RESUMO
ß-Caryophyllene (BCP), a bicyclic sesquiterpene that is a component of the essential oils of various spice and food plants, has been described as a selective CB2 cannabinoid receptor agonist. In the present study, the effect of BCP on angiogenesis was investigated. It was found that conditioned media (CM) from BCP-treated hypoxic A549 lung cancer cells exhibited a concentration-dependent inhibitory effect on human umbilical vein endothelial cell (HUVEC) tube formation induced by CM from vehicle-treated hypoxic A549 cells. There was an associated concentration-dependent decrease in the proangiogenic factor vascular endothelial growth factor (VEGF) in the CM, with both BCP inhibitory effects (tube formation, VEGF secretion) being CB2 receptor-dependent. A reduction of the transcription factor hypoxia-inducible factor 1α (HIF-1α) was furthermore detected. The antiangiogenic and VEGF-lowering properties of BCP were confirmed when CM from another lung cancer cell line, H358, were tested. When directly exposed to HUVECs, BCP showed no significant effect on tube formation, but at 10 µM, impaired VEGF receptor 2 (VEGFR2) phosphorylation triggered by recombinant VEGF in a CB2 receptor-independent manner. In summary, BCP has a dual antiangiogenic effect on HUVECs, manifested in the inhibition of tube formation through modulation of the tumor cell secretome and additionally in the inhibition of VEGF-induced VEGFR2 activation. Because the CB2 agonist has no psychoactive properties, BCP should continue to be evaluated preclinically for further antitumor effects.
Assuntos
Neoplasias Pulmonares , Sesquiterpenos Policíclicos , Fator A de Crescimento do Endotélio Vascular , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Regulação para Baixo , Secretoma , Fatores de Crescimento do Endotélio Vascular , Hipóxia , Meios de Cultivo CondicionadosRESUMO
Next to iron (Fe), recent phytoplankton-enrichment experiments identified manganese (Mn) to (co-)limit Southern Ocean phytoplankton biomass and species composition. Since taxonomic diversity affects aggregation time and sinking rate, the efficiency of the biological carbon pump is directly affected by community structure. However, the impact of FeMn co-limitation on Antarctic primary production, community composition, and the subsequent export of carbon to depth requires more investigation. In situ samplings of 6 stations in the understudied southern Weddell Sea revealed that surface Fe and Mn concentrations, primary production, and carbon export rates were all low, suggesting a FeMn co-limited phytoplankton community. An Fe and Mn addition experiment examined how changes in the species composition drive the aggregation capability of a natural phytoplankton community. Primary production rates were highest when Fe and Mn were added together, due to an increased abundance of the colonial prymnesiophyte Phaeocystis antarctica. Although the community remained diatom dominated, the increase in Phaeocystis abundance led to highly carbon-enriched aggregates and a 4-fold increase in the carbon export potential compared to the control, whereas it only doubled in the Fe treatment. Based on the outcome of the FeMn-enrichment experiment, this region may suffer from FeMn co-limitation. As the Weddell Sea represents one of the most productive Antarctic marginal ice zones, our findings highlight that in response to greater Fe and Mn supply, changes in plankton community composition and primary production can have a disproportionally larger effect on the carbon export potential.
Assuntos
Diatomáceas , Haptófitas , Ferro , Manganês , Carbono , Fitoplâncton/fisiologia , Diatomáceas/fisiologia , Regiões Antárticas , Oceanos e MaresRESUMO
Brown tides caused by the pelagophyte Aureococcus anophagefferens have frequently occurred in the Bohai Sea since 2009 and have led to a dramatic collapse of the local scallop culture. To determine why brown tides occurred in the Bohai Sea rather than in other eutrophic coastal waters of China, phytoplankton communities and nutrients were evaluated and nutrient addition experiments were conducted in the Qinhuangdao coastal area. The concentration of dissolved organic nitrogen (DON) was nearly five times higher than that of dissolved inorganic nitrogen (DIN) during brown tides. High levels of phytoplankton biomass and nutrients were observed in the inshore waters, and the patterns of different nutrients were heterogeneous, which could be due to the uneven distribution of pelagophytes and non-brown tide phytoplankton populations (NBTP). The nutrient enrichment results indicated that the growth of the phytoplankton community was nitrogen-limited. Enrichment of DON, especially urea, could promote the growth of pelagophytes during the development stages of the brown tide. In brief, the results of this study imply that the unique nutrient profile (rich in DON but deficient in DIN) could support the outbreak of brown tides in the inshore waters of Qinhuangdao.
Assuntos
Fitoplâncton , Estramenópilas , Nitrogênio/análise , Nutrientes , Biomassa , ChinaRESUMO
RATIONALE: More than half of surveyed microalgae and over 90% of harmful algae have an obligate requirement for vitamin B12 , but methods for directly measuring dissolved B12 in seawater are scarce due to low concentrations and rapid light-induced hydrolysis. METHODS: We present a method to detect and measure the four main congeners of vitamin B12 dissolved in seawater. The method includes solid-phase extraction, separation by ultrahigh-performance liquid chromatography and detection by triple-quadrupole tandem mass spectrometry utilizing an electrospray ion source. This method was applied to coastal field samples collected in the German Bay, Baltic Sea and the Danish Limfjord system. RESULTS: The total dissolved B12 pool ranged between 0.5 and 2.1 pM. Under ambient conditions methyl-B12 and adenosyl-B12 were nearly fully hydrolyzed to hydroxy-B12 in less than 1 h. Hydroxy-B12 and a novel, corresponding isomer were the main forms of B12 found at all field sites. This isomer eluted well after the OH-B12 peak and was also detected in commercially available OH-B12 . Both compounds showed very high similarity in their collision-induced dissociation spectra. CONCLUSIONS: The high instability of the biologically active forms of Me-B12 and Ado-B12 towards hydrolysis was shown, highlighting the importance of reducing the duration of the extraction protocol. In addition, the vitamin B12 pool in the study area was mostly comprised of a previously undescribed isomer of OH-B12 . Further studies into the structure of this isomer and its bioavailability are needed.
Assuntos
Hidroxocobalamina , Água do Mar , Hidroxocobalamina/análise , Água do Mar/química , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Extração em Fase Sólida/métodos , Vitamina B 12/análise , Vitaminas/análise , Cromatografia Líquida de Alta Pressão/métodosRESUMO
While it has been recently demonstrated that both iron (Fe) and manganese (Mn) control Southern Ocean (SO) plankton biomass, how in particular Mn governs phytoplankton species composition remains yet unclear. This study, for the first time, highlights the importance of Mn next to Fe for growth of two key SO phytoplankton groups at two locations in the Drake Passage (West and East). Even though the bulk parameter chlorophyll a indicated Fe availability as main driver of both phytoplankton assemblages, the flow cytometric and microscopic analysis revealed FeMn co-limitation of a key phytoplankton group at each location: at West the dominant diatom Fragilariopsis and one subgroup of picoeukaryotes, which numerically dominated the East community. Hence, the limitation by both Fe and Mn and their divergent requirements among phytoplankton species and groups can be a key factor for shaping SO phytoplankton community structure.
Assuntos
Diatomáceas , Fitoplâncton , Clorofila A , Ferro , ManganêsRESUMO
A breeding colony of notothenioid icefish (Neopagetopsis ionah, Nybelin 1947) of globally unprecedented extent has been discovered in the southern Weddell Sea, Antarctica. The colony was estimated to cover at least â¼240 km2 of the eastern flank of the Filchner Trough, comprised of fish nests at a density of 0.26 nests per square meter, representing an estimated total of â¼60 million active nests and associated fish biomass of >60,000 tonnes. The majority of nests were each occupied by 1 adult fish guarding 1,735 eggs (±433 SD). Bottom water temperatures measured across the nesting colony were up to 2°C warmer than the surrounding bottom waters, indicating a spatial correlation between the modified Warm Deep Water (mWDW) upflow onto the Weddell Shelf and the active nesting area. Historical and concurrently collected seal movement data indicate that this concentrated fish biomass may be utilized by predators such as Weddell seals (Leptonychotes weddellii, Lesson 1826). Numerous degraded fish carcasses within and near the nesting colony suggest that, in death as well as life, these fish provide input for local food webs and influence local biogeochemical processing. To our knowledge, the area surveyed harbors the most spatially expansive continuous fish breeding colony discovered to date globally at any depth, as well as an exceptionally high Antarctic seafloor biomass. This discovery provides support for the establishment of a regional marine protected area in the Southern Ocean under the Convention on the Conservation of Antarctic Marine Living Resources (CCAMLR) umbrella. VIDEO ABSTRACT.
Assuntos
Focas Verdadeiras , Animais , Regiões Antárticas , Peixes , Cadeia Alimentar , ÁguaRESUMO
Krill and salps are important for carbon flux in the Southern Ocean, but the extent of their contribution and the consequences of shifts in dominance from krill to salps remain unclear. We present a direct comparison of the contribution of krill and salp faecal pellets (FP) to vertical carbon flux at the Antarctic Peninsula using a combination of sediment traps, FP production, carbon content, microbial degradation, and krill and salp abundances. Salps produce 4-fold more FP carbon than krill, but the FP from both species contribute equally to the carbon flux at 300 m, accounting for 75% of total carbon. Krill FP are exported to 72% to 300 m, while 80% of salp FP are retained in the mixed layer due to fragmentation. Thus, declining krill abundances could lead to decreased carbon flux, indicating that the Antarctic Peninsula could become a less efficient carbon sink for anthropogenic CO2 in future.
Assuntos
Ciclo do Carbono , Carbono/metabolismo , Euphausiacea/metabolismo , Água do Mar/análise , Animais , Regiões Antárticas , Fezes/químicaRESUMO
The 'Iron Hypothesis' suggests a fertilization of the Southern Ocean by increased dust deposition in glacial times. This promoted high primary productivity and contributed to lower atmospheric pCO2. In this study, the diatom Pseudo-nitzschia subcurvata, known to form prominent blooms in the Southern Ocean, was grown under simulated glacial and interglacial climatic conditions to understand how iron (Fe) availability (no Fe or Fe addition) in conjunction with different pCO2 levels (190 and 290 µatm) influences growth, particulate organic carbon (POC) production and photophysiology. Under both glacial and interglacial conditions, the diatom grew with similar rates. In comparison, glacial conditions (190 µatm pCO2 and Fe input) favored POC production by P. subcurvata while under interglacial conditions (290 µatm pCO2 and Fe deficiency) POC production was reduced, indicating a negative effect caused by higher pCO2 and low Fe availability. Under interglacial conditions, the diatom had, however, thicker silica shells. Overall, our results show that the combination of higher Fe availability with low pCO2, present during the glacial ocean, was beneficial for the diatom P. subcurvata, thus contributing more to primary production during glacial compared to interglacial times. Under the interglacial ocean conditions, on the other hand, the diatom could have contributed to higher carbon export due to its higher degree of silicification.
Assuntos
Dióxido de Carbono/metabolismo , Corantes/química , Diatomáceas/crescimento & desenvolvimento , Ferro/metabolismo , Atmosfera , Corantes/metabolismo , Poeira , Minerais/química , Oceanos e Mares , Fotossíntese , Água do Mar , TemperaturaRESUMO
Over the last decades, it has been reported that the habitat of the Southern Ocean (SO) key species Antarctic krill (Euphausia superba) has contracted to high latitudes, putatively due to reduced winter sea ice coverage, while salps as Salpa thompsoni have extended their dispersal to the former krill habitats. To date, the potential implications of this population shift on the biogeochemical cycling of the limiting micronutrient iron (Fe) and its bioavailability to SO phytoplankton has never been tested. Based on uptake of fecal pellet (FP)-released Fe by SO phytoplankton, this study highlights how efficiently krill and salps recycle Fe. To test this, we collected FPs of natural populations of salps and krill, added them to the same SO phytoplankton community, and measured the community's Fe uptake rates. Our results reveal that both FP additions yielded similar dissolved iron concentrations in the seawater. Per FP carbon added to the seawater, 4.8 ± 1.5 times more Fe was taken up by the same phytoplankton community from salp FP than from krill FP, suggesting that salp FP increased the Fe bioavailability, possibly through the release of ligands. With respect to the ongoing shift from krill to salps, the potential for carbon fixation of the Fe-limited SO could be strengthened in the future, representing a negative feedback to climate change.
Assuntos
Euphausiacea/metabolismo , Fezes/química , Ferro/metabolismo , Oceanos e Mares , Fitoplâncton/metabolismo , Animais , Regiões Antárticas , Ciclo do Carbono , Mudança Climática , EcossistemaRESUMO
Fluorescent natural compounds have been identified in several marine hosts of microalgae. Their prevalence, and the energy the host is expending on their synthesis, suggests an important, yet poorly understood ecological role. It has been suggested that some of these natural products may enhance the photosynthesis of microbial symbionts. In this study, the effect of Ageladine A (Ag A), a pH-dependent fluorophore found in sponges of the genus Agelas, on the photosynthesis of nine microalgal species and strains was examined. The data showed that the variety of effects of Ag A additions differed between species, and even strains within a species. While in one strain of Synechococcus sp., the presence of Ag A increased gross photosynthesis under UV light exposure, it decreased in another. And while in the chlorophyte T. chuii overall metabolic activity was greatly reduced under all forms of lighting, photosynthesis in T. lutea was positively affected by the addition of Ag A. The variety of effects of Ag A on photosynthesis observed in this study indicate a complex interaction of Ag A with microalgal cells and suggests that a host may be able to shape its own symbiotic microbiome with self-produced natural products.
Assuntos
Agelas/microbiologia , Microalgas/fisiologia , Fotossíntese/efeitos dos fármacos , Pirróis/farmacologia , Simbiose/fisiologia , Animais , Microalgas/classificação , Pirróis/metabolismo , Simbiose/efeitos dos fármacosRESUMO
In several marine hosts of microalgae, fluorescent natural products may play an important role. While the ecological function of these compounds is not well understood, an interaction of these molecules with the photosynthesis of the symbionts has been suggested. In this study, the effect of Ageladine A (Ag A), a pH-dependent fluorophore found in sponges of the genus Agelas, on microalgal fluorescence was examined. The spectra showed an accumulation of Ag A within the cells, but with variable impacts on fluorescence. While in two Synechococcus strains, fluorescence of phycoerythrin increased significantly, the fluorescence of other Synechococcus strains was not affected. In four out of the five eukaryote species examined, chlorophyll a (Chl a) fluorescence intensity was modulated. In Tisochrysis lutea, for example, the position of the fluorescence emission maximum of Chl a was shifted. The variety of these effects of Ag A on microalgal fluorescence suggests that fluorophores derived from animals could play a crucial role in shaping the composition of marine host/symbiont systems.
Assuntos
Agelas/química , Microalgas/efeitos dos fármacos , Pirróis/farmacologia , Simbiose , Animais , Clorofila A/química , Fluorescência , Micrasterias/efeitos dos fármacos , Micrasterias/metabolismo , Microalgas/metabolismo , Fotossíntese/efeitos dos fármacos , Fotossíntese/efeitos da radiação , Ficobilissomas/química , Ficobilissomas/efeitos dos fármacos , Ficoeritrina/química , Pigmentos Biológicos/química , Pirróis/isolamento & purificação , Especificidade da Espécie , Espectrometria de Fluorescência , Synechococcus/efeitos dos fármacos , Synechococcus/metabolismo , Raios UltravioletaRESUMO
Dual optical frequency combs are an appealing solution to many optical measurement techniques due to their high spectral and temporal resolution, high scanning speed, and lack of moving parts. However, industrial and field-deployable applications of such systems are limited due to a high-cost factor and intricacy in the experimental setups, which typically require a pair of locked femtosecond lasers. Here, we demonstrate a single oscillator which produces two mode-locked output beams with a stable repetition rate difference. We achieve this via inserting two 45°-cut birefringent crystals into the laser cavity, which introduces a repetition rate difference between the two polarization states of the cavity. To mode-lock both combs simultaneously, we use a semiconductor saturable absorber mirror (SESAM). We achieve two simultaneously operating combs at 1050 nm with 175-fs duration, 3.2-nJ pulses and an average power of 440 mW in each beam. The average repetition rate is 137 MHz, and we set the repetition rate difference to 1 kHz. This laser system, which is the first SESAM mode-locked femtosecond solid-state dual-comb source based on birefringent multiplexing, paves the way for portable and high-power femtosecond dual-combs with flexible repetition rate. To demonstrate the utility of the laser for applications, we perform asynchronous optical sampling (ASOPS) on semiconductor thin-film structures with the free-running laser system, revealing temporal dynamics from femtosecond to nanosecond time scales.
RESUMO
While harmful algal blooms caused by the ichthyotoxic dinoflagellate, Cochlodinium (Margalefidinium) polykrikoides, are allelopathic and may have unique associations with bacteria, a comprehensive assessment of the planktonic communities associated with these blooms has been lacking. Here, we used high-throughput amplicon sequencing to assess size fractionated (0.2 and 5 µm) bacterial (16S) and phytoplankton assemblages (18S) associated with blooms of C. polykrikoides during recurrent blooms in NY, USA. Over a three-year period, samples were collected inside ('patch') and outside ('non-patch') dense accumulations of C. polykrikoides to assess the microbiome associated with these blooms. Eukaryotic plankton communities of blooms had significantly lower diversity than non-bloom samples, and non-bloom samples hosted 30 eukaryotic operational taxonomic units (OTUs) not found within blooms, suggesting they may have been allelopathically excluded from blooms. Differential abundance analyses revealed that C. polykrikoides blooms were significantly enriched in dinoflagellates (p<0.001) and the experimental enrichment of C. polykrikoides led to a significant increase in the relative abundance of eight genera of dinoflagellates but a significant decline in other eukaryotic plankton. Amoebophrya co-dominated both within- and near- C. polykrikoides blooms and was more abundant in bloom patches. The core bacterial microbiome of the >0.2µm fraction of blooms was dominated by an uncultured bacterium from the SAR11 clade, while the >5µm size fraction was co-dominated by an uncultured bacterium from Rhodobacteraceae and Coraliomargarita. Two bacterial lineages within the >0.2µm fraction, as well as the Gammaproteobacterium, Halioglobus, from the >5µm fraction were unique to the microbiome of blooms, while there were 154 bacterial OTUs only found in non-bloom waters. Collectively, these findings reveal the unique composition and potential function of eukaryotic and prokaryotic communities associated with C. polykrikoides blooms.
Assuntos
Dinoflagellida/microbiologia , Células Eucarióticas/microbiologia , Proliferação Nociva de Algas/fisiologia , Fitoplâncton/microbiologia , Células Procarióticas/microbiologia , Bactérias/genética , Estuários , Microbiota/genética , New YorkRESUMO
This study is a proof of concept that the sponge derived pyrrole-imidazole alkaloid Ageladine A acts as an additional light harvesting molecule for photosynthesis of symbionts of marine sponges. The absorbance of Ageladine A is in the UV range and fluoresces blue, matching the blue absorbance of chlorophyll a. A joint modeling and experimental approach demonstrates that Ageladine A increases photosynthetic O2 production of Synechococcus bacillaris WH5701 (CCMP1333), when the cells are exposed to UV light, which is marginally used for photosynthesis. Due to the presence of Ageladine A, production of O2 increased 2.54 and 3.1-fold, in the experiments and the model, respectively.
Assuntos
Fotossíntese , Poríferos/metabolismo , Pirróis/química , Synechococcus/metabolismo , Animais , Oxigênio/química , Oxigênio/metabolismo , Fotossíntese/efeitos da radiação , Complexo de Proteína do Fotossistema II/metabolismo , Simbiose , Raios UltravioletaRESUMO
Cyanobacteria are fundamental components of aquatic phytoplankton communities and some taxa can cause harmful blooms in coastal ecosystems. Harmful cyanobacterial blooms are typically comprised of multiple strains of a single genus or species that cannot be resolved microscopically. Florida Bay, USA, has experienced harmful cyanobacterial blooms that have been associated with the loss of eelgrass, spiny lobsters, and general food web disruption for more than two decades. To identify the strain or strains of cyanobacteria forming blooms in Florida Bay, samples were collected across the system over an annual cycle and analyzed via DNA sequencing using cyanobacterial-specific 16S rRNA gene primers, flow cytometry, and scanning electron microscopy. Analyses demonstrated that the onset of blooms in Florida Bay was coincident with a transformation of the cyanobacterial populations. When blooms were absent, the cyanobacterial population in Florida Bay was dominated by phycoerythrin-containing Synechococcus cells that were most similar to strains within Clade III. As blooms developed, the cyanobacterial community transitioned to dominance by phycocyanin-containing Synechococcus cells that were coated with mucilage, chain-forming, and genetically most similar to the coastal strains within Clade VIII. Clade VIII strains of Synechococcus are known to grow rapidly, utilize organic nutrients, and resist top-down control by protozoan grazers and viruses, all characteristics consistent with observations of cyanobacterial blooms in Florida Bay. Further, the strains of Synechococcus blooming in this system are genetically distinct from the species previously thought to cause blooms in Florida Bay, Synechococcus elongatus. Collectively, this study identified the causative organism of harmful cyanobacterial blooms in Florida Bay, demonstrates the dynamic nature of cyanobacterial stains within genera in an estuary, and affirms factors promoting Synechococcus blooms.
Assuntos
Cianobactérias/classificação , Cianobactérias/crescimento & desenvolvimento , Proliferação Nociva de Algas , Baías , Cianobactérias/genética , Cianobactérias/isolamento & purificação , Florida , RNA Ribossômico 16S/genética , Synechococcus/classificação , Synechococcus/genética , Synechococcus/crescimento & desenvolvimento , Synechococcus/isolamento & purificaçãoRESUMO
The effects of coastal acidification on the growth and toxicity of the saxitoxin-producing dinoflagellate Alexandrium fundyense were examined in culture and ecosystem studies. In culture experiments, Alexandrium strains isolated from Northport Bay NY, USA, and the Bay of Fundy, Canada, grew significantly faster (16 -190%; p<0.05) when exposed to elevated levels of pCO2 (~ 800- 1900µatm) compared to lower levels (~390µatm). Exposure to higher levels of pCO2 also resulted in significant increases (71 - 81%) in total cellular toxicity (fg STX eq. cell-1) in the Northport Bay strain, while no changes in toxicity were detected in the Bay of Fundy strain. The positive relationship between pCO2 enhancement and elevated growth was reproducible using natural populations from Northport; Alexandrium densities were significantly and consistently enhanced when natural populations were incubated at 1500 µatm pCO2, a value at the upper range of those recorded in Northport Bay, 390 - 1500 µatm. During natural Alexandrium blooms in Northport Bay, pCO2 concentrations increased over the course of a bloom to more than 1700µatm and were highest in regions with the greatest Alexandrium abundances, suggesting Alexandrium may be further exacerbating acidification or be especially adapted to these extreme, acidified conditions. The co-occurrence of Alexandrium blooms and elevated pCO2 represents a previously unrecognized, compounding environmental threat to coastal ecosystems. The ability of elevated pCO2 to enhance the growth and toxicity of Alexandrium indicates that acidification promoted by eutrophication or climate change can intensify these, and perhaps other, harmful algal blooms.
RESUMO
While vitamin B(12) has recently been shown to co-limit the growth of coastal phytoplankton assemblages, the cycling of B-vitamins in coastal ecosystems is poorly understood as planktonic uptake rates of vitamins B(1) and B(12) have never been quantified in tandem in any aquatic ecosystem. The goal of this study was to establish the relationships between plankton community composition, carbon fixation, and B-vitamin assimilation in two contrasting estuarine systems. We show that, although B-vitamin concentrations were low (pM), vitamin concentrations and uptake rates were higher within a more eutrophic estuary and that vitamin B(12) uptake rates were significantly correlated with rates of primary production. Eutrophic sites hosted larger bacterial and picoplankton abundances with larger carbon normalized vitamin uptake rates. Although the >2 µm phytoplankton biomass was often dominated by groups with a high incidence of vitamin auxotrophy (dinoflagellates and diatoms), picoplankton (<2 µm) were always responsible for the majority of B(12)-vitamin uptake. Multiple lines of evidence suggest that heterotrophic bacteria were the primary users of vitamins among the picoplankton during this study. Nutrient/vitamin amendment experiments demonstrated that, in the Summer and Fall, vitamin B(12) occasionally limited or co-limited the accumulation of phytoplankton biomass together with nitrogen. Combined with prior studies, these findings suggest that picoplankton are the primary producers and users of B-vitamins in some coastal ecosystems and that rapid uptake of B-vitamins by heterotrophic bacteria may sometimes deprive larger phytoplankton of these micronutrients and thus influence phytoplankton species succession.
RESUMO
Familial hemophagocytic lymphohistiocytosis (FHL) is a genetically determined hyperinflammatory syndrome caused by uncontrolled immune response mediated by T-lymphocytes, natural killer (NK) cells, and macrophages. STXBP2 mutations have recently been associated with FHL5. To better characterize the genetic and clinical spectrum of FHL5, we analyzed a cohort of 185 patients with suspected FHL for mutations in STXBP2. We detected biallelic mutations in 37 patients from 28 families of various ethnic origins. Missense mutations and mutations affecting 1 of the exon 15 splice sites were the predominant changes detectable in this cohort. Patients with exon 15 splice-site mutations (n = 13) developed clinical manifestations significantly later than patients with other mutations (median age, 4.1 year vs 2 months) and showed less severe impairment of degranulation and cytotoxic function of NK cells and CTLs. Patients with FHL5 showed several atypical features, including sensorineural hearing deficit, abnormal bleeding, and, most frequently, severe diarrhea that was only present in early-onset disease. In conclusion, we report the largest cohort of patients with FHL5 so far, describe an extended disease spectrum, and demonstrate for the first time a clear genotype-phenotype correlation.
Assuntos
Linfo-Histiocitose Hemofagocítica/genética , Proteínas Munc18/genética , Mutação , Adolescente , Adulto , Teste de Degranulação de Basófilos , Criança , Pré-Escolar , Estudos de Coortes , Análise Mutacional de DNA , Epistasia Genética , Feminino , Estudos de Associação Genética , Humanos , Lactente , Recém-Nascido , Linfo-Histiocitose Hemofagocítica/classificação , Linfo-Histiocitose Hemofagocítica/etnologia , Masculino , Modelos Biológicos , Proteínas Munc18/fisiologia , Mutação/fisiologia , Proteínas Qa-SNARE/genética , Adulto JovemRESUMO
The first catalytic asymmetric synthesis of ß-sultones is reported. This development has enabled a rapid access to a number of highly enantioenriched biologically interesting sulfonyl and sulfinyl compound classes, which makes use of the inherent ring strain of the four-membered heterocycles. The products possess either two vicinal stereocenters, such as in ß-hydroxy-sulfonamides, -sulfonates, -sulfones, -sulfonic acids, -sulfinic acids, γ-sultines, and γ-sultones or a single stereocenter, such as in α-branched alkyl or allyl sulfonic acids. This work also represents the first application of sulfene intermediates in asymmetric catalysis. The reactivity of a sulfene normally acting as an electrophile could be reverted by the formation of a nucleophilic zwitterionic sulfene-amine adduct. To achieve a combination of high enantioselectivity and reactivity, cooperative catalytic action of a chiral nucleophilic tertiary amine (the cinchona alkaloid derivative diydroquinine 2,5-diphenyl-4,6-pyrimidinediyl diether ((DHQ)(2)PYR)) and Bi(OTf)(3) or In(OTf)(3) was of primary importance.
Assuntos
Aldeídos/química , Ácidos de Lewis/química , Sulfamerazina/química , Compostos de Sulfidrila/química , Sulfonas/química , Catálise , Estrutura Molecular , EstereoisomerismoRESUMO
Harmful algal blooms (HABs) cause significant economic and ecological damage worldwide. Despite considerable efforts, a comprehensive understanding of the factors that promote these blooms has been lacking, because the biochemical pathways that facilitate their dominance relative to other phytoplankton within specific environments have not been identified. Here, biogeochemical measurements showed that the harmful alga Aureococcus anophagefferens outcompeted co-occurring phytoplankton in estuaries with elevated levels of dissolved organic matter and turbidity and low levels of dissolved inorganic nitrogen. We subsequently sequenced the genome of A. anophagefferens and compared its gene complement with those of six competing phytoplankton species identified through metaproteomics. Using an ecogenomic approach, we specifically focused on gene sets that may facilitate dominance within the environmental conditions present during blooms. A. anophagefferens possesses a larger genome (56 Mbp) and has more genes involved in light harvesting, organic carbon and nitrogen use, and encoding selenium- and metal-requiring enzymes than competing phytoplankton. Genes for the synthesis of microbial deterrents likely permit the proliferation of this species, with reduced mortality losses during blooms. Collectively, these findings suggest that anthropogenic activities resulting in elevated levels of turbidity, organic matter, and metals have opened a niche within coastal ecosystems that ideally suits the unique genetic capacity of A. anophagefferens and thus, has facilitated the proliferation of this and potentially other HABs.