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In people with multiple sclerosis (MS), newborn and surviving oligodendrocytes (OLs) can contribute to remyelination, however, current therapies are unable to enhance or sustain endogenous repair. Low intensity repetitive transcranial magnetic stimulation (LI-rTMS), delivered as an intermittent theta burst stimulation (iTBS), increases the survival and maturation of newborn OLs in the healthy adult mouse cortex, but it is unclear whether LI-rTMS can promote remyelination. To examine this possibility, we fluorescently labelled oligodendrocyte progenitor cells (OPCs; Pdgfrα-CreER transgenic mice) or mature OLs (Plp-CreER transgenic mice) in the adult mouse brain and traced the fate of each cell population over time. Daily sessions of iTBS (600 pulses; 120 mT), delivered during cuprizone (CPZ) feeding, did not alter new or pre-existing OL survival but increased the number of myelin internodes elaborated by new OLs in the primary motor cortex (M1). This resulted in each new M1 OL producing ~ 471 µm more myelin. When LI-rTMS was delivered after CPZ withdrawal (during remyelination), it significantly increased the length of the internodes elaborated by new M1 and callosal OLs, increased the number of surviving OLs that supported internodes in the corpus callosum (CC), and increased the proportion of axons that were myelinated. The ability of LI-rTMS to modify cortical neuronal activity and the behaviour of new and surviving OLs, suggests that it may be a suitable adjunct intervention to enhance remyelination in people with MS. [ABSTRACT FROM AUTHOR]

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Despite the sensitivity of ecosystems in extreme conditions, only 0.029% of the Antarctic continent is currently granted special protection as Antarctic Specially Protected Area (ASPA). Additionally, protected areas are unevenly distributed and unrepresentative of the biodiversity of Antarctica. The Antarctic Treaty Consultative Parties are thus striving to establish a more coherent network of protected areas. In this context, the Otto-von-Gruber-Gebirge was identified as an area highly worthy of protection due to its unique ecosystem including one of the largest snow petrel breeding sites, and relative pristine nature. However, in the process of designation, an update of knowledge, particularly of the population status of snow petrel in the area, was recognized to be needed. This study was aimed at estimating a population census of snow petrel breeding pairs in the Lake Untersee catchment, an important subarea of the potentially protected area. Investigations were severely limited by the remoteness and harsh conditions of the area, enabling only a short fieldwork period with limited resources. Thus, a combination of remote sensing and traditional methods was applied. We conducted a ground survey of a smaller reference area, including locating nest sites and assessing nest site characteristics. Snow petrels usually nest in the cavities of large boulders and we thus classified habitat suitability based on boulder presence. To do so, the study area was remotely surveyed by unpiloted aerial vehicles to gain orthophotomosaics in sufficient resolution to distinguish on-ground conditions for breeding. We then calculated nest site densities for the reference area. We also studied nest site data such as nest cavity depth, orientation, and attendance to gain basic knowledge of the characteristics of the breeding site. Finally, we measured a sample of four live snow petrels to determine which morph was present at the site. We were able to obtain nest site data and to extrapolate it, which produced population numbers of 11,765 breeding pairs for the whole study area. This underpins the size of the breeding site and thereby its importance for the species. [ABSTRACT FROM AUTHOR]

Environmental conservation requires identification of biological and ecological values, application of protection measures and, thereafter, regular and periodic sampling. The protection of Antarctic values is important for the conservation of the Antarctic environment. In Antarctica, multiple sites with unique values are provided with protection as Antarctic Specially Protected Areas, through the mechanisms of the Antarctic Treaty System. This study explores the relationship between research, scientific fieldwork activities and conservation values of different Antarctic Specially Protected Areas in the western Antarctic Peninsula region using as an exemplar the sampling effort and spatial coverage of the Chilean National Antarctic Science Program (PROCIEN). The results of this study reveal (a) the importance of the Field Work Report (FWR) as an Antarctic value data collecting tool and (b) the importance of the scientific stations and their associated research sites for improving knowledge of Antarctic ecosystems and underpinning sustainable Antarctic Scientific programs and expeditions. We identified a southward expansion over time of the sampling coverage of the PROCIEN, from initially restricted activities around the South Shetland Islands (62°S) towards South Bay (64°S) and Marguerite Bay (68°S). We discuss our findings in the context of climate change threats and suggest some refinements in management plans that could strengthen the effectiveness of Antarctic Specially Protected Areas. Finally, collaborations, coordination and agreements between Antarctic stakeholders are key factors in the effectiveness of Antarctic protection. [ABSTRACT FROM AUTHOR]

Despite the sensitivity of ecosystems in extreme conditions, only 0.029% of the Antarctic continent is currently granted special protection as Antarctic Specially Protected Area (ASPA). Additionally, protected areas are unevenly distributed and unrepresentative of the biodiversity of Antarctica. The Antarctic Treaty Consultative Parties are thus striving to establish a more coherent network of protected areas. In this context, the Otto-von-Gruber-Gebirge was identified as an area highly worthy of protection due to its unique ecosystem including one of the largest snow petrel breeding sites, and relative pristine nature. However, in the process of designation, an update of knowledge, particularly of the population status of snow petrel in the area, was recognized to be needed. This study was aimed at estimating a population census of snow petrel breeding pairs in the Lake Untersee catchment, an important subarea of the potentially protected area. Investigations were severely limited by the remoteness and harsh conditions of the area, enabling only a short fieldwork period with limited resources. Thus, a combination of remote sensing and traditional methods was applied. We conducted a ground survey of a smaller reference area, including locating nest sites and assessing nest site characteristics. Snow petrels usually nest in the cavities of large boulders and we thus classified habitat suitability based on boulder presence. To do so, the study area was remotely surveyed by unpiloted aerial vehicles to gain orthophotomosaics in sufficient resolution to distinguish on-ground conditions for breeding. We then calculated nest site densities for the reference area. We also studied nest site data such as nest cavity depth, orientation, and attendance to gain basic knowledge of the characteristics of the breeding site. Finally, we measured a sample of four live snow petrels to determine which morph was present at the site. We were able to obtain nest site data and to extrapolate it, which produced population numbers of 11,765 breeding pairs for the whole study area. This underpins the size of the breeding site and thereby its importance for the species.

BGP, the de-facto standard protocol for exchanging routes on a network-wide basis called AS employs invalid routes. Recently, a data object called Autonomous System Provider Authorization (ASPA) was proposed as a new specification for verifying PATH information in BGP security. In this paper, we shed light on the effectiveness of ASPAs in a partial deployment alongside the conventional BGP through experiments based on a real AS topology. To this end, we also present a novel simulation tool, LOTUS, for BGP route exchange, including ASPAs. We then evaluate deployments of ASPAs and their verification with LOTUS for two cases on network topology in Japan: the case in deployment from ASes whose number of connections with other ASes is large, i.e., deployment from top ASes, and the case in deployment from ASes at the end of the network topology, i.e., deployment from leaf-node ASes. As a result, we confirm that the number of victim ASes decreases in the former case, while ASPAs provide no advantage in the latter case. Notably, the number of victim ASes decreases by about 96% on average by deploying the verification with ASPAs in the top-eight ASes. Based on these results, we further conduct extensive experiments in the deployment from the top ASes, whereby ASes outside the network topology advertise malicious routes to the victim ASes. We also discuss a case whereby an adversary tries to leverage ASPAs. Our promising results show that the adversary will no longer obtain an advantage even by leveraging ASPAs.

The leukodystrophy Canavan disease is a fatal white matter disorder caused by loss-of-function mutations of the aspartoacylase-encoding ASPA gene. There are no effective treatments available and experimental gene therapy trials have failed to provide sufficient amelioration from Canavan disease symptoms. Preclinical studies suggest that Canavan disease-like pathology can be addressed by either ASPA gene replacement therapy or by lowering the expression of the N-acetyl-L-aspartate synthesizing enzyme NAT8L. Both approaches individually prevent or even reverse pathological aspects in Canavan disease mice. Here, we combined both strategies and assessed whether intracranial adeno-associated virus-mediated gene delivery to a Canavan disease mouse model at 12 weeks allows for reversal of existing pathology. This was enabled by a single vector dual-function approach. In vitro and in vivo biopotency assessment revealed significant knockdown of neuronal Nat8l paired with robust ectopic aspartoacylase expression. Following nomination of the most efficient cassette designs, we performed proofof-concept studies in post-symptomatic Aspa-null mice. Late-stage gene therapy resulted in a decrease of brain vacuoles and long-term reversal of all pathological hallmarks, including loss of body weight, locomotor impairments, elevated N-acetyl-L-aspartate levels, astrogliosis, and demyelination. These data suggest feasibility of a dual-function vector combination therapy, directed at replacing aspartoacylase with concomitantly suppressing N-acetyl-L-aspartate production, which holds potential to permanently alleviate Canavan disease symptoms and expands the therapeutic window towards a treatment option for adult subjects. [ABSTRACT FROM AUTHOR]

The leukodystrophy Canavan disease is a fatal white matter disorder caused by loss-of-function mutations of the aspartoacylase-encoding ASPA gene. There are no effective treatments available and experimental gene therapy trials have failed to provide sufficient amelioration from Canavan disease symptoms. Preclinical studies suggest that Canavan disease-like pathology can be addressed by either ASPA gene replacement therapy or by lowering the expression of the N-acetyl-L-aspartate synthesizing enzyme NAT8L. Both approaches individually prevent or even reverse pathological aspects in Canavan disease mice. Here, we combined both strategies and assessed whether intracranial adeno-associated virus-mediated gene delivery to a Canavan disease mouse model at 12 weeks allows for reversal of existing pathology. This was enabled by a single vector dual-function approach. In vitro and in vivo biopotency assessment revealed significant knockdown of neuronal Nat8l paired with robust ectopic aspartoacylase expression. Following nomination of the most efficient cassette designs, we performed proof-of-concept studies in post-symptomatic Aspa-null mice. Late-stage gene therapy resulted in a decrease of brain vacuoles and long-term reversal of all pathological hallmarks, including loss of body weight, locomotor impairments, elevated N-acetyl-L-aspartate levels, astrogliosis, and demyelination. These data suggest feasibility of a dual-function vector combination therapy, directed at replacing aspartoacylase with concomitantly suppressing N-acetyl-L-aspartate production, which holds potential to permanently alleviate Canavan disease symptoms and expands the therapeutic window towards a treatment option for adult subjects.

Implementing effective conservation action requires spatial prioritization exercises to be functionally integrated with a process for developing an implementation strategy. There is great potential for animal tracking data to inform marine management in the Southern Ocean. Using information on penguin distribution, a set of marine Important Bird Areas (mIBAs) has recently been identified around Antarctica. Large-scale spatial analyses like this are key to guide resources and the attention of decision-makers towards areas of significant value. Yet, protecting marine resources requires translating prioritization exercises into legally-binding conservation measures. Here we use one of the largest gentoo colonies in Antarctica as a case study to explore pathways for the utilization of the mIBAs approach in the design and implementation of conservation measures in the Southern Ocean. For scientists and organizations willing to have a policy impact, there are two main routes to contribute to Antarctic Treaty System (ATS) decision-making: through Parties' National Delegations, or through Experts and Observers. We provide three main recommendations for incorporating the results of spatial prioritization analyses into the agenda of ATS governance bodies using the mIBAs approach: 1. Differentiate the potential contribution of mIBAs to spatial prioritization from the potential contribution to conservation planning, two different stages in the conservation process; 2. Use methods, criteria and data for delineating boundaries of potential conservation areas according to the stage of the conservation process that the outputs are expected to contribute to; 3. Understand how Antarctic mIBAs might fit into the ATS conservation measures framework and ongoing deliberations. • Animal tracking data is useful to inform marine management in the Southern Ocean • Spatial prioritization exercises must be translated into conservation measures. • We show ways to include spatial analysis into the Antarctic Treaty System agenda. [ABSTRACT FROM AUTHOR]

Escherichia coli uses the C4‐dicarboxylate transporter DcuA for L‐aspartate/fumarate antiport, which results in the exploitation of L‐aspartate for fumarate respiration under anaerobic conditions and for nitrogen assimilation under aerobic and anaerobic conditions. L‐Aspartate represents a high‐quality nitrogen source for assimilation. Nitrogen assimilation from L‐aspartate required DcuA, and aspartase AspA to release ammonia. Ammonia is able to provide by established pathways the complete set of intracellular precursors (ammonia, L‐aspartate, L‐glutamate, and L‐glutamine) for synthesizing amino acids, nucleotides, and amino sugars. AspA was regulated by a central regulator of nitrogen metabolism, GlnB. GlnB interacted with AspA and stimulated its L‐aspartate deaminase activity (NH3‐forming), but not the reverse amination reaction. GlnB stimulation required 2‐oxoglutarate and ATP, or uridylylated GlnB‐UMP, consistent with the activation of nitrogen assimilation under nitrogen limitation. Binding to AspA was lost in the GlnB(Y51F) mutant of the uridylylation site. AspA, therefore, represents a new type of GlnB target that binds GlnB (with ATP and 2‐oxoglutarate), or GlnB‐UMP (with or without effectors), and both situations stimulate AspA deamination activity. Thus, AspA represents the central enzyme for nitrogen assimilation from L‐aspartate, and AspA is integrated into the nitrogen assimilation network by the regulator GlnB. [ABSTRACT FROM AUTHOR]

Introduction: Canavan disease is an autosomal recessive disorder that causes accumulation of N-acetyl ASPArtic acid in the brain due to ASPArtoacylase deficiency with homozygous or compound heterozygous pathogenic variants in the ASPA gene located on the short arm of chromosome 17. Clinical findings are hypotonia, progressive macrocephaly, deafness, nystagmus, blindness, and brain atrophy., Case Presentation: A one-year-old female case was evaluated in our medical genetics clinic for hypotonia, nystagmus, and strabismus. Chromosome analysis and array-comparative genomic hybridization showed no pathology. Clinical exome sequencing by next-generation sequencing was performed and a homozygous likely pathogenic variant NM_000049.4( ASPA ):c.857C > A p.(Ala286Asp) was identified. Sanger sequencing of the parents showed that the index case had a homozygous genotype, the father was heterozygous and the mother had a wild genotype for the identified variant in ASPA . A single nucleotide polymorphism (SNP) array test was planned for the family to explain this homozygosity and a loss of maternal heterozygosity was determined in the 17p13.3-p13.2 region of the ASPA gene., Conclusion: In this report, we aimed to present the first case of Canavan disease with maternal loss of heterozygosity in the ASPA gene., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 S. Karger AG, Basel.)

Background: Canavan disease is an autosomal recessive, neurodegenerative disorder caused by mutations in ASPA, a gene encoding the enzyme aspartoacylase. Patients present with macrocephaly, developmental delay, hypotonia, vision impairment and accumulation of N-acetylaspartic acid. Progressive white matter changes occur in the central nervous system. The disorder is often fatal in early childhood, but milder forms exist. Materials and methods: Case report. Results: We present the case of a 31-year-old male with mild/juvenile Canavan disease who had severe vision loss due to a retinal degeneration resembling retinitis pigmentosa. Prior to this case, vision loss in Canavan disease had been attributed to optic atrophy based on fundoscopic evidence of optic nerve pallor. Investigations for an alternative cause for our patient's retinal degeneration were non-revealing. Conclusion: We wonder if retinal degeneration may not have been previously recognized as a feature of Canavan disease. We highlight findings from animal models of Canavan disease to further support the association between Canavan disease and retinal degeneration. [ABSTRACT FROM AUTHOR]

Leukodystrophies (LDs) are a heterogeneous group of rare and progressive genetic diseases that affect brain, spinal cord, and often the peripheral nerves. They are characterized by abnormal development or destruction of the myelin sheath of the brain. This study was aimed to search for the causative variants in three unrelated consanguineous families presented with LD. Detailed clinical investigations were carried out on probands in three unrelated consanguineous families of Pakistani origin. Targeted gene sequencing and Whole Exome Sequencing (WES) were performed for variant identification. Candidate variants were checked for co‐segregation with the phenotype using Sanger sequencing. Public databases including ExAC, gnomAD, dbSNP, and the 1,000 Genome Project were searched to determine frequencies of the alleles. Conservation of the missense variants was ensured by aligning orthologous protein sequences from diverse vertebrate species. Targeted gene sequencing identified a novel homozygous missense mutation [c.2135G > A, p.(Arg712His) in the ATP Binding Cassette Subfamily D Member 1 (ABCD1; OMIM# 300371) in three affected siblings in family A.WES followed by validation by Sanger sequencing revealed previously reported homozygous missense variants [c.162C > A; p.(Asn54Lys)] in ASPA (OMIM# 608034) in family B and [c.361G > C,p.(Gly121Arg)] in ARSA (OMIM# 607574) in family C. Investigation of three families underlies importance of WES as an amazing diagnostic tool for conclusive determination of a specific type of LD. Further, the study would assist in carrier testing and prenatal diagnosis of the affected families. In addition, searching for common variants in the genes causing LD would help in designing low‐cost targeted variation testing in patients. [ABSTRACT FROM AUTHOR]

O presente artigo busca analisar os efeitos da recente Cúpula América do Sul – Países Árabes, realizada em Brasília nos dias 10 e 11 de maio de 2005, no Brasil.

Pasteurella multocida (P. multocida), a causative agent of fowl cholera, is an important pathogen in the poultry industry. In the present study, we found that the inactivated vaccine of P. multocida grown in an iron-restricted medium provided better protection than that grown in normal medium. Thus, we adopted a comparative proteomics approach, by using two-dimensional gel electrophoresis (2-DE), coupled with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF MS), to profile the supernatant proteins associated with P. multocida under both conditions. Eleven upregulated proteins were identified, including aspartate ammonia-lyase (AspA), diacylglycerol kinase (DgK), 30S ribosomal protein S6 (RpsF), and eight outer membrane proteins (OMPs). To further characterize the three novel supernatant proteins identified under iron-restricted conditions, the AspA, DgK and RpsF proteins were expressed and purified, and used as immunogens to vaccinate chickens. The results showed that AspA, DgK and RpsF proteins induced 80.0%, 66.7%, and 80.0% immunity, respectively. These data indicate that the three novel proteins identified in the supernatant of the culture media might play important roles in the survival of bacteria under iron-restricted conditions, and thus protect chickens against P. multocida. These findings also suggest that the proteins identified can be used as subunit vaccines. [ABSTRACT FROM AUTHOR]

An ultra‐wide bandwidth, high‐efficiency, small‐size and low‐profile waveguide antenna is presented in this study. To extend the bandwidth without increasing the antenna size, the bowtie shape slot and the stepped square coaxial transition in a ridged waveguide cavity are utilised. The proposed antenna is well suited to use as an element for the phased array with the wide‐angle scanning capability, and such array is a good candidate for the synthetic aperture radar (SAR) application. The development of an active solid phased array (ASPA) utilising bowtie slot waveguide antenna as the element is presented to illustrate the design procedure. The proposed ASPA is fabricated and the measured results are provided to demonstrate that the proposed array has good performance in field pattern and impedance matching over the full X‐band (8–12 GHz). The ASPA's operating frequency band is cantered at 10 GHz with bandwidth 40%. This ASPA has been integrated into the latest SAR system with the maximum ground resolution of 0.05 m, and the SAR image is also provided at the end of this study. [ABSTRACT FROM AUTHOR]

Abstract Resveratrol (RSV) is a small compound first identified as an activator of sirtuin 1 (SIRT1), a key factor in mediating the effects of caloric restriction. Since then, RSV received great attention for its widespread beneficial effects on health and in connection to many diseases. RSV improves the metabolism and the mitochondrial function, and more recently it was shown to restore fatty acid β-oxidation (FAO) capacities in patient fibroblasts harboring mutations with residual enzyme activity. Many of RSV's beneficial effects are mediated by the transcriptional coactivator PGC-1α, a direct target of SIRT1 and a master regulator of the mitochondrial fatty acid oxidation. Despite numerous studies RSV's mechanism of action is still not completely elucidated. Our aim was to investigate the effects of RSV on gene regulation on a wide scale, possibly to detect novel genes whose up-regulation by RSV may be of interest with respect to disease treatment. We performed Next Generation Sequencing of RNA on normal fibroblasts treated with RSV. To investigate whether the effects of RSV are mediated through SIRT1 we expanded the analysis to include SIRT1-knockdown fibroblasts. We identified the aspartoacylase (ASPA) gene, mutated in Canavan disease, to be strongly up-regulated by RSV in several cell lines, including Canavan disease fibroblasts. We further link RSV to the up-regulation of other genes involved in myelination including the glial specific transcription factors POU3F1 , POU3F2 , and myelin basic protein (MBP). We also observe a strong up-regulation by RSV of the riboflavin transporter gene SLC52a1. Mutations in SLC52a1 cause transient multiple acyl-CoA dehydrogenase deficiency (MADD). Our analysis of alternative splicing identified novel metabolically important genes affected by RSV, among which is particularly interesting the α subunit of the stimulatory G protein (Gsα), which regulates the cellular levels of cAMP through adenylyl cyclase. We conclude that in fibroblasts RSV stimulates the PGC-1α and p53 pathways, and up-regulates genes affecting the glucose metabolism, mitochondrial β-oxidation, and mitochondrial biogenesis. We further confirm that RSV might be a relevant treatment in the correction of FAO deficiencies and we suggest that treatment in other metabolic disorders including Canavan disease and MADD might be also beneficial. [ABSTRACT FROM AUTHOR]

Background: Lateral gene transfer (LGT), also known as horizontal gene transfer, into multicellular eukaryotes with differentiated tissues, particularly gonads, continues to be met with skepticism by many prominent evolutionary and genomic biologists. A detailed examination of 26 animal genomes identified putative LGTs in invertebrate and vertebrate genomes, concluding that there are fewer predicted LGTs in vertebrates/chordates than invertebrates, but there is still evidence of LGT into chordates, including humans. More recently, a reanalysis of a subset of these putative LGTs into vertebrates concluded that there is not horizontal gene transfer in the human genome. One of the genes in dispute is an N-acyl-aromatic-L-amino acid amidohydrolase (ENSG00000132744), which encodes ACY3. This gene was initially identified as a putative bacteria-chordate LGT but was later debunked as it has a significant BLAST match to a more recently deposited genome of Saccoglossus kowalevskii, a flatworm, Metazoan, and hemichordate. Results: Using BLAST searches, HMM searches, and phylogenetics to assess the evidence for LGT, gene loss, and rate variation in ACY3/ASPA homologues, the most parsimonious explanation for the distribution of ACY3/ASPA genes in eukaryotes involves both gene loss and bacteria-animal LGT, albeit LGT that occurred hundreds of millions of years ago prior to the divergence of gnathostomes. Conclusions: ACY3/ASPA is most likely a bacteria-animal LGT. LGTs at these time scales in the ancestors of humans are not unexpected given the many known, well-characterized, and adaptive LGTs from bacteria to insects and nematodes. [ABSTRACT FROM AUTHOR]

Canavan disease is a leukodystrophy caused by mutations in the ASPA gene. This gene encodes the enzyme that converts N-acetylaspartate into acetate and aspartic acid. In Canavan disease, spongiform encephalopathy of the brain causes progressive mental retardation, motor deficit and death. We have isolated a mouse with a novel ethylnitrosourea-induced mutation in Aspa. This mutant, named deaf14, carries a c.516T>A mutation that is predicted to cause a p.Y172X protein truncation. No full-length ASPA protein is produced in deaf14 brain and there is extensive spongy degeneration. Interestingly, we found that deaf14 mice have an attenuated startle in response to loud noise. The first auditory brainstem response peak has normal latency and amplitude but peaks II, III, IV and V have increased latency and decreased amplitude in deaf14 mice. Our work reveals a hitherto unappreciated pathology in a mouse model of Canavan disease, implying that auditory brainstem response testing could be used in diagnosis and to monitor the progression of this disease.

This article critiques interregionalism as a concept that is trapped in the European Union (EU) foreign policy toolkit narrative, which in turn structures what can be said meaningfully and legitimately about interregionalism. Drawing on the experience of the Arab–South American (ASPA) Summit, it shows that, when speaking on interregionalism in International Relations (IR), one need not be speaking about the EU interregional model, which is understood as a vertical relationship established between the EU and an objectified regional partner of its choice. Rather, a broader definition for interregionalism is proposed, one that builds up from the basic ‘region-to-region’ dialogue–arrangement–cooperation and interrogates the meaning it has for those who engage in this practice. This was made possible by the construction of a framework for the analysis of the practices that lead to the materialisation of the ASPA interregional discourse and that reveal how this form of interregionalism in the Global South ‘matters’ in IR. [ABSTRACT FROM PUBLISHER]

The disruption of aspartoacylase enzyme’s catalytic activity causes fatal neurodegenerative Canavan disease. By molecular dynamics and docking methods, here we studied two deleterious mutations that have been identified in the Canavan patients’ genotype E285A, F295S, and revealed the possible cause for the enzyme inhibition due to the drastic changes in active site dynamics, loss of interactions among Arg 71, Arg 168 and the substrate and pKa value of critical Glu178 residue. In addition to changes in the enzyme dynamics, free energy calculations show that the binding energy of substrate decreases dramatically up on mutations. [ABSTRACT FROM AUTHOR]

ABSTRACT We describe 14 patients with 12 novel missense mutations in ASPA, the gene causing Canavan disease (CD). We developed a method to study the effect of these 12 variants on the function of aspartoacylase-the hydrolysis of N-acetyl- l-aspartic acid (NAA) to aspartate and acetate. The wild-type ASPA open reading frame (ORF) and the ORFs containing each of the variants were transfected into HEK293 cells. Enzyme activity was determined by incubating cell lysates with NAA and measuring the released aspartic acid by LC-MS/MS. Clinical data were obtained for 11 patients by means of questionnaires. Four patients presented with a non-typical clinical picture or with the milder form of CD, whereas seven presented with severe CD. The mutations found in the mild patients corresponded to the variants with the highest residual enzyme activities, suggesting that this assay can help evaluate unknown variants found in patients with atypical presentation. We have detected a correlation between clinical presentation, enzyme activity, and genotype for CD. [ABSTRACT FROM AUTHOR]

O presente artigo busca delinear os rumos e as expectativas para a Cúpula América do Sul – Países Árabes, a ser realizada nos dias 10 e 11 de maio de 2005.

O presente artigo busca realizar um balanço da Cúpula América do Sul – Países Árabes, realizada em Brasília nos dias 10 e 11 de maio de 2005.

Should the entire Antarctic continent and the surrounding islands be recognised as a ‘protected area’ or as a continent where certain areas, just like anywhere else, may be designated as protected areas? To find an answer to this question, this paper first discusses the most important agreements and declarations on environmental protection in Antarctica. Next, these instruments are compared with the components of IUCN’s ‘protected area’ definition (2008). In the light of this overall protection of Antarctica, the instrument of designating areas as Antarctic Specially Protected Areas (ASPAs) is discussed on the basis of a quick scan of 42 management plans for existing ASPAs. It is concluded that Antarctica could indeed be considered as a protected area and that the ASPA instrument is so shaped to provide specific areas with ‘extra protection’ by regulating human activities in those areas with a high level of detail. However, the continuous increase in human activities in Antarctica raises concerns with respect to the scope and completeness of the existing legal instruments. These concerns regarding the overall protection of Antarctica could become an argument for applying the ASPA instrument in respect of larger areas to ensure the comprehensive protection of at least certain parts of Antarctica. This would make the ASPA system more comparable with protected area systems in other parts of the world; however, strengthening the overall protection of Antarctica – parallel to the further development of the ‘specially’ protected area system - would be more consistent with Antarctica’s protected status as has developed since the Antarctic Treaty was signed 50 years ago.

O presente artigo analisa as principais características, o desenvolvimento histórico e os rumos das relações entre os países árabes e os da América do Sul.

This study analyzed how spatial distribution of Himantormia lugubris is affected by the microenvironment in the Antarctic Specially Protected Area (ASPA) No. 171 located in the Barton Peninsula of King George Island that belongs to the maritime Antarctic. In order to determine the population structure of H. lugubris growing in Baekje Hill within ASPA No. 171, we counted the individuals of different size groups after dividing the population into 5 growth stages according to mean diameter as follows: ≤ 1 cm, 1-3 cm, 3-5 cm, 5-10 cm, and ≥ 10 cm. The count of H. lugubris individuals in each growth stage was converted into its percentage with respect to the entire population, which yielded the finding that stages 1 through 5 accounted for 32.8%, 25.3%, 15.9%, 22.5%, and 3.5%, respectively. This suggests that the population of H. lugubris in ASPA No. 171 has a stable reverse J-shaped population structure, with the younger individuals outnumbering mature ones. The mean density of H. lugubris was 17.6/0.25 m², mean canopy cover 13.3%, and the mean dry weight 37.8 g/0.25 m². It began to produce spore in the sizes over 3 cm, and most individuals measuring 5-10 cm were adults with sexually mature apothecia. The spatial distribution of H. lugubris was highly heterogeneous. The major factors influencing its distribution and performance were found to be the period covered by snow, wind direction, moisture, size of the substrate, and canopy cover of Usnea spp. Based on these factors, we constructed a prediction model for estimating the spatial distribution of H. lugubris. Conclusively, the major factors for the spatial distribution of H. lugubris were snow, wind, substrate and the competition with Usnea spp. These results are important for understanding of the distribution in the maritime Antarctic and evolution of H. lugubris that claims a unique life history and ecological niche. [ABSTRACT FROM AUTHOR]

Propionibacterium freudenreichii is crucial in Swiss-type cheese manufacture. Classic propionic acid fermentation yields the nutty flavor and the typical eyes. Co-metabolism of aspartate pronounces the flavor of the cheese; however, it also increases the size of the eyes, which can induce splitting and reduce the cheese quality. Aspartase (EC 4.3.1.1) catalyzes the deamination of aspartate, yielding fumarate and ammonia. The aspartase activity varies considerably among P. freudenreichii strains. Here, the correlation between aspartase activity and the locus of aspartase-encoding genes (aspA) and dcuA encoding the C4-dicarboxylate transporter was investigated in 46 strains to facilitate strain selection for cheese culture. Low aspartase activity was correlated with a particular genomic rearrangement: low in vitro aspartase activity always occurred in strains with gene clusters aspA - dcuA where the dcuA was frameshifted, producing a stop codon or was disrupted by an ISL3-like element. The low aspartase activity could be due to the protein sequence of the aspartase or a dysfunctional DcuA. The highest values of aspartase activity were detected in strains with aspA1 - aspA2-dcuA with a DcuA sequence sharing 99.07 – 100% identity with the DcuA sequence of strain DSM 20271 T and an additional C4-dicarboxylate transporter belonging to the DcuAB family. • Strain-dependent ability of P. freudenreichii to utilize aspartate alters cheese quality — important in culture design. • P. freudenreichii strains exhibit a diverse gene arrangement around the aspartase-encoding gene. • Low aspartase-active P. freudenreichii strains revealed a specific gene arrangement around the aspartase-encoding gene. [ABSTRACT FROM AUTHOR]

Comparative analysis of rhamnose-positive Y. pestis strains, which are traditionally recognized as the biovar altaica, was performed with the use of molecular typing. The strains were isolated from the natural plague foci of the Changay mountainous system and the Sailugem natural plague focus in Mongolia. The Russian part of the latter is known as the Altai Mountains focus (focus 36). All isolates were compared with the other rhamnose-positive vole strains from the natural plague foci located in the grassland of Xilingol (focus L, China), the plateau of Qinghai-Tibet (focus M, China), the Gissarian Ridge (focus 34, Tadjikistan and Uzbekistan), and the Talassian Ridge (focus 40, Kyrgyzstan). The strains studied formed a single cluster with two branches, of which the first branch included the talassica (0.PE4?), qinghaiensis (0.PE4ab), and xilingolensis (0.PE4cd) phylogenetic groups, while the second included the hissarica (0.PE9) and altaica (0.PE1) phylogenetic groups. The results of molecular typing suggest that several strains from the Qinghai group of the Mongolian foci belong to the qinghaiensis and xilingolensis biovars but not to the altaica biovar. [ABSTRACT FROM AUTHOR]

Campylobacter jejuni is the most frequent cause of human food-borne bacterial gastroenteritis but its physiology and biochemistry are poorly understood. Only a few amino-acids can be catabolised and these are known to be important for host colonization. Here we have established methods for rapid high throughput analyses of global metabolism in C. jejuni using direct injection mass spectrometry (DIMS) to compare metabolite fingerprints of wild-type and mutant strains. Principal component analyses show that the metabolic fingerprint of mutants that have a genomic deletion in genes for key amino-acid catabolic enzymes (either sdaA, serine dehydratase; aspA, aspartase or aspB, aspartate:glutamate transaminase) can easily be distinguished from the isogenic parental strain. Assignment of putative metabolites showed predictable changes directly associated with the particular metabolic lesion in these mutants as well as more extensive changes in the aspA mutant compared to the sdaA or aspB strains. Further analyses of a cj0150c mutant strain, which has no obvious phenotype, suggested a role for Cj0150 in the conversion of cystathionine to homocysteine. Our results show that DIMS is a useful technique for probing the metabolism of this important pathogen and may help in assigning function to genes encoding novel enzymes with currently unknown metabolic roles. [ABSTRACT FROM AUTHOR]

Scullin and Murray monoliths are thought to hold the largest concentration of breeding seabirds in East Antarctica. The monoliths were designated as an Antarctic Specially Protected Area (ASPA No. 164) in 2005 in recognition of the global importance of the seabird assemblages and to protect their outstanding ecological and scientific values. The management plan for the Scullin and Murray Monoliths ASPA encourages regular seabird population monitoring using methods such as aerial photography, but the complex logistics of accessing this remote site has until now limited quantitative assessment of the seabird populations to a single survey in 1986/87. In December 2010 we photographed the Adélie penguin population to provide the population counts presented here. We discuss the potential biases and uncertainties in estimating the breeding population from both the recent and 1980s population count data. [ABSTRACT FROM AUTHOR]

To evaluate the avian influenza virus (AIV) circulation in Antarctic and sub-Antarctic penguins we carried out a serosurvey on six species from Livingston, Marion and Gough islands. Seropositivity against AIV was performed on serum samples using a competitive enzyme-linked immunosorbent assay and haemagglutination and neuraminidase inhibition assays. Some oropharyngeal and cloacal swabs were also assayed to detect influenza virus genomes by real time reverse transcription-polymerase chain reaction. Overall, 12.1% (n = 140) penguins were seropositive to AIV. By species, we detected 5% (n = 19) and 11% (n = 18) seroprevalence in sub-Antarctic rockhopper penguins (Eudyptes spp.) from Gough and Marion islands, respectively, 42% (n = 33) seroprevalence in macaroni penguins (Eudyptes chysolophus Brandt), but no positives in the three other species, gentoo (Pygoscelis papua Forster; n = 25) and chinstrap penguins (P. antarctica Forster; n = 16), from Livingston Island and king penguins (Aptenodytes patagonicus Miller; n = 27) from Marion Island. While seropositivity reflected previous exposure to the AIV, the influenza genome was not detected. Our results indicate that AIV strains have circulated in penguin species in the sub-Antarctic region, but further studies are necessary to determine the precise role that such penguin species play in AIV epidemiology and if this circulation is species (or genus) specific. [ABSTRACT FROM PUBLISHER]

Comparative analysis of 57 strains of Y. pestis subsp. microtus bv. caucasica was carried out using molecular typing. The results obtained indicate the presence of three independent phylogenetic groups and indicate the advisability of isolation of the Leninakan mountain mesofocus from the Transcaucasian highland focus into an independent focus, as well as inclusion of part of the Pre-Araks low-mountain focus as the mesofocus along with the Pre-Sevan mountain and Zangezur-Karabakh mountain mesofoci into the Transcaucasian highland plague focus. It is shown that the strains circulating in the East Caucasus highland focus of plague are the most ancient branch of the caucasica biovar, and possibly of the entire phylogenetic tree of Y. pestis. [ABSTRACT FROM AUTHOR]

Heterotrophic bacteria isolated from five aquatic microbial mat samples from different locations in continental Antarctica and the Antarctic Peninsula were compared to assess their biodiversity. A total of 2,225 isolates obtained on different media and at different temperatures were included. After an initial grouping by whole-genome fingerprinting, partial 16S rRNA gene sequence analysis was used for further identification. These results were compared with previously published data obtained with the same methodology from terrestrial and aquatic microbial mat samples from two additional Antarctic regions. The phylotypes recovered in all these samples belonged to five major phyla, Actinobacteria, Bacteroidetes, Proteobacteria, Firmicutes and Deinococcus- Thermus, and included several potentially new taxa. Ordination analyses were performed in order to explore the variance in the diversity of the samples at genus level. Habitat type (terrestrial vs. aquatic) and specific conductivity in the lacustrine systems significantly explained the variation in bacterial community structure. Comparison of the phylotypes with sequences from public databases showed that a considerable proportion (36.9%) is currently known only from Antarctica. This suggests that in Antarctica, both cosmopolitan taxa and taxa with limited dispersal and a history of long-term isolated evolution occur. [ABSTRACT FROM AUTHOR]

The American Sociological Association and the American Society for Public Administration are widely recognized as being among the premier professional associations in their respective fields within academia and beyond. Although a commitment to the promotion of ethical competence among their members is clearly viewed by both organizations as being central to the accomplishment of their missions, their techniques for doing so have included unique, as well as similar initiatives, to include, perhaps most importantly, periodic reviews and revisions of their marquee Codes of Ethics. While these reviews, which have been undertaken from an intra-disciplinary perspective, have been productive, it is the position of the authors that to approach future reviews of their ethics codes, and other ethics initiatives, from an interdisciplinary, collaborative perspective could serve to facilitate even more insightful modifications. To that end, this paper 1) provides a comprehensive, comparative overview of the ethics initiatives of the two professional associations, 2) presents a summary of what the authors will have learned with respect to the feasibility of continuing to pursue the proposed collaboration between the two associations, and 3) if it is determined that continuing efforts are warranted, presents a formal plan for moving the initiative forward toward a positive conclusion with regard to the ASA and ASPA as well as for potential expansion to other organizations. [ABSTRACT FROM AUTHOR]

Abstract: Canavan disease (CD MIM#271900) is a rare autosomal recessive neurodegenerative disorder presenting in early infancy. The course of the disease is variable, but it is always fatal. CD is caused by mutations in the ASPA gene, which codes for the enzyme aspartoacylase (ASPA), which breaks down N-acetylaspartate (NAA) to acetate and aspartic acid. The lack of NAA-degrading enzyme activity leads to excess accumulation of NAA in the brain and deficiency of acetate, which is necessary for myelin lipid synthesis. Glyceryltriacetate (GTA) is a short-chain triglyceride with three acetate moieties on a glycerol backbone and has proven an effective acetate precursor. Intragastric administration of GTA to tremor mice results in greatly increased brain acetate levels, and improved motor functions. GTA given to infants with CD at a low dose (up to 0.25g/kg/d) resulted in no improvement in their clinical status, but also no detectable toxicity. We present for the first time the safety profile of high dose GTA (4.5g/kg/d) in 2 patients with CD. We treated 2 infants with CD at ages 8months and 1year with high dose GTA, for 4.5 and 6months respectively. No significant side effects and no toxicity were observed. Although the treatment resulted in no motor improvement, it was well tolerated. The lack of clinical improvement might be explained mainly by the late onset of treatment, when significant brain damage was already present. Further larger studies of CD patients below age 3months are required in order to test the long-term efficacy of this drug. [Copyright &y& Elsevier]

Research in extremely delicate environments must be sensitive to the need to minimize impacts caused simply through the presence of research personnel. This study investigates the effectiveness of current advice relating to travel on foot over Antarctic vegetation-free soils. These are based on the concentration of impacts through the creation of properly signed and identified paths. In order to address these impacts, we quantified three factors - resistance to compression, bulk density and free-living terrestrial arthropod abundance - in areas of human activity over five summer field seasons at the Byers Peninsula (Livingston Island, South Shetland Islands). Studies included instances of both experimentally controlled use and natural non-controlled situations. The data demonstrate that a minimum human presence is sufficient to alter both physical and biological characteristics of Byers Peninsula soils, although at the lowest levels of human activity this difference was not significant in comparison with adjacent undisturbed control areas. On the other hand, a limited resilience of physical properties was observed in Antarctic soils, thus it is crucial not to exceed the soil's natural recovery capability. [ABSTRACT FROM AUTHOR]

Abstract: Spongiform degeneration is characterized by vacuolation in nervous tissue accompanied by neuronal death and gliosis. Although spongiform degeneration is a hallmark of prion diseases, this pathology is also present in the brains of patients suffering from Alzheimer’s disease, diffuse Lewy body disease, human immunodeficiency virus (HIV) infection, and Canavan’s spongiform leukodystrophy. The shared outcome of spongiform degeneration in these diverse diseases suggests that common cellular mechanisms must underlie the processes of spongiform change and neurodegeneration in the central nervous system. Immunohistochemical analysis of brain tissues reveals increased ubiquitin immunoreactivity in and around areas of spongiform change, suggesting the involvement of ubiquitin–proteasome system dysfunction in the pathogenesis of spongiform neurodegeneration. The link between aberrant ubiquitination and spongiform neurodegeneration has been strengthened by the discovery that a null mutation in the E3 ubiquitin–protein ligase mahogunin ring finger-1 (Mgrn1) causes an autosomal recessively inherited form of spongiform neurodegeneration in animals. Recent studies have begun to suggest that abnormal ubiquitination may alter intracellular signaling and cell functions via proteasome-dependent and proteasome-independent mechanisms, leading to spongiform degeneration and neuronal cell death. Further elucidation of the pathogenic pathways involved in spongiform neurodegeneration should facilitate the development of novel rational therapies for treating prion diseases, HIV infection, and other spongiform degenerative disorders. [Copyright &y& Elsevier]

Aspartoacylase (ASPA) is an oligodendrocyte-restricted enzyme that catalyzes the hydrolysis of neuronally derived N-acetylaspartate (NAA) to acetate and aspartic acid. ASPA deficiency leads to the fatal childhood autosomal recessive leukodystrophy Canavan disease (CD). Here we demonstrate that the previously described ENU-induced nur7 mouse mutant is caused by a nonsense mutation, Q193X, in the Aspa gene (Aspanur7). Homozygous Aspanur7nur7 mice do not express detectable Aspa protein and display an early-onset spongy degeneration of CNS myelin with increased NAA levels similar to that observed in CD patients. In addition, CNS regions rich in neuronal cell bodies also display vacuolization. Interestingly, distinct myelin rich areas, such as the corpus callosum, optic nerve, and spinal cord white matter appear normal in Aspanur7/nur7 mice. Reduced cerebroside synthesis has been demonstrated in CD patients and animal models. To determine the potential relevance of this observation in disease pathogenesis, we generated Aspanur7/nur7 mice that were heterozygous for a null allele of the gene that encodes the enzyme UDP-galactose:ceramide galactosyltransferase (Cgt), which is responsible for catalyzing the synthesis of the abundant myelin galactolipids. Despite reduced amounts of cerebrosides, the Aspanur7/nur7;Cgt+/- mice were not more severely affected than the Aspanur7 mutants, suggesting that diminished cerebroside synthesis is not a major contributing factor in disease pathogenesis. Furthermore, we found that myelin degeneration leads to significant axonal loss in the cerebellum of older Aspanur7 mutants. This finding suggests that axonal pathology caused by CNS myelin defects may underlie the neurological disabilities that CD patients develop at late stages of the disease. [ABSTRACT FROM AUTHOR]

Abstract: This study describes the approach used to verify the species identity of 23 erythromycin-resistant Campylobacter isolates whose identity was initially determined based mainly on the results of the rapid hippurate hydrolysis test or the results of the API-Campy identification system. Species identification of the isolates investigated was confirmed by repeating hippurate hydrolysis using a modification of the rapid hydrolysis test, in addition to performing three genetic-based assays. The original identification was verified in 69.6% of the isolates. The remaining isolates showed discrepancies in identity as determined by results of the identification assays performed. A duplex PCR assay, targeting the hipO and aspA genes, indicated the existence of mixed cultures of C. jejuni and C. coli in the frozen stocks of two of these isolates. [Copyright &y& Elsevier]