Antibody response to Panton-Valentine Leukocidin, a Staphylococcus aureus virulence factor, in pediatric patients from Texas Children's Hospital in Houston, Texas

Staphylococcus aureus is an important human pathogen of global health significance, whose frequency is increasing and whose persistence and versatility allow it to remain established in communities worldwide. An observed significant increase in infections, particularly in children with no predisposing risk factors or medical conditions, led to an investigation into pediatric humoral immune response to Panton-Valentine Leukocidin (PVL) and to other antigens expressed by S. aureus that represent the important classes of virulence activities. Patients who were diagnosed with staphylococcal infections were enrolled (n=60), and serum samples collected at the time of admission were analyzed using ELISA and Western blot to screen for immune response to the panel of recombinant proteins. The dominant circulating immunoglobulin titers in this pediatric population were primarily IgG, were specific, and were directed against LukF and LukS, while suppression of other important virulence factors in the presence of PVL was suggested. Patients with invasive infections (osteomyelitis, pneumonia or myositis) had higher titers against LukF and LukS compared to patients with non-invasive infections (abscesses, cellulitis or lymphadenitis). In patients with osteomyelitis, antibody responses to LukF and LukS were higher than antibody responses to any other virulence factor examined. This description of immune response to selected virulence factors of S. aureus caused by isolates of the USA300 lineage in children is novel. Antibody titers also correlated with markers of inflammation. The significance of these correlations remains to be understood.^

TRANSMISSION DYNAMICS OF ENTERIC BACTERIA IN DAY-CARE CENTERS, HOUSTON, TEXAS

An investigation was undertaken to evaluate the role of fomites in the transmission of diarrhea in day-care centers (DCC) and to elucidate the paths by which enteric organisms spread within this setting.^ During a nine-month period (December 1980-August 1981) extensive culturing of inanimate objects, as well as children and staff was done routinely each month and again repeated during diarrhea outbreaks. Air was sampled from the classrooms and toilets using a Single-Stage Sieve Sampler (Ross Industries, Midland, VA.). Stool samples were collected from both ill and well children and staff in the affected rooms only during outbreaks. Environmental samples were processed for Shigella, salmonella and fecal coliforms while stools were screened for miscellaneous enteropathogens.^ A total of 11 outbreaks occurred in the 5 DCC during the study period. Enteric pathogens were recovered in 7 (64%) of the outbreaks. Multiple pathogens were identified in 3 outbreaks. The most frequently identified pathogen in stools was Giardia lamblia which was recovered in 5 (45%) of the outbreaks. Ten of the 11 (91%) outbreaks occurred in children less than 12 months of age.^ Environmental microbiology studies together with epidemiologic information revealed that enteric organisms were transmitted from person-to-person. On routine sampling, fecal coliforms were most frequently isolated from tap handles and diaper change areas. Contamination with fetal coliforms was wide-spread during diarrhea outbreaks. Fecal coliforms were recovered with significantly greater frequency from hands, toys and other classroom objects during outbreaks than during non-outbreak period. Salmonella typhimurium was recovered from a table top during an outbreak of Salmonellosis. There was no association between the level of enteric microbial contamination in the toilet areas and the occurrence of outbreaks. No evidence was found to indicate that enteric organisms were spread by the airborne route via aerosols.^ Toys, other classroom objects and contaminated hands probably play a major role in the transmission of enteropathogens during day-care center outbreaks. The presence of many enteric agents in the environment undoubtedly explains the polymicrobial etiology of the day-care center associated diarrhea outbreaks. ^

APPLICATION OF THE BRAINSTEM EVOKED RESPONSE (BER) TO NEUROTOXICITY EVALUATION OF THE AUDITORY SYSTEM: ASSESSMENT OF INORGANIC LEAD-INDUCED OTOTOXICITY

An experimental procedure was developed using the Brainstem Evoked Response (BER) electrophysiological technique to assess the effect of neurotoxic substances on the auditory system. The procedure utilizes Sprague-Dawley albino rats who have had dural electrodes implanted in their skulls, allowing neuroelectric evoked potentials to be recorded from their brainstems. Latency and amplitude parameters derived from the evoked potentials help assess the neuroanatomical integrity of the auditory pathway in the brainstem. Moreover, since frequency-specific auditory stimuli are used to evoke the neural responses, additional audiometric information is obtainable. An investigation on non-exposed control animals shows the BER threshold curve obtained by tests at various frequencies very closely approximates that obtained by behavioral audibility tests. Thus, the BER appears to be a valid measure of both functional and neuroanatomical integrity of the afferent auditory neural pathway.^ To determine the usefulness of the BER technique in neurobehavioral toxicology research, a known neurotoxic agent, Pb, was studied. Female Sprague-Dawley rats were dosed for 45 days with low levels of Pb acetate in their drinking water, after which BER recordings were obtained. The Pb dosages were determined from the findings of an earlier pilot study. One group of 6 rats received normal tap water, one group of 7 rats received a solution of 0.1% Pb, and another group of 7 rats received a solution of 0.2% Pb. After 45 days, the three groups exhibited blood Pb levels of 4.5 (+OR-) 0.43 (mu)g/100 ml, 37.8 (+OR-) 4.8 (mu)g/100 ml and 47.3 (+OR-) 2.7 (mu)g/100 ml, respectively.^ The results of the BER recording indicated evoked response waveform latency abnormalities in both the Pb-treated groups when midrange frequency (8 kHz to 32 kHz) stimuli were used. For the most part, waveform amplitudes did not vary significantly from control values. BER recordings obtained after a 30-day recovery period indicated the effects seen in the 0.1% Pb group had disappeared. However, those anomalies exhibited by the 0.2% Pb group either remained or increased in number. This outcome indicates a longer lasting or possibly irreversible effect on the auditory system from the higher dose of Pb. The auditory pathway effect appears to be in the periphery, at the level of the cochlea or the auditory (VIII) nerve. The results of this research indicate the BER technique is a valuable and sensitive indicator of low-level toxic effects on the auditory system.^

Evidence for the role of agonist binding frequency in receptor -mediated activation of adenylate cyclase

$\beta$-adrenergic receptor-mediated activation of adenylate cyclase exhibits an agonist-specific separation between the dose/response curve (characterized by the EC$\sb{50}$) and the dose/binding curve (characterized by the K$\sb{\rm d}$). Cyclase activity can be near-maximal when receptor occupancy is quite low (EC$\sb{50}$ $\ll$ K$\sb{\rm d}$). This separation between the binding and response curves can be explained by the assumption that the rate of cyclase activation is proportional to the concentration of agonist-bound receptors, since the receptor is mobile and can activate more than one cyclase (the Collision Coupling Model of Tolkovsky and Levitzki). Here it is established that agonist binding frequency plays an additional role in adenylate cyclase activation in S49 murine lymphoma cells. Using epinephrine (EC$\sb{50}$ = 10 nM, K$\sb{\rm d}$ = 2 $\mu$M), the rate of cyclase activation decreased by 80% when a small (1.5%) receptor occupancy was restricted (by addition of the antagonist propranolol) to a small number (1.5%) of receptors rather than being proportionally distributed among the cell's entire population of receptors. Thus adenylate cyclase activity is not proportional to receptor occupancy in all circumstances. Collisions between receptor and cyclase pairs apparently occur a number of times in rapid sequence (an encounter); the high binding frequency of epinephrine ensures that discontiguous regions of the cell surface experience some period of agonist-bound receptor activity per small unit time minimizing "wasted" collisions between activated cyclase and bound receptor within an encounter. A contribution of agonist binding frequency to activation is thus possible when: (1) the mean lifetime of the agonist-receptor complex is shorter than the mean encounter time, and (2) the absolute efficiency (intrinsic ability to promote cyclase activation per collision) of the agonist-receptor complex is high. These conclusions are supported by experiments using agonists of different efficiencies and binding frequencies. These results are formalized in the Encounter Coupling Model of adenylate cyclase activation, which takes into explicit account the agonist binding frequency, agonist affinity for the $\beta$-adrenergic receptor, agonist efficiency, encounter frequency and the encounter time between receptor and cyclase. ^

Mid-Wisconsin to Holocene permafrost and landscape dynamics based on a drained lake basin core from the northern Seward Peninsula, Northwest Alaska

Permafrost-related processes drive regional landscape dynamics in the Arctic terrestrial system. A better understanding of past periods indicative of permafrost degradation and aggradation is important for predicting the future response of Arctic landscapes to climate change. Here, we used a multi-proxy approach to analyze a ~4 m long sediment core from a drained thermokarst lake basin on the northern Seward Peninsula in western Arctic Alaska (USA). Sedimentological, biogeochemistical, geochronological, micropaleontological (ostracoda, testate amoeba) and tephra analyses were used to determine the long-term environmental Early-Wisconsin to Holocene history preserved in our core for Central Beringia. Yedoma accumulation dominated throughout the Early to Late-Wisconsin but was interrupted by wetland formation from 44.5 to 41.5 ka BP. The latter was terminated by deposition of 1 m of volcanic tephra, most likely originating from the South Killeak Maar eruption at about 42 ka BP. Yedoma deposition continued until 22.5 ka BP and was followed by a depositional hiatus in the sediment core between 22.5 and 0.23 ka BP. We interpret this hiatus as due to intense thermokarst activity in the areas surrounding the site, which served as a sediment source during the Late-Wisconsin to Holocene climate transition. The lake forming the modern basin on the upland initiated around 0.23 ka BP, which drained catastrophically in spring 2005. The present study emphasizes that Arctic lake systems and periglacial landscapes are highly dynamic and permafrost formation as well as degradation in Central Beringia was controlled by regional to global climate patterns and as well as by local disturbances.

(Table 1) Bioclimatic subzones and soil characteristics along the Yamal Arctic Transect, northwestern Siberia

Sustainability of tundra vegetation under changing climate on the Yamal Peninsula, northwestern Siberia, home to the world's largest area of reindeer husbandry, is of crucial importance to the local native community. An integrated investigation is needed for better understanding of the effects of soils, climate change and grazing on tundra vegetation in the Yamal region. In this study we applied a nutrient-based plant community model - ArcVeg - to evaluate how two factors (soil organic nitrogen (SON) levels and grazing) interact to affect tundra responses to climate warming across a latitudinal climatic gradient on the Yamal Peninsula. Model simulations were driven by field-collected soil data and expected grazing patterns along the Yamal Arctic Transect (YAT), within bioclimate subzones C (high arctic), D (northern low arctic) and E (southern low arctic). Plant biomass and NPP (net primary productivity) were significantly increased with warmer bioclimate subzones, greater soil nutrient levels and temporal climate warming, while they declined with higher grazing frequency. Temporal climate warming of 2 °C caused an increase of 665 g/m**2 in total biomass at the high SON site in subzone E, but only 298 g/m**2 at the low SON site. When grazing frequency was also increased, total biomass increased by only 369 g/m**2 at the high SON site in contrast to 184 g/m**2 at the low SON site in subzone E. Our results suggest that high SON can support greater plant biomass and plant responses to climate warming, while low SON and grazing may limit plant response to climate change. In addition to the first order factors (SON, bioclimate subzones, grazing and temporal climate warming), interactions among these significantly affect plant biomass and productivity in the arctic tundra and should not be ignored in regional scale studies.

Ice velocities of Nordenskiöldbreen glacier, Svalbard

Precise measurements of ice-flow velocities are necessary for a proper understanding of the dynamics of glaciers and their response to climate change. We use stand-alone single-frequency GPS receivers for this purpose. They are designed to operate unattended for 1-3 years, allowing uninterrupted measurements for long periods with hourly temporal resolution. We present the system and illustrate its functioning using data from 9 GPS receivers deployed on Nordenskiöldbreen, Svalbard, for the period 2006-2009. The accuracy of the receivers is 1.62 m based on the standard deviation in the average location of a stationary reference station (NBRef). Both the location of NBRef and the observed flow velocities agree within one standard deviation with DGPS measurements. Periodicity (6, 8, 12, 24 h) in the NBRef data is largely explained by the atmospheric, mainly ionospheric, influence on the GPS signal. A (weighed) running-average on the observed locations significantly reduces the standard deviation and removes high frequency periodicities, but also reduces the temporal resolution. Results show annual average velocities varying between 40 and 55 m/yr at stations on the central flow-line. On weekly to monthly time-scales we observe a peak in the flow velocities (from 60 to 90 m/yr) at the beginning of July related to increased melt-rates. No significant lag is observed between the timing of the maximum speed between different stations. This is likely due to the limited temporal resolution after averaging in combination with the relatively small distance (max. ±13 km) between the stations.

Seasonal changes in labile organic matter composition on the continental shelf and bathyal sediments of the Cretan Sea

Bacterial abundance, biomass and cell size were studied in the oligotrophic sediments of the Cretan Sea (Eastern Mediterranean), in order to investigate their response to the seasonal varying organic matter (OM) inputs. Sediment samples were collected on a seasonal basis along a transect of seven stations (ranging from 40 to 1570 m depth) using a multiple-corer. Bacterial parameters were related to changes in chloroplastic pigment equivalents (CPE), the biochemical composition (proteins, lipids, carbohydrates) of the sedimentary organic matter and the OM flux measured at a fixed station over the deep basin (1570 m depth). The sediments of the Cretan Sea represent a nutrient depleted ecosystem characterised by a poor quality organic matter. All sedimentary organic compounds were found to vary seasonally, and changes were more evident on the continental shelf than in deeper sediments. Bacterial abundance and biomass in the sediments of the Cretan Sea (ranging from 1.02 to 4.59 * 10**8 cells/g equivalent to 8.7 and 38.7 µgC/g) were quite high and their distribution appeared to be closely related to the input of fresh organic material. Bacterial abundance and biomass were sensitive to changes in nutrient availability, which also controls the average cell size and the frequency of dividing cells. Bacterial abundance increased up to 3-fold between August '94 and February '95 in response to the increased amount of sedimentary proteins and CPE, indicating that benthic bacteria were constrained more by changes in quality rather than the quantity of the sedimentary organic material. Bacterial responses to the food inputs were clearly detectable down to 10 cm depth. The distribution of labile organic compounds in the sediments appeared to influence the vertical patterns of bacterial abundance and biomass. Cell size decreased significantly with water depth. Bacterial abundance and biomass were characterised by clear seasonal changes in response to seasonal OM pulses. The strong coupling between protein flux and bacterial biomass together with the strong bacterial dominance over the total biomass suggest that the major part of the carbon flow was channelled through the bacteria and the benthic microbial loop.

Plant frequency and cover abundance at three sites on Disko Island in 1967/1970 and 2009

We report on a revisit in 2009 to sites where vegetation was recorded in 1967 and 1970 on Disko Island, West Greenland. Re-sampling of the same clones of the grass Phleum alpinum after 39 years showed complete stability in biometrics but dramatic earlier onset of various phenological stages that were not related to changes in population density. In a fell-field community, there was a net species loss, but in a herb-slope community, species losses balanced those that were gained. The type of species establishing and increasing in frequency and/or cover abundance at the fell-field site, particularly prostrate dwarf shrubs, indicates a possible start of a shift towards a heath, rather than a fell-field community. At the herb-slope site, those species that established or increased markedly in frequency and/or cover abundance indicate a change to drier conditions. This is confirmed both by the decrease in abundance of Alchemilla glomerulans and Epilobium hornemanii, and the drying of a nearby pond. The causes of these changes are unknown, although mean annual temperature has risen since 1984.

Pollen record and calculated holocene vegetation and climate dynamics from Sihailongwan Maar Lake, NE China

High-resolution palynological analysis on annually laminated sediments of Sihailongwan Maar Lake (SHL) provides new insights into the Holocene vegetation and climate dynamics of NE China. The robust chronology of the presented record is based on varve counting and AMS radiocarbon dates from terrestrial plant macro-remains. In addition to the qualitative interpretation of the pollen data, we provide quantitative reconstructions of vegetation and climate based on the method of biomization and weighted averaging partial least squares regression (WA-PLS) technique, respectively. Power spectra were computed to investigate the frequency domain distribution of proxy signals and potential natural periodicities. Pollen assemblages, pollen-derived biome scores and climate variables as well as the cyclicity pattern indicate that NE China experienced significant changes in temperature and moisture conditions during the Holocene. Within the earliest phase of the Holocene, a large-scale reorganization of vegetation occurred, reflecting the reconstructed shift towards higher temperatures and precipitation values and the initial Holocene strengthening and northward expansion of the East Asian summer monsoon (EASM). Afterwards, summer temperatures remain at a high level, whereas the reconstructed precipitation shows an increasing trend until approximately 4000 cal. yr BP. Since 3500 cal. yr BP, temperature and precipitation values decline, indicating moderate cooling and weakening of the EASM. A distinct periodicity of 550-600 years and evidence of a Mid-Holocene transition from a temperature-triggered to a predominantly moisture-triggered climate regime are derived from the power spectra analysis. The results obtained from SHL are largely consistent with other palaeoenvironmental records from NE China, substantiating the regional nature of the reconstructed vegetation and climate patterns. However, the reconstructed climate changes contrast with the moisture evolution recorded in S China and the mid-latitude (semi-)arid regions of N China. Whereas a clear insolation-related trend of monsoon intensity over the Holocene is lacking from the SHL record, variations in the coupled atmosphere-Pacific Ocean system can largely explain the reconstructed changes in NE China.

Modelling calving front dynamics using a level-set method: application to Jakobshavn Isbræ, West Greenland, links model results in MATLAB format

Calving is a major mechanism of ice discharge of the Antarctic and Greenland ice sheets, and a change in calving front position affects the entire stress regime of marine terminating glaciers. The representation of calving front dynamics in a 2-D or 3-D ice sheet model remains non-trivial. Here, we present the theoretical and technical framework for a level-set method, an implicit boundary tracking scheme, which we implement into the Ice Sheet System Model (ISSM). This scheme allows us to study the dynamic response of a drainage basin to user-defined calving rates. We apply the method to Jakobshavn Isbræ, a major marine terminating outlet glacier of the West Greenland Ice Sheet. The model robustly reproduces the high sensitivity of the glacier to calving, and we find that enhanced calving triggers significant acceleration of the ice stream. Upstream acceleration is sustained through a combination of mechanisms. However, both lateral stress and ice influx stabilize the ice stream. This study provides new insights into the ongoing changes occurring at Jakobshavn Isbræ and emphasizes that the incorporation of moving boundaries and dynamic lateral effects, not captured in flow-line models, is key for realistic model projections of sea level rise on centennial timescales.

Shoreline change on nine reef islands over a seven-decade period

Atoll islands are subject to a variety of processes that influence their geomorphological development. Analysis of historical shoreline changes using remotely sensed images has become an efficient approach to both quantify past changes and estimate future island response. However, the detection of long-term changes in beach width is challenging mainly for two reasons: first, data availability is limited for many remote Pacific islands. Second, beach environments are highly dynamic and strongly influenced by seasonal or episodic shoreline oscillations. Consequently, remote-sensing studies on beach morphodynamics of atoll islands deal with dynamic features covered by a low sampling frequency. Here we present a study of beach dynamics for nine islands on Takú Atoll, Papua New Guinea, over a seven-decade period. A considerable chronological gap between aerial photographs and satellite images was addressed by applying a new method that reweighted positions of the beach limit by identifying "outlier" shoreline positions. On top of natural beach variability observed along the reweighted beach sections, we found that one third of the analyzed islands show a statistically significant decrease in reweighted beach width since 1943. The total loss of beach area for all islands corresponds to 44% of the initial beach area. Variable shoreline trajectories suggest that changes in beach width on Takú Atoll are dependent on local control (that is, human activity and longshore sediment transport). Our results show that remote imagery with a low sampling frequency may be sufficient to characterize prominent morphological changes in planform beach configuration of reef islands.