FZD6, MATN2 AND SLC25A32, POSSIBLE CANDIDATE GENES IN NONSYNDROMIC CLEFT LIP AND PALATE

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect with a multifactorial etiology. Despite decades of research, the genetic underpinnings of NSCLP still remain largely unexplained. A genome wide association study (GWAS) of a large NSCLP African American family with seven affected individuals across three generations found evidence for linkage at 8q21.3-24.12 (LOD = 2.98). This region contained three biologically relevant candidate genes: Frizzled-6 (FZD6) (LOD = 2.8), Matrilin-2 (MATN2) (LOD = 2.3), and Solute Carrier Family 25, Member 32 (SLC26A32) (LOD = 1.6). Sequencing of the coding regions and the 5’ and 3’ UTRs of these genes in two affected family members identified a rare intronic variant, rs138557689 (c.-153+432A>C), in FZD6. The rs138557689/C allele segregated with the NSCLP phenotype; in silico analysis predicted and EMSA analysis showed that the 138557689/C allele creates new DNA binding sites. FZD6 is part of the WNT pathway, which is involved in craniofacial development, including midface development and upper lip fusion. Our novel findings suggest that an alteration in FZD6 gene regulation may perturb this tightly controlled biological pathway and in turn contribute to the development of NSCLP in this family. Studies are underway to further define how the rs138557689/C variant affects expression of FZD6.

Cataract surgery in cancer patients and its impact on quality of life as measured by the National Eye Institute Visual Functioning Questionnaire - 25 (NEI-VFQ-25)

Purpose. The measurement of quality of life has become an important topic in healthcare and in the allocation of limited healthcare resources. Improving the quality of life (QOL) in cancer patients is paramount. Cataract removal and lens implantation appears to improve patient well-being of cancer patients, though a formal measurement has never been published in the US literature. In this current study, National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), a validated vision quality of life metric, was used to study the change in vision-related quality of life in cancer patients who underwent cataract extraction with intraocular lens implantation. ^ Methods. Under an IRB approved protocol, cancer patients who underwent cataract surgery with intraocular lens implantation (by a single surgeon) from December 2008 to March 2011, and who had completed a pre- and postoperative NEI-VFQ-25 were retrospectively reviewed. Post-operative data was collected at their routine 4-6 week post-op visit. Patients' demographics, cancer history, their pre and postoperative ocular examinations, visual acuities, and NEI-VFQ-25 with twelve components were included in the evaluation. The responses were evaluated using the Student t test, Spearman correlation and Wilcoxon signed rank test. ^ Results. 63 cases of cataract surgery (from 54 patients) from the MD Anderson Cancer Center were included in the study. Cancer patients had a significant improvement in the visual acuity (P<0.0001) postoperatively, along with a significant increase in vision-related quality of life (P<0.0001). Patients also had a statistically significant improvement in ten of the twelve subcategories which are addressed in the NEI-VFQ-25. ^ Conclusions. In our study, cataract extraction and intraocular implantation showed a significant impact on the vision-related quality of life in cancer patients. Although this study includes a small sample size, it serves as a positive pilot study to evaluate and quantify the impact of a surgical intervention on QOL in cancer patients and may help to design a larger study to measure vision related QOL per dollar spent for health care cost in cancer patients.^

Using spatial linear models with SAR and CAR structure to examine Texas lung cancer incidence rates

Scholars have found that socioeconomic status was one of the key factors that influenced early-stage lung cancer incidence rates in a variety of regions. This thesis examined the association between median household income and lung cancer incidence rates in Texas counties. A total of 254 individual counties in Texas with corresponding lung cancer incidence rates from 2004 to 2008 and median household incomes in 2006 were collected from the National Cancer Institute Surveillance System. A simple linear model and spatial linear models with two structures, Simultaneous Autoregressive Structure (SAR) and Conditional Autoregressive Structure (CAR), were used to link median household income and lung cancer incidence rates in Texas. The residuals of the spatial linear models were analyzed with Moran's I and Geary's C statistics, and the statistical results were used to detect similar lung cancer incidence rate clusters and disease patterns in Texas.^

Pollen records of the Bykovsky Peninsula

New pollen and radiocarbon data from the Bykovsky Peninsula document the Late Pleistocene and Holocene environmental history of the Laptev Sea coast. More than 60 AMS-14C and conventional 14C dates indicate that the deposits accumulated during the last 60,000 radiocarbon yr BP. High concentration of green alga colonies (Pediustrum and Botryococcus) in the investigated sediment show that sedimentation was mostly in shallow water environments. Scarce grass and sedge communities dominated the vegetation 53-60 kyr BP. Climate was cold and dry. Open Poaceae and Cypcraccae associations with Asteraceae, Ranunculaceae, and Cichoriaceac, dominated in the area about 48-42.5 kyr BP. Steppic communities with Artemisia and shrubby tundra communities with Salix and Betula sect. Nanae were also present. Climate was dry, but relatively warm. Vegetation cover became denser about 42.5-33.5 kyr BP, reflecting more favorable climate conditions. Scarce Poaceae communities with some Caryophyllaceae, Asteraceae, Cichoriaceae, and Selaginella rupestris covered the Bykovsky Peninsula area during the Sartan (Late Weichselian) stage about 26-16 kyr BP. Disturbed, uncovered soils were very common in the area. Climate was extremely cold and dry. Poaceae and Cyperaceae associations with Caryophyllaceae, Asteraceae, Cichoriaceae dominated the vegetation in the late Sartan, ca 16-12.2 kyr BP. Climate was significantly warmer than in the early Sartan time. The lee Complex sedimentation was interrupted about 12 kyr BP; most likely it was connected with the beginning of the Allerod warnring. Shrubby (Betula sect. Nanae, Alnusfnuicosa, Salix, Ericales) tundra was widely distributed on the Bykovsky Peninsula during the early-middle Holacene. Climate was most favorable between 8200 and 4500 yr BP. Vegetation became similar to modern after 4500 yr BP, suggesting a deterioration of climate.

Properties and faunal abundances of level sea ice and sea-ice ridges in the Chukchi/Beaufort Seas and Canada Basin

The abundances and distribution of metazoan within-ice meiofauna (13 stations) and under-ice fauna (12 stations) were investigated in level sea ice and sea-ice ridges in the Chukchi/Beaufort Seas and Canada Basin in June/July 2005 using a combination of ice coring and SCUBA diving. Ice meiofauna abundance was estimated based on live counts in the bottom 30 cm of level sea ice based on triplicate ice core sampling at each location, and in individual ice chunks from ridges at four locations. Under-ice amphipods were counted in situ in replicate (N=24-65 per station) 0.25 m**2 quadrats using SCUBA to a maximum water depth of 12 m. In level sea ice, the most abundant ice meiofauna groups were Turbellaria (46%), Nematoda (35%), and Harpacticoida (19%), with overall low abundances per station that ranged from 0.0 to 10.9 ind/l (median 0.8 ind/l). In level ice, low ice algal pigment concentrations (<0.1-15.8 µg Chl a /l), low brine salinities (1.8-21.7) and flushing from the melting sea ice likely explain the low ice meiofauna concentrations. Higher abundances of Turbellaria, Nematoda and Harpacticoida also were observed in pressure ridges (0-200 ind/l, median 40 ind/l), although values were highly variable and only medians of Turbellaria were significantly higher in ridge ice than in level ice. Median abundances of under-ice amphipods at all ice types (level ice, various ice ridge structures) ranged from 8 to 114 ind/m**2 per station and mainly consisted of Apherusa glacialis (87%), Onisimus spp. (7%) and Gammarus wilkitzkii (6%). Highest amphipod abundances were observed in pressure ridges at depths >3 m where abundances were up to 42-fold higher compared with level ice. We propose that the summer ice melt impacted meiofauna and under-ice amphipod abundance and distribution through (a) flushing, and (b) enhanced salinity stress at thinner level sea ice (less than 3 m thickness). We further suggest that pressure ridges, which extend into deeper, high-salinity water, become accumulation regions for ice meiofauna and under-ice amphipods in summer. Pressure ridges thus might be crucial for faunal survival during periods of enhanced summer ice melt. Previous estimates of Arctic sea ice meiofauna and under-ice amphipods on regional and pan-Arctic scales likely underestimate abundances at least in summer because they typically do not include pressure ridges.

Impact of ocean acidification and warming on respiration, heart rate and acid-base status of Mytilus edulis from the North Sea

Anthropogenic climate change confronts marine organisms with rapid trends of concomitant warming and CO2 induced ocean acidification. The survival and distribution of species partly depend on their ability to exploit their physiological plasticity during acclimatization. Therefore, in laboratory studies the effects of simulated future ocean acidification on thermal tolerance, energy metabolism and acid-base regulation capacity of the North Sea population of the blue mussel Mytilus edulis were examined. Following one month of pre-acclimation to 10 °C and control CO2 levels, mussels were exposed for two weeks to control and projected oceanic CO2 levels (390, 750 and 1120 µatm) before being subjected to a stepwise warming protocol between 10 °C and 31 °C (+ 3 °C each night). Oxygen consumption and heart rates, anaerobic metabolite levels and haemolymph acid-base status were determined at each temperature. CO2 exposure left oxygen consumption rate unchanged at acclimation temperature but caused a somewhat stronger increase during acute warming and thus mildly higher Q10-values than seen in controls. Interestingly, the thermally induced limitation of oxygen consumption rate set in earlier in normocapnic than in hypercapnic (1120 µatm CO2) mussels (25.2 °C vs. 28.8 °C), likely due to an onset of metabolic depression in the control group following warming. However, the temperature induced increase in heart rate became limited above 25 °C in both groups indicating an unchanged pejus temperature regardless of CO2 treatment. An upper critical temperature was reached above 28 °C in both treatments indicated by the accumulation of anaerobic metabolites in the mantle tissue, paralleled by a strong increase in haemolymph PCO2 at 31 °C. Ocean acidification caused a decrease in haemolymph pH. The extracellular acidosis remained largely uncompensated despite some bicarbonate accumulation. In all treatments animals developed a progressive warming-induced extracellular acidosis. A stronger pH drop at around 25 °C was followed by stagnating heart rates. However, normocapnic mussels enhanced bicarbonate accumulation at the critical limit, a strategy no longer available to hypercapnic mussels. In conclusion, CO2 has small effects on the response patterns of mussels to warming, leaving thermal thresholds largely unaffected. High resilience of adult North Sea mussels to future ocean acidification indicates that sensitivity to thermal stress is more relevant in shaping the response to future climate change.

(Table 1) Biovolume variations of cyanobacteria and total phytoplankton in the Frederiksborg Slotsso, Denmark

Several studies have shown that submerged macrophytes provide a refuge for zooplankton against fish predation, whereas the role of emergent and floating-leaved species, which are often dominant in eutrophic turbid lakes, is far less investigated. Zooplankton density in open water and amongst emergent and floating-leaved vegetation was monitored in a small, eutrophic lake (Frederiksborg Slotsso) in Denmark during July-October 2006. Emergent and floating-leaved macrophytes harboured significantly higher densities of pelagic as well as plant-associated zooplankton species, compared to the open water, even during periods where the predation pressure was presumably high (during the recruitment of 0+ fish fry). Zooplankton abundance in open water and among vegetation exhibited low values in July and peaked in August. Bosmina and Ceriodaphnia dominated the zooplankton community in the littoral vegetated areas (up to 4,400 ind/l among Phragmites australis and 11,000 ind/l between Polygonum amphibium stands), whereas the dominant species in the pelagic were Daphnia (up to 67 ind/l) and Cyclops (41 ind/l). The zooplankton density pattern observed was probably a consequence of concomitant modifications in the predation pressure, refuge availability and concentration of cyanobacteria in the lake. It is suggested that emergent and floating-leaved macrophytes may play an important role in enhancing water clarity due to increased grazing pressure by zooplankton migrating into the plant stands. As a consequence, especially in turbid lakes, the ecological role of these functional types of vegetation, and not merely that of submerged macrophyte species, should be taken into consideration.

Oceanographical and meterological observations in the Westafrican area of upwelling during the 'Deutsche Nordatlantische Expedition' 1937

In 1937 the "Meteor" performed the cruises of the first part of the "Deutsche Nordatlantische Expedition". This publication treats seven stations of three-day-anchoring occupied during that time, five of which are located on the shelf, one on the continental slope and one on a ridge between the Capverde islands. The Bohnecke current meter, an instrument developed for the expedition, is described briefly and it's accuracy studied by comparing the measurements of two instruments which operated simultaneously at the same depth. It is shown that it is very sensitive for movements of the anchored ship because of the very short measuring intervall (2 minutes). The influence of the ship's movements could not be eliminated completely, the mode of using the instrument at different depths being unsuitable for this. Considering the stratification the accuracy of it's representation by the mean temperature and salinity distributionis studied. It is shown that under certain conditions a distribution estimated from observed values gives more exact results. This especially applies to the TS-diagram. Station Meteor336, located on the shelf near Cape Juby, shows temperatures 4 °C less than the open ocean and so belongs to the area of upwelling. During the observation period, however, internal tides are prominent. The diurnal component is of considerable influence, the distinction from inertial oscillations (25.5 hours) not being possible, however. Station Meteor341, on the shelf off Spanish-Sahara, gives an excellent example of the movements in the centre of the area of upwelling. Changing it's direction by 45° at the beginning of the measurements, the wind causes a change of current direction at all depths which, after some inertial oscillations (period 28.3 hours), settles down to a final value. At the beginning and the end of the observations the current at the upper depths is directed off-shore, the angle between current and wind being 22°, while at the lower depths it is orientated towards the shore. The depth of the upper homogenous layer gives the origin of the water transported upwards When during the inertial oscillations the current goes offshore at all depths temporarily, a sudden disturbance occurs in the temperature measurements. Station Meteor311 is located similar to station Meteor341 but was occupied one month earlier. At that time the wind situation was unnormal, the usual wind direction of 45° occuring at the end of the station. Therefore an unnormally high vertical shear of current speed and direction has been observed, the current vector being directed off-shore at the surface and near the bottom, towards the coast inbetween. The TS-diagram shows that the bottom water is replaced first so that upwelling does not occur during observation time. The state reached at the end of the station does not seem to be stable. Station Meteor369, on the continental slope, is governed by internal waves. Besides the internal tide of 12.4 hours a wave of 6.5 hour period is observed, being possibly amplified by the large bottom slope. In 40 - 60 m depth, where the thermocline is located, a wave with 3.3 hour period is observed which is argued to be an internal boundary wave. Station Meteor334 is located on the shelf NW of the mouth of the Senegal river. A marked temperature stratification, associated with large disturbances, and nearly constant salinity have been found there. The current was going slowly towards S or SW in the upper 20 - 30 m, towards N underneath. At the boundary of the current systems intense turbulence developed,including as it seems a water type of less salinity which is transported from the Senegal river by the lower current. Station Meteor327, located at 100 m depth between two of the Capverde islands, shows oceanic characteristics. The semidiurnal tide is found mainly, the diurnal component having considerable influence. Furtheron an internal wave of 6 hour period is seen the maximum amplitude of which is moving slowly downwards. Two possibilities of explaining it are discussed. Station Meteor366 is found in the area of ceasing winds off the coast of upper Guinea. The temperature there depends strongly on the depth, the salinity being nearly constant. The currents are divided into an upper and a lower system with large variations in both of them. A change of wind direction of nearly 90° is supposed to be the reason. The variations in salinity accordingly are interpreted as the influence of fresh water outflow from land which is felt in a different way at different wind directions. In the last section the daily changes in air and water temperature are studied. The upwelling having large influence on these, a centre of the area of upwelling can be located at about 100 miles north of Cape Blanc (Station Meteor311). The semidiurnal tidal component is compared with previous results for the Atlantic Ocean yielding considerable differences for the direction and time of occurence of the current maximum which might be due to the topographical influences around the shelf.

Pollen analysis of sediment cores from the mouth of the river Congo to Walvis Bay and Lüderitz

The distribution of pollen in marine sediments is used to record vegetation changes over the past 30,000 years on the adjacent continent. A transect of marine pollen sequences from the mouth of the river Congo (~5°S) to Walvis Bay and Lüderitz (~25°S) shows vegetation changes in Congo, Angola and Namibia from the last glacial period into the Holocene. The comparison of pollen records from different latitudes provides information about the latitudinal shift of open forest and savannahs (Poaceae pollen), the extension of lowland forest (rain forest pollen) and Afromontane forest (Podocarpus pollen), and the position of the desert fringe (pollen of Caryophyllaceae, Chenopodiaceae and Amaranthaceae). High Cyperaceae pollen percentages in sediments from the last glacial period off the mouth of the river Congo suggest the presence of open swamps rather than savannah vegetation in the Congo Basin. Pollen from Restionaceae in combination with Stoebe-type pollen (probably from Elytropappus) indicates a possible northwards extension of winter rain vegetation during the last glacial period. The record of Rhizophora (mangrove) pollen is linked to erosion of the continental shelf and sea-level rise. Pollen influx is highest off river mouths (10-2000 grains year**-1 cm**-2), close to the coast (300-6000 grains year**-1 cm**-2), but is an order of magnitude lower at sites situated far from the continent (<10 grains year**-1 cm**-2).

Grains size and components distribution in turbidite layesr of ODP Leg 101

Textural and compositional differences were found between gravity-flow sheets in an open-ocean environment on the northern slope of Little Bahama Bank (Site 628, Pliocene turbidite sequence) and in a closed-basin depositional setting (Site 632, Quaternary turbidite sequence). Mud-supported debris-flow sheets were cored at Site 628. Average mean grain size of the turbidite samples was lower, mud content was higher, and sorting was poorer than in comparable samples from Site 632. This reflects the deposition of proximal, low-energy turbidity currents and debris flows on a base-ofslope carbonate apron. No mud-supported debris-flow sheets were deposited in the investigated sediment sequence of Hole 632A. Many larger turbidity currents from around the margins of Exuma Sound may have reached this central basin setting, depositing sediments that had been transported over longer distances. Planktonic components dominate in the grain-sized fraction (500-1000 µm) of turbidite samples from Hole 628A, while platform detritus is rare. We interpreted this as resulting from the erosion and reworking of a large area of open-ocean slope sediments by gravity flows. In contrast, large amounts of benthic and platform components were found in the turbidite samples of Hole 632A. This may be explained by the fact that the slopes of the enclosed Exuma Sound are steep, and turbidity currents bypassed much of these slopes through pronounced channels, delivering more shallow-water detritus to the deep basin. Erosion of slope sediments, a possible source area of planktonic detritus, is assumed to be low. The small slope area in relation to the larger surrounding platform areas and lower production of planktonic components in the enclosed waters of Exuma Sound may also explain the observed low number of planktonic components at Hole 632A. Turbidite material from both open-ocean and enclosed-basin environments was deposited at Site 635.

Oxygen-isotope composition, temperature and depth of formation of chert at DSDP Leg 62 Holes

We measured oxygen-isotope compositions of 16 siliceous rocks from Deep Sea Drilling Project Sites 463, 464, 465, and 466 (Leg 62). Samples are from deposits that range in age from about 40 to 103 m.y. and that occur at sub-bottom depths of 9 to 461 meters. Mean d18O values range from 28.4 to 36.8 per mil and 36.0 ± 0.3 per mil for quartz-rich and opal-CTrich rocks, respectively. d18O values in chert decrease with increasing sub-bottom depth; the slope of the d18O/depth curve is less steep for Site 464 than for the other sites which indicates that chert at Site 464 formed at higher temperatures than chert at Sites 463, 465, and 466. Temperatures of formation of cherts were 7 to 42°C, using the silica-water fractionation factor of Knauth and Epstein (1976), or 19 to 56°C, using the equation of Clayton et al. (1972). Temperatures in the sediment where the cherts now occur are lower than their isotopically determined temperatures of formation, which means that the cherts record an earlier history when temperatures in the sediment section were greater. Estimated sediment temperatures when the cherts formed are comparable to, but generally slightly lower than, those calculated from Knauth and Epstein's equation. The isotopic composition of cherts is more closely related to environment of formation (diagenetic environment) or paleogeothermal gradients, than to paleoclimates (bottom-water temperatures). Opal-CT-rich rocks may better record paleo-bottom-water temperature. In Leg 62 cherts, better crystallinity of quartz corresponds to lower d18O values; this implies progressively higher temperatures of equilibration between quartz and water during maturation of quartz. The interrelationship of d18O and crystallinity is noted also in continental-margin deposits such as the Monterey Formation - but for higher temperatures. The apparent temperature difference between open-ocean and continental-margin deposits can be explained by the dominant control of temperature on silica transformation in the rapidly deposited continental-margin deposits, whereas time, as well as temperature, has a strong influence on the transformations in open-ocean deposits. Comparisons between the chemistry and d18O values of cherts reveal two apparent trends: both boron and SiO2 increase as d18O increases. However, the correspondence between SiO2 and d18O is only apparent, because the two cherts lowest in SiO2 are also the most deeply buried, so the trend actually reflects depth of burial. The correspondence between boron and d18O supports the conclusion that boron is incorporated in the quartz crystal structure during precipitation