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This study describes an artisanal simulator made with gelatin to teach ultrasound-guided fine needle puncture during practical classes in veterinary or medical sciences education. A three-phase experimental set allowed the students to practice ultrasound-guided fine needle puncture, aspiration, and injection in three different target structures. This cost-effective simulator may be an alternative to the use of expensive devices or the use of live animals during practical classes.

Neste artigo são utilizadas categorias analíticas para a caracterização das concepções de professores relativas à imagem da ciência. Discute-se também a importância das concepções epistemológicas como balizador de ações da prática profissional docente. Esta pesquisa apresenta um Estudo de Caso no qual foram coletadas as respostas de um questionário-padrão e os dados foram avaliados utilizando-se relações com análises estatísticas. Identificou-se que as categorias utilizadas revelaram metaconhecimentos acerca da autonomia profissional docente e do enfoque formativo adotados em um curso de formação de professores de Química. Para finalizar, defende-se que a compreensão da epistemologia de professores em formação pode promover melhorias e direcionar as ações formativas para contextos de inovação e de avanços nas práticas curriculares.

A total coloring of a graph $G = (V, E)$ is an assignment of colors to vertices and edges such that neither two adjacent vertices nor two incident edges get the same color, and, for each edge, the end-points and the edge itself receive different colors. Any valid total coloring induces a partition of the elements of $G$ into total matchings, which are defined as subsets of vertices and edges that can take the same color. In this paper, we propose Integer Linear Programming models for both the Total Coloring and the Total Matching problems, and we study the strength of the corresponding Linear Programming relaxations. The total coloring is formulated as the problem of finding the minimum number of total matchings that cover all the graph elements. This covering formulation can be solved by a Column Generation algorithm, where the pricing subproblem corresponds to the Weighted Total Matching Problem. Hence, we study the Total Matching Polytope. We introduce three families of nontrivial valid inequalities: vertex-clique inequalities based on standard clique inequalities of the Stable Set Polytope, congruent-$2k3$ cycle inequalities based on the parity of the vertex set induced by the cycle, and even-clique inequalities induced by complete subgraphs of even order. We prove that congruent-$2k3$ cycle inequalities are facet-defining only when $k = 4$, while the vertex-clique and even-cliques are always facet-defining. Finally, we present preliminary computational results of a Column Generation algorithm for the Total Coloring Problem and a Cutting Plane algorithm for the Total Matching Problem., Comment: 29 pages, 5 figures

Chronic lymphocytic leukemia (CLL) cells express the interleukin-23 receptor (IL-23R) chain, but the expression of the complementary IL-12Rβ1 chain requires cell stimulation via surface CD40 molecules (and not via the B-cell receptor [BCR]). This stimulation induces the expression of a heterodimeric functional IL-23R complex and the secretion of IL-23, initiating an autocrine loop that drives leukemic cell expansion. Based on the observation in 224 untreated Binet stage A patients that the cases with the lowest miR-146b-5p concentrations had the shortest time to first treatment (TTFT), we hypothesized that miR-146b-5p could negatively regulate IL-12Rβ1 side chain expression and clonal expansion. Indeed, miR-146b-5p significantly bound to the 3′-UTR region of the IL-12Rβ1 mRNA in an in vitro luciferase assay. Downregulation of miR-146b-5p with specific miRNA inhibitors in vitro led to the upregulation of the IL-12Rβ1 side chain and expression of a functional IL-23R complex similar to that observed after stimulation of the CLL cell through the surface CD40 molecules. Expression of miR-146b-5p with miRNA mimics in vitro inhibited the expression of the IL-23R complex after stimulation with CD40L. Administration of a miR-146b-5p mimic to NSG mice, successfully engrafted with CLL cells, caused tumor shrinkage, with a reduction of leukemic nodules and of IL-12Rβ1–positive CLL cells in the spleen. Our findings indicate that IL-12Rβ1 expression, a crucial checkpoint for the functioning of the IL-23 and IL-23R complex loop, is under the control of miR-146b-5p, which may represent a potential target for therapy since it contributes to the CLL pathogenesis. This trial is registered at www.clinicaltrials.gov as NCT00917540.

New biomass crop hybrids for bioeconomic expansion require yield projections to determine their potential for strategic land use planning in the face of global challenges. Our biomass growth simulation incorporates radiation interception and conversion efficiency. Models often use leaf area to predict interception which is demanding to determine accurately, so instead we use low-cost rapid light interception measurements using a simple laboratory-made line ceptometer and relate the dynamics of canopy closure to thermal time, and to measurements of biomass. We apply the model to project the European biomass potentials of new market-ready hybrids for 2020–2030. Field measurements are easier to collect, the calibration is seasonally dynamic and reduces influence of weather variation between field sites. The model obtained is conservative, being calibrated by crops of varying establishment and varying maturity on less productive (marginal) land. This results in conservative projections of miscanthus hybrids for 2020–2030 based on 10% land use conversion of the least (productive) grassland and arable for farm diversification, which show a European potential of 80.7–89.7 Mt year−1 biomass, with potential for 1.2–1.3 EJ year−1 energy and 36.3–40.3 Mt year−1 carbon capture, with seeded Miscanthus sacchariflorus × sinensis displaying highest yield potential. Simulated biomass projections must be viewed in light of the field measurements on less productive land with high soil water deficits. We are attempting to model the results from an ambitious and novel project combining new hybrids across Europe with agronomy which has not been perfected on less productive sites. Nevertheless, at the time of energy sourcing issues, seed-propagated miscanthus hybrids for the upscaled provision of bioenergy offer an alternative source of renewable energy. If European countries provide incentives for growers to invest, seeded hybrids can improve product availability and biomass yields over the current commercial miscanthus variety.

Evidências crescentes sugerem que a farmacoterapia pode ser benéfica para alguns pacientes com transtorno da compulsão alimentar, um transtorno alimentar caracterizado por episódios repetitivos de consumo incontrolável de quantidades anormalmente grandes de alimentos sem comportamentos inadequados de perda de peso. Diante disso, este estudo teve como objetivo avaliar a eficácia de alternativas terapêuticas farmacológicas no tratamento do transtorno da compulsão alimentar. Assim, realizou-se uma revisão sistemática a partir da seleção de estudos científicos publicados nos anos de 2017 a 2022. Com base na análise e interpretação dos dados, concluiu-se que alternativas terapêuticas farmacológicas são recursos complementares tanto no tratamento do transtorno da compulsão alimentar como de sintomas de desordem alimentar e não substitutas. Nesse sentido, o uso de medicamentos tais como fluoxetina, lisdexamfetamina e simplicifolia, aliado a outros tratamentos, como a psicoterapia, podem ser eficazes para pacientes e suas necessidades específicas.

Due to its versatility and storability, biomass is an important resource for renewable materials and energy. Miscanthus hybrids combine high yield potential, low input demand, tolerance of certain marginal land types and several ecosystem benefits. To date, miscanthus breeding has focussed on increasing yield potential by maximising radiation interception through: (1) selection for early emergence, (2) increasing the growth rate to reach canopy closure as fast as possible, and (3) delayed flowering and senescence. The objective of this study is to compare early season re-growth in miscanthus hybrids cultivated across Europe. Determination of differences in early canopy development on end-of-year yield traits is required to provide information for breeding decisions to improve future crop performance. For this purpose, a trial was planted with four miscanthus hybrids (two novel seed-based hybrids M. sinensis × sinensis [M sin × sin] and M. sacchariflorus × sinensis [M sac × sin], a novel rhizome-based M sac × sin and a standard Miscanthus × giganteus [M × g] clone) in the UK, Germany, Croatia and Italy, and was monitored in the third and fourth growing season. We determined differences between the hybrids in base temperature, frost sensitivity and emergence strategy. M × g and M sac × sin mainly emerged from belowground plant organs, producing fewer but thicker shoots at the beginning of the growing season but these shoots were susceptible to air frosts (determined by recording 0°C 2 m above ground surface). By contrast, M sin × sin emerged 10 days earlier, avoiding damage by late spring frosts and producing a high number of thinner shoots from aboveground shoots. Therefore, we recommend cultivating M sac × sin at locations with low risk and M sin × sin at locations with higher risk of late spring frosts. Selecting miscanthus hybrids that produce shoots throughout the vegetation period is an effective strategy to limit the risk of late frost damage and avoid reduction in yield from a shortened growing season.

Un matching totale di un grafo G = (V,E) è un sottoinsieme di G tale che i suoi elementi, cioè vertici e spigoli, sono a coppie non adiacenti. In questo contesto, il Total Matching Problem richiede di trovare un matching totale di dimensione massima. Questo problema è stato principalmente studiato in letteratura da un punto di vista della teoria dei grafi. Tuttavia, a causa del forte collegamento con noti problemi combinatorici dello Stable Set Problem e del Matching Problem, il problema viene trattato da un punto di vista tipico della programmazione intera. In questa Tesi, viene presentato un approccio poliedrale al Total Matching Problem, e quindi, si introduce il corrispondente politopo, ovvero il Total Matching Polytope. Al meglio della nostra conoscenza, tale problema non è stato ancora affrontato da una prospettiva poliedrale. Vengono introdotte diverse famiglie di disuguaglianze valide: disuguaglianze vertex-clique basate su disuguaglianze di clique del politopo dell'insieme stabile, disuguaglianze di cicli congruent-2k3 cycles basate sulla parità dell'insieme dei vertici indotte dal ciclo, disuguaglianze even-clique indotte da sottografi completi di ordine pari e, balanced e non lifted balanced disuguaglianze bicliques basate su grafi bipartiti completi, dove la famiglia bilanciata ha la partizione degli insiemi di vertici di uguale dimensione, mentre la seconda classe ha ogni partizione di vertice di dimensioni diverse. Si dimostra che le disuguaglianze di ciclo congruent-2k3 sono faccette quando k = 4, e per grafi cubici, in determinate condizioni. Le non balanced lifted biclique disuguaglianze sono ottenute mediante una procedura di lifting e definiscono le faccette per grafi bipartiti. Mentre le clique di vertice, le even clique e le balanced bicliques definiscono sempre faccette. Inoltre, una prima descrizione lineare completa viene fornita per alberi e grafi bipartiti completi. Per quest'ultima famiglia, la caratterizzazione completa si ottiene proiettando un politopo di dimensione superiore nello spazio originario. Ciò porta a dare anche una formulazione estesa di piccola dimensione per il Total Matching Politopo di grafi bipartiti completi. Un altro problema correlato al Total Matching Problem è il Total Coloring Problem. Qualsiasi partizione degli elementi in matching totali induce una colorazione di G, ovvero, ad ogni matching totale viene assegnato una classe di colore. Quindi, una colorazione totale è un'assegnazione di colori a vertici e spigoli tale che né due vertici adiacenti né due spigoli incidenti hanno lo stesso colore e, per ogni spigolo, le estremità e lo spigolo stesso devono ricevere colori diversi.In questa Tesi si propongono modelli di Programmazione Lineare Intera per problemi di Colorazione Totale, e viene studiata la forza del corrispondente rilassamento lineare continuo. La colorazione totale è formulata come il problema di trovare il numero minimo di matching totali che coprano tutti gli elementi del grafo. Questa formulazione di copertura può essere risolta da un algoritmo di generazione di colonne, dove il sottoproblema corrisponde al problema di matching totale pesato. Infine, vengono presentati risultati computazionali di un algoritmo di generazione di colonne per il Total Coloring Problem e di piani di taglio per il problema del Total Matching. A total matching of a graph G = (V, E) is a subset of G such that its elements, i.e. vertices and edges, are pairwise not adjacent. In this context, the Total Matching Problem calls for a total matching of maximum size. This problem has been mainly studied in the literature from a graph theoretical point of view. However, due to the strong connection with well-known combinatorial problems of the Stable Set Problem and the Matching Problem, we focus on an integer programming point of view. In this Thesis, we present a polyhedral approach to the Total Matching Problem, and hence, we introduce the corresponding polytope, namely the Total Matching Polytope. To the best of our knowledge, we are the first to tackle the problem from a polyhedral perspective. We introduce several families of valid inequalities: vertex-clique inequalities based on standard clique inequalities of the Stable Set Polytope, congruent-2k3 cycle inequalities based on the parity of the vertex set induced by the cycle, even-clique inequalities induced by complete subgraphs of even order, and, balanced and non-balanced lifted biclique inequalities based on complete bipartite graphs, where the balanced family has the partition of the vertex sets of equal-size, whereas for the second class each vertex partition has different size. We prove that congruent-2k3 cycle inequalities are facet-defining when k = 4, and for cubic graphs, under certain conditions. The non-balanced lifted biclique inequalities are obtained by a lifting procedure and are facet-defining for bipartite graphs. While the vertex-clique, even-clique, and balanced biclique inequalities are always facet-defining. In addition, we provide a first linear complete description for Trees and Complete Bipartite Graphs. For the latter family, the complete characterization is obtained by projecting a higher-dimension polytope onto the original space. This leads to also give an extended formulation of small size for the Total Matching Polytope of Complete Bipartite Graphs. Another problem related to the Total Matching Problem is the Total Coloring Problem. Any partition of the elements into total matchings induces a coloring of G, that is, each total matching is assigned to a color class. Hence, a total coloring is an assignment of colors to vertices and edges such that neither two adjacent vertices nor two incident edges get the same color, and, for each edge, the endpoints and the edge itself receive different colors. In this Thesis, we propose Integer Linear Programming models for Total Coloring problems, and we study the strength of the corresponding Linear Programming relaxations. The total coloring is formulated as the problem of finding the minimum number of total matchings that cover all the graph elements. This covering formulation can be solved by a Column Generation algorithm, where the pricing subproblem corresponds to the Weighted Total Matching Problem. Finally, we present computational results of a Column Generation algorithm for the Total Coloring Problem and a Cutting Plane algorithm for the Total Matching Problem.

E Extratos de secreções de anfíbios da família Bufonidae têm sido estudados pelo potencial de controle direto de fitopatógenos, bem como na ativação de mecanismos de defesa contra doenças em plantas. Assim, este estudo analisa os efeitos de extratos de secreções glandulares de Rhaebo guttatus e Rhinela marina contra o fungo Phakopsora pachyrhizi e na biometria de plantas de soja da cultivar TMG 132 RR. Aos 30 dias após semeadura, notou-se o surgimento espontâneo da doença e, dois dias após o surgimento das primeiras pústulas, as plantas foram tratadas com extratos de secreções glandulares nas concentrações de 0,1; 0,2; 0,3; 0,4 e 0,5 mg mL-1, acibenzolar-S-metil (500 L ha) e água destilada. Com relação ao número total de trifólios, teores de clorofila a, b e total não houve diferença estatística entre os tratamentos. Nas avaliações biométricas, o extrato de secreção glandular de R. guttatus proporcionou diferença estatística apenas na variável altura de plantas. Quando as plantas foram tratadas com extrato de secreção glandular de R. marina, houve diferença estatística no número de nódulos, porém, sem diferença estatística para as demais variáveis analisadas. Conclui-se que extratos de secreções glandulares de R. guttatus e R. marina não controlam ferrugem asiática da soja; porém concentrações de 0,1mg mL-1, 0,2 mg mL-1 e 0,3 mg mL-1 de extrato de secreção glandular de R. guttatus promovem maior altura de plantas e extrato de secreção glandular de R. marina, nas concentrações de 0,1mg mL-1, 0,2 mg mL-1 e 0,4 mg mL-1, afeta negativamente o número de nódulos. Palavras-chave: altura de plantas; glândulas parotóides; Rhaebo guttatus; Rhinella marina; oleaginosa. Effect of extracts from amphibian glandular secretions on asian rust (Phakopsora pachyrhizi) and biometry of soybean plants ABSTRACT: Extracts from secretions of amphibians of the Bufonidae family were studied for their potential for direct control of phytopathogens, as well as for the activation of mechanism of defense against plant diseases. Thus, this study assessed the effects of glandular secretion extracts from Rhaebo guttatus and Rhinella marina against the fungi Phakopsora pachyrhizi and biometric responses on TMG 132 RR soybean cultivar. Thirty days after seeding, a spontaneously arise of the disease was noticed and, two days after the arise of the first pustules, plants were treated with glandular secretion extracts at the concentrations 0,1; 0,2; 0,3; 0,4 e 0,5 mg mL-1, acibenzolar-S-methyl (500 L ha) and distilled water. None of the treatments resulted in statistical differences at the photosynthetic rates of the plants for chlorophyll a, chlorophyll b and total chlorophyll content. For the biometrical evaluations, glandular secretion extracts of R. guttatus resulted in statistical difference only for the variable plant height variable. Glandular secretion extracts from R. marina resulted in statistical difference only for number of root nodules but was not significant for the remaining variables. The results showed that glandular secretion extracts from R. guttatus and R. marina does not control Asian soybean rust; however glandular secretion extracts from R. guttatus at the concentrations 0,1mg mL-1, 0,2 mg mL-1 e 0,3 mg mL-1 promotes greater plant height. The glandular secretion extracts from R. marina at the 0,1mg mL-1, 0,2 mg mL-1 e 0,4 mg mL-1 negatively affects the number of plant nodules. Keywords: height of plants; paratoid gland; Rhaebo guttatus; Rhinella marina; oleaginous.

Schistosomiasis is an endemic parasitic disease in several tropical countries. In Brazil, the only prevalent species of parasite responsible for schistosomiasis is Schistosoma mansoni. Neuroschistosomiasis is the second most frequent form of infection and the primary ectopic manifestation, with predominant involvement of the lower thoracic spinal cord and lumbar and lumbosacral regions. The frequent contact of children with contaminated ponds and the immaturity of their immune systems make this age group especially susceptible to infection by this parasite. Therefore, neuroschistosomiasis mansoni should always be considered in cases of transverse myelitis in children from endemic regions. The treatment for this condition is quite simple and effective, resulting in total recovery of neurological deficits if the diagnosis is made early.

The article presents a historical analysis of the emergence of the city of Guará in the Federal District, narrated in the pages of the newspaper Correio Braziliense at the end of the 60's. The objective is to analyze the narratives created in the pages of the newspaper about the city that will become the Guará and how this story ends up in a successful representation of the "revolution" in the pages of the newspaper. The origin of the city was given with the name of Mutirão da Novacap, as a settlement aimed at workers of Novacap, of the Industry and Food Sector, due to housing problems of the new capital. The Guará is the result of the transformation process of a settlement in the city. This change in status also served as propaganda in the pages of Correio Braziliense. Following in the footsteps of Maria Helena Rolim Capelato, we use the newspapers as a source, we seek to unveil the ideology described in its pages as to the historicity present in the formation of the city. Finally, we seek to discuss the context of the emergence of the city to perceive, how its residents were settled, to realize if this was the same model of housing occupation of the capital, and finally the propaganda made at the time of the inauguration of Guará in the pages of this newspaper., O artigo apresenta uma análise histórica do surgimento da cidade do Guará no Distrito Federal, narrado nas páginas do jornal Correio Braziliense no fim da década de 60. O objetivo é analisar as narrativas criadas nas páginas do jornal sobre a cidade que virá a ser o Guará e como essa história acaba em uma representação de sucesso da “revolução” nas páginas do jornal. A origem da cidade se deu com o nome de Mutirão da Novacap, como um assentamento voltado a trabalhadores da Novacap, do Setor de Indústria e Alimentação, em função de problemas de moradia da nova capital. O Guará é resultado do processo de transformação de um assentamento na cidade. Essa mudança de status serviu ainda como propaganda nas páginas do Correio Braziliense. Seguindo os passos de Maria Helena Rolim Capelato, nos servimos dos jornais como fonte, para desvelar o ideário descrito em suas páginas quanto a historicidade presente na formação da cidade. Por fim, buscamos discutir o contexto do surgimento da cidade de modo a perceber como foram assentados os seus moradores, perceber se esse foi o mesmo modelo de ocupação habitacional da capital, e finalmente a propaganda feita à época da inauguração do Guará nas páginas desse jornal. &nbsp

ObjectiveTrained immunity (TI) is a de facto memory program of innate immune cells, characterized by immunometabolic and epigenetic changes sustaining enhanced production of cytokines. TI evolved as a protective mechanism against infections; however, inappropriate activation can cause detrimental inflammation and might be implicated in the pathogenesis of chronic inflammatory diseases. In this study, we investigated the role of TI in the pathogenesis of giant cell arteritis (GCA), a large-vessel vasculitis characterized by aberrant macrophage activation and excess cytokine production.MethodsMonocytes from GCA patients and from age- and sex-matched healthy donors were subjected to polyfunctional studies, including cytokine production assays at baseline and following stimulation, intracellular metabolomics, chromatin immunoprecipitation-qPCR, and combined ATAC/RNA sequencing. Immunometabolic activation (i.e. glycolysis) was assessed in inflamed vessels of GCA patients with FDG-PET and immunohistochemistry (IHC), and the role of this pathway in sustaining cytokine production was confirmed with selective pharmacologic inhibition in GCA monocytes.ResultsGCA monocytes exhibited hallmark molecular features of TI. Specifically, these included enhanced IL-6 production upon stimulation, typical immunometabolic changes (e.g. increased glycolysis and glutaminolysis) and epigenetic changes promoting enhanced transcription of genes governing pro-inflammatory activation. Immunometabolic changes of TI (i.e. glycolysis) were a feature of myelomonocytic cells in GCA lesions and were required for enhanced cytokine production.ConclusionsMyelomonocytic cells in GCA activate TI programs sustaining enhanced inflammatory activation with excess cytokine production.

Chronic lymphocytic leukemia (CLL) is a hematological disorder with complex clinical and biological behavior. TP53 mutational status and cytogenetic assessment of the deletion of the corresponding locus (17p13.1) are considered the most relevant biomarkers associated with pharmaco-predictive response, chemo-refractoriness, and worse prognosis in CLL patients. The implementation of Next Generation Sequencing (NGS) methodologies in the clinical laboratory allows for comprehensively analyzing the TP53 gene and detecting mutations with allele frequencies ≤10%, that is, "subclonal mutations". We retrospectively studied TP53 gene mutational status by NGS in 220 samples from 171 CLL patients. TP53 mutations were found in 60/220 (27.3%) samples and 47/171 (27.5%) patients. Interestingly, subclonal mutations could be detected in 31/60 samples (51.7%) corresponding to 25 patients (25/47, 53.2%). We identified 44 distinct subclonal TP53 mutations clustered in the central DNA-binding domain of p53 protein (exons 5-8, codons 133-286). Missense mutations were predominant (80%), whereas indels, nonsense, and splice site variants were less represented. All subclonal TP53 variants but one [p.(Pro191fs)] were already described in NCI and/or Seshat databases as "damaging" and/or "probably damaging" mutations (38/44, 86% and 6/44, 14%, respectively). Longitudinal samples were available for 37 patients. Almost half of them displayed at least one TP53 mutant subclone, which could be alone (4/16, 25%) or concomitant with other TP53 mutant clonal ones (12/16, 75%); different patterns of mutational dynamics overtimes were documented. In conclusion, utilization of NGS in our "real-life" cohort of CLL patients demonstrated an elevated frequency of subclonal TP53 mutations. This finding indicates the need for precisely identifying these mutations during disease since the clones carrying them may become predominant and be responsible for therapy failures.

A deficiência de nutrientes essenciais na dieta, como ferro, zinco, iodo e vitamina A, desencadeia um grave problema nutricional de âmbito mundial denominado fome oculta. A biofortificação de vegetais tem sido utilizada como alternativa para combater a desnutrição, melhorando as culturas regionais, de modo a possibilitar o acesso de todos aos nutrientes necessários. Nesse cenário, a batata-doce biofortificada vem sendo utilizada como alternativa no combate à fome oculta por possuir alto teor de carotenoides com atividade pró-vitamina A. Para facilitar sua incorporação em diversos tipos de alimentos, a batata-doce pode ser transformada em farinha. Este trabalho teve por objetivo a obtenção e caracterização físico-química de farinha de batata-doce ‘Beauregard’ desidratada em estufa com circulação de ar e por atomização. Para as farinhas foi realizada a análise da composição centesimal, capacidade de hidratação e de solubilidade em água, e teor de carotenoides totais, sendo esse último também determinado na matéria-prima in natura, pelo fato de serem compostos sensíveis que podem ser afetados pelo processamento. Os resultados demonstraram que os diferentes processos de secagem afetaram o teor de umidade e de carotenoides totais do produto final, mas não os demais componentes. Houve redução de 24,37 % e 49,43 % de carotenoides totais para as farinhas obtidas por estufa e por atomização, respectivamente, quando comparadas à batata-doce in natura. Porém, mesmo havendo redução do teor de carotenoides totais, ambas as farinhas podem ser consideradas como contendo alto conteúdo de vitamina A, suprindo a ingestão diária recomendada (IDR) para adultos, contribuindo para o aumento do teor dessa vitamina na dieta.

Funding: This study was supported by the Swiss National Science Foundation (grant P2BEP3_195232) and by the Academy of Finland (project 323527 and project 329251). Species' range shifts and local extinctions caused by climate change lead to community composition changes. At large spatial scales, ecological barriers, such as biome boundaries, coastlines, and elevation, can influence a community's ability to shift in response to climate change. Yet, ecological barriers are rarely considered in climate change studies, potentially hindering predictions of biodiversity shifts. We used data from two consecutive European breeding bird atlases to calculate the geographic distance and direction between communities in the 1980s and their compositional best match in the 2010s and modeled their response to barriers. The ecological barriers affected both the distance and direction of bird community composition shifts, with coastlines and elevation having the strongest influence. Our results underscore the relevance of combining ecological barriers and community shift projections for identifying the forces hindering community adjustments under global change. Notably, due to (macro)ecological barriers, communities are not able to track their climatic niches, which may lead to drastic changes, and potential losses, in community compositions in the future. Publisher PDF

Klebsiella pneumoniae is a nosocomial pathogen and an important propagator of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. Like other Gram-negative bacteria, they secrete outer membrane vesicles (OMVs) that distribute virulence and resistance factors. Here, we subjected a K. pneumoniae-XDR to subinhibitory concentrations of meropenem, amikacin, polymyxin B, and a combination of these agents to evaluate changes in the protein cargo of OMVs through liquid chromatography–tandem mass spectrometry (LC-MS/MS). Genome sequencing of the clinical isolate K. pneumoniae strain HCD1 (KpHCD1) revealed the presence of 41 resistance genes and 159 virulence factors. We identified 64 proteins in KpHCD1-OMVs modulated with different antibiotic treatments involved in processing genetic information, environmental information, cell envelope formation, energy metabolism, and drug resistance. The OMV proteome expression profile suggests that OMVs may be associated with pathogenicity, survival, stress response, and resistance dissemination.

Images incorporate a wealth of information from a robot's surroundings. With the widespread availability of compact cameras, visual information has become increasingly popular for addressing the localisation problem, which is then termed as Visual Place Recognition (VPR). While many applications use high-resolution cameras and high-end systems to achieve optimal place-matching performance, low-end commercial systems face limitations due to resource constraints and relatively low-resolution and low-quality cameras. In this paper, we analyse the effects of image resolution on the accuracy and robustness of well-established handcrafted VPR pipelines. Handcrafted designs have low computational demands and can adapt to flexible image resolutions, making them a suitable approach to scale to any image source and to operate under resource limitations. This paper aims to help academic researchers and companies in the hardware and software industry co-design VPR solutions and expand the use of VPR algorithms in commercial products., The paper has been accepted for presentation at the Active Methods in Autonomous Navigation Workshop, part of the 2023 International Conference on Robotics and Automation (ICRA)

Perennial grains provide various ecosystem services compared to the annual counterparts thanks to their extensive root system and permanent soil cover. However, little is known about the evolution and diversification of perennial grains rhizosphere and its ecological functions over time. In this study, a suite of -OMICSs - metagenomics, enzymomics, metabolomics and lipidomics - was used to compare the rhizosphere environment of four perennial wheat lines at the first and fourth year of growth in comparison with an annual durum wheat cultivar and the parental species Thinopyrum intermedium. We hypothesized that wheat perenniality has a greater role in shaping the rhizobiome composition, biomass, diversity, and activity than plant genotypes because perenniality affects the quality and quantity of C input – mainly root exudates – hence modulating the plant-microbes crosstalk. In support of this hypothesis, the continuous supply of sugars in the rhizosphere along the years created a favorable environment for microbial growth which is reflected in a higher microbial biomass and enzymatic activity. Moreover, modification in the rhizosphere metabolome and lipidome over the years led to changes in the microbial community composition favoring the coexistence of more diverse microbial taxa, increasing plant tolerance to biotic and abiotic stresses. Despite the dominance of the perenniality effect, our data underlined that the OK72 line rhizobiome distinguished from the others by the increase in abundance of Pseudomonas spp., most of which are known as potential beneficial microorganisms, identifying this line as a suitable candidate for the study and selection of new perennial wheat lines.

Membranous glomerulonephritis (MGN) is a rare extra-hematological autoimmune complication of chronic lymphocytic leukemia (CLL), clinically characterized by nephrotic-range proteinuria and, less frequently, renal failure. Because of the rarity of this condition, there is no standardized treatment. Chlorambucil and fludarabine-based regimens, possibly combined with rituximab, have been historically the most frequent therapeutic approaches, with renal response obtained in about two-third of the patients. However, responses are often transient and partial. Here we describe the first patient with rituximab-refractory, CLL-related MGN successfully treated with the Bcl-2 antagonist venetoclax. Nephrotic syndrome resolved as soon as three months after venetoclax initiation, with no unexpected toxicities. At the last follow-up, 17 months after venetoclax start, renal response persists, with proteinuria below 0.5 g/24 hours. This case suggests that targeted agents, particularly Bcl-2 antagonists, might be suitable options for patients with renal autoimmune disorders arising in the context of CLL.

Insects living in nutritionally poor environments often establish long-term relationships with intracellular bacteria that supplement their diets and improve their adaptive and invasive powers. Even though these symbiotic associations have been extensively studied on physiological, ecological and evolutionary levels, few studies have focused on the molecular dialogue between host and endosymbionts to identify genes and pathways involved in endosymbiosis control and dynamics. We simultaneously analyzed host and endosymbiont gene expression during the life cycle of the cereal weevilSitophilus oryzae, from larval stages to adults, with a particular emphasis on emerging adults where the endosymbiontSodalis pierantoniusexperiences a contrasted growth-climax-elimination dynamics. We unraveled a constant arms race in which different biological functions are intertwined and coregulated across both partners. These include immunity, metabolism, metal control, apoptosis, and bacterial stress response. Particularly, genes from the Hippo regulatory pathway are specifically induced by endosymbiont growth, while the regulation of metal ions constitutes the basis of the arms race between the two partners at the onset of the bacterial load climax. The study of these tightly regulated functions, which are at the center of symbiotic regulations, provides evidence on how hosts and bacteria finely tune their gene expression and respond to different physiological challenges constrained by insect development in a nutritionally limited ecological niche.Graphical Abstract

The file contains supplementary Materials and Methods

Supplementary Methods

Centrosome anomalies contribute to tumorigenesis, but it remains unclear how they are generated in lethal cancer phenotypes. Here, it is demonstrated that human microsatellite instable (MSI) and BRAFV600E-mutant colorectal cancers with a lethal rhabdoid phenotype are characterized by inactivation of centrosomal functions. A splice site mutation that causes an unbalanced dosage of rootletin (CROCC), a centrosome linker component required for centrosome cohesion and separation at the chromosome 1p36.13 locus, resulted in abnormally shaped centrosomes in rhabdoid cells from human colon tissues. Notably, deleterious deletions at 1p36.13 were recurrent in a subgroup of BRAFV600E-mutant and microsatellite stable (MSS) rhabdoid colorectal cancers, but not in classical colorectal cancer or pediatric rhabdoid tumors. Interfering with CROCC expression in near-diploid BRAFV600E-mutant/MSI colon cancer cells disrupts bipolar mitotic spindle architecture, promotes tetraploid segregation errors, resulting in a highly aggressive rhabdoid-like phenotype in vitro. Restoring near-wild-type levels of CROCC in a metastatic model harboring 1p36.13 deletion results in correction of centrosome segregation errors and cell death, revealing a mechanism of tolerance to mitotic errors and tetraploidization promoted by deleterious 1p36.13 loss. Accordingly, cancer cells lacking 1p36.13 display far greater sensitivity to centrosome spindle pole stabilizing agents in vitro. These data shed light on a previously unknown link between centrosome cohesion defects and lethal cancer phenotypes providing new insight into pathways underlying genome instability.Implications: Mis-segregation of chromosomes is a prominent feature of chromosome instability and intratumoral heterogeneity recurrent in metastatic tumors for which the molecular basis is unknown. This study provides insight into the mechanism by which defects in rootletin, a centrosome linker component causes tetraploid segregation errors and phenotypic transition to a clinically devastating form of malignant rhabdoid tumor. Mol Cancer Res; 16(9); 1385–95. ©2018 AACR.

Supplementary Table 1. Clinicopathological, immunohistochemical and molecular features of the 12 rhabdoid colorectal cancers7 Supplementary Table 2. Somatic mutations of candidate genes (15 out of 20 are reported) shared by the two rhabdoid cancers at exome sequencing Supplementary Table 3. Rhabdoid colorectal cancers (RC): molecular alterations, centrosome aberrations and ploidy Supplementary Table 4. Rhabdoid tumours of infants (RI): molecular alterations, centrosome aberrations, and ploidy Supplementary Table 5: Clinicopathologic and molecular features of classical colorectal cancers analyzed Supplementary Table 6. Sequencing and Reverse transcription PCR primers Supplementary Table 6B. SMARCB1 regions covered by the custom panel used for next-generation target sequencing Supplementary Table 7. CROCC regions covered by the custom panel used for next-generation targeted sequencing Supplementary Table 8. Antibodies employed and working conditions for immunohistochemistry, immunofluorescence or western blot analysis of tissues and cell lines Supplementary Table 9. Rhabdoid colorectal cancer reported in literature between 1993-2015

Supplementary Table S1: list of antibodies used in this study for western blots (WB), immunofluorescence (IF) and immunohistochemistry (IHC.)

S1. Whole exome sequencing analysis of two rhabdoid colorectal cancers (RC). S2. Non-silent somatic mutations in rhabdoid tumours are enriched in centrosome-microtubule components. S3. Effect of CROCC mutations on centrosome phenotype. S4. CROCC expression profiling in classical colorectal cancers (CRCs). S5. Allelic loss at the 1p36.13 locus correlates with chromosomal instability in colorectal cancer cells. S6. Centrosome and chromosome instability in colorectal cancer cells. S7. Mitotic errors and impaired cell cycle caused by stable CROCC depletion in RKO cells. S8. Invasive behavior of colorectal cancer cells triggered by CROCC depletion. S9. Mitotic aberrations suppressed by CROCC or microtubule stabilizing agents in metastatic T84 and HT29 colorectal cancer cells.

Supplementary Table S2: differential blood cell count of mice treated with ONC212, 2-DG, or the combination of both agents.

Supplementary Table S3: blood chemistry results of mice treated with ONC212 or the combination of ONC212 and 2-DG

This paper provides debt ratio projections and heat maps that indicate widening pockets of vulnerability in Asia and the Pacific. It discusses the challenges for policy makers working to restore public finances after a series of crises. While the outlook does not yet suggest a widespread debt meltdown looming in the region, the global environment presents major challenges. Obstacles to economic growth and rising borrowing costs risk jeopardizing efforts to restore public finances and to ensure their sustainability. Economies in or close to distress face complications from a complex creditors landscape.

Medical writing assistance was provided by Sarah Stowell of Alligent Europe (Envision Pharma Group), funded by Incyte Biosciences International Sàrl. The ubiquitous, early-stage expression, efficient internalization, limited off-target effects, and high disease specificity of CD19 make it an attractive therapeutic target. Currently available anti-CD19 therapies have demonstrated particular promise in patients with relapsed or refractory B-cell non-Hodgkin lymphoma. Selection of the most appropriate treatment strategy should be based on individual patient characteristics and the goal of therapy. However, evidence and knowledge about the sequencing of anti-CD19 therapies are limited. Here, we review the current evidence for CD19 as a target in diffuse large B-cell lymphoma and consider approaches to the use of anti-CD19 therapy.

A dialogue between Mariátegui’s thought and the solidarity economy, identifying convergences and lessons, finds that the solidarity economy encounters Mariáteguist thought in its critique of positivist modernity and dogmatic Marxism and its proposal of an emancipating and decolonizing praxis as a heroic creation. The solidarity economy provides the foundations for the material and spiritual reproduction of community and nature through the political work forged in everyday associative and self-managed labor. Un diálogo entre el pensamiento de Mariátegui y la economía solidaria, identificando convergencias y lecciones, nos muestra que la economía solidaria va al encuentro del pensamiento mariateguista en su crítica de la modernidad positivista y el marxismo dogmático, así como su propuesta de una praxis emancipadora y descolonizadora como creación heroica. La economía solidaria sienta las bases para la reproducción material y espiritual de la comunidad y la naturaleza a través del trabajo político forjado en la labor cotidiana asociativa y autogestionada.

Miscanthus is a leading perennial biomass crop that can produce high yields on marginal lands. Moisture content is a highly relevant biomass quality trait with multiple impacts on efficiencies of harvest, transport, and storage. The dynamics of moisture content during senescence and overwinter ripening are determined by genotype × environment interactions. In this paper, unmanned aerial vehicle (UAV)-based remote sensing was used for high-throughput plant phenotyping (HTPP) of the moisture content dynamics during autumn and winter senescence of 14 contrasting hybrid types (progeny of M. sinensis x M. sinensis [M. sin x M. sin, eight types] and M. sinensis x M. sacchariflorus [M. sin x M. sac, six types]). The time series of moisture content was estimated using machine learning (ML) models and a range of vegetation indices (VIs) derived from UAV-based remote sensing. The most important VIs for moisture content estimation were selected by the recursive feature elimination (RFE) algorithm and were BNDVI, GDVI, and PSRI. The ML model transferability was high only when the moisture content was above 30%. The best ML model accuracy was achieved by combining VIs and categorical variables (5.6% of RMSE). This model was used for phenotyping senescence dynamics and identifying the stay-green (SG) trait of Miscanthus hybrids using the generalized additive model (GAM). Combining ML and GAM modeling, applied to time series of moisture content values estimated from VIs derived from multiple UAV flights, proved to be a powerful tool for HTPP.

The red-footed falcon (Falco vespertinus) is a species that is of great interest to conservation. Because of this, understanding the red-footed falcon’s flight behavior is important for the conservation of this species. In this context, by using accurate GPS data-loggers, in 2019 and 2020, we analyzed its flight activity at the two largest colonies in Italy, and we collected 5840 GPS points. At night, all of the surveyed individuals were active during all of the hourly intervals, and they were in flight for about 10% of the time (40% in the daytime). The nocturnal flight activity showed a dual pattern: frequent and long-distance flights before sunrise (22.22% of time in flight; maximum distance from nest > 3 km) and after sundown (32.14% of time in flight; maximum distance from nest > 12 km), and limited and short-distance flights late at night (10 p.m.–5 a.m.

We reconstruct the 3D fault model of the structures causative of the 2010–2014 Pollino seismic activity by integrating structural–geological and high-resolution seismological data. We constrained the model at the surface with fault-slip data, and at depth, by using the distributions of selected high-quality relocated hypocenters. Relocations were performed through the non-linear Bayloc algorithm, followed by the double-difference relative location method HypoDD applied to a 3D P-wave velocity model. Geological and seismological data highlight an asymmetric active extensional fault system characterized by an E- to NNE-dipping low-angle detachment, with high-angle synthetic splays, and SW- to WSW-dipping, high-angle antithetic faults. Hypocenter clustering and the time–space evolution of the seismicity suggest that two sub-parallel WSW-dipping seismogenic sources, the Rotonda–Campotenese and Morano–Piano di Ruggio faults, are responsible for the 2010–2014 seismicity. The area of the seismogenic patches obtained projecting the hypocenters of the early aftershocks on the 3D fault planes, are consistent with the observed magnitude of the strongest events (Mw=5.2, and Mw=4.3). Since earthquake-scaling relationships provide maximum expected magnitudes of Mw=6.4 for the Rotonda–Campotenese and Mw=6.2 for the Morano–Piano di Ruggio faults, we may suppose that, during the sequence, the two structures did not entirely release their seismic potential. The reconstructed 3D fault model also points out the relationships between the activated fault system and the western segment of the Pollino Fault. The latter was not involved in the recent seismic activity but could have acted as a barrier to the southern propagation of the seismogenic faults, limiting their dimensions and the magnitude of the generated earthquakes.

Este estudo teórico-crítico fundamenta-se na Psicologia Cultural-Histórica e no materialismo histórico e dialético com objetivo de promover reflexões sobre os conceitos de masculinidades dissidentes racializadas e de sujeito na perspectiva dialética da subjetividade individual e subjetividade social atravessadas pelos fenômenos sociais da cisheteronormatividade e do racismo. Através das relações sociais de sexo-gênero-raça pudemos pensar as masculinidades dissidentes racializadas de bichas pretas sob olhar dialético das categorias de sujeito e subjetividade social da Teoria da Subjetividade proposta por Fernando González Rey. Ambas as categorias se mostram adequadas para estudos sobre masculinidades. O sujeito é aquele que abre vias próprias de subjetivação nos espaços normativos com produções subjetivas a partir de suas vivências; a subjetividade social integra a dimensão qualitativa das configurações subjetivas sociais e individuais dos sujeitos e dos espaços sociais nos quais se transita. A bicha preta no processo de tornar-se sujeito e nos modos de ser e existir desestabiliza os espaços sociais e confronta a lógica binária cisheteronormativa e o racismo. As bichas denotam identidades, configurações subjetivas e modos de existir em constante tensionamento subjetivo e objetivo para sobreviver, resistir, existir e amar. A realidade tensionada dialeticamente produz terremotos de emoções e sentimentos que reivindicam as masculinidades dissidentes racializadas nos seus espaços afetivos e sociais.

PDF file - 175K, Supplementary Table S1. Clinical and prognostic parameters of cases analyzed by gene expression profiling arrays (45 cMBL and 115 Rai0-CLL) and by miRNA expression profiling arrays (39 cMBL and 111 Rai0-CLL). Supplementary Table S2. List of the 302 modulated genes identified by the supervised multiclass analysis comparing cMBL and Rai0-CLL samples stratified according to IGVH mutational status at the 90th percentile of false discovery rate (FDR) equal to 0. The SAM score(d) and the contrast values of each class are reported for each gene. Negative values indicates down-regulation, positive up-regulation. In bold italic are marked the eight genes that showed different modulation depending on Rai0-CLL or cMBL configuration. Supplementary Table S3. List of the 18 modulated miRNAs in the supervised multiclass analysis comparing cMBL and Rai0-CLL samples stratified according to IGVH mutational status at q-value 0. The SAM score(d) and the contrast values of each class are reported for each gene. Negative values indicates down-regulation, positive up-regulation.

Purpose: Deregulated expression of miRNAs has been shown in multiple myeloma (MM). A promising strategy to achieve a therapeutic effect by targeting the miRNA regulatory network is to enforce the expression of miRNAs that act as tumor suppressor genes, such as miR-34a.Experimental Design: Here, we investigated the therapeutic potential of synthetic miR-34a against human MM cells in vitro and in vivo.Results: Either transient expression of miR-34a synthetic mimics or lentivirus-based miR-34a-stable enforced expression triggered growth inhibition and apoptosis in MM cells in vitro. Synthetic miR-34a downregulated canonic targets BCL2, CDK6, and NOTCH1 at both the mRNA and protein level. Lentiviral vector-transduced MM xenografts with constitutive miR-34a expression showed high growth inhibition in severe combined immunodeficient (SCID) mice. The anti-MM activity of lipidic-formulated miR-34a was further shown in vivo in two different experimental settings: (i) SCID mice bearing nontransduced MM xenografts; and (ii) SCID-synth-hu mice implanted with synthetic 3-dimensional scaffolds reconstituted with human bone marrow stromal cells and then engrafted with human MM cells. Relevant tumor growth inhibition and survival improvement were observed in mice bearing TP53-mutated MM xenografts treated with miR-34a mimics in the absence of systemic toxicity.Conclusions: Our findings provide a proof-of-principle that formulated synthetic miR-34a has therapeutic activity in preclinical models and support a framework for development of miR-34a–based treatment strategies in MM patients. Clin Cancer Res; 18(22); 6260–70. ©2012 AACR.

Characterization of the new α-373 antibody and *373-ELISA (S1); Levels of different CgA-related analytes in peripheral-blood and bone marrow plasma samples obtained from normal subjects and MM patients stratified according to renal failure and treatment with proton pump inhibitors (S2); BM plasma levels of different CgA forms in MM patients at diagnosis in different disease stages (S3); MM and endothelial cells produce the urinary-type plasminogen activator (S4); Alignment of CgA sequence from different species (S5).

PDF file - 111K, In vivo activity of miR-34a in RPMI-8226 xenografts

PDF file - 106K, Systemic delivery of formulated miR34a mimics affects the growth of MM xenografts

PDF file - 78K, Quantitative analysis of miR-34a levels in retrieved tumors

Supplementary Figures S1-S2 and Supplementary Tables S1-S5.

PDF file - 22K, Distribution of the most frequently utilized IGHV. The histogram shows the percentages of VH sequences used in cMBL compared to Rai0-CLL cases.