Phylogenetic biome conservatism as a key concept for an integrative understanding of evolutionary history: Galliformes and Falconiformes as study cases

Biomes are climatically and biotically distinctive macroecological units that formed over geological time scales. Their features consolidate them as ‘evolutionary scenarios’, with their own diversification dynamics. Under the concept of phylogenetic niche conservatism, we assessed, for the first time, the evolution of biome occupation in birds. We aimed to analyse patterns of adaptation to different climatic regimes and the determinant factors for colonization of emerging biomes by clades from different ancestral biomes. In this work, we reconstructed the biome occupation history of two clades of birds (Galliformes and Falconiformes) under an integrative perspective through a comprehensive review of ecological, phylogenetic, palaeontological and biogeographical evidence. Our findings for both groups are consistent with a scenario of phylogenetic biome conservatism and highlight the importance of changes in climate during the Miocene in the adaptation and evolution of climatic niches. In particular, our results indicate high biome conservatism associated with biomes situated in some of the extremes of the global climate gradient (evergreen tropical rainforest, steppe and tundra) for both bird taxa. Finally, the historical dynamics of tropical seasonal biomes, such as tropical deciduous woodlands and savannas, appear to have played a preponderant role during the diversification processes of these bird lineages.Depto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEMinisterio de Ciencia e Innovación (MICINN)Universidad Complutense de MadridColombian administrative Department for Science and InnovationDirección General de Investigaciones of Universidad Santiago de CaliTalent Attraction Program of the Madrid GovernmentUniversidad Complutense de Madridpu

Anisolepis longicauda

Anisolepis longicauda is listed as Vulnerable because the extent of occurrence is approximately 7,750 km2, the species occurs in two locations (defined by habitat loss from dam construction), and there is an ongoing decline in the extent and quantity of its habitat as a result of the construction of the Yacireta dam.Fil: Arzamendia, Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Fitzgerald, L.. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Giraudo, Alejandro Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Kacoliris, F.. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo; ArgentinaFil: Montero, R.. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Pelegrin, Nicolas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; ArgentinaFil: Scrocchi Manfrini, Gustavo Jose. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Williams, J.. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo; Argentin

Cenários de desenvolvimento sustentável no Pantanal em função de tendências hidroclimáticas.

Nesta feita uma análise prospectiva do futuro hidrológico do Pantanal sob a perspectiva de dados pretéritos, da mudança do clima com base em relações entre o nível máximo do Rio Paraguai, interação oceano-atmosfera e precipitação na América do Sul. A cenarização hidroclimática, incluindo a componente humana, permite ainda identificar adaptações e oportunidades para as próximas décadas, também em função de mudanças e tendências da economia mundial.bitstream/CPAP-2009-09/56873/1/DOC98.pd

Discordant bioinformatic predictions of antimicrobial resistance from whole-genome sequencing data of bacterial isolates: an inter-laboratory study.

Antimicrobial resistance (AMR) poses a threat to public health. Clinical microbiology laboratories typically rely on culturing bacteria for antimicrobial-susceptibility testing (AST). As the implementation costs and technical barriers fall, whole-genome sequencing (WGS) has emerged as a 'one-stop' test for epidemiological and predictive AST results. Few published comparisons exist for the myriad analytical pipelines used for predicting AMR. To address this, we performed an inter-laboratory study providing sets of participating researchers with identical short-read WGS data from clinical isolates, allowing us to assess the reproducibility of the bioinformatic prediction of AMR between participants, and identify problem cases and factors that lead to discordant results. We produced ten WGS datasets of varying quality from cultured carbapenem-resistant organisms obtained from clinical samples sequenced on either an Illumina NextSeq or HiSeq instrument. Nine participating teams ('participants') were provided these sequence data without any other contextual information. Each participant used their choice of pipeline to determine the species, the presence of resistance-associated genes, and to predict susceptibility or resistance to amikacin, gentamicin, ciprofloxacin and cefotaxime. We found participants predicted different numbers of AMR-associated genes and different gene variants from the same clinical samples. The quality of the sequence data, choice of bioinformatic pipeline and interpretation of the results all contributed to discordance between participants. Although much of the inaccurate gene variant annotation did not affect genotypic resistance predictions, we observed low specificity when compared to phenotypic AST results, but this improved in samples with higher read depths. Had the results been used to predict AST and guide treatment, a different antibiotic would have been recommended for each isolate by at least one participant. These challenges, at the final analytical stage of using WGS to predict AMR, suggest the need for refinements when using this technology in clinical settings. Comprehensive public resistance sequence databases, full recommendations on sequence data quality and standardization in the comparisons between genotype and resistance phenotypes will all play a fundamental role in the successful implementation of AST prediction using WGS in clinical microbiology laboratories

Effectiveness of TNF-α blockade in the treatment of refractory non-infectious scleritis: a multicentre study

OBJECTIVES: To evaluate the efficacy of tumour necrosis factor (TNF)-α inhibitors in refractory non-infectious scleritis. METHODS: We carried out a retrospective study assessing the efficacy of TNF-α inhibitors in the treatment of scleritis, scleritis relapses, glucocorticoid (GC)-sparing effect, impact on best-corrected visual acuity (BCVA) and safety profile. RESULTS: Nineteen patients (28 eyes) were eligible for analysis. Scleritis inflammatory grading significantly improved from baseline to the last follow-up (median ± IQR 2±4 and 0±0 respectively, p=0.0006). Scleritis relapses significantly decreased between the 12 months preceding and following biologic therapy (p=0.001). Mean GC dosage decreased from baseline (19.00±13.56 mg) to the last follow-up (7.59±5.56 mg) (p=0.003). No significant differences regarding BCVA were observed. Two AEs were recorded (1 severe urticaria and 1 case of pneumonia and paradoxical psoriasis). CONCLUSIONS: TNF-α inhibitors are effective in the treatment of scleritis while allowing a GC-sparing effect and preserving BCVA

P2X receptors: epithelial ion channels and regulators of salt and water transport.

When the results from electrophysiological studies of renal epithelial cells are combined with data from in vivo tubule microperfusion experiments and immunohistochemical surveys of the nephron, the accumulated evidence suggests that ATP-gated ion channels, P2X receptors, play a specialized role in the regulation of ion and water movement across the renal tubule and are integral to electrolyte and fluid homeostasis. In this short review, we discuss the concept of P2X receptors as regulators of salt and water salvage pathways, as well as acknowledging their accepted role as ATP-gated ion channels

Depression in Alzheimer''s Disease: A Delphi Consensus on Etiology, Risk Factors, and Clinical Management

Background: Alzheimer''s disease (AD) and other forms of dementia are among the most common causes of disability in the elderly. Dementia is often accompanied by depression, but specific diagnostic criteria and treatment approaches are still lacking. This study aimed to gather expert opinions on dementia and depressed patient management to reduce heterogeneity in everyday practice. Methods: Prospective, multicenter, 2-round Modified Delphi survey with 53 questions regarding risk factors (11), signs and symptoms (7), diagnosis (8), and treatment (27) of depression in dementia, with a particular focus on AD. The questionnaire was completed by a panel of 37 expert physicians in neurodegenerative diseases (19 neurologists, 17 psychiatrists, and 1 geriatrician). Results: Consensus was achieved in 40 (75.5%) of the items: agreement in 33 (62.3%) and disagreement in 7 (13.2%) of them. Among the most relevant findings, depression in the elderly was considered an early sign (prodromal) and/or a dementia risk factor, so routine cognitive check-ups in depressed patients should be adopted, aided by clinical scales and information from relatives. Careful interpretation of neuropsychological assessment must be carried out in patients with depression as it can undermine cognitive outcomes. As agreed, depression in early AD is characterized by somatic symptoms and can be differentiated from apathy by the presence of sadness, depressive thoughts and early-morning awakening. In later-phases, symptoms of depression would include sleep-wake cycle reversal, aggressive behavior, and agitation. Regardless of the stage of dementia, depression would accelerate its course, whereas antidepressants would have the opposite effect. Those that improve cognitive function and/or have a dual or multimodal mode of action were preferred: Duloxetine, venlafaxine/desvenlafaxine, vortioxetine, tianeptine, and mirtazapine. Although antidepressants may be less effective than in cognitively healthy patients, neither dosage nor treatment duration should differ. Anti-dementia cholinesterase inhibitors may have a synergistic effect with antidepressants. Exercise and psychological interventions should not be applied alone before any pharmacological treatment, yet they do play a part in improving depressive symptoms in demented patients. Conclusions: This study sheds light on several unresolved clinical challenges regarding depression in dementia patients. Further studies and specific recommendations for this comorbid patient population are still needed.

The Second Transmembrane Domain of P2X7 Contributes to Dilated Pore Formation

Activation of the purinergic receptor P2X7 leads to the cellular permeability of low molecular weight cations. To determine which domains of P2X7 are necessary for this permeability, we exchanged either the C-terminus or portions of the second transmembrane domain (TM2) with those in P2X1 or P2X4. Replacement of the C-terminus of P2X7 with either P2X1 or P2X4 prevented surface expression of the chimeric receptor. Similarly, chimeric P2X7 containing TM2 from P2X1 or P2X4 had reduced surface expression and no permeability to cationic dyes. Exchanging the N-terminal 10 residues or C-terminal 14 residues of the P2X7 TM2 with the corresponding region of P2X1 TM2 partially restored surface expression and limited pore permeability. To further probe TM2 structure, we replaced single residues in P2X7 TM2 with those in P2X1 or P2X4. We identified multiple substitutions that drastically changed pore permeability without altering surface expression. Three substitutions (Q332P, Y336T, and Y343L) individually reduced pore formation as indicated by decreased dye uptake and also reduced membrane blebbing in response to ATP exposure. Three others substitutions, V335T, S342G, and S342A each enhanced dye uptake, membrane blebbing and cell death. Our results demonstrate a critical role for the TM2 domain of P2X7 in receptor function, and provide a structural basis for differences between purinergic receptors. © 2013 Sun et al

Intestinal secretory and absorptive functions in Trichinella spiralis mouse model of postinfective gut dysfunction: role of bile acids

ABSTRACT Objective: Observations showing that bile acid malabsorption is frequent in irritable bowel syndrome (IBS) suggest that alterations in bile acid-induced secretion and absorption could contribute to IBS-associated diarrhoea. The secretory response to bile acids, fluid transport and bile absorption was examined in intestinal tissues from a Trichinella spiralis mouse model of postinfectious gut dysfunction in vitro. Changes in the protein expression of apical sodium-dependent bile acid transporter (ASBT) were also measured. Design: T. spiralis-infected mice were killed at 18 and 25 days postinfection. Jejunal, ileal, proximal and distal colon segments were exposed to taurodeoxycholic acid (TDCA) or cholic acid. Short circuit current (SCC) increases were determined. Tritiated taurocholic acid (3H-TCA) absorption was determined in everted jejunal and ileal sacs. ASBT protein expression was determined by Western blot analysis and immunohistochemistry. Results: Basal SCC increased in ileum and distal colon at 18 and 25 days postinfection, respectively. Ileal SCC responses to TDCA and cholic acid were enhanced at 18 days postinfection. Distal colon SCC response to TDCA was raised at 18 days postinfection but was significantly reduced by 25 days. Ileal 3H-TCA uptake was significantly reduced at 18 and 25 days postinfection. Surprisingly, increased ASBT expression was observed in infected animals. Conclusions: In a T. spiralis model of postinfectious gut dysfunction, decreased bile absorption and enhanced secretion in response to bile acids was observed. Decreased absorption was not, however, caused by decreased ASBT as increased expression was observed. If similar events occur postinfection, the combined effects of these disturbances may contribute to some symptoms observed in postinfectious IBS patients. Irritable bowel syndrome (IBS) is an extremely common disorder that affects up to 20% of the general population and is responsible for almost half of the referrals to gastroenterologists. 1 2 Surprisingly, the cause of IBS is poorly understood and several pathophysiological mechanisms have been implicated. [3] 11 Although bile acid malabsorption (BAM) has generally been regarded an infrequent cause of chronic diarrhoea, recent improvements in the techniques employed for assessing BAM have demonstrated that it is a much more common cause of diarrhoea than originally considered. 12 13 This has been highlighted by the recent and unexpected evidence that BAM was observed in 33% of patients with diarrhoea-predominant IBS. 13 Bile acids are synthesised in the liver and secreted into the small intestine where they facilitate fat and fat-soluble vitamin absorption. Although some bile uptake occurs in the jejunum, the main route for circulation of bile back into the liver is by active reabsorption in the terminal ileum by the apical sodium-dependent bile acid transporter (ASBT). Dysfunction of ASBT is accompanied by an interruption in the enterohepatic bile circulation, allowing bile acids to enter the colon in increased concentrations. 14 15 This subsequently induces diarrhoea as bile acids stimulate chloride ion (Cl 2 ) secretion and powerful propagating contractions in the colon. 16 Although IBS has generally been considered a motility disorder, it seems likely that the condition may involve changes in fluid and electrolyte transport across the intestinal epithelium, because diarrhoea and mucus hypersecretion are well-recognised features. In addition, intestinal secretory mechanisms may be more sensitive to secretogogues, such as bile acids, during IBS. Oddsson and colleagues 17 have shown that the small intestine in IBS patients has a greater secretory response to low bile acid concentrations. Recent work in our laboratory and by others has established the characteristics of bile acid-induced secretion and ileal bile acid absorption in normal and mast cell-deficient mice. 18-21 Similar studies have not been performed in a murine model of postinfectious gut dysfunction. The T. spiralisinfected mouse is a widely acknowledged model of postinfectious gut dysfunction in which visceral hypersensitivity and persistently altered motility, which mimic the hyperreactive state in IBS, are observed. 10 22 T. spiralis infection has two phases. Postinfectious gut dysfunction occurs after the enteric phase, when the worm is expelled from the intestine. There is also a skeletal muscle phase during which the worm is present in muscle (for the duration of the mouse's life) despite gut expulsion. Although infection with the nematode initially generates an intestinal inflammatory response that resolves after worm expulsion from the intestine, functional changes such as increased motility, visceral hypersensitivitity and increased muscle thickness persist. The current study determined the secretory effects of cholic acid and taurodeoxycholic acid (TDCA) in the small intestine and colon of T. spiralis-infected mice at two postinfective timepoints. In addition, studies were performed to investigate whether passive bile uptake in the jejunum and active bile absorption in the terminal ileum was also impaired in these mice. Furthermore, changes in the expression of ASBT after infection were determined in an attempt to correlate these with any observed differences in bile salt absorption. MATERIALS AND METHODS Animals Experiments were performed on intestinal tissues from T. spiralis-infected and non-infected mice killed by cervical dislocation in accordance with UK Home Office regulations and with local Ethical Committee approval. Male Swiss mice (age 12-13 weeks) were obtained from Sheffield Field Laboratories and were allowed free access to food and water. Infection with T. spiralis Stock mice infected with T. spiralis were killed to obtain larvae for infecting mice to be used in experimental procedures. Larvae were recovered from stock mice by pepsin (0.5%) and hydrochloric acid (0.5%) digestion of the skeletal muscle as described by Castro and Fairbain. Measurement of transintestinal electrical activity Ussing chambers were used to measure changes in ion transport through the electrical correlate, short circuit current (SCC). Segments of jejunum (immediately distal to the ligament of Treitz), terminal ileum (6 cm before the caecum), proximal colon and distal colon were stripped of the outer muscle layers, which removed the myenteric plexus as well as the muscle coat but left intact the submucosal and mucosal plexus. Tissue was allowed to stabilise for 15 minutes after mounting, and readings of electrical activity were subsequently taken at one minute intervals. After five minutes of basal readings, either cholic acid (Sigma, St Louis, Missouri, USA) or TDCA (Sigma) was added to the serosal side and readings were taken for a further 15 minutes. We have previously looked at the effects of both the mucosal and serosal application of several bile acids to the small intestine and found a concentration of 1 mmol to be effective only from the serosal side. 19 Therefore bile acid secretion is initiated by action at the serosal side of the enterocyte. The actual effective concentration is likely to be considerably less because of the diffusion barrier, represented by subepithelial tissues, which needs to be overcome. Furthermore, in the ileum, sodium-dependent bile acid absorption also increases SCC, so to avoid this component of the overall SCC change that occurs when bile acids are applied mucosally, serosal application (when absorption is not activated) was chosen. An aliquot of 100 ml cholic acid or TDCA, dissolved in ethanol and saline, respectively, was added to the 5 ml bathing solution to yield a final concentration of 1 mmol for both substances. Preliminary studies identified that neither ethanol nor saline, added serosally, had any significant effect on basal electrical activity. The SCC generated by the sheets after bile acid administration was calculated as described above using Ohm's law. Measurement of intestinal fluid transport The transport of fluid by the mucosa was measured in everted sacs taken from proximal jejunum and terminal ileum. A 5-7 cm intestinal segment, everted on a glass rod, was filled with 0.2 ml Krebs bicarbonate saline containing 10 mmol glucose (serosal fluid) and was incubated for 30 minutes in 15 ml Krebs bicarbonate saline containing 10 mmol mannitol (mucosal fluid) at 37uC in a shaking water bath. Results are expressed as mucosal fluid transport (MFT), which is the sum of the increase in the volume (weight of tissue) of serosal fluid in the sac after incubation (serosal fluid transport) and that taken up by the gut itself (gut fluid uptake) and values were related to the initial wet weight of the empty sac (ml/g initial wet weight/ 30 minutes). Measurement of 3H-TCA absorption The absorption of taurocholic acid (TCA) was also assessed in the same everted sacs by adding TCA (1 mmol; Sigma) together with 3H-TCA (2.5 mCi/100 ml; PerkinElmer Life Sciences, Boston, Massachusetts, USA) to the mucosal fluid. At the end of the incubation period the serosal fluid was collected. The sac was deproteinised using 10% sodium tungstate (1.25 ml) and 0.33 MH 2 SO 4 (1.25 ml), homogenised and then filtered. Scintillation fluid (3 ml; Emulsifer-safe; Packard Biosciences, USA) was added to 100 ml samples of initial mucosal fluid, final mucosal fluid, final serosal fluid and gut homogenate, and radioactivity was determined using a liquid scintillation analyser (Packard TRI-CARB, 1900XR; Packard Biosciences, Pangbourne, Berkshire, UK). TCA absorption was expressed in two ways: first, as the amount taken up by the sac (mmol/g initial wet weight/30 minutes) and second as the T/M ratio, i.e. the ratio of the TCA concentration in the tissue water compared with its concentration in the mucosal fluid at the end of the incubation period, whereby a T/M ratio greater than 1 indicated active transport. Intestinal inflammation Preparation of epithelial cell homogenates for ASBT expression studies Epithelial cell homogenates were prepared from the three contiguous 3 cm segments of the most distal part of the small intestine. All further steps were performed with the preparations kept on ice. Segments were opened in the longitudinal axis and washed in isotonic saline (0.9% NaCl) to discard adhering luminal content. Mucosa were scraped with a clean glass rod. The mucosal scrapings of three animals were suspended in 5 ml buffer A (10 mmol Tris/HCl/0.13 mol NaCl/5 mmol EDTA, pH 7.4) and stirred gently for 30 minutes at 4uC. Cells were collected by centrifugation (3 min, 2000 rpm, 4uC) and suspended in 500 ml buffer B (10 mmol Tris/HCl/0.3 mol mannitol, pH 7.2) and 20 ml of a protease inhibitor cocktail (Roche, Hertfordshire, UK) to a concentration of approximately 1-2 mg/ ml. The samples containing proteins were stored at 220uC until use. The protein concentration was determined by the Bradford method (Biorad Laboratories, Munchen, Germany). Samples were solubilised in 56 sodium dodecylsulfate (SDS) sample buffer containing 0.125 mmol Tris?Cl, pH 6.8, 10% SDS, 50% glycerol, 10% mercaptoethanol and 0.005% bromophenol blue, and then boiled at 100uC for 5 minutes