Mercury contamination and life history traits of Allis shad <Emphasis Type="Italic">Alosa alosa</Emphasis> (Linnaeus, 1758) and Twaite shad <Emphasis Type="Italic">Alosa fallax</Emphasis> (Lacépède, 1803) in the Gironde estuary (South West France)

Mercury concentration [Hg] was assessed in 20 adult Allis shad Alosa alosa (54–59 cm) and 20 adult Twaite shad Alosa fallax (36–44 cm) collected during their spawning migration in the Dordogne and the Garonne rivers (France). [Hg] was measured in the gills, dorsal muscle, liver and kidney. Twaite shad exhibited higher [Hg] than Allis shad. Median [Hg] values were [Hg]_Gills = 0.33 μg g⁻¹ (dw), [Hg]_Muscle = 1.22 μg g⁻¹, [Hg]_Liver = 1.99 μg g⁻¹, [Hg]_Kidney = 1.93 μg g⁻¹ for Twaite shad and [Hg]_Gills = 0.06 μg g⁻¹, [Hg]_Muscle = 0.20 μg g⁻¹, [Hg]_Liver = 1.18 μg g⁻¹, [Hg]_Kidney = 1.08 μg g⁻¹ for Allis shad. In order to understand such differences, we investigated some life history traits of the two species: migratory history, age (3–6 years), size at age (an expression of growth) and the number of spawning events (0–2 events). The difference in estuarine residence time between the juveniles of both species, which was assumed to influence [Hg], was investigated using otolith Sr:Ca ratio. The microchemical analysis revealed a significant difference in the residence time of juveniles in the estuary (medians are 21 d and 10 d for Twaite shad and Allis shad, respectively) but this residence time seems too short to influence [Hg] (Allis shad: r _spearman < 0.128; Twaite shad: r _spearman < −0.340). As both species show the same age structure, the influence of age on [Hg] was negligible. The literature shows that the differences in growth and in the number of spawning events reported in our study are in favour of a higher [Hg] for Twaite shad than for Allis shad. Although trophic status was not investigated here, the literature reveals that it is another factor that could produce higher [Hg] in Twaite shad, since its diet includes higher trophic levels than Allis shad. Guest editors: S. Dufour, E. Prévost, E. Rochard & P. Williot Fish and diadromy in Europe (ecology, management, conservation)     

Life history changes in Atlantic salmon from the River Dee,Wales

The change in life history of Atlantic salmon (Salmo salar L.) on the River Dee over the last 60 years is described. Over the last 60 years, salmon have shown a change in run timing, the majority currently entering the river between August and October compared with prior to June. This has coincided with a change in the sea age composition, which was dominated by multi-sea winter salmon prior to the 1980s after which the proportion of 1sea-winter fish increased until they now dominate the mature population. Growth rates of salmon in fresh water remained relatively stable until the mid-1980s and then increased. By the end of the 1990s juvenile salmon were, by the end of their first and second year, respectively, ∼60 and ∼19%, on average, larger than they were between the late 1930s and mid-1980s. This has been reflected in a change in the age composition of smolts where the mean smolt age has declined from ∼2 years prior to the 1980s to ∼1.6 years in the late 1990s. There was no observed trend in post-smolt (marine) growth for salmon. Size at return for 1SW salmon appeared stable while there is some evidence of an increase in mean length of 2SW salmon at the end of the 1990s. A steady state life history model was developed which suggests an increase in the instantaneous rate of mortality by 2.9% from 1.495 year⁻¹ in 1937/1938 to 1.538 year⁻¹ in 1967/1969 and by 21.6% to 1.870 year⁻¹ in 1997/1999. This is considered to explain the shift in mean age at maturity from 5.2 to 4.8 to 3.9 years for the three periods examined. There is close agreement between the observed mean age at maturity and that predicted by the model suggesting optimal lifetime reproductive success. Guest editors: S. Dufour, E. Prévost, E. Rochard & P. Williot Fish and diadromy in Europe (ecology, management, conservation)     

Long term results of age-related macular degeneration therapy with prednisolone acetate--special refer to peripheral visual field changes

In the north Croatian Adriatic area in the period of seven years (from January 2001 to September 2007) 475 patients (39 to 80 years of age) with dry form of age related macular degeneration (AMD) were diagnosed. Complete ophthalmologic examination with special reference to visual field testing (Perimetric analysis) was performed. Peripheral visual field defects were found in 85% of patients. Elderly patients with more advanced forms of macular degeneration had more peripheral visual field defects. In 400 patients corticosteroid therapy (5 mg Prednisolonacetate, anterior H-inject, Winthorp) was administered via parabulbar injections every day/five days. Control group consisted of 75 patients treated with regular polyvitamine therapy (Lutein, Beta Karoten, Vitamin E). Patients treated with corticosteroids had peripheral visual field improvements from 10 to 25 degrees and central field improvements from 5 to 20%. In the control group treated with vitamins, central visual field showed improvements from 0.5 to 1% in 43 patients but without peripheral visual field improvements after 6 months.     

A Dinoflagellate Amylax triacantha with Plastids of the Cryptophyte Origin: Phylogeny,Feeding Mechanism,and Growth and Grazing Responses

The gonyaulacalean dinoflagellates Amylax spp. were recently found to contain plastids of the cryptophyte origin, more specifically of Teleaulax amphioxeia. However, not only how the dinoflagellates get the plastids of the cryptophyte origin is unknown but also their ecophysiology, including growth and feeding responses as functions of both light and prey concentration, remain unknown. Here, we report the establishment of Amylax triacantha in culture, its feeding mechanism, and its growth rate using the ciliate prey Mesodinium rubrum (= Myrionecta rubra) in light and dark, and growth and grazing responses to prey concentration and light intensity. The strain established in culture in this study was assigned to A. triacantha, based on morphological characteristics (particularly, a prominent apical horn and three antapical spines) and nuclear SSU and LSU rDNA sequences. Amylax triacantha grew well in laboratory culture when supplied with the marine mixotrophic ciliate M. rubrum as prey, reaching densities of over 7.5 × 10³ cells/ml. Amylax triacantha captured its prey using a tow filament, and then ingested the whole prey by direct engulfment through the sulcus. The dinoflagellate was able to grow heterotrophically in the dark, but the growth rate was approximately two times lower than in the light. Although mixotrophic growth rates of A. triacantha increased sharply with mean prey concentrations, with maximum growth rate being 0.68/d, phototrophic growth (i.e. growth in the absence of prey) was ?0.08/d. The maximum ingestion rate was 2.54 ng C/Amylax/d (5.9 cells/Amylax/d). Growth rate also increased with increasing light intensity, but the effect was evident only when prey was supplied. Increased growth with increasing light intensity was accompanied by a corresponding increase in ingestion. In mixed cultures of two predators, A. triacantha and Dinophysis acuminata, with M. rubrum as prey, A. triacantha outgrew D. acuminata due to its approximately three times higher growth rate, suggesting that it can outcompete D. acuminata. Our results would help better understand the ecophysiology of dinoflagellates retaining foreign plastids.     

Disentangling subpopulations in single-molecule FRET and ALEX experiments with photon distribution analysis

Among the advantages of the single-molecule approach when used to study biomolecular structural dynamics and interaction is its ability to distinguish between and independently observe minor subpopulations. In a single-molecule Förster resonance energy transfer (FRET) and alternating laser excitation diffusion experiment, the various populations are apparent in the resultant histograms. However, because histograms are calculated based on the per-burst mean FRET and stoichiometry ratio and not on the internal photon distribution, much of the acquired information is lost, thereby reducing the capabilities of the method. Here we suggest what to our knowledge is a novel statistical analysis tool that significantly enhances these capabilities, and we use it to identify and isolate static and dynamic subpopulations. Based on a kernel density estimator and a proper photon distribution analysis, for each individual burst, we calculate scores that reflect properties of interest. Specifically, we determine the FRET efficiency and brightness ratio distributions and use them to reveal 1), the underlying structure of a two-state DNA-hairpin and a DNA hairpin that is bound to DNA origami; 2), a minor doubly labeled dsDNA subpopulation concealed in a larger singly labeled dsDNA; and 3), functioning DNA origami motors concealed within a larger subpopulation of defective motors. Altogether, these findings demonstrate the usefulness of the proposed approach. The method was developed and tested using simulations, its rationality is described, and a computer algorithm is provided.     

The dual action of glioma-derived exosomes on neuronal activity: synchronization and disruption of synchrony

Seizures represent a frequent symptom in gliomas and significantly impact patient morbidity and quality of life. Although the pathogenesis of tumor-related seizures is not fully understood, accumulating evidence indicates a key role of the peritumoral microenvironment. Brain cancer cells interact with neurons by forming synapses with them and by releasing exosomes, cytokines, and other small molecules. Strong interactions among neurons often lead to the synchronization of their activity. In this paper, we used an in vitro model to investigate the role of exosomes released by glioma cell lines and by patient-derived glioma stem cells (GSCs). The addition of exosomes released by U87 glioma cells to neuronal cultures at day in vitro (DIV) 4, when neurons are not yet synchronous, induces synchronization. At DIV 7–12 neurons become highly synchronous, and the addition of the same exosomes disrupts synchrony. By combining Ca²⁺ imaging, electrical recordings from single neurons with patch-clamp electrodes, substrate-integrated microelectrode arrays, and immunohistochemistry, we show that synchronization and de-synchronization are caused by the combined effect of (i) the formation of new neuronal branches, associated with a higher expression of Arp3, (ii) the modification of synaptic efficiency, and (iii) a direct action of exosomes on the electrical properties of neurons, more evident at DIV 7–12 when the threshold for spike initiation is significantly reduced. At DIV 7–12 exosomes also selectively boost glutamatergic signaling by increasing the number of excitatory synapses. Remarkably, de-synchronization was also observed with exosomes released by glioma-associated stem cells (GASCs) from patients with low-grade glioma but not from patients with high-grade glioma, where a more variable outcome was observed. These results show that exosomes released from glioma modify the electrical properties of neuronal networks and that de-synchronization caused by exosomes from low-grade glioma can contribute to the neurological pathologies of patients with brain cancers.Subject terms: Neuroscience, Preclinical research     

Role of the four conserved histidine residues in the amidotransferase domain of carbamoyl phosphate synthetase

Carbamoyl phosphate synthetase from Escherichia coli catalyzes the formation of carbamoyl phosphate from ATP, bicarbonate, and glutamine. The amidotransferase activity of this enzyme is catalyzed by the smaller of the two subunits of the heterodimeric protein. The roles of four conserved histidine residues within this subunit were probed by site-directed mutagenesis to asparagine. The catalytic activities of the H272N and H341N mutants are not significantly different than that of the wild-type enzyme. The H353N mutant is unable to utilize glutamine as a nitrogen source in the synthetase reaction or the partial glutaminase reaction. However, binding to the glutamine active site is not impaired in the H353N enzyme since glutamine is found to activate the partial ATPase reaction by 40% with a Kd of 54 microM. The H312N mutant has a Michaelis constant for glutamine that is 2 orders of magnitude larger than the wild-type value, but the maximal rate of glutamine hydrolysis is unchanged. These results are consistent with His-353 functioning as a general acid/base catalyst for proton transfers while His-312 serves a critical role for the binding of glutamine to the active site.     

Logistic regression model training based on the approximate homomorphic encryption

Background

Security concerns have been raised since big data became a prominent tool in data analysis. For instance, many machine learning algorithms aim to generate prediction models using training data which contain sensitive information about individuals. Cryptography community is considering secure computation as a solution for privacy protection. In particular, practical requirements have triggered research on the efficiency of cryptographic primitives.

Methods

This paper presents a method to train a logistic regression model without information leakage. We apply the homomorphic encryption scheme of Cheon et al. (ASIACRYPT 2017) for an efficient arithmetic over real numbers, and devise a new encoding method to reduce storage of encrypted database. In addition, we adapt Nesterov’s accelerated gradient method to reduce the number of iterations as well as the computational cost while maintaining the quality of an output classifier.

Results

Our method shows a state-of-the-art performance of homomorphic encryption system in a real-world application. The submission based on this work was selected as the best solution of Track 3 at iDASH privacy and security competition 2017. For example, it took about six minutes to obtain a logistic regression model given the dataset consisting of 1579 samples, each of which has 18 features with a binary outcome variable.

Conclusions

We present a practical solution for outsourcing analysis tools such as logistic regression analysis while preserving the data confidentiality.

     

Global Renal Gene Expression Profiling Analysis in B2-Kinin Receptor Null Mice: Impact of Diabetes

Diabetic nephropathy (DN), the leading cause of end-stage renal failure, is clinically manifested by albuminuria and a progressive decline in glomerular filtration rate. The risk factors and mechanisms that contribute to the development and progression of DN are still incompletely defined. To address the involvement of bradykinin B₂-receptors (B₂R) in DN, we used a genome wide approach to study the effects of diabetes on differential renal gene expression profile in wild type and B₂R knockout (B₂R^−/−) mice. Diabetes was induced with streptozotocin and plasma glucose levels and albumin excretion rate (AER) were measured at predetermined times throughout the 23 week study period. Longitudinal analysis of AER indicated that diabetic B₂R^−/−D null mice had a significantly decreased AER levels compared to wild type B₂R^+/+D mice (P = 0.0005). Results from the global microarray study comparing gene expression profiles among four groups of mice respectively: (B₂R^+/+C, B₂R^+/+D, B₂R^−/−C and B₂R^−/−D) highlighted the role of several altered pathological pathways in response to disruption of B₂R and to the diabetic state that included: endothelial injury, oxidative stress, insulin and lipid metabolism and inflammatory process with a marked alteration in the pro-apoptotic genes. The findings of the present study provide a global genomics view of biomarkers that highlight the mechanisms and putative pathways involved in DN.