Association between Choroidal Characteristics and Systemic Severity in Amyloidosis

PURPOSE: This study aimed to describe the choroidal features of ocular amyloidosis using multimodal imaging, to correlate these findings with systemic involvement, and to propose a choroidal grading system. METHODS: Eleven patients with systemic amyloidosis were reviewed retrospectively. Each case was assigned a grade according to the severity of choroidal findings as determined by both enhanced depth imaging optical coherence tomography and indocyanine green angiography. The severity of systemic amyloidosis was then correlated with the choroidal involvement. RESULTS: On indocyanine green angiography, all patients exhibited hyperfluorescent spots in the late stage and were classified according to preexisting criteria. On enhanced depth imaging optical coherence tomography, hyperreflective foci were seen in the choriocapillaris and Sattler's layer in Grade 1, partial loss of Sattler's layer was additionally seen in Grade 2, and a dense hyperreflective Haller's layer was seen in Grade 3. Choroidal grading scores were significantly correlated with the systemic severity score (P = 0.0014, Pearson's correlation coefficient; ρ = 0.83). CONCLUSION: With ocular amyloidosis, evaluation of choroidal characteristics using multimodal imaging may serve as a biomarker for systemic involvement

DADA: data assimilation for the detection and attribution of weather and climate-related events

A new nudging method for data assimilation, delay‐coordinate nudging, is presented. Delay‐coordinate nudging makes explicit use of present and past observations in the formulation of the forcing driving the model evolution at each time step. Numerical experiments with a low‐order chaotic system show that the new method systematically outperforms standard nudging in different model and observational scenarios, also when using an unoptimized formulation of the delay‐nudging coefficients. A connection between the optimal delay and the dominant Lyapunov exponent of the dynamics is found based on heuristic arguments and is confirmed by the numerical results, providing a guideline for the practical implementation of the algorithm. Delay‐coordinate nudging preserves the easiness of implementation, the intuitive functioning and the reduced computational cost of the standard nudging, making it a potential alternative especially in the field of seasonal‐to‐decadal predictions with large Earth system models that limit the use of more sophisticated data assimilation procedures

Bow shocks, nova shells, disc winds and tilted discs: the nova-like V341 Ara has it all

V341 Ara was recently recognized as one of the closest (d ≃ 150 pc) and brightest (V ≃ 10) nova-like cataclysmic variables. This unique system is surrounded by a bright emission nebula, likely to be the remnant of a recent nova eruption. Embedded within this nebula is a prominent bow shock, where the system’s accretion disc wind runs into its own nova shell. In order to establish its fundamental properties, we present the first comprehensive multiwavelength study of the system. Long-term photometry reveals quasi-periodic, super-orbital variations with a characteristic time-scale of 10–16 d and typical amplitude of ≃1 mag. High-cadence photometry from theTransiting Exoplanet Survey Satellite (TESS) reveals for the first time both the orbital period and a ‘negative superhump’ period. The latter is usually interpreted as the signature of a tilted accretion disc. We propose a recently developed disc instability model as a plausible explanation for the photometric behaviour. In our spectroscopic data, we clearly detect antiphased absorption and emission-line components. Their radial velocities suggest a high mass ratio, which in turn implies an unusually low white-dwarf mass. We also constrain the wind mass-loss rate of the system from the spatially resolved [O III] emission produced in the bow shock; this can be used to test and calibrate accretion disc wind models. We suggest a possible association between V341 Ara and a ‘guest star’ mentioned in Chinese historical records in AD 1240. If this marks the date of the system’s nova eruption, V341 Ara would be the oldest recovered nova of its class and an excellent laboratory for testing nova theory

Characterization of a Human Cell Line Stably Over-Expressing the Candidate Oncogene, Dual Specificity Phosphatase 12

Analysis of chromosomal rearrangements within primary tumors has been influential in the identification of novel oncogenes. Identification of the "driver" gene(s) within cancer-derived amplicons is, however, hampered by the fact that most amplicons contain many gene products. Amplification of 1q21-1q23 is strongly associated with liposarcomas and microarray-based comparative genomic hybridization narrowed down the likely candidate oncogenes to two: the activating transcription factor 6 (atf6) and the dual specificity phosphatase 12 (dusp12). While atf6 is an established transcriptional regulator of the unfolded protein response, the potential role of dusp12 in cancer remains uncharacterized.To evaluate the oncogenic potential of dusp12, we established stable cell lines that ectopically over-express dusp12 in isolation and determined whether this cell line acquired properties frequently associated with transformed cells. Here, we demonstrate that cells over-expressing dusp12 display increased cell motility and resistance to apoptosis. Additionally, over-expression of dusp12 promoted increased expression of the c-met proto-oncogene and the collagen and laminin receptor intergrin alpha 1 (itga1) which is implicated in metastasis.Collectively, these results suggest that dusp12 is oncologically relevant and exposes a potential association between dusp12 and established oncogenes that could be therapeutically targeted

Chemical and Physical Environmental Conditions Underneath Mat- and Canopy-Forming Macroalgae, and Their Effects on Understorey Corals

Disturbed coral reefs are often dominated by dense mat- or canopy-forming assemblages of macroalgae. This study investigated how such dense macroalgal assemblages change the chemical and physical microenvironment for understorey corals, and how the altered environmental conditions affect the physiological performance of corals. Field measurements were conducted on macroalgal-dominated inshore reefs in the Great Barrier Reef in quadrats with macroalgal biomass ranging from 235 to 1029 g DW m−2 dry weight. Underneath mat-forming assemblages, the mean concentration of dissolved oxygen was reduced by 26% and irradiance by 96% compared with conditions above the mat, while concentrations of dissolved organic carbon and soluble reactive phosphorous increased by 26% and 267%, respectively. The difference was significant but less pronounced under canopy-forming assemblages. Dissolved oxygen declined and dissolved inorganic carbon and alkalinity increased with increasing algal biomass underneath mat-forming but not under canopy-forming assemblages. The responses of corals to conditions similar to those found underneath algal assemblages were investigated in an aquarium experiment. Coral nubbins of the species Acropora millepora showed reduced photosynthetic yields and increased RNA/DNA ratios when exposed to conditions simulating those underneath assemblages (pre-incubating seawater with macroalgae, and shading). The magnitude of these stress responses increased with increasing proportion of pre-incubated algal water. Our study shows that mat-forming and, to a lesser extent, canopy-forming macroalgal assemblages alter the physical and chemical microenvironment sufficiently to directly and detrimentally affect the metabolism of corals, potentially impeding reef recovery from algal to coral-dominated states after disturbance. Macroalgal dominance on coral reefs therefore simultaneously represents a consequence and cause of coral reef degradation

Alpine bogs of southern Spain show human-induced environmental change superimposed on long-term natural variations

Recent studies have proved that high elevation environments, especially remote wetlands, are exceptional ecological sensors of global change. For example, European glaciers have retreated during the 20th century while the Sierra Nevada National Park in southern Spain witnessed the first complete disappearance of modern glaciers in Europe. Given that the effects of climatic fluctuations on local ecosystems are complex in these sensitive alpine areas, it is crucial to identify their long-term natural trends, ecological thresholds, and responses to human impact. In this study, the geochemical records from two adjacent alpine bogs in the protected Sierra Nevada National Park reveal different sensitivities and long-term environmental responses, despite similar natural forcings, such as solar radiation and the North Atlantic Oscillation, during the late Holocene. After the Industrial Revolution both bogs registered an independent, abrupt and enhanced response to the anthropogenic forcing, at the same time that the last glaciers disappeared. The different response recorded at each site suggests that the National Park and land managers of similar regions need to consider landscape and environmental evolution in addition to changing climate to fully understand implications of climate and human influence.This study was supported by the project P11-RNM 7332 of the “Junta de Andalucía”, the projects CGL2013-47038-R and CGL2015-67130-C2-1-R of the “Ministerio de Economía y Competitividad of Spain and Fondo Europeo de Desarrollo Regional FEDER” and the research group RNM0190 and RNM309 (Junta de Andalucía). A.G.-A. was also supported by a Marie Curie Intra-European Fellowship of the 7th Framework Programme for Research, Technological Development and Demonstration of the European Commission (NAOSIPUK. Grant Number: PIEF-GA-2012-623027) and by a Ramón y Cajal Fellowship RYC-2015-18966 of the Spanish Government (Ministerio de Economía y Competividad). J.L.T. was also supported by a Small Research Grant by the Carnegie Trust for the Universities of Scotland and hosted the NAOSIPUK project (PIEF-GA-2012-623027). M. J. R-R acknowledges the PhD funding provided by Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía (P11-RNM 7332)

27 years of benthic and coral community dynamics on turbid, highly urbanised reefs off Singapore

Coral cover on reefs is declining globally due to coastal development, overfishing and climate change. Reefs isolated from direct human influence can recover from natural acute disturbances, but little is known about long term recovery of reefs experiencing chronic human disturbances. Here we investigate responses to acute bleaching disturbances on turbid reefs off Singapore, at two depths over a period of 27 years. Coral cover declined and there were marked changes in coral and benthic community structure during the first decade of monitoring at both depths. At shallower reef crest sites (3–4 m), benthic community structure recovered towards pre-disturbance states within a decade. In contrast, there was a net decline in coral cover and continuing shifts in community structure at deeper reef slope sites (6–7 m). There was no evidence of phase shifts to macroalgal dominance but coral habitats at deeper sites were replaced by unstable substrata such as fine sediments and rubble. The persistence of coral dominance at chronically disturbed shallow sites is likely due to an abundance of coral taxa which are tolerant to environmental stress. In addition, high turbidity may interact antagonistically with other disturbances to reduce the impact of thermal stress and limit macroalgal growth rates

Holocene geochemical footprint from Semiarid alpine wetlands in southern Spain

Here we provide the geochemical dataset that our research group has collected after 10 years of investigation in the Sierra Nevada National Park in southern Spain. These data come from Holocene sedimentary records from four alpine sites (ranging from ∼2500 to ∼3000 masl): two peatlands and two shallow lakes. Different kinds of organic and inorganic analyses have been conducted. The organic matter in the bulk sediment was characterised using elemental measurements and isotope-ratio mass spectrometry (EA-IRMS). Leaf waxes in the sediment were investigated by means of chromatography with flame-ionization detection and mass spectrometry (GC-FID, GC-MS). Major, minor and trace elements of the sediments were analysed with atomic absorption (AAS), inductively coupled plasma mass spectrometry (ICP-MS), as well as X-ray scanning fluorescence. These data can be reused by environmental researchers and soil and land managers of the Sierra Nevada National Park and similar regions to identify the effect of natural climate change, overprinted by human impact, as well as to project new management policies in similar protected areas.Universidad de Granada. Departamento de Estratigrafía y PaleontologíaJunta de Andalucía: Grupos de investigación RNM190 y RNM309Junta de Andalucía: Proyecto P11-RNM-7332España, Ministerio de Economía y Competitividad: Proyecto CGL2013-47038-RRamón y Cajal Fellowship: RYC-2015-18966Small Research Grant by the Carnegie Trust for the Universities of ScotlandMarie Curie Intra-European Fellowship of the 7th Framework Programme for Research, Technological Development and Demonstration of the European Commission: NAOSIPUK. Grant Number: PIEF-GA-2012-62302

Ablation of Dido3 compromises lineage commitment of stem cells in vitro and during early embryonic development

The death inducer obliterator (Dido) locus encodes three protein isoforms, of which Dido3 is the largest and most broadly expressed. Dido3 is a nuclear protein that forms part of the spindle assembly checkpoint (SAC) and is necessary for correct chromosome segregation in somatic and germ cells. Here we report that specific ablation of Dido3 function in mice causes lethal developmental defects at the onset of gastrulation. Although these defects are associated with centrosome amplification, spindle malformation and a DNA damage response, we provide evidence that embryonic lethality of the Dido3 mutation cannot be explained by its impact on chromosome segregation alone. We show that loss of Dido3 expression compromises differentiation of embryonic stem cells in vitro and of epiblast cells in vivo, resulting in early embryonic death at around day 8.5 of gestation. Close analysis of Dido3 mutant embryoid bodies indicates that ablation of Dido3, rather than producing a generalized differentiation blockade, delays the onset of lineage commitment at the primitive endoderm specification stage. The dual role of Dido3 in chromosome segregation and stem cell differentiation supports the implication of SAC components in stem cell fate decisions

A review of the current treatment methods for posthaemorrhagic hydrocephalus of infants

Posthaemorrhagic hydrocephalus (PHH) is a major problem for premature infants, generally requiring lifelong care. It results from small blood clots inducing scarring within CSF channels impeding CSF circulation. Transforming growth factor – beta is released into CSF and cytokines stimulate deposition of extracellular matrix proteins which potentially obstruct CSF pathways. Prolonged raised pressures and free radical damage incur poor neurodevelopmental outcomes. The most common treatment involves permanent ventricular shunting with all its risks and consequences