Joel Fuhrman, M.D. Excess dietary salt is notorious for increasing blood pressure – blood volume increases, placing more stress on blood vessel walls. This forces the heart to pump harder against the pressure, and also structural changes that harden the vessel wall (this hardening is called stenosis) occur in response to these high pressures.About one-third [...]
Background: High enzyme loading is a major economic bottleneck for the commercial processing of pretreated lignocellulosic biomass to produce fermentable sugars. Optimizing the enzyme cocktail for specific types of pretreated biomass allows for a significant reduction in enzyme loading without sacrificing hydrolysis yield. This is especially important for alkaline pretreatments such as Ammonia fiber expansion [...]
Huntington’s disease (HD), caused by a CAG repeat expansion in the huntingtin (HTT) gene, is characterized by abnormal protein aggregates and motor and cognitive dysfunction. Htt protein is ubiquitously expressed, but the striatal medium spiny neuron (MSN) is most susceptible to dysfunction and death. Abnormal gene expression represents a core pathogenic feature of HD, but [...]
Nuclear movement relative to cell bodies is a fundamental process during certain aspects of mammalian retinal development. During the generation of photoreceptor cells in the cell division cycle, the nuclei of progenitors oscillate between the apical and basal surfaces of the neuroblastic layer (NBL). This process is termed interkinetic nuclear migration (INM). Furthermore, newly formed [...]
Parkin, whose mutations cause Parkinson disease (PD), controls oxidative stress by limiting the expression of monoamine oxidases (MAO)—mitochondrial enzymes responsible for the oxidative de-amination of dopamine. Here, we show that parkin performed this function by increasing the ubiquitination and degradation of estrogen-related receptors (ERR), orphan nuclear receptors that play critical roles in the transcription regulation [...]
There has been growing evidence for extensive diversity of alternative splicing in human populations. Genetic variants within the 5′ splice site can cause splicing differences among human individuals and constitute an important class of human disease mutations. In this study, we explored whether natural variations of splicing could reveal important signals of 5′ splice site [...]
Cited2 is a transcriptional coactivator that is required for normal development of the embryo and placenta. Cited2-null mice die during gestation with fully penetrant heart defects and partially penetrant laterality defects. The laterality defects occur due to the loss of Nodal expression in the left lateral plate mesoderm (LPM). The cause of the heart defects [...]
The infantile neuronal ceroid lipofuscinosis (INCL) is a devastating neurodegenerative lysosomal storage disease. Despite our knowledge that palmitoyl-protein thioesterase-1 (PPT1)-deficiency causes INCL, the molecular mechanism(s) of neurodegeneration and the drastically reduced lifespan of these patients remain poorly understood. Consequently, an effective treatment for this disease is currently unavailable. We previously reported that oxidative stress-mediated abnormality [...]
Genetics of Holoprosencephaly (HPE), a congenital malformation of the developing human forebrain, is due to multiple genetic defects. Most genes that have been implicated in HPE belong to the sonic hedgehog signaling pathway. Here we describe a new candidate gene isolated from array comparative genomic hybridization redundant 6qter deletions, DELTA Like 1 (DLL1), which is [...]
Mutations in the RS1 gene that encodes the discoidin domain containing retinoschisin cause X-linked juvenile retinoschisis (XLRS), a common macular degeneration in males. Disorganization of retinal layers and electroretinogram abnormalities are hallmarks of the disease and are also found in mice deficient for the orthologous murine protein, indicating that retinoschisin is important for the maintenance [...]
Congenital abnormalities of the kidney and urinary tract are some of the most common defects detected in the unborn child. Kidney growth is controlled by the GDNF/RET signalling pathway, but the molecular events required for the activation of RET downstream targets are still poorly understood. Here we show that SOX9, a gene involved in campomelic [...]
Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscular dystrophy caused by a polyalanine expansion mutation in the coding region of the poly-(A) binding protein nuclear 1 (PABPN1) gene. In unaffected individuals, (GCG)6 encodes the first 6 alanines in a homopolymeric stretch of 10 alanines. In most patients, this (GCG)6 repeat is expanded to (GCG)8–13, leading [...]
Methylation at CpG sites is a critical epigenetic modification in mammals. Altered DNA methylation has been suggested to be a central mechanism in development, some disease processes and cellular senescence. Quantifying the extent and identity of epigenetic changes in the aging process is therefore potentially important for understanding longevity and age-related diseases. In the current [...]
Using segregation analyses, control of malaria parasites has previously been linked to a major gene within the chromosomal region 5q31–33, but also to complex genetic factors in which effects are under substantial age-dependent influence. However, the responsible gene variants have not yet been identified for this chromosomal region. In order to perform association analyses of [...]
Rett syndrome (RTT) is a neurodevelopmental disorder with no efficient treatment that is caused in the majority of cases by mutations in the gene methyl-CpG binding-protein 2 (MECP2). RTT becomes manifest after a period of apparently normal development and causes growth deceleration, severe psychomotor impairment and mental retardation. Effective animal models for RTT are available [...]
We recently described mitochondrial pathology in neurons of transgenic mice with genes associated with Parkinson’s disease (PD). Now we describe severe mitochondrial damage in glial cells of the mesencephalon in mice carrying a targeted deletion of parkin (PaKO) or overexpressing doubly mutated human alpha-synuclein (asyn). The number of mitochondria with altered morphology in glial cells [...]
