RNA binding and RNA remodeling activities of the half-a-tetratricopeptide (HAT) protein HCF107 underlie its effects on gene expression.

The half-a-tetratricopeptide repeat (HAT) motif is a helical repeat motif found in proteins that influence various aspects of RNA metabolism, including rRNA biogenesis, RNA splicing, and polyadenylation. This functional association with RNA suggested that HAT repeat tracts might bind RNA. However, RNA binding activity has not been reported for any HAT repeat tract, and recent literature has emphasized a protein binding role. In this study, we show that a chloroplast-localized HAT protein, HCF107, is a sequence-specific RNA binding protein. HCF107 consists of 11 tandem HAT repeats and short flanking regions that are also predicted to form helical hairpins. The minimal HCF107 binding site spans ∼11 nt, consistent with the possibility that HAT repeats bind RNA through a modular one repeat-1 nt mechanism. Binding of HCF107 to its native RNA ligand in the psbH 5' UTR remodels local RNA structure and protects the adjacent RNA from exonucleases in vitro. These activities can account for the RNA stabilizing, RNA processing, and translational activation functions attributed to HCF107 based on genetic data. We suggest that analogous activities contribute to the functions of HAT domains found in ribonucleoprotein complexes in the nuclear-cytosolic compartment.

Iron requirements based upon iron absorption tests are poorly predicted by haematological indices in patients with inactive inflammatory bowel disease.

Fe deficiency and Fe-deficiency anaemia are common in patients with inflammatory bowel disease (IBD). Traditional clinical markers of Fe status can be skewed in the presence of inflammation, meaning that a patient's Fe status can be misinterpreted. Additionally, Fe absorption is known to be down-regulated in patients with active IBD. However, whether this is the case for quiescent or mildly active disease has not been formally assessed. The present study aimed to investigate the relationship between Fe absorption, Fe requirements and standard haematological indices in IBD patients without active disease. A group of twenty-nine patients with quiescent or mildly active IBD and twenty-eight control subjects undertook an Fe absorption test that measured sequential rises in serum Fe over 4 h following ingestion of 200 mg ferrous sulphate. At baseline, serum Fe, transferrin saturation, non-transferrin-bound Fe (NTBI), ferritin and soluble transferrin receptor were all measured. Thereafter (30-240 min), only serum Fe and NTBI were measured. Fe absorption did not differ between the two groups (P = 0·9; repeated-measures ANOVA). In control subjects, baseline haematological parameters predicted Fe absorption (i.e. Fe requirements), but this was not the case for patients with IBD. Fe absorption is normal in quiescent or mildly active IBD patients but standard haematological parameters do not accurately predict Fe requirements.

Vagus nerve stimulation in children with mitochondrial electron transport chain deficiencies.

We retrospectively investigated outcome data for vagus nerve stimulation (VNS) in children less than 12 years of age with intractable seizures and mitochondrial disease. Five children with a mitochondrial disease, due to electron transport chain deficiency, were studied. Information was collected from clinic visits prior to, and subsequent to, VNS implantation. Data were collected by type and frequency of seizures, encephalogram and neuroimaging findings, and medication history. Four of the children had predominantly myoclonic seizures, while the other child had focal seizures with secondary generalization and myoclonic seizures. All five children did not have significant reduction in seizure frequency with VNS. VNS may not be an effective method to control myoclonic seizures in children with electron transport chain disorders.

Vagus nerve stimulation for intractable seizures in children.

Forty-three children less than 12 years of age having intractable seizures were treated with vagus nerve stimulation. Five children were monitored for <12 months, 16 children for 12 to 17 months, and 22 children for > or =18 months with overall median seizure reduction of 55%. Thirty-seven percent had at least 90% reduction. Vagus nerve stimulation was effective in children with generalized, mixed, and partial medically refractory seizures.

Osmolarity and spectrophotometric property of brilliant blue green define the degree of toxicity on retinal pigment epithelial cells exposed to surgical endoilluminator.

OBJECTIVE: To evaluate the effect of varying concentrations of brilliant blue green (BBG) and their different biochemical characteristics on retinal pigment epithelial (RPE) cells under xenon light source illumination at varying distances to identify safe parameters for intraoperative use. METHODS: Human retinal RPE cells (ARPE-19) were exposed to two concentrations (0.25 and 0.50 mg/mL) of BBG and illuminated with a xenon surgical illuminator at varying distances (10 and 25 mm), intensity levels, and time intervals (1, 5, and 15 minutes). Additionally, the effect of osmolarity was examined by diluting BBG in different concentrations of glucose. Cytotoxicity of BBG and osmolarity effects on cell viability were evaluated using a WST-1 assay. Light absorption and emission characteristic of BBG in different solvents were measured using a plate reader at different wavelengths. Lastly, the activity of caspase-3 was also studied. RESULTS: Cell viability of ARPE-19 cells was 77.4%±12.7%, 78.7%±17.0%, and 65.0%±19.7% at 1, 5, and 15 minutes to exposure of high illumination xenon light at 10 mm (P<0.05) compared to controls. At both distances of illumination (10 and 25 mm), similar cell viabilities were seen between 1 and 5 minutes of exposure. However, there was a decline in viability when the illumination was carried out to 15 minutes in all groups (P<0.05). There was no significant reduction in cell viability in presence or absence of xenon light in different osmolar solutions concentrations of glucose (P>0.05). Maximal light absorption of BBG was noted between 540 and 680 nm. Activated caspase-3 level was not significant in both the concentrations of BBG (P>0.05). CONCLUSION: Our findings suggest that BBG at 0.25 mg/mL during vitreoretinal surgery is safe and not toxic to RPE cells up to 5 minutes under focal high illumination (10 mm) and up to 15 minutes under medium diffuse illumination (25 mm). BBG was safe to be mixed with isotonic glucose solution at the concentration range of 2.5%-10%, regardless of the illumination status.

Inland and Near Shore Water Profiles Derived from the High Altitude Multiple Altimeter Beam Experimental Lidar (MABEL).

The Advanced Topographic Laser Altimeter System (ATLAS) on the Ice, Cloud, and Land Elevation Satellite (ICESat-2) mission is a six beam, low energy, high repetition rate, 532 nm laser transmitter with photon counting detectors. Although designed primarily for detecting height changes in icecaps, sea ice and vegetation, the polar-orbital satellite will observe global surface water during its designed three year life span, including inland water bodies, coasts, and open oceans. In preparation for the mission, an ICESat-2 prototype or the Multiple Altimeter Beam Experimental Lidar (MABEL), was built and flown on high altitude aircraft experiments over a range of inland and near-shore targets. The purpose was to test the ATLAS concept and to provide a database for developing an algorithm that detects along track surface water height and light penetration under a range of atmospheric and water conditions. The current analysis examines the datasets of three MABEL transects observed from 20 km above ground of coastal and inland waters conducted in 2012 and 2013. Transects ranged from about 2 to 12 km in length and included the middle Chesapeake Bay, the near shore Atlantic coast at Virginia Beach, and Lake Mead. Results indicate MABEL's high capability for retrieving surface water height statistics with a mean height precision of approximately 5-7 cm per 100m segment length. Profiles of attenuated subsurface backscatter, characterized using a Signal to Background Ratio written in Log10 base, or LSBR 0 , were observed over a range of 1.3 to 9.3 meters depending on water clarity and atmospheric background. Results indicate that observable penetration depth, although primarily dependent on water properties, was greatest when solar background rate was low. Near shore bottom reflectance was detected only at the Lake Mead site down to maximum of 10 m under a clear night sky and low turbidity of approximately 1.6 Nephelometric Turbidity Units (NTU). The overall results suggest that the feasibility of retrieving operational surface water height statistics from space-based photon counting systems such as ATLAS is very high for resolutions down to about 100m, even in partly cloudy conditions. The capability to observe subsurface backscatter profiles is achievable but requires much longer transects of several hundreds of meters.

Dietary fortificant iron intake is negatively associated with quality of life in patients with mildly active inflammatory bowel disease.

BACKGROUND: Iron deficiency anaemia and oral iron supplementation have been associated negatively with quality of life, and with adverse effects, respectively, in subjects with inflammatory bowel disease (IBD). Hence, the risk-benefit ratio of oral iron is not understood in this patient group. The present case-control study investigated whether dietary iron intake impacts on quality of life in IBD patients. METHODS: Quality of life, habitual dietary iron intakes and iron requirements were assessed in 29 patients with inactive or mildly active IBD as well as in 28 healthy control subjects. RESULTS: As expected, quality of life was worse in IBD patients as a whole in comparison to healthy controls according to EuroQol score and EuroQol VAS percentage (6.9 ± 1.6 vs 5.3 ± 0.6; p< 0.0001 and 77 ± 14% vs 88 ± 12%; p=0.004 respectively). For IBD subjects, 21/29 were iron deplete based upon serum iron responses to oral iron but, overall, were non-anaemic with mean haemoglobin of 13.3 ± 1.5 g/dL, and there was no difference in their quality of life compared to 8/29 iron replete subjects (Hb 14.0 ± 0.8 g/dL). Interestingly, total dietary iron intake was significantly negatively associated with quality of life in IBD patients, specifically for non-haem iron and, more specifically, for fortificant iron. Moreover, for total non-haem iron the negative association disappeared when fortificant iron values were subtracted. Finally, further sub-analysis indicated that the negative association between (fortificant) dietary iron intake and quality of life in IBD patients is driven by findings in patients with mildly active disease rather than in patients with quiescent disease. CONCLUSIONS: Iron deficiency per se (i.e. without concomitant anaemia) does not appear to further affect quality of life in IBD patients with inactive or mildly active disease. However, in this preliminary study, dietary iron intake, particularly fortificant iron, appears to be significantly negatively associated with quality of life in patients with mildly active disease.

Iron status is inversely associated with dietary iron intakes in patients with inactive or mildly active inflammatory bowel disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) frequently appear iron deplete but whether this is a reflection of dietary iron intakes is not known. METHODS: Dietary data were collected from 29 patients with inactive or mildly-active IBD and 28 healthy controls using a validated food frequency questionnaire that measured intakes of iron and its absorption modifiers. Non-haem iron availability was estimated using a recently developed algorithm. Subjects were classified for iron status based upon data from a concomitant and separately published study of iron absorption. Absorption was used to define iron status because haematological parameters are flawed in assessing iron status in inflammatory conditions such as IBD. RESULTS: Dietary intakes of total iron, non-haem iron and vitamin C were significantly greater in IBD patients who were iron replete compared to those who were iron deplete (by 48%, 48% and 94% respectively; p≤0.05). The predicted percentage of available non-haem iron did not differ between these groups (19.7 ± 2.0% vs 19.3 ± 2.0% respectively; p=0.25). However, because of the difference in iron intake, the overall amount of absorbed iron did (2.4 ± 0.8 mg/d vs 1.7 ± 0.5 mg/d; p=0.013). No such differences were observed in the healthy control subjects. CONCLUSIONS: In IBD, iron status is more closely related to the quality and quantity of dietary iron intake than in the general healthy population.