MAP3K4 promotes fetal and placental growth by controlling the receptor tyrosine kinases IGF1R/IR and Akt signaling pathway.

Disruption of fetal growth results in severe consequences to human health, including increased fetal and neonatal morbidity and mortality, as well as potential lifelong health problems. Molecular mechanisms promoting fetal growth represent potential therapeutic strategies to treat and/or prevent fetal growth restriction (FGR). Here, we identify a previously unknown role for the mitogen-activated protein kinase kinase kinase 4 (MAP3K4) in promoting fetal and placental growth.

Structure-function analysis of the SHOC2-MRAS-PP1C holophosphatase complex.

Receptor tyrosine kinase (RTK)-RAS signalling through the downstream mitogen-activated protein kinase (MAPK) cascade regulates cell proliferation and survival. The SHOC2-MRAS-PP1C holophosphatase complex functions as a key regulator of RTK-RAS signalling by removing an inhibitory phosphorylation event on the RAF family of proteins to potentiate MAPK signalling. SHOC2 forms a ternary complex with MRAS and PP1C, and human germline gain-of-function mutations in this complex result in congenital RASopathy syndromes.

Coordinated regulation of Rel expression by MAP3K4, CBP, and HDAC6 controls phenotypic switching.

Coordinated gene expression is required for phenotypic switching between epithelial and mesenchymal phenotypes during normal development and in disease states. Trophoblast stem (TS) cells undergo epithelial-mesenchymal transition (EMT) during implantation and placentation. Mechanisms coordinating gene expression during these processes are poorly understood.

Synthesis of novel 5-substituted-2-aminotetralin analogs: 5-HT and 5-HT G protein-coupled receptor affinity, 3D-QSAR and molecular modeling.

The serotonin 5-HT G protein-coupled receptor (GPCR) is a proposed pharmacotherapeutic target for a variety of central and peripheral indications, albeit, there are no approved drugs selective for binding 5-HT. We previously reported that a lead analog based on the 5-substituted-N,N-disubstituted-1,2,3,4-tetrahydronaphthalen-2-amine (5-substituted-2-aminotetralin, 5-SAT) scaffold binds with high affinity at the 5-HT GPCR, and can treat symptoms of autism in mouse models; subsequently, the lead was found to have high affinity at the 5-HT GPCR. Herein, we report the synthesis of novel 5-SAT analogs to develop a 3-dimensional quantitative structure-affinity relationship (3D-QSAR) at the human 5-HT receptor for comparison with similar studies at the highly homologous 5-HT receptor.

Evaluation of Synthetic Cytochrome P-Mimetic Metalloporphyrins To Facilitate "Biomimetic" Biotransformation of a Series of mGlu Allosteric Ligands.

Allosteric ligands within a given chemotype can have the propensity to display a wide range of pharmacology, as well as unexpected changes in GPCR subtype selectivity, typically mediated by single-atom modifications to the ligand. Due to the unexpected nature of these "molecular switches", chemotypes with this property are typically abandoned in lead optimization. Recently, we have found that in vivo oxidative metabolism by CYPs can also engender molecular switches within allosteric ligands, changing the mode of pharmacology and leading to unwanted toxicity.

GALNT3 Maintains the Epithelial State in Trophoblast Stem Cells.

O-GalNAc glycosylation is initiated in the Golgi by glycosyltransferases called GALNTs. Proteomic screens identified >600 O-GalNAc-modified proteins, but the biological relevance of these modifications has been difficult to determine. We have discovered a conserved function for GALNT3 in trophoblast stem (TS) cells, blastocyst trophectoderm, and human mammary epithelial cells (HMECs).

Correction: Growth and survival relationships of 71 tree species with nitrogen and sulfur deposition across the conterminous U.S.

[This corrects the article DOI: 10.1371/journal.pone.

Growth and survival relationships of 71 tree species with nitrogen and sulfur deposition across the conterminous U.S.

Atmospheric deposition of nitrogen (N) influences forest demographics and carbon (C) uptake through multiple mechanisms that vary among tree species. Prior studies have estimated the effects of atmospheric N deposition on temperate forests by leveraging forest inventory measurements across regional gradients in deposition. However, in the United States (U.

Reforestation can sequester two petagrams of carbon in US topsoils in a century.

Soils are Earth's largest terrestrial carbon (C) pool, and their responsiveness to land use and management make them appealing targets for strategies to enhance C sequestration. Numerous studies have identified practices that increase soil C, but their inferences are often based on limited data extrapolated over large areas. Here, we combine 15,000 observations from two national-level databases with remote sensing information to address the impacts of reforestation on the sequestration of C in topsoils (uppermost mineral soil horizons).

Estimating litter carbon stocks on forest land in the United States.

Forest ecosystems are the largest terrestrial carbon sink on earth, with more than half of their net primary production moving to the soil via the decomposition of litter biomass. Therefore, changes in the litter carbon (C) pool have important implications for global carbon budgets and carbon emissions reduction targets and negotiations. Litter accounts for an estimated 5% of all forest ecosystem carbon stocks worldwide.

An Orally Active Phenylaminotetralin-Chemotype Serotonin 5-HT7 and 5-HT1A Receptor Partial Agonist that Corrects Motor Stereotypy in Mouse Models.

Stereotypy (e.g., repetitive hand waving) is a key phenotype of autism spectrum disorder, Fragile X and Rett syndromes, and other neuropsychiatric disorders, and its severity correlates with cognitive and attention deficits.

Temperature drives global patterns in forest biomass distribution in leaves, stems, and roots.

Whether the fraction of total forest biomass distributed in roots, stems, or leaves varies systematically across geographic gradients remains unknown despite its importance for understanding forest ecology and modeling global carbon cycles. It has been hypothesized that plants should maintain proportionally more biomass in the organ that acquires the most limiting resource. Accordingly, we hypothesize greater biomass distribution in roots and less in stems and foliage in increasingly arid climates and in colder environments at high latitudes.

Status and future of the forest health indicators program of the USA.

For two decades, the US Department of Agriculture, Forest Service, has been charged with implementing a nationwide field-based forest health monitoring effort. Given its extensive nature, the monitoring program has been gradually implemented across forest health indicators and inventoried states. Currently, the Forest Service's Forest Inventory and Analysis program has initiated forest health inventories in all states, and most forest health indicators are being documented in terms of sampling protocols, data management structures, and estimation procedures.

Progress in developing analytical and label-based dietary supplement databases at the NIH Office of Dietary Supplements.

Although an estimated 50% of adults in the United States consume dietary supplements, analytically substantiated data on their bioactive constituents are sparse. Several programs funded by the Office of Dietary Supplements (ODS) at the National Institutes of Health enhance dietary supplement database development and help to better describe the quantitative and qualitative contributions of dietary supplements to total dietary intakes. ODS, in collaboration with the United States Department of Agriculture, is developing a Dietary Supplement Ingredient Database (DSID) verified by chemical analysis.

Dietary supplement ingredient database (DSID): Preliminary USDA studies on the composition of adult multivitamin/mineral supplements.

The Nutrient Data Laboratory of the United States Department of Agriculture (USDA) is collaborating with the Office of Dietary Supplements (ODS), the National Center for Health Statistics (NCHS), and other government agencies to design and populate a dietary supplement ingredient database (DSID). This analytically based, publicly available database will provide reliable estimates of vitamin and mineral content of dietary supplement (DS) products. The DSID will initially be populated with multivitamin/mineral (MVM) products because they are the most commonly consumed supplements.

Obtaining CHPA certification: was it worth it?

Required to achieve CHPA certification late in his career, the author relates his doubts about undertaking the challenge, his stress in studying for and taking the exam, and the new challenges he is facing after passing it.

Measuring vitamins and minerals in dietary supplements for nutrition studies in the USA.

This article illustrates the importance of having analytical data on the vitamin and mineral contents of dietary supplements in nutrition studies, and describes efforts to develop an analytically validated dietary supplement ingredient database (DSID) by a consortium of federal agencies in the USA. Preliminary studies of multivitamin mineral supplements marketed in the USA that were analyzed as candidates for the DSID are summarized. Challenges are summarized, possible future directions are outlined, and some related programs at the Office of Dietary Supplements, National Institutes of Health are described.

Progress in development of an integrated dietary supplement ingredient database at the NIH Office of Dietary Supplements.

Several activities of the Office of Dietary Supplements (ODS) at the National Institutes of Health involve enhancement of dietary supplement databases. These include an initiative with US Department of Agriculture to develop an analytically substantiated dietary supplement ingredient database (DSID) and collaboration with the National Center for Health Statistics to enhance the dietary supplement label database in the National Health and Nutrition Examination Survey (NHANES). The many challenges that must be dealt with in developing an analytically supported DSID include categorizing product types in the database, identifying nutrients, and other components of public health interest in these products and prioritizing which will be entered in the database first.

Breast cancer in Native American women treated at an urban-based Indian health referral center 1982-2003.

Background: Breast cancer incidence and survival varies by race and ethnicity. There are limited data regarding breast cancer in Native American women.

Methods: A retrospective chart review was performed of 139 women diagnosed with breast cancer and treated at Phoenix Indian Medical Center in Phoenix, AZ between January 1, 1982 and December 31, 2003.

Ambulatory alveolar bone grafting.

Background: Traditional practice for alveolar cleft closure requires postoperative hospital convalescence in an unfamiliar, disruptive hospital setting. An outpatient iliac crest alveolar bone grafting protocol was devised to optimize patient care.

Methods: A retrospective review of the senior author's experience over 5 years (1998 to 2004) of ambulatory alveolar cleft closure was compared with the previous 5-year period (1993 to 1998) of inpatient convalescence.

Carney syndrome and the plastic surgeon: presentation, recognition, and evaluation.

Carney syndrome is a rare clinical entity usually treated by plastic surgeons. We present a patient with Carney syndrome and review the literature emphasising the plastic and reconstructive surgical aspects of the syndrome.