UPF1, a Conserved Nonsense-Mediated mRNA Decay Factor, Regulates Cyst Wall Protein Transcripts in Giardia lamblia

The Giardia lamblia cyst wall is required for survival outside the host and infection. Three cyst wall protein (cwp) genes identified to date are highly up-regulated during encystation. However, little is known of the molecular mechanisms governing their gene regulation. Messenger RNAs containing premature stop codons are rapidly degraded by a nonsense-mediated mRNA decay (NMD) system to avoid production of non-functional proteins. In addition to RNA surveillance, NMD also regulates thousands of naturally occurring transcripts through a variety of mechanisms. It is interesting to know the NMD pathway in the primitive eukaryotes. Previously, we have found that the giardial homologue of a conserved NMD factor, UPF1, may be functionally conserved and involved in NMD and in preventing nonsense suppression. In this study, we tested the hypothesis that NMD factors can regulate some naturally occurring transcripts in G. lamblia. We found that overexpression of UPF1 resulted in a significant decrease of the levels of CWP1 and cyst formation and of the endogenous cwp1-3, and myb2 mRNA levels and stability. This indicates that NMD could contribute to the regulation of the cwp1-3 and myb2 transcripts, which are key to G. lamblia differentiation into cyst. Interestingly, we also found that UPF1 may be involved in regulation of eight other endogenous genes, including up-regulation of the translation elongation factor gene, whose product increases translation which is required for NMD. Our results indicate that NMD factor could contribute to the regulation of not only nonsense containing mRNAs, but also mRNAs of the key encystation-induced genes and other endogenous genes in the early-diverging eukaryote, G. lamblia

Lagrangian Fibrations with designed singular fibres

We study Lagrangian Fibrations with designed singular fibers. The idea is to construct a K3 surface X as a minimal resolution of the singularities of a double cover Y of the plane branched along a reduced but possibly reducible singular sextic Σ. Moreover, we assume that Σ has at worst A-D-E singularities. This freeness of choosing Σ allows us to construct many examples of singular fibres with various singularities. We find an explicit description of the singular fibers of the Lagrangian Fibrations f : M_X(0,2H,χ) → |2H|. The results shed also some light on the correlation between the degree of the discriminant divisor ∆ and the topology of the corresponding moduli space.Wir studieren Lagrangefaserungen mit vorgegebenen singulaeren Fasern. Die Idee besteht darin, eine K3-Flaeche X als minimale Aufloesung von Singularitaeten einer 2 : 1 Ueberlagerung zu konstruieren, die entlang einer reduzierten, aber moeglicherweise reduziblen singulaeren Sextik Σ verzweigt ist. Außerdem nehmen wir an, dass Σ hoechstens A-D-E Singularitaeten besitzt. Diese Freiheit bei der Wahl von Σ erlaubt es uns, viele Beispiele von singulaeren Fasern mit verschiedenen Singularitaeten zu konstruieren. Wir finden eine explizite Beschreibung der singulaeren Fasern der Lagrangefaserung f : M_X(0,2H,χ) → |2H|. Die Ergebnisse beleuchten die Korrelation zwischen dem Grad des Diskriminantendivisors ∆ und der Topologie des zugrundeliegenden Modulraumes

Inter-rater reliability of the Full Outline of UnResponsiveness score and the Glasgow Coma Scale in critically ill patients : a prospective observational study

The Glasgow Coma Scale (GCS) is the most widely used scoring system for comatose patients in intensive care. Limitations of the GCS include the impossibility to assess the verbal score in intubated or aphasic patients, and an inconsistent inter-rater reliability. The FOUR (Full Outline of UnResponsiveness) score, a new coma scale not reliant on verbal response, was recently proposed. The aim of the present study was to compare the inter-rater reliability of the GCS and the FOUR score among unselected patients in general critical care. A further aim was to compare the inter-rater reliability of neurologists with that of intensive care unit (ICU) staff

Role of Family Planning in Women With Multiple Sclerosis in Switzerland: Results of the Women With Multiple Sclerosis Patient Survey

<p>Background: Women of child bearing age with multiple sclerosis (MS) must carefully consider treatments when planning a family, since disease modifying drugs (DMDs) are contraindicated during pregnancy.</p><p>Objectives: This questionnaire-based study aimed to improve understanding of the effect of family planning on treatment decisions in female, Swiss MS patients.</p><p>Methods: Female patients with MS (aged 18–55 years) participated in the 26-question survey between September 2014 and August 2015. Information captured included patient background, family planning status, treatment course, and previous pregnancies.</p><p>Results: In total, 271 questionnaires distributed from 15 MS centres were returned for analysis. Of these, 250 (92.3%) participants received DMD therapy and 106 (39.1%) wanted children or were pregnant. Significantly more patients with a short-term plan to conceive within 2 years were treated with injectables (19/54) compared with those without a plan to conceive (19/108; p = 0.013). A proportionally greater number of women not planning to conceive took oral (34/108) or infusion therapies (41/108) compared with those with a short- (13/54 and 16/54, respectively) or medium-term (after 2 years or more; infusion therapy only, 14/44) plan to conceive.</p><p>Conclusion: The study highlights that pregnancy remains an important yet unresolved concern in the treatment of MS patients. Nearly all women received DMD treatment, and type of DMD treatment was influenced by family planning, with significantly more women with a short-term plan to conceive using injectables.</p

IgM deposits on skin nerves in anti-myelin-associated glycoprotein neuropathy.

Anti-myelin-associated glycoprotein (anti-MAG) neuropathy is a chronic demyelinating neuropathy with predominant involvement of large sensory fibers and deposits of IgM and complement on sural nerve myelinated fibers. We assessed the presence of IgM deposits on skin myelinated nerve fibers and the involvement of unmyelinated axons in anti-MAG neuropathy. Skin biopsies were performed in 14 patients with anti-MAG neuropathy, in 8 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and in 2 patients with IgM paraproteinemic neuropathy. Biopsies were taken at the proximal thigh in 20 patients, at the distal leg in 21 patients, at the proximal arm in 13 patients, and at the hand or fingertip in 10 patients. We found IgM deposits on dermal myelinated fibers in all anti-MAG neuropathy patients, with a greater prevalence at the distal site of the extremities. Deposits were located throughout the length of the fibers and at the paranodal loops. CIDP and IgM paraproteinemic neuropathies did not show any deposit of IgM. Anti-MAG neuropathy and CIPD patients showed a decrease in epidermal nerve fiber density reflecting an associated axonal loss. In anti-MAG neuropathy, both large- and small-diameter nerve fibers are affected, and specific deposits of IgM are found on skin myelinated nerve fibers

Scattered-wave-packet formalism with applications to barrier scattering and quantum transistors

The scattered wave formalism developed for a quantum subsystem interacting with reservoirs through open boundaries is applied to one- or two-dimensional barrier scattering and quantum transistors. The total wave function is divided into incident and scattered components. Markovian outgoing wave boundary conditions are imposed on the scattered or total wave function by either the ratio or polynomial methods. For barrier scattering problems, accurate time-dependent transmission probabilities are obtained through the integration of the modified time-dependent Schrodinger equations for the scattered wave function. For quantum transistors, the time-dependent transport is studied for a quantum wave packet propagating through the conduction channel of a field effect transistor. This study shows that the scattered wave formalism significantly reduces computational effort relative to other open boundary methods and demonstrates wide applications to quantum dynamical processes.Robert Welch Foundation F-0362Chemical Engineerin