G1/S Cell Cycle Regulated Transcription and Genome Stability

Initiation of a new round of cell proliferation in eukaryotic cells is associated with coordinated transcriptional activation of genes during the G1-to-S transition. In the fission yeast Schizosaccharomyces pombe, genes involved in DNA replication are tightly regulated by the transcription factor MBF during G1/S. Recently, the MBF-associated corepressors Nrm1p and Yox1p were shown to have a non-redundant role in a negative feedback loop mechanism to repress MBF-dependent transcription outside of G1. Activation of the DNA replication checkpoint results in persistent expression of MBF-dependent genes. Here we show that in response to DNA replication stress both Yox1p and Nrm1p dissociate from MBF at promoters, leading to de-repression of MBF targets. Inactivation of Yox1p is an essential part of the checkpoint response. Cds1p checkpoint protein kinase-dependent phosphorylation of Yox1p promotes its dissociation from the MBF transcription factor. We establish that phosphorylation of Yox1p at Ser114 and Thr115 is required for maximal checkpoint-dependent activation of the G1/S cell-cycle transcriptional programme. G1/S transcription includes many genes required for replication and recovery of stalled replication forks. Although persistent expression of the G1/S transcriptional programme is an important part of the DNA replication checkpoint response we show that constitutive expression of the same group of genes outside of G1 and S is detrimental for cells undergoing normal cell cycle progression. Cells abrogated for nrm1+ and yox1+ experience increased genomic instability. We demonstrate that a delicate balance exists between levels of DNA replication initiation factors and CDK activity in these cells. Disruption of this balance induces further genome instability, a hallmark of cancer development

Marsupial chromosome DNA content and genome size assessed from flow karyotypes: invariable low autosomal GC content.

Extensive chromosome homologies revealed by cross-species chromosome painting between marsupials have suggested a high level of genome conservation during evolution. Surprisingly, it has been reported that marsupial genome sizes vary by more than 1.2 Gb between species. We have shown previously that individual chromosome sizes and GC content can be measured in flow karyotypes, and have applied this method to compare four marsupial species. Chromosome sizes and GC content were calculated for the grey short-tailed opossum (2n = 18), tammar wallaby (2n = 16), Tasmanian devil (2n = 14) and fat-tailed dunnart (2n = 14), resulting in genome sizes of 3.41, 3.31, 3.17 and 3.25 Gb, respectively. The findings under the same conditions allow a comparison between the four species, indicating that the genomes of these four species are 1-8% larger than human. We show that marsupial genomes are characterized by a low GC content invariable between autosomes and distinct from the higher GC content of the marsupial × chromosome

Evaluation of lean practices in warehouses: an analysis of Brazilian reality

© 2020, Emerald Publishing Limited. Purpose: This article aims to investigate the most applied lean warehouse practices in Brazilian warehouses. Design/methodology/approach: To perform this research, three phases were conducted: a literature review, a multiple case study, and an analysis of lean warehouses practices implementation by an engineering committee. Thus, both qualitative and quantitative approaches were used. Additionally, the study has an applied nature, with an exploratory and descriptive character. Findings: Results showed that regardless of the type of criterion used, the most implanted practices are those that do not involve investments in technology. On the other hand, practices like RFID and Cross Docking systems were not found in any of the operations, which shows numerous possibilities for improvement. Originality/value: The main contribution of this article is to initiate a debate about the management and productivity of Brazilian warehouses, a theme still little explored by the academic community despite the importance that the logistic scenario represents for Brazil as an emerging country and leader in Latin America, participating actively in several global supply chains

From recovery to regaining control of life - the perspectives of people with stroke, their carers and health professionals.

AIM: To understand how people with stroke and carers adapt over time, and how health professionals support transition to home. METHOD: A multi-perspective, prospective, qualitative, longitudinal study was conducted using in-depth semi-structured interviews one and six months after inpatient discharge. Twenty-four participants (eight triads, including people with stroke, carers and health professionals) were included. Thematic and narrative analysis facilitated identification of cross-cutting themes according to individual trajectories post-stroke. FINDINGS: A major theme: "regaining control of life" suggested a shift in perspective after six months at home. Four sub-themes help to understand the triads' perspectives over time: i) importance of team involvement; ii) differences in perceived roles within the triad; iii) differences in expectations and collaboration within the triad and iv) planning a different future. People who were involved in supporting adaptation and rehabilitation processes were reported differently between triads and over time, showing the complexity of interrelations. A reduction in professional involvement was matched by changes in participants' goals and expectations. CONCLUSION: Findings suggest the importance of a dyadic perspective and a gradual increase in people with stroke and carers' active engagement. Professionals' approach throughout rehabilitation should be modified according to people with stroke and carers' changing needs and expectations.IMPLICATIONS FOR REHABILITATIONDivergence in perspectives about priorities and goals between the person with stroke their carers and healthcare professionals can lead to the creation of different agendas within rehabilitation.An open dialogue and decision-making process that involves both the person with stroke and carers is highly recommended for the identification of shared rehabilitation goals and to support ongoing recovery post discharge.A tailored approach to rehabilitation is required which focusses on shared priorities and includes individual or collective support for the person with stroke and their carers.Ongoing consultation about the desires of the person with stroke about rehabilitation, priorities and goals is important in order to tailor the professional approach to the stage individuals are at with their coping and adjustment post stroke

Herpetic geometric glossitis: Acyclovir resistant case in a patient with acute myelogenous leukemia

Herpes simplex virus (HSV) infections in an immunocompromised host may be atypical in location and morphology. Lesions are more extensive and aggressive, slow healing or nonhealing and extremely painful. Intraoral lesions are ulcerative and may involve any intraoral, oropharyngeal, or esophageal site. Herpetic geometric glossitis is a recently described form of lingual HSV infection in an immunocompromised patient. It was described as ulcer on the dorsum of the tongue sensitive for acyclovir therapy. A patient is presented with acute myelogenous leukemia that developed herpetic geometric glossitis which was acyclovir resistant.53113313

From recovery to regaining control of life - the perspectives of people with stroke, their carers and health professionals.

AIM: To understand how people with stroke and carers adapt over time, and how health professionals support transition to home. METHOD: A multi-perspective, prospective, qualitative, longitudinal study was conducted using in-depth semi-structured interviews one and six months after inpatient discharge. Twenty-four participants (eight triads, including people with stroke, carers and health professionals) were included. Thematic and narrative analysis facilitated identification of cross-cutting themes according to individual trajectories post-stroke. FINDINGS: A major theme: "regaining control of life" suggested a shift in perspective after six months at home. Four sub-themes help to understand the triads' perspectives over time: i) importance of team involvement; ii) differences in perceived roles within the triad; iii) differences in expectations and collaboration within the triad and iv) planning a different future. People who were involved in supporting adaptation and rehabilitation processes were reported differently between triads and over time, showing the complexity of interrelations. A reduction in professional involvement was matched by changes in participants' goals and expectations. CONCLUSION: Findings suggest the importance of a dyadic perspective and a gradual increase in people with stroke and carers' active engagement. Professionals' approach throughout rehabilitation should be modified according to people with stroke and carers' changing needs and expectations.IMPLICATIONS FOR REHABILITATIONDivergence in perspectives about priorities and goals between the person with stroke their carers and healthcare professionals can lead to the creation of different agendas within rehabilitation.An open dialogue and decision-making process that involves both the person with stroke and carers is highly recommended for the identification of shared rehabilitation goals and to support ongoing recovery post discharge.A tailored approach to rehabilitation is required which focusses on shared priorities and includes individual or collective support for the person with stroke and their carers.Ongoing consultation about the desires of the person with stroke about rehabilitation, priorities and goals is important in order to tailor the professional approach to the stage individuals are at with their coping and adjustment post stroke

Inhibitory action of phenothiazinium dyes against Neospora caninum.

Neospora caninum is an Apicomplexan parasite related to important losses in livestock, causing abortions and decreased fertility in affected cows. Several chemotherapeutic strategies have been developed for disease control; however, no commercial treatment is available. Among the candidate drugs against neosporosis, phenothiazinium dyes, offer a low cost-efficient approach to parasite control. We report the anti-parasitic effects of the phenothiaziums Methylene Blue (MB), New Methylene Blue (NMB), 1,9-Dimethyl Methylene Blue (DMMB) and Toluidine Blue O (TBO) on N. caninum, using in vitro and in vivo models. The dyes inhibited parasite proliferation at nanomolar concentrations (0.019-1.83 μM) and a synergistic effect was achieved when Methylene Blue was combined with New Methylene Blue (Combination Index = 0.84). Moreover, the phenothiazinium dyes improved parasite clearance when combined with Pyrimethamine (Pyr). Combination of Methylene Blue + 1,9-Dimethyl Methylene Blue demonstrated superior efficacy compared to Pyrimethamine based counterparts in an in vivo model of infection. We also observed that Methylene Blue, New Methylene Blue and 1,9-Dimethyl Methylene Blue increased by 5000% the reactive oxygen species (ROS) levels in N. caninum tachyzoites. Phenothiazinium dyes represent an accessible group of candidates with the potential to compound future formulations for neosporosis control

Surgical Determinants of Patient-Reported Outcomes following Postmastectomy Reconstruction in Women with Breast Cancer.

This national prospective cohort study compared the patient-reported outcomes of breast cancer patients undergoing postmastectomy autologous reconstruction to those who had breast implants, in terms of aesthetic appearance; levels of psychological, physical, and sexual well-being; and overall satisfaction. Of 5063 women who underwent immediate reconstruction (n = 3349) or delayed reconstruction (n = 1714) between January 1, 2008, and March 31, 2009, in England, 2923 women who gave informed consent were sent validated, procedure-specific, 18-month follow-up questionnaires. Outcome scale scores ranged from 0 (poor) to 100 (excellent); multiple linear regression was used to adjust scores for patient and treatment characteristics. Two thousand two hundred eighty-nine women (78 percent) returned completed questionnaires (immediate reconstruction, n = 1528; delayed reconstruction, n = 761). For immediate reconstruction, mean overall satisfaction scores for the various techniques ranged from 67 to 85 (median, 67 to 93). For delayed reconstruction, mean overall satisfaction scores ranged from 70 to 85 (median, 75 to 100). For both groups, similar gradients were observed for the other outcome scales across techniques. Reconstruction using patients' own tissues tended to have higher mean adjusted scores compared with those techniques using implants alone (p < 0.0001 for aesthetic appearance, psychological well-being, sexual well-being, and satisfaction with outcomes for immediate and delayed reconstruction groups). Women who underwent autologous reconstruction tended to report greater satisfaction than those who underwent implant reconstruction. These results can inform patients of the anticipated outcomes of their selected surgery, but further research is required to confirm whether autologous reconstruction is superior in general. Therapeutic, II

Effects of high fat diet on salivary alpha-amylase serum parameters and food consumption in rats

Salivary a-amylase, a major protein in saliva, has been described as a marker for sympathetic nervous system activity, hence for metabolic energy balance. In this context, its expression in overweight and obesity is of interest. Rats fed with a diet enriched with sunflower oil differentially gained weight yielding two subgroups according to their susceptibility (OP) or resistance (OR) to obesity. Elevated plasmatic levels of leptin in the OP subgroup and altered plasmatic lipid profiles (lower triglycerides and higher total choles- terol/HDL ratio compared to controls) in OR subgroup were observed. Animals from OP subgroup presented higher a-amylase expression and activity even prior to the dietary treatment, suggesting that this salivary protein may constitute a putative indicator of susceptibility for fat tissue accumulation. After 18 weeks of high-fat diet consumption, salivary a-amylase levels did not significantly changed in OP subgroup, but increased 3-fold in OR subgroup. The raise of a-amylase for the latter might represent an adaptation to lower starch intake. These results suggest that salivary a-amylase secretion might be useful to predict susceptibility for weight gain induced by high-fat diet consumption.This paper is funded by FEDER Funds through the Operational Programme for Competitiveness Factors-COMPETE and National Funds through FCT-Foundation for Science and Technology under the Strategic Projects PEst-C/AGR/UI01, PEst-OE/AGR/ UI0115/2014, 15/2011, PEst-C/SAU/LA0001/2011 and PEst-C/QUI/ UI0062/2011. Authors acknowledge also the financial support from the Portuguese Science Foundation (FCT) in the form of Post- Doctoral grant (SFRH/BPD/63240/2009) of Elsa Lamy. The Portu- guese Science Foundation (FCT) played no role in the develop- ment of the present work or upon its submission for publication