cssi/SciSciGPT-SciSciNet huggingface dataset:
Uterine artery hemodynamic adaptations through the menstrual cycle into early pregnancy.

OBJECTIVE: To estimate the time course of human uterine artery vascular adaptation through the menstrual cycle into early pregnancy. METHODS: We prospectively measured the uterine artery pulsatility index, peak systolic velocity, and volumetric blood flow during the menstrual cycle and at 4, 6, and 12 weeks of pregnancy in women who conceived. Upper extremity radial artery hemodynamic changes were examined as a control vessel. Ten subjects conceived within 12 months of menstrual cycle studies. Analyses were performed using repeated measures analysis of variance with P < .05 accepted for significance. RESULTS: In women who conceived, uterine artery peak systolic velocity demonstrated a significant increase during the period of observation, which began after cycle day 10 (0.36 × 0.02 meters per second) of the menstrual cycle and continued though 12 menstrual weeks (1.05 ± 0.10 meters per second, P < .001). Uterine artery pulsatility index decreased significantly during the observation window from 3.0 ± 0.2 in the follicular phase to 1.6 ± 0.2 at 12 menstrual weeks (P < .001). Blood flow in the uterine artery increased significantly from cycle day 10 (22.2 ± 1.8 mL per minute) to 12 menstrual weeks’ gestation (150.2 ± 40.3 mL per minute, P < .001). These patterns were significantly different from the patterns observed for the radial artery. CONCLUSION: Uterine artery hemodynamic adaptation in early pregnancy follows a continuum established during the menstrual cycle. These adaptations result in decreased uterine artery impedance and increased blood flow. These changes differ from those observed in the upper extremity radial artery (control vessel) suggesting independence of regional pelvic and systemic hemodynamic adaptations.
Origin of GABAergic neurons in the human neocortex

The mammalian neocortex contains two major classes of neurons, projection and local circuit neurons. Projection neurons contain the excitatory neurotransmitter glutamate, while local circuit neurons are inhibitory, containing GABA. The complex function of neocortical circuitry depends on the number and diversity of GABAergic (gamma-aminobutyric-acid-releasing) local circuit neurons. Using retroviral labelling in organotypic slice cultures of the embryonic human forebrain, we demonstrate the existence of two distinct lineages of neocortical GABAergic neurons. One lineage expresses Dlx1/2 and Mash1 transcription factors, represents 65% of neocortical GABAergic neurons in humans, and originates from Mash1-expressing progenitors of the neocortical ventricular and subventricular zone of the dorsal forebrain. The second lineage, characterized by the expression of Dlx1/2 but not Mash1, forms around 35% of the GABAergic neurons and originates from the ganglionic eminence of the ventral forebrain. We suggest that modifications in the expression pattern of transcription factors in the forebrain may underlie species-specific programmes for the generation of neocortical local circuit neurons and that distinct lineages of cortical interneurons may be differentially affected in genetic and acquired diseases of the human brain.
Salt- and osmotic stress-induced choline monooxygenase expression in Kochia scoparia is ABA-independent

Choline monooxygenase (CMO) is the first regulatory enzyme in the biosynthetic pathway for glycine betaine, an effective osmoprotectant in Kochia scoparia, a highly drought- and salt-tolerant species. In seedlings, CMO transcript levels are rapidly increased in response to both NaCl and osmotic stress treatments. The mRNA level in shoots was substantially higher than in roots. The rapid induction seen in whole plants was in contrast to the apparent down-regulation observed in suspension-cultured K. scoparia cells in response to the same salt stress. Treatment with exogenous abscisic acid (ABA) or fluridone shows that CMO induction proceeds via an ABA-independent signal transduction pathway. Examination of the CMO upstream regulatory region reveals a number of stress response-related elements, some of which may be involved in the stress tolerance shown by this species.
Visible Light Sensitized CO2 Activation by the Tetraaza [CoIIN4H(MeCN)]2+ Complex Investigated by FT-IR Spectroscopy and DFT Calculations

In situ FT-IR measurements and electronic structure calculations are reported for the reduction of CO2 catalyzed by the macrocyclic complex [CoIIN4H]2+ (N4H = 2,12-dimethyl-3,7,11,17-tetraazabicyclo-[11.3.1]-heptadeca-1(17),2,11,13,15-pentaene). Beginning from the [CoIIN4H]2+ resting state of the complex in wet acetonitrile solution, two different visible light sensitizers with substantially different reducing power are employed to access reduced states. Accessing reduced states of the complex with a [Ru(bpy)3]2+ sensitizer yields an infrared band at 1670 cm–1 attributed to carboxylate, which is also observed for an authentic sample of the one-electron reduced complex [CoN4H(MeCN)]+ in CO2 saturated acetonitrile solution. The results are interpreted based on calculations using the pure BP86 functional that correctly reproduces experimental geometries. Continuum solvation effects are also included. The calculations show that Co is reduced to CoI in the first reduction, which is consistent with experimental...
Small-angle behaviour of the polarization in p-d elastic scattering

Abstract Measurements of the polarization in p-d scattering at 11.6 MeV show a minimum in the asymmetry distribution at 29° c.m. This observation seems to be consistent with spin-orbit effects in the p-d interaction at this energy.
Functional evaluation of transformer insulation

IN THE PAST few years a strong trend has developed toward the evaluation of electrical insulation by functional testing. It seems generally agreed that (a) the present AIEE, A, B, and H temperature classifications are no longer adequate, and (b) functional tests rather than chemical structure alone should provide the basis for classification. For example, several recent AIEE papers have proposed various accelerated life test procedures for deciding whether a given material or system will have a satisfactory life expectancy at a continuous hot-spot temperature of 105, 130, or 180 C and, therefore, can be designated properly as Class A, B, or H.
Additive effects of combination treatment with anti-inflammatory and neuroprotective agents in experimental autoimmune encephalomyelitis.

Abstract We studied the effects of combination treatment with an anti-inflammatory agent, interferon (IFN)-β, and a putative neuroprotective agent, an estrogen receptor (ER)-β ligand, during EAE. Combination treatment significantly attenuated EAE disease severity, preserved axonal densities in spinal cord, and reduced CNS inflammation. Combining ERβ treatment with IFNβ reduced IL-17, while it abrogated IFNβ-mediated increases in Th1 and Th2 cytokines from splenocytes. Additionally, combination treatment reduced VLA-4 expression on CD4+ T cells, while it abrogated IFNβ-mediated decreases in MMP-9. Our data demonstrate that combination treatments can result in complex effects that could not have been predicted based on monotherapy data alone.
The four biplanes with k = 9

Abstract An exhaustive computer search has established the existence of precisely four biplanes with k = 9. One of the self-dual biplanes is new and a description is provided in terms of its automorphism group. The λ-chain structures for all four biplanes are tabulated.
Basic fibroblast growth factor prevents death of lesioned cholinergic neurons in vivo

Cutting the axons of the cholinergic neurons that project to the hippocampal formation results in death of most of these cells1,2. Previous studies have shown that administration of nerve growth factor before or at the same time as the lesion will prevent this cell death3,4. Here we demonstrate that basic fibroblast growth factor (FGF) administered into the brain reduces the death of cholinergic neurons in the medial septum and diagonal band of Broca after transection of their axons, in both young adult and aged rats. Moreover, FGF can partially protect against death of cholinergic neurons even when administered two days after axonal transection. These results indicate a possible function for FGF in the normal support of basal forebrain cholinergic neurons, but its range of activity could be wider, for FGF also supports non-cholinergic neurons in vitro5,6, it is localized in many of the central nervous system neurons7, and it is found in relatively high concentrations in the brain8.
The American Society of Hematology: a success at age 50

The American Society of Hematology (ASH) turns 50 years old in 2008, and we have much to celebrate. Over those years the Society established its principles: to promote both the art and science of hematology and to hold a high-quality Educational Meeting. ASH membership has grown from a few hundred curious attendees at a planning meeting in 1957 to more than 15,000 members today, and the annual meeting has grown from a scientific session of 5 papers at the planning meeting to more than 500 oral presentations and nearly 2,500 poster presentations at the 2007 meeting. The modern ASH promotes cutting-edge science, sponsors research by scholars from all over the globe, helps train the next generation of clinician-scientists, lobbies Congress and several other governmental agencies on behalf of its clinician and scientist members, and publishes the foremost scholarly journal in the field of hematology, Blood, designed to provide its readership with timely reviews, expert opinion on clinical hematology, practice-changing clinical trials, and insightful basic science. The next 50 years of ASH are likely to see many profound changes, but one thing is almost certain-our dedication to fostering clinical and scientific excellence in hematology will continue as the Society's raison d'etre.
CHARACTERISTICS OF SOME BINARY TRANSITION METAL HYDRIDES.

Abstract The purpose of this report is to review some of the recent results obtained in the study of binary transition metal hydrides. In addition to published work, previously unpublished data from the Sandia Laboratories is included. Subjects covered are the distinct and unusual properties of these hydrides, their preparation, and their kinetic, thermodynamic, and structural properties.
Contributions of Herpes Simplex Virus 1 Envelope Proteins to Entry by Endocytosis

Herpes simplex virus (HSV) proteins specifically required for endocytic entry but not direct penetration have not been identified. HSVs deleted of gE, gG, gI, gJ, gM, UL45, or Us9 entered cells via either pH-dependent or pH-independent endocytosis and were inactivated by mildly acidic pH. Thus, the required HSV glycoproteins, gB, gD, and gH-gL, may be sufficient for entry regardless of entry route taken. This may be distinct from entry mechanisms employed by other human herpesviruses.
Geophysical observations of Kilauea Volcano, Hawaii, 2. Constraints on the magma supply during November 1975–September 1977

Abstract Following a 22-month hiatus in eruptive activity, Kilauea volcano extruded roughly 35 × 10 6 m 3 of tholeiitic basalt from vents along its middle east rift zone during 13 September–1 October, 1977. The lengthy prelude to this eruption began with a magnitude 7.2 earthquake on 29 November, 1975, and included rapid summit deflation episodes in June, July, and August 1976 and February 1977. Synthesis of seismic, geodetic, gravimetric, and electrical self-potential observations suggests the following model for this atypical Kilauea eruptive cycle. Rapid summit deflation initiated by the November 1975 earthquake reflected substantial migration of magma from beneath the summit region of Kilauea into the east and southwest rift zones. Simultaneous leveling and microgravity observations suggest that 40–90 × 10 6 m 3 of void space was created within the summit magma chamber as a result of the earthquake. If this volume was filled by magma from depth before the east rift zone intrusive event of June 1976, the average rate of supply was 6–13 × 10 6 m 3 /month, a rate that is consistent with the value of 9 × 10 6 m 3 /month suggested from observations of long-duration Kilauea eruptions. Essentially zero net vertical change was recorded at the summit during the 15-month period beginning with the June 1976 intrusion and ending with the September 1977 eruption. This fact suggests that most magma supplied from depth during this interval was eventually delivered to the east rift zone, at least in part during four rapid summit deflation episodes. Microearthquake epicenters migrated downrift to the middle east rift zone for the first time during the later stages of the February 1977 intrusion, an occurrence presumably reflecting movement of magma into the eventual eruptive zone. This observation was confirmed by tilt surveys in May 1977 that revealed a major inflation center roughly 30 km east of the summit in an area of anomalous steaming and forest kill first noted in March 1976.
CURRENT CONCEPTS OF GASTRIC ANALYSIS.

This report briefly outlines current views regarding the physiology of gastric secretion and its measurement, with reference to newer analyses—including gastric blood-group substances, proteins, and enzymes. Maximal stimulation with histamine or betazole (Histalog) is preferred as a quantitative approach to the measurement of gastric acid output.
Investigation of deformation and microstructural evolution in Grade 91 ferritic–martensitic steel by in situ high-energy X-rays

Abstract In situ wide- and small-angle X-ray scattering (WAXS/SAXS) were used to characterize microstructural evolution in Grade 91 ferritic–martensitic steel during tensile tests at room temperature (RT) and 650 °C. Elastic lattice strains in the Fe matrix, M 23 C 6 and MX precipitates were measured from peak shifts in WAXS patterns. Load transfer, as evidenced by precipitates developing much higher lattice strain than the Fe matrix in the plastic regime, was found for the RT test but was not obvious at 650 °C. Detailed peak-broadening analysis as a function of strain, using modified Williamson–Hall plots, indicates strong dislocation activity in the Fe matrix during the RT test which can be divided into two stages: (i) dislocation multiplication (from 0 to 4.0% strain) and (ii) formation of dislocation walls and cells (after 4.0% strain). This framework is consistent with the observed precipitate strain response and can describe the macroscopic flow stress behavior. At 650 °C, Fe peaks broadened much less with increasing strain, indicating a low dislocation density and providing an explanation for the low precipitate strains and macroscopic flow stress at this temperature. Changes in SAXS intensity were used to infer nanoscale void formation, which occurred immediately after necking at RT but long after necking at 650 °C. Most voids were concentrated at the necking center, and the RT specimen developed more voids than the 650 °C specimen.
Efetividade dos contracetivos orais após cirurgia bariátrica – revisão baseada na evidência

Resumo Introducao A cirurgia bariatrica e um procedimento cada vez mais utilizado no tratamento da obesidade e suas comorbilidades. As mulheres em idade fertil submetidas a este procedimento constituem um grupo que merece particular atencao. Existe o consenso de que a gravidez deva ser evitada pelo menos ate um ano apos a cirurgia, dado as complicacoes materno‐fetais associadas, pelo que uma contracecao eficaz e essencial. Os contracetivos orais sao amplamente utilizados, no entanto, a cirurgia de bypass gastrico pode condicionar uma diminuicao da capacidade absortiva destes farmacos. E objetivo desta revisao avaliar a efetividade dos contracetivos orais nas mulheres submetidas a cirurgia bariatrica. Metodos Foi realizada uma pesquisa sistematica da literatura nas bases de dados TRIP Database , Cochrane Library , DARE, Bandolier , National Guideline Clearing House , NeLH Guidelines Finder e Medline , entre janeiro de 2002 e janeiro de 2012, em ingles, espanhol e portugues. Resultados Dos 12 artigos encontrados, 3 cumpriam os criterios de inclusao definidos: uma revisao sistematica (NE 2a), um estudo de cohort (NE 2b) e uma revisao classica (NE 4). A revisao sistematica conclui que, apesar de a evidencia ser limitada, nao se verifica diminuicao substancial da efetividade dos contracetivos orais. O ensaio clinico nao aconselha a utilizacao de contracetivos orais e privilegia os metodos contracetivos que nao utilizem a via oral. A revisao classica aponta para a falencia dos contracetivos orais apos a cirurgia bariatrica e a diminuicao da capacidade absortiva apos cirurgia de bypass gastrico. Discussao A evidencia existente sobre a efetividade dos contracetivos orais e limitada a um numero reduzido de estudos. Nao foi identificada uma diminuicao substancial da efetividade dos contracetivos orais nos estudos incluidos. O uso de contracetivos orais apos cirurgia bariatrica tem uma forca de recomendacao C.
Exploring new service models: Can consolidating public service points improve response to customer needs?

Abstract This article describes an experimental “integrated service point” that combines the desks and staff who perform reference and circulation at one of M.I.T.’s five main libraries. The Integrated Service Point concept was previously presented as “United We Stand, Divided We Fail?” at the April 1999 ACRL conference in Detroit.
In vitro measurements of porcine anterior column units under free swelling.

The objectives of this study are to present a 2-D optical method for measuring gross kinematics of porcine anterior column units (ACUs) exposed to swelling with no applied load, provide a detailed error analysis of the 2-D optical measurement technique, and present a 2-D radiographic technique for measuring the distribution of x-ray intensity through an axial slice of the disc. The 2-D optical technique was sufficient for detecting the flexion-extension behavior of the ACUs tested. The error analysis concluded that the use of a second camera to quantify out of plane movement of the specimen would greatly improve the accuracy of the measurement of angle. The 2-D radiographic technique provided limited information on changes in intradiscal material. It was also limited in its accuracy and dependability (i.e., only 5 out of 13 specimens provided radiographs suitable for this analysis). The results of this study indicate that a relationship might exist between the flexion-extension behavior observed from swelling and intradiscal shifts of matter. Further work is needed to confirm this relationship.
The P2 protein of bovine root myelin: isolation and some clinical and immunological properties.

— A small basic protein (mol.wt. 12,000), referred to as the P2 protein, was extracted with dilute acid from delipidated bovine root myelin and purified by ion exchange chromatography on cellulose phosphate. It appeared homogeneous on polyacrylamide gel electrophoresis. The P2 protein had a distinctly different amino acid composition than the larger basic protein (mol.wt. 18,000), referred to as the P1 protein, that is also present in peripheral nerve myelin. It contained relatively more hydrophobic residues and much less histidine and proline. The P2 protein conjugated with peroxidase was bound by lymph node cells and infiltrates in rabbits sensitized with whole bovine root myelin. No binding was evident with the bovine central nervous system myelin basic protein. Chemically and immunologically, the P2 protein appears to be specific to peripheral nervous system myelin. The isolated P2 protein produced mild clinical symptoms of experimental allergic neuritis, but no histological evidence of disease. It was suggested that the P2 protein is an important antigen for experimental allergic neuritis, and that its antigenic determinants are likely to be conformation-dependent.
Removal of230Th and231Pa from the open ocean

Concentrations of230Th and231Pa were measured in particulate matter collected by sediment traps deployed in the Sargasso Sea (Site S2), the north equatorial Atlantic (site E), and the north equatorial Pacific (Site P) as well as in particles collected by in situ filtration at Site E. Concentrations of dissolved Th and Pa were determined by extraction onto manganese dioxide adsorbers at Site P and at a second site in the Sargasso Sea (site D). Dissolved230Th/231Pa activity ratios were 3–6 at Sites P and D. In contrast, for all sediment trap samples from greater than 2000 m, unsupported230Th/231Pa ratios were 22–35 (average 29.7). Ratios were lower in particulate matter sampled at shallower depths. Particles filtered at 3600 m and 5000 m at Site E had ratios of 50 and 40. Results show that suspended particulate matter in the open ocean preferentially scavenges Th relative to Pa. Most of the230Th produced by decay of234U in the open ocean is removed by adsorption to settling particulate matter. In contrast, less than 50% of the231Pa produced by decay of235U is removed from the water column by this mechanism. Mixing processes transport the remainder to other sinks.
Binding of the MLL PHD3 finger to histone H3K4me3 is required for MLL-dependent gene transcription

The MLL (mixed-lineage leukemia) proto-oncogene encodes a histone methyltransferase that creates the methylated histone H3K4 epigenetic marks, commonly associated with actively transcribed genes. In addition to its canonical histone methyltransferase SET domain, the MLL protein contains three plant homeodomain (PHD) fingers that are well conserved between species but whose potential roles and requirements for MLL function are unknown. Here, we demonstrate that the third PHD domain of MLL (PHD3) binds histone H3 trimethylated at lysine 4 (H3K4me3) with high affinity and specificity and H3K4me2 with 8-fold lower affinity. Biochemical and structural analyses using NMR and fluorescence spectroscopy identified key amino acids essential for the interaction with H3K4me3. Site-directed mutations of the residues involved in recognition of H3K4me3 compromised in vitro H3K4me3 binding but not in vivo localization of full-length MLL to chromatin sites in target promoters of MEIS1 and HOXA genes. Whereas intact PHD3 finger was necessary for MLL occupancy at these promoters, H3K4me3 binding was critical for MLL transcriptional activity. These results demonstrate that MLL occupancy and target gene activation can be functionally separated. Furthermore, these findings reveal that MLL not only "writes" the H3K4me3 mark but also binds the mark, and this binding is required for the transcriptional maintenance functions of MLL.
When Race Makes No Difference: Marriage and the Military

While "retreatfrom marriage" rates have been on the risefor all Americans, there has been an increasing divergence in family patterns between blacks and whites, with the former experiencing markedly higher divorce, nonmarital childbearing and nevermarrying rates. Explanations generallyfocus on theories rangingfrom economic class stratification to normative differences. I examine racial marriage trends when removed from society and placed in a structural context that minimizes racial and economic stratification. I compare nuptial patterns within the military, a total institution in the Goffmanian sense, which serves as a natural controlfor the arguments presented in the literature on the retreatfrom marriage. Through a combination of event history and propensity score matching analyses using the NLSY79, Ifind that black-white difference in marriage patterns disappears in the military. Concern regarding marital dissolution, the increasing trend not to marry at all,
Quantitative analysis of arterial flow properties for detection of non-calcified plaques in ECG-gated coronary CT angiography

We are developing a computer-aided detection system to assist radiologists in detection of non-calcified plaques (NCPs) in coronary CT angiograms (cCTA). In this study, we performed quantitative analysis of arterial flow properties in each vessel branch and extracted flow information to differentiate the presence and absence of stenosis in a vessel segment. Under rest conditions, blood flow in a single vessel branch was assumed to follow Poiseuille’s law. For a uniform pressure distribution, two quantitative flow features, the normalized arterial compliance per unit length ( C u ) and the normalized volumetric flow ( Q ) along the vessel centerline, were calculated based on the parabolic Poiseuille solution. The flow features were evaluated for a two-class classification task to differentiate NCP candidates obtained by prescreening as true NCPs and false positives (FPs) in cCTA. For evaluation, a data set of 83 cCTA scans was retrospectively collected from 83 patient files with IRB approval. A total of 118 NCPs were identified by experienced cardiothoracic radiologists. The correlation between the two flow features was 0.32. The discriminatory ability of the flow features evaluated as the area under the ROC curve (AUC) was 0.65 for C u and 0.63 for Q in comparison with AUCs of 0.56-0.69 from our previous luminal features. With stepwise LDA feature selection, volumetric flow (Q) was selected in addition to three other luminal features. With FROC analysis, the test results indicated a reduction of the FP rates to 3.14, 1.98, and 1.32 FPs/scan at sensitivities of 90%, 80%, and 70%, respectively. The study indicated that quantitative blood flow analysis has the potential to provide useful features for the detection of NCPs in cCTA.
A prospective study of hand-held Doppler ultrasonography by emergency physicians in the evaluation of suspected deep-vein thrombosis

A prospective study was conducted in the emergency departments of two community hospitals to assess the accuracy of Doppler ultrasonography performed by emergency physicians in the evaluation of patients with symptoms suggestive of deep-vein thrombosis. Seventy-eight extremities in 76 patients were evaluated by both Doppler ultrasonography and contrast venography. Thirty-six Doppler examinations were normal, 26 were abnormal, and 15 were equivocal. Of the unequivocal examinations, three were false-negative and nine were false-positive. These data represent a sensitivity of 85%, specificity of 79%, negative predictive value of 92%, and positive predictive value of 65%. Negative predictive value improved to 100% among a subgroup of low-risk patients, and positive predictive value improved to 80% among a subgroup of high-risk patients. Our study suggests that Doppler ultrasonography is highly predictive of a negative venogram, particularly in the low-risk patient. Further study with a larger population is needed. The availability and noninvasiveness of Doppler ultrasonography make it a useful adjunct in the evaluation of suspected deep-vein thrombosis in the ED.
Chronic, noninvasive glucocorticoid administration suppresses limbic endocannabinoid signaling in mice.

Abstract Limbic endocannabinoid signaling is known to be sensitive to chronic stress; however, studies investigating the impact of prolonged exposure to glucocorticoid hormones have been limited by the concurrent exposure to the stress of daily injections. The present study was designed to examine the effects of a noninvasive approach to alter plasma corticosterone (CORT) on the endocannabinoid system. More precisely, we explored the effects of a 4-week exposure to CORT dissolved in the drinking water of mice (100 μg/ml) and measured cannabinoid CB 1 receptor binding, endocannabinoid content, activity of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH), and mRNA expression of both the CB 1 receptor and FAAH in both the hippocampus and amygdala. Our data demonstrate that CORT decreases CB 1 receptor binding site density in both the hippocampus and amygdala and also reduced anandamide (AEA) content and increased FAAH activity within both structures. These changes in both CB 1 receptor binding and FAAH activity were not accompanied by changes in mRNA expression of either the CB 1 receptor or FAAH in either brain region. Interestingly, our CORT delivery regimen significantly increased 2-AG concentrations within the hippocampus, but not the amygdala. Collectively, these data demonstrate that the confounder of injection stress is sufficient to conceal the ability of protracted exposure to glucocorticoids to reduce CB 1 receptor density and augment AEA metabolism within limbic structures. This article is part of a Special Issue entitled: Stress, Emotional Behavior and the Endocannabinoid System.
An autoradiographic demonstration of blood cell renewal inStyela clava (Urochordata: Ascidiaeea)

The blood cells ofStyela clava were shown by autoradiography with tritiated thymidine to be renewed after several weeks. Proliferating lymphocytes and leucocytes occurred in the lymph nodules and blood channels of the body. Vacuolated cells did not proliferate but differentiated from a precursor cell type.
Binding and Internalization of Lipopolysaccharide by Cla-1, a Human Orthologue of Rodent Scavenger Receptor B1

Scavenger receptor, class B, type I (SR-BI) mediates selective uptake of high density lipoprotein (HDL) cholesteryl ester. SR-BI recognizes HDL, low density lipoprotein (LDL), exchangeable apolipoproteins, and protein-free lipid vesicles containing negatively charged phospholipids. Lipopolysaccharides (LPS) are highly glycosylated anionic phospholipids contributing to septic shock. Despite significant structural similarities between anionic phospholipids and LPS, the role of SR-BI in LPS uptake is unknown. Cla-1, the human SR-BI orthologue, was determined to be a LPS-binding protein and endocytic receptor mediating the binding and internalization of lipoprotein-free, monomerized LPS. LPS strongly competed with HDL, lipidfree apoA-I and apoA-II for HDL binding to the mouse RAW cells. Stably transfected HeLa cells expressing Cla-1-bound LPS with a Kd of about 16 microg/ml, and had a 3-4-fold increase in binding capacity and LPS uptake. Bodipy-labeled LPS uptake was found to initially accumulate in the plasma membrane and subsequently in a perinuclear region identified predominantly as the Golgi complex. Bodipy-LPS and Alexa-apoA-I had staining that colocalized on the cell surface and intracellularly indicating similar transport mechanisms. When associated with HDL, LPS uptake was increased in Cla-1 overexpressing HeLa cells by 5-10-fold. Cla-1-associated 3H-LPS uptake exceeded 125I-apolipoprotein uptake by 5-fold indicating a selective LPS uptake. Upon interacting with Cla-1 overexpressing HeLa cells, the complex (Bodipy-LPS/Alexa 488 apolipoprotein-labeled HDL) bound and was internalized as a holoparticle. Intracellularly, LPS and apolipoproteins were sorted to different intracellular compartments. With LPS-associated HDL, intracellular LPS co-localized predominantly with transferrin, indicating delivery to an endocytic recycling compartment. Our study reveals a close similarity between Cla-1-mediated selective LPS uptake and the recently described selective lipid sorting by rodent SR-BI. In summary, Cla-1 was found to bind and internalize monomerized and HDL-associated LPS, indicating that Cla-1 may play important role in septic shock by affecting LPS cellular uptake and clearance.
Inhibition of Mrp2- and Ycf1p-mediated transport by reducing agents: evidence for GSH transport on rat Mrp2

Abstract Mammalian Mrp2 and its yeast orthologue, Ycf1p, mediate the ATP-dependent cellular export of a variety of organic anions. Ycf1p also appears to transport the endogenous tripeptide glutathione (GSH), whereas no ATP-dependent GSH transport has been detected in Mrp2-containing mammalian plasma membrane vesicles. Because GSH uptake measurements in isolated membrane vesicles are normally carried out in the presence of 5–10 mM dithiothreitol (DTT) to maintain the tripeptide in the reduced form, the present study examined the effects of DTT and other sulfhydryl-reducing agents on Ycf1p- and Mrp2-mediated transport activity. Uptake of S -dinitrophenyl glutathione (DNP-SG), a prototypic substrate of both proteins, was measured in Ycf1p-containing Saccharomyces cerevisiae vacuolar membrane vesicles and in Mrp2-containing rat liver canalicular plasma membrane vesicles. Uptake was inhibited in both vesicle systems in a concentration-dependent manner by DTT, dithioerythritol, and β-mercaptoethanol, with concentrations of 10 mM inhibiting by ∼40%. DTT’s inhibition of DNP-SG transport was noncompetitive. In contrast, ATP-dependent transport of [ 3 H]taurocholate, a substrate for yeast Bat1p and mammalian Bsep bile acid transporters, was not significantly affected by DTT. DTT also inhibited the ATP-dependent uptake of GSH by Ycf1p. As the DTT concentration in incubation solutions containing rat liver canalicular plasma membrane vesicles was gradually decreased, ATP-dependent GSH transport was now detected. These results demonstrate that Ycf1p and Mrp2 are inhibited by concentrations of reducing agents that are normally employed in studies of GSH transport. When this inhibition was partially relieved, ATP-dependent GSH transport was detected in rat liver canalicular plasma membranes, indicating that both Mrp2 and Ycf1p are able to transport GSH by an ATP-dependent mechanism.
Gender differences in lethal violence: Historical trends in the relationship between homicide and suicide rates, 1960–2000

This study examines historical trends in the relationship between homicide and suicide rates and considers the extent to which gender differences exist in that relationship. From the perspective of the integrated homicide-suicide theory, gender differences in the homicidesuicide relationship stem from differences in the manner in which males and females attribute blame and responsibility for negative life events. Consistent with expectations, the data indicate that females engage in less homicide but in more suicide than males. Seemingly unrelated regression techniques were used to further examine gender differences in the relationship between homicide and suicide rates by analyzing U.S. data for 1960 through 2000. The results indicate more gender similarities than differences in that temporal trends in the production and direction of lethal violence for both males and females tend to be associated with similar social and economic factors.
Activation of p44/42 MAPK plays a role in the TBT-induced loss of human natural killer (NK) cell function

Natural killer (NK) cells destroy (lyse) tumor cells, virally infected cells, and antibody-coated cells. Previous studies indicated that exposure to the environmental contaminant tributyltin (TBT) decreases the lytic function of NK cells and activates mitogen-activated protein kinases (MAPK), including p44/42 (Aluoch and Whalen Toxicology 209:263–277, 2005). If activation of p44/42 is required for TBT-induced decreases of lytic function, then activation of p44/42 to similar extents by pharmacological agents such as phorbol 12-myristate 13-acetate (PMA) should mimic to some extent changes induced in NK cells with TBT exposures. NK cells were exposed to PMA concentrations between 0.25 and 10 nM for 10 min, 1 h, and 6 h before determining the lytic function (51Cr release assay) and phosphorylation state of MAPKs (Western blot). A 1-h exposure of NK cells to 5 nM PMA resulted in a loss of lytic function of 47%. Western blot analysis showed that a 1-h exposure to 5 nM PMA caused a sixfold increase in phospho-p44/42 levels. Previous studies showed a fivefold increase in phospho-p44/42 in response to a 1-h exposure to 300 nM TBT. Exposure to 300 nM TBT caused about a 40% decrease in lytic function. This study supports the hypothesis that p44/42 activation (as seen with TBT exposures) can cause a loss of NK-cell lytic function.
HIV-1 envelope glycoproteins induce activation of activated protein-1 in CD4+ T cells.

Activation of CD4 positive T cells is a primary requirement for human immunodeficiency virus (HIV) entry, efficient HIV replication, and progression to AIDS. Utilizing CD4 positive T cell lines and purified T cells from normal individuals, we have demonstrated that native envelope glycoproteins of HIV, gp160, can induce activation of transcription factor, activated protein-1 (AP-1). The stimulatory effects of gp160 are mediated through the CD4 molecule, since treatment of gp160 with soluble CD4-IgG abrogates its activity, and CD4 negative T cell lines fail to be stimulated with gp160. Immunoprecipitation of the gp160-induced nuclear extracts with polyclonal antibodies to Fos and Jun proteins indicates that AP-1 complex is comprised of members of these family of proteins. The gp160-induced AP-1 complex is dependent upon protein tyrosine phosphorylation and is protein synthesis-independent. This stimulation can also be abolished by inhibitors of protein kinase C, but it is unaffected by calcium channel blocker or cyclosporine A. This gp160 treatment adversely affects the functional capabilities of T cells; pretreatment of CD4+ T cells with gp160 for 4 h at 37°C inhibited anti-CD3-induced interleukin-2 secretion. Effects similar to gp160 were seen with anti-CD4 mAb. The aberrant activation of AP-1 by gp160 in CD4 positive T cells could result in up-regulation of cytokines containing AP-1 sites, e.g. interleukin-3 and granulocyte macrophage colony-stimulating factor, and concurrently lead to T cell unresponsiveness by inhibiting interleukin-2 secretion.
Synthesis, Structures, Dynamics, and Ethylene Polymerization Activity of Nickel Complexes Containing an ortho-Methoxy-aryl Diphosphine Ligand

The Ni coordination chemistry of {(2-OMe-4-Me-Ph)2P}2NMe (2, PNP) has been studied. The reaction of (dimethoxyethane)NiBr2 with 2 yields {PNP}NiBr2 (3, 75%). The reaction of Ni(cod)2 (cod = 1,5-cyclooctadiene) with 2 equiv of 2 affords {PNP}2Ni (4, 61%). The reaction of Ni(cod)2 with 1 equiv of 2 yields {PNP}Ni(cod) (5, 90%) via initial formation of 4 (50%), followed by comproportionation with Ni(cod)2. X-ray crystallographic analyses of 3 and 4 show that the methoxy groups do not coordinate to Ni but reveal the presence of weak CH---Ni interactions involving the ortho aryl hydrogens, and weak CH−π interactions involving the OMe hydrogens and the aryl rings. The reaction of 5 with [H(OEt2)2][B(3,5-(CF3)2C6H3)4] or [H(OEt2)2][B(C6F5)4] generates a cationic species formulated as {PNP}Ni(codH)+ (6) on the basis of ESI-MS data. Cation 6, generated in situ from Ni(cod)2/2/[H(OEt2)2][B(3,5-(CF3)2C6H3)4] or 5/[H(OEt2)2][B(C6F5)4], catalyzes ethylene polymerization.
Personalized medicine: applying ‘omics’ to lung fibrosis

Idiopathic pulmonary fibrosis (IPF), the most common fibrotic lung disease, is a chronic disease of unknown etiology with a very high mortality. Personalized medicine focuses on the use of the individual’s molecular and ‘omic’ (i.e., genomic, epigenomic and proteomic) information to direct more efficient and cost-effective strategies for prevention, diagnosis, outcome prediction and treatment of diseases. In this review, we describe the use and promise of applying ‘omic’ technologies to the familial and sporadic forms of IPF as a means to personalize diagnosis and outcome prediction in IPF. The validation and implementation of such approaches will be crucial to personalize IPF patient care, prioritize lung transplant and stratify patients for drug studies, as well as, in the future, predict response to therapies as they emerge.
Short stature, hyperkalemia and acidosis: A defect in renal transport of potassium

Short stature, hyperkalemia, and acidosis: A defect in renal transport of potassium. An eleven-year-old boy presented with short stature, hyperkalemia, and metabolic acidosis. No endocrine cause for a short stature could be demonstrated. Renal function, as assessed by inulin and PAH clearances, concentrating and diluting capacity, and ability to acidify the urine and to excrete net acid, was normal. No defect was detected in adrenal secretion of, or renal responsiveness to, aldosterone. A low renal threshold for bicarbonate was documented which apparently explained the acidosis. However, correction of the acidosis by administration of sodium bicarbonate did not influence the hyperkalemia, making it unlikely that an abnormality in bicarbonate reabsorption was the primary defect. Chlorothiazide induced a fall in serum potassium and a rise in serum bicarbonate to normal levels. During bicarbonate loading the rates of excretion of potassium in urine were consistently below those observed in control subjects. It appeared, therefore, that the patient had a primary abnormality in potassium excretion. The resulting hyperkalemia caused urinary loss of bicarbonate and systemic acidosis. Correction of both the acidosis and hyperkalemia by chronic administration of chlorothiazide and sodium bicarbonate has resulted in resumption of normal growth. Retard de croissance, hyperkalieme et acidose: Un deficit du transport renal du potassium. Un enfant de 11 ans avait un retard de croissance, une hyperkaliemie et une acidose metabolique. Aucune cause endocrine du retard de croissance n'a ete trouvee. La fonction renale, estimee par les clearances de l'inuline et du PAH, la capacite de concentration et de dilution et la capacite d'acidifier l'urine, etait normales. Aucun deficit de la secretion d'aldosterone ou de la reponse renale a l'aldosterone n'a ete mis en evidence. Un seuil renal bas des bicarbonates a ete decouvert, qui explique apparemment l'acidose. Cependant la correction de l'acidose par l'administration de bicarbonate de sodium n'a pas influence l'hyperkaliemie, ce qui rend peu probable que le deficit de la reabsorption de bicarbonate soit la cause de l'ensemble. Le Chlorothiazide a determine une baisse de la kalieme et une augmentation du bicarbonate plasmatique jusqu'a des valeurs normales. Pendant une charge en bicarbonate les debits d'excretion du potassium dans les urines ont ete nettement inferieurs a ceux obtenus chez des sujets temoins. Il apparait donc que le malade a une anomalie primitive de l'excretion de potassium. L'hyperkaliemie qui en est la consequence a determine une perte de bicarbonate dans les urines et une acidose systemique. La correction de l'acidose et de l'hyperkaliemie par l'administration permanente de Chlorothiazide et de bicarbonate de sodium a eu pour resultat une reprise de la croissance normale.
In vivo distribution of 14C radiolabeled soman ((3,3-dimethyl-2-butoxy)-methylphosphorylfluoride) in the central nervous system of the rat

Abstract Radiolabeled 14 C soman, a potent anticholinesterase, was administered to rats at a dose of 0.75 LD 50 (17.3 μg/kg, i.m.). Prior to being quick frozen, the animals were held for 2 min, 32 min or 48 h after dosing. Analysis of autoradiographs taken from cryostat sections through the central nervous system (CNS) showed that at 2 and 32 min radiolabel was primarily distributed in the blood, the choroid plexus and the cerebrospinal fluid (CSF), with several brain nuclei showing small increases in labeling density. At 48 h there was marked accumulation of radiolabel in the caudate and accumbens nuclei compared to all other brain areas. The above results showed little similarity between cholinesterase localization and distribution of radiolabel.
Surface effects in the crystal growth of calcium oxalate monohydrate

The rates of growth of calcium oxalate monohydrate crystals have been measured under conditions of constant supersaturation over a range of concentrations and in the presence of an inhibitor,N,N,N′,N′-ethylenediaminetetra(methylene phosphonic) acid ENTMP. Changes in the measured specific surface area during the growth reactions are consistent with the observed morphologies of the developing crystals. Well-aged seed crystals undergo a rapid crystal lattice perfection during the initial stages of the reaction which is accompanied by a marked decrease in specific surface area. Initial rates of crystallization are therefore markedly dependent upon the surface properties of the seed crystals. These results emphasize the importance of using well-developed pregrown crystal surfaces in designing experimental studies of the characterization of the mechanism of crystal growth. This is especially important when comparing the influence of adsorbing inhibitor molecules on the crystal growth reactions. The adsorption of ENTMP at the crystal surfaces has been investigated by equilibrium and electrophoretic mobility measurements.
Development and Characterization of a Reliable Mouse Model of Colorectal Cancer Metastasis to the Liver

Colorectal cancer (CRC) is the third most frequent cancer and the third leading cause of cancer deaths in the United States (American Cancer Society, Cancer facts and figures 2012, 20121). The major cause of death is metastasis and frequently, the target organ is the liver. Successful metastasis depends on acquired properties in cancer cells that promote invasion and migration, and on multiple interactions between tumors and host-derived cells in the microenvironment. These processes, however, occur asymptomatically, thus, metastasis remains poorly understood and often diagnosed only at the final stage. To facilitate the elucidation of the mechanisms underlying these processes and to identify the molecular regulators, particularly at the early stages, we developed a mouse model of hepatic metastasis of CRC by cecal implantation of a mouse adenocarcinoma cell line in an immune competent host that reliably recapitulates all steps of tumor growth and metastasis within a defined period. By in vivo selection, we isolated cells of varying metastatic potential. The most highly metastatic CT26-FL3 cells produced liver metastasis as early as 10 days after implantation in 90 % of host mice. These cells expressed elevated levels of genes whose products promote invasion, migration, and mobilization of bone marrow derived cells (BMDCs). Mice bearing tumors from CT26-FL3 had elevated serum levels of OPN, MMP9, S100A8, S100A9, SAA3, and VEGFA that promote invasion and BMDC mobilization, and showed enhanced BMDC recruitment to the liver where they established a pre-metastatic niche. This model provides an important platform to characterize metastatic cells and elucidate tumor–host interactions and mechanisms that drive liver metastasis of CRC.
XIV—Modern Moral Philosophy Again: Isolating the Promulgation Problem

In recent years, the virtues have made a dramatic reappearance in Anglophone ethics, and it is safe to credit Elizabeth Anscombe with sparking this interest in her 1958 essay, ‘Modern Moral Philosophy’. In urging a return to Aristotle, Anscombe sets us a task that she does not know how to complete. Her bafflement should set constraints on interpreting the essay. I argue that Anscombe's complaints against neo-Kantianism and social contract were of a piece with her sense that virtue-centred ethics presented serious philosophical challenges. The problem becomes clear when we notice that accounting for just interaction requires that various agents act from a single source. The uniformity cannot rest on an accidental convergence of individuals (hence cannot be built up, person by person). Nor can it be a simple matter of the internalization of social norms. Neo-Aristotelians taking their cue from Anscombe seek that source in our species. But even after we have rejected empiricist accounts of our species, the hard work of explaining how something of virtue belongs to our kind remains to be done.
Physical preseparation for chemistry experiments

The availability of physically preseparated isotopes for chemistry experiment opens up completely new possibilities, especially for chemical investigations of transactinide elements. Many restrictions present in conventional methods that were used very successfully in the past can be overcome by using preseparated isotopes. An overview of experiments that were performed with preseparated isotopes is given. Studies of β-diketonates of group 4 elements are described in some more detail and used as an example to demonstrate the power of the method. Production of preseparated long-lived transactinide isotopes is outlined and, lastly, the new preseparator TASCA which is currently being installed at GSI, Darmstadt, is briefly described.