Induction of circadian conidiation by rubidium chloride

Induction of circadian conidiation by rubidium chlorid

Complex folding and misfolding effects of deer-specific amino acid substitutions in the β2-α2 loop of murine prion protein

The β2–α2 loop of PrPC is a key modulator of disease-associated prion protein misfolding. Amino acids that differentiate mouse (Ser169, Asn173) and deer (Asn169, Thr173) PrPC appear to confer dramatically different structural properties in this region and it has been suggested that amino acid sequences associated with structural rigidity of the loop also confer susceptibility to prion disease. Using mouse recombinant PrP, we show that mutating residue 173 from Asn to Thr alters protein stability and misfolding only subtly, whilst changing Ser to Asn at codon 169 causes instability in the protein, promotes oligomer formation and dramatically potentiates fibril formation. The doubly mutated protein exhibits more complex folding and misfolding behaviour than either single mutant, suggestive of differential effects of the β2–α2 loop sequence on both protein stability and on specific misfolding pathways. Molecular dynamics simulation of protein structure suggests a key role for the solvent accessibility of Tyr168 in promoting molecular interactions that may lead to prion protein misfolding. Thus, we conclude that ‘rigidity’ in the β2–α2 loop region of the normal conformer of PrP has less effect on misfolding than other sequence-related effects in this region

The POM Monoclonals: A Comprehensive Set of Antibodies to Non-Overlapping Prion Protein Epitopes

PrPSc, a misfolded and aggregated form of the cellular prion protein PrPC, is the only defined constituent of the transmissible agent causing prion diseases. Expression of PrPC in the host organism is necessary for prion replication and for prion neurotoxicity. Understanding prion diseases necessitates detailed structural insights into PrPC and PrPSc. Towards this goal, we have developed a comprehensive collection of monoclonal antibodies denoted POM1 to POM19 and directed against many different epitopes of mouse PrPC. Three epitopes are located within the N-terminal octarepeat region, one is situated within the central unstructured region, and four epitopes are discontinuous within the globular C-proximal domain of PrPC. Some of these antibodies recognize epitopes that are resilient to protease digestion in PrPSc. Other antibodies immunoprecipitate PrPC, but not PrPSc. A third group was found to immunoprecipitate both PrP isoforms. Some of the latter antibodies could be blocked with epitope-mimicking peptides, and incubation with an excess of these peptides allowed for immunochromatography of PrPC and PrPSc. Amino-proximal antibodies were found to react with repetitive PrPC epitopes, thereby vastly increasing their avidity. We have also created functional single-chain miniantibodies from selected POMs, which retained the binding characteristics despite their low molecular mass. The POM collection, thus, represents a unique set of reagents allowing for studies with a variety of techniques, including western blotting, ELISA, immunoprecipitation, conformation-dependent immunoassays, and plasmon surface plasmon resonance-based assays

Berberine, a popular dietary supplement for human and animal health: Quantitative research literature analysis a review

Berberine is an alkaloid with a wide range of reported beneficial health effects. The current work provides an extensive literature analysis on berberine. Bibliometric data were identified by means of the search string TOPIC=(berberin* OR umbellatine*), which yielded 5,547 publications indexed in the Web of Science Core Collection electronic database. The VOSviewer software generated bubble maps to visualize semantic terms with citation results. The ratio of original articles to reviews was 13.6:1. The literature has been growing more quickly since the 2010s. Major contributing countries were China, the United States, India, Japan, and South Korea. Most of the publications appeared in journals specialized in pharmacology pharmacy, biochemistry molecular biology, chemistry, and plant science. Some of the frequently mentioned chemicals/chemical classes were alkaloid, palmatine, jatrorrhizine, coptisine, isoquinoline, and sanguinarine. The prevalent medical conditions under investigation included Alzheimers disease, cancer, diabetes, and obesity.Acknowledge the support by the Polish KNOW (LeadingNational Research Centre) Scientific Consortium “Healthy Animal-Safe Food,” decision of Ministry of Science and Higher Education No. 05-1/KNOW2/2015 and the European Union under the European Regional Development Fund (Homing/2017-4/41). Antoni Sureda has been supported by the Institute of Health Carlos III (Project CIBEROBN CB12/03/30038). Joanna Feder-Kubis was financed by the Polish Ministry of Science and Higher Education for the Faculty of Chemistry of Wrocław University of Science and Technology.info:eu-repo/semantics/publishedVersio

A Classification Method Based on Principal Components of SELDI Spectra to Diagnose of Lung Adenocarcinoma

Lung cancer is the leading cause of cancer death worldwide, but techniques for effective early diagnosis are still lacking. Proteomics technology has been applied extensively to the study of the proteins involved in carcinogenesis. In this paper, a classification method was developed based on principal components of surface-enhanced laser desorption/ionization (SELDI) spectral data. This method was applied to SELDI spectral data from 71 lung adenocarcinoma patients and 24 healthy individuals. Unlike other peak-selection-based methods, this method takes each spectrum as a unity. The aim of this paper was to demonstrate that this unity-based classification method is more robust and powerful as a method of diagnosis than peak-selection-based methods.The results showed that this classification method, which is based on principal components, has outstanding performance with respect to distinguishing lung adenocarcinoma patients from normal individuals. Through leaving-one-out, 19-fold, 5-fold and 2-fold cross-validation studies, we found that this classification method based on principal components completely outperforms peak-selection-based methods, such as decision tree, classification and regression tree, support vector machine, and linear discriminant analysis.The classification method based on principal components of SELDI spectral data is a robust and powerful means of diagnosing lung adenocarcinoma. We assert that the high efficiency of this classification method renders it feasible for large-scale clinical use

Solution Structure and Dynamics of the I214V Mutant of the Rabbit Prion Protein

Background: The conformational conversion of the host-derived cellular prion protein (PrP C) into the disease-associated scrapie isoform (PrP Sc) is responsible for the pathogenesis of transmissible spongiform encephalopathies (TSEs). Various single-point mutations in PrP C s could cause structural changes and thereby distinctly influence the conformational conversion. Elucidation of the differences between the wild-type rabbit PrP C (RaPrP C) and various mutants would be of great help to understand the ability of RaPrP C to be resistant to TSE agents. Methodology/Principal Findings: We determined the solution structure of the I214V mutant of RaPrP C (91–228) and detected the backbone dynamics of its structured C-terminal domain (121–228). The I214V mutant displays a visible shift of surface charge distribution that may have a potential effect on the binding specificity and affinity with other chaperones. The number of hydrogen bonds declines dramatically. Urea-induced transition experiments reveal an obvious decrease in the conformational stability. Furthermore, the NMR dynamics analysis discloses a significant increase in the backbone flexibility on the pico- to nanosecond time scale, indicative of lower energy barrier for structural rearrangement. Conclusions/Significance: Our results suggest that both the surface charge distribution and the intrinsic backbone flexibility greatly contribute to species barriers for the transmission of TSEs, and thereby provide valuable hints fo

Stab Injury to the Preauricular Region With Laceration of the External Carotid Artery Without Involvement of the Facial Nerve: a Case Report

BACKGROUND: Open injuries to the face involving the external carotid artery are uncommon. These injuries are normally associated with laceration of the facial nerve because this nerve is more superficial than the external carotid artery. Hence, external carotid artery lesions are usually associated with facial nerve dysfunction. We present an unusual case report in which the patient had an injury to this artery with no facial nerve compromise. CASE PRESENTATION: A 25-year-old Portuguese man sustained a stab wound injury to his right preauricular region with a broken glass. Immediate profuse bleeding ensued. Provisory tamponade of the wound was achieved at the place of aggression by two off-duty doctors. He was initially transferred to a district hospital, where a large arterial bleeding was observed and a temporary compressive dressing was applied. Subsequently, the patient was transferred to a tertiary hospital. At admission in the emergency room, he presented a pulsating lesion in the right preauricular region and slight weakness in the territory of the inferior buccal branch of the facial nerve. The physical examination suggested an arterial lesion superficial to the facial nerve. However, in the operating theater, a section of the posterior and lateral flanks of the external carotid artery inside the parotid gland was identified. No lesion of the facial nerve was observed, and the external carotid artery was repaired. To better understand the anatomical rationale of this uncommon clinical case, we dissected the preauricular region of six cadavers previously injected with colored latex solutions in the vascular system. A small triangular space between the two main branches of division of the facial nerve in which the external carotid artery was not covered by the facial nerve was observed bilaterally in all cases. CONCLUSIONS: This clinical case illustrates that, in a preauricular wound, the external carotid artery can be injured without facial nerve damage. However, no similar description was found in the reviewed literature, which suggests that this must be a very rare occurrence. According to the dissection study performed, this is due to the existence of a triangular space between the cervicofacial and temporofacial nerve trunks in which the external carotid artery is not covered by the facial nerve or its branches.info:eu-repo/semantics/publishedVersio

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)