Crystal Structure of Human TWEAK in Complex with the Fab Fragment of a Neutralizing Antibody Reveals Insights into Receptor Binding.

The tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine playing a key role in tissue regeneration and remodeling. Dysregulation of TWEAK signaling is involved in various pathological processes like autoimmune diseases and cancer. The unique interaction with its cognate receptor Fn14 makes both ligand and receptor promising targets for novel therapeutics. To gain insights into this important signaling pathway, we determined the structure of soluble human TWEAK in complex with the Fab fragment of an antibody selected for inhibition of receptor binding. In the crystallized complex TWEAK is bound by three Fab fragments of the neutralizing antibody. Homology modeling shows that Fab binding overlaps with the putative Fn14 binding site of TWEAK. Docking of the Fn14 cysteine rich domain (CRD) to that site generates a highly complementary interface with perfectly opposing charged and hydrophobic residues. Taken together the presented structure provides new insights into the biology of TWEAK and the TWEAK/Fn14 pathway, which will help to optimize the therapeutic strategy for treatment of related cancer types and autoimmune diseases

Year-round population dynamics of Limacina spp. early stages in a high-Arctic fjord (Adventfjorden, Svalbard)

The thecosome pteropods Limacina helicina and L. retroversa are important contributors to the zooplankton community in high-latitude environments but little is known about their distribution and life cycle under polar conditions. We collected the early life stages (< 1 mm) of the thecosome population in 2012 and 2013 at a bi-weekly to monthly resolution in fjord highly influenced by Arctic waters as well as Atlantic inflows (Adventfjorden, Svalbard, 78°N), together with environmental parameters. L. retroversa only occurred episodically, in association with the inflow of Atlantic water, with low numbers and random size distributions. This suggests that this boreal species does not fulfill its life cycle in Adventfjorden. In contrast, young specimens of L. helicina were present during the entire study. Veligers hatched in late summer/autumn and measured 0.14 mm on average. They grew with rates of 0.0006 mm day− 1 over the 10–11 months of development. Only thereafter, growth accelerated by one order of magnitude and maximal rates were reached in autumn (0.0077 mm day− 1). Our results indicate that L. helicina reaches a size of 1 mm after approximately 1.5 years in Adventfjorden. We therefore suggest that L. helicina overwinters the first year as a small juvenile and that it needs at least 2 years to reach an adult size of 5 mm in Adventfjorden. This reveals an complex and delicate aspect of the life-cycle of L. helicina and further research is needed to determine if it makes the population especially vulnerable towards climate changes

The Use of Sentinel-2 for Chlorophyll-a Spatial Dynamics Assessment: A Comparative Study on Different Lakes in Northern Germany

Eutrophication of inland waters is an environmental issue that is becoming more common with climatic variability. Monitoring of this aquatic problem is commonly based on the chlorophyll-a concentration monitored by routine sampling with limited temporal and spatial coverage. Remote sensing data can be used to improve monitoring, especially after the launch of the MultiSpectral Instrument (MSI) on Sentinel-2. In this study, we compared the estimation of chlorophyll-a (chl-a) from different bio-optical algorithms using hyperspectral proximal remote sensing measurements, from simulated MSI responses and from an MSI image. For the satellite image, we also compare different atmospheric corrections routines before the comparison of different bio-optical algorithms. We used in situ data collected in 2019 from 97 sampling points across 19 different lakes. The atmospheric correction assessment showed that the performances of the routines varied for each spectral band. Therefore, we selected C2X, which performed best for bands 4 (root mean square error—RMSE = 0.003), 5 (RMSE = 0.004) and 6 (RMSE = 0.002), which are usually used for the estimation of chl-a. Considering all samples from the 19 lakes, the best performing chl-a algorithm and calibration achieved a RMSE of 16.97 mg/m3. When we consider only one lake chain composed of meso-to-eutrophic lakes, the performance improved (RMSE: 10.97 mg/m3). This shows that for the studied meso-to-eutrophic waters, we can reliably estimate chl-a concentration, whereas for oligotrophic waters, further research is needed. The assessment of chl-a from space allows us to assess spatial dynamics of the environment, which can be important for the management of water resources. However, to have an accurate product, similar optical water types are important for the overall performance of the bio-optical algorithm

Applications of Variability Analysis Techniques for Continuous Glucose Monitoring Derived Time Series in Diabetic Patients

Methods from non-linear dynamics have enhanced understanding of functional dysregulation in various diseases but received less attention in diabetes. This retrospective cross-sectional study evaluates and compares relationships between indices of non-linear dynamics and traditional glycemic variability, and their potential application in diabetes control. Continuous glucose monitoring provided data for 177 subjects with type 1 (n = 22), type 2 diabetes (n = 143), and 12 non-diabetic subjects. Each time series comprised 576 glucose values. We calculated Poincaré plot measures (SD1, SD2), shape (SFE) and area of the fitting ellipse (AFE), multiscale entropy (MSE) index, and detrended fluctuation exponents (α1, α2). The glycemic variability metrics were the coefficient of variation (%CV) and standard deviation. Time of glucose readings in the target range (TIR) defined the quality of glycemic control. The Poincaré plot indices and α exponents were higher (p &lt; 0.05) in type 1 than in the type 2 diabetes; SD1 (mmol/l): 1.64 ± 0.39 vs. 0.94 ± 0.35, SD2 (mmol/l): 4.06 ± 0.99 vs. 2.12 ± 1.04, AFE (mmol2/l2): 21.71 ± 9.82 vs. 7.25 ± 5.92, and α1: 1.94 ± 0.12 vs. 1.75 ± 0.12, α2: 1.38 ± 0.11 vs. 1.30 ± 0.15. The MSE index decreased consistently from the non-diabetic to the type 1 diabetic group (5.31 ± 1.10 vs. 3.29 ± 0.83, p &lt; 0.001); higher indices correlated with lower %CV values (r = -0.313, p &lt; 0.001). In a subgroup of type 1 diabetes patients, insulin pump therapy significantly decreased SD1 (-0.85 mmol/l), SD2 (-1.90 mmol/l), and AFE (-16.59 mmol2/l2), concomitantly with %CV (-15.60). The MSE index declined from 3.09 ± 0.94 to 1.93 ± 0.40 (p = 0.001), whereas the exponents α1 and α2 did not. On multivariate regression analyses, SD1, SD2, SFE, and AFE emerged as dominant predictors of TIR (β = -0.78, -1.00, -0.29, and -0.58) but %CV as a minor one, though α1 and MSE failed. In the regression models, including SFE, AFE, and α2 (β = -0.32), %CV was not a significant predictor. Poincaré plot descriptors provide additional information to conventional variability metrics and may complement assessment of glycemia, but complexity measures produce mixed results

Factors controlling plankton community production, export flux, and particulate matter stoichiometry in the coastal upwelling system off Peru

Eastern boundary upwelling systems (EBUS) are among the most productive marine ecosystems on Earth. The production of organic material is fueled by upwelling of nutrient-rich deep waters and high incident light at the sea surface. However, biotic and abiotic factors can modify surface production and related biogeochemical processes. Determining these factors is important because EBUS are considered hotspots of climate change, and reliable predictions of their future functioning requires understanding of the mechanisms driving the biogeochemical cycles therein. In this field experiment, we used in situ mesocosms as tools to improve our mechanistic understanding of processes controlling organic matter cycling in the coastal Peruvian upwelling system. Eight mesocosms, each with a volume of ∼55 m3, were deployed for 50 d ∼6 km off Callao (12∘ S) during austral summer 2017, coinciding with a coastal El Niño phase. After mesocosm deployment, we collected subsurface waters at two different locations in the regional oxygen minimum zone (OMZ) and injected these into four mesocosms (mixing ratio ≈1.5 : 1 mesocosm: OMZ water). The focus of this paper is on temporal developments of organic matter production, export, and stoichiometry in the individual mesocosms. The mesocosm phytoplankton communities were initially dominated by diatoms but shifted towards a pronounced dominance of the mixotrophic dinoflagellate (Akashiwo sanguinea) when inorganic nitrogen was exhausted in surface layers. The community shift coincided with a short-term increase in production during the A. sanguinea bloom, which left a pronounced imprint on organic matter C : N : P stoichiometry. However, C, N, and P export fluxes did not increase because A. sanguinea persisted in the water column and did not sink out during the experiment. Accordingly, export fluxes during the study were decoupled from surface production and sustained by the remaining plankton community. Overall, biogeochemical pools and fluxes were surprisingly constant for most of the experiment. We explain this constancy by light limitation through self-shading by phytoplankton and by inorganic nitrogen limitation which constrained phytoplankton growth. Thus, gain and loss processes remained balanced and there were few opportunities for blooms, which represents an event where the system becomes unbalanced. Overall, our mesocosm study revealed some key links between ecological and biogeochemical processes for one of the most economically important regions in the oceans

Shelled pteropods in peril: Assessing vulnerability in a high CO2 ocean

The impact of anthropogenic ocean acidification (OA) on marine ecosystems is a vital concern facing marine scientists and managers of ocean resources. Euthecosomatous pteropods (holoplanktonic gastropods) represent an excellent sentinel for indicating exposure to anthropogenic OA because of the sensitivity of their aragonite shells to the OA conditions less favorable for calcification. However, an integration of observations, experiments and modelling efforts is needed to make accurate predictions of how these organisms will respond to future changes to their environment. Our understanding of the underlying organismal biology and life history is far from complete and must be improved if we are to comprehend fully the responses of these organisms to the multitude of stressors in their environment beyond OA. This review considers the present state of research and understanding of euthecosomatous pteropod biology and ecology of these organisms and considers promising new laboratory methods, advances in instrumentation (such as molecular, trace elements, stable isotopes, palaeobiology alongside autonomous sampling platforms, CT scanning and high-quality video recording) and novel field-based approaches (i.e. studies of upwelling and CO2 vent regions) that may allow us to improve our predictive capacity of their vulnerability and/or resilience. In addition to playing a critical ecological and biogeochemical role, pteropods can offer a significant value as an early-indicator of anthropogenic OA. This role as a sentinel species should be developed further to consolidate their potential use within marine environmental management policy making

Mating Clione limacina (Phipps, 1774)

In July 2010 the authors observed two mating specimens of Clione limacina (Phipps, 1774) in the surface water of the Arctic Kongsfjord, Svalbard (78° 57.6564' N, 12° 2.55558' E). Clione limacina is a holopelagic gastropod mollusc that belongs to the monophyletic group Pteropoda, which members are characterized by the possession of paired, wing-like appendages. These "wings" constitute a modified gastropod foot and are used for active swimming. Two subgroups of pteropods exist, the shelled Thecosomata and the unshelled Gymnosomata. Gymnosome species are hard to study for a variety of reasons and thus our knowledge on these animals is still very limited, in particular when it comes to behavioral observations. Here we present rare video footage of two mating specimens of Clione limacina, which have been transferred into a plastic bowl for closer observation. Specimens were facing each other on their ventral sides and kept swimming slowly during the whole period. The cephalic copulatory apparatus, which contains a long and slender accessory organ and a penis is everted in both specimens. The free accessory copulatory organs are wrapped around the partner and the penes are inserted into the matesÕ posterior genital opening. The transfer of a spermatophore from the anterior male genital opening along the penis is clearly visible. Fertilization is reported to be reciprocal in this species. Although the mating process has been described previously, the functional physiology of involved anatomical structures (i.e. complex glandular systems) in the formation of the spermatophores and spawn remains obscure