The Lyman alpha reference sample. VII. Spatially resolved Hα\alpha kinematics

We present integral field spectroscopic observations with the Potsdam Multi Aperture Spectrophotometer of all 14 galaxies in the $z\sim 0.1$ Lyman Alpha Reference Sample (LARS). We produce 2D line of sight velocity maps and velocity dispersion maps from the Balmer $\alpha$ (H$\alpha$) emission in our data cubes. These maps trace the spectral and spatial properties of the LARS galaxies' intrinsic Ly$\alpha$ radiation field. We show our kinematic maps spatially registered onto the Hubble Space Telescope H$\alpha$ and Lyman $\alpha$ (Ly$\alpha$) images. Only for individual galaxies a causal connection between spatially resolved H$\alpha$ kinematics and Ly$\alpha$ photometry can be conjectured. However, no general trend can be established for the whole sample. Furthermore, we compute non-parametric global kinematical statistics -- intrinsic velocity dispersion $\sigma_0$, shearing velocity $v_\mathrm{shear}$, and the $v_\mathrm{shear}/\sigma_0$ ratio -- from our kinematic maps. In general LARS galaxies are characterised by high intrinsic velocity dispersions (54\,km\,s$^{-1}$ median) and low shearing velocities (65\,km\,s$^{-1}$ median). $v_\mathrm{shear}/\sigma_0$ values range from 0.5 to 3.2 with an average of 1.5. Noteworthy, five galaxies of the sample are dispersion dominated systems with $v_\mathrm{shear}/\sigma_0 <1$ and are thus kinematically similar to turbulent star forming galaxies seen at high redshift. When linking our kinematical statistics to the global LARS Ly$\alpha$ properties, we find that dispersion dominated systems show higher Ly$\alpha$ equivalent widths and higher Ly$\alpha$ escape fractions than systems with $v_\mathrm{shear}/\sigma_0 > 1$. Our result indicates that turbulence in actively star-forming systems is causally connected to interstellar medium conditions that favour an escape of Ly$\alpha$ radiation.Comment: 26 pages, 15 figures, accepted for publication in A&

Mitotic phosphorylation by NEK6 and NEK7 reduces the microtubule affinity of EML4 to promote chromosome congression

EML4 is a microtubule-associated protein that promotes microtubule stability. We investigated its regulation across the cell cycle and found that EML4 was distributed as punctate foci along the microtubule lattice in interphase but exhibited reduced association with spindle microtubules in mitosis. Microtubule sedimentation and cryo–electron microscopy with 3D reconstruction revealed that the basic N-terminal domain of EML4 mediated its binding to the acidic C-terminal tails of α- and β-tubulin on the microtubule surface. The mitotic kinases NEK6 and NEK7 phosphorylated the EML4 N-terminal domain at Ser144 and Ser146 in vitro, and depletion of these kinases in cells led to increased EML4 binding to microtubules in mitosis. An S144A-S146A double mutant not only bound inappropriately to mitotic microtubules but also increased their stability and interfered with chromosome congression. In addition, constitutive activation of NEK6 or NEK7 reduced the association of EML4 with interphase microtubules. Together, these data support a model in which NEK6- and NEK7-dependent phosphorylation promotes the dissociation of EML4 from microtubules in mitosis in a manner that is required for efficient chromosome congression

Population genetic diversity and fitness in multiple environments

<p>Abstract</p> <p>Background</p> <p>When a large number of alleles are lost from a population, increases in individual homozygosity may reduce individual fitness through inbreeding depression. Modest losses of allelic diversity may also negatively impact long-term population viability by reducing the capacity of populations to adapt to altered environments. However, it is not clear how much genetic diversity within populations may be lost before populations are put at significant risk. Development of tools to evaluate this relationship would be a valuable contribution to conservation biology. To address these issues, we have created an experimental system that uses laboratory populations of an estuarine crustacean, <it>Americamysis bahia </it>with experimentally manipulated levels of genetic diversity. We created replicate cultures with five distinct levels of genetic diversity and monitored them for 16 weeks in both permissive (ambient seawater) and stressful conditions (diluted seawater). The relationship between molecular genetic diversity at presumptive neutral loci and population vulnerability was assessed by AFLP analysis.</p> <p>Results</p> <p>Populations with very low genetic diversity demonstrated reduced fitness relative to high diversity populations even under permissive conditions. Population performance decreased in the stressful environment for all levels of genetic diversity relative to performance in the permissive environment. Twenty percent of the lowest diversity populations went extinct before the end of the study in permissive conditions, whereas 73% of the low diversity lines went extinct in the stressful environment. All high genetic diversity populations persisted for the duration of the study, although population sizes and reproduction were reduced under stressful environmental conditions. Levels of fitness varied more among replicate low diversity populations than among replicate populations with high genetic diversity. There was a significant correlation between AFLP diversity and population fitness overall; however, AFLP markers performed poorly at detecting modest but consequential losses of genetic diversity. High diversity lines in the stressful environment showed some evidence of relative improvement as the experiment progressed while the low diversity lines did not.</p> <p>Conclusions</p> <p>The combined effects of reduced average fitness and increased variability contributed to increased extinction rates for very low diversity populations. More modest losses of genetic diversity resulted in measurable decreases in population fitness; AFLP markers did not always detect these losses. However when AFLP markers indicated lost genetic diversity, these losses were associated with reduced population fitness.</p

Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing:a population-based study

Background&lt;p&gt;&lt;/p&gt; Familial hypercholesterolaemia (FH) is a common Mendelian condition which, untreated, results in premature coronary heart disease. An estimated 88% of FH cases are undiagnosed in the UK. We previously validated a method for FH mutation detection in a lipid clinic population using next generation sequencing (NGS), but this did not address the challenge of identifying index cases in primary care where most undiagnosed patients receive healthcare. Here, we evaluate the targeted use of NGS as a potential route to diagnosis of FH in a primary care population subset selected for hypercholesterolaemia.&lt;p&gt;&lt;/p&gt; Methods&lt;p&gt;&lt;/p&gt; We used microfluidics-based PCR amplification coupled with NGS and multiplex ligation-dependent probe amplification (MLPA) to detect mutations in LDLR, APOB and PCSK9 in three phenotypic groups within the Generation Scotland: Scottish Family Health Study including 193 individuals with high total cholesterol, 232 with moderately high total cholesterol despite cholesterol-lowering therapy, and 192 normocholesterolaemic controls.&lt;p&gt;&lt;/p&gt; Results&lt;p&gt;&lt;/p&gt; Pathogenic mutations were found in 2.1% of hypercholesterolaemic individuals, in 2.2% of subjects on cholesterol-lowering therapy and in 42% of their available first-degree relatives. In addition, variants of uncertain clinical significance (VUCS) were detected in 1.4% of the hypercholesterolaemic and cholesterol-lowering therapy groups. No pathogenic variants or VUCS were detected in controls.&lt;p&gt;&lt;/p&gt; Conclusions&lt;p&gt;&lt;/p&gt; We demonstrated that population-based genetic testing using these protocols is able to deliver definitive molecular diagnoses of FH in individuals with high cholesterol or on cholesterol-lowering therapy. The lower cost and labour associated with NGS-based testing may increase the attractiveness of a population-based approach to FH detection compared to genetic testing with conventional sequencing. This could provide one route to increasing the present low percentage of FH cases with a genetic diagnosis

Gas exchange mechanisms in preterm infants on HFOV - a computational approach

High-frequency oscillatory ventilation (HFOV) is a commonly used therapy applied to neonates requiring ventilatory support during their first weeks of life. Despite its wide application, the underlying gas exchange mechanisms promoting the success of HVOF in neonatal care are not fully understood until today. In this work, a highly resolved computational lung model, derived from Magnetic Resonance Imaging (MRI) and Infant Lung Function Testing (ILFT), is used to reveal the reason for highly efficient gas exchange during HFOV, in the preterm infant. In total we detected six mechanisms that facilitate gas exchange during HFOV: (i) turbulent vortices in large airways;(ii) asymmetric in-and expiratory flow profiles;(iii) radial mixing in main bronchi;(iv) laminar flow in higher generations of the respiratory tract;(v) pendelluft;(vi) direct ventilation of central alveoli. The illustration of six specific gas transport phenomena during HFOV in preterm infants advances general knowledge on protective ventilation in neonatal care and can support decisions on various modes of ventilatory therapy at high frequencies

A case report and brief review of the literature on bilateral retinal infarction following cardiopulmonary bypass for coronary artery bypass grafting

Postoperative visual loss is a devastating perioperative complication. The commonest aetiologies are anterior ischaemic optic neuropathy (AION), posterior ischaemic optic neuropathy (PION), and central retinal artery occlusion (CRAO). These appear to be related to certain types of operation, most commonly spinal and cardiac bypass procedures; with the rest divided between: major trauma causing excessive blood loss; head/neck and nasal or sinus surgery; major vascular procedures (aortic aneurysm repair, aorto-bifemoral bypass); general surgery; urology; gynaecology; liposuction; liver transplantation and duration of surgery. The non-surgical risk factors are multifactorial: advanced age, prolonged postoperative anaemia, positioning (supine v prone), alteration of venous drainage of the retina, hypertension, smoking, atherosclerosis, hyperlipidaemia, diabetes, hypercoagulability, hypotension, blood loss and large volume resuscitation. Other important cardiac causes are septic emboli from bacterial endocarditis and emboli caused by atrial myxomata. The majority of AION cases occur during CPB followed by head/neck surgery and prone spine surgery. CPB is used to allow coronary artery bypass grafting on a motionless heart. It has many side-effects and complications associated with its use and we report here a case of bilateral retinal infarction during routine coronary artery bypass grafting in a young male patient with multiple risk factors for developing this complication despite steps to minimise its occurrence