Mechanisms of TGF-beta1-induced neuronal plasticity in Aplysia

Transforming growth factor beta-1 (TGF-β1) is a cytokine and neurotrophic factor whose neuromodulatory effects in Aplysia californica were recently described. Previous results demonstrated that TGF-β1 induces long-term increases in the efficacy of sensorimotor synapses, a neural correlate of sensitization of the defensive tail withdrawal reflex. These results provided the first evidence that a neurotrophic factor regulates neuronal plasticity associated with a simple form of learning in Aplysia, and raised many questions regarding the nature of the modulation. No homologs of TGF-β had previously been identified in Aplysia, and thus, it was not known whether components of TGF-β1 signaling pathways were present in Aplysia. Furthermore, the signaling mechanisms engaged by TGF-β1 had not been identified, and it was not known whether TGF-β1 regulated other aspects of neuronal function.^ The present investigation into the actions of TGF-β1 was initiated by examining the distribution of the type II TGF-β1 receptor, the ligand binding receptor. The receptor was widely distributed in the CNS and most neurons exhibited somatic and neuritic immunoreactivity. In addition, the ability of TGF-β1 to activate the cAMP/PKA and MAPK pathways, known to regulate several important aspects of neuronal function, was examined. TGF-β1 acutely decreased cAMP levels in sensory neurons, activated MAPK and triggered translocation of MAPK to the nucleus. MAPK activation was critical for both short- and long-term regulation of neuronal function by TGF-β1. TGF-β1 acutely decreased synaptic depression induced by low frequency stimuli in a MAPK-dependent manner. This regulation may result, at least in part, from the modulation of synapsin, a major peripheral synaptic vesicle protein. TGF-β1 stimulated MAPK-dependent phosphorylation of synapsin, a process believed to regulate synaptic vesicle mobilization from reserve to readily-releasable pools of neurotransmitter. In addition to its acute effect on synaptic efficacy, TGF-β1 also induced long-term increases in sensory neuron excitability. Whereas transient exposure to TGF-β1 was not sufficient to drive short-or long-term changes in excitability, prolonged exposure to TGF-β1 induced long-term changes in excitability that depended on MAPK. The results of these studies represent significant progress toward an understanding of the role of TGF-β1 in neuronal plasticity. ^

The role of UV radiation in the development of myeloid malignancy in Rag2 knockout mice

Excessive exposure to the UV radiation present in sunlight can lead to the development of skin cancer in humans. Majority of the UV-induced skin tumors in immune-competent mice are highly antigenic in nature. Additionally, they exhibit a high frequency of mutations in the p53 gene, which arise very early in the course of UV radiation and most of them disappear before the development of skin tumors. ^ Initially, this study was to determine whether UV radiation induces skin tumors much earlier in immune deficient Rag2 knockout mice than in immune-competent mice, and if so, compare their antigenic properties and p53 mutation spectra. However, chronic UV irradiation (10 kJ/m2) induced myeloproliferative disease (MPD) as early as 4 weeks in Rag2 knockout mice instead of skin tumors. Conversely, unirradiated Rag2 knockout mice developed MPD at a low frequency, but the frequency increased with the animal's age. Although the UV-irradiated wild type mice (B6129) developed MPD, its frequency was lower and the occurrence much later than the Rag2 knockout mice. ^ This observation led to our new hypothesis that UV irradiation plays a role in the development of MPD in Rag2 knockout mice. After 4 weeks of UV radiation, both histopathology (myeloid:erythroid ratio, number of blast cells) and flow cytometry (mature myeloid, granulocytes and immature cells) demonstrated an increased number of mice affected with the disease in the UV-irradiated Rag2 knockout group than the other groups. ^ We also investigated the role of cytokines and absence of T and B cells in the development of MPD in the Rag2 knockout mice. Results indicated that IL-3 and IL-3Rα chain expression was upregulated in the spleens of the UV-irradiated Rag2 knockout mice (4 weeks). Reconstitution of the Rag2 knockout mice with T and B cells abrogated the UV-accelerated development of MPD. Both histopathology and flow cytometric analysis (mature myeloid cells, granulocytes) showed a decrease in the number of mice affected with the disease in the UV-irradiated, reconstituted group rather than any other group. In summary, this study provides the first experimental evidence that exposure to UV irradiation can lead to the development of MPD in immune deficient mice. ^

Fort Richardson Ordnance Detonations and the Harbor Porpoise: A Case Study in Marine Mammal Bioacoustics

Hearing is extremely important for cetaceans because it is their “principal sense” (Weilgart, 2007) thus the harbor porpoise and other marine animals are highly dependent on sound for survival. This is why we should care about the impact of noise on animals like the harbor porpoise. Since sound travels so well in water, an explosion, sonar, boat noise, etc. can affect a very large area and thus many different species of marine mammals. Although military actions such as low frequency sonar have made recent news, noise has been affecting cetaceans, especially beaked whales, since at least 1991 (Weilgart, 2007). This study is an investigation of the possible impacts of artillery detonated on land on harbor porpoise hearing and covers some of the history of Fort Richardson, the legal and historical aspects and history of this type of concern, the science and physics of sound, marine mammal hearing and general biology of the harbor porpoise. Data were collected at the Fort Richardson Army base during June of 2007 by researchers from the University of Connecticut and the University of Rhode Island and will be used to determine the possible impacts that these detonations could have on the harbor porpoise.

The influence of social connectedness and self-esteem on participant retention in a bi-ethnic longitudinal study

In prospective studies it is essential that the study sample accurately represents the target population for meaningful inferences to be drawn. Understanding why some individuals do not participate, or fail to continue to participate, in longitudinal studies can provide an empirical basis for the development of effective recruitment and retention strategies to improve response rates. This study examined the influence of social connectedness and self-esteem on long-term retention of participants, using secondary data from the “San Antonio Longitudinal Study of Aging” (SALSA), a population-based study of Mexican Americans (MAs) and European Americans (EAs) aged over 65 years residing in San Antonio, Texas. We tested the effect of social connectedness, self-esteem and socioeconomic status on participant retention in both ethnic groups. In MAs only, we analyzed whether acculturation and assimilation moderated these associations and/or had a direct effect on participant retention. ^ Low income, low frequency of social contacts and length of recruitment interval were significant predictors of non-completer status. Participants with low levels of social contacts were almost twice as likely as those with high levels of social contacts to be non-completers, even after adjustment for age, sex, ethnic group, education, household income, and recruitment interval (OR = 1.95, 95% CI: 1.26–3.01, p = 0.003). Recruitment interval consistently and strongly predicted non-completer status in all the models tested. Depending on the model, for each year beyond baseline there was a 25–33% greater likelihood of non-completion. The only significant interaction, or moderating, effect observed was between social contacts and cultural values among MAs. Specifically, MAs with both low social contacts and low acculturation on cultural values (i.e., placed high value on preserving Mexican cultural origins) were three and half times more likely to be non-completers compared with MAs in other subgroups comprised of the combination of these variables, even after adjustment for covariates. ^ Long term studies with older and minority participants are challenging for participant retention. Strategies can be designed to enhance retention by paying special attention to participants with low social contacts and, in MAs, participants with both low social contacts and low acculturation on cultural values. Minimizing the time interval between baseline and follow-up recruitment, and maintaining frequent contact with participants during this interval should also be is integral to the study design.^

Is H. pylori infection associated with diarrhea in a cohort of 3- to 8-year-old Colombian children?

The Estudio Comunitario sobre la Salud del Niño cohort study followed 326 3- to 8-year-old Colombian children for 4 years to observe the natural history of Helicobacter pylori infection and identify risk factors for acquisition, recurrence and persistence. Acute H. pylori infection during childhood may predispose to other enteric infections and therefore increase the risk of diarrheal disease. This dissertation aimed to estimate the effect of H. pylori infection on the occurrence of diarrhea and parasitic co-infections. The analysis used Generalized Estimating Equations to obtain odds ratios to estimate relative risks for diarrhea and the Zhang-Yu algorithm to estimate relative risks for on parasitic infections. Andersen-Gill models were used to estimate rate ratios for the effect of H. pylori status on the recurrence of parasitic infections. H. pylori status was classified for the entire follow-up duration in 1 of 3 categories: persistently positive, intermittently positive, and persistently negative. Multivariable models included child’s sex, age, symptoms, medication use, and socio-environmental factors. H. pylori infection was weakly and imprecisely associated with diarrheal disease, which occurred at an unexpectedly low frequency in this study. Persistently H. pylori-positive children had a somewhat higher incidence of reported diarrhea than intermittently positive or persistently negative children. Stratified analysis revealed that the presence of specific helminthes modified the effect of persistent H. pylori infection on diarrhea. The incidence of any parasitic infections was higher in children with persistent H. pylori infection relative to those with intermittent or persistently negative status, but this association did not hold when adjusted for the full set of selected covariates. The effects of H. pylori persistent status were similar for the occurrence or recurrence of Giardia duodenalis, Entamoeba histolytica, and Ascaris lumbricoides. These results show that H. pylori frequently co-exists with other parasites in Andean children and suggest that intermittently H. pylori–positive children might be at a lower risk of parasitic infections than persistently positive children. The relationship of H. pylori infection, helminthic infection and diarrheal disease should be further explored in studies that devote more intensive resources to accurate ascertainment of diarrhea.^

Stable isotope ratios and chemistry on corals from the Caribbean Sea

Instrumental climate data are limited in length and only available with low spatial coverage before the middle of the 20th century. This is too short to reliably determine and interpret decadal and longer scale climate variability and to understand the underlying mechanisms with sufficient accuracy. A proper knowledge of past variability of the climate system is needed to assess the anthropogenic impact on climate and ecosystems, and also important with regard to long-range climate forecasting. Highly-resolved records of past climate variations that extend beyond pre-industrial times can significantly help to understand long-term climate changes and trends. Indirect information on past environmental and climatic conditions can be deduced from climate-sensitive proxies. Large colonies of massive growing tropical reef corals have been proven to sensitively monitor changes in ambient seawater. Rapid skeletal growth, typically ranging between several millimeters to centimeters per year, allows the development of proxy records at sub-seasonal resolution. Stable oxygen isotopic composition and trace elemental ratios incorporated in the aragonitic coral skeleton can reveal a detailed history of past environmental conditions, e.g., sea surface temperature (SST). In general, coral-based reconstructions from the tropical Atlantic region have lagged behind the extensive work published using coral records from the Indian and Pacific Oceans. Difficulties in the analysis of previously utilized coral archives from the Atlantic, typically corals of the genera Montastrea and Siderastrea, have so far exacerbated the production of long-term high-resolution proxy records. The objective of this study is the evaluation of massive fast-growing corals of the species Diploria strigosa as a new marine archive for climate reconstructions from the tropical Atlantic region. For this purpose, coral records from two study sites in the eastern Caribbean Sea (Guadeloupe, Lesser Antilles; and Archipelago Los Roques, Venezuela) were examined. At Guadeloupe, a century-long monthly resolved multi-proxy coral record was generated. Results present the first d18O (Sr/Ca)-SST calibration equations for the Atlantic braincoral Diploria strigosa, that are robust and consistent with previously published values using other coral species from different regions. Both proxies reflect local variability of SST on a sub-seasonal scale, which is a precondition for studying seasonally phase-locked climate variations, as well as track variability on a larger spatial scale (i.e., in the Caribbean and tropical North Atlantic). Coral Sr/Ca reliably records local annual to interannual temperature variations and is higher correlated to in-situ air temperature than to grid-SST. The warming calculated from coral Sr/Ca is concurrent with the strong surface temperature increase at the study site during the past decades. Proxy data show a close relationship to major climate signals from the tropical Pacific and North Atlantic (the El Niño Southern Oscillation (ENSO) and the North Atlantic Oscillation (NAO)) affecting the seasonal cycle of SST in the North Tropical Atlantic (NTA). Coral oxygen isotopes are also influenced by seawater d18O (d18Osw) which is linked to the hydrological cycle, and capture large-scale climate variability in the NTA region better than Sr/Ca. Results from a quantitative comparison between extreme events in the two most prominent modes of external forcing, namely the ENSO and NAO, and respective events recorded in seasonal coral d18O imply that SST variability at the study site is highly linked to Pacific and North Atlantic variability, by this means supporting the assumptions of observational- and model-based studies which suggest a strong impact of ENSO and NAO forcings onto the NTA region through a modulation of trade wind strength in winter. Results from different spectral analysis tools suggest that interannual climate variability recorded by the coral proxies is II largely dictated by Pacific ENSO forcing, whereas at decadal and longer timescales the influence of the NAO is dominan. tThe Archipelago Los Roques is situated in the southeastern Caribbean Sea, north of the Venezuelan coast. Year-to-year variations in monthly resolved coral d18O of a nearcentury- long Diploria strigosa record are significantly correlated with SST and show pronounced multidecadal variations. About half of the variance in coral d18O can be explained by variations in seawater d18O, which can be estimated by calculating the d18Oresidual via subtracting the SST component from measured coral d18O. The d18Oresidual and a regional precipitation index are highly correlated at low frequencies, suggesting that d18Osw variations are primarily atmospheric-driven. Warmer SSTs at Los Roques broadly coincide with higher precipitation in the southeastern Caribbean at multidecadal time scales, effectively strengthening the climate signal in the coral d18O record. The Los Roques coral d18O record displays a strong and statistically significant relationship to different indices of hurricane activity during the peak of the Atlantic hurricane season in boreal summer and is a particularly good indicator of decadal-multidecadal swings in the latter indices. In general, the detection of long-term changes and trends in Atlantic hurricane activity is hampered due to the limited length of the reliable instrumental record and the known inhomogeneity in the observational databases which result from changes in observing practice and technology over the years. The results suggest that coral-derived proxy data from Los Roques can be used to infer changes in past hurricane activity on timescales that extend well beyond the reliable record. In addition, the coral record exhibits a clear negative trend superimposed on the decadal to multidecadal cycles, indicating a significant warming and freshening of surface waters in the genesis region of tropical cyclones during the past decades. The presented coral d18O time series provides the first and, so far, longest continuous coral-based record of hurricane activity. It appears that the combination of both signals (SST and d18Osw) in coral d18O leads to an amplification of large-scale climate signals in the record, and makes coral d18O even a better proxy for hurricane activity than SST alone. Atlantic hurricane activity naturally exhibits strong multidecadal variations that are associated with the Atlantic Multidecadal Oscillation (AMO), the major mode of lowfrequency variability in the North Atlantic Ocean. However, the mechanisms underlying this multidecadal variability remain controversial, primarily because of the limited instrumental record. The Los Roques coral d18O displays strong multidecadal variability with a period of approximately 60 years that is closely related to the AMO, making the Archipelago Los Roques a very sensitive location for studying low-frequency climate variability in the Atlantic Ocean. In summary, the coral records presented in this thesis capture different key climate variables in the north tropical Atlantic region very well, indicating that fast-growing Diploria strigosa corals represent a promising marine archive for further proxy-based reconstructions of past climate variability on a range of time scales.

Síndrome de Melkersson-Rosenthal : un caso de difícil resolución

Presentamos un informe sobre un caso clínico incompleto de un Síndrome de Melkersson-Rosenthal (SMR). Los motivos de la presentación son: la baja frecuencia de aparición de esta patología, el manejo diagnóstico llevado a cabo en nuestro pacien- te, el estudio detallado de esta enfermedad, las dificultades terapéuti- cas que ofreció este caso, y el intercambio de experiencias que pudiera resultar de esta presentación. Fue estudiado minuciosamente para con- firmar el proceso clínico, histológico, ver las posibles etiologías, diag- nósticos diferenciales. Finalmente se establecieron acciones terapéuti- cas con variados resultados.

Enfermedad de Creutzfeld Jakob, desafío diagnóstico : reporte de dos casos en la ciudad de Mendoza

La enfermedad de Creutzfeldt-Jakob (ECJ) es una afección neurodege-nerativa rápidamente progresiva y mortal producida por priones. Es la más común de las encefalopatías espongiformes. La hipótesis prevalente sugiere que se inicia y propaga por conversión de una proteína priónica normal (PrP) en una isoforma conformacional anormal (PrPreS), que se acumula en el cerebro causando destrucción neuronal. Se reporta el caso de dos pacientes asistido en el Servicio de Neurología del Hospital Lagomaggiore de la ciudad de Mendoza en el período de 2 años: mujer de 49 años con cuadro de deterioro cognitivo rápidamente progresivo asociado a trastorno de la marcha y ataxia de 2 meses de evolución; y varón de 54 años con conductas inapropiadas y desorientación temporo-espacial de 20 días de evolución. Ambos con EEG compatible y proteína 14.3.3 positiva, falleciendo semanas después del diagnóstico. Se discute ambos casos, los cuales representaron un desafío diagnóstico dada la baja frecuencia y escaso reconocimiento de esta entidad en nuestro medio, debiendo debe ser considerado en pacientes que evolucionan a una demencia rápidamente progresiva.

Geometric parameters of shoreface profiles of Laptev Sea erosion coast (Table 1)

Field investigations of the Laptev Sea shoreface morphology were carried out (1) off erosional shores composed of unconsolidated sediments, (2) off the modern delta shores of the Lena River, and (3) off rocky shores. It was found that profiles off erosional shores had a concave shape. This shape is not well described by commonly applied power functions, a feature, which is in disagreement with the generally accepted concept of the equilibrium shape of shoreface profiles. The position of the lower shoreface boundary is determined by the elevation of the coastal lowland inundated during the last transgression (at -5 to -10 m) and may easily be recognized by a sharp, an order of magnitude decrease in the mean inclination of the sea floor. The mean shoreface inclination depends on sediment grain-size and ranges from 0.0022 to 0.033. The concave shape of the shoreface did not change substantially during the last 20-30 years, which indicates that shoreline retreat did not slow down and hence suggests continued intensive coastal erosion in the 21st century. The underwater part of the Lena River delta extends up to 35 km offshore. Its upper part is formed by a shallow and up to 18-km wide bench, which reaches depths of 2-3 m along the outer edge. The evolution of the delta was irregular. Whereas some parts of the delta are advancing rapidly (58 m/year), other parts are eroding. Comparison of measured profiles with older bathymetric data gave an opportunity to evaluate the changes of the underwater delta over past decades. Bathymetric surveys of the seabed around the delta can thus contribute towards a quantification of the sediment budget of the river-sea system. In addition, some sections of the Laptev Sea coast are composed of bedrock that has a comparatively low resistance to wave erosion. These sections may supply a considerable amount of sediment, especially if the cliffs are high. This source must therefore also be taken into account when assessing the contribution of shore erosion to the Laptev Sea sediment budget.

Stable oxygen isotope record of Globigerinoides ruber of ODP Site 133-820 off the Great Barriere Reef

Oxygen-isotope ratio measurements are presented for the planktonic species Globigerinoides ruber collected from shallow-water, upper-slope sediments from Holes 820A and 820B in 280 m of water, on the seaward edge of the Great Barrier Reef. Correlation of the Site 820 isotope curve with deep-sea reference curves of the Pacific Ocean (Core V28-238, Hole 677A, Hole 607A) permits the definition of isotope stages 1 to 19 in the top 145 m of Holes 820A and 820B. However, paleontological data indicate that stages 4 and 7 might be missing and that two hiatuses occur at a depth of 8.05 to 12.1 and 34.55 to 35.8 mbsf. Using deep-sea Hole 677A as a reference for ice-volume variations, we determine the difference in isotopic signature between it and Site 820. We propose that this difference is a regional signal representing a progressive 4°C increase in surface-water temperature at Site 820. The proposed temperature change was initiated at about 400 k.y. and corresponds to a change from high-to-low frequency variations in Pleistocene isotope signals. We postulate that these changes may have catalyzed the growth of the Great Barrier Reef. The shift also coincides with changes in seismic character and some physical and chemical sediment characteristics.

Measurements of velocity-dependent and slip-dependent frictional strength in laboratory friction experiments on natural samples from IODP Expedition 316 and ODP Hole 190-1174B

Slowslip forms part of the spectrum of fault behaviour between stable creep and destructive earthquakes. Slow slip occurs near the boundaries of large earthquake rupture zones and may sometimes trigger fast earthquakes. It is thought to occur in faults comprised of rocks that strengthen under fast slip rates, preventing rupture as a normal earthquake, or on faults that have elevated pore-fluid pressures. However, the processes that control slow rupture and the relationship between slow and normal earthquakes are enigmatic. Here we use laboratory experiments to simulate faulting in natural rock samples taken from shallow parts of the Nankai subduction zone, Japan, where very low-frequency earthquakes - a form of slow slip - have been observed.We find that the fault rocks exhibit decreasing strength over millimetre-scale slip distances rather than weakening due to increasing velocity. However, the sizes of the slip nucleation patches in our laboratory simulations are similar to those expected for the very lowfrequency earthquakes observed in Nankai. We therefore suggest that this type of fault-weakening behaviour may generate slow earthquakes. Owing to the similarity between the expected behaviour of slow earthquakes based on our data, and that of normal earthquakes during nucleation, we suggest that some types of slow slip may represent prematurely arrested earthquakes.