Alexander disease:the road ahead

Alexander disease is a rare neurodegenerative disorder caused by mutations in the glial fibrillary acidic protein,a type III intermediate filament protein expressed in astrocytes.Both early(infantile or juvenile)and adult onsets of the disease are known and,in both cases,astrocytes present characteristic aggregates,named Rosenthal fibers.Mutations are spread along the glial fibrillary acidic protein sequence disrupting the typical filament network in a dominant manner.Although the presence of aggregates suggests a proteostasis problem of the mutant forms,this behavior is also observed when the expression of wild-type glial fibrillary acidic protein is increased.Additionally,several isoforms of glial fibrillary acidic protein have been described to date,while the impact of the mutations on their expression and proportion has not been exhaustively studied.Moreover,the posttranslational modification patterns and/or the protein-protein interaction networks of the glial fibrillary acidic protein mutants may be altered,leading to functional changes that may modify the morphology,positioning,and/or the function of several organelles,in turn,impairing astrocyte normal function and subsequently affecting neurons.In particular,mitochondrial function,redox balance and susceptibility to oxidative stress may contribute to the derangement of glial fibrillary acidic protein mutant-expressing astrocytes.To study the disease and to develop putative therapeutic strategies,several experimental models have been developed,a collection that is in constant growth.The fact that most cases of Alexander disease can be related to glial fibrillary acidic protein mutations,together with the availability of new and more relevant experimental models,holds promise for the design and assay of novel therapeutic strategies.

Added after Anoxia-Reoxigenation Stress, Genistein Rescues from Death the Rat Embryo Cortical Neurons

Estrogens and phytoestrogens have neuroprotective effect against neuronal damage induced by cerebral ischemia /reperfusion (I/R) injury. In preceding studies, the phytoestrogen effects have been assessed by administration previous to the ischemic period, conditions which are unusual to apply to the treatment of human stroke. Here we present a study on neuroprotection afforded by genistein on rat embryo cortical neurons subjected to oxygen and glucose deprivation (OGD) followed by re-oxigenation, when added after the stress stimulus. At 1 and 2 h of OGD times and after 24 h of reperfusion, cell viability, necrotic, apoptotic and autophagic cell death and different parameters related to oxidative stress and mitochondrial dysfunction were measured in the absence and presence of 1 μM genisteine. We found an in-creasing loss of neuronal viability after 1-5 h of OGD which was only reversed in part by 24 h of reperfusion. These changes were preceded by increases in ROS generation, caspase-3 activation, LDH release and increase in LC3B lipi-dation, indicative of autophagia. Treatment with 1 μM genistein during the 24 h reperfusion significantly attenuated neuronal necrosis and autophagia induced by 1 and 2 h of OGD exposure. Genistein also decreased ROS generation and lipid-peroxidation induced by 2 h of OGD. These results suggest an important neuroprotective effect of genistein against transient post-ischemic-like

Genetic Diversity of the Endemic Xantus’ Hummingbird Using 16 Novel Polymorphic Microsatellite Loci, and Their Cross Amplification between Six Related Species

A set of 16 microsatellite loci was developed and characterized for the Xantus’ hummingbird (Hylocharis xantusii) by using 454 next-generation sequencing. Twenty-five H. xantusii samples from one population were genotyped;all loci were polymorphic, with the number of alleles ranging from three to ten. The mean observed heterozygosity was 0.681 for all loci. No significant linkage disequilibrium was detected, but five loci (Hxan05, 06, 09, 13 and 14) showed deviation from Hardy-Weinberg equilibrium. These microsatellite loci are the first to be characterized for H. xantusii. A moderate to high level of cross-species amplification was observed across the six hummingbird species (31% - 87.5%), with the best cross amplification results observed in the closest related species (H. leucotis, Cynanthus latirostris, Calypte costae). The availability of these molecular tools allows assessing questions integrating population genetics, ecology, conservation, and evolutionary history for H. xantusii and for other phyogenetically related species.

Presence of Infectious Hypodermal and Haematopoietic Necrosis Virus (IHHNV) in Native Shrimps from Southern Mexico

A survey for Infectious Hypodermal and Haematopoietic Necrosis Virus (IHHNV) and White Spot Syndrome Virus (WSSV) was performed during two catching seasons of native shrimps in the Yucatan Coast in the Gulf of Mexico. The mtDNA COI barcode identified two endemic species;the southern pink shrimp Penaeus notialis (Pérez Fantante, 1967) and the northern pink shrimp Penaeus brasiliensis (Latreille, 1987) (previously described as Farfantepenaeus brasiliensis). The prevalence of IHHNV was of 18.18% in 2016, and of 8.57% in 2017. All organisms tested negative for WSSV. This is the first identification of wild shrimps in the state of Yucatan Mexico by mtDNA COI barcode as well as the first identification of IHHNV in such species. The presence of IHHNV in wild shrimps populations has a potential of persisting in the coast of Yucatan with putative detrimental effect on local fisheries because once established in natural waters and hosts;such pathogens are almost impossible to eradicate.

Citrus oils as chain transfer agents in the cross-metathesis degradation of polybutadiene in block copolymers using Ru-alkylidene catalysts

The cross-metathesis degradation of poly(styrene-co-butadiene) (styrene, 30 wt%) (SB-1) and poly(styrene-co-butadiene) (styrene, 21 wt%) (SB- 2) in the presence of essential oils and d-limo-nene as chain transfer agents (CTAs) using Rualkylidene catalysts (PCy3)2(Cl)2Ru = CHPh (I) and (1,3-diphenyl-4,5-dihydroimidazol-2-ylidene) (PCy3)Cl2Ru=CHPh (II) was studied. Terpene-terminated butadiene oligomers and polystyrene blocks were obtained as products of the degradation of SB-1 and SB-2. Catalysts I and II showed high activity in the degradation of SB copolymers to produce the low molecular weight products (Mn = 276 - 335 g·mol-1) and yields ranging from 91% - 95%. The cross-metathesis degradation of copolymers in organic solvents and in citrus oils (mandarin, orange and lemon oils) proceeded with similar efficiency and resulted in the same molecular weight butadiene oligomers. According to GS/MS (EI) analysis, the main products of the degradation of SB-1 copolymer with d-limonene were limonene-terminated oligomers of series Am (m = 1 - 4).

Differences in arsenic, molybdenum, barium, and other physicochemical relationships in groundwater between sites with and without mining activities

The characteristic relationships of trace metals and other water quality parameters in a specific region can be affected by anthropogenic activeties. Since the mid-18th century in the southwestern part of the Baja California Peninsula, intermittent gold mining activities have been developed. We analyzed 36 water quality parameters in accordance with the procedures suggested by international agencies to evaluate the impact of this activity and the time of year on the mobilization of trace element levels and their relationships in groundwater. Quantifiable levels of molybdenum help to establish the area influenced by ore deposits because it is one of the three elements in the paragenesis associated to gold. Arsenic in sites closer to ore burning areas was associated with cobalt, indicating the potential presence of a by-product generated from arsenolite;whereas in the non-mineralized area, it was associated with barium, forming a compound that tends to precipitate, thereby maintaining a natural geochemical control in this region. From the sites sampled, 45% exceeded the limit for arsenic (10 μg/l) established by international agencies. During area monitoring with annual precipitation of 207 mm, only seven of 36 parameters analyzed showed significant differences in relation to time of year.

New Interpretations about Clonal Architecture for the Sour Pitaya (<i>Stenocereus gummosus</i>, Cactaceae), Arising from Microsatellite Markers of <i>de novo</i>Isolation and Characterization

The use of molecular markers has improved the ecological and evolutionary research in the case of clonal reproduction species, allowing the identification of boundaries among clonal modules (ramets), genetic individuals (genets), and populations. Microsatellite markers were developed for Stenocereus gummosus, a columnar cactus with both sexual and clonal reproduction which is distributed in the Sonoran Desert, Mexico. 454-Pyrosequencing reads were analyzed to detect microsatellite markers. Forty primer pairs were screened to look for polymorphism. Nine loci were genotyped for two S. gummosus localities. Sampling strategy was intended to avoid collecting a genetic individual more than once, considering that clonal architecture for this cactus was previously deduced as clumped. Polymorphic loci exhibited low allele count, ranging from 2 - 7 (mean of 3.78 ± 0.62 SE);mean heterozygosity values were 0.221 and 0.234 HO and 0.408 and 0.306 HE, with FIS of 0.383 and 0.299, for peninsular and continental localities respectively. Unexpectedly, some multilocus genotypes were found repeated within locality, which were assumed as clones since data was evaluated as sufficient (clonal richness R of 0.966 and 0.897). These results were different from those previously reported: the distribution of clones might as well be intermingled, having a minimum ramet dispersion distance of 30 m. This characteristic was also consistent with the recent colonization proposed for this and other arid lands plants. A wider genetic neighborhood, due to clone dispersion might affect diversity indexes while increasing the chance of geitonogamy and mating among relatives. The markers isolation and its population characterization allowed addressing new questions about S. gummosus ecology, clonal reproduction and reproductive biology.

Analysis of the Degree of Quality of Fish Fillet in Refrigeration

Fish is a highly nutritious food widely consumed around the world. The production of fish for human consumption is from capture fishing and aquaculture activities. Tilapia is considered one of the fish with the highest production worldwide, being a source of quality protein at an affordable price. On the other hand, and in addition to its nutritional properties, fish is highly susceptible to deterioration and contamination, mainly due to its intrinsic properties, making it able to consume it for short periods of time, so to extend its availability, it is subjected to common conservation processes like refrigeration. Therefore, the present study is focused on the analysis of the degree of freshness and quality of tilapia fillet through sensory evaluation during refrigerated storage for 12 days. The results indicated that the tilapia fillet during storage had a grade of first quality from day 0 to 4th of storage recommended for consumption, second quality on the 6th day and out of quality from the 8th of storage, the latter being not recommended for human consumption.

Early Detection of White Spot Syndrome Virus(WSSV)in Isolated Hemocytes of Litopenaeus vannamei

To date, White Spot Syndrome (WSS) produced by the White Spot Syndrome Virus (WSSV) causes one of the most severe diseases infecting penaeid shrimps worldwide. Although a vast amount of studies has elucidated pathogenesis in live infection models, there is still little information about the interaction of WSSV infections using in vitro models in the whiteleg shrimp Litopenaeus vannamei (L. vannamei) hemocytes. In this study, a WSSV infection kinetics was performed using total hemocytes isolated from healthy L. vannamei organisms and maintained in in vitro conditions using isotonic solution for shrimp (ISS). The infected experimental cells received ≈ 30,000 viral copies of WSSV. The viability of the hemocytes (control and infected group) was measured during the kinetics with trypan blue exclusion method and cells were maintained up to 6 hpi (post-infection) with non-significant differences of viability between both groups. WSSV replication was assessed using RT- PCR at the RNA expression level of the early viral gene Ie1 and transcripts were detected as early as 30 min pi. Hemocytes from WSSV group showed disrupted integrity, degranulation and irregular shape. This study provides evidence of the capability of WSSV to infect and replicates in L. vannamei hemocytes using in vitro assays in short times as 30 min.

Dobesilate for dry age-related macular degeneration

We have evaluated the effects of intravitreal dobesilate, a synthetic fibroblast growth factor inhibitor, in patients with dry age-related macular degeneration, an inflammatory-related retinal disease without available treatment up to date. 36 eyes from 36 patients with dry age-related macular degeneration were treated with a single intravitreal dobesilate injection. The end points were the improvement from baseline visual acuity and normalization of retinal histology at one month. Intravitreal dobesilate injection resulted in a significant improvement in functional and anatomical outcomes at one month after injection. Our results suggest that intravitreal dobesilate may increase the chance of visual acuity gain in dry age-related macular degeneration, even in cases with initial low vision. This study supports the findings of previously published case reports, regarding the short-term improvement in visual acuity by intravitreal dobesilate injection in different degenerative retinal diseases.

Stress Biomarkers in the Giant Manta Mobula birostris Associated to Tourism in the Revillagigedo National Park, Mexico

A constant increase in dive tourism over the past years in the Revillagigedo National Park, Mexico, could result in a stressful scenario for giant mantas (Mobula birostris). The purpose of this study was to determine the degree of oxidative stress in terms of changes in catalase units (CAT) and muscle glycogen concentration in this species during two periods of different tourism intensity in this protected area. A total of 21 muscle biopsies were collected in March (peak tourism) and November (lower tourism), 2019. Stress biomarkers were analysed by commercial kits from the company Cayman Chemical. Oxidative stress (catalase activity) was significantly higher during the period with lower tourism (p = 0.002), compared to the period with more tourism, suggesting the presence of the general adaptation syndrome. In males, there was a significant difference (p = 0.0005) in oxidative stress between periods of different tourism intensity, suggesting that the reproductive season may be a stressor. Morphotypes showed different oxidative stress (p = 0.031);however, the reason is unknown. No statistical differences were detected in glycogen concentrations between the tourism periods (p = 0.123), probably because this polysaccharide is not a proper indicator of chronic stress in giant mantas. Based on these findings, giant mantas may have an adequate response in terms of oxidative stress due to an increase in tourism;however the observed increase in catalase suggests that it is within the tolerance range of these organisms.

PDRG1 at the interface between intermediary metabolism and oncogenesis

PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damageregulated gene 1(PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. High-throughput studies identified the PDRG1 protein in a variety of macromolecular complexes involved in processes that are altered in cancer cells. For example, this oncogene has been found as part of the RNA polymerase Ⅱ complex, the splicing machinery and nutrient sensing machinery, although its role in these complexes remains unclear. More recently, the PDRG1 protein was found as an interaction target for the catalytic subunits of methionine adenosyltransferases. These enzymes synthesize S-adenosylmethionine, the methyl donor for, among others, epigenetic methylations that occur on the DNA and histones. In fact, downregulation of S-adenosylmethionine synthesis is the first functional effect directly ascribed to PDRG1. The existence of global DNA hypomethylation, together with increased PDRG1 expression, in many tumor cells highlights the importance of this interaction as one of the putative underlying causes for cell transformation. Here, we will review the accumulated knowledge on this oncogene, emphasizing the numerous aspects that remain to be explored.

Protein kinase clk/STY is differentially regulated during erythroleukemia cell differentiation: a bias toward the skipped splice variant characterizes postcommitment stages

Clk/STY is a LAMMER protein kinase capable to phosphorylate serine/arginine-rich (SR) proteins that modulate pre-mRNA splicing. Clk/STY alternative splicing generates transcripts encoding a full-length kinase and a truncated catalyti-cally inactive protein. Here we showed that clk/STY, as well as other members of the family (e.g. clk2, clk3 and clk4),are up-regulated during HMBA-induced erythroleukemia cell differentiation. mRNAs coding for the full-length and thetruncated forms were responsible for the overall increased expression. In clk/STY, however, a switch was observed forthe ratio of the two alternative spliced products. In undifferentiated cells the full-length transcript was more abundantwhereas the transcript encoding for the truncated form predominated at latter stages of differentiation. Surprisingly,overexpression of clk/STY did not alter the splicing switch upon differentiation in MEL cells. These results suggest thatclk/STY might contribute to control erythroid differentiation by a mechanism that implicates a balance between thesetwo isoforms.

Improvement in the signs and symptoms of dry eye disease with dobesilate eye drops

Background:Dry eye is a multifactor disease of the tear film and ocular surface that substantially affects quality of life.Case presentation:Dobesilate administered as eye drops was well tolerated and effective in treating both the objective signs and subjective symptoms of dry eye disease in this 2-week study.Conclusion:To the best of our knowledge,this is the first clinical report of using dobesilate in eye drops.Dobesilate may provide a novel approach to treating drying diseases of the eye.

A functional variant in the CD209 promoter is associated with DQ2-negative celiac disease in the Spanish population

AIM： To address the role of CD209 in celiac disease （CD） patients. Non-human leukocyte antigen （HLA） genetic factors in CD predisposition are poorly understood, and environmental factors like infectious pathogens may play a role. CD209 is a dendritic and macrophage surface molecule involved in pathogen recognition and immune activation. Recently, a functional variant in the promoter of the CD209 gene （-336A/G） has been shown to affect the transcriptional CD209 activity in vitro and it has been associated with a higher susceptibility to/or severity of infection. METHODS： The study population was composed of two case-control cohorts of 103 and 386 CD patients and 312 y 419 healthy controls as well as a panel of 257 celiac families. Genotyping for the -336A/G CD209 promoter polymorphism was performed using a TaqMan 5＇ allelic discrimination assay. HLA-DQ was determined by hybridization with allele specific probes. RESULTS： Initially, the case-control and familial studies did not find any association of the -336 A/G CD209 genetic variant with CD susceptibility. However, the stratification by HLA-DQ2 did reveal a significant association of CD209 promoter polymorphism in the HLA-DQ2 （-） group （carrier A vs GG in DQ2 （-） vs DQ2 （＋） patients （P = 0.026, OR = 3.71）. CONCLUSION： The -336G CD209 allele seems to be involved in CD susceptibility in HLA-DQ2 （-） patients. Our results might suggest a possible role of pathogens in the onset of a minor group of CD patients.

Dramatic resolution of vitreous hemorrhage after an intravitreal injection of dobesilate

Vitreous hemorrhages are important clinical manifestations of proliferative diabetic retinopathy. Non-cleared vitreous hemorrhages could lead to hemosiderosis bulbi and glaucoma. Here, we describe the case of a type 2 diabetic patient presenting anterior segment and vitreous hemorrhages that resolved three days after treatment with a single intravitreal injection of dobesilate.

墨西哥帕丘卡卵胎生条纹强棱蜥的繁殖周期(英文)

本文报道墨西哥伊达尔戈州帕丘卡地区干旱环境中卵胎生条纹强棱蜥的繁殖周期及特征。测定墨西哥两个科学收藏馆的浸制标本获得数据。雌雄个体达到性成熟时的体长相等,为40.0mm。雄体睾丸重量在5月开始增加,至7、8月达到最大。睾丸重量变化与降雨量、温度和光周期均无关。雌体卵泡重量在7月开始增加,并一直持续至10月。从11月至次年7月,雌体怀有胚胎。卵黄发生及胚胎发育与光周期、温度和降雨量无关。窝仔数与雌体体长呈正相关。平均窝仔数为5.2±0.2个(2-10个)。

Masting effect on alpha and beta avian diversity in fragmented forests of relict?endangered Mexican Beech(Fagus grandifolia subsp.mexicana)

Background:Tropical montane cloud forests are one of the most important hotspots on Earth and show presence of relict-endemic and endangered species,representing about 14%of the total tropical forest worldwide.Synchronous seed production or masting in tropical montane cloud tree species is a widespread reproductive strategy of decidu-ous and evergreen broad-leaved tree associations to decrease costs of reproduction and ensure offspring.Masting event maintains a high avian diversity,which can be modified by phenological process(seed production and non-seed production).Methods:The main aim of this study was to assess alpha and beta avian diversity and whether the composition of the trophic guild modifies among phenological processes and between two fragmented relict-endangered Mexican Beech(Fagus grandifolia subsp.mexicana)forests(Medio Monte and El Gosco)in the Mexican state of Hidalgo.In addi-tion,we evaluated beechnut production.Results:We recorded 36 bird species,11 of them included in some conservation risk status,and 5 endemic species.Alpha diversity values were dissimilar in avian richness(q=0)among phenological processes and between frag-mented beech forests.Avian communities among three phenological processes and between fragmented forests were structurally similar,dominated during immature seeds the Brown-backed Solitaire(granivores-insectivores-frugivores);during mature seeds the White-crowned Parrot(Pionus senilis,granivores-frugivores);and the Dwarf Jay(Cyanolyca nana,insectivores)was abundant during low seed quality.The complementarity index was high among phenological processes and low between forests.We found a high bird turnover value between immature seeds—mature seeds and during mature seeds—low seed quality.Furthermore,a similar pattern was recorded between the two study forests.Seed production showed a high number of undamaged beechnuts in Medio Monte,while in El Gosco beechnuts were attacked by insects.Conclusions:Our results reflect that masting phenological process and contrasting study forests'structure influence the shifts in alpha and beta diversity of seed and non-seed bird consumers.Our study reaffirms the importance of continuing studies throughout masting in all the Mexican Beech forests to address regional efforts in preserving the relict-ecological interactions.

Oxidative stress indicators in human and bottlenose dolphin leukocytes in response to a pro-inflammatory challenge

Marine mammals undergo cycles of tissue ischemia and reperfusion during the dive response.Reperfusion injury can result in oxidative tissue damage and the activation of a pro-inflammatory immune response.The risk of oxidative damage is reduced by antioxidants.Our hypothesis is that the reported higher antioxidant defenses within marine mammal tissues provide additional protection in situations that produce oxidative stress,like inflammation,in comparison to terrestrial mammal tissues.Leukocytes were isolated from the whole blood of Pacific bottlenose dolphins(Tursiops truncatus gilli)and humans(Homo sapiens)and were exposed to lipopolysaccharides(LPS,10μg/mL)in vitro to simulate a pro-inflammatory challenge.Oxidative stress indicators,including superoxide radical(O_(2)^(•−))production,activities of superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GPx),glutathione reductase(GR),and glutathione S-transferase(GST),as well as oxidative protein damage,were quantified by spectrophotometry.Following 48 h under experimental conditions,bottlenose dolphin leukocytes produced 1.9 times more O_(2)^(•−)but displayed 2.0 times lower protein carbonyl concentrations compared to human leukocytes.Following 48 h under experimental conditions,bottlenose dolphin leukocytes displayed 7.9,2.0,11.1,and 3.3 times more activities of CAT,GPx,GR,and GST,respectively,compared to human leukocytes.These results suggest that,under cell culture conditions,the antioxidant defenses in bottlenose dolphin leukocytes provide additional protection against pro-inflammatory challenges in comparison to human leukocytes,likely as an adaptive advantage.