C-Jun N-terminal kinase controls TDP-43 accumulation in stress granules induced by oxidative stress

Background

TDP-43 proteinopathies are characterized by loss of nuclear TDP-43 expression and formation of C-terminal TDP-43 fragmentation and accumulation in the cytoplasm. Recent studies have shown that TDP-43 can accumulate in RNA stress granules (SGs) in response to cell stresses and this could be associated with subsequent formation of TDP-43 ubiquinated protein aggregates. However, the initial mechanisms controlling endogenous TDP-43 accumulation in SGs during chronic disease are not understood. In this study we investigated the mechanism of TDP-43 processing and accumulation in SGs in SH-SY5Y neuronal-like cells exposed to chronic oxidative stress. Cell cultures were treated overnight with the mitochondrial inhibitor paraquat and examined for TDP-43 and SG processing.

Results

We found that mild stress induced by paraquat led to formation of TDP-43 and HuR-positive SGs, a proportion of which were ubiquitinated. The co-localization of TDP-43 with SGs could be fully prevented by inhibition of c-Jun N-terminal kinase (JNK). JNK inhibition did not prevent formation of HuR-positive SGs and did not prevent diffuse TDP-43 accumulation in the cytosol. In contrast, ERK or p38 inhibition prevented formation of both TDP-43 and HuR-positive SGs. JNK inhibition also inhibited TDP-43 SG localization in cells acutely treated with sodium arsenite and reduced the number of aggregates per cell in cultures transfected with C-terminal TDP-43 162-414 and 219-414 constructs.

Conclusions

Our studies are the first to demonstrate a critical role for kinase control of TDP-43 accumulation in SGs and may have important implications for development of treatments for FTD and ALS, targeting cell signal pathway control of TDP-43 aggregation.     

A molecular phylogeny of the cosmopolitan hyperdiverse genus Hydraena Kugelann (Coleoptera,Hydraenidae)

With almost 900 described species, Hydraena Kugelann (Hydraenidae) is one of the largest genera among Coleoptera. The subgeneric classification of Hydraena has been controversial, with 11 subgeneric names having so far been attributed to it. Some of these, Haenydra Rey and Spanglerina Perkins, have been treated as valid genera, as subgenera or as species groups. The most recent complete treatment of the genus, based on a cladistic analysis of morphological characters, recognized two major lineages, and only these were classified as subgenera: Hydraenopsis (mainly Gondwanan distribution), and Hydraena s.str. (mainly Laurasian). Here, we reconstruct the phylogeny of Hydraena using 212 species plus several outgroups and approximately 4 kb of sequence data from two nuclear (SSU and LSU) and four mitochondrial genes (cox1, rrnL, trnL and nad1). Data were aligned with two different strategies of multiple alignment (implemented in mafft and prank ), and the phylogenies reconstructed using maximum likelihood and Bayesian methods. We estimated approximate ages of the main nodes using a relaxed molecular clock with Bayesian methods, and an a priori evolutionary rate of 0.01 substitutions/site/million years (Ma) plus a calibration point based on a biogeographical split. We found strong support for the monophyly of Hydraena and many of the clades recognized with morphological data. The following clades are considered as subgenera: Phothydraena Kuwert, Spanglerina Perkins, Holcohydraena Kuwert, Hydraenopsis Janssens and Hydraena s.str. The placement of three species groups, two Neotropical (H. multispina group, H. paeminosa group) and one South African/Madagascan (H. monikae group), is uncertain, and they are considered incertae sedis within Hydraena. The origin of the genus was estimated to be in the Lower Eocene, with many species complexes diversifying in the Pleistocene. Dispersal events seem to have played a key role in order to determine the current distribution of the species groups in the southern hemisphere (mainly in Hydraenopsis).     

Reproductive responses to photoperiod and temperature by diapausing and nondiapausing populations of Sesamia nonagrioides Lef. (Lepidoptera − Noctuidae)

Abstract.  The influence of long- and short-day cycles on ovipostion and egg hatch of the corn stalk borer, Sesamia nonagrioides were investigated at a range of temperatures. Oviposition was suppressed when insects are exposed to long days through their immature stages and then transferred to short days after mating. Moreover, mean oviposition and egg hatch increased from 15 to 27.5 °C, whereas oviposition declined significantly at 30 °C at both photoperiodic regimes. Females derived from a diapausing population exposed to long days after mating showed a significantly higher egg production compared to females derived from a nondiapausing population. However, when females from a diapausing population were left to oviposit under short days, fewer eggs were produced compared to those exposed to long days after mating. Thus, photoperiod appears to affect reproductive traits of this species in a quantitative manner. Larval diapause duration is positively correlated with fecundity of the adults. There is also a positive correlation between pupal weight of individuals derived from a diapausing population and the postdiapause fecundity of adults.     

Structure of the unusual explosive fruits of the early diverging angiosperm Illicium (Schisandraceae s.l., Austrobaileyales)

All Illicium spp. have explosive fruits, which is a unique character among the basal grade of angiosperms. Illicium fruits consist of several ventrally dehiscing follicles developing from conduplicate carpels, with a prominent, slightly postgenitally fused ventral slit. The closure of the ventral slit is also secured by two mirror‐symmetrical massive longitudinal sclerenchymatous bands in the mesocarp along the edges and by turgor pressure. The pericarp differentiates into a fleshy (or coriaceous) peripheral zone (exocarp and mesocarp) with numerous ethereal‐oil‐containing cells and a sclerenchymatous (single‐layered, palisade) inner zone (endocarp). Dehydration of the fleshy zone of the pericarp and partial compression of the epidermal sclereids with U‐shaped wall thickenings lining the ventral suture are instrumental in explosive fruitlet dehiscence. Generally, the fruit structure of Illicium differs dramatically from those in other early diverging angiosperms. Gynoecium and fruit structure (and a probable early Cretaceous divergence from the Schisandra‐Kadsura clade) provide evidence for treatment of Illicium as separate from Schisandraceae s.s. © 2013 The Linnean Society of London, Botanical Journal of the Linnean Society, 2013 , 171 , 640–654.     

ZnCl2 catalyzed new coumarinyl-chalcones as cytotoxic agents

A new series of coumarin-yl-chalcone derivatives (3a-m) had been designed and synthesized through different reactions such as aromatic addition, cyclization and Claisen-Schmidt reactions in good yields (54–78%). 5-acetyl-4-(2-hydroxyphenyl) -6-methyl-3, 4-dihydropyrimidin-2(1H) -one (1) has been synthesized by multi-component one pot reaction of salicylaldehyde, methyl acetoacetate and urea, which was further reacted with malonic acid employing ZnCl₂ catalyst to yield 5-acetyl-4-(4-hydroxy-2-oxo-2H-chromen-8-yl) -6-methyl-3, 4-dihydropyrimidin-2(1H) -one (2). The title compounds (3a-m) were synthesised by reacting 5-acetyl-4-(4-hydroxy-2-oxo-2H-chromen-8-yl) -6-methyl-3, 4-dihydropyrimidin-2(1H)-one (2) with different aromatic aldehydes in the presence of potassium hydroxide. In silico studies, a preliminary screening method for predicting the anti-cancer activity was performed for the synthesized compounds (3a-m) against Src, Alb tyrosine kinase and homology model protein (PDB ID: 4csv). The derivatives 3h and 3m showed moderate binding energies. The in vitro cytotoxic activity was evaluated for the compounds 3h and 3m by using human cancer cell-line morphology and MTT assay against three human cell-lines A549 (Lung), Jurkat (Leukemia) and MCF-7 (Breast). The results indicate that the derivatives 3h and 3m display significant anti-cancer activity, however it was found to be less cytotoxic when compared to the standard used i.e. Imatinib.     

Phylogeny of Psephenidae (Coleoptera: Byrrhoidea) based on larval, pupal and adult characters

Abstract.  We conducted the first comprehensive phylogenetic analysis of Psephenidae, based on 143 morphological characters of adults, larvae and pupae and coded for 34 taxa, representing three outgroups and 31 psephenid genera, including four undescribed ones. A strict consensus tree calculated (439 steps, consistency index = 0.45, retention index = 0.75) from the two most-parsimonious cladograms indicated that the monophyly of the family and subfamilies is supported, with the exception of Eubriinae, which is paraphyletic when including Afroeubria . Here a new subfamily, Afroeubriinae ( subfam.n. ), is formally established for Afroeubria . The analysis also indicated that the 'streamlined' larva is a derived adaptive radiation. Here, suprageneric taxonomy and the evolution of some significant characters are discussed. Keys are provided to the subfamilies and genera of Psephenidae considering larvae, adults and pupae.     

Cohesin's ATPase activity is stimulated by the C-terminal Winged-Helix domain of its kleisin subunit

BACKGROUND: Cohesin, a multisubunit protein complex conserved from yeast to humans, holds sister chromatids together from the onset of replication to their separation during anaphase. Cohesin consists of four core subunits, namely Smc1, Smc3, Scc1, and Scc3. Smc1 and Smc3 proteins are characterized by 50-nm-long anti-parallel coiled coils flanked by a globular hinge domain and an ABC-like ATPase head domain. Whereas Smc1 and Smc3 heterodimerize via their hinge domains, the kleisin subunit Scc1 connects their ATPase heads, and this results in the formation of a large ring. Biochemical studies suggest that cohesin might trap sister chromatids within its ring, and genetic evidence suggests that ATP hydrolysis is required for the stable association of cohesin with chromosomes. However, the precise role of the ATPase domains remains enigmatic. RESULTS: Characterization of cohesin's ATPase activity suggests that hydrolysis depends on the binding of ATP to both Smc1 and Smc3 heads. However, ATP hydrolysis at the two active sites is not per se cooperative. We show that the C-terminal winged-helix domain of Scc1 stimulates the ATPase activity of the Smc1/Smc3 heterodimer by promoting ATP binding to Smc1's head. In contrast, we do not detect any effect of Scc1's N-terminal domain on Smc1/Smc3 ATPase activity. CONCLUSIONS: Our studies reveal that Scc1 not only connects the Smc1 and Smc3 ATPase heads but also regulates their ATPase activity.     

A portable system for collecting anatomical joint angles during stair ascent: a comparison with an optical tracking device

Background

Assessments of stair climbing in real-life situations using an optical tracking system are lacking, as it is difficult to adapt the system for use in and around full flights of stairs. Alternatively, a portable system that consists of inertial measurement units (IMUs) can be used to collect anatomical joint angles during stair ascent. The purpose of this study was to compare the anatomical joint angles obtained by IMUs to those calculated from position data of an optical tracking device.

Methods

Anatomical joint angles of the thigh, knee and ankle, obtained using IMUs and an optical tracking device, were compared for fourteen healthy subjects. Joint kinematics obtained with the two measurement devices were evaluated by calculating the root mean square error (RMSE) and by calculating a two-tailed Pearson product-moment correlation coefficient (r) between the two signals.

Results

Strong mean correlations (range 0.93 to 0.99) were found for the angles between the two measurement devices, as well as an average root mean square error (RMSE) of 4 degrees over all the joint angles, showing that the IMUs are a satisfactory system for measuring anatomical joint angles.

Conclusion

These highly portable body-worn inertial sensors can be used by clinicians and researchers alike, to accurately collect data during stair climbing in complex real-life situations.

     

Differential taphonomy of modern brachiopods (San Juan Islands, Washington State): effect of intrinsic factors on damage and community-level abundance

The differences in shell structure and population turnover between organic-poor, impunctate (Hemithiris) and organic-rich, punctate brachiopod (Terebratalia) in a mixed-bottom, siliciclastic setting (San Juan Islands, WA) lead to different taphonomic damage and fidelity with respect to community-level abundance in death assemblages. In comparing shell interiors of similar-sized specimens, Terebratalia is predominantly affected by fibre detachment and shows almost no microbioerosion at the SEM scale; whereas, Hemithiris shows less marked fibre detachment at the SEM scale and is more intensely affected by microbioerosion both at SEM and light microscope (LM) scales. Fibre detachment related to rapid, microbially-induced organic matter decay appears to be the main destructive process acting on Terebratalia. Higher bioerosion levels in Hemithiris at SEM and LM scales are probably related to a combination of a low maceration rate and a preferential settlement by borers. From their vastly different abundances in life assemblages it can be deduced that Terebratalia produces dead shells at a much higher rate than Hemithiris. Therefore, the proportion of altered Terebratalia, relative to Hemithiris, is expected to be decreased due to its higher production of recently dead cohorts. That Terebratalia is also characterized by high damage levels shows that differential population turnover alone is not responsible for the differences in taphonomic damage. This shows that organic-rich and organic-poor shells are characterized by differential post-mortem durability. Although very few Hemithiris are present in the life assemblages, high durability ensures its relative over-representation in death assemblages. Terebratalia is not strongly under-represented in death assemblages, despite its high destruction rate, because of large production of recently dead shells. Even with the biasing effect of differential durability, the good fidelity reported in previous live-dead studies can be enhanced by higher population turnover of numerically dominant taxa, leading to constant input of recently dead shells into death assemblages.