54 research outputs found
Spatial and topological organization of DNA chains induced by gene co-localization
Transcriptional activity has been shown to relate to the organization of
chromosomes in the eukaryotic nucleus and in the bacterial nucleoid. In
particular, highly transcribed genes, RNA polymerases and transcription factors
gather into discrete spatial foci called transcription factories. However, the
mechanisms underlying the formation of these foci and the resulting topological
order of the chromosome remain to be elucidated. Here we consider a
thermodynamic framework based on a worm-like chain model of chromosomes where
sparse designated sites along the DNA are able to interact whenever they are
spatially close-by. This is motivated by recurrent evidence that there exists
physical interactions between genes that operate together. Three important
results come out of this simple framework. First, the resulting formation of
transcription foci can be viewed as a micro-phase separation of the interacting
sites from the rest of the DNA. In this respect, a thermodynamic analysis
suggests transcription factors to be appropriate candidates for mediating the
physical interactions between genes. Next, numerical simulations of the polymer
reveal a rich variety of phases that are associated with different topological
orderings, each providing a way to increase the local concentrations of the
interacting sites. Finally, the numerical results show that both
one-dimensional clustering and periodic location of the binding sites along the
DNA, which have been observed in several organisms, make the spatial
co-localization of multiple families of genes particularly efficient.Comment: Figures and Supplementary Material freely available on
http://dx.doi.org/10.1371/journal.pcbi.100067
Calcium Ions Promote Formation of Amyloid β-Peptide (1–40) Oligomers Causally Implicated in Neuronal Toxicity of Alzheimer's Disease
Amyloid β-peptide (Aβ) is directly linked to Alzheimer's disease (AD). In its monomeric form, Aβ aggregates to produce fibrils and a range of oligomers, the latter being the most neurotoxic. Dysregulation of Ca2+ homeostasis in aging brains and in neurodegenerative disorders plays a crucial role in numerous processes and contributes to cell dysfunction and death. Here we postulated that calcium may enable or accelerate the aggregation of Aβ. We compared the aggregation pattern of Aβ(1–40) and that of Aβ(1–40)E22G, an amyloid peptide carrying the Arctic mutation that causes early onset of the disease. We found that in the presence of Ca2+, Aβ(1–40) preferentially formed oligomers similar to those formed by Aβ(1–40)E22G with or without added Ca2+, whereas in the absence of added Ca2+ the Aβ(1–40) aggregated to form fibrils. Morphological similarities of the oligomers were confirmed by contact mode atomic force microscopy imaging. The distribution of oligomeric and fibrillar species in different samples was detected by gel electrophoresis and Western blot analysis, the results of which were further supported by thioflavin T fluorescence experiments. In the samples without Ca2+, Fourier transform infrared spectroscopy revealed conversion of oligomers from an anti-parallel β-sheet to the parallel β-sheet conformation characteristic of fibrils. Overall, these results led us to conclude that calcium ions stimulate the formation of oligomers of Aβ(1–40), that have been implicated in the pathogenesis of AD
Consensus guideline for the diagnosis and treatment of aromatic l-amino acid decarboxylase (AADC) deficiency
Rare neonatal diabetes insipidus and associated late risks: Case report
<p>Abstract</p> <p>Background</p> <p>Most cases of neonatal central diabetes insipidus are caused by an injury, which often results in other handicaps in the patient. The infant’s prognosis will be determined by his or her own early age and disability as well as by the physician’s skill. However, the rarity of this condition prevents the acquisition of personal experience dealing with it.</p> <p>Case Presentation</p> <p> A neonatal hemorrhagic stroke, caused by an aortic coarctation, caused right lower limb paresis, swallowing disability, and central diabetes insipidus in a term infant. The scant oral intake, as a consequence of his disability, caused progressive undernutrition which closed a vicious circle, delaying his development and his ability to overcome the swallowing handicap. On the other hand, nasal desmopressin absorption was blocked by several common colds, resulting in brain bleeding because of severe dehydration. This even greater brain damage hampered the improvement of swallowing, closing a second harmful circle. Moreover, a devastating central myelinolysis with quadriplegia, caused by an uncontrolled intravenous infusion, consummated a pernicious sequence, possibly unreported.</p> <p>Conclusions</p> <p>The child’s overall development advanced rapidly when his nutrition was improved by gastrostomy: This was a key effect of nutrition on his highly sensitive neurodevelopment. Besides, this case shows potential risks related to intranasal desmopressin treatment in young children.</p
Isolation of methotrexate-resistant cell lines in Petunia hybrida upon stepwise selection procedure
Dihydrofolate reductase from Daucus carota cell suspension cultures: purification, molecular and kinetic characterization
PRICKLE2 revisited—further evidence implicating PRICKLE2 in neurodevelopmental disorders
Elevated amounts of methotrexate-binding protein, different from normal dihydrofolate reductase, in a petunia MTXR-cell line
Targeted next generation sequencing: the diagnostic value in early-onset epileptic encephalopathy
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