Control of cell adhesion and compartmentalization in the intestinal epithelium

Continuous cell renewal in the intestinal mucosa occurs without disrupting the integrity of the epithelial layer. Despite the restrictions imposed by strong cell-to-cell adhesions, epithelial intestinal cells migrate constantly between tissue compartments. Alterations in cell adhesion and compartmentalization play key roles in diseases of the intestine. In particular, decreased E-cadherin-mediated adhesion during inflammatory bowel disease and loss of EphB/ephrin-B-mediated compartmentalization in colorectal cancer have recently emerged as key players of these prevalent pathologies. Here we will review our current knowledge on how cell-to-cell adhesion, migration and cell positioning are coordinated in the intestinal epithelium. We will highlight what the in vivo genetic analysis of intestinal epithelium has taught us about the complex regulation of cell adhesion and migration in homeostasis and disease. © 2011 Elsevier Inc

An Acute Increase of Dietary Protein Intake Elicits Positive Cellular Metabolic Adaptations in Healthy Males

There is emerging literature demonstrating that restricting dietary carbohydrate (CHO) intake might upregulate cellular markers of mitochondrial biogenesis. Mitochondria quantity and density has been linked with increased endurance performance, reduction in type 2 diabetes and improved insulin sensitivity. A number of transcriptional cellular markers have been identified as key regulators of this process. PURPOSE: To determine the influence of 7 days dietary manipulation on resting metabolic rate (RMR), body composition and transcriptional markers of mitochondrial biogenesis. METHOD: Forty-six healthy male participants (mean ± SD; age (years), body mass (kg), height (cm); 28 ± 5, 75.6 ± 11.1, 178.0 ± 4.9, respectively) were recruited and randomised to one of four conditions: energy matched high protein (PRO-EM), energy restricted high protein (PRO-ER), energy matched high carbohydrate (CHO-EM) or energy restricted high carbohydrate (CHO-ER). Macronutrient ratios (PRO:CHO:FAT) of 40:30:30 and 60:10:30 were used for high protein and high carbohydrate conditions, respectively. Calorific intake for energy restricted groups was matched to RMR. Participants visited the laboratory on 3 occasions across 15 days. On days 0, 7 and 15 participants completed assessments of body composition (DEXA) and RMR (indirect calorimetry), prior to providing a muscle biopsy from the vastus lateralis for later analysis of transcriptional markers via real-time polymerase chain reaction. Between days 1 & 7 and 7 & 14 participants consumed their habitual and prescribed diets, respectively. Laboratory testing was completed following an overnight fast and at the same time of day on each occasion. RESULTS: No difference in RMR was observed in any group across all time points. AMPK, PGC-1a, SIRT1 and PPAR expression was increased in the PRO-ER group (1.32, 1.20, 1.45 and 1.41 fold, respectively). Transcriptional markers were not affected in either CHO group. The CHO-ER group demonstrated a greater loss in lean mass relative to the PRO-EM (-2.22 vs -0.35%,) and body mass loss relative to both CHO-EM and PRO-EM (-2.85 vs -0.95 vs -1.47%) (P < 0.05). CONCLUSION: A restriction energy intake combined with increased protein consumption for 7 days increases transcriptional markers of mitochondrial biogenesis

Vegetación del sector malacitano-axarquiense (Comarca de la Axarquía. Montes de Málaga y Corredor de Colmenar). Málaga (España).

Vegetación del sector Malacitano-Axarquiense (Comarca de La Axarquía, Montes de Málaga y Corredor de Colmenar). Málaga (España). Se ha realizado un estudio fitocenológico, florístico y fitogeográfico del sector Malacitano-Axarquiense (provincia Bética, Región Mediterránea), que coincide en gran medida con la comarca natural de la Axarquía, Montes de Málaga y Corredor de Colmenar (provincia de Málaga, Andalucía, España). Bioclimáticamente aparecen los pisos termomediterráneo seco y subhúmedo y el piso mesomediterráneo subhúmedo. Se propone una sectorización fitogeográfica a un nivel inferior al de sector, con 5 unidades: unidad Axarquiense (la más oriental), unidad Montes de Málaga (la de mayor elevación y precipitación anual), unidad Almogía (la más occidental), unidad Hacho de Pizarra (geomorfológicamente aislada) y unidad Corredor de Colmenar (al norte de las anteriores). Se han recolectado algunos táxones de interés por su grado de amenaza, por estar protegidos, por ser endemismos o muy escasos. El territorio presenta una elevada cantidad de sintaxones (85) si tenemos en cuenta que ha sufrido una fuerte antropización por la influencia de la ciudad de Málaga y por la gran extensión de cultivos marginales. De estos sintaxones destacan algunas novedades como un tipo de alcornocal (Centaureo sempervirentis-Quercetum suberis) o una alianza de pastizales vivaces otoñales (Ranunculion bullati). Se han catalogado 13 series de vegetación: 4 de tipo climatófilo caracterizadas por vegetación climácica de árboles planifolios (Quercus rotundifolia, Quercus suber); 6 edafohidrófilas con vegetación climácica dominada por árboles caducifolios (Populus alba, Ulmus minor, Fraxinus angustifolia) o arbustos de riberas o niveles freáticos (Salix pedicellata, Neirum oleander, Tamarix africana); 3 edafoxerófilas caracterizadas climácicamente por arbustos relictuales (Maytenus senegalensis, Juniperus turbinata) o árboles (Olea sylvestris). La vegetación de complejos edafogénicos se desarrolla en suelos con niveles freáticos (Coriaria myrtifolia), lagunas (hidrófitos), dunas y arenales (psammófitos) y acantilados litorales (Limonium malacitanum). Se aportan en este trabajo el esquema sintaxonómico, los inventarios y/o tablas fitosociológicas de novedades o interés especial y un mapa fitogeográfico.Vegetation of the Axarquia, Montes de Malaga and Colmenar Corridor (Malacitano- Axarquiense phytogeographical sector) Málaga (Spain). A series of phytocoenological, floristic and phytogeographical studies have been made in the Malacitano-Axarquiense sector (Betica province, Mediterranean region) that corresponds to the local territories of Axarquía, Montes de Málaga and Corredor de Colmenar (Malaga province, Andalusia, Spain). The bioclimatic belts of the studied territory are thermomediterranean dry and subhumid and mesomediterranean subhumid. The proposed phytogeographical division under sector level delimits 5 units: Axarquiense (eastern most), Montes de Málaga (the highest and with higher rainfall), Almogía (western most), Hacho de Pizarra (lithologically isolated) and Corredor de Colmenar (located at the north of the others). Some interesting plants have been pointed out due to its endangered status or being protected by law, endemics or rare.In the studied territory develop a large number of sintaxa (85) if we consider that the land has suffered a strong man influence (large expanse of dry-farmed crops) and it is very near to the city of Málaga.Some sintaxa stand out: a new type of Quercus suber forest (Centaureo sempervirentis-Quercetum suberis) and a new alliance for autumnal geophyte grasslands (Ranunculion bullati). A total amount of 13 vegetation series have been catalogued: 4 series are climactic and characterised by sclerophyll broad-leaved trees (Quercus rotundifolia, Quercus suber); 6 edaphohydrophyllic series with climax characterised by deciduous trees (Populus alba, Ulmus minor, Fraxinus angustifolia) or tall shrubs (Salix pedicellata, Neirum oleander, Tamarix africana) in riversides or underground water tables; 3 edaphoxerophyllic series characterised by relict shrublands (Maytenus senegalensis, Juniperus turbinata) or trees (Olea sylvestris). The vegetation that develops in mosaic-complexes corresponds to damp soils (Coriaria myrtifolia), pools (hydrophytes), dunes and sandy areas (psammophytes) and coastal cliffs (Limonium malacitanum). This work includes a syntaxonomical scheme, relevés or tables for interesting new phytosociological sintaxa and a phytogeographical map

Vegetación de la cordillera antequerana oriental (Subsector Torcalense). Málaga-Granada (España).

Vegetación de la cordillera Antequerana Oriental (subsector Torcalense). Málaga-Granada.España. Se ha realizado un estudio fitocenológico, florístico y fitogeográfico del subsector Torcalense en su parte sudoriental (sector Antequerano, provincia Bética, Región Mediterránea), que abarca diversas sierras del Arco Calizo Central de Málaga y que se adentran en Granada (Andalucía, España). Bioclimáticamente aparecen los pisos termomediterráneo subhúmedo, mesomediterráneo subhúmedo-húmedo y supramediterráneo húmedo. Se propone una sectorización fitogeográfica a un nivel inferior al de sector, con 2 unidades: unidad Pedrizas (la más occidental), y unidad de Zafarraya (más oriental). Se han seleccionado algunos táxones de interés por su grado de amenaza (ej. Salvia candelabrum), por estar protegidos (ej. Prunus mahaleb) o por ser endemismos torcalenses (Saxifraga biternata) o muy escasos (ej. Narcissus elegans).El territorio presenta una elevada cantidad de sintaxones (49) si tenemos en cuenta su pequeña extensión y homogeneidad litológica. De estos sintaxones destacan algunas novedades como un nuevo tipo de quejigal (Vinco difformis-Quercetum fagineae). Se han catalogado 8 series de vegetación: 4 de tipo climatófilo caracterizadas por vegetación climácica de árboles planifolios, perennifolios o marcescentes (Quercus rotundifolia, Quercus faginea) 1 edafoxerófila con acebuches (Olea sylvestris) y 3 edafohidrófilas con vegetación climácica dominada por árboles caducifolios (Ulmus minor, Fraxinus angustifolia) o arbustos (Nerium oleander) de riberas o niveles freáticos. La vegetación de complejos edafogénicos se desarrolla en karst (Acer monspessulanum) o lagunas (Ranunculus saniculifolius, R. tricophyllus). Se aportan en este trabajo las especies de interés, el esquema sintaxonómico, los inventarios y/o tablas fitosociológicas de novedades o interés especial y un mapa fitogeográfico.Vegetation of the eastern Antequera mountain range (Torcalense subsector). Malaga-Granada.Spain. We have studied the vegetation and flora of the south-eastern Torcalense phytogeographical subsector (Antequerano sector, Bética province, Mediterranean region). This area comprises several mountain ranges in the centre of the province of Malaga and entering western Granada province. Three bioclimatic belts have been detected: thermomediterranean subhumid, mesomediterranean subhumid-humid and supramediterranean humid. Two phytogeographical units, under subsector level, are proposed: Pedrizas unit (western) and Zafarraya unit (eastern). Some interesting taxa have been found in the territory; they are endangered (e.g. Salvia candelabrum), protected (e. g. Prunus mahaleb), local endemism (Saxifraga biternata) or scarce plant (e. g. Narcissus elegans). The studied area shows a high number of plant communities (49) if we take into account its little area and homogeneous lithology. We point out some new syntaxa as a Quercus faginea forest (Vinco difformis-Quercetum fagineae). A total of 8 vegetation series have been detected: 4 series are climatophyllous and characterised by sclerophyllous or winter-deciduous broad-leafed trees (Quercus rotundifolia, Quercus faginea); 1 edaphoxerophyllic series is characterised by Olea sylvestris; 3 series are edaphohidrophyllic and characterised by deciduous trees (Ulmus minor, Fraxinus angustifolia) or tall shrubs (Nerium oleander) in riversides and river beds with underground water tables. The vegetation that develops as mosaic-complexes belongs to karst (Acer monspessulanum) or pools (Ranunculus saniculifolius, R.tricophyllus). The more interesting species, a syntaxonomical scheme, relevés and tables, and a phytogeographical map are included

Quantifying Social Asymmetric Structures

Many social phenomena involve a set of dyadic relations among agents whose actions may be dependent. Although individualistic approaches have frequently been applied to analyze social processes, these are not generally concerned with dyadic relations nor do they deal with dependency. This paper describes a mathematical procedure for analyzing dyadic interactions in a social system. The proposed method mainly consists of decomposing asymmetric data into their symmetrical and skew-symmetrical parts. A quantification of skew-symmetry for a social system can be obtained by dividing the norm of the skew-symmetrical matrix by the norm of the asymmetric matrix. This calculation makes available to researchers a quantity related to the amount of dyadic reciprocity. Regarding agents, the procedure enables researchers to identify those whose behavior is asymmetric with respect to all agents. It is also possible to derive symmetric measurements among agents and to use multivariate statistical techniques

SARS-CoV-2 Catalonia contact tracing program : evaluation of key performance indicators

Background: Guidance on SARS-CoV-2 contact tracing indicators have been recently revised by international public health agencies. The aim of the study is to describe and analyse contact tracing indicators based on Catalonia's (Spain) real data and proposing to update them according to recommendations. Methods: Retrospective cohort analysis including Catalonia's contact tracing dataset from 20 May until 31 December 2020. Descriptive statistics are performed including sociodemographic stratification by age, and differences are assessed over the study period. Results: We analysed 923,072 contacts from 301,522 SARS-CoV-2 cases with identified contacts (67.1% contact tracing coverage). The average number of contacts per case was 4.6 (median 3, range 1-243). A total of 403,377 contacts accepted follow-up through three phone calls over a 14-day quarantine period (84.5% of contacts requiring follow-up). The percentage of new cases declared as contacts 14 days prior to diagnosis evolved from 33.9% in May to 57.9% in November. All indicators significantly improved towards the target over time (p < 0.05 for all four indicators). Conclusions: Catalonia's SARS-CoV-2 contact tracing indicators improved over time despite challenging context. The critical revision of the indicator's framework aims to provide essential information in control policies, new indicators proposed will improve system delay's follow-up. The study provides information on COVID-19 indicators framework experience from country's real data, allowing to improve monitoring tools in 2021-2022. With the SARS-CoV-2 pandemic being so harmful to health systems and globally, is important to analyse and share contact tracing data with the scientific community

Internal control genes for quantitative RT-PCR expression analysis in mouse osteoblasts, osteoclasts and macrophages

<p>Abstract</p> <p>Background</p> <p>Real-time quantitative RT-PCR (qPCR) is a powerful technique capable of accurately quantitating mRNA expression levels over a large dynamic range. This makes qPCR the most widely used method for studying quantitative gene expression. An important aspect of qPCR is selecting appropriate controls or normalization factors to account for any differences in starting cDNA quantities between samples during expression studies. Here, we report on the selection of a concise set of housekeeper genes for the accurate normalization of quantitative gene expression data in differentiating osteoblasts, osteoclasts and macrophages. We implemented the use of geNorm, an algorithm that determines the suitability of genes to function as housekeepers by assessing expression stabilities. We evaluated the expression stabilities of 18S, ACTB, B2M, GAPDH, HMBS and HPRT1 genes.</p> <p>Findings</p> <p>Our analyses revealed that 18S and GAPDH were regulated during osteoblast differentiation and are not suitable for use as reference genes. The most stably expressed genes in osteoblasts were ACTB, HMBS and HPRT1 and their geometric average constitutes a suitable normalization factor upon which gene expression data can be normalized. In macrophages, 18S and GAPDH were the most variable genes while HMBS and B2M were the most stably expressed genes. The geometric average of HMBS and B2M expression levels forms a suitable normalization factor to account for potential differences in starting cDNA quantities during gene expression analysis in macrophages. The expression stabilities of the six candidate reference genes in osteoclasts were, on average, more variable than that observed in macrophages but slightly less variable than those seen in osteoblasts. The two most stably expressed genes in osteoclasts were HMBS and B2M and the genes displaying the greatest levels of variability were 18S and GAPDH. Notably, 18S and GAPDH were the two most variably expressed control genes in all three cell types. The geometric average of HMBS, B2M and ACTB creates an appropriate normalization factor for gene expression studies in osteoclasts.</p> <p>Conclusion</p> <p>We have identified concise sets of genes suitable to use as normalization factors for quantitative real-time RT-PCR gene expression studies in osteoblasts, osteoclasts and macrophages.</p

Visualizing the Anthropocene dialectically: Jessica Woodworth and Peter Brosens’ eco-crisis trilogy

The ambition of this article is to propose a way of visualizing the Anthropocene dialectically. As suggested by the Dutch atmospheric chemist Paul Crutzen and the professor of biology Eugene F. Stoermer, the term Anthropocene refers to a historical period in which humankind has turned into a geological force that transforms the natural environment in such a way that it is hard to distinguish between the human and the natural world. Crutzen and Stoermer explain that the Anthropocene has begun after the Holocene, the geological epoch that followed the last ice age and lasted until the industrial revolution. Drawing on a number of figures such as the “tenfold” increase in urbanisation, the extreme transformation of land surface by human action, the use of more than 50% of all accessible fresh water by humans, and the massive increase in greenhouse emissions, Crutzen and Stoermer conclude that the term Anthropocene describes aptly mankind's influence on ecological and geological cycles (Crutzen & Stoermer, 2000, p.17). The wager of this article is that we need to identify ways to visualize the Anthropocene dialectically and I proceed to do so using as a case study Jessica Woodworth's and Peter Brosen's trilogy on the conflict between humans and nature, which consists of Khadak (2006), Altiplano (2009), and The Fifth Season (La Cinquième Saison, 2012)

Gamma-Secretase-Dependent and -Independent Effects of Presenilin1 on β-Catenin·Tcf-4 Transcriptional Activity

Presenilin1 (PS1) is a component of the γ-secretase complex mutated in cases of Familial Alzheimer's disease (FAD). PS1 is synthesized as a 50 kDa peptide subsequently processed to two 29 and 20 kDa subunits that remain associated. Processing of PS1 is inhibited by several mutations detected in FAD patients. PS1 acts as negative modulator of β-catenin·Tcf-4 transcriptional activity. In this article we show that in murine embryonic fibroblasts (MEFs) the mechanisms of action of the processed and non-processed forms of PS1 on β-catenin·Tcf-4 transcription are different. Whereas non-processed PS1 inhibits β-catenin·Tcf-4 activity through a mechanism independent of γ-secretase and associated with the interaction of this protein with plakoglobin and Tcf-4, the effect of processed PS1 is prevented by γ-secretase inhibitors, and requires its interaction with E- or N-cadherin and the generation of cytosolic terminal fragments of these two cadherins, which in turn destabilize the β-catenin transcriptional cofactor CBP. Accordingly, the two forms of PS1 interact differently with E-cadherin or β-catenin and plakoglobin: whereas processed PS1 binds E-cadherin with high affinity and β-catenin or plakoglobin weakly, the non-processed form behaves inversely. Moreover, contrarily to processed PS1, that decreases the levels of c-fos RNA, non-processed PS1 inhibits the expression c-myc, a known target of β-catenin·Tcf-4, and does not block the activity of other transcriptional factors requiring CBP. These results indicate that prevention of PS1 processing in FAD affects the mechanism of repression of the transcriptional activity dependent on β-catenin

Evidence Based Selection of Housekeeping Genes

For accurate and reliable gene expression analysis, normalization of gene expression data against housekeeping genes (reference or internal control genes) is required. It is known that commonly used housekeeping genes (e.g. ACTB, GAPDH, HPRT1, and B2M) vary considerably under different experimental conditions and therefore their use for normalization is limited. We performed a meta-analysis of 13,629 human gene array samples in order to identify the most stable expressed genes. Here we show novel candidate housekeeping genes (e.g. RPS13, RPL27, RPS20 and OAZ1) with enhanced stability among a multitude of different cell types and varying experimental conditions. None of the commonly used housekeeping genes were present in the top 50 of the most stable expressed genes. In addition, using 2,543 diverse mouse gene array samples we were able to confirm the enhanced stability of the candidate novel housekeeping genes in another mammalian species. Therefore, the identified novel candidate housekeeping genes seem to be the most appropriate choice for normalizing gene expression data