RESUMO
From April 2016, carfilzomib, in combination with lenalidomide and dexamethasone (KRD), became available for use in the daily practice in Italy for patients with relapsed or refractory multiple myeloma (RRMM). We performed a retrospective survey at 14 different institutions from Southern Italy in order to evaluate patient characteristics and treatment results from an unselected series of patients treated accordingly so far. One hundred and twenty-three consecutive patients were included, with a median of 2 previous lines of therapy (range 1-9) and a median age of 63 years (range 39-82). At the time of analysis, median number of courses administered is 11 (range 1-34), and all patients are evaluable for response. Overall response rate including complete remission, very good partial remission, and partial remission is 85%. After a median follow-up of 27 months, median overall and progression-free survival are 33 and 23 months, respectively. Sixty-three patients are alive and between them, 45 (37%) are in continuous remission. Sixty patients have died (49%), mainly from progressive disease. There were 6 treatment-related deaths (5% of the whole patient population). Overall, hematological and non-hematological toxicity were manageable, mostly on outpatient basis. Arterial hypertension has been observed in 43 cases (35%) but did not lead to treatment interruption. Our data demonstrate that in real life, KRD is highly effective and well tolerated in the majority of patients with RRMM.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Dexametasona/administração & dosagem , Lenalidomida/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Oligopeptídeos/administração & dosagem , Inquéritos e Questionários , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/administração & dosagem , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/epidemiologia , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Larval gypsy moths, Lymantria dispar (Lepidoptera:Lymantriidae) were co-infected with the L. dispar nucleopolyhedrovirus (LdMNPV) and the Cotesia melanoscela (Hymenoptera:Braconidae) polydnavirus (CmeBV). CmeBV was given along with a parasitoid egg and calyx products in a stinging event, or in the form of an injection of calyx-derived extract. LdMNPV was delivered per os, integrated into artificial diet. Mortality from all sources was recorded over the subsequent three-week period. Neither parasitism nor injections of purified CmeBV with toxin had any effect on the amount of mortality caused by concurrent challenges with LdMNPV.
Assuntos
Baculoviridae , Infecções por Vírus de DNA , Mariposas/virologia , Polydnaviridae , Animais , Larva/virologiaRESUMO
Policy and practitioners' initiatives to stimulate sustainable consumption have so far failed to have notable impact on individuals' behaviors. The current commentary is a plea to social and sustainability scientists, particularly to economists dealing with sustainable agri-food systems, to dig deeper into the notion of narratives to trigger societal dynamics that stir consumers toward more sufficient lifestyles. As dominant cultural narratives have a critical role in shaping shared meanings and acceptable behaviors, in the future they could guide dramatic changes in individuals' conduct, triggering drastic modifications of current consumption patterns. Based on the power that concepts as the Circular Economy and the Anthropocene have had in the recent past, a future step to develop an ecological worldview across society, and nourish individual identities deeply committed with the preservation of natural ecosystems, is working on narratives based on the notion of human-nature interdependence.
RESUMO
Accumulating reports of negative impacts of tourist activities on wildlife emphasize the importance of closely monitoring focal populations. Although some effects are readily noticed, more subtle ones such as changes in physiological functions of individuals might go overlooked. Based on evidence of altered physiology associated with ecotourism on Magellanic penguins Spheniscus magellanicus, here we performed an integrated assessment using a diverse physiological toolkit together with more traditional fitness-related measures to better understand mechanisms and potential consequences. Chicks exposed to tourism showed altered immune parameters and elevated flea prevalence, reinforcing previous findings. Tourism-exposed female, but not male, chicks also showed relatively lower hematocrit and plasma protein levels, providing evidence consistent with a sex-specific response to tourist visitation. Physiological alterations detected in tourism-exposed young chicks (week 1-2) were maintained and the effect on flea infestation increased during the study period (week 4-5 of post-hatch). Despite the effects on physiology, these did not seem to translate into immediate fitness costs. No detectable tourism effects were found on brood sex ratios, chick growth and body condition, and survival until week 5-6 post-hatch. We detected no effects on reproductive output and only a marginal effect on nest survival during incubation despite previous reports of tourism-associated alterations in stress indices of adults. This disconnection could result if the physiological changes are not strong enough to impact fitness, if effects balance each other out, or if changes are part of a copying strategy. Alternatively, the physiological alterations might only show impacts later in the brooding cycle or even after chick emancipation from their parents. Our results suggest that integrative monitoring of potential anthropogenic impacts on wildlife should include evaluation of physiological mechanisms and individual-level responses in populations exposed to human activities.
Assuntos
Spheniscidae , Animais , Masculino , Humanos , Feminino , Spheniscidae/fisiologia , Animais Selvagens/fisiologia , Reprodução , Proteínas Sanguíneas , TurismoRESUMO
Dental pulp undergoes a number of changes passing from healthy status to inflammation due to deep decay. These changes are regulated by several genes resulting differently expressed in inflamed and healthy dental pulp, and the knowledge of the processes underlying this differential expression is of great relevance in the identification of the pathogenesis of the disease. In this study, the gene expression profile of inflamed and healthy dental pulps were compared by microarray analysis, and data obtained were analyzed by Ingenuity Pathway Analysis (IPA) software. This analysis allows to focus on a variety of genes, typically expressed in inflamed tissues. The comparison analysis showed an increased expression of several genes in inflamed pulp, among which IL1β and CD40 resulted of particular interest. These results indicate that gene expression profile of human dental pulp in different physiological and pathological conditions may become an useful tool for improving our knowledge about processes regulating pulp inflammation.
Assuntos
Antígenos CD40/fisiologia , Polpa Dentária/metabolismo , Interleucina-1beta/fisiologia , Análise de Sequência com Séries de Oligonucleotídeos , Pulpite/metabolismo , Transcriptoma , Adulto , Antígenos CD40/genética , Humanos , Interleucina-1beta/genética , Pulpite/etiologiaRESUMO
On the basis of a preliminary screening of seven different samples of Sicilian grape pomace, the 'Nerello Mascalese' sample NM2 was selected for an ethanol preparative extraction. The defatted NM2 EtOH extract was subjected to DPPH() and GAE assays, showing good radical scavenging activity (SC(50)=9.9 microg/mL) and a GAE value of 397.7 mg/g extract. HPLC-DAD analysis of NM2 extract allowed a quantitative determination of the main anthocyanins (AN) and flavonols/flavonol glycosides (FL/FG). Aliquots of the NM2 extract were subjected to three different fractionation protocols (FP1, FP2 and FP3). The fractions were examined by DPPH() and GAE assays, and subjected to HPLC-DAD analysis for the quantitative determination of the main AN and FL/FG. FP3 allowed obtaining a polyphenol-enriched fraction with SC(50)=14.8 microg/mL and GAE=184.1mg/g of fraction, accounting for only 1.3% in weight of the EtOH extract. Some considerations about the relationship between antioxidant activity and AN/FL/FG HPLC-DAD profiles are also reported.
Assuntos
Antioxidantes/isolamento & purificação , Etanol/isolamento & purificação , Flavonoides/isolamento & purificação , Fenóis/isolamento & purificação , Vitis/química , Vinho , Antocianinas/análise , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Flavonóis/análise , Sequestradores de Radicais Livres/análise , Glicosídeos/análise , Polifenóis , SicíliaRESUMO
The presence of Campylobacter species was studied in three Antarctic penguin species, Adélie (Pygoscelis adeliae), chinstrap (Pygoscelis antarctica) and gentoo (Pygoscelis papua). A total of 390 penguins were captured in 12 different rookeries along the Antarctic Peninsula with differences in the amount of human visitation: six colonies were highly visited [Stranger Point, King George Island (P. papua and P. adeliae); Hannah Point, Livingston Island (P. papua and P. antarctica); Deception Island (P. antarctica); and Paradise Bay, Antarctic Peninsula (P. papua)], and six colonies were rarely visited [Devil's Point, Byers Peninsula, Livingston Island (P. papua); Cierva Cove, Antarctic Peninsula (P. papua); Rongé Island (P. papua and P. antarctica); Yalour Island (P. adeliae); and Avian Island (P. adeliae)]. A total of 23 strains were isolated from penguins from nine different rookeries. Campylobacter lari subsp. lari was isolated from eight samples (seven from P. papua and one from P. adeliae); C. lari subsp. concheus from 13 (ten from P. adeliae and three from P. antarctica) and C. volucris from two samples (both from P. papua). We did not find any significant differences in the prevalence of Campylobacter spp. between the populations in highly and rarely visited areas. This is the first report of C. lari subsp. concheus and C. volucris isolation from penguins in the Antarctic region.
Assuntos
Campylobacter/isolamento & purificação , Spheniscidae/microbiologia , Animais , Regiões Antárticas , Campylobacter/classificação , IlhasRESUMO
TFIIIB, TFIIIC2, and PTF/SNAPC are heteromultimeric general transcription factors (GTFs) needed for expression of genes encoding small cytoplasmic (scRNAs) and small nuclear RNAs (snRNAs). Their activity is stimulated by viral oncogenes, such as SV40 large T antigen and Adenovirus E1A, and is repressed by specific transcription factors (STFs) acting as anti-oncogenes, such as p53 and pRb. GTFs role as final targets of critical signal transduction pathways, that control cell proliferation and differentiation, and their involvement in gene expression regulation suggest that the genes encoding them are potential proto-oncogenes or anti-oncogenes or may be otherwise involved in the pathogenesis of inherited genetic diseases. To test our hypothesis through the positional candidate gene approach, we have determined the physical localization in the human genome of the 11 genes, encoding the subunits of these GTFs, and of three genes for proteins associated with TFIIIB (GTF3BAPs). Our data, obtained by chromosomal in situ hybridization, radiation hybrids and somatic cell hybrids analysis, demonstrate that these genes are present in the human genome as single copy sequences and that some cluster to the same cytogenetic band, alone or in combination with class II GTFs. Intriguingly, some of them are localized within chromosomal regions where recurrent, cytogenetically detectable mutations are seen in specific neoplasias, such as neuroblastoma, uterine leyomioma, mucoepidermoid carcinoma of the salivary glands and hemangiopericytoma, or where mutations causing inherited genetic diseases map, such as Peutz-Jeghers syndrome. Their molecular function and genomic position make these GTF genes interesting candidates for causal involvement in oncogenesis or in the pathogenesis of inherited genetic diseases.
Assuntos
Predisposição Genética para Doença , Genoma Humano , Neoplasias/etiologia , Fatores de Transcrição TFIII/genética , Fatores de Transcrição/genética , Mapeamento Cromossômico , Humanos , Neoplasias/genética , Fator de Transcrição TFIIIBRESUMO
Understanding the behavioral basis of dispersal and colonization is critical in biological control systems, where success of a natural enemy depends in part on its ability to find and move to new host patches. We studied behavior of the specialist weevil Rhinoncomimus latipes Korotyaev, a biological control agent of mile-a-minute weed, Persicaria perfoliata (L.) H. Gross, by releasing weevils at the forest edge and monitoring their colonization of potted host plants arrayed along the edge, out into the open field, and into the forest. Both distance from the release cage and habitat where plants were located affected colonization, with more than twice as many weevils found on plants at 2 m than at 6 or 14 m; at 14 m, 6-8 times as many weevils colonized plants along the forest edge compared with plants in the open field or within the forest. In a second experiment, weevils that were released in an open field 12 m from the forest edge initially flew in all directions, but again ultimately colonized more plants at the edge than out in the open field. This species may be adapted to seek host plants at the forest edge, because P. perfoliata generally is found in riparian corridors in its native range and along forest edges in North America. Results suggest that R. latipes will move successfully to new P. perfoliata patches along wooded edges, but may not readily locate isolated patches in the open or those embedded in forests.
Assuntos
Comportamento Animal , Ecossistema , Gorgulhos/fisiologia , Animais , Voo Animal , Controle Biológico de Vetores , Dinâmica Populacional , Luz SolarRESUMO
The quantitative gas--liquid chromatographic analysis of non-protein amino acids, in the presence of protein amino acids, is described. The amino acids were determined as their N-trifluoroacetyl n-butyl esters on an ethylene glycol adipate column. The relative molar responses of 38 amino acids are reported.
Assuntos
Aminoácidos/análise , Cromatografia Gasosa , Aminobutiratos/análise , Cromatografia Líquida , Ésteres/análise , Indicadores e Reagentes , Métodos , Ácido TrifluoracéticoRESUMO
The quantitative analysis of protein and non-protein amino acids by gas-liquid chromatography is described. The amino acids are determined as their n-butyl N-trifluoroacetyl esters on an OV-17 (methylphenyl silicone polymer) column. The relative molar responses of 16 protein and 30 non-protein amino acids are reported.
Assuntos
Aminoácidos/análise , Proteínas/análise , Cromatografia Gasosa , MétodosRESUMO
Bioactivity-guided fractionation of the lipid extract of Crithmum maritimum using the brine shrimp lethality assay led to the isolation of three bioactive compounds. Two of these are known C17 polyacetylenic metabolites, falcarinol [1] and falcarindiol [2], previously isolated from several species of the Umbelliferae and Araliaceae. The third active principle was identified as O-geranylvanillin [3], an aromatic ether described in the literature as a synthetic compound but unknown as a natural product. Cytotoxic activity of the pure compounds was significant for 1 and 2, much less intense for 3.
Assuntos
Plantas Medicinais/química , Alcinos , Animais , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antifúngicos/toxicidade , Artemia , Benzaldeídos/química , Benzaldeídos/isolamento & purificação , Benzaldeídos/toxicidade , Di-Inos , Álcoois Graxos/química , Álcoois Graxos/isolamento & purificação , Álcoois Graxos/toxicidade , Espectroscopia de Ressonância Magnética , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Sicília , Espectrofotometria Infravermelho , Espectrofotometria UltravioletaRESUMO
Site-directed covalent modification of proteins is currently used to study the molecular structure of enzyme active sites. Radioactive labels together with protein sequencing by Edman degradation have been previously employed to identify the site of modification. One drawback of such a procedure is that most reagents are not commercially available in radioactive form. Moreover, the covalent bond formed upon reaction of the label with the protein may be labile under the conditions of Edman degradation. By combining reverse-phase high-performance liquid chromatography (RP-HPLC) and fast atom bombardment (FAB) mass spectrometry, we have been able to identify the modified sites of horse heart cytochrome c after reaction with iodine. By using this procedure it has been possible to ascertain that, among the four tyrosines contained in the sequence of horse heart cytochrome c, only tyrosine 74 is converted into the monoiodinated derivative. The data demonstrate also the absence of unwanted secondary reactions. The technique avoids the use of radioactive materials and prevents losses of the label since Edman degradation is not required to identify the modified peptides. These results indicate that FAB mass spectrometry along with RP-HPLC is potentially a powerful technique to study chemical modifications of proteins.
Assuntos
Grupo dos Citocromos c/análise , Aminoácidos/análise , Animais , Cromatografia Líquida de Alta Pressão , Cavalos , Humanos , Iodo/análise , Espectrometria de Massas , Dados de Sequência Molecular , Miocárdio/enzimologia , Peptídeos/análise , Hidrolisados de Proteína/análise , Tripsina , Tirosina/análiseRESUMO
A novel ether lipid, (-)-(R)-1-O-geranylgeranylglycerol, has been isolated from the brown alga Dilophus fasciola and its structure proved by spectroscopic methods and chemical degradation.
Assuntos
Éteres/isolamento & purificação , Eucariotos/análise , Glicerídeos/isolamento & purificação , Phaeophyceae/análiseRESUMO
By in situ chromosomal hybridization, and by somatic cell and radiation hybrid analysis, we have determined the genomic position of the human genes encoding four TAFII subunits of TFIID (TAFII150, TAFII105, TAFII68, TAFII18), the three subunits of TFIIA (TFIIA35 and TFIIA19, both encoded by the same gene, and TFIIA12), CDK8, and SURB7. All of these proteins are bona fide components of human class II holoenzymes as well as targets of signal transduction pathways that regulate genome expression. The genes encoding them are present in the human genome in a single copy and are localized at 8q23, 18q11.2, 17q11.1-11.2, 1p21, 14q31, 15q21-23, 13q12, and 12p12, respectively. We have mapped all of them to chromosomal regions where hereditary genetic diseases have been localized or which are involved in malignancies, which makes them potential candidates for a causal involvement in these phenotypes.
Assuntos
Quinases Ciclina-Dependentes , Proteínas de Ligação a DNA/genética , Proteínas Serina-Treonina Quinases/genética , Fatores de Transcrição TFII/genética , Fatores de Transcrição/genética , Transcrição Gênica/genética , Anormalidades Múltiplas/genética , Cromossomos Humanos , Quinase 8 Dependente de Ciclina , Dosagem de Genes , Genoma Humano , Humanos , Hibridização In Situ , Complexo Mediador , Mapeamento de Híbridos Radioativos , Fator de Transcrição TFIIA , Fator de Transcrição TFIIDRESUMO
Human SL1 is a general transcription initiation factor (GTF) essential for RNA polymerase I to start rRNA synthesis at class I promoters. It is comprised of the TATA box-binding protein (TBP) and three TBP-associated factors (TAF(I)48, TAF(I)63 and TAF(I)110). We have determined that the human genes TAF1A, TAF1B and TAF1C, encoding these three TAF(I) polypeptides, are localized at lq42, 2p25 and 16q24, respectively. All three genes are present as single copies in the human genome and map to different chromosomes, as shown by somatic cell hybrid panel and radiation hybrid panel analysis and FISH. Two of these genes, TAF1C and TAF1B, are transcribed into multiple RNAs, as determined through Northern analysis of mRNA from various human organs and cell lines. If translated into different polypeptides, this could result in production of variant isoforms of SL1 with different activation potentials.
Assuntos
Proteínas de Ligação a DNA/genética , Mapeamento Físico do Cromossomo , Proteínas Pol1 do Complexo de Iniciação de Transcrição , Fatores Associados à Proteína de Ligação a TATA , Fator de Transcrição TFIID , Fatores de Transcrição/genética , Alelos , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 2/genética , Proteínas de Ligação a DNA/química , Ligação Genética/genética , Humanos , Células Híbridas , Hibridização in Situ Fluorescente , Polimorfismo de Fragmento de Restrição , Isoformas de Proteínas/genética , RNA Mensageiro/análise , RNA Mensageiro/genética , Fatores de Transcrição/química , Células Tumorais CultivadasRESUMO
The gypsy moth (Lymantria dispar L.) nuclear polyhedrosis virus was genetically engineered for nonpersistence by removal of the gene coding for polyhedrin production and stabilized using a coocclusion process. A beta-galactosidase marker gene was inserted into the genetically engineered virus (LdGEV) so that infected larvae could be tested for its presence using a colorimetric assay. In 1993, LdGEV-infected gypsy moths were released in a forested plot in Massachusetts to test for spread and persistence. A similar forested plot 2 km away served as a control. For 3 years (1993-1995), gypsy moths were established in the two plots in Massachusetts to serve as test and control populations. Each week, larvae were collected from both plots. These field-collected larvae were reared individually, checked for mortality, and then tested for the presence of beta-galactosidase. Other gypsy moth larvae were confined on LdGEV-contaminated foliage for 1 week and then treated as the field-collected larvae. The LdGEV was sought in bark, litter, and soil samples collected from each plot. To verify the presence of the LdGEV, polymerase chain reaction, slot blot DNA hybridization, and restriction enzyme analysis were also used on larval samples. Field-collected larvae infected with the engineered virus were recovered in the release plot in 1993, but not in subsequent years; no field-collected larvae from the control plot contained the engineered virus. Larvae confined on LdGEV-contaminated foliage were killed by the virus. No LdGEV was recovered from bark, litter, or soil samples from either of the plots.