Mitochondrial protein import

The transport of nuclear-encoded proteins from the cytosol into mitochondria is mediated by targeting (signal) sequences present on precursor forms. Most precursors of the mitochondrial matrix possess amino-terminal signals which characteristically contain hydroxylated and basic amino acids and lack acidic residues. With a minority of precursor proteins, internal sequence motifs can direct proteins to the mitochondria (Pfanner, N., Hoeben, P., Tropschug, M. and Neupert, W. (1987) J. Biol. Chem. 262, 14851–14854). The presence of a mitochondrial targeting sequence alone, however, is not sufficient for specific targeting to the organelle and further to the various subcompartments. There is the need for components which recognise the targeting sequences and others which keep the precursor protein in a translocation-competent form. Beyond the recognition step, components are required which mediate translocation across the mitochondrial membranes. Mitochondria possess two translocation machineries, one in the outer membrane and one in the inner membrane. The matrix space harbors a number of factors which participate in the import of proteins, in their unfolding and folding. Energy is required at several steps of these processes

XDJ1, a gene encoding a novel non-essential DnaJ homologue from Saccharomyces cerevisiae

The gene encoding a novel DnaJ-like protein, termed Xdj1, has been identified by amplification of Saccharomyces cerevisiae genomic DNA. An open reading frame of 1380 bp was detected. Disruption of XDJ1 did not yield any detectable new phenotype. A double-deletion strain containing a disruption of both XDJ1 and YDJ1, another gene coding for a DnaJ-like protein, was still viable. Under a variety of growth conditions, no XDJ1 transcripts could be detected by Northern blot analysis and no translation product was found by immunoblotting with antibody against Xdj1 produced in Escherichia coli. Thus, XDJ1 is either expressed only under very specific conditions or represents a silent gene

Response order effects in dichotomous questions: the impact of administration mode

Die Autoren untersuchen primäre und Folge-Effekte auf das Antwortverhalten von Befragten. Dabei wird davon ausgegangen, daß die Positionierung der Antwortkategorien bei dichotomen Fragestellungen die Beantwortung beeinflußt. Datenbasis sind split-ballot Experimente, die seit den 50er Jahren vom Institut Allensbach durchgeführt worden sind. Ihnen liegt eine Quota-Auswahl von 2000 erwachsenen Personen in der Bundesrepublik zugrunde. Es zeigt sich eine begründbare Kohärenz im Hinblick auf das Auftreten von Effekten. Unter der Annahme, daß keine unplausible Antwortkategorie vorgelegt wird, läßt sich ein Zusammenhang zwischen der Wahl und dem Wahrnehmungsgrad einer Antwortkategorie feststellen, der vom Format der Präsentation abhängt. Antworteffekte können ausgeschaltet werden, wenn sie durch eine kognitive Beeinflußung, die von einer übergeordneten Fragestellung ausgeht. (HN

Seizures and prolonged recovery from general anaesthesia in a horse with guttural pouch mycosis undergoing bilateral arterial coil embolisation

An 11-year-old Holstein mare was referred after profuse bilateral epistaxis due to fungal plaques. Clinical evaluation was unremarkable except for mild tachycardia. General anaesthesia was induced for coil embolisation of the left internal carotid artery, right external carotid and maxillary arteries. Under anaesthesia, cardiorespiratory stability was ensured, and six coils were deployed under fluoroscopy, whereas three previously deployed coils were found. During recovery from anaesthesia, generalised seizures, fast horizontal nystagmus and a breath-holding breathing pattern were evident. Diazepam and medetomidine were administered, but the seizures resumed shortly after. After the administration of hypertonic saline solution and hydrocortisone, the seizures ceased. However, the horse remained unresponsive for 3 hours despite supportive care consisting of oxygen, glucose, fluid therapy and warming. Although a poor prognosis was presumed, the horse recovered after one attempt, 180 minutes after isoflurane cessation. The present case report highlights the importance of adequate support during recovery from anaesthesia

Heat strengthening of lead-tin bronze alloyed with nickel

Investigate the process of thermal hardening of bronze without heat treatment. Determined phase, which is the cause for age-hardening of the nickel bronze alloy by heat strengthening

Response order effects in long lists: primacy, recency, and asymetric contrast effects

Die Autoren untersuchen primäre, Folge- und asymmetrische Kontrast-Effekte auf das Antwortverhalten von Befragten. Es wird davon ausgegangen, daß die Positionierung von alternativen Antwortkategorien (hier fünf alternative Kategorien) innerhalb einer Fragestellung die Beantwortung beeinflußt. Datenbasis sind split-ballot Experimente, die seit den 50er Jahren vom Institut Allensbach durchgeführt worden sind. Darüber hinaus sind Ergebnisse einer ähnlich angelegten früheren Studie, die Effekte in Fragestellungen mit zwei oder drei Antwortkategorien mißt, berücksichtigt. Hypothetisch wird davon ausgegangen, daß die Berücksichtigung einer Antwortalternative von deren Wahrnehmungsgrad abhängt, der durch seine Positionierung gesteuert werden kann. Bei mündlicher Fragestellung werden die letzten Antwortkategorien häufiger gewählt, bei schriftlich vorliegender Fragestellung die ersten. Andere Bedingungen, die Auswahlprozesse unabhängig von der Positionierung der Antwortkategorien hervorrufen, machen die Annahmen über den angenommenen Einfluß der Positionierung unwirksam. Insgesamt decken Auswahlprozesse Mängel in der Argumentation auf und zeigen damit die Unzulänglichkeit einer bestimmten Antwortkategorie. Unabhängig von den Wahrnehmungsprozessen kann der Gehalt bestimmter Antwortkategorien die Kriterien beeinflussen, die Befragte bei Werturteilen anlegen. (HN

Rating scales: numeric values may change the meaning of scale labels

Unter der Fragestellung, inwieweit die Ergebnisse bei Befragungen von der Skalierung und den numerischen Werten der Skalierung abhängig sind, wurden Vergleichsbefragungen zum Lebenserfolg durchgeführt (Fragestellung: 'Wie erfolgreich waren Sie bisher in Ihrem Leben?'). Bei der ersten Versuchsanordnung wurde die Skalierung von 0 ('überhaupt nicht erfolgreich') bis 10 ('außerordentlich erfolgreich') gewählt, bei der zweiten Anordnung wurde die Skalierung von -5 bis +5 gewählt. Es stellte sich heraus, daß im ersten Fall 34 Prozent der Befragten einen Wert zwischen 0 und 5 wählten, während im zweiten Fall lediglich 13 Prozent den äquivalenten Werten - also im Bereich -5 bis 0 - zustimmten. Es zeigte sich damit, daß numerische Werte die Interpretation von Skalierungen subjektiv beeinflussen. (psz)'Three experiments indicate that the numeric values provided as part of a rating scale may influence resprondents' interpretation of a endpoint labels. In experiment 1, a representative sample of German adults rated their success in life along an 11-point rating scale, with the endpoints labeled 'not at all successful' and 'extremely successful'. When the numeric values ranged from 0 ('not at all successful') to 10 ('extremely successful'), 34 percent of the respondents endorsed values between 0 and 5. However, only 13 percent endorsed formally equivalent values between -5 and 0, when the scale ranged from -5 ('not at all successful') to +5 ('extremely successful'). Experiment 2 provided an extended conceptual replication of this finding, and experiment 3 demonstrates that recipients of a respondent's report draw different inferences from formally equivalent, but numerically different values. In combination, the findings indicate that respondents use the numeric values to disambiguate the meaning of scale labels, resulting in different interpretations and, accordingly, different subjective scale anchors.' (author's abstract

Low-density lipoprotein cholesterol goal attainment in patients with clinical evidence of familial hypercholesterolemia and elevated Lp(a)

Background: Although potent lipid-lowering therapies are available, patients commonly fall short of recommended low-density lipoprotein cholesterol (LDL-C) levels. The aim of this study was to examine the relationship between familial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] and LDL-C goal attainment, as well as the prevalence and severity of coronary artery disease (CAD). Moreover, we characterized patients failing to meet recommended LDL-C goals. Methods: We performed a cross-sectional analysis in a cohort of patients undergoing cardiac catheterization. Clinical FH was determined by the Dutch Clinical Lipid Network Score, and Lp(a) >= 50 mg/dL (approximate to 107 nmol/L) was considered elevated. Results: A total of 838 participants were included. Overall, the prevalence of CAD was 72%, and 62% received lipid-lowering treatment. The prevalence of clinical FH (probable and definite FH) was 4%, and 19% had elevated Lp(a) levels. With 35%, LDL-C goal attainment was generally poor. Among the participants with clinical FH, none reached their LDL-C target. Among patients with elevated Lp(a), LDL-C target achievement was only 28%. The prevalence and severity of CAD were higher in participants with clinical FH (86% prevalence) and elevated Lp(a) (80% prevalence). Conclusion: Most participants failed to meet their individual LDL-C goals according to the ESC 2016 and 2019 guidelines. In particular, high-risk patients with clinical FH or elevated Lp(a) rarely met their target for LDL-C. The identification of these patients and more intense treatment approaches are crucial for the improvement of CAD primary and secondary prevention

The mature part of proNGF induces the structure of its pro-peptide

AbstractHuman nerve growth factor (NGF) belongs to the structural family of cystine knot proteins, characterized by a disulfide pattern in which one disulfide bond threads through a ring formed by a pair of two other disulfides connecting two adjacent β-strands. Oxidative folding of NGF revealed that the pro-peptide of NGF stimulates in vitro structure formation. In order to learn more about this folding assisting protein fragment, a biophysical analysis of the pro-peptide structure has been performed. While proNGF is a non-covalent homodimer, the isolated pro-peptide is monomeric. No tertiary contacts stabilize the pro-peptide in its isolated form. In contrast, the pro-peptide appears to be structured when bound to the mature part. The results presented here demonstrate that the mature part stabilizes the structure in the pro-peptide region. This is the first report that provides a biophysical analysis of a pro-peptide of the cystine knot protein family