RESUMO
Mountains are the water towers of the world, supplying a substantial part of both natural and anthropogenic water demands1,2. They are highly sensitive and prone to climate change3,4, yet their importance and vulnerability have not been quantified at the global scale. Here we present a global water tower index (WTI), which ranks all water towers in terms of their water-supplying role and the downstream dependence of ecosystems and society. For each water tower, we assess its vulnerability related to water stress, governance, hydropolitical tension and future climatic and socio-economic changes. We conclude that the most important (highest WTI) water towers are also among the most vulnerable, and that climatic and socio-economic changes will affect them profoundly. This could negatively impact 1.9 billion people living in (0.3 billion) or directly downstream of (1.6 billion) mountainous areas. Immediate action is required to safeguard the future of the world's most important and vulnerable water towers.
Assuntos
Abastecimento de Água , Altitude , Conservação dos Recursos Naturais , Humanos , Fatores Socioeconômicos , ÁguaRESUMO
The pathogenesis of rheumatoid arthritis (RA) is incompletely understood. Human endogenous retroviruses (HERVs) and their superantigenic envelope protein (env) have been implicated in the pathogenesis of RA. In the present investigation, the arthritogenic potential of the superantigen staphylococcal enterotoxin A (SEA) has been investigated. In the present investigation, the bacterial superantigen staphylococcal enterotoxin A (SEA) was injected into the right knee joint of 15 Lewis rats. Further nine animals received saline. Animals were sacrificed one, five and 10 days after the injection, respectively. The antigens CD3, CD4, CD8, MHC class I, MHC class II, Pax5 and CD138 were investigated by immunohistochemistry on cryo-sections. After intra-articular SEA injection, the inflammation was initially dominated by CD8+ T cells. In the course of the investigation, the numbers of CD4+, Pax5+, CD138+ and MHC class II+ cells increased. CD3 was expressed in low numbers as compared to CD8. After saline injection, no similar inflammatory response has been detected. The arthritis induced by the superantigen SEA may be a novel model for inflammatory joint diseases, that is rheumatoid arthritis or juvenile idiopathic arthritis.
Assuntos
Artrite Experimental/imunologia , Artrite Experimental/patologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Enterotoxinas/imunologia , Superantígenos/imunologia , Animais , Artrite Reumatoide/patologia , Linfócitos B/imunologia , Complexo CD3/metabolismo , Antígenos CD4/metabolismo , Antígenos CD8/metabolismo , Modelos Animais de Doenças , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Masculino , Fator de Transcrição PAX5/metabolismo , Ratos , Ratos Endogâmicos Lew , Sindecana-1/metabolismoRESUMO
On 7 February 2021, a catastrophic mass flow descended the Ronti Gad, Rishiganga, and Dhauliganga valleys in Chamoli, Uttarakhand, India, causing widespread devastation and severely damaging two hydropower projects. More than 200 people were killed or are missing. Our analysis of satellite imagery, seismic records, numerical model results, and eyewitness videos reveals that ~27 × 106 cubic meters of rock and glacier ice collapsed from the steep north face of Ronti Peak. The rock and ice avalanche rapidly transformed into an extraordinarily large and mobile debris flow that transported boulders greater than 20 meters in diameter and scoured the valley walls up to 220 meters above the valley floor. The intersection of the hazard cascade with downvalley infrastructure resulted in a disaster, which highlights key questions about adequate monitoring and sustainable development in the Himalaya as well as other remote, high-mountain environments.
RESUMO
In the present investigation, T-cell subsets of the previously described superantigen-induced encephalitis [9] have been investigated in 16 Lewis rats in comparison with four controls. Three days after intracerebral injection of Staphylococcal Enterotoxin A (SEA) or saline, 1.5 x 10(7) ConA-activated splenocytes were loaded i.v. animals were sacrificed after 0.5, 3 or 5 days, followed by immunohistochemical investigation of CD3, CD4 and CD8. Pronounced perivascular cuffing was identified 0.5 days after splenocyte injection and declined thereafter. The majority of the perivascular round cells consisted of CD8+ T-cells (65%) and CD4+ T-cells (10%). Less than 20% of the perivascular round cells were CD3+. The reduced expression of CD3 relative to e.g. CD8 is presumably due to the previous superantigenic stimulus. The presented data may be of relevance for the pathogenesis of infectious or autoimmune encephalitis, e.g. in multiple sclerosis.
Assuntos
Antígenos CD/biossíntese , Encefalite/imunologia , Esclerose Múltipla/imunologia , Subpopulações de Linfócitos T/metabolismo , Transferência Adotiva , Animais , Antígenos CD/genética , Modelos Animais de Doenças , Encefalite/induzido quimicamente , Enterotoxinas/administração & dosagem , Imuno-Histoquímica , Esclerose Múltipla/terapia , Ratos , Ratos Endogâmicos Lew , Superantígenos/administração & dosagem , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/patologiaRESUMO
Superantigens were suggested to play a role in the pathogenesis of different autoimmune diseases including multiple sclerosis (MS). Previously, it was demonstrated that local expression of the superantigen, staphylococcal enterotoxin A (SEA) in the brain of rats may lead to encephalitis which was amplified by using intravenous injection of concanavalin A (ConA)-activated splenocytes. In the present investigation, gene expression was studied in the rat brain 8 days after an injection of 50 mul of 1 mg/ml SEA or saline and 5 days after an intravenous injection of 1 x 10(7) ConA-activated spleen cells. Of 8800 genes investigated (Affymetrix, rat genome U34A), the expression of 106 genes was significantly and at least threefold increased with SEA, while the expression of 29 genes was decreased at least threefold. Increased gene expression was compatible with an intracerebral inflammatory response mediated by antigen-presenting cells and CD8+ T lymphocytes. Elevated chemokines comprised RANTES (CCL5), osteopontin, MCP-1 (CCL2) and CXCL10. Further, genes with increased expression were assigned to the extracellular matrix, microglia/macrophage cell elements, astrocytes (GFAP) and phagocytosis. There was considerable conformity between previously reported gene expression profiles for experimental autoimmune encephalomyelitis (EAE) or MS and the present findings. Our data are in line with the concept that T-cell superantigen locally expressed in the central nervous system induces an inflammatory response. Therefore, the study of gene expression profiles does not seem to allow clear conclusions with respect to the aetiology of central nervous system autoimmune diseases.
Assuntos
Encefalite/genética , Enterotoxinas/imunologia , Regulação da Expressão Gênica , Superantígenos/genética , Animais , Células Apresentadoras de Antígenos/imunologia , Astrócitos/metabolismo , Encéfalo/imunologia , Encéfalo/patologia , Linfócitos T CD8-Positivos/imunologia , Quimiocinas/biossíntese , Quimiocinas/genética , Encefalite/induzido quimicamente , Encefalite/imunologia , Encefalite/patologia , Enterotoxinas/efeitos adversos , Inflamação/patologia , Macrófagos/imunologia , Masculino , Camundongos , Microglia/imunologia , Ratos , Ratos Endogâmicos LewAssuntos
Retrovirus Endógenos/imunologia , Esclerose Múltipla Crônica Progressiva/imunologia , Superantígenos/imunologia , Apoptose/imunologia , Axônios/imunologia , Linfócitos B/imunologia , Encéfalo/imunologia , Retrovirus Endógenos/genética , Infecções por Vírus Epstein-Barr/imunologia , Humanos , Degeneração Neural/imunologia , Bandas Oligoclonais/sangue , Oligodendroglia/imunologia , Linfócitos T/imunologia , TransativadoresRESUMO
BACKGROUND: Charcot-Marie-Tooth disease (CMT) type 1A is the most common form of CMT 1 and one of the autosomal dominant demyelinating hereditary motor and sensory neuropathies (HMSN). Cranial nerves may be frequently subclinically affected in CMT disease. However manifest clinical signs of cranial nerve involvement are rare. METHODS: This case comprise neurological, ophthalmological, internal medicine and ear-nose-throat investigation, motor and sensory nerve conduction velocity, auditory evoked potentials and orbicularis-oculi reflex measurements, lumbar puncture and blood examination, inclusive molecular genetic testing, as well as electrocardiogram and cranial imaging such as computer tomography and magnetic resonance imaging RESULTS: The present case shows a Charcot-Marie-Tooth (CMT) 1A patient with complete unilateral oculomotor palsy in combination with predominant ipsilateral subclinical trigeminal demyelination. A combined of third and fifth cranial nerves as in our patient has not been reported yet. CONCLUSIONS: This case shows cranial nerve involvement as an unusual leading symptom of CMT 1A. It may remind us that hereditary neuropathies have to be taken into consideration in patients with slowly progressing unilateral or asymmetric cranial neuropathies.
Assuntos
Doença de Charcot-Marie-Tooth/fisiopatologia , Nervos Cranianos/fisiopatologia , Neuropatia Hereditária Motora e Sensorial/fisiopatologia , Adulto , Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Doenças Desmielinizantes/complicações , Doenças Desmielinizantes/diagnóstico , Doenças Desmielinizantes/fisiopatologia , Neuropatia Hereditária Motora e Sensorial/diagnóstico , Humanos , Masculino , Fenótipo , ReflexoRESUMO
An attempt was made to separate the isoenzymes and subunits of pig liver esterase by capillary zone electrophoresis. This enzyme is a complex mixture and is strongly adsorbed on a fused-silica capillary. However, by simply adding a cationic fluorosurfactant to the running buffer, adsorption was significantly reduced. The effects of adding a zwitterionic and a neutral fluorosurfactant were also investigated. Large changes in the elution pattern were observed when using different combinations of these additives. Mixtures of different fluorosurfactants added to the running buffer can therefore be utilized in strategies for optimization of the separation selectivity.
Assuntos
Eletroforese/métodos , Esterases/análise , Flúor , Isoenzimas/análise , Fígado/enzimologia , Tensoativos , Animais , SuínosRESUMO
It is well known that the size of the sympathetic skin response (SSR) depends on the stimulus strength. In the present investigation train stimuli (TS) were employed to study the behavior of the SSR when recruited above the usual level. The SSR was obtained in healthy human subjects over the palm of the hand after supramaximal single stimuli (SS) and trains of three (TS; interstimulus interval 3 ms) over the ipsilateral superficial radial nerve in 15 healthy volunteers. Ipsilateral to the stimulus site SSR amplitudes were 5.7 ± 5.3 (SS) and 7.7 ± 5.9 mV (TS; p < 0.001), and contralateral 6.3 ± 6.3 (SS) and 7.2 ± 4.9 mV (TS; not significant). The relative gain in amplitude after TS vs. SS was negatively correlated with the SSR amplitude after SS ipsilateral (p < 0.0005) and contralateral to the stimulus site (p < 0.01). The increase in SSR amplitudes after TS compared with SS is in line with temporal summation of the excitatory synaptic input in neurons generating the SSR. Driving the SSR with TS is of possible relevance for the investigation of disorders of the peripheral or central autonomic nervous system.
RESUMO
This paper describes the use of fluorosurfactants as buffer additives for capillary electrophoretic separation of proteins and peptides. Due to fluorosurfactant bilayer formation at the capillary inner wall, the surface charge can be adjusted and even reversed. If the running buffer pH is kept at a level where the proteins have the same sign of charge as the wall, electrostatic repulsion will be obtained. The protein wall adsorption can therefore be reduced and the separation performance can be noticeably increased. The separation performance can also be further improved by including mixtures of different types of fluorosurfactants in the running buffer. The buffer system can accordingly be adapted for a certain separation problem. Mechanisms for the use of fluorosurfactants for wall deactivation in capillary electrophoretic protein separations is discussed in the present work and some examples of applications are also presented.
Assuntos
Eletroforese Capilar/instrumentação , Hidrocarbonetos Fluorados/química , Peptídeos/isolamento & purificação , Proteínas/isolamento & purificação , Tensoativos/química , Adsorção , Soluções Tampão , Fenômenos Químicos , Físico-Química , Eletroforese Capilar/métodos , Dióxido de Silício/química , Eletricidade Estática , Propriedades de SuperfícieRESUMO
In an earlier report (Litborn, E., Emmer, A., Roeraade, J., Anal. Chim. Acta 1999, 401, 11-19, we described a technique for performing chemistry in chip-based vials. A major problem, solvent evaporation, was partially remedied by using a closed humidity chamber. In this paper we report an improved technique for performing parallel reactions in open, 15 nL volume, chip-based vials. The evaporation of solvent from the reaction fluid was continuously compensated by addition of solvent via an array of microcapillaries. The suitability of the method was demonstrated by performing eight separate peptide maps of myoglobin in parallel, using the three enzymes trypsin, alpha-chymotrypsin and endoproteinase Glu-C. The total amount of myoglobin utilized to perform the eight digests was less than 100 pmol. The corresponding amount of enzymes was ca. 0.1 pmol per reaction. In order to evaluate the operating limits of the technique, a study of the evaporation of solvents from a series of vials with proportionally smaller volumes operated at different temperatures was performed. The results showed that the concept for continuous compensation of solvent evaporation should be applicable to reaction volumes down to 30 pL.
Assuntos
Eletroforese Capilar/métodos , Proteínas/análise , Animais , Físico-Química/métodos , Humanos , Proteínas/químicaRESUMO
Extracts prepared from Antarctic krill (Euphausia superba), mainly consisting of acidic proteolytic enzymes, have been studied with capillary electrophoretic techniques. Approximately 50 repeatable peaks were obtained with capillary zone electrophoresis on an untreated fused-silica capillary using a phosphate buffer containing anionic and cationic fluorosurfactant additives as separation medium. A faster separation was achieved on a polyvinyl alcohol coated capillary. Quantitative variations of individual proteins regarding different krill enzyme batches were noted. In the krill samples trypsin-like serine proteinase, carboxypeptidase A and carboxypeptidase B were tentatively identified.