Opposite Roles of NMDA Receptors in Relapsing and Primary Progressive Multiple Sclerosis

Synaptic transmission and plasticity mediated by NMDA receptors (NMDARs) could modulate the severity of multiple sclerosis (MS). Here the role of NMDARs in MS was first explored in 691 subjects carrying specific allelic variants of the NR1 subunit gene or of the NR2B subunit gene of this glutamate receptor. The analysis was replicated for significant SNPs in an independent sample of 1548 MS subjects. The C allele of rs4880213 was found to be associated with reduced NMDAR-mediated cortical excitability, and with increased probability of having more disability than the CT/TT MS subjects. MS severity was higher in the CC group among relapsing-remitting MS (RR-MS) patients, while primary progressive MS (PP-MS) subjects homozygous for the T allele had more pronounced clinical worsening. Mean time to first relapse, but not to an active MRI scan, was lower in the CC group of RR-MS patients, and the number of subjects with two or more clinical relapses in the first two years of the disease was higher in CC compared to CT/TT group. Furthermore, the percentage of relapses associated with residual disability was lower in subjects carrying the T allele. Lesion load at the MRI was conversely unaffected by the C or T allele of this SNP in RR-MS patients. Axonal and neuronal degeneration at the optical coherence tomography was more severe in the TT group of PP-MS patients, while reduced retinal nerve fiber thickness had less consequences on visual acuity in RR-MS patients bearing the T allele. Finally, the T allele was associated with preserved cognitive abilities at the Rao’s brief repeatable neuropsychological battery in RR-MS. Signaling through glutamate NMDARs enhances both compensatory synaptic plasticity and excitotoxic neurodegeneration, impacting in opposite ways on RR-MS and PP-MS pathophysiological mechanisms.     

Alternative pathways of liana communities in the forests of northwestern Argentina

Liana dynamics in secondary and mature forests are well known in tropical areas dominated by native tree species. Outside the tropics and in secondary forests invaded by exotic species, knowledge is scarce. In this study, we compare liana communities between secondary and mature forests dominated by native species in a subtropical montane area of Sierra de San Javier, Tucuman, Argentina. Additionally, we evaluate changes of liana communities in secondary forests with increasing densities of Ligustrum lucidum and Morus alba, two of the most invasive exotic trees of the area. We surveyed liana species richness and density in three 30-year secondary patches, four 60-year secondary patches, and four mature patches dominated by native tree species, to analyze changes in liana communities with forest age. Within each patch, we sampled 10–25 20 × 20 m quadrats. Additionally, we surveyed liana density and species richness in secondary forest patches with different densities of L. lucidum and M. alba. In native-dominated forests, liana species richness increased and showed a tendency of increasing basal area from 30-year secondary forests to mature forests. Liana density was highly variable, and most of the species were shared between native-dominated secondary and mature forests. Liana density and species richness decreased with L. lucidum density, whereas in secondary forests highly dominated by M. alba, lianas increased in density. Overall, lianas followed different pathways influenced by native forest succession and exotic tree invasions.     

Spatiotemporal variations in density and biomass of rocky reef fish in a biogeographic climatic transition zone: trends over 9 years,inside and outside the only nearshore no-take marine-protected area on the southern Brazilian coast

Biogeographical transition zones are important areas to investigate evolutionary ecological questions, but long-term population monitoring is needed to better understand ecological processes that govern population variations in such edge environments. The southernmost Brazilian rocky reefs are the southern limit of distribution for 96% of the tropical ichthyofauna of the western Atlantic. The Arvoredo Marine Biological Reserve is the only nearshore no-take marine-protected area (MPA) located in this transition zone. The main aim was to investigate how the populations of rocky reef fish species vary in density and biomass in space and over time, inside and outside the Arvoredo MPA. This study presents results based on a 9 year (2008–2017) underwater visual census monitoring study to evaluate the density and biomass of key fish species. Variations in density and biomass were detected for most species. Factors and mechanisms that may have influenced spatial variation are habitat structural complexity and protection from fisheries. Temporal variations, otherwise, may have been influenced by species proximity to their distributional limit, in synergy with density-dependent mechanisms and stochastic winter temperature oscillations. The MPAs harbour higher density and biomass for most species. Nonetheless, a prominent temporal decline in the recruitment of Epinephelus marginatus calls into question the continuous effectiveness of the MPA.     

A CRYGC gene mutation associated with autosomal dominant pulverulent cataract

Purpose

To describe at molecular level a family with pulverulent congenital cataract associated with a CRYGC gene mutation.

Methods

One family with several affected members with pulverulent congenital cataract and 230 healthy controls were examined. Genomic DNA from leukocytes was isolated to analyze the CRYGA-D cluster, CX46, CX50 and MIP genes through high-resolution melting curve and DNA sequencing.

Results

DNA sequencing in the affected members revealed the c.143G>A mutation (p.R48H) in exon 2 of the CRYGC gene; 230 healthy controls and ten healthy relatives were also analyzed and none of them showed the c.143G>A mutation. No other polymorphisms or mutations were found to be present.

Conclusion

In the present study, we described a family with pulverulent congenital cataract that segregated the c.143G>A mutation (p.R48H) in the CRYGC gene. A few mutations have been described in the CRYGC gene in autosomal dominant cataract, none of them with pulverulent cataract making clear the clinical heterogeneity of congenital cataract. This mutation has been associated with the phenotype of congenital cataract but also is considered an SNP in the NCBI data base. Our data and previous report suggest that p.R48H could be a disease-causing mutation and not an SNP.     

Immunogenic properties of a lettuce-derived C4(V3)6 multiepitopic HIV protein

Elicitation of broad humoral immune responses is a critical factor in the development of effective HIV vaccines. In an effort to develop low-cost candidate vaccines based on multiepitopic recombinant proteins, this study has been undertaken to assess and characterize the immunogenic properties of a lettuce-derived C4(V3)6 multiepitopic protein. This protein consists of V3 loops corresponding to five different HIV isolates, including MN, IIIB, RF, CC, and RU. In this study, both Escherichia coli and lettuce-derived C4(V3)6 have elicited local and systemic immune responses when orally administered to BALB/c mice. More importantly, lettuce-derived C4(V3)6 has shown a higher immunogenic potential than that of E. coli-derived C4(V3)6. Moreover, when reactivity of sera from mice immunized with C4(V3)6 are compared with those elicited by a chimeric protein carrying a single V3 sequence, broader responses have been observed. The lettuce-derived C4(V3)6 has elicited antibodies with positive reactivity against V3 loops from isolates MN, RF, and CC. In addition, splenocyte proliferation assays indicate that significant T-helper responses are induced by the C4(V3)6 immunogen. Taken together, these findings account for the observed elicitation of broader humoral responses by the C4(V3)6 multiepitopic protein. Moreover, they provide further validation for the production of multiepitopic vaccines in plant cells as this serves not only as a low-cost expression system, but also as an effective delivery vehicle for orally administered immunogens.     

Deregulation of excitatory neurotransmission underlying synapse failure in Alzheimer's disease

Alzheimer′s disease (AD) is the most common form of dementia in the elderly. Memory loss in AD is increasingly attributed to soluble oligomers of the amyloid‐β peptide (AβOs), toxins that accumulate in AD brains and target particular synapses. Glutamate receptors appear to be centrally involved in synaptic targeting by AβOs. Once bound to neurons, AβOs dysregulate the activity and reduce the surface expression of both N‐methyl‐d ‐aspartate (NMDA) and 2‐amino‐3‐(3‐hydroxy‐5‐methyl‐isoxazol‐4‐yl)propanoic acid (AMPA) types of glutamate receptors, impairing signaling pathways involved in synaptic plasticity. In the extracellular milieu, AβOs promote accumulation of the excitatory amino acids, glutamate and d ‐serine. This leads to overactivation of glutamate receptors, triggering abnormal calcium signals with noxious impacts on neurons. Here, we review key findings linking AβOs to deregulated glutamate neurotransmission and implicating this as a primary mechanism of synapse failure in AD. We also discuss strategies to counteract the impact of AβOs on excitatory neurotransmission. In particular, we review evidence showing that inducing neuronal hyperpolarization via activation of inhibitory GABA_A receptors prevents AβO‐induced excitotoxicity, suggesting that this could comprise a possible therapeutic approach in AD.     

Very fine‐scale population genetic structure of sympatric asterinid sea stars with benthic and pelagic larvae: influence of mating system and dispersal potential

The present study investigated the fine‐scale population genetic structure of sympatric asterinid sea stars with contrasting modes of larval development (benthic versus pelagic). Parvulastra exigua lacks a dispersive life phase yet is one of the worlds most widely distributed and abundant sea stars, whereas Meridiastra calcar, a sea star with a dispersive larva, has a more limited regional scale distribution. Populations of P. exigua sampled from tide pools on three adjacent headlands showed significant genetic substructure (mitochodrial DNA control region) at fine spatial scales (tide pools < 300 m apart: F_ST = 0.249, P < 0.01; headlands 5–15 km apart: F_ST = 0.125, P = 0.04). As expected, M. calcar populations sampled from the same headlands did not exhibit significant genetic structuring (F_ST = 0.029, P = 0.14). The life‐history traits of P. exigua, a mixed mating system (selfing + outcrossing), pseudocopulation among closely‐related conspecifics, and an entirely benthic life cycle with a philopatric larva, undoubtedly influence its strong genetic structure across fine spatial scales. Localized genetic structure, especially at the very fine‐scale of tide pools, would not be detected in the more typical regional scale approaches adopted by most studies of marine invertebrate populations. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2013, ●●, ●●–●●.     

Adaptation of the 3H-Leucine Incorporation Technique to Measure Heterotrophic Activity Associated with Biofilm on the Blades of the Seaweed Sargassum spp.

The ecological interaction between microorganisms and seaweeds depends on the production of secondary compounds that can influence microbial diversity in the water column and the composition of reef environments. We adapted the ³H-leucine incorporation technique to measure bacterial activity in biofilms associated with the blades of the macroalgae Sargassum spp. We evaluated (1) if the epiphytic bacteria on the blades were more active in detritus or in the biofilm, (2) substrate saturation and linearity of ³H-leucine incorporation, (3) the influence of specific metabolic inhibitors during ³H-leucine incorporation under the presence or absence of natural and artificial light, and (4) the efficiency of radiolabeled protein extraction. Scanning electron microscopy showed heterogeneous distribution of bacteria, diatoms, and polymeric extracellular secretions. Active bacteria were present in both biofilm and detritus on the blades. The highest ³H-leucine incorporation was obtained when incubating blades not colonized by macroepibionts. Incubations done under field conditions reported higher ³H-leucine incorporation than in the laboratory. Light quality and sampling manipulation seemed to be the main factors behind this difference. The use of specific metabolic inhibitors confirmed that bacteria are the main group incorporating ³H-leucine but their association with primary production suggested a symbiotic relationship between bacteria, diatoms, and the seaweed.     

Identification of clinical,epidemiological and laboratory risk factors for leprosy reactions during and after multidrug therapy

This cross-sectional retrospective study evaluated 440 leprosy patients; 57% (251/440) had leprosy reactions during and/or after multidrug therapy, 80.5% (202/251) of whom presented with multibacillary leprosy. At diagnosis, positive bacterial index (BI) [odds ratio (OR) = 6.39; 95% confidence interval (CI): 4.1-10.1)] or polymerase chain reaction (PCR) (OR = 9.15; 95% CI: 5.4-15.5) in skin smears, anti-phenolic glycolipid-1 (anti-PGL-1) ELISA (OR = 4.77; 95% CI: 2.9-7.9), leucocytosis (OR = 9.97; 95% CI: 3.9-25.7), thrombocytopenia (OR = 5.72; 95% CI: 2.3-14.0) and elevated lactate dehydrogenase (OR = 2.38; 95% CI: 1.4-4.0) were potential markers for the development of reactions during treatment. After treatment, positive BI (OR = 8.47; 95% CI: 4.7-15.3) and PCR (OR = 6.46; 95% CI: 3.4-12.3) in skin smears, anti-PGL-1 ELISA (OR = 2.25; 95% CI: 1.3-3.9), anaemia (OR = 2.36; 95% CI: 1.2-4.5), leucocytosis (OR = 4.14; 95% CI: 1.5-11.6) and thrombocytopenia (OR = 3.70; 95% CI: 1.3-2.2) were risk factors for the occurrence of reactions during the study period. The identification of groups with an increased risk for developing reactions will allow for the timely development of a treatment plan to prevent nerve damage and, therefore, the appearance of the disabling sequelae associated with the stigma of leprosy.     

Engineering production of antihypertensive peptides in plants

To date, a number of antihypertensive peptides (AHPs) have been identified. Most of these are derived from proteins present in common edible consumables, including milk, egg, and plant foods. Consumption of these foods serves as means of AHP delivery and thus contributing favorable health benefits. It is hypothesized that food crops, either over-expressing AHP precursor proteins or producing particular peptides as heterologous components, may serve as viable vehicles for production and delivery of functional foods as alternative hypertension therapies. In recent years, genetic engineering efforts have been undertaken to add value to functional foods. Pioneering approaches have been pursued in several crop plants, such as rice and soybean. In this review, a summary of current tools used for discovery of new AHPs, as well as strategies and perspectives of capitalizing on these AHPs in genetic engineering efforts will be presented and discussed. The implications of these efforts on the development of functional foods for preventing and treating hypertension are also presented.