Prevalence of obese patients in a primary care setting

Objective: Previous research has addressed the relationship between BMI and chronic disease in primary care; however, little has been done with regard to the association between obesity and depression in primary care. The purpose of this paper is to assess the relationship between obesity and chronic conditions including depression. Research Methods and Procedures : Data from primary care patients seen at a university‐based family medicine clinic in the southeastern United States were extracted for the time between January 1, 1999 and January 1, 2002. Data extracted included most recent height and weight, age, ethnicity, pregnancy status, number of office visits, blood pressure, cholesterol, hemoglobin A_1C, current diagnoses, and medications. Results : A total of 8197 patients were included in the analysis. Sixty‐nine percent of patients seen in a 3‐year period were either overweight or obese. Comparing blood pressure, cholesterol, diagnoses, and medications between BMI groups found differences in virtually all categories. Diagnoses of high cholesterol, hypertension, diabetes, and depression significantly increased for obese patients. Discussion : Obese patients are over‐represented in primary care, and this over‐representation of obesity correlates with several diagnoses, including depression. Depression is a chronic disease that may interfere with health‐related behaviors and must be addressed within the health care system.     

柠檬酸合酶的分子生物学研究进展

柠檬酸合酶（citrate synthase,CS）是细胞内多种重要代谢途径的关键酶。CS可催化草酰乙酸和乙酰辅酶A之间的缩合反应生成柠檬酸和辅酶A。通常革兰氏阳性细菌、古菌以及真核细胞的CS为同源二聚体,而革兰氏阴性细菌的CS为同源六聚体。根据其在细胞内的定位不同,CS可分为线粒体CS、乙醛酸循环体CS、过氧化物酶体CS。这些同工酶在能量代谢、植物脂肪的代谢、脂肪酸的氧化及细胞解毒过程中起着重要作用。不同来源的CS空间结构、催化机制和动力学性质十分相似。针对其生化特性、空间结构特点、催化机制以及分子进化等研究进展进行综述。     

Structural insights into the design of nonpeptidic isothiazolidinone-containing inhibitors of protein-tyrosine phosphatase 1B

Structural analyses of the protein-tyrosine phosphatase 1B (PTP1B) active site and inhibitor complexes have aided in optimization of a peptide inhibitor containing the novel (S)-isothiazolidinone (IZD) phosphonate mimetic. Potency and permeability were simultaneously improved by replacing the polar peptidic backbone of the inhibitor with nonpeptidic moieties. The C-terminal primary amide was replaced with a benzimidazole ring, which hydrogen bonds to the carboxylate of Asp(48), and the N terminus of the peptide was replaced with an aryl sulfonamide, which hydrogen bonds to Asp(48) and the backbone NH of Arg(47) via a water molecule. Although both substituents retain the favorable hydrogen bonding network of the peptide scaffold, their aryl rings interact weakly with the protein. The aryl ring of benzimidazole is partially solvent exposed and only participates in van der Waals interactions with Phe(182) of the flap. The aryl ring of aryl sulfonamide adopts an unexpected conformation and only participates in intramolecular pi-stacking interactions with the benzimidazole ring. These results explain the flat SAR for substitutions on both rings and the reason why unsubstituted moieties were selected as candidates. Finally, substituents ortho to the IZD heterocycle on the aryl ring of the IZD-phenyl moiety bind in a small narrow site adjacent to the primary phosphate binding pocket. The crystal structure of an o-chloro derivative reveals that chlorine interacts extensively with residues in the small site. The structural insights that have led to the discovery of potent benzimidazole aryl sulfonamide o-substituted derivatives are discussed in detail.     

Synchrony in the phenology of a culturally iconic spring flower

We examine the flowering phenology of the cultural iconic Spring Snowflake Leucojum vernum, a considerable tourist attraction, recorded from two sites in western Poland. Flowering dates at the two sites were closely correlated but about 6 days later at the more natural area. The end of flowering was associated with the start of canopy leafing. Early flowering was related to a longer flowering season which may benefit ecotourism under future climate warming.     

Physiological ecology of desert biocrust moss following 10 years exposure to elevated CO₂: evidence for enhanced photosynthetic thermotolerance

In arid regions, biomes particularly responsive to climate change, mosses play an important biogeochemical role as key components of biocrusts. Using the biocrust moss Syntrichia caninervis collected from the Nevada Desert Free Air CO₂ Enrichment Facility, we examined the physiological effects of 10 years of exposure to elevated CO₂, and the effect of high temperature events on the photosynthetic performance of moss grown in CO₂‐enriched air. Moss exposed to elevated CO₂ exhibited a 46% decrease in chlorophyll, a 20% increase in carbon and no difference in either nitrogen content or photosynthetic performance. However, when subjected to high temperatures (35–40°C), mosses from the elevated CO₂ environment showed higher photosynthetic performance and photosystem II (PSII) efficiency compared to those grown in ambient conditions, potentially reflective of a shift in nitrogen allocation to components that offer a higher resistance of PSII to heat stress. This result suggests that mosses may respond to climate change in markedly different ways than vascular plants, and observed CO₂‐induced photosynthetic thermotolerance in S. caninervis will likely have consequences for future desert biogeochemistry.     

mTOR-Dependent Cell Survival Mechanisms

The mechanistic target of rapamycin (mTOR) kinase is a conserved regulator of cell growth, proliferation, and survival. In cells, mTOR is the catalytic subunit of two complexes called mTORC1 and mTORC2, which have distinct upstream regulatory signals and downstream substrates. mTORC1 directly senses cellular nutrient availability while indirectly sensing circulating nutrients through growth factor signaling pathways. Cellular stresses that restrict growth also impinge on mTORC1 activity. mTORC2 is less well understood and appears only to sense growth factors. As an integrator of diverse growth regulatory signals, mTOR evolved to be a central signaling hub for controlling cellular metabolism and energy homoeostasis, and defects in mTOR signaling are important in the pathologies of cancer, diabetes, and aging. Here we discuss mechanisms by which each mTOR complex might regulate cell survival in response to metabolic and other stresses.The mechanistic target of rapamycin (mTOR) is a highly conserved serine/threonine protein kinase belonging to the phosphatidylinositol kinase-related kinase (PIKK) family and in mammalian cells is a central regulator of cell growth, proliferation, and survival (for review, see Sengupta et al. 2010; Zoncu et al. 2010). As its name implies, mTOR is the target of the naturally occurring compound rapamycin, which in association with the FK506-binding protein (FKBP12) is an allosteric inhibitor of mTOR. Although rapamycin is now known to only partially inhibit mTOR activity, derivatives of the drug have important clinical applications in oncology, in preventing restenosis after angioplasty, and as an immunosuppressant following organ transplants.     

The First Record of a Trans-Oceanic Sister-Group Relationship between Obligate Vertebrate Troglobites

We show using the most complete phylogeny of one of the most species-rich orders of vertebrates (Gobiiformes), and calibrations from the rich fossil record of teleost fishes, that the genus Typhleotris, endemic to subterranean karst habitats in southwestern Madagascar, is the sister group to Milyeringa, endemic to similar subterranean systems in northwestern Australia. Both groups are eyeless, and our phylogenetic and biogeographic results show that these obligate cave fishes now found on opposite ends of the Indian Ocean (separated by nearly 7,000 km) are each others closest relatives and owe their origins to the break up of the southern supercontinent, Gondwana, at the end of the Cretaceous period. Trans-oceanic sister-group relationships are otherwise unknown between blind, cave-adapted vertebrates and our results provide an extraordinary case of Gondwanan vicariance.     

Delineating the role of the HLA-DR4 "shared epitope" in susceptibility versus resistance to develop arthritis

In humans, HLA-DR alleles sharing amino acids at the third hypervariable region with DRB1*0401(shared epitope) are associated with a predisposition to rheumatoid arthritis, whereas DRB1*0402 is not associated with such a predisposition. Both DRB1*0402 and DRB1*0401 occur in linkage with DQ8 (DQB1*0302). We have previously shown that transgenic (Tg) mice expressing HLA-DRB1*0401 develop collagen-induced arthritis. To delineate the role of "shared epitope" and gene complementation between DR and DQ in arthritis, we generated DRB1*0402, DRB1*0401.DQ8, and DRB1*0402.DQ8 Tg mice lacking endogenous class II molecules, AE(o). DRB1*0402 mice are resistant to develop arthritis. In double-Tg mice, the DRB1*0401 gene contributes to the development of collagen-induced arthritis, whereas DRB1*0402 prevents the disease. Humoral response to type II collagen is not defective in resistant mice, although cellular response to type II collagen is lower in *0402 mice compared with *0401 mice. *0402 mice have lower numbers of T cells in thymus compared with *0401 mice, suggesting that the protective effect could be due to deletion of autoreactive T cells. Additionally, DRB1*0402 mice have a higher number of regulatory T cells and show increased activation-induced cell death, which might contribute toward protection. In DRB1*0401.DQ8 mice, activated CD4(+) T cells express class II genes and can present DR4- and DQ8-restricted peptides in vitro, suggesting a role of class II(+) CD4 T cells locally in the joints. The data suggest that polymorphism in DRB1 genes determines predisposition to develop arthritis by shaping the T cell repertoire in thymus and activating autoreactive or regulatory T cells.