Provenance Analysis of the Cretaceous Hornbrook Formation of northern California and southern Oregon

The provenance of the Cretaceous Hornbrook Formation, deposited unconformably on the eastern terranes of the Klamath Mountains of northern California and southern Oregon, may prove critical to reconstructing the complex Cretaceous paleogeography of this region. Sandstone petrography from each of the five members of the Hornbrook Formation indicates a variable source region with elements from basement uplift, transitional continent, recycled orogen, and dissected arc sources. A conglomerate clast count from the Klamath River Conglomerate member is broadly consistent with sandstone petrography, but yielded more quartzite and fewer volcanic clasts than the sand-sized fraction. This reflects the different susceptibility to weathering and diagenesis of these rock types. Likewise, Klamath River Conglomerate quartzite clasts contain a Precambrian detrital zircon age distribution very similar to that found in the Antelope Mountain Quartzite within the Yreka subterrane of the eastern Klamath Mountains while all the other Precambrian zircons from the Hornbrook Formation resemble northern Sierra Nevada terranes. This discrepancy suggests that the quartzite was not broken down into sand-sized grains during transport, but rocks from plutonic arc sources were disaggregated. In addition, detrital zircon age spectra from sandstones throughout the strata of the Hornbrook Formation clearly show that the provenance of the Hornbrook Formation changed with time and was not limited to the Klamath Mountains, contrary to past assumptions. In the Mesozoic detrital zircon age distribution, the reduction in the Early Cretaceous peak and the appearance of a Late Cretaceous peak suggests increasing input from an active magmatic arc other than a Klamath Mountain source. This age signature is supported by the variability of the sandstone petrography, the decreasing volcanic input, and the decreasing amount of zirconium, which demonstrate either the dissection of a magmatic arc source and/or multiple source regions. Furthermore, the members of the Hornbrook Formation correlate with the combined detrital zircon distributions of the Great Valley Basin more closely than with the combined distributions of the Methow Basin. This data supports past interpretations of the Hornbrook Basin as part of an extensive forearc basin that included the Great Valley Basin and possibly the Ochoco Basin where more research is needed. With the exception of the quartzite clasts in the basal member, Precambrian ages are rare, and Paleozoic ages, common in the Klamath Mountains, occur only in the youngest member of the Hornbrook Formation. Thus, the changing provenance of the Hornbrook Formation likely reflects sediment input from the Klamath Mountains activity and from an adjacent Jurassic-Cretaceous magmatic arc

Understanding a Critical Basinal Link in Cretaceous Cordilleran Paleogeography: Detailed Provenance of the Hornbrook Formation, Oregon and California

The Hornbrook Formation is a Cretaceous overlap assemblage that rests unconformably on accreted terranes and plutons of the Klamath Mountains in southern Oregon and northern California. The combined results of sandstone petrography, detrital zircon U-Pb age and Hf isotopic systematics, and whole-rock Nd analysis document an abrupt change in sediment sources for the Hornbrook Formation during the Late Cretaceous. The lower members of the Hornbrook Formation record provenance in the Klamath Mountains and the Sierran Foothills belt that is characterized by detrital zircon age distributions with large Jurassic and Early Cretaceous peaks (170-130 Ma) and positive zircon Hf and whole-rock Nd values. In contrast, upper members of the Hornbrook Formation include abundant sediment derived from the Cretaceous Sierran Batholith that is characterized by large Cretaceous peaks (120-85 Ma) in detrital zircon age distributions and less positive zircon Hf and whole-rock Nd values. A similar Late Cretaceous provenance shift is present in the Great Valley Group of California, which likely formed the southern continuation of the Hornbrook basin during deposition of the upper Hornbrook members. These provenance results may reflect changing plate kinematics along the U.S. Cordilleran margin during the Late Cretaceous, including extension and subsidence in the Klamath Mountains and Blue Mountains regions followed by rapid uplift of the main Sierra Nevada Batholith. Thus, the detailed provenance signature for the Hornbrook Formation presented here records regional tectonic events in the mid- to Late Cretaceous U.S. Cordillera, and suggests that the Hornbrook Formation and Great Valley Group shared similar sources but remained separate basins until mid- to Late Cretaceous time

A Qualitative Study of Anticipated Decision Making around Type 2 Diabetes Genetic Testing: the Role of Scientifically Concordant and Discordant Expectations

Type 2 diabetes mellitus (T2DM) genetic testing is undergoing clinical trials to measure the efficacy of genetic counseling for behavior‐based risk reduction. The expectations patients bring to the testing process may play an important role in individual outcomes. We conducted a qualitative exploration of anticipated decision‐making and expectations around T2DM genetic testing. Semi‐structured interviews were completed with Mexican Americans (n = 34), non‐Hispanic Black Americans (n = 39), and non‐Hispanic White Americans (n = 39) at risk for T2DM. Transcripts were analyzed for themes. Most participants would accept T2DM genetic testing in order to motivate risk‐reducing behaviors or apprise family members of their risk. Participants who would decline testing wished to avoid emotional distress or believed the test would not reveal new risk information. Non‐Hispanic Whites and those with college education declined genetic testing more often than other groups. Those without college education were more likely to have testing expectations that were discordant with current science, such as conflating genetic testing with common ‘blood tests.’ Understanding expectations and decision‐making factors around T2DM genetic testing will better prepare healthcare professionals to counsel their patients. This may lead to a higher efficacy of T2DM genetic testing and counseling.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147076/1/jgc40469.pd

FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs.

Chondrodystrophy in dogs is defined by dysplastic, shortened long bones and premature degeneration and calcification of intervertebral discs. Independent genome-wide association analyses for skeletal dysplasia (short limbs) within a single breed (PBonferroni = 0.01) and intervertebral disc disease (IVDD) across breeds (PBonferroni = 4.0 × 10-10) both identified a significant association to the same region on CFA12. Whole genome sequencing identified a highly expressed FGF4 retrogene within this shared region. The FGF4 retrogene segregated with limb length and had an odds ratio of 51.23 (95% CI = 46.69, 56.20) for IVDD. Long bone length in dogs is a unique example of multiple disease-causing retrocopies of the same parental gene in a mammalian species. FGF signaling abnormalities have been associated with skeletal dysplasia in humans, and our findings present opportunities for both selective elimination of a medically and financially devastating disease in dogs and further understanding of the ever-growing complexity of retrogene biology

The Lantern Vol. 12, No. 3, June 1944

• A Peek Through a Byberry Window • Fragment • My Grudge Against the Fiction Detective • Haunting Refrain • The World and I • They Said • The Brook • By Their Fruits Ye Shall Know Them : 1944 Fogel Prize Essay • Why • Green Leaf • Night Drama • In That Same Hour • The Greeks Had a Word For It • The Call of War • The Promise of a Pearl • The Apiaryhttps://digitalcommons.ursinus.edu/lantern/1033/thumbnail.jp

Survivorship care for older adults with cancer: U13 conference report

Older adult cancer survivors currently account for almost 60% of all cancer survivors. The number of older cancer survivors will continue to increase as the population ages and as patients’ live longer after a cancer diagnosis. As part of cancer center accreditation, the American College of Surgeons Commission on Cancer® (CoC) has placed great importance on survivorship care planning. While the CoC has set standards for general survivorship care, there is sparse evidence on how to best care for older adult cancer survivors. Concern exists among the medical community that survivorship care plans could increase paperwork without improving outcomes. Given the diverse and unique needs of older adult cancer survivors, the inter-professional team provides a structure and process for survivorship care built around the particular needs of older adults. The Cancer and Aging Research Group (CARG), in partnership with the NIA/NCI, held a U13 conference in May 2015 in part to discuss survivorship care for older adults with cancer. This report discusses four themes that emerged from one section of the conference: (1) survivorship care is a process that continually evolves to meet the needs of older adults; (2) older adult cancer survivors have unique needs and care plans should be tailored to meet these needs; (3) the inter-professional team is ideally suited to structure survivorship care of older adults; (4) patient advocacy must be encouraged throughout the cancer care continuum. As evidence based survivorship practices develop, the unique needs of older adults need to be given substantial attention

Diet-induced maternal obesity impacts feto-placental growth and induces sex-specific alterations in placental morphology, mitochondrial bioenergetics, dynamics, lipid metabolism and oxidative stress in mice.

Funder: Department of Physiology, Development and Neuroscience Seed FundingFunder: Isaac Newton Trust Research GrantFunder: Medical Research Council PhD StipendFunder: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior FellowshipAIM: The current study investigated the impact of maternal obesity on placental phenotype in relation to fetal growth and sex. METHODS: Female C57BL6/J mice were fed either a diet high in fat and sugar or a standard chow diet, for 6 weeks prior to, and during, pregnancy. At day 19 of gestation, placental morphology and mitochondrial respiration and dynamics were assessed using high-resolution respirometry, stereology, and molecular analyses. RESULTS: Diet-induced maternal obesity increased the rate of small for gestational age fetuses in both sexes, and increased blood glucose concentrations in offspring. Placental weight, surface area, and maternal blood spaces were decreased in both sexes, with reductions in placental trophoblast volume, oxygen diffusing capacity, and an increased barrier to transfer in males only. Despite these morphological changes, placental mitochondrial respiration was unaffected by maternal obesity, although the influence of fetal sex on placental respiratory capacity varied between dietary groups. Moreover, in males, but not females, maternal obesity increased mitochondrial complexes (II and ATP synthase) and fission protein DRP1 abundance. It also reduced phosphorylated AMPK and capacity for lipid synthesis, while increasing indices of oxidative stress, specifically in males. In females only, placental mitochondrial biogenesis and capacity for lipid synthesis, were both enhanced. The abundance of uncoupling protein-2 was decreased by maternal obesity in both fetal sexes. CONCLUSION: Maternal obesity exerts sex-dependent changes in placental phenotype in association with alterations in fetal growth and substrate supply. These findings may inform the design of personalized lifestyle interventions or therapies for obese pregnant women

FAS promoter polymorphism: outcome of childhood acute myeloid leukemia. A children's oncology group report.

PURPOSE: FAS is a cell surface receptor involved in apoptotic signal transmission. Deregulation of this pathway results in down-regulation of apoptosis and subsequent persistence of a malignant clone. A single nucleotide polymorphism resulting in guanine-to-adenine transition in the FAS promoter region (position -1377) is thought to reduce stimulatory protein 1 transcription factor binding and decrease FAS expression. Previous work has shown increased risk of developing acute myeloid leukemia (AML) in adult patients with a variant allele at this site. The same authors have shown that the presence of an adenine residue rather than a guanine residue at -1,377 bp significantly attenuates transcription factor stimulatory protein 1 binding and may contribute to a reduction in FAS expression and ultimately to the enrichment of apoptosis-resistant clones in AML. We hypothesized that FAS genotype by altering susceptibility to apoptosis might affect outcome of childhood AML therapy. EXPERIMENTAL DESIGN: Four hundred forty-four children treated for de novo AML on a uniform protocol were genotyped for FAS 1377. RESULTS: There were no significant differences in overall survival, event-free survival, treatment-related mortality, or relapse rate between patients with FAS 1377GG genotype versus 1377GA/1377AA genotypes. CONCLUSIONS: FAS 1377 genotype does not alter outcome of de novo AML in children

Genome-Wide Association Analysis Identifies a Mutation in the Thiamine Transporter 2 (SLC19A3) Gene Associated with Alaskan Husky Encephalopathy

Alaskan Husky Encephalopathy (AHE) has been previously proposed as a mitochondrial encephalopathy based on neuropathological similarities with human Leigh Syndrome (LS). We studied 11 Alaskan Husky dogs with AHE, but found no abnormalities in respiratory chain enzyme activities in muscle and liver, or mutations in mitochondrial or nuclear genes that cause LS in people. A genome wide association study was performed using eight of the affected dogs and 20 related but unaffected control AHs using the Illumina canine HD array. SLC19A3 was identified as a positional candidate gene. This gene controls the uptake of thiamine in the CNS via expression of the thiamine transporter protein THTR2. Dogs have two copies of this gene located within the candidate interval (SLC19A3.2 – 43.36–43.38 Mb and SLC19A3.1 – 43.411–43.419 Mb) on chromosome 25. Expression analysis in a normal dog revealed that one of the paralogs, SLC19A3.1, was expressed in the brain and spinal cord while the other was not. Subsequent exon sequencing of SLC19A3.1 revealed a 4bp insertion and SNP in the second exon that is predicted to result in a functional protein truncation of 279 amino acids (c.624 insTTGC, c.625 C>A). All dogs with AHE were homozygous for this mutation, 15/41 healthy AH control dogs were heterozygous carriers while 26/41 normal healthy AH dogs were wild type. Furthermore, this mutation was not detected in another 187 dogs of different breeds. These results suggest that this mutation in SLC19A3.1, encoding a thiamine transporter protein, plays a critical role in the pathogenesis of AHE.University of California, Davis. School of Veterinary Medicine. Center for Companion Animal Healt