The flip-graph of the 4-dimensional cube is connected

Flip-graph connectedness is established here for the vertex set of the 4-dimensional cube. It is found as a consequence that this vertex set has 92 487 256 triangulations, partitioned into 247 451 symmetry classes.Comment: 20 pages, 3 figures, revised proofs and notation

Protein glycosylation and tumor microenvironment alterations driving cancer hallmarks

Decades of research have disclosed a plethora of alterations in protein glycosylation that decisively impact in all stages of disease and ultimately contribute to more aggressive cell phenotypes. The biosynthesis of cancer-associated glycans and its reflection in the glycoproteome is driven by microenvironmental cues and these events act synergistically toward disease evolution. Such intricate crosstalk provides the molecular foundations for the activation of relevant oncogenic pathways and leads to functional alterations driving invasion and disease dissemination. However, it also provides an important source of relevant glyco(neo)epitopes holding tremendous potential for clinical intervention. Therefore, we highlight the transversal nature of glycans throughout the currently accepted cancer hallmarks, with emphasis on the crosstalk between glycans and the tumor microenvironment stromal components. Focus is also set on the pressing need to include glycans and glycoconjugates in comprehensive panomics models envisaging molecular-based precision medicine capable of improving patient care. We foresee that this may provide the necessary rationale for more comprehensive studies and molecular-based intervention.The authors wish to acknowledge the Portuguese Foundation for Science and Technology (FCT) for the human resources grants: PhD grant SFRH/BD/111242/2015 (AP), and FCT auxiliary researcher grant CEECIND/03186/2017 (JF). FCT is co-financed by European Social Fund (ESF) under Human Potential Operation Programme (POPH) from National Strategic Reference Framework (NSRF). The authors also acknowledge the Portuguese Oncology Institute of Porto Research Centre (CI-IPOP-29-2014; CI-IPOP-58-2015), the PhD Program in Biomedical Sciences of ICBAS-University of Porto, and the Early stage cancer treatment, driven by context of molecular imaging (ESTIMA) framework (NORTE-01-0145-FEDER-000027). The authors were also supported by the CANCER project (NORTE-01-0145-FEDER-000029) co-funded through the NORTE-45-2015-02

Voracity of coccinellid species on different phenological stages of the olive pest Saissetia Oleae (homoptera, coccidae)

Coccinellidae are well known predators in agroecosystems. In olive groves they may exert control against scales, such as the black scale, Saissetia oleae (Olivier, 1791). Laboratory studies on the consumption of three phenological stages (eggs, first and second instar nymphs) of S. oleae by four coccinellid species (Chilocorus bipustulatus, Scymnus (Pullus) subvillosus, Scymnus (Mimopullus) mediterraneus and Scymnus (Scymnus) interruptus) were carried out. C. bipustulatus presented a significantly high consumption of eggs, first and second instar nymphs compared with the other species. All coccinellids consumed eggs and first instar nymphs; however the second instar nymphs were only consumed by S. interruptus and C. bipustulatus. In a second experiment, larval stages of C. bipustulatus were reared on different phenological stages of S. oleae. Coccinellid larvae fed with eggs or first instar nymphs completed their life cycle, contrarily to those that were fed with second instar nymphs. The apparent voracity of C. bipustulatus on the different phenological stages of S. oleae is an aspect that suggests the possible use of this coccinellid species in biological control programs against this pest in olive groves

Immune phenotype of chronic liver disease

Immune disorders in chronic liver disease may reflect common host propensities or disease-specific factors. Our aim was to determine the principal bases for these expressions. Four hundred fifty-one patients with various chronic liver diseases were assessed prospectively for concurrent immune disorders. Individuals with immune diseases were more frequently women (73% vs 60%, P = 0.02) and they had HLA DR4 more often than counterparts with other HLA (46% vs 23%, P = 0.000008). The association between HLA DR4 and immune disease was apparent within individual liver diseases and within different categories of liver disease. Women with HLA DR4 had a higher frequency of immune disease than women without HLA DR4 (52% vs 22%, P < or = 0.000001), and they also had immune diseases more commonly than DR4-positive men (52% vs 31%, P = 0.03). DR4-positive men, however, had higher frequencies of immune disease than DR4-negative men, especially in the nonimmune types of liver disease (26% vs 4%, P = 0.002). We conclude that HLA DR4 and female gender constitute an immune phenotype that is an important basis for autoimmune expression in chronic liver disease

Response of coccinellid community to the dimethoate application in olive groves in northeastern Portugal

In this work we assessed the effects of the application of dimethoate on the coccinellid community. The field work was carried out on a weekly basis, in two different olive groves, from April to November of 2002 and 2003 and captured coccinellids were identified to species level. Principal response curves (PRC) method was used to analyse the effect of the dimethoate application on the abundance of coccinellid species. A total of 23 species were identified from the two olive groves. Nine species occurred in both olive groves and in the two years of the study. Scymnus interruptus was the dominant species in the control grove with 46.4% of the total Coccinellidae recovered while in the grove treated with dimethoate, Rhyzobius chrysomeloides represented 35.7% of the total number captured. PCR showed that the main effect of the treatment was a significant reduction of the abundance of the most common species of the coccinellid community (S. interruptus and Chilocorus bipustulatus) in the treated grove. This can also have implications on the preservation of ecological functions associated with coccinellids, namely their role as control agents of olive pests.En este trabajo se analizan los efectos de la aplicación de dimetoato en la comunidad de coccinélidos. El trabajo de campo se ha realizado en dos olivares, semanalmente, de abril a noviembre en 2002 y 2003, y los coccinélidos capturados se han identificado hasta el nivel de especie. Se han utilizado las principales curvas de respuesta (PRC) para analizar el efecto que produce la aplicación de dimetoato en la abundancia de especies de coccinélidos. Se encontraron un total de 23 especies de coccinélidos en los dos olivares, nueve de ellas comunes en los dos olivares y en los dos años de estudio. Scymnus interruptus fue la especie dominante en el olivar no tratado con dimetoato (46,4% del total de coccinélidos capturados), mientras que en el olivar tratado Rhyzobius chrysomeloides representó el 35,7% del total de las capturas. Las PRC demuestran que el principal efecto producido al aplicar dimetoato ha sido una reducción significativa de la abundancia de las especies más comunes de la comunidad de coccinélidos (S. interruptus y Chilocorus bipustulatus) en el olivar tratado. Esto puede tener implicaciones en la conservación de las funciones ecológicas asociadas a los coccinélidos como, por ejemplo, su papel como agentes de control de las plagas del olivo. Palabras clave adicionales: abundancia de especies, agricultura ecológica, Coccinellidae, curvas de respuesta principal, manejo integrado de plagas, Olea europaea

The unique regulation of iron-sulfur cluster biogenesis in a Gram-positive bacterium

Iron-sulfur clusters function as cofactors of a wide range of proteins, with diverse molecular roles in both prokaryotic and eukaryotic cells. Dedicated machineries assemble the clusters and deliver them to the final acceptor molecules in a tightly regulated process. In the prototypical Gram-negative bacterium Escherichia coli, the two existing iron-sulfur cluster assembly systems, iron-sulfur cluster (ISC) and sulfur assimilation (SUF) pathways, are closely interconnected. The ISC pathway regulator, IscR, is a transcription factor of the helix-turn-helix type that can coordinate a [2Fe-2S] cluster. Redox conditions and iron or sulfur availability modulate the ligation status of the labile IscR cluster, which in turn determines a switch in DNA sequence specificity of the regulator: cluster-containing IscR can bind to a family of gene promoters (type-1) whereas the clusterless form recognizes only a second group of sequences (type-2). However, iron-sulfur cluster biogenesis in Gram-positive bacteria is not so well characterized, and most organisms of this group display only one of the iron-sulfur cluster assembly systems. A notable exception is the unique Gram-positive dissimilatory metal reducing bacterium Thermincola potens, where genes from both systems could be identified, albeit with a diverging organization from that of Gram-negative bacteria. We demonstrated that one of these genes encodes a functional IscR homolog and is likely involved in the regulation of iron-sulfur cluster biogenesis in T. potens. Structural and biochemical characterization of T. potens and E. coli IscR revealed a strikingly similar architecture and unveiled an unforeseen conservation of the unique mechanism of sequence discrimination characteristic of this distinctive group of transcription regulators.We thank Jorge Vieira for help with Automatic Detection of Positively Selected Sites. We acknowledge the European Synchrotron Radiation Facility (ESRF) for provision of synchrotron radiation facilities and thank the ESRF staff for help with data collection. Microscale thermophoresis data collection was carried out at the Campus Science Support Facilities Protein Technologies Facility (www.csf.ac.at). This work was funded by Fundo Europeu de Desenvolvimento Regional through the Operational Competitiveness Programme-COMPETE and by national funds through Fundacao para a Ciencia e a Tecnologia under project FCOMP-01-0124-FEDER-028116 (PTDC/BBB - BEP/2127/2012) and PhD Fellowship SFRH/BD/66461/2009 (to J.A.S.). The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under BioStruct-X (Grant Agreement 283570)