302 research outputs found
Initial Impact of the Gabíkovo Hydroelectric Scheme on the Species Richness and Composition of 0+ Fish Assemblages in the Slovak Flood Plain, River Danube
No full textRelatively little information exists on the effects of hydroelectric schemes on 0+ fish composition in large European rivers because few or no pre-impact data exist. We compared 0+ fish species richness and composition, relative density, fish size as well as available and used habitat using data from 12 floodplain sites sampled just prior to (1992) and four years after (1996) the start of operations of the Gabíkovo hydropower station on the River Danube (Slovakia). We also used modelling techniques to assess the change in species richness and habitat use and to predict 1996 occurrences from the 1992 data set. The floodplain was greatly modified by the hydroscheme. Only 12 of 27 sites sampled in August 1992 were extant in August 1996. Therefore, all four channel types identified (flowing, abandoned, weir, wing-dam) were more lentic in 1996 than in 1992, with increased width, smaller-sized sediment (silt, clay) and greater amounts of macrophytes. After the operations of the hydroscheme, the overall relative density of fishes (individuals per surface area) of all ages decreased, with the exception of 0+ fishes, despite a slight reduction in 0+ fish density in all channel types except weirs. Species number increased from 25 to 28, although in all channel types there was a change in the composition of the 0+ fish assemblages, with rheophiles generally replaced by limnophiles and migrants from the lower Danube. The two most important microhabitat variables were the proportion of macrophytes and gravel, the latter being the factor distinguishing 0+ fish microhabitat use in 1992 (preferences) and 1996 (indifference or avoidance). Species richness and 0+ fish density in 1996 could be predicted from the 1992 data using simple log-linear models (density, richness, sample number). Species-specific occurrence in 1996 could not be predicted using environmental/fish data from 1992 with multiple regression or generalized additive models (GAM). However, the overall GAM from 1992 could predict overall fish occurrence in 1996
Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes and Zic2 reduce bone mass in young mice
No full textFractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed μCT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2 Lp/+ ) or Celsr1 (Celsr1 Crsh/+ ) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3 Sp2H/+ ) had minimal effects on bone mass. Zic2 mutation (Zic2 Ku/+ ) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass.</p
Investigating the Cause of Central Nervous System Defects in Glycine Decarboxylase-Deficient Mice
No full textGlycine decarboxylase (GLDC) is part of the glycine cleavage system, which is a highly conserved multi-enzyme complex specific to mitochondrial folate one carbon metabolism. Mutations in GLDC are associated with common birth defects: neural tube defects (NTDs) and congenital hydrocephalus, and are known to cause Non-Ketotic Hyperglycinaemia (NKH) - a rare neurometabolic disease in humans.
Neural tube defects (NTDs) are the second most common global congenital abnormality, which arise when the neural tube - the precursor to the brain and spinal cord - fails to close. We generated and characterised Gldc-deficient (GldcGT1/GT2) gene trap mice as a model to investigate the causative mechanisms of NTDs. In this study, I delve into transcriptomic and metabolomic changes caused by GLDC loss of function. Our data highlight disruptions in mitochondrial abundance and redox balance, which imply that mitochondrial dysfunction and oxidative stress in the neuroepithelium may contribute to the causation of NTDs in Gldc-deficient embryos.
In addition, a proportion of Gldc-deficient mice develop hydrocephalus, which manifests as enlarged brain ventricles (ventriculomegaly) at late foetal stages. It is not known whether excess glycine or 1C deficiency leads to hydrocephalus. Here, my findings show that the lack of glycine-derived 1C units may lead to the abnormal development of the subcommissural organ, which is likely to underlie aqueduct stenosis that results in a non-communicating hydrocephalus.
Furthermore, to investigate tissue and cell-specific requirements for GLDC during development, I characterise the Gldc mRNA and protein expression patterns in mouse and human tissues. We also use genetic approaches to generate conditional knockout and rescue models to assess the tissue-specific requirements for Gldc in neural tube closure and foetal brain development. Understanding the causative factors of these congenital phenotypes will advance our approaches towards preventative measures and treatments
<it>The Casey Holter memorial lecture: </it>genetics and embryology of neural tube defects
No full textBedrock Geologic Map of the Disappointment Lake Area, Lake County, Northeastern Minnesota
No full textThis map was created by PRC Field Camp students under the guidance of Dr. Dean Peterson, Duluth Metals
Limited Senior Vice President of Exploration, and Dr. George Hudak, Associate Professor of Geology at the
University of Wisconsin Oshkosh. The purpose of this map is to further understand the relationship between
the Duluth Complex and the older Archean metasediment, volcanic and volcaniclastic rocks in the area which
were last mapped in the early 1940's by Gruner. This map will also facilitate undergraduate research theses
studies.
This map is the result of seven days of field mapping by the authors in 2009. Access to the 955 outcrops
included in this project was achieved through extensive mapping of shorelines within the Disappointment,
Parent and Snowbank Lakes field area combined with multiple traverses through dense bush and swamp
areas. This is the first detailed map of the area produced at a 1:10,000 scale.Mulvey, Lucy; Ross, Cabin; Zeitler, Joseph; Pendleton, Matthew; McCarthy, Andrew; Copp, Lee; Nowak, Robert; Hudak, George J; Peterson, Dean M. (2009). Bedrock Geologic Map of the Disappointment Lake Area, Lake County, Northeastern Minnesota. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/257367
Female leaders in commercial real estate : to the women following in their footsteps
No full textThesis (S.M.)--Massachusetts Institute of Technology, Program in Real Estate Development in Conjunction with the Center for Real Estate, 2009.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student submitted PDF version of thesis.Includes bibliographical references (p. 71-73).Within commercial real estate, women are not as likely as men to achieve senior-level executive positions. Commercial real estate has been slow to change in terms of achieving gender parity, and though improvements have been made in the status of women in leadership positions, gender-based disparity still exists. The purpose of this study is to shed more light on the facilitators and barriers to career advancement of women in commercial real estate who have achieved top-level leadership positions. Thirteen women holding senior-level management positions in the commercial real estate industry were interviewed regarding facilitators to career advancement and notable barriers, the role of mentors, and work-life balance issues. What route did these women take to the top and what did they encounter along the way? Each story told involved some combination of diligent work, the pursuit of opportunities, and the will to succeed. The results from this study supported much of the research that has been done on this topic. Gender barriers, biases, and stereotypes were met along the way, but these women succeeded in spite of these barriers. The women attribute their success to facilitators of career advancement such as a strong work ethic, relationship building and risk-taking. While this thesis shed light on the careers of women in commercial real estate, it also raises at least two questions. How similar are the career paths of women and men in commercial real estate in terms of facilitators and barriers to advancement? Does the glass ceiling appear thin or non-existent once female executives are above it?by Jodie Copp Poirier.S.M
Foregut separation and tracheo-oesophageal malformations: the role of tracheal outgrowth, dorso-ventral patterning and programmed cell death
No full textForegut division-the separation of dorsal (oesophageal) from ventral (tracheal) foregut components-is a crucial event in gastro-respiratory development, and frequently disturbed in clinical birth defects. Here, we examined three outstanding questions of foregut morphogenesis. The origin of the trachea is suggested to result either from respiratory outgrowth or progressive septation of the foregut tube. We found normal foregut lengthening despite failure of tracheo-oesophageal separation in Adriamycin-treated embryos, whereas active septation was observed only in normal foregut morphogenesis, indicating a primary role for septation. Dorso-ventral patterning of Nkx2.1 (ventral) and Sox2 (dorsal) expression is proposed to be critical for tracheo-oesophageal separation. However, normal dorso-ventral patterning of Nkx2.1 and Sox2 expression occurred in Adriamycin-treated embryos with defective foregut separation. In contrast, Shh expression shifts dynamically, ventral-to-dorsal, solely during normal morphogenesis, particularly implicating Shh in foregut morphogenesis. Dying cells localise to the fusing foregut epithelial ridges, with disturbance of this apoptotic pattern in Adriamycin, Shh and Nkx2.1 models. Strikingly, however, genetic suppression of apoptosis in the Apaf1 mutant did not prevent foregut separation, indicating that apoptosis is not required for tracheo-oesophageal morphogenesis. Epithelial remodelling during septation may cause loss of cell-cell or cell-matrix interactions, resulting in apoptosis (anoikis) as a secondary consequence
Investigating the impact of dolutegravir on embryonic development
No full textDolutegravir (DTG) is an integrase strand transfer inhibitor recommended as part
of first line treatment for people living with HIV, including pregnant women. In
2018, the Botswana Harvard AIDS institute partnership noticed an increase in
frequency of neural tube defects (NTDs) among babies of women taking DTG in
their Tsepamo birth surveillance study. NTDs occur when neurulation fails and
can affect both cranial and spinal regions.
This study aimed to investigate the effect of DTG on embryonic development in
neurulation stage mouse embryos and human gastruloids. Culture of wild-type
mouse embryos with DTG showed no increase in NTDs, however, culturing a
genetically susceptible mouse strain resulted in a significant increase in
exencephaly, particularly affecting the midbrain and forebrain. Human gastruloids
display symmetry breaking and axial elongation similarly to gastrulation stage
human embryos. Treatment with DTG resulted in abnormalities in lineage
specification and patterning.
To understand the mechanism causing these abnormalities, mouse embryonic
fibroblasts (MEFs) generated from the genetically susceptible strain were treated
with DTG. Seahorse assays and MitoTracker dyes were used to assess energy
metabolism and reactive oxygen species (ROS) production. DTG-treated MEFs
showed decreased mitochondrial respiration and increased compensatory
glycolysis, but not significantly. DTG-treated cells showed decreased ROS levels
and increased mitochondrial network complexity. The increased rates of
exencephaly observed in genetically susceptible embryos treated with DTG could
not be rescued with myo-inositol supplementation, but there was preliminary
evidence that folic acid may lower risk of DTG-related NTDs. This thesis suggests
that DTG can significantly increase the risk of failed neural tube closure when
combined with genetic susceptibility. I propose that DTG may cause gene
expression changes, possibly during gastrulation, and alters energy metabolism
by pushing cells to a more glycolytic state. Identifying the mechanisms causing
increased NTDs will allow development of measures to reduce these
abnormalities
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