angiotensin at a cellular level contributes to the modulation of blood pressure. Specifically, we demonstrate the oxidative switch of angiotensinogen to its more active sulphydryl-bridged form in the maternal circulation in pre-eclampsia-the hypertensive crisis of pregnancy that threatens the health and survival of both mother and child.
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Angiotensinógeno/química , Angiotensinógeno/metabolismo , Angiotensinas/metabolismo , Procesamiento Proteico-Postraduccional , Secuencia de Aminoácidos , Angiotensinógeno/sangre , Angiotensinas/química , Presión Sanguínea , Cristalografía por Rayos X , Disulfuros/química , Disulfuros/metabolismo , Femenino , Humanos , Cinética , Modelos Moleculares , Datos de Secuencia Molecular , Oxidación-Reducción , Estrés Oxidativo , Preeclampsia/sangre , Preeclampsia/metabolismo , Embarazo , Conformación Proteica , Renina/química , Renina/metabolismoAsunto(s)
Hemorragia Gastrointestinal/cirugía , Enfermedades del Íleon/cirugía , Fiebre Tifoidea/diagnóstico , Úlcera/cirugía , Adolescente , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/microbiología , Humanos , Enfermedades del Íleon/etiología , Enfermedades del Íleon/microbiología , Masculino , Fiebre Tifoidea/complicaciones , Fiebre Tifoidea/microbiología , Úlcera/microbiologíaRESUMEN
An Eritrean-born man observed over an extended period had upper gastrointestinal symptoms, fever, hepatosplenomegaly and pancytopenia in the setting of advanced HIV infection and poor adherence to antiretroviral therapy. Despite thorough investigation, it was not until a repeat gastroscopic examination and gastric biopsy were performed 18 months after initial presentation that Leishmania infection was diagnosed. The species was identified by polymerase chain reaction assay as L. donovani. Physicians managing HIV-infected patients from regions where Leishmania is endemic should consider visceral leishmaniasis, even in patients who have not lived in a Leishmania-endemic region for many years.
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Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Leishmania infantum/aislamiento & purificación , Leishmaniasis Visceral/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Adulto , Antirretrovirales/uso terapéutico , Antiprotozoarios/uso terapéutico , Humanos , Leishmaniasis Visceral/tratamiento farmacológico , Masculino , Cooperación del PacienteRESUMEN
ADAM17 (where ADAM is 'a disintegrin and metalloproteinase') can rapidly modulate cell-surface signalling events by the proteolytic release of soluble forms of proligands for cellular receptors. Many regulatory pathways affect the ADAM17 sheddase activity, but the mechanisms for the activation are still not clear. We have utilized a cell-based ADAM17 assay to show that thiol isomerases, specifically PDI (protein disulfide isomerase), could be responsible for maintaining ADAM17 in an inactive form. Down-regulation of thiol isomerases, by changes in the redox environment (for instance as elicited by phorbol ester modulation of mitochondrial reactive oxygen species) markedly enhanced ADAM17 activation. On the basis of ELISA binding studies with novel fragment antibodies against ADAM17 we propose that isomerization of the disulfide bonds in ADAM17, and the subsequent conformational changes, form the basis for the modulation of ADAM17 activity. The shuffling of disulfide bond patterns in ADAMs has been suggested by a number of recent adamalysin crystal structures, with distinct disulfide bond patterns altering the relative orientations of the domains. Such a mechanism is rapid and reversible, and the role of thiol isomerases should be investigated further as a potential factor in the redox regulation of ADAM17.
Asunto(s)
Proteínas ADAM/metabolismo , Regulación hacia Abajo , Proteína Disulfuro Isomerasas/metabolismo , Proteínas ADAM/genética , Proteína ADAM17 , Línea Celular Tumoral , Células HeLa , Humanos , Proteína Disulfuro Isomerasas/genéticaRESUMEN
BACKGROUND: Ras signaling regulates a number of important processes in the heart, including cell growth and hypertrophy. Although it is known that defective Ras signaling is associated with Noonan, Costello, and other syndromes that are characterized by tumor formation and cardiac hypertrophy, little is known about factors that may control it. Here we investigate the role of Ras effector Ras-association domain family 1 isoform A (RASSF1A) in regulating myocardial hypertrophy. METHODS AND RESULTS: A significant downregulation of RASSF1A expression was observed in hypertrophic mouse hearts, as well as in failing human hearts. To further investigate the role of RASSF1A in cardiac (patho)physiology, we used RASSF1A knock-out (RASSF1A(-)(/)(-)) mice and neonatal rat cardiomyocytes with adenoviral overexpression of RASSF1A. Ablation of RASSF1A in mice significantly enhanced the hypertrophic response to transverse aortic constriction (64.2% increase in heart weight/body weight ratio in RASSF1A(-)(/)(-) mice compared with 32.4% in wild type). Consistent with the in vivo data, overexpression of RASSF1A in cardiomyocytes markedly reduced the cellular hypertrophic response to phenylephrine stimulation. Analysis of molecular signaling events in isolated cardiomyocytes indicated that RASSF1A inhibited extracellular regulated kinase 1/2 activation, likely by blocking the binding of Raf1 to active Ras. CONCLUSIONS: Our data establish RASSF1A as a novel inhibitor of cardiac hypertrophy by modulating the extracellular regulated kinase 1/2 pathway.