253 research outputs found
Recent increase in the incidence of non-Hodgkin's lymphoma among young men and women in Denmark.
Time-related trends in the incidence of non-Hodgkin's lymphoma (NHL) in Denmark were analysed for the period 1943-89. A total of 13 822 patients (7565 men and 6257 women) were included in the study. In men, world-standardised incidence rates per 100 000 population increased from 2.5 in 1943-47 to 9.3 in 1988-89. In women, a similar increase was seen, i.e. from 1.9 in 1943-47 to 6.5 per 100 000 population in 1988-89. For all birth cohorts, the male-to-female incidence ratio was highest among young subjects and fell significantly after the age of 29 years. Trends in age-specific incidence were analysed separately for two periods, i.e. 1943-77 and 1978-89, reflecting an early, pre-AIDS period and a later period possibly influenced by AIDS. In both periods, the incidence of NHL increased in all age groups. However, in recent years a noticeable increase in incidence averaging 8% annually was observed in men and women aged 40-49 years. A number of factors including changes in the perception of NHL and in the diagnostic methods available are considered insufficient to explain the observed increase. The remarkable and parallel time trends observed in young men and women in recent years indicate that factors other than AIDS must be considered
Near-edge x-ray absorption fine structure investigation of graphene
We report the near-edge x-ray absorption fine structure (NEXAFS) spectrum of
a single layer of graphite (graphene) obtained by micromechanical cleavage of
Highly Ordered Pyrolytic Graphite (HOPG) on a SiO2 substrate. We utilized a
PhotoEmission Electron Microscope (PEEM) to separately study single- double-
and few-layers graphene (FLG) samples. In single-layer graphene we observe a
splitting of the pi* resonance and a clear signature of the predicted
interlayer state. The NEXAFS data illustrate the rapid evolution of the
electronic structure with the increased number of layers.Comment: 5 pages, 4 figure
Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification.
Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromosome 21q21.3 and identified bi-allelic variants in JAM2. JAM2 encodes for the junctional-adhesion-molecule-2, a key tight-junction protein in blood-brain-barrier permeability. We show that JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient's fibroblasts, consistent with a loss-of-function mechanism. We show that the human phenotype is replicated in the jam2 complete knockout mouse (jam2 KO). Furthermore, neuropathology of jam2 KO mouse showed prominent vacuolation in the cerebral cortex, thalamus, and cerebellum and particularly widespread vacuolation in the midbrain with reactive astrogliosis and neuronal density reduction. The regions of the human brain affected on neuroimaging are similar to the affected brain areas in the myorg PFBC null mouse. Along with JAM3 and OCLN, JAM2 is the third tight-junction gene in which bi-allelic variants are associated with brain calcification, suggesting that defective cell-to-cell adhesion and dysfunction of the movement of solutes through the paracellular spaces in the neurovascular unit is a key mechanism in CNS calcification
Heterozygous De Novo UBTF Gain-of-Function Variant Is Associated with Neurodegeneration in Childhood.
Ribosomal RNA (rRNA) is transcribed from rDNA by RNA polymerase I (Pol I) to produce the 45S precursor of the 28S, 5.8S, and 18S rRNA components of the ribosome. Two transcription factors have been defined for Pol I in mammals, the selectivity factor SL1, and the upstream binding transcription factor (UBF), which interacts with the upstream control element to facilitate the assembly of the transcription initiation complex including SL1 and Pol I. In seven unrelated affected individuals, all suffering from developmental regression starting at 2.5-7 years, we identified a heterozygous variant, c.628G\u3eA in UBTF, encoding p.Glu210Lys in UBF, which occurred de novo in all cases. While the levels of UBF, Ser388 phosphorylated UBF, and other Pol I-related components (POLR1E, TAF1A, and TAF1C) remained unchanged in cells of an affected individual, the variant conferred gain of function to UBF, manifesting by markedly increased UBF binding to the rDNA promoter and to the 5\u27- external transcribed spacer. This was associated with significantly increased 18S expression, and enlarged nucleoli which were reduced in number per cell. The data link neurodegeneration in childhood with altered rDNA chromatin status and rRNA metabolism
Novel fibronectin mutations and expansion of the phenotype in spondylometaphyseal dysplasia with âcorner fracturesâ
Heterozygous pathogenic variants in the FN1 gene, encoding fibronectin (FN), have recently been shown to be associated with a skeletal disorder in some individuals affected by spondylometaphyseal dysplasia with âcorner fracturesâ (SMD-CF). The most striking feature characterizing SMD-CF is irregularly shaped metaphyses giving the appearance of âcorner fracturesâ. An array of secondary features, including developmental coxa vara, ovoid vertebral bodies and severe scoliosis, may also be present. FN is an important extra cellular matrix component for bone and cartilage development. Here we report five patients affected by this subtype of SMD-CF caused by five novel FN1 missense mutations: p.Cys123Tyr, p.Cys169Tyr, p.Cys213Tyr, p.Cys231Trp and p.Cys258Tyr. All individuals shared a substitution of a cysteine residue, disrupting disulfide bonds in the FN type-I assembly domains located in the N-terminal assembly region. The abnormal metaphyseal ossification and âcorner fractureâ appearances were the most remarkable clinical feature in these patients. In addition, generalized skeletal fragility with low-trauma bilateral femoral fractures was identified in one patient. Interestingly, the distal femoral changes in this patient healed with skeletal maturation. Our report expands the phenotypic and genetic spectrum of the FN1-related SMD-CF and emphasizes the importance of FN in bone formation and possibly also in the maintenance of bone strength.Peer reviewe
Expanding the mutational landscape and clinical phenotype of the YIF1B related brain disorder
Truncating mutations in YIF1B cause a progressive encephalopathy with various degrees of mixed movement disorder, microcephaly, and epilepsy
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