Identification of Saccharomyces cerevisiae genes involved in the resistance to multiple stresses during Very-High-Gravity and lignocellulosic biomass industrial fermentations

Most of the current processes for bioethanol production are based on the use of Very-High-Gravity (VHG) technology and the processing of lignocellulosic biomass, limited by the high osmotic pressure and ethanol concentration in the fermentation medium, and by inhibitors resulting from biomass pre-treatments, respectively. Aiming the optimization of strains for industrial bioethanol production an integrated approach was undertaken to identify genes required for simultaneous yeast resistance to different fermentation-related stresses. The integration of previous chemogenomics data was used to identify eight genes whose expression confers simultaneous resistance to high concentrations of glucose, acetic acid and ethanol, chemical stresses relevant for VHG fermentations; and eleven genes conferring simultaneous resistance to different inhibitors present during lignocellulosic fermentations. The expression of BUD31 and HPR1 lead to the increase of both ethanol yield and fermentation rate, while PHO85, VRP1 and YGL024w expression is required for maximal ethanol production in VHG fermentations. Five genes, ERG2, PRS3, RAV1, RPB4 and VMA8 were found to contribute to the maintenance of cell viability in wheat straw hydrolysate and/or for maximal fermentation rate of this substrate [1]. Moreover, the yeast disruptome was screened for strains with increased susceptibility to inhibitory compounds present in an industrial lignocellulosic hydrolysate obtained from wheat straw. With this genome-wide analysis, 42 determinants of resistance to inhibitors were identified showing a high susceptibility phenotype compared to the parental strain. The identified genes stand as preferential targets for genetic engineering manipulation to generate more robust and efficient industrial strains

Iliac artery false aneurysm twelve years after allograft nephrectomy

We report a case of a non-infected right external iliac artery false aneurysm. The patient was a 44 year-old woman on chronic peritoneal dialysis had had an allograft nephrectomy 12 years before and who presented with acute abdominal pain. Ultrasound and CT-scan showed a saccular aneurysm arising from the right external iliac artery. A large false aneurysm was identified during surgery, from donor arterial vessel remaining in situ after graft nephrectomy. Resection of the false aneurysm, with ligation of the right external iliac artery and interposition of a femorofemoral graft was successfully performed, with an uneventful post-operative recovery. False aneurysms after renal allograft nephrectomy are very rare. To our knowledge, this is the longest reported period of time between na nephrectomy and clinical evidence of a false aneurysm.info:eu-repo/semantics/publishedVersio

Fungal peritonitis in peritoneal dialysis patients: is previous antibiotic therapy an essential condition?

The aim of this study was to analyse the clinical and microbiological features of fungal peritonitis, in chronic peritoneal dialysis patients, focusing on non-traditional risk factors for this feared complication. From 2001 to 2004, five episodes of fungal peritonitis were diagnosed in five different patients, accounting for 4.5% of all peritonitis cases seen during this period. Candida spp. were the most frequent isolates. In all cases, peritoneal dialysis catheter removal and switching to haemodialysis were necessary. In these five cases of fungal peritonitis only one was preceded by antibiotic use, within the previous 3 months, the classical risk factor for fungal peritonitis. Identifying predisposing factors usually not taken into account, may lead to an early diagnosis and to a better understanding of fungal peritonitis pathogenesis.info:eu-repo/semantics/publishedVersio

Internalization of methotrexate conjugates by folate receptor-α

The folate antagonist methotrexate is a cytotoxic drug used in the treatment of several cancer types. Methotrexate entry into the cell is mediated by two main transport systems: the reduced folate carrier and membrane-associated folate receptors. These transporters differ considerably in their mechanism of (anti)folate uptake, substrate specificity and tissue specificity. Although the mechanism of action of the reduced folate carrier is fairly well-established, that of the folate receptor has remained doubtful. The development of specific folate receptor-targeted antifolates would be accelerated if additional mechanistic data becomes available. In this work, we used two fluorescent-labeled conjugates of methotrexate, differently linked at the terminal groups, to clarify the uptake mechanism by the folate receptor-α. The results demonstrate the importance of methotrexate amino groups in the interaction with the folate receptor-α.E.A. (SFRH/BD/122952/2016) and J.N. (SFRH/BD/121673/ 2016) hold scholarships from the Portuguese Foundation for Science and Technology (FCT). This study was supported by the FCT under the scope of the strategic funding of the UID/ BIO/04469/2013 unit and the COMPETE 2020 (POCI-010145-FEDER-006684) and BioTecNorte operation (NORTE01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020Programa Operacional Regional do Norte. This work has also received funding from the European Union 7th Framework Programme (FP7/2007−2013), under Grant Agreement NMP4-LA-2009228827 NANOFOL, and the Horizon 2020 research and innovation program under Grant Agreement NMP-06-2015683356 FOLSMART.info:eu-repo/semantics/publishedVersio

Maternal prenatal hair cortisol is associated with prenatal depressive symptom trajectories

Maternal prenatal cortisol levels have been inconsistently associated with self-reports of prenatal psychological distress (PD). Previous research has linked hair cortisol concentration (HCC) evaluating cumulatively the previous months with cross-sectional PD measures that usually cover the past week(s), which may lead to misleading conclusions on their relations. We aimed to investigate how maternal HCC relates to cumulative PD measures across pregnancy. Maternal prenatal cortisol levels have been inconsistently associated with self-reports of prenatal psychological distress (PD). Previous research has linked hair cortisol concentration (HCC) evaluating cumulatively the previous months with cross-sectional PD measures that usually cover the past week(s), which may lead to misleading conclusions on their relations. We aimed to investigate how maternal HCC relates to cumulative PD measures across pregnancy. Methods Subjects (N = 595) were drawn from the FinnBrain Birth Cohort Study. Maternal HCC was measured from hair samples collected at gestational week (gwk) 24 (HCC1, n = 467) and at delivery (HCC2, n = 222). As HCC1 and HCC2 comprised mostly of different subjects, they were considered as independent populations. Maternal PD assessments at gwks 14, 24, and 34 were the Edinburgh Postnatal Depression Scale (EPDS), the anxiety subscale of the Symptom Checklist (SCL-90), the Pregnancy-Related Anxiety Questionnaire -Revised2 (PRAQ-R2), and a daily hassles scale. Cumulative PD comprised of the mean scores of two consecutive assessments (mean1 = gwks 14 and 24; mean2 = gwks 24 and 34). In addition, EPDS and SCL scores were modelled by using growth mixture modelling to identify symptom trajectory categories. Regression models were adjusted for age, body mass index, education and use of selective serotonin/serotonin-norepinephrine reuptake inhibitor medication. Results In the adjusted regression model, higher HCC2 was related to the “consistently elevated” prenatal depressive symptoms trajectory in comparison to “consistently low” (β =.71, p =.021) and “low and increasing” (β =.82, p = .011) symptom trajectories. Additionally, the cumulative mean (mean 1) of daily hassles in relationships was associated with HCC1 (β = 0.25, p = .004). General or pregnancy-related anxiety symptoms were unrelated to HCC after adjustment for the covariates. Conclusions The assessment of cumulative or trajectory measures of PD can reveal important associations with maternal prenatal HCC, even though the associations are generally weak. Of the different dimensions of PD, prenatal trajectories of depressive symptoms were most consistently linked with end-pregnancy HCC levels.Academy of Finland (grant #134950 to HK and grant #308176 to LK), Jane and Aatos Erkko Foundation, Signe and Ane Gyllenberg Foundation, and State Research Grants. Preparation of the manuscript has been funded by Juho Vainio Foundation (PM), Finnish Brain Foundation (PM), and Yrjö Jahnsson Foundation (LK, grants #6976 and #6847). AJR is an FCT Investigator Fellow (IF/00883/2013) and is funded by projects POCI-01-0145-FEDER-016428; POCI-01-0145-FEDER-029071 and POCI-01-0145-FEDER-00703

Parallel Lineage-Tracing Studies Establish Fibroblasts as the Prevailing In Vivo Adipocyte Progenitor.

Summary: Despite decades of studies suggesting that the in vivo adipocyte progenitor resides within the vascular niche, the exact nature of this progenitor remains controversial because distinct studies have attributed adipogenic properties to multiple vascular cell types. Using Cre recombinases labeling distinct vascular lineages, we conduct parallel lineage tracing experiments to assess their degree of contribution to de novo adipogenesis. Although we detect occasional adipocytes that were lineage traced by endothelial or mural recombinases, these are rare events. On the other hand, platelet-derived growth factor receptor alpha (PDGFRα)-expressing adventitial or capsular fibroblasts make a significant contribution to adipocytes in all depots and experimental settings tested. Our data also suggest that fibroblasts transition to an intermediate beige adipocyte phenotype prior to differentiating to a mature white adipocyte. These observations, together with histological analyses revealing that adipose tissue fibroblasts express the mural cell marker PDGFRβ, harmonize a highly controversial field with implications for multiple human diseases, including the pandemic of obesity. : Cattaneo et al. used genetic fate mapping in murine models to test the adipogenic potential of distinct cell types of the vascular wall. These parallel lineage-tracing experiments reveal that fibroblasts are the sole vascular cell type with significant adipocyte progenitor activity, giving rise to brown, beige, and white adipocytes. Keywords: adipogenesis, obesity, vascular wall, lineage tracing, endothelium, mural cells, fibroblast

Evidence for lack of direct causality between pain and affective disturbances in a rat peripheral neuropathy model

[Epub ahead of print]Chronic pain is frequently accompanied by the manifestation of emotional disturbances and cognitive deficits. While a causality relation between pain and emotional/cognitive disturbances is generally assumed, several observations suggest a temporal dissociation and independent mechanisms. We therefore studied Sprague-Dawley rats that presented a natural resistance to pain manifestation in a neuropathy model (spared nerve injury [SNI]) and compared their performance in a battery of behavioral paradigms-anxiety, depression and fear memory-with animals that presented a pain phenotype. Afterward, we performed an extensive volumetric analysis across prefrontal, orbitofrontal and insular cortical areas. The majority of SNI animals manifested mechanical allodynia (low threshold [LT]), but 13% were similar to Sham controls (high threshold [HT]). Readouts of spontaneous hypersensivity (paw flinches) were also significantly reduced in HT and correlated with allodynia. To increase the specificity of our findings, we segregated the SNI animals in those with left (SNI-L) and right (SNI-R) lesions and the lack of association between pain and behavior still remains. Left-lesioned animals, independent of the LT or HT phenotype, presented increased anxiety-like behaviors and decreased well-being. In contrast, we found that the insular cortex (agranular division) was significantly smaller in HT than in LT. To conclude, pain and emotional disturbances observed following nerve injury are to some extent segregated phenomena. Also, HT and LT SNI presented differences in insular volumes, an area vastly implicated in pain perception, suggesting a supraspinal involvement in the manifestation of these phenotypes.This work has been funded by the European Regional Development Fund (FEDER), through the Competitiveness Factors Operational Programme (COMPETE) and the Northern Portugal Regional Operational Programme (NORTE 2020) under the Portugal 2020 Partnership Agreement (project NORTE-01-0145-FEDER-000023). It was also funded by National and International funds, through the Foundation for Science and Technology (FCT), under the scope of the projects POCI-01-0145- FEDER-007038 and PTDC/NEU-SCC/5301/2014 and by the IASP Early Career Research Grant 2015. Researchers were supported by FCT grant numbers PD/BD/114117/2015 (MRG via Inter-University Doctoral Programme in Ageing and Chronic Disease, PhDOC), SFRH/BD/109111/2015 (AMC via PhD Program in Health Sciences), SFRH/BD/52291/2013 (ME via PhDOC), SFRH/BD/89936/2012 (SB via PhD Program in Health Sciences (Applied)), PDE/BDE/113604/2015 (RM via PhD Program in Health Sciences (Applied)), PDE/BDE/113601/2015 (PSM via PhD Program in Health Sciences (Applied)) and SFRH/BPD/80118/2011 (HA). ARS integrated the Master Programme in Health Sciences of the School of Medicine, University of Minho.info:eu-repo/semantics/acceptedVersio