Cytochrome oxidase subunit VI of Trypanosoma brucei is imported without a cleaved presequence and is developmentally regulated at both RNA and protein levels

Mitochondrial respiration in the African trypanosome undergoes dramatic developmental stage regulation. This requires co-ordinated control of components encoded by both the nuclear genome and the kinetoplast, the unusual mitochondrial genome of these parasites. As a model for understanding the co-ordination of these genomes, we have examined the regulation and mitochondrial import of a nuclear-encoded component of the cytochrome oxidase complex, cytochrome oxidase subunit VI (COXVI). By generating transgenic trypanosomes expressing intact or mutant forms of this protein, we demonstrate that COXVI is not imported using a conventional cleaved presequence and show that sequences at the N-terminus of the protein are necessary for correct mitochondrial sorting. Analyses of endogenous and transgenic COXVI mRNA and protein expression in parasites undergoing developmental stage differentiation demonstrates a temporal order of control involving regulation in the abundance of, first, mRNA and then protein. This represents the first dissection of the regulation and import of a nuclear-encoded protein into the cytochrome oxidase complex in these organisms, which were among the earliest eukaryotes to possess a mitochondrion

The Role of Deontic Logic in the Specification of Information Systems

In this paper we discuss the role that deontic logic plays in the specification of information systems, either because constraints on the systems directly concern norms or, and even more importantly, system constraints are considered ideal but violable (so-called `soft¿ constraints).\ud To overcome the traditional problems with deontic logic (the so-called paradoxes), we first state the importance of distinguishing between ought-to-be and ought-to-do constraints and next focus on the most severe paradox, the so-called Chisholm paradox, involving contrary-to-duty norms. We present a multi-modal extension of standard deontic logic (SDL) to represent the ought-to-be version of the Chisholm set properly. For the ought-to-do variant we employ a reduction to dynamic logic, and show how the Chisholm set can be treated adequately in this setting. Finally we discuss a way of integrating both ought-to-be and ought-to-do reasoning, enabling one to draw conclusions from ought-to-be constraints to ought-to-do ones, and show by an example the use(fulness) of this

Technical Note: Method to correlate whole‐specimen histopathology of radical prostatectomy with diagnostic MR imaging

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134778/1/mp1016.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134778/2/mp1016_am.pd

Limitations of Prostate Biopsy in Detection of Cribriform and Intraductal Prostate Cancer

Funding Information: Acknowledgments: Rui M. Bernardino is supported by Fundacao para a Ciencia e a Tecnologia (2022.13386.BD). Publisher Copyright: © 2023 European Association of UrologyBackground: The presence of cribriform morphology and intraductal carcinoma (IDC) in prostate biopsies and radical prostatectomy specimens is an adverse prognostic feature that can be used to guide treatment decisions. Objective: To assess how accurately biopsies can detect cribriform morphology and IDC cancer by examining matched biopsy and prostatectomy samples. Design, setting, and participants: Patients who underwent radical prostatectomy at The Princess Margaret Cancer Centre between January 2015 and December 2022 and had cribriform morphology and/or IDC in the surgical specimen were included in the study. Outcome measurements and statistical analysis: We used detection sensitivity to evaluate the level of agreement between biopsy and prostatectomy samples regarding the presence of cribriform morphology and IDC. Results and limitations: Of the 287 men who underwent radical prostatectomy, 241 (84%) had cribriform morphology and 161 (56%) had IDC on final pathology. The sensitivity of prostate biopsy, using radical prostatectomy as the reference, was 42.4% (95% confidence interval [CI] 36–49%) for detection of cribriform morphology and 44.1% (95% CI 36–52%) for detection of IDC. The sensitivity of prostate biopsy for detection of either IDC or cribriform morphology was 52.5% (95% CI 47–58%). Among patients who underwent multiparametric magnetic resonance imaging–guided biopsies, the sensitivity was 54% (95% CI 39–68%) for detection of cribriform morphology and 37% (95% CI 19–58%) for detection of IDC. Conclusions: Biopsy has low sensitivity for detecting cribriform morphology and IDC. These limitations should be incorporated into clinical decision-making. Biomarkers for better detection of these histological patterns are needed. Patient summary: Prostate biopsy is not an accurate method for detecting two specific types of prostate cancer cells, called cribriform pattern and intraductal prostate cancer, which are associated with unfavorable prognosis.proofepub_ahead_of_prin

Подсистема автономного программно-аппаратного комплекса для индуктивного долгосрочного прогноза осредненных значений метеопараметров

The research of the inductive method of long-term (forestalling to 0,5 year) prognosis of average decade air s temperature on the basis of principle of analogies was executed and it s sufficient was shown. The research of the offered approach was also conducted: in the base of spatial models without principle of analogies; in the polynomial harmonic base; the analysis of middle quality of the inductive prognostic method for cases of the analogue principle usage and without it

The Suppressor of AAC2 Lethality SAL1 Modulates Sensitivity of Heterologously Expressed Artemia ADP/ATP Carrier to Bongkrekate in Yeast

The ADP/ATP carrier protein (AAC) expressed in Artemia franciscana is refractory to bongkrekate. We generated two strains of Saccharomyces cerevisiae where AAC1 and AAC3 were inactivated and the AAC2 isoform was replaced with Artemia AAC containing a hemagglutinin tag (ArAAC-HA). In one of the strains the suppressor of ΔAAC2 lethality, SAL1, was also inactivated but a plasmid coding for yeast AAC2 was included, because the ArAACΔsal1Δ strain was lethal. In both strains ArAAC-HA was expressed and correctly localized to the mitochondria. Peptide sequencing of ArAAC expressed in Artemia and that expressed in the modified yeasts revealed identical amino acid sequences. The isolated mitochondria from both modified strains developed 85% of the membrane potential attained by mitochondria of control strains, and addition of ADP yielded bongkrekate-sensitive depolarizations implying acquired sensitivity of ArAAC-mediated adenine nucleotide exchange to this poison, independent from SAL1. However, growth of ArAAC-expressing yeasts in glycerol-containing media was arrested by bongkrekate only in the presence of SAL1. We conclude that the mitochondrial environment of yeasts relying on respiratory growth conferred sensitivity of ArAAC to bongkrekate in a SAL1-dependent manner. © 2013 Wysocka-Kapcinska et al

Why Give Birth in Health Facility? Users' and Providers' Accounts of Poor Quality of Birth Care in Tanzania.

In Tanzania, half of all pregnant women access a health facility for delivery. The proportion receiving skilled care at birth is even lower. In order to reduce maternal mortality and morbidity, the government has set out to increase health facility deliveries by skilled care. The aim of this study was to describe the weaknesses in the provision of acceptable and adequate quality care through the accounts of women who have suffered obstetric fistula, nurse-midwives at both BEmOC and CEmOC health facilities and local community members. Semi-structured interviews involving 16 women affected by obstetric fistula and five nurse-midwives at maternity wards at both BEmOC and CEmOC health facilities, and Focus Group Discussions with husbands and community members were conducted between October 2008 and February 2010 at Comprehensive Community Based Rehabilitation in Tanzania and Temeke hospitals in Dar es Salaam, and Mpwapwa district in Dodoma region. Health care users and health providers experienced poor quality caring and working environments in the health facilities. Women in labour lacked support, experienced neglect, as well as physical and verbal abuse. Nurse-midwives lacked supportive supervision, supplies and also seemed to lack motivation. There was a consensus among women who have suffered serious birth injuries and nurse midwives staffing both BEmOC and CEmOC maternity wards that the quality of care offered to women in birth was inadequate. While the birth accounts of women pointed to failure of care, the nurses described a situation of disempowerment. The bad birth care experiences of women undermine the reputation of the health care system, lower community expectations of facility birth, and sustain high rates of home deliveries. The only way to increase the rate of skilled attendance at birth in the current Tanzanian context is to make facility birth a safer alternative than home birth. The findings from this study indicate that there is a long way to go

The 2019 International Society of Urological Pathology (ISUP) Consensus Conference on Grading of Prostatic Carcinoma

Five years after the last prostatic carcinoma grading consensus conference of the International Society of Urological Pathology (ISUP), accrual of new data and modification of clinical practice require an update of current pathologic grading guidelines. This manuscript summarizes the proceedings of the ISUP consensus meeting for grading of prostatic carcinoma held in September 2019, in Nice, France. Topics brought to consensus included the following: (1) approaches to reporting of Gleason patterns 4 and 5 quantities, and minor/tertiary patterns, (2) an agreement to report the presence of invasive cribriform carcinoma, (3) an agreement to incorporate intraductal carcinoma into grading, and (4) individual versus aggregate grading of systematic and multiparametric magnetic resonance imaging-targeted biopsies. Finally, developments in the field of artificial intelligence in the grading of prostatic carcinoma and future research perspectives were discussed

Use pattern of maternal health services and determinants of skilled care during delivery in Southern Tanzania: implications for achievement of MDG-5 targets

Almost two decades since the initiation of the Safe motherhood Initiative, Maternal Mortality is still soaring high in most developing countries. In 2000 WHO estimated a life time risk of a maternal death of 1 in 16 in Sub- Saharan Africa while it was only 1 in 2800 in developed countries. This huge discrepancy in the rate of maternal deaths is due to differences in access and use of maternal health care services. It is known that having a skilled attendant at every delivery can lead to marked reductions in maternal mortality. For this reason, the proportion of births attended by skilled health personnel is one of the indicators used to monitor progress towards the achievement of the MDG-5 of improving maternal health. Cross sectional study which employed quantitative research methods. We interviewed 974 women who gave birth within one year prior to the survey. Although almost all (99.8%) attended ANC at least once during their last pregnancy, only 46.7% reported to deliver in a health facility and only 44.5% were assisted during delivery by a skilled attendant. Distance to the health facility (OR = 4.09 (2.72-6.16)), discussion with the male partner on place of delivery (OR = 2.37(1.75-3.22)), advise to deliver in a health facility during ANC (OR = 1.43 (1.25-2.63)) and knowledge of pregnancy risk factors (OR 2.95 (1.65-5.25)) showed significant association with use of skilled care at delivery even after controlling for confounding factors. Use of skilled care during delivery in this district is below the target set by ICPD + of attaining 80% of deliveries attended by skilled personnel by 2005. We recommend the following in order to increase the pace towards achieving the MDG targets: to improve coverage of health facilities, raising awareness for both men and women on danger signs during pregnancy/delivery and strengthening counseling on facility delivery and individual birth preparedness