Effects of structural marsh management and salinity on sediments, hydrology, invertebrates, and waterbirds in marsh ponds during winter on the Gulf Coast Chenier Plain

Compositions of wintering waterbird communities are dependent upon food accessibility (via water depth), biomasses and sizes of their invertebrate prey, which in turn are influenced by the hydrology and sediments of wetland habitats. The hydrology and sediments of marsh ponds on the Gulf Coast Chenier Plain probably are affected by structural marsh management (levees, water control structures and impoundments; SMM) and salinity; therefore, SMM and salinity ultimately may affect wintering waterbird communities. Accordingly, I measured sediment and hydrologic variables, biomasses and sizes of common aquatic invertebrates, and densities of common wintering waterbird species in ponds of impounded freshwater (IF), impounded oligohaline (IO), impounded mesohaline (IM), and unimpounded mesohaline (UM) marshes during winters 1997-1998 to 1999-2000 on Rockefeller State Wildlife Refuge, near Grand Chenier, Louisiana. SMM affected sediment and hydrologic variables, which negatively affected biomasses of Nematoda and secondarily increased those of Ostracoda. However, few waterbird species possess the capacity to capture these small prey; consequently, I predicted that avian species that consume invertebrates would not be among those differentiating waterbird communities between ponds of IM and UM marshes. Comparisons of waterbird densities provided inconsistent results with this prediction because some shorebird and waterfowl species that feed heavily on invertebrates were those that primarily differentiated waterbird communities between ponds of IM and UM marshes. My comparison of IF, IO, and IM marsh ponds indicated that, except for salinity, they differed little in sediment and hydrologic variables. Accordingly, these marshes only differed in biomass of Oligochaeta; consequently, I predicted that avian species that consume invertebrates would not be among those differentiating waterbird communities among ponds of IF, IO, and IM marshes. Accordingly, their waterbird communities primarily differed in densities of waterbird species that feed on vegetation. In conclusion, some waterbird species exclusively used ponds of UM marshes rather than ponds of IM marshes, and most species had highest densities in IF marshes when water depth favored those that maximized their densities. Consequently, My results suggest that marsh managers should focus on the preservation of UM and IF marshes for the conservation of wintering waterbird populations of the Gulf Coast Chenier Plain

Fragile X Mental Retardation 1 and Filamin A Interact Genetically in Drosophila Long-Term Memory

The last decade has witnessed the identification of single-gene defects associated with an impressive number of mental retardation syndromes. Fragile X syndrome, the most common cause of mental retardation for instance, results from disruption of the FMR1 gene. Similarly, Periventricular Nodular Heterotopia, which includes cerebral malformation, epilepsy and cognitive disabilities, derives from disruption of the Filamin A gene. While it remains unclear whether defects in common molecular pathways may underlie the cognitive dysfunction of these various syndromes, defects in cytoskeletal structure nonetheless appear to be common to several mental retardation syndromes. FMR1 is known to interact with Rac, profilin, PAK and Ras, which are associated with dendritic spine defects. In Drosophila, disruptions of the dFmr1 gene impair long-term memory (LTM), and the Filamin A homolog (cheerio) was identified in a behavioral screen for LTM mutants. Thus, we investigated the possible interaction between cheerio and dFmr1 during LTM formation in Drosophila. We show that LTM specifically is defective in dFmr1/cheerio double heterozygotes, while it is normal in single heterozygotes for either dFmr1 or cheerio. In dFmr1 mutants, Filamin (Cheerio) levels are lower than normal after spaced training. These observations support the notion that decreased actin cross-linking may underlie the persistence of long and thin dendritic spines in Fragile X patients and animal models. More generally, our results represent the first demonstration of a genetic interaction between mental retardation genes in an in vivo model system of memory formation

An assay for social interaction in Drosophila fragile X mutants

We developed a novel assay to examine social interactions in Drosophila and, as a first attempt, apply it here at examining the behavior of Drosophila Fragile X Mental Retardation gene (dfmr1) mutants. Fragile X syndrome is the most common cause of single gene intellectual disability (ID) and is frequently associated with autism. Our results suggest that dfmr1 mutants are less active than wild-type flies and interact with each other less often. In addition, mutants for one allele of dfmr1, dfmr1B55, are more likely to come in close contact with a wild-type fly than another dfmr1B55 mutant. Our results raise the possibility of defective social expression with preserved receptive abilities. We further suggest that the assay may be applied in a general strategy of examining endophenoypes of complex human neurological disorders in Drosophila, and specifically in order to understand the genetic basis of social interaction defects linked with ID

Specific EEG resting state biomarkers in FXS and ASD.

BACKGROUND: Fragile X syndrome (FXS) and autism spectrum disorder (ASD) are neurodevelopmental conditions that often have a substantial impact on daily functioning and quality of life. FXS is the most common cause of inherited intellectual disability (ID) and the most common monogenetic cause of ASD. Previous literature has shown that electrophysiological activity measured by electroencephalogram (EEG) during resting state is perturbated in FXS and ASD. However, whether electrophysiological profiles of participants with FXS and ASD are similar remains unclear. The aim of this study was to compare EEG alterations found in these two clinical populations presenting varying degrees of cognitive and behavioral impairments. METHODS: Resting state EEG signal complexity, alpha peak frequency (APF) and power spectral density (PSD) were compared between 47 participants with FXS (aged between 5-20), 49 participants with ASD (aged between 6-17), and 52 neurotypical (NT) controls with a similar age distribution using MANCOVAs with age as covariate when appropriate. MANCOVAs controlling for age, when appropriate, and nonverbal intelligence quotient (NVIQ) score were subsequently performed to determine the impact of cognitive functioning on EEG alterations. RESULTS: Our results showed that FXS participants manifested decreased signal complexity and APF compared to ASD participants and NT controls, as well as altered power in the theta, alpha and low gamma frequency bands. ASD participants showed exaggerated beta power compared to FXS participants and NT controls, as well as enhanced low and high gamma power compared to NT controls. However, ASD participants did not manifest altered signal complexity or APF. Furthermore, when controlling for NVIQ, results of decreased complexity in higher scales and lower APF in FXS participants compared to NT controls and ASD participants were not replicated. CONCLUSIONS: These findings suggest that signal complexity and APF might reflect cognitive functioning, while altered power in the low gamma frequency band might be associated with neurodevelopmental conditions, particularly FXS and ASD

PDE-4 inhibition rescues aberrant synaptic plasticity in Drosophila and mouse models of fragile X syndrome.

Fragile X syndrome (FXS) is the leading cause of both intellectual disability and autism resulting from a single gene mutation. Previously, we characterized cognitive impairments and brain structural defects in a Drosophila model of FXS and demonstrated that these impairments were rescued by treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium. A well-documented biochemical defect observed in fly and mouse FXS models and FXS patients is low cAMP levels. cAMP levels can be regulated by mGluR signaling. Herein, we demonstrate PDE-4 inhibition as a therapeutic strategy to ameliorate memory impairments and brain structural defects in the Drosophila model of fragile X. Furthermore, we examine the effects of PDE-4 inhibition by pharmacologic treatment in the fragile X mouse model. We demonstrate that acute inhibition of PDE-4 by pharmacologic treatment in hippocampal slices rescues the enhanced mGluR-dependent LTD phenotype observed in FXS mice. Additionally, we find that chronic treatment of FXS model mice, in adulthood, also restores the level of mGluR-dependent LTD to that observed in wild-type animals. Translating the findings of successful pharmacologic intervention from the Drosophila model into the mouse model of FXS is an important advance, in that this identifies and validates PDE-4 inhibition as potential therapeutic intervention for the treatment of individuals afflicted with FXS

Common and Distinct Genetic Properties of ESCRT-II Components in Drosophila

BACKGROUND: Genetic studies in yeast have identified class E vps genes that form the ESCRT complexes required for protein sorting at the early endosome. In Drosophila, mutations of the ESCRT-II component vps25 cause endosomal defects leading to accumulation of Notch protein and increased Notch pathway activity. These endosomal and signaling defects are thought to account for several phenotypes. Depending on the developmental context, two different types of overgrowth can be detected. Tissue predominantly mutant for vps25 displays neoplastic tumor characteristics. In contrast, vps25 mutant clones in a wild-type background trigger hyperplastic overgrowth in a non-autonomous manner. In addition, vps25 mutant clones also promote apoptotic resistance in a non-autonomous manner. PRINCIPAL FINDINGS: Here, we genetically characterize the remaining ESCRT-II components vps22 and vps36. Like vps25, mutants of vps22 and vps36 display endosomal defects, accumulate Notch protein and--when the tissue is predominantly mutant--show neoplastic tumor characteristics. However, despite these common phenotypes, they have distinct non-autonomous phenotypes. While vps22 mutations cause strong non-autonomous overgrowth, they do not affect apoptotic resistance. In contrast, vps36 mutations increase apoptotic resistance, but have little effect on non-autonomous proliferation. Further characterization reveals that although all ESCRT-II mutants accumulate Notch protein, only vps22 and vps25 mutations trigger Notch activity. CONCLUSIONS/SIGNIFICANCE: The ESCRT-II components vps22, vps25 and vps36 display common and distinct genetic properties. Our data redefine the role of Notch for hyperplastic and neoplastic overgrowth in these mutants. While Notch is required for hyperplastic growth, it appears to be dispensable for neoplastic transformation

Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue

Prevalence, symptoms, and treatment of depression suggest that major depressive disorders (MDD) present sex differences. Social stress-induced neurovascular pathology is associated with depressive symptoms in male mice; however, this association is unclear in females. Here, we report that chronic social and subchronic variable stress promotes blood-brain barrier (BBB) alterations in mood-related brain regions of female mice. Targeted disruption of the BBB in the female prefrontal cortex (PFC) induces anxiety- and depression-like behaviours. By comparing the endothelium cell-specific transcriptomic profiling of the mouse male and female PFC, we identify several pathways and genes involved in maladaptive stress responses and resilience to stress. Furthermore, we confirm that the BBB in the PFC of stressed female mice is leaky. Then, we identify circulating vascular biomarkers of chronic stress, such as soluble E-selectin. Similar changes in circulating soluble E-selectin, BBB gene expression and morphology can be found in blood serum and postmortem brain samples from women diagnosed with MDD. Altogether, we propose that BBB dysfunction plays an important role in modulating stress responses in female mice and possibly MDD

Recurrent Diplopia in a Pediatric Patient with Bickerstaff Brainstem Encephalitis

Introduction. Acute complete external ophthalmoplegia is a rare finding in clinical practice that is associated with diseases affecting the neuromuscular junction, the oculomotor nerves, or the brainstem. Ophthalmoplegia has been reported with acute ataxia in Miller Fisher syndrome (MFS) and Bickerstaff brainstem encephalitis (BBE). Up to 95% of these cases are associated with anti-GQ1b antibodies. Only a small number of cases of anti-GQ1b negative MFS have been documented in pediatric patients. This is the first case reporting a recurrence of ocular symptoms in an anti-GQ1b antibody negative patient with BBE. Case Presentation. An 8-year-old Caucasian boy presented with complete external ophthalmoplegia without ptosis, cerebellar ataxia, and a disturbance of consciousness. He had recently recovered from a confirmed Campylobacter jejuni infection. On subsequent laboratory testing he was anti-GQ1b antibody negative. He had a recurrence of diplopia at four-week follow-up. Conclusions. This patient’s recurrence of diplopia was treated with a five-week course of oral corticosteroids which did not worsen his condition, and this may be a therapeutic option for similar patients. We will discuss the symptoms and treatment of reported pediatric cases of anti-GQ1b antibody negative cases of MFS and the variation between cases representing a spectrum of illness

Leveraging Knowledge Graphs and Natural Language Processing for Automated Web Resource Labeling and Knowledge Mobilization in Neurodevelopmental Disorders: Development and Usability Study

BackgroundPatients and families need to be provided with trusted information more than ever with the abundance of online information. Several organizations aim to build databases that can be searched based on the needs of target groups. One such group is individuals with neurodevelopmental disorders (NDDs) and their families. NDDs affect up to 18% of the population and have major social and economic impacts. The current limitations in communicating information for individuals with NDDs include the absence of shared terminology and the lack of efficient labeling processes for web resources. Because of these limitations, health professionals, support groups, and families are unable to share, combine, and access resources. ObjectiveWe aimed to develop a natural language–based pipeline to label resources by leveraging standard and free-text vocabularies obtained through text analysis, and then represent those resources as a weighted knowledge graph. MethodsUsing a combination of experts and service/organization databases, we created a data set of web resources for NDDs. Text from these websites was scraped and collected into a corpus of textual data on NDDs. This corpus was used to construct a knowledge graph suitable for use by both experts and nonexperts. Named entity recognition, topic modeling, document classification, and location detection were used to extract knowledge from the corpus. ResultsWe developed a resource annotation pipeline using diverse natural language processing algorithms to annotate web resources and stored them in a structured knowledge graph. The graph contained 78,181 annotations obtained from the combination of standard terminologies and a free-text vocabulary obtained using topic modeling. An application of the constructed knowledge graph is a resource search interface using the ordered weighted averaging operator to rank resources based on a user query. ConclusionsWe developed an automated labeling pipeline for web resources on NDDs. This work showcases how artificial intelligence–based methods, such as natural language processing and knowledge graphs for information representation, can enhance knowledge extraction and mobilization, and could be used in other fields of medicine