Oral levodopa rescues retinal morphology and visual function in a murine model of human albinism

Albinism is a group of disorders characterized by pigment deficiency and abnormal retinal development. Despite being a common cause for visual impairment worldwide, there is a paucity of treatments and patients typically suffer lifelong visual disability. Residual plasticity of the developing retina in young children with albinism has been demonstrated, suggesting a post‐natal window for therapeutic rescue. L‐3, 4 dihydroxyphenylalanine (L‐DOPA), a key signalling molecule which is essential for normal retinal development, is known to be deficient in albinism. In this study, we demonstrate for the first time that post‐natal L‐DOPA supplementation can rescue retinal development, morphology and visual function in a murine model of human albinism, but only if administered from birth or 15 days post‐natal age.     

Taurine modulates hepatic oxidative status and gut inflammatory markers of European seabass (Dicentrarchus labrax) fed plant feedstuffs-based diets

Amino Acids - This study aimed to evaluate the effect of taurine (tau) supplementation to low fishmeal (FM) diets on growth performance, oxidative status, and immune response of European seabass...     

The dual functionality of antimicrobial peptides Os and Os‐C in human leukocytes

Antimicrobial peptides (AMPs), Os and Os‐C, have been identified as multifunctional peptides with antibacterial, antiendotoxin, and anti‐inflammatory properties. For further development of Os and Os‐C as therapeutic peptides, it is essential to evaluate these effects in human mononuclear (MN) and polymorphonuclear (PMN) leukocytes. The cytotoxicity and the effects of both peptides on MN and PMN morphology were determined with the Alamar‐Blue assay and scanning electron microscopy, respectively. The ability of Os and Os‐C to induce reactive oxygen species (ROS) and to protect against 2,2′‐azobis(2‐amidinopropane) dihydrochloride–induced oxidative damage in both cell populations was evaluated using 2′,7′‐dichlorofluorescin diacetate (DCFH‐DA). Using fluorescently labeled peptides, the ability of the peptides to cross the cell membranes of MN and PMN was also evaluated. At the minimum bactericidal concentrations of Os and Os‐C, neither peptide was cytotoxic. Os caused morphological features of toxicity at 100 μM, entered MN cells, and also protected these cells against oxidative damage. Os‐C caused MN and PMN leukocyte activation associated with ROS formation and was unable to penetrate cell membranes, indicating extracellular membrane interactions. This study confirms that both Os and Os‐C at less than 100 μM are not cytotoxic. The MN‐specific uptake of Os identifies it as a cell‐specific cargo‐carrier peptide, with additional anti‐inflammatory properties. In contrast, the ability of Os‐C to activate MN and PMN cells implies that this peptide should be further evaluated as an AMP, which, in addition to its ability to eradicate infection, can further enhance host immunity. These novel characteristics of Os and Os‐C indicate that these AMPs as peptides can be further developed for specific applications.     

Using behavioral observation for the longitudinal study of anger regulation in middle childhood

Assessing anger regulation via self-reports is fraught with problems, especially among children. Behavioral observation provides an ecologically valid alternative for measuring anger regulation. The present study uses data from two waves of a longitudinal study to present a behavioral observation approach for measuring anger regulation in middle childhood. At T1, 599 children from Germany (6–10 years old) were observed during an anger eliciting task, and the use of anger regulation strategies was coded. At T2, 3 years later, the observation was repeated with an age-appropriate version of the same task. Partial metric measurement invariance over time demonstrated the structural equivalence of the two versions. Maladaptive anger regulation between the two time points showed moderate stability. Validity was established by showing correlations with aggressive behavior, peer problems, and conduct problems (concurrent and predictive criterion validity). The study presents an ecologically valid and economic approach to assessing anger regulation strategies in situ.     

Unravelling the interactions of the environmental host Acanthamoeba castellanii with fungi through the recognition by mannose‐binding proteins

Free‐living amoebae (FLAs) are major reservoirs for a variety of bacteria, viruses, and fungi. The most studied mycophagic FLA, Acanthamoeba castellanii (Ac), is a potential environmental host for endemic fungal pathogens such as Cryptococcus spp., Histoplasma capsulatum, Blastomyces dermatitides, and Sporothrix schenckii. However, the mechanisms involved in this interaction are poorly understood. The aim of this work was to characterize the molecular instances that enable Ac to interact with and ingest fungal pathogens, a process that could lead to selection and maintenance of possible virulence factors. The interaction of Ac with a variety of fungal pathogens was analysed in a multifactorial evaluation that included the role of multiplicity of infection over time. Fungal binding to Ac surface by living image consisted of a quick process, and fungal initial extrusion (vomocytosis) was detected from 15 to 80 min depending on the organism. When these fungi were cocultured with the amoeba, only Candida albicans and Cryptococcus neoformans were able to grow, whereas Paracoccidioides brasiliensis and Sporothrix brasiliensis displayed unchanged viability. Yeasts of H. capsulatum and Saccharomyces cerevisiae were rapidly killed by Ac; however, some cells remained viable after 48 hr. To evaluate changes in fungal virulence upon cocultivation with Ac, recovered yeasts were used to infect Galleria mellonella, and in all instances, they killed the larvae faster than control yeasts. Surface biotinylated extracts of Ac exhibited intense fungal binding by FACS and fluorescence microscopy. Binding was also intense to mannose, and mass spectrometry identified Ac proteins with affinity to fungal surfaces including two putative transmembrane mannose‐binding proteins (MBP, L8WXW7 and MBP1, Q6J288). Consistent with interactions with such mannose‐binding proteins, Ac–fungi interactions were inhibited by mannose. These MBPs may be involved in fungal recognition by amoeba and promotes interactions that allow the emergence and maintenance of fungal virulence for animals.     

Laying characteristics of one- and two-year old pheasants (Phasianus colchicus, L.)

The aim ofthe study was to assess laying traits, the weight of eggs and characters ofthe laying rhythm of pheasants in the first and second years of reproduction. Pheasants (10 cockerels and 50 hens) were kept in aviaries. Daily, individual control of laying was performed beginning with the day of the first laying and ending with the last egg. The following parameters were evaluated: age at first laying, length of the laying period, number of laid eggs and the average weight of the egg in the 8th week of laying. The laying rhythm was also assessed and comprised: the number of egg clutches, the number of eggs in a clutch, the number of eggs in the longest clutch, the number of intervals, the length of intervals and the longest interval between clutches. During the first period of reproduction, in comparison with the second, pheasants laid slightly more eggs of similar average weight. The first laying period was longer than the second and was characterised by a greater number of egg clutches and greater number of intervals between clutches. The greatest number of eggs was laid in 10-egg and longer clutches, although the l-egg clutches were the most numerous. A positive correlation was found between the number of eggs and the number of clutches, the greatest number of eggs in a clutch and the number of intervals between clutches. The similar values of the reproductive characters of one- and two-year old pheasants point to the possibility of longer utilization of these birds than only for one laying period. On the other hand, the considerable variability between the experimental hens with regard to the number and the length of egg clutches, as well as the intervals between them, indicate the possibility to carry out selection taking into account traits characterising the laying rhythm.     

Group G streptococcal IgG binding molecules FOG and protein G have different impacts on opsonization by C1q

Recent epidemiological data on diseases caused by beta-hemolytic streptococci belonging to Lancefield group C and G (GCS, GGS) underline that they are an emerging threat to human health. Among various virulence factors expressed by GCS and GGS isolates from human infections, M and M-like proteins are considered important because of their anti-phagocytic activity. In addition, protein G has been implicated in the accumulation of IgG on the bacterial surface through non-immune binding. The function of this interaction, however, is still unknown. Using isogenic mutants lacking protein G or the M-like protein FOG (group G streptococci), respectively, we could show that FOG contributes substantially to IgG binding. A detailed characterization of the interaction between IgG and FOG revealed its ability to bind the Fc region of human IgG and its binding to the subclasses IgG1, IgG2, and IgG4. FOG was also found to bind IgG of several animal species. Surface plasmon resonance measurements indicate a high affinity to human IgG with a dissociation constant of 2.4 pm. The binding site was localized in a central motif of FOG. It has long been speculated about anti-opsonic functions of streptococcal Fc-binding proteins. The presented data for the first time provide evidence and, furthermore, indicate functional differences between protein G and FOG. By obstructing the interaction between IgG and C1q, protein G prevented recognition by the classical pathway of the complement system. In contrast, IgG that was bound to FOG remained capable of binding C1q, an effect that may have important consequences in the pathogenesis of GGS infections.     

The lactate dehydrogenases encoded by the ldh and ldhB genes in Lactococcus lactis exhibit distinct regulation and catalytic properties - comparative modeling to probe the molecular basis

Lactococcus lactis FI9078, a construct carrying a disruption of the ldh gene, converted approximately 90% of glucose into lactic acid, like the parental strain MG1363. This unexpected lactate dehydrogenase activity was purified, and ldhB was identified as the gene encoding this protein. The activation of ldhB was explained by the insertion of an IS905-like element that created a hybrid promoter in the intergenic region upstream of ldhB. The biochemical and kinetic properties of this alternative lactate dehydrogenase (LDHB) were compared to those of the ldh-encoded enzyme (LDH), purified from the parental strain. In contrast to LDH, the affinity of LDHB for NADH and the activation constant for fructose 1,6-bisphosphate were strongly dependent on pH. The activation constant increased 700-fold, whereas the K(m) for NADH increased more than 10-fold, in the pH range 5.5-7.2. The two enzymes also exhibited different pH profiles for maximal activity. Moreover, inorganic phosphate acted as a strong activator of LDHB. The impact of replacing LDH by LDHB on the physiology of L. lactis was assessed by monitoring the evolution of the pools of glycolytic intermediates and cofactors during the metabolism of glucose by in vivo NMR. Structural analysis by comparative modeling of the two proteins showed that LDH has a slightly larger negative charge than LDHB and a greater concentration of positive charges at the interface between monomers. The calculated pH titration curves of the catalytic histidine residues explain why LDH maintains its activity at low pH as compared to LDHB, the histidines in LDH showing larger pH titration ranges.     

Differential effects of antiepileptic drugs on human bone cells

Antiepileptic drugs (AED) have been associated to in vivo deleterious consequences in bone tissue. The present work aimed to characterize the cellular and molecular effects of five different AED on human osteoclastogenesis and osteblastogenesis. It was observed that the different drugs had the ability to differentially modulate both processes, in a way dependent on the identity and dose of the AED. Shortly, valproic acid stimulated either osteoclastogenesis and osteoblastogenesis, whereas carbamazepine, gabapentin, and lamotrigine revealed an opposite behavior; topiramate elicited a decrease of osteoclast development and an increase in osteoblast differentiation. This is the first report describing the direct effects of different AED on human primary bone cells, which is a very important issue, because these drugs are usually consumed in long-term therapeutics, with acknowledged in vivo effects in bone tissue.     

The omnivorous triggerfish Melichthys niger is a functional herbivore on an isolated Atlantic oceanic island

This study evaluated the functional role of the highly generalist omnivore Melichthys niger in the remote St. Peter and St Paul's Archipelago (SPSPA), Brazil, where grazing herbivorous fishes are very scarce. We analysed patterns of distribution from zero to 30 m deep during three time intervals during the day and sampled different aspects of their feeding behaviour, including diel feeding rate, feeding substrate and diet. The density of M. niger increased with depth (26–30 m) and decreased by the end of the day. Although M. niger did not present a typical herbivore diel feeding pattern, they targeted the epilithic algal matrix as their primary feeding substrate, ingesting predominantly algae and detritus. The characteristic Caulerpa racemosa var. peltata from SPSPA was ingested only as detached fronds. We suggest that in the isolated SPSPA, the single species M. niger may perform a unique role as a link between benthic primary production and higher levels. Further studies on the trophic ecology of omnivorous species are necessary to better understand their roles in a reef system, especially in impoverished areas where they are likely to play a crucial role.