PROPERTIES OF ACATALASIC CELLS GROWING IN VITRO

Acatalasia, a disease due to homozygosity for a Mendelian gene, is characterized by the absence of the enzyme catalase from the tissues of the human body. Red cells from heterozygotes have enzyme activities about one-half normal. In this paper, the development of cell lines from skin biopsies on an affected homozygote, a heterozygote, and eight control patients is described. The cell type is the euploid "fibroblast." It was found that acatalasic cells lacked the enzyme, even after growing for many months in a medium rich in catalase. The control lines all had mean catalase activities double or more that of the heterozygous line. Selection experiments, in which the growth of cells exposed for 20 minutes to varying concentrations of hydrogen peroxide was measured, did not provide a system for preferentially eliminating acatalasic cells. Certain other experiments bearing on the enzymatic defect in this disease were performed

Treatment algorithm for infants diagnosed with spinal muscular atrophy through newborn screening

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by the degeneration of alpha motor neurons in the spinal cord, leading to muscular atrophy. SMA is caused by deletions or mutations in the survival motor neuron 1 gene (SMN1). In humans, a nearly identical copy gene, SMN2, is present. Because SMN2 has been shown to decrease disease severity in a dose-dependent manner, SMN2 copy number is predictive of disease severity. To develop a treatment algorithm for SMA-positive infants identified through newborn screening based upon SMN2 copy number. A working group comprised of 15 SMA experts participated in a modified Delphi process, moderated by a neutral third-party expert, to develop treatment guidelines. The overarching recommendation is that all infants with two or three copies of SMN2 should receive immediate treatment (n = 13). For those infants in which immediate treatment is not recommended, guidelines were developed that outline the timing and appropriate screens and tests to be used to determine the timing of treatment initiation. The identification SMA affected infants via newborn screening presents an unprecedented opportunity for achievement of maximal therapeutic benefit through the administration of treatment pre-symptomatically. The recommendations provided here are intended to help formulate treatment guidelines for infants who test positive during the newborn screening process

Evolution in the Volumetric Type Ia Supernova Rate from the Supernova Legacy Survey

We present a measurement of the volumetric Type Ia supernova (SN Ia) rate (SNR_Ia) as a function of redshift for the first four years of data from the Canada-France-Hawaii Telescope (CFHT) Supernova Legacy Survey (SNLS). This analysis includes 286 spectroscopically confirmed and more than 400 additional photometrically identified SNe Ia within the redshift range 0.1<z<1.1. The volumetric SNR_Ia evolution is consistent with a rise to z~1.0 that follows a power-law of the form (1+z)^alpha, with alpha=2.11+/-0.28. This evolutionary trend in the SNLS rates is slightly shallower than that of the cosmic star-formation history over the same redshift range. We combine the SNLS rate measurements with those from other surveys that complement the SNLS redshift range, and fit various simple SN Ia delay-time distribution (DTD) models to the combined data. A simple power-law model for the DTD (i.e., proportional to t^-beta) yields values from beta=0.98+/-0.05 to beta=1.15+/-0.08 depending on the parameterization of the cosmic star formation history. A two-component model, where SNR_Ia is dependent on stellar mass (Mstellar) and star formation rate (SFR) as SNR_Ia(z)=AxMstellar(z) + BxSFR(z), yields the coefficients A=1.9+/-0.1 SNe/yr/M_solar and B=3.3+/-0.2 SNe/yr/(M_solar/yr). More general two-component models also fit the data well, but single Gaussian or exponential DTDs provide significantly poorer matches. Finally, we split the SNLS sample into two populations by the light curve width (stretch), and show that the general behavior in the rates of faster-declining SNe Ia (0.8<s<1.0) is similar, within our measurement errors, to that of the slower objects (1.0<s<1.3) out to z~0.8.Comment: Accepted in A

Patterns of woodboring beetle activity following fires and bark beetle outbreaks in montane forests of California, USA

Increasingly frequent and severe drought in the western United States has contributed to more frequent and severe wildfires, longer fire seasons, and more frequent bark beetle outbreaks that kill large numbers of trees. Climate change is expected to perpetuate these trends, especially in montane ecosystems, calling for improved strategies for managing Western forests and conserving the wildlife that they support. Woodboring beetles (e.g., Buprestidae and Cerambycidae) colonize dead and weakened trees and speed succession of habitats altered by fire or bark beetles, while serving as prey for some early-seral habitat specialists, including several woodpecker species. To understand how these ecologically important beetles respond to different sources of tree mortality, we sampled woodborers in 16 sites affected by wildfire or bark beetle outbreak in the previous one to eight years. Study sites were located in the Sierra Nevada, Modoc Plateau, Warner Mountains, and southern Cascades of California, USA. We used generalized linear mixed models to evaluate hypotheses concerning the response of woodboring beetles to disturbance type, severity, and timing; forest stand composition and structure; and tree characteristics.</p

Ancestry reported by white adults with cutaneous melanoma and control subjects in central Alabama

BACKGROUND: We sought to evaluate the hypothesis that the high incidence of cutaneous melanoma in white persons in central Alabama is associated with a predominance of Irish and Scots descent. METHODS: Frequencies of country of ancestry reports were tabulated. The reports were also converted to scores that reflect proportional countries of ancestry in individuals. Using the scores, we computed aggregate country of ancestry indices as estimates of group ancestry composition. HLA-DRB1*04 allele frequencies and relationships to countries of ancestry were compared in probands and controls. Results were compared to those of European populations with HLA-DRB1*04 frequencies. RESULTS: Ninety evaluable adult white cutaneous melanoma probands and 324 adult white controls reported countries of ancestry of their grandparents. The respective frequencies of Ireland, and Scotland and "British Isles" reported countries of ancestry were significantly greater in probands than in controls. The respective frequencies of Wales, France, Italy and Poland were significantly greater in controls. 16.7% of melanoma probands and 23.8% of controls reported "Native American" ancestry; the corresponding "Native American" country of ancestry index was not significantly different in probands and controls. The frequency of HLA-DRB1*04 was significantly greater in probands, but was not significantly associated with individual or aggregate countries of ancestry. The frequency of DRB1*04 observed in Alabama was compared to DRB1*04 frequencies reported from England, Wales, Ireland, Orkney Island, France, Germany, and Australia. CONCLUSION: White adults with cutaneous melanoma in central Alabama have a predominance of Irish, Scots, and "British Isles" ancestry and HLA-DRB1*04 that likely contributes to their high incidence of cutaneous melanoma

Including ELSI research questions in newborn screening pilot studies

Background The evidence review processes for adding new conditions to state newborn screening (NBS) panels rely on data from pilot studies aimed at assessing the potential benefits and harms of screening. However, the consideration of ethical, legal, and social implications (ELSI) of screening within this research has been limited. This paper outlines important ELSI issues related to newborn screening policy and practices as a resource to help researchers integrate ELSI into NBS pilot studies. Approach Members of the Bioethics and Legal Workgroup for the Newborn Screening Translational Research Network facilitated a series of professional and public discussions aimed at engaging NBS stakeholders to identify important existing and emerging ELSI challenges accompanying NBS. Results Integrating ELSI questions into pilot studies will help NBS programs to better understand the potential impact of screening for a new condition on newborns and families, and make crucial policy decisions aimed at maximized benefits and mitigating the potential negative medical or social implications of screening