The Musashi 1 Controls the Splicing of Photoreceptor-Specific Exons in the Vertebrate Retina

Alternative pre-mRNA splicing expands the coding capacity of eukaryotic genomes, potentially enabling a limited number of genes to govern the development of complex anatomical structures. Alternative splicing is particularly prevalent in the vertebrate nervous system, where it is required for neuronal development and function. Here, we show that photoreceptor cells, a type of sensory neuron, express a characteristic splicing program that affects a broad set of transcripts and is initiated prior to the development of the light sensing outer segments. Surprisingly, photoreceptors lack prototypical neuronal splicing factors and their splicing profile is driven to a significant degree by the Musashi 1 (MSI1) protein. A striking feature of the photoreceptor splicing program are exons that display a switch-like pattern of high inclusion levels in photoreceptors and near complete exclusion outside of the retina. Several ubiquitously expressed genes that are involved in the biogenesis and function of primary cilia produce highly photoreceptor specific isoforms through use of such “switchlike” exons. Our results suggest a potential role for alternative splicing in the development of photoreceptors and the conversion of their primary cilia to the light sensing outer segments

Cervical spine reposition errors after cervical flexion and extension

BACKGROUND: Upright head and neck position has been frequently applied as baseline for diagnosis of neck problems. However, the variance of the position after cervical motions has never been demonstrated. Thus, it is unclear if the baseline position varies evenly across the cervical joints. The purpose was to assess reposition errors of upright cervical spine. METHODS: Cervical reposition errors were measured in twenty healthy subjects (6 females) using video-fluoroscopy. Two flexion movements were performed with a 20 s interval, the same was repeated for extension, with an interval of 5 min between flexion and extension movements. Cervical joint positions were assessed with anatomical landmarks and external markers in a Matlab program. Reposition errors were extracted in degrees (initial position minus reposition) as constant errors (CEs) and absolute errors (AEs). RESULTS: Twelve of twenty-eight CEs (7 joints times 4 repositions) exceeded the minimal detectable change (MDC), while all AEs exceeded the MDC. Averaged AEs across the cervical joints were larger after 5 min’ intervals compared to 20 s intervals (p < 0.05). CONCLUSIONS: This is the first study to demonstrate single joint reposition errors of the cervical spine. The cervical spine returns to the upright positions with a 2° average absolute difference after cervical flexion and extension movements in healthy adults. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12891-017-1454-z) contains supplementary material, which is available to authorized users

The 2011 Eruption of the Recurrent Nova T Pyxidis; the Discovery, the Pre-eruption Rise, the Pre-eruption Orbital Period, and the Reason for the Long Delay

We report the discovery by M. Linnolt on JD 2455665.7931 (UT 2011 April 14.29) of the sixth eruption of the recurrent nova T Pyxidis. This discovery was made just as the initial fast rise was starting, so with fast notification and response by observers worldwide, the entire initial rise was covered (the first for any nova), and with high time resolution in three filters. The speed of the rise peaked at 9 mag/day, while the light curve is well fit over only the first two days by a model with a uniformly expanding sphere. We also report the discovery by R. Stubbings of a pre-eruption rise starting 18 days before the eruption, peaking 1.1 mag brighter than its long-time average, and then fading back towards quiescence 4 days before the eruption. This unique and mysterious behavior is only the fourth known anticipatory rise closely spaced before a nova eruption. We present 19 timings of photometric minima from 1986 to February 2011, where the orbital period is fast increasing with P/dot{P}=313,000 yrs. From 2008-2011, T Pyx had a small change in this rate of increase, so that the orbital period at the time of eruption was 0.07622950+-0.00000008 days. This strong and steady increase of the orbital period can only come from mass transfer, for which we calculate a rate of 1.7-3.5x10^-7 Mo/yr. We report 6116 magnitudes between 1890 and 2011, for an average B=15.59+-0.01 from 1967-2011, which allows for an eruption in 2011 if the blue flux is nearly proportional to the accretion rate. The ultraviolet-optical-infrared spectral energy distribution is well fit by a power law with flux proportional to nu^1.0, although the narrow ultraviolet region has a tilt with a fit of \nu^{1/3}. We prove that most of the T Pyx light is not coming from a disk, or any superposition of blackbodies, but rather is coming from some nonthermal source.Comment: ApJ submitted, 62 pages, 8 figures; much added data, updated analysi

Clinical management and outcome of adult patients with extracorporeal life support device–associated intracerebral hemorrhage—a neurocritical perspective and grading

Intracerebral hemorrhage (ICH) is a devastating complication in patients treated with extracorporeal membrane oxygenation (ECMO) due to respiratory or cardiac issues. Neurosurgical evaluation and management of such cases has only insufficiently been studied. We conducted a retrospective, cohort study of adult patients treated with ECMO between January 2007 and January 2017 in a tertiary healthcare center. Demographics, clinical data, coagulation status, ICH characteristics, and treatment modalities were analyzed. The primary outcome parameter was defined as mortality caused by ICH during ECMO. 525 patients with ECMO therapy were eligible for analysis. An overall incidence for any type of intracranial bleeding of 12.3% was found. Small hemorrhages accounted for 6.4% and acute subdural and epidural hematoma for 1.2%. Twenty-four (4.6%) patients developed ICH, and 11 patients (46%) died due to the ICH. Mortality was significantly higher in patients with larger ICH volumes (86.8 +/- 34.8 ml vs 9.9 +/- 20.3 ml, p < 0.001), intraventricular hemorrhage (83% vs 8%, p = 0.01), and a fluid level inside the ICH (75% vs 31%, p = 0.04). All patients were classified according to the bleeding pattern on the initial CT scan into 3 types. Patients with type 1 bleeding were statistically more likely to die (p < 0.001). In 15 out of 24 patients (63%), correction of the coagulation status was possible within 12 h after ICH onset. Seven out of 9 patients (78%) without early coagulation correction died compared to 2 out of 15 patients (13%), in whom early coagulation correction was successful (p = 0.01). This is the first study evaluating the course and management of patients experiencing an ICH under ECMO therapy and establishing an ICH classification based on the bleeding patterns. Early correction of the coagulation is of paramount importance in the treatment of these patients

7-Deazaguanine modifications protect phage DNA from host restriction systems

Genome modifications are central components of the continuous arms race between viruses and their hosts. The archaeosine base (G+), which was thought to be found only in archaeal tRNAs, was recently detected in genomic DNA of Enterobacteria phage 9g and was proposed to protect phage DNA from a wide variety of restriction enzymes. In this study, we identify three additional 2′-deoxy-7-deazaguanine modifications, which are all intermediates of the same pathway, in viruses: 2′-deoxy-7-amido-7-deazaguanine (dADG), 2′-deoxy-7-cyano-7-deazaguanine (dPreQ0) and 2′-deoxy-7- aminomethyl-7-deazaguanine (dPreQ1). We identify 180 phages or archaeal viruses that encode at least one of the enzymes of this pathway with an overrepresentation (60%) of viruses potentially infecting pathogenic microbial hosts. Genetic studies with the Escherichia phage CAjan show that DpdA is essential to insert the 7-deazaguanine base in phage genomic DNA and that 2′-deoxy-7-deazaguanine modifications protect phage DNA from host restriction enzymes

Gendered endings: Narratives of male and female suicides in the South African Lowveld

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s11013-012-9258-y. Copyright @ Springer Science+Business Media, LLC 2012.Durkheim’s classical theory of suicide rates being a negative index of social solidarity downplays the salience of gendered concerns in suicide. But gendered inequalities have had a negative impact: worldwide significantly more men than women perpetrate fatal suicides. Drawing on narratives of 52 fatal suicides in Bushbuckridge, South Africa, this article suggests that Bourdieu’s concepts of ‘symbolic violence’ and ‘masculine domination’ provide a more appropriate framework for understanding this paradox. I show that the thwarting of investments in dominant masculine positions have been the major precursor to suicides by men. Men tended to take their own lives as a means of escape. By contrast, women perpetrated suicide to protest against the miserable consequences of being dominated by men. However, contra the assumption of Bourdieu’s concept of ‘habitus’, the narrators of suicide stories did reflect critically upon gender constructs

Agree to Agree: Agreement in the Minimalist Programme

Agreement is a pervasive phenomenon across natural languages. Depending on one’s definition of what constitutes agreement, it is either found in virtually every natural language that we know of, or it is at least found in a great many. Either way, it seems to be a core part of the system that underpins our syntactic&nbsp; knowledge. Since the introduction of the operation of Agree in Chomsky (2000), agreement phenomena and the mechanism that underlies agreement have garnered a lot of attention in the Minimalist literature and have received different theoretical treatments at different stages. Since then, many different phenomena&nbsp; involving dependencies between elements in syntax, including movement or not, have been accounted for using Agree. The mechanism of Agree thus provides a powerful tool to model dependencies between syntactic elements far beyond φ-feature agreement. The articles collected in this volume further explore these topics&nbsp; and contribute to the ongoing debates surrounding agreement. The authors gathered in this book are internationally reknown experts in the field of Agreement