Operando Identification of the Reversible Skin Layer on Co3O4 as a Three-Dimensional Reaction Zone for Oxygen Evolution.
Co oxides and oxyhydroxides have been studied extensively in the past as promising electrocatalysts for the oxygen evolution reaction (OER) in neutral to alkaline media. Earlier studies showed the formation of an ultrathin CoO x (OH) y skin layer on Co3O4 at potentials above 1.15 V vs reversible hydrogen electrode (RHE), but the precise influence of this skin layer on the OER reactivity is still under debate. We present here a systematic study of epitaxial spinel-type Co3O4 films with defined (111) orientation, prepared on different substrates by electrodeposition or physical vapor deposition. The OER overpotential of these samples may vary up to 120 mV, corresponding to two orders of magnitude differences in current density, which cannot be accounted for by differences in the electrochemically active surface area. We demonstrate by a careful analysis of operando surface X-ray diffraction measurements that these differences are clearly correlated with the average thickness of the skin layer. The OER reactivity increases with the amount of formed skin layer, indicating that the entire three-dimensional skin layer is an OER-active interphase. Furthermore, a scaling relationship between the reaction centers in the skin layer and the OER activity is established. It suggests that two lattice sites are involved in the OER mechanism.


Across-habitat comparison of diazotroph activity in the subarctic.
Nitrogen (N) fixation by N2-fixing bacteria (diazotrophs) is the primary N input to pristine ecosystems like boreal forests and subarctic and arctic tundra. However, the contribution by the various diazotrophs to habitat N2 fixation remains unclear. We present results from in situ assessments of N2 fixation of five diazotroph associations (with a legume, lichen, feather moss, Sphagnum moss and free-living) incorporating the ground cover of the associations in five typical habitats in the subarctic (wet and dry heath, polygon-heath, birch forest, mire). Further, we assessed the importance of soil and air temperature, as well as moisture conditions for N2 fixation. Across the growing season, the legume had the highest total as well as the highest fraction of N2 fixation rates at habitat level in the heaths (>85 % of habitat N2 fixation), whereas the free-living diazotrophs had the highest N2 fixation rates in the polygon heath (56 %), the lichen in the birch forest (87 %) and Sphagnum in the mire (100 %). The feather moss did not contribute more than 15 % to habitat N2 fixation in any of the habitats despite its high ground cover. Moisture content seemed to be a major driver of N2 fixation in the lichen, feather moss and free-living diazotrophs. Our results show that the range of N2 fixers found in pristine habitats contribute differently to habitat N2 fixation and that ground cover of the associates does not necessarily mirror contribution.


Magnolia dealbata seeds extract exert cytotoxic and chemopreventive effects on MDA-MB231 breast cancer cells.
Cancer prevention remains a high priority for the scientific world. Magnolia dealbata Zucc (Magnoliaceae), a Mexican endemic species, is used for the empirical treatment of cancer. To evaluate the cytotoxic and cancer chemopreventive effects of an ethanol extract of Magnolia dealbata seeds (MDE). The cytotoxic effect of MDE, at concentrations ranging from 1 to 200 µg/ml, on human cancer cells and human nontumorigenic cells was evaluated using the MTT assay for 48 h. The apoptotic activities of MDE 25 μg/ml on MDA-MB231 breast cancer cells were evaluated using the TUNEL assay and the detection of caspase 3 using immunofluorescence analysis for 48 h, each. The chemopreventive effect was evaluated by administrating different doses of MDE, between 1 and 50 mg/kg, injected intraperitoneally daily into athymic mice which were implanted with MDA-MB231 cells during 28 days. The growth and weight of tumors were measured. MDE showed cytotoxic effects on MDA-MB231 cells (IC₅₀ = 25 µg/ml) and exerted pro-apoptotic activities as determined by DNA fragmentation in MDA-MB231 cells. MDE 25 µg/ml also induces the activation of caspase 3 in MDA-MB231 cells. These results suggest that Magnolia dealbata may be an optimal source of the bioactive compounds: honokiol (HK) and magnolol (MG). MDE 50 mg/kg i.p. exerted chemopreventive effects by inhibiting the growth of MDA-MB231 tumor by 75% in athymic mice, compared to the control group. MDE exerts cytotoxic, apoptotic and chemopreventive activities on MDA-MB231 human cancer cells.


Questions About Quantifiers: Symbolic and Nonsymbolic Quantity Processing by the Brain.
One approach to understanding how the human cognitive system stores and operates with quantifiers such as "some," "many," and "all" is to investigate their interaction with the cognitive mechanisms for estimating and comparing quantities from perceptual input (i.e., nonsymbolic quantities). While a potential link between quantifier processing and nonsymbolic quantity processing has been considered in the past, it has never been discussed extensively. Simultaneously, there is a long line of research within the field of numerical cognition on the relationship between processing exact number symbols (such as "3" or "three") and nonsymbolic quantity. This accumulated knowledge can potentially be harvested for research on quantifiers since quantifiers and number symbols are two different ways of referring to quantity information symbolically. The goal of the present review is to survey the research on the relationship between quantifiers and nonsymbolic quantity processing mechanisms and provide a set of research directions and specific questions for the investigation of quantifier processing.


Percutaneous renal biopsy.
Percutaneous renal biopsy (PRB) is an integral part of the clinical practice of nephrology. It is essential in the diagnosis of glomerular, vascular, and tubulointerstitial diseases of the kidney, providing information that is invaluable in prognosis and patient management. The use of real-time ultrasound and automated biopsy needles has simplified and improved the success and safety of this procedure. In the recent past, we have seen a shift of the PRB from nephrologists to radiologists and this has raised appropriate concern that loss of this procedure may undermine the nephrologist's status as a subspecialist. We must continue to properly train young nephrologists in the proper technique and value of performing renal biopsy procedures or we stand to lose control of a procedure that was an integral part of the development of our subspecialty.


Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms.
We sought to determine the effects of cardiac resynchronization therapy (CRT) in New York Heart Association (NYHA) functional class II heart failure (HF) and NYHA functional class I (American College of Cardiology/American Heart Association stage C) patients with previous HF symptoms. Cardiac resynchronization therapy improves left ventricular (LV) structure and function and clinical outcomes in NYHA functional class III and IV HF with prolonged QRS. Six hundred ten patients with NYHA functional class I or II heart failure with a QRS > or =120 ms and a LV ejection fraction < or =40% received a CRT device (+/-defibrillator) and were randomly assigned to active CRT (CRT-ON; n = 419) or control (CRT-OFF; n = 191) for 12 months. The primary end point was the HF clinical composite response, which scores patients as improved, unchanged, or worsened. The prospectively powered secondary end point was LV end-systolic volume index. Hospitalization for worsening HF was evaluated in a prospective secondary analysis of health care use. The HF clinical composite response end point, which compared only the percent worsened, indicated 16% worsened in CRT-ON compared with 21% in CRT-OFF (p = 0.10). Patients assigned to CRT-ON experienced a greater improvement in LV end-systolic volume index (-18.4 +/- 29.5 ml/m2 vs. -1.3 +/- 23.4 ml/m2, p < 0.0001) and other measures of LV remodeling. Time-to-first HF hospitalization was significantly delayed in CRT-ON (hazard ratio: 0.47, p = 0.03). The REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) trial demonstrates that CRT, in combination with optimal medical therapy (+/-defibrillator), reduces the risk for heart failure hospitalization and improves ventricular structure and function in NYHA functional class II and NYHA functional class I (American College of Cardiology/American Heart Association stage C) patients with previous HF symptoms. (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [REVERSE]; NCT00271154).


Podocytes undergo phenotypic changes and express macrophagic-associated markers in idiopathic collapsing glomerulopathy.
Collapsing glomerulopathy (CG), a severe form of focal segmental glomerulosclerosis (FSG), is characterized by tuft retraction and consolidation in numerous glomeruli and changes in podocyte morphology and topography. Other glomeruli are less affected. Collapsing glomerulopathy is also characterized by tubulointerstitial atrophy and fibrosis. The pathophysiology of the glomerular and tubulointerstitial lesions is poorly understood. We studied renal tissue of five Black and three White patients, all human immuno-deficiency virus (HIV) negative, with nephrotic syndrome, renal failure, and histological evidence of CG. Immunohistochemistry identified normal podocyte phenotypes by podocalyxin, vimentin and complement receptor 1 (CR1) labeling. Three monoclonal antibodies were used to further characterize podocyte epitopes: anti-CD68 clone KP1, anti-CD68 clone PG-M1 and anti-M130 clone M18 (Ber-MAC3). Light microscopy of collapsed glomeruli showed podocyte swelling, vacuolization, multinucleation, "cobblestone-like" alignment around the glomerular tuft, and pseudo-crescent formation in Bowman's space. In collapsed glomeruli, podocalyxin, vimentin and CR1 labeling tagged both normal and vacuolated podocytes still attached to the GBM, but labeling was not found in cobblestone-like podocytes or in podocytes detached from the GBM. Conversely, numerous podocytes undergoing detachment and shedding into Bowman's space expressed macrophagic-associated epitopes. Cells with macrophagic-associated epitopes clumped in cystically dilated tubules and were aligned in tubules of smaller caliber. Their appearance was that of viable cells. There was no morphologic indication that these cells expressing macrophage-associated antigens originated from outside the glomeruli or outside the tubules. We conclude that in CG podocytes detach from the GBM, lose their normal podocytic phenotype and acquire macrophage differentiation antigens. The presence of cells with such antigens in tubular lumens suggests that detached metaplastic podocytes progress along the tubule or, alternatively, that CG tubular cells also undergo metaplastic changes into macrophage-like cells.


Timing is everything: Onset timing moderates the crossmodal influence of background sound on taste perception.
Recent evidence demonstrates that the presentation of crossmodally corresponding auditory stimuli can modulate the taste and hedonic evaluation of various foods (an effect often called "sonic seasoning"). To further understand the mechanism underpinning such crossmodal effects, the time at which a soundtrack was presented relative to tasting was manipulated in a series of experiments. Participants heard two soundtracks corresponding to sweet and bitter tastes either exclusively during or after chocolate tasting (Experiment 1) or during and before chocolate tasting (Experiment 2). The results revealed that the soundtracks affected chocolate taste ratings only if they were presented before or during tasting but not if they were heard after tasting. Moreover, participants' individual soundtrack-taste association mediated the strength of the sonic seasoning effect. These results therefore imply that the modulatory effect of sound on taste was not driven by retrospective interpretation of the taste experience, but by mechanisms such as priming and crossmodal association. Taken together, these studies demonstrate the complex interplay of cognitive mechanisms that likely underlie sonic seasoning effects. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Aortic input impedance in heart failure: comparison with normal subjects and its changes during vasodilator therapy.
This study was aimed at the evaluation of aortic impedance in patients with congestive heart failure. Aortic impedance (simultaneous measurements of aortic pressure and blood flow), mean (Wm) and pulsatile (Wp) powers were compared in 11 normal subjects and in 12 patients with heart failure. Pulse wave velocity (C: modified Moëns-Korteweg equation, simultaneous measurements of aortic pressure and radius) was determined under control conditions in all normal subjects and in 7 patients with heart failure. Impedance curves in patients with heart failure were characterized by increased values of the impedance modulus at 0 Hz (peripheral resistance) and at low frequencies. The characteristic impedance, C, and phase were not different from normal subjects. In six patients with heart failure, impedance curves were studied during nitroprusside infusion. During the infusion of the vasodilator, the impedance modulus at 0 Hz and at low frequencies decreased. The characteristic impedance was unchanged. The zero intercept of the phase was shifted towards lower frequencies. These results show that the changes in impedance curves in patients with heart failure are due to greater peripheral resistance and wave reflection. During nitroprusside infusion the stroke volume increased and the aortic blood flow became more pulsatile (greater values of low frequency components). This modification accounts for the increased values of Wm and Wp, and is related to decreased peripheral resistance and wave reflection.


A Case of Sclerosing Polycystic Adenoma of the Parotid Gland.
Sclerosing polycystic adenoma (SPA) is a rare salivary gland tumor with about 100 cases reported in the literature. We describe a case of SPA in the parotid gland and review the diagnostic tools used for identifying SPA. A 24-year-old male with a two-year history of right-sided face mass, initially thought to be pleomorphic adenoma of the parotid gland after fine needle aspiration (FNA). Following superficial parotidectomy, histologic features were consistent with SPA. This case illustrates the challenge of pre-operative assessment for SPA. Recent study has suggested SPA is a neoplasm and definitive treatment is surgical excision.


Interactive effects of landscape history and current management on dispersal trait diversity in grassland plant communities.
Plant communities and their ecosystem functions are expected to be more resilient to future habitat fragmentation and deterioration if the species comprising the communities have a wide range of dispersal and persistence strategies. However, the extent to which the diversity of dispersal and persistence traits in plant communities is determined by the current and historical characteristics of sites and their surrounding landscape has yet to be explored.Using quantitative information on long-distance seed dispersal potential by wind and animals (dispersal in space) and on species' persistence/longevity (dispersal in time), we (i) compared levels of dispersal and persistence trait diversity (functional richness, FRic, and functional divergence, FDiv) in seminatural grassland plant communities with those expected by chance, and (ii) quantified the extent to which trait diversity was explained by current and historical landscape structure and local management history - taking into account spatial and phylogenetic autocorrel.Null model analysis revealed that more grassland communities than expected had a level of trait diversity that was lower or higher than predicted, given the level of species richness. Both the range (FRic) and divergence (FDiv) of dispersal and persistence trait values increased with grassland age. FDiv was mainly explained by the interaction between current grazing intensity and the amount of grassland habitat in the surrounding landscape in 1938.Synthesis. The study suggests that the variability of dispersal and persistence traits in grassland plant communities is driven by deterministic assembly processes, with both history and current management (and their interactions), playing a major role as determinants of trait diversity. While a long continuity of grazing management is likely to have promoted the diversity of dispersal and persistence traits in present-day grasslands, communities in sites that are well grazed at the present day, and were also surrounded by large amounts of grassland in the past, showed the highest diversity of dispersal and persistence strategies. Our results indicate that the historical context of a site within a landscape will influence the extent to which current grazing management is able to maintain a diversity of dispersal and persistence strategies and buffer communities (and their associated functions) against continuing habitat fragmentation.


Effect of obesity on platelet reactivity and response to low-dose aspirin.
Insufficient platelet function suppression by aspirin is a predictor of cardiovascular events in high-risk patients. The authors assessed the impact of obesity on platelet responsiveness before and after 2 weeks of aspirin 81 mg/d in 2014 people. Obese individuals had greater baseline platelet reactivity. Comparing obese and nonobese individuals after aspirin therapy, results for aggregometry to collagen were 6.7 vs 6.1 ohms, P=.008; aggregometry to adenosine diphosphate were 13.1 vs 11.8 ohms,P<.0001; aggregometry to arachidonic acid (AA) were 4.9% vs 8.3% nonzero aggregation, P=.002; urinary excretion of 11-dehydro-thromboxane B2 (Tx-M) were 4.9% vs 8.3% nonzero aggregation, P=.002; and aspirin resistance were 26.% vs 20.5%, P=.002; respectively. These remained significantly different for AA aggregation and Tx-M excretion after adjustment for covariates. Obese individuals have greater native platelet reactivity and retain greater reactivity after suppression by aspirin.


Histopathologic study of temporal bone and eustachian tube in oculoauriculovertebral spectrum.
Bilateral temporal bone specimens from a 21-month-old girl and a left temporal bone-eustachian tube (ET) specimen from a full-term female newborn, both with oculoauriculovertebral spectrum, were studied histopathologically. The external and middle ears demonstrated severe anomalies, similar to those of previous reports describing the histopathologic findings of this syndrome. In addition, despite having a normal auricle, the 21-month-old child had bilateral hypoplastic cochleas as seen in Mondini dysplasia. The newborn had several anomalies of the ET, including a widely opened cartilaginous portion of the ET lumen and absence of the lateral lamina of the ET cartilage. We discuss the implications of the observed anomalies with regard to developmental and clinical issues.


Global conformation of a self-cleaving hammerhead RNA.
Phylogenetic and biochemical studies of RNA have provided a wealth of information regarding secondary structure; however, knowledge of tertiary structure has been more difficult to obtain. In the current work, electrophoretic and hydrodynamic measurements have yielded the global conformations of a self-cleaving "hammerhead" RNA, both prior to and following self-cleavage. The pre- and post-cleavage structures appear to have nearly identical conformations in which the three helices assume a roughly coplanar arrangement with well-defined interhelix angles. Following self-cleavage, one of the three helix stems (stem I) undergoes a slight (< 10 degrees) realignment, although the relative positions of the other two stems remain unchanged. Extension of stem III from (nominally) three base pairs to nine base pairs, known to dramatically enhance the rate of self-cleavage, results in a substantial (approximately 70 degrees) realignment of stems I and II. The current study represents an approach for studying other nonhelical elements in RNA.


Direct methods for characterizing high-intensity focused ultrasound transducers using acoustic streaming.
Two techniques are presented for noninvasively determining the intensity field of high-intensity focused ultrasound transducers in a liquid medium. The techniques are based upon the streaming velocity induced in the liquid by the absorbed ultrasound beam. The approaches are similar to an iterative streaming method previously reported, but the present approaches are "direct:" The differential operations of the Navier-Stokes equations are performed directly upon the experimentally measured streaming velocity, rather than through an iterative approach that minimizes the difference between a theoretical estimate of the streaming velocity and the one measured experimentally. As such, the direct methods are much faster than the iterative technique. The price paid for the increase in speed is smaller spatial coverage; the direct techniques are applicable only where accurate streaming velocity is available. Comparisons performed in the range 100-1000 W/cm(2) focal intensity showed differences between the direct methods and the iterative streaming technique to be less than 20%. Similar differences were observed in low-power comparisons with hydrophone measurements.


Pseudo optimization of radiotherapy treatment planning.
A chain consisting of three computer programs has been developed for treatment planning of external beam radiotherapy without manual intervention. Apart from the data necessary to identify the patient, the institute, etc., the input consists only of the anatomical information indicated on an outline sheet. Firstly, combinations of incidence directions for a two or three-beam set-up are judged by the first program. Then a limited number of these combinations is selected by this program. For every beam of each selected combination a set of wedges and weights is calculated. Next the dose distributions belonging to each combination with wedges and weights are judged by the second program. Finally, the isodose pattern of the dose distribution judged the best is determined by the third program. The judgement of incidence directions is done by coarse score functions corresponding to a set of criteria. The judgement of dose distribution is done by detailed score functions corresponding to another set of criteria. These criteria with their score functions are treated in some detail. The use of the programs in the clinic is discusses and results are shown.


UV-B induced differential transcription of psbD genes encoding the D2 protein of Photosystem II in the cyanobacterium Synechocystis 6803.
UV-B irradiation of intact Synechocystis sp. PCC 6803 cells results in the loss of Photosystem II activity, which can be repaired via de novo synthesis of the D1 and D2 reaction center subunits. A key step in the repair process is the differential transcription of the psbA2 and psbA3 genes, coding for identical D1 polypeptides [Máté et al. (1998) J Biol Chem 273: 17439-17444]. In the present work, we investigated for the first time the effect of UV-B irradiation on the transcription of the psbD1 and psbD2 genes encoding identical D2 polypeptides. By using gene-specific S1 nuclease protection assay we showed differential UV-B induced transcription of the two psbD genes: the level of psbD1 mRNA was increased 1.5-2 fold, whereas the accumulation of psbD2 mRNA was 5-7 fold. The induction of psbD2 transcript accumulation by low intensity light was specific for the UV-B range. UV-A emission from the applied UV source, as well as 100 muE m(-2) s(-1) white light had negligible effect. Increase in the psbD2 mRNA level was observed at very low UV-B intensities, which did not cause damage to the function and protein structure of PS II. Expression patterns of chimeric genes containing the promoter regions of the psbD1, psbD2 genes fused to the firefly luciferase (luc) reporter gene showed similar induction as observed for the endogenous psbD genes. Our findings demonstrate that UV-B radiation induces differential expression of the of the psbD1 and psbD2 genes. We propose that the primarily expressed psbD2 serves as a UV stress gene and participates in a rapid defense response against UV-B stress. This effect is regulated, at least partially, at the level of transcription.


[Local shRNA modulation of phosphatidylinositol 3-kinase signaling pathway reduces intimal hyperplasia in vein grafts: experiment with rats].
To investigate whether knockdown Pik3cb p110beta subunit by shRNA in autologous vein grafts can reduce intimal hyperplasia. 180 adult SD rats underwent carotid artery bypass graft surgery by using the autologous branch of jugular vein, and they were randomly divided into 6 equal groups: Group A (with the jugular vein grafts treated with 25% Pluronic F-127 only), Group B (with the graft treated with the plasmid encoding shRNA targeting Pik3cb p110beta subunit, pU6-Pik3cb-shRNA-1), Group C (with the graft treated with the plasmid encoding shRNA targeting Pik3cb p110beta subunit, pU6-Pik3cb-shRNA-2), Group D (with the graft treated with the half pU6-Pik3cb-shRNA-1 and pU6-Pik3cb-shRNA-2), and Group E (with the graft treated with the pGenesil-1 scramble shRNA), and Group F (with the jugular vein grafts treated with wortmannin). Specimens of jugular vein graft were harvested 1, 3, 7, 14, and 28 days after surgery to assess the neointimal hyperplasia. Another 18 rats were randomly divided into 6 equal groups as mentioned above to be used in a parallel experiment: 72 h after surgery specimens of jugular vein graft were harvested to undergo fluorescence quantitative real-time PCR and Western blotting to detect the mRNA expression of P13K p110beta subunit and the protein expression of phosphorylated Akt - phospho-Akt (Thr 308) and phospho-Akt (Ser473)-, and mTOR (Ser 2448). And another 9 rats received jugular vein grafts treated with the pGenesil-1 scramble shRNA, and on the postoperative days 1, 2, and 3 respectively 3 rats were killed to undergo fluorescence staining to detect the transfection efficacy. The transfection rate of the plasmid pGenesil-1 was 60% in the vascular smooth muscle cells and 90% in the endothelial cells. The thickness of tunica intima 28 days after the surgery of the pU6-Pik3cb-shRNA-1, pU6-Pik3cb-shRNA-2, 1/2 (shRNA1 + shRNA2), and wortmannin groups were (34.6 +/- 2.7) microm, (39.4 +/- 2.5) microm, (36.7 +/- 2.9) microm, and (40.6 +/- 3.1) microm respectively, all significantly lower than that of the control group (61.8 +/- 4.3 microm, P < 0.05). The expression levels of phospho-Akt (Thr 308), phospho-Akt (Ser 473), and mTOR of the shRNA intervention and wortmannin groups were all down-regulated. Knockdown of Pik3cb in interposition carotid artery branch of jugular vein grafts reduces intimal hyperplasia with the possible mechanism of downregulation of phosphatidylinositol 3-kinase signaling through Akt, with resultant decreases in VASC growth and survival. Modulation of the phosphatidylinositol 3-kinase pathway through knockdown Pik3cb may represent a novel therapy to prevent vein graft intimal hyperplasia after bypass grafting.


HS-142-1, a Novel Non-peptide Antagonist for Atrial Natriuretic Peptide Receptor, Selectively Inhibits Particulate Guanylyl Cyclase and Lowers Cyclic GMP in LLC-PK1 Cells.
HS-142-1, a novel atrial natriuretic peptide (ANP) antagonist isolated from the culture broth of Aureobasidium sp., selectively inhibits ANP-induced cyclic GMP accumulation in porcine kidney epithelial LLC-PK1 cells. At concentrations from 0.1 to 100 μg/ml (= 2.5 × 10(-8) - 2.5 × 10(-5) M, given the mean molecular weight is 4, 000), HS-142-1 prevents intracellular cyclic GMP accumulation initiated by 10(-8) M rat ANP in a dose-dependent manner, but not cyclic GMP accumulation produced by 10(-5) M sodium nitroprusside. HS-142-1 alone has no effects on the basal level of cyclic GMP seen in the absence of ANP. No change of intracellular cyclic AMP was observed upon the treatment of the cells with HS-142-1. Further, the selectivity of HS-142-1 for the guanylyl cyclase-linked receptor was confirmed by affinity labeling studies with bovine adrenocortical membranes. HS-142-1 specifically abolished the labeling of the guanylyl cyclase-linked 135-kDa band in a dose-dependent manner, but not the labeling of the 60-kDa band not coupled to the guanylyl cyclase. These results show that HS-142-1 selectively inhibits ANP-mediated accumulation of cyclic GMP in LLC-PK1 cells through interacting with guanylyl cyclase-linked receptors.


N-Acetylcysteine Use in Non-Acetaminophen-Induced Acute Liver Failure.
This article will review the available evidence related to the management of non-acetaminophen induced acute liver failure with N-acetylcysteine. Randomized controlled trials and a meta-analysis were included in this review. The efficacy of N-acetylcysteine in the treatment of acute liver failure from causes other than acetaminophen toxicity was evaluated. The efficacy of N-acetylcysteine in non-acetaminophen-induced acute liver failure is limited to specific patient populations. Patients classified as Coma Grade I or II are more likely to benefit from the use of this agent. The use of N-acetylcysteine is associated with improved transplant-free survival, not overall survival, in adults. N-Acetylcysteine does not improve the overall survival of patients with non-acetaminophen-induced acute liver failure but may be beneficial in those patients with Coma Grades I-II. Liver transplantation remains the only definitive therapy in advanced disease.


What Happens in the Thymus Does Not Stay in the Thymus: How T Cells Recycle the CD4+-CD8+ Lineage Commitment Transcriptional Circuitry To Control Their Function.
MHC-restricted CD4(+) and CD8(+) T cells are at the core of most adaptive immune responses. Although these cells carry distinct functions, they arise from a common precursor during thymic differentiation, in a developmental sequence that matches CD4 and CD8 expression and functional potential with MHC restriction. Although the transcriptional control of CD4(+)-CD8(+) lineage choice in the thymus is now better understood, less was known about what maintains the CD4(+) and CD8(+) lineage integrity of mature T cells. In this review, we discuss the mechanisms that establish in the thymus, and maintain in postthymic cells, the separation of these lineages. We focus on recent studies that address the mechanisms of epigenetic control of Cd4 expression and emphasize how maintaining a transcriptional circuitry nucleated around Thpok and Runx proteins, the key architects of CD4(+)-CD8(+) lineage commitment in the thymus, is critical for CD4(+) T cell helper functions.


[Fatigue in hematological patients treated with allogeneic stem cell transplantation].
Fatigue and poor physical function are well-known symptoms in cancer patients. Allogeneic stem cell transplantation is an established treatment for certain cancer diagnoses, especially leukaemia. The aim of this study was to investigate physical function and fatigue in relation to allogeneic stem cell transplantation. 21 patients awaiting allogeneic stem cell transplantation were included in a descriptive follow-up design. Fatigue and physical function was assessed by a standardized test programme consisting of a stair test, a test of maximum oxygen uptake and questionnaires on physical activity and fatigue prior to transplantation as well as 3 and 6 months after transplantation. 10 men and 11 women were included. The mean age was 39 years (19-60). Prior to transplantation patients had a low maximum oxygen uptake and reported more fatigue than the Danish general population. Physical fatigue rather than mental fatigue was pronounced both before and after transplantation. No significant changes in the parameters were found from before transplant to 6 months after transplant. The results indicate that prior to transplantation patients have poor physical function and increased physical fatigue. The symptoms seem to persist 6 months after transplantation. This could indicate a need for an extensive rehabilitation programme following transplantation.


Rehabilitation of emergent awareness of errors post traumatic brain injury: A pilot intervention.
Impaired awareness of errors is common following traumatic brain injury (TBI) and can be a barrier to successful rehabilitation. The objective of this study was to develop and evaluate a computer-based intervention programme aimed at improving error awareness in individuals with TBI. A further aim was to explore its effects on metacognitive awareness and variability of performance. Participants were 11 individuals with TBI and impaired error awareness who performed a sustained attention task twice-weekly for four weeks. The intervention consisted of audio-visual feedback-on-errors during the sustained attention task. Six participants received audio-visual feedback-on-error, five did not receive feedback. Emergent and metacognitive awareness were measured pre- and post-intervention. Between-groups comparisons of emergent awareness from pre- to post-intervention showed that audio-visual feedback-on-error improved emergent awareness compared to no feedback-on-error. Some changes in metacognitive awareness of executive behaviours as a result of feedback were observed. Audio-visual feedback-on-error improved emergent awareness in individuals with TBI following a four-week/eight-session intervention. This improvement was not observed in the no-feedback group. This pilot intervention is not a stand-alone treatment but it has potential to be usefully incorporated into cognitive or clinical rehabilitation programmes to improve emergent awareness.


Psychosocial morbidity associated with patterns of family functioning in palliative care: baseline data from the Family Focused Grief Therapy controlled trial.
Family Focused Grief Therapy (FFGT) is a new model of brief intervention, which is commenced during palliative care for those families shown to be at high risk of poor adaptation, and continued preventively into bereavement with the aim of improving family functioning and reducing the morbid consequences of grief. In this paper, baseline data on 81 families (363 individuals) selected by screening from a palliative care population are explored to confirm our previously reported observation that high levels of psychosocial morbidity are positively associated with worsening family dysfunction. The Family Relationships Index (FRI) was used for screening and the Family Assessment Device (FAD) as an independent family outcome measure. The Beck Depression Inventory (BDI), Brief Symptom Inventory (BSI) and Social Adjustment Scale (SAS) were the psychosocial measures. Families were classified according to their functioning based on the FRI. To allow for correlated family data, statistical analyses employed the generalized estimating equation (GEE) method, controlling for gender and depression (BDI). Screening of 257 families (701 individuals) revealed 74 (29%) well-functioning families and 183 (71%) at some risk of morbid outcome. Of the latter, 81 (44%) gave informed consent to enter a randomized controlled trial of FFGT. Patients had a mean age of 57 years, 51% were male and they suffered from cancer, with a median length of illness from diagnosis to death of 25 months. In accordance with the FFGT model, their family types were identified as Intermediate 51%, Sullen 26% and Hostile 23%. These were significantly associated with steadily increasing levels of distress (BSI) and poor social adjustment (SAS). The FAD confirmed the concurrent accuracy of the FRI. As significantly greater levels of psychosocial morbidity were present in families whose functioning as a group was poorer, support was generated for a clinical approach that screens for families rather than individuals at high risk. The predictive validity of the FRI as a screening measure was confirmed. Overall, these baseline data point to the importance of a family-centred model of care.


Role of the chemokine receptors CXCR3 and CCR4 in human pulmonary fibrosis.
The chemokine receptors CXCR3 and CCR4 have recently been described as playing a pivotal role in the mouse model of bleomycin-induced fibrosis. To evaluate the role of these receptors in human idiopathic pulmonary fibrosis (IPF). We studied 57 patients: 18 with IPF, 17 with non-IPF (nIPF), 12 with sarcoidosis, and 10 healthy control subjects. We evaluated the expression of CXCR3 and CCR4 in blood and bronchoalveolar lavage (BAL) T lymphocytes by flow cytometry and the chemokine CXCL10, CXCL11 and CCL17 BAL concentration by singular immunoassay. Patients with IPF had a significantly lower CXCR3 and a higher CCR4 expression on BAL CD4 T cells compared with the other groups. Among patients with IPF, those treated with corticosteroids exhibited higher CXCR3 and lower CCR4 expression compared with untreated patients. CXCR3 expression correlated with BAL lymphocytes and CCR4 with BAL neutrophils and eosinophils. CXCL10 levels correlated with the expression of CXCR3 on BAL CD4 cells. CXCL11 was undetectable in almost all patients, whereas CCL17 was primarily detectable in patients with IPF. The percentage of BAL CCR4CD4 cells negatively correlated with DL(CO). The changes in the total lung capacity, VC, and of the alveolar-arterial PO2 gradient in patients with IPF and those with nIPF 6 to 12 mo after the first evaluation were associated with CD4CXCR3 percentage on BAL cells. We found an imbalance in CXCR3/CCR4 expression on BAL CD4 lymphocytes and reduced CXCL10 BAL levels in patients with IPF, suggesting a pivotal role of these molecules in IPF.


Oncostatin M induces angiogenesis and cartilage degradation in rheumatoid arthritis synovial tissue and human cartilage cocultures.
To investigate the role of oncostatin M (OSM) in cell adhesion, angiogenesis, and matrix degradation in rheumatoid arthritis (RA) synovial tissue and normal human cartilage. Human dermal microvascular endothelial cell (HDMEC) and RA synovial fibroblast (RASF) proliferation and intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression were assessed by a bromodeoxyuridine proliferation assay and flow cytometry. HDMEC tubule formation and migration were assessed by Matrigel culture and migration assay. Production of matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in RA synovial explants, and proteoglycan/glycosaminoglycan (GAG) release, vascular endothelial growth factor (VEGF), and angiopoietin 2 production from RASF/normal cartilage cocultures were assessed by enzyme-linked immunosorbent assay and immunohistology. HDMEC/RASF proliferation was induced by OSM and interleukin-1beta (IL-1beta), alone and in combination. OSM enhanced cell surface expression of ICAM-1, but not VCAM-1, on endothelial cells and RASFs. OSM increased endothelial cell tubule formation and migration. In RA synovial explants, OSM induced production of MMP-1 and TIMP-1. When OSM was combined with IL-1beta, however, the MMP-1:TIMP-1 ratio was significantly increased. OSM potentiated IL-1beta-induced MMP-1 and MMP-13 expression in normal human cartilage/RASF cocultures, resulting in a significant increase in the MMP:TIMP ratio. In OSM/IL-1beta- stimulated cocultures, cartilage sections demonstrated significant proteoglycan depletion that was paralleled by a significant increase in GAG release in supernatants. Finally, compared with either cytokine alone, the combination of OSM and IL-1beta significantly induced VEGF production in RASF/cartilage cocultures. These data suggest that OSM promotes angiogenesis and endothelial cell migration and potentiates the effects of IL-1beta in promoting extracellular matrix turnover and human cartilage degradation. Furthermore, the induction of VEGF in cocultures supports the hypothesis of a link between angiogenesis and cartilage degradation.


Three-dimensional Tissue Engineered Aligned Astrocyte Networks to Recapitulate Developmental Mechanisms and Facilitate Nervous System Regeneration.
Neurotrauma and neurodegenerative disease often result in lasting neurological deficits due to the limited capacity of the central nervous system (CNS) to replace lost neurons and regenerate axonal pathways. However, during nervous system development, neuronal migration and axonal extension often occur along pathways formed by other cells, referred to as "living scaffolds". Seeking to emulate these mechanisms and to design a strategy that circumvents the inhibitory environment of the CNS, this manuscript presents a protocol to fabricate tissue engineered astrocyte-based "living scaffolds". To create these constructs, we employed a novel biomaterial encasement scheme to induce astrocytes to self-assemble into dense three-dimensional bundles of bipolar longitudinally-aligned somata and processes. First, hollow hydrogel micro-columns were assembled, and the inner lumen was coated with collagen extracellular-matrix. Dissociated cerebral cortical astrocytes were then delivered into the lumen of the cylindrical micro-column and, at a critical inner diameter of <350 µm, spontaneously self-aligned and contracted to produce long fiber-like cables consisting of dense bundles of astrocyte processes and collagen fibrils measuring <150 µm in diameter yet extending several cm in length. These engineered living scaffolds exhibited >97% cell viability and were virtually exclusively comprised of astrocytes expressing a combination of the intermediate filament proteins glial-fibrillary acidic protein (GFAP), vimentin, and nestin. These aligned astrocyte networks were found to provide a permissive substrate for neuronal attachment and aligned neurite extension. Moreover, these constructs maintain integrity and alignment when extracted from the hydrogel encasement, making them suitable for CNS implantation. These preformed constructs structurally emulate key cytoarchitectural elements of naturally occurring glial-based "living scaffolds" in vivo. As such, these engineered living scaffolds may serve as test-beds to study neurodevelopmental mechanisms in vitro or facilitate neuroregeneration by directing neuronal migration and/or axonal pathfinding following CNS degeneration in vivo.


The historical development of juvenile mortality and adult longevity in zoo-kept carnivores.
Zoos need to evaluate their aim of high husbandry standards. One way of approaching this is to use the demographic data that has been collected by participating zoos for decades, assessing historical change over time to identify the presence or absence of progress. Using the example of carnivores, with data covering seven decades (1950-2019), 13 carnivore families, and 95 species, we show that juvenile mortality has decreased, and adult longevity increased, over this interval. While no reason for complacency, the results indicate that the commitment of zoos to continuously improve is having measurable consequences.


Immune-inflammatory activation after a single laparotomy in a rat model: effect of adenosine, lidocaine and Mg2+ infusion to dampen the stress response.
Our aim was to examine the effect of low-volume 0.9% NaCl adenosine, lidocaine and Mg2+ (ALM) 'drip' on early immune-inflammatory activation after a single laparotomy with no further manipulation. Male Sprague-Dawley rats were anesthetized and randomly assigned to one of the groups, baseline, 1 h infusion 0.9% NaCl ± ALM and metrics, 1 h infusion and 6-h metrics, and 6 h continuous infusion and metrics. Complete blood count, acid-base balance, systemic levels of IL-6 and IL-10, and coagulation status were measured. After 1 h, there was a disproportionate increase in circulating neutrophils between saline and ALM groups despite an identical 45% fall in lymphocytes. Disproportionate increases also occurred in platelet counts 1 h after surgery, and saline controls had increased respiratory alkalosis at 6 h with higher lactate. Systemic inflammation was also evident after 1 h in both groups (plasma IL-6 increase) and was amplified in saline-controls after 6 h. The ALM group increased anti-inflammatory cytokine IL-10. Surgery was not associated with acute coagulopathy; however, there were significant reductions in fibrinolysis. Following a single laparotomy, ALM infusion appeared to reduce stress-induced release of neutrophils and platelets into the circulation, and reduced acid-base disturbance. After 1 h, both groups had similar IL-6 levels, but ALM animals had increased IL-10, indicating improved inflammatory balance. The uncoupling of inflammation and coagulation activation but not fibrinolysis may offer a unique opportunity to investigate differential activation of innate immunity in response to sterile injury in this model.


Autocrine-paracrine factors and vascular remodeling in hypertension.
Despite decades of intense research, the etiology of essential hypertension remains one of the major enigmas of clinical medicine. On the basis of recent advances in the vascular biology of hypertension two important paradigms have emerged that offer promise in solving this enigma: 1) the concept of vascular remodeling, and 2) the concept of vascular autocrine-paracrine factors as determinants of vascular resistance. These concepts are interrelated because vascular autocrine-paracrine factors appear to mediate the process of vascular remodeling. This review focuses on these two emerging paradigms and their potential importance in elucidating the pathogenic mechanisms of hypertension.


Hyperuricemic renal failure in nonhematologic solid tumors: a case report and review of the literature.
Tumor lysis syndrome (TLS) is an oncologic emergency that is caused by massive tumor cell lysis. It is commonly associated with hematological cancers like leukemia and lymphoma and uncommonly with solid nonhematologic tumors as well. However, spontaneous tumor lysis syndrome (STLS) without any cytotoxic chemotherapy rarely occurs in solid tumors. We describe a case of STLS in a metastatic adenocarcinoma of unknown primary and review the literature of STLS in solid non-hematologic tumors to identify various risk factors for pathogenesis of this entity.


Glycan/Protein-Stable Isotope Labeling in Cell Culture for Enabling Concurrent Quantitative Glycomics/Proteomics/Glycoproteomics.
The complexity and heterogeneity of protein glycosylation present an analytical challenge to the studies of characterization and quantitation. Various LC-MS-based quantitation strategies have emerged in recent decades. Metabolic stable isotope labeling has been developed to enhance the accurate LC/MS-based quantitation between different cell lines. Stable isotope labeling by amino acids in a cell culture (SILAC) is the most widely used metabolic labeling method in proteomic analysis. However, it can only label the peptide backbone and is thus limited in glycomic studies. Here, we present a metabolic isotope labeling strategy, named GlyProSILC (Glycan Protein Stable Isotope Labeling in Cell Culture), that can label both the glycan motif and peptide backbone from the same batch of cells. It was performed by feeding cells with a heavy medium containing amide-15N-glutamine, 13C6-arginine (Arg6), and 13C6-15N2-lysine (Lys8). No significant change of cell line metabolism after GlyProSILC labeling was observed based on transcriptomic, glycomic, and proteomic data. The labeling conditions, labeling efficiency, and quantitation accuracy were investigated. After quantitation correction, we simultaneously quantified 62 N-glycans, 574 proteins, and 344 glycopeptides using the same batch of mixed 231BR/231 cell lines. So far, GlyProSILC provides an accurate and effective quantitation approach for glycomics, proteomics, and glycoproteomics in a cell culture system.


Visual attention capacity after right hemisphere lesions.
Recently there has been a growing interest in visual short-term memory (VSTM) including the neural basis of the function. Processing speed, another main aspect of visual attention capacity, has received less investigation. For both cognitive functions human lesion studies are sparse. We used a whole report experiment for estimation of these two parameters in 22 patients with right side stroke. Psychophysical performance was analyzed using Bundesen's [Bundesen, C. (1990). A theory of visual attention. Psychological Review, 97, 523-547] Theory of Visual Attention (TVA) and compared statistically to lesion location and size measured by MRI. Visual processing speed was impaired in the contralesional hemifield for most patients, but typically preserved ipsilesionally, even after large cortico-subcortical lesions. When bilateral deficits in processing speed occurred, they were related to damage in the right middle frontal gyrus or leukoaraiosis. The storage capacity of VSTM was also normal for most patients, but deficits were found after severe leukoaraiosis or large strokes extending deep into white matter. Thus, the study demonstrated the importance of white-matter connectivity for both VSTM capacity and ipsilesional processing speed. The study also showed that lesions in a large region of the right hemisphere, including the putamen, insula, and inferior frontal cortex, do not lead to general deficits in the capacity of visual attention.


Mammalian lipids: structure, synthesis and function.
Lipids are essential constituents of cellular membranes. Once regarded merely as structural components, lipids have taken centre stage with the discovery of their roles in cell signalling and in the generation of bioactive metabolites. Lipids regulate many physiological functions of cells and alterations in membrane lipid metabolism are associated with major diseases including cancer, Type II diabetes, cardiovascular disease and immune disorders. Understanding lipid diversity, their synthesis and metabolism to generate signalling molecules will provide insight into the fundamental function of the cell. This review summarises the biosynthesis of the lipids of the mammalian cell; phospholipids, sphingolipids and cholesterol and how lipid diversity is achieved. The fatty acids (FAs) are the main building blocks of lipids and contribute to the diversity. Lipid synthesis is intimately connected to their transport within cells; the contribution by proteins that transport lipids, lipid transport proteins will be described. Cellular lipids are metabolised by phospholipases, lipid kinases and phosphatases to make new bioactive metabolites. These transient bioactive metabolites allow cells to respond to the external environment to maintain cellular health. The function of individual metabolites is also highlighted. Bioactive metabolites can be second messengers, or released to the external medium to regulate other cells. Alternatively, bioactive lipids also provide a platform for reversible recruitment of proteins to membranes using their lipid-binding domains. The wide range of physiological processes in which a specific involvement of lipids has been identified explains the need for lipid diversity present in mammalian cells.


BILATERAL DIFFERENCES IN THE HUMAN OCCIPITAL ELECTROENCEPHALOGRAM WITH UNILATERAL PHOTIC DRIVING.
Differential activity was induced in the electroencephalograms of the occipital lobes by limiting intermittent photic stimulation to the right or left halves of the two retinas. The results indicate that the driving of one hemisphere also affects the opposite hemisphere and that the amount and pattern of the effect is determined by the hemisphere being directly stimulated.


simAIRR: simulation of adaptive immune repertoires with realistic receptor sequence sharing for benchmarking of immune state prediction methods.
Machine learning (ML) has gained significant attention for classifying immune states in adaptive immune receptor repertoires (AIRRs) to support the advancement of immunodiagnostics and therapeutics. Simulated data are crucial for the rigorous benchmarking of AIRR-ML methods. Existing approaches to generating synthetic benchmarking datasets result in the generation of naive repertoires missing the key feature of many shared receptor sequences (selected for common antigens) found in antigen-experienced repertoires. We demonstrate that a common approach to generating simulated AIRR benchmark datasets can introduce biases, which may be exploited for undesired shortcut learning by certain ML methods. To mitigate undesirable access to true signals in simulated AIRR datasets, we devised a simulation strategy (simAIRR) that constructs antigen-experienced-like repertoires with a realistic overlap of receptor sequences. simAIRR can be used for constructing AIRR-level benchmarks based on a range of assumptions (or experimental data sources) for what constitutes receptor-level immune signals. This includes the possibility of making or not making any prior assumptions regarding the similarity or commonality of immune state-associated sequences that will be used as true signals. We demonstrate the real-world realism of our proposed simulation approach by showing that basic ML strategies perform similarly on simAIRR-generated and real-world experimental AIRR datasets. This study sheds light on the potential shortcut learning opportunities for ML methods that can arise with the state-of-the-art way of simulating AIRR datasets. simAIRR is available as a Python package: https://github.com/KanduriC/simAIRR.


Elevated glycemia and brain glucose utilization predict BDNF lowering since early life.
Obesity and diabetes associate with neurodegeneration. Brain glucose and BDNF are fundamental in perinatal development. BDNF is related to brain health, food intake and glucose metabolism. We characterized the relationship between glycemia and/or brain glucose utilization (by 18FDG-PET during fasting and glucose loading), obesity and BDNF in 4-weeks old (pre-obese) and 12-weeks old (obese) Zucker fa/fa rats, and their age-matched fa/+ controls. In 75 human infants, we assessed cord blood BDNF and glucose levels, appetite regulating hormones, body weight and maternal factors. Young and adult fa/fa rats showed glucose intolerance and brain hyper-utilization compared to controls. Glycemia and age were positively related to brain glucose utilization, and were negative predictors of BDNF levels. In humans, fetal glycemia was dependent on maternal glycemia at term, and negatively predicted BDNF levels. Leptin levels were associated with higher body weight and lower BDNF levels. Glucose intolerance and elevated brain glucose utilization already occur in young, pre-obese rats, suggesting that they precede obesity onset in Zucker fatty rats. Glycemic elevation and brain glucose overexposure predict circulating BDNF deficiency since perinatal and early life. Future studies should evaluate whether the control of maternal and fetal glycemia during late intrauterine development can prevent these unfavorable interactions.


Comparison of tolvaptan treatment between patients with the SIADH and congestive heart failure: a single-center experience.
Tolvaptan is a very effective treatment for hypervolemic or euvolemic hyponatremia. We compared the clinical efficacy of and response to tolvaptan in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and congestive heart failure (CHF). We retrospectively reviewed the medical records of 50 patients (SIADH, n = 30; CHF, n = 20) who were prescribed tolvaptan between July 2013 and October 2015. Tolvaptan was prescribed when the serum sodium level was < 125 mmol/L and the standard treatment failed. Normonatremia was defined as a serum sodium level of > 135 mmol/L. After the initiation of tolvaptan therapy, there was an immediate response in the urine volume and serum sodium level in all patients. The improvements in the urine volume and serum sodium concentration were highest within the first 24 hours of treatment. In addition, the mean change in the serum sodium level during the first 24 hours was significantly higher in patients with SIADH than in those with CHF (∆Na, 9.9 ± 4.5 mmol/L vs. 6.9 ± 4.4 mmol/L, respectively; p = 0.025). Also, the mean maintenance dose was lower, and the total duration of tolvaptan use was slightly shorter in the SIADH group than CHF group (21.5 ± 14.9 days vs. 28.0 ± 20.1 days, p = 0.070). The early response to tolvaptan treatment was better in patients with SIADH than in those with CHF. Thus, the tolvaptan treatment strategy should be differed between patients with SIADH and those with CHF.


A review of patients with glutaric aciduria type 1 at Inkosi Albert Luthuli Central Hospital, Durban, South Africa.
Glutaric aciduria type 1 (GA1) is an organic acidaemia. The objective of this study was to describe the profile of patients diagnosed with GA1 at Inkosi Albert Luthuli Central Hospital, Durban, South Africa from 2007 to 2015. We identified 6 children (4 girls, 2 boys) in a retrospective review. The mean age at diagnosis was 12 months. Clinical findings on presentation were encephalopathic crises (n=4), hypotonia (n=4) and macrocephaly (n=5). Other complications included seizures (n=4), dystonia (n=3) and bulbar dysfunction (n=4). Urine organic acid screens showed elevated glutaric acid levels (n=6). Five patients tested positive for the A293T mutation on the glutarylco-enzyme A (CoA) dehydrogenase gene. Abnormalities on magnetic resonance imaging screening included hyperintense basal ganglia (n=6), widened perisylvian fissures (n=6), and an abnormal signal in the cerebral peduncles (n=5) and central tegmental tract (n=4). All patients were treated with L-carnitine and dietary modification. Two patients had a static clinical course, 1 patient gained milestones, and 3 have shown further neuroregression.


Magnesium and other nutrient deficiencies as possible causes of hypertension and low birthweight.
7.2 per cent of babies born in England and Wales in 1986 had birthweights below 2,500 g. Low birthweight and hypertension are associated. European trials have reported that oral supplementation with physiological amounts of magnesium during pregnancy reduces pregnancy hypertension and also miscarriage, preterm birth and fetal growth retardation. Magnesium deficiency causes hypertension and low birthweight in animals. In humans deficiency of thiamin and other B vitamins has also been reported to cause pregnancy hypertension and low birthweight. Magnesium and B vitamins are essential for the same biochemical reactions in energy metabolism. There is evidence that magnesium consumption of substantial numbers of women in Europe and North America is too low to support a healthy pregnancy. Magnesium and thiamin are lost in processing many foods. British trials of magnesium supplementation are advocated. It is suggested that more attention should be given to magnesium in nutritional advice.


Cardioprotective Role of Tumor Necrosis Factor Receptor-Associated Factor 2 by Suppressing Apoptosis and Necroptosis.
Programmed cell death, including apoptosis, mitochondria-mediated necrosis, and necroptosis, is critically involved in ischemic cardiac injury, pathological cardiac remodeling, and heart failure progression. Whereas apoptosis and mitochondria-mediated necrosis signaling is well established, the regulatory mechanisms of necroptosis and its significance in the pathogenesis of heart failure remain elusive. We examined the role of tumor necrosis factor receptor-associated factor 2 (Traf2) in regulating myocardial necroptosis and remodeling using genetic mouse models. We also performed molecular and cellular biology studies to elucidate the mechanisms by which Traf2 regulates necroptosis signaling. We identified a critical role for Traf2 in myocardial survival and homeostasis by suppressing necroptosis. Cardiac-specific deletion of Traf2 in mice triggered necroptotic cardiac cell death, pathological remodeling, and heart failure. Plasma tumor necrosis factor α level was significantly elevated in Traf2-deficient mice, and genetic ablation of TNFR1 largely abrogated pathological cardiac remodeling and dysfunction associated with Traf2 deletion. Mechanistically, Traf2 critically regulates receptor-interacting proteins 1 and 3 and mixed lineage kinase domain-like protein necroptotic signaling with the adaptor protein tumor necrosis factor receptor-associated protein with death domain as an upstream regulator and transforming growth factor β-activated kinase 1 as a downstream effector. It is important to note that genetic deletion of RIP3 largely rescued the cardiac phenotype triggered by Traf2 deletion, validating a critical role of necroptosis in regulating pathological remodeling and heart failure propensity. These results identify an important Traf2-mediated, NFκB-independent, prosurvival pathway in the heart by suppressing necroptotic signaling, which may serve as a new therapeutic target for pathological remodeling and heart failure.


The value of arterial spin labelling (ASL) perfusion MRI in the assessment of post-treatment progression in adult glioma: A systematic review and meta-analysis.
The distinction between viable tumor and therapy-induced changes is crucial for the clinical management of patients with gliomas. This study aims to quantitatively assess the efficacy of arterial spin labeling (ASL) biomarkers, including relative cerebral blood flow (rCBF) and absolute cerebral blood flow (CBF), for the discrimination of progressive disease (PD) and treatment-related effects. Eight articles were included in the synthesis after searching the literature systematically. Data have been extracted and a meta-analysis using the random-effect model was subsequently carried out. Diagnostic accuracy assessment was also performed. This study revealed that there is a significant difference in perfusion measurements between groups with PD and therapy-induced changes. The rCBF yielded a standardized mean difference (SMD) of 1.25 [95% CI 0.75, 1.75] (p < .00001). The maximum perfusion indices (rCBFmax and CBFmax) both showed equivalent discriminatory ability, with SMD of 1.35 [95% CI 0.78, 1.91] (p < .00001) and 1.56 [95% CI 0.79, 2.33] (p < .0001), respectively. Similarly, accuracy estimates were comparable among ASL-derived metrices. Pooled sensitivities [95% CI] were 0.85 [0.67, 0.94], 0.88 [0.71, 0.96], and 0.93 [0.73, 0.98], and pooled specificities [95% CI] were 0.83 [0.71, 0.91], 0.83 [0.67, 0.92], 0.84 [0.67, 0.93], for rCBF, rCBFmax and CBFmax, respectively. Corresponding HSROC area under curve (AUC) [95% CI] were 0.90 [0.87, 0.92], 0.92 [0.89, 0.94], and 0.93 [0.90, 0.95]. These results suggest that ASL quantitative biomarkers, particularly rCBFmax and CBFmax, have the potential to discriminate between glioma progression and therapy-induced changes.


Physical activity levels of patients undergoing bariatric surgery in the Longitudinal Assessment of Bariatric Surgery study.
Bariatric surgery candidates' physical activity (PA) level might contribute to the variability of weight loss and body composition changes following bariatric surgery. However, there is little research describing the PA of patients undergoing bariatric surgery to inform PA recommendations in preparation for, and following, surgery. We describe the PA assessment in the Longitudinal Assessment of Bariatric Surgery-2 study at 6 sites in the United States and report preoperative PA level. We also examined the relationships between objectively determined PA level and the patient's body mass index and self-reported purposeful exercise. The participants wore an accelerometer and completed a PA diary. Standardized measures of height and weight were obtained. Of the 757 participants, 20% were sedentary (<5000 steps/d), 34% had low activity (5000-7499 steps/d), 27% were somewhat active (7500-9999 steps/d), 14% were active (10,000-12,499 steps/d), and 6% were highly active (>or=12,500 steps/d). Body mass index was inversely related to the mean number of steps daily and the mean number of steps each minute during the most active 30 minutes of each day. The most commonly reported activities were walking (44%), gardening (11%), playing with children (10%), and stretching (7%). The self-reported minutes of exercise accounted for 2% of the variance in the objectively determined steps. Patients present for bariatric surgery with a wide range of PA levels, with almost one half categorized as somewhat active or active. Body mass index was inversely related to the total amount and intensity of PA. Few patients reported a regular preoperative exercise regimen, suggesting most PA is accumulated from activities of daily living. Patients' report of daily minutes of walking or exercise might not be a reliable indication of their PA level.


CHARACTERIZATION OF A GENE ENCODING THE LIGHT-HARVESTING VIOLAXANTHIN-CHLOROPHYLL PROTEIN OF NANNOCHLOROPSIS SP. (EUSTIGMATOPHYCEAE).
In contrast to vascular plants, green algae, and diatoms, the major light-harvesting complex of the marine eustigmatophyte genus Nannochloropsis is a violaxanthin-chlorophyll a protein complex that lacks chlorophylls b and c. The isolation of a single polypeptide from the light-harvesting complex of Nannochloropsis sp. (IOLR strain) was previously reported (Sukenik et al. 1992). The NH2 -terminal amino acid sequence of this polypeptide was significantly similar to NH2 -terminal sequences of the light-harvesting fucoxanthin, chlorophyll a/c polypeptides from the diatom Phaeodactylum tricornutum Bohlin. Using polyclonal antibodies raised to the Nannochloropsis light-harvesting polypeptide, a gene encoding this polypeptide was isolated from a cDNA expression library. The deduced amino acid sequence of the Nannochloropsis violaxanthin-chlorophyll a polypeptide reveals a 36 amino acid presequence followed by 173 amino acids that constitute the mature polypeptide. The mature polypeptide has 30%-40% sequence identity to the diatom fucoxanthin-chlorophyll a/c polypeptides and less then 27% identity to the green algal and vascular plant light-harvesting chlorophyll polypeptides that bind both chlorophylls a and b. Its molecular mass, as deduced from the gene sequence, is 18.4 kDa with three putative transmembrane helices and several residues that may be involved in chlorophyll binding. The cDNA encoding the violaxanthin-chlorophyll a polypeptide was used to isolate and characterize a 10 kb genomic fragment containing the entire gene. The open reading frame was interrupted by five introns ranging in size from 123 to 449 bp. The intron borders have typical eukaryotic GT … AG sequences.


Strategies for obstacle avoidance during walking in the cat.
Avoiding obstacles is essential for successful navigation through complex environments. This study aimed to clarify what strategies are used by a typical quadruped, the cat, to avoid obstacles during walking. Four cats walked along a corridor 2.5 m long and 25 or 15 cm wide. Obstacles, small round objects 2.5 cm in diameter and 1 cm in height, were placed on the floor in various locations. Movements of the paw were recorded with a motion capture and analysis system (Visualeyez, PTI). During walking in the wide corridor, cats' preferred strategy for avoiding a single obstacle was circumvention, during which the stride direction changed while stride duration and swing-to-stride duration ratio were preserved. Another strategy, stepping over the obstacle, was used during walking in the narrow corridor, when lateral deviations of walking trajectory were restricted. Stepping over the obstacle involved changes in two consecutive strides. The stride preceding the obstacle was shortened, and swing-to-stride ratio was reduced. The obstacle was negotiated in the next stride of increased height and normal duration and swing-to-stride ratio. During walking on a surface with multiple obstacles, both strategies were used. To avoid contact with the obstacle, cats placed the paw away from the object at a distance roughly equal to the diameter of the paw. During obstacle avoidance cats prefer to alter muscle activities without altering the locomotor rhythm. We hypothesize that a choice of the strategy for obstacle avoidance is determined by minimizing the complexity of neuro-motor processes required to achieve the behavioral goal.NEW & NOTEWORTHY In a study of feline locomotor behavior we found that the preferred strategy to avoid a small obstacle is circumvention. During circumvention, stride direction changes but length and temporal structure are preserved. Another strategy, stepping over the obstacle, is used in narrow walkways. During overstepping, two strides adjust. A stride preceding the obstacle decreases in length and duration. The following stride negotiating the obstacle increases in height while retaining normal temporal structure and nearly normal length.


The current and projected economic burden of Parkinson's disease in the United States.
Parkinson's disease (PD), following Alzheimer's disease, is the second-most common neurodegenerative disorder in the United States. A lack of treatment options for changing the trajectory of disease progression, in combination with an increasing elderly population, portends a rising economic burden on patients and payers. This study combined information from nationally representative surveys to create a burden of PD model. The model estimates disease prevalence, excess healthcare use and medical costs, and nonmedical costs for each demographic group defined by age and sex. Estimated prevalence rates and costs were applied to the U.S. Census Bureau's 2010 to 2050 population data to estimate current and projected burden based on changing demographics. We estimate that approximately 630,000 people in the United States had diagnosed PD in 2010, with diagnosed prevalence likely to double by 2040. The national economic burden of PD exceeds $14.4 billion in 2010 (approximately $22,800 per patient). The population with PD incurred medical expenses of approximately $14 billion in 2010, $8.1 billion higher ($12,800 per capita) than expected for a similar population without PD. Indirect costs (e.g., reduced employment) are conservatively estimated at $6.3 billion (or close to $10,000 per person with PD). The burden of chronic conditions such as PD is projected to grow substantially over the next few decades as the size of the elderly population grows. Such projections give impetus to the need for innovative new treatments to prevent, delay onset, or alleviate symptoms of PD and other similar diseases.


Unusual site of recurrent musculoskeletal hydatid cyst: case report and brief review of the literature.
A case of a large multiplex recurrent hydatid cyst involving the left gluteal muscle and the left iliopsoas, accompanied with degeneration of the musculature of the left upper leg is presented along with a review of the relevant literature. Very few such cases have been reported worldwide. The presented case is also distinguished by the involvement of muscles of distant anatomic areas.


Optimization of thermoelectric performance of SrSi2-based alloys via the modification in band structure and phonon-point-defect scattering.
Thermoelectric properties of alkaline-earth-metal disilicides are strongly dependent on their electronic band structure in the vicinity of the Fermi level. In particular, the strontium disilicide, SrSi2 with a narrow band gap of about few tens of meV is composed of non-toxic, naturally abundant elements, and its thermoelectric properties are very sensitive to the substitution/alloying with third elements. In this article, we summarize the thermoelectric performance of substituted and Sr-deficient/Sr-rich SrSi2 alloys to realize the high thermoelectric figure-of-merit (ZT) for practical applications in the electronic and thermoelectric aspects, and also to explore the alternative routes to further improve its ZT value.


Phospholipids as cancer biomarkers: Mass spectrometry-based analysis.
Lipids, particularly phospholipids (PLs), are key components of cellular membrane. PLs play important and diverse roles in cells such as chemical-energy storage, cellular signaling, cell membranes, and cell-cell interactions in tissues. All these cellular processes are pertinent to cells that undergo transformation, cancer progression, and metastasis. Thus, there is a strong possibility that some classes of PLs are expected to present in cancer cells and tissues in cellular physiology. The mass spectrometric soft-ionization techniques, electrospray ionization (ESI), and matrix-assisted laser desorption/ionization (MALDI) are well-established in the proteomics field, have been used for lipidomic analysis in cancer research. This review focused on the applications of mass spectrometry (MS) mainly on ESI-MS and MALDI-MS in the structural characterization, molecular composition and key roles of various PLs present in cancer cells, tissues, blood, and urine, and on their importance for cancer-related problems as well as challenges for development of novel PL-based biomarkers. The profiling of PLs helps to rationalize their functions in biological systems, and will also provide diagnostic information to elucidate mechanisms behind the control of cancer, diabetes, and neurodegenerative diseases. The investigation of cellular PLs with MS methods suggests new insights on various cancer diseases and clinical applications in the drug discovery and development of biomarkers for various PL-related different cancer diseases. PL profiling in tissues, cells and body fluids also reflect the general condition of the whole organism and can indicate the existence of cancer and other diseases. PL profiling with MS opens new prospects to assess alterations of PLs in cancer, screening specific biomarkers and provide a basis for the development of novel therapeutic strategies. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 37:107-138, 2018.


New 3,4-seco-Grayanane Diterpenoids from the Flowers of Pieris japonica.
Three new 3,4-seco-grayanane diterpenoids, neopierisoids D-F (2-4), and a new natural one, neopierisoid C (1), were isolated from the flowers of Pieris japonica. Their structures were elucidated on the basis of extensive spectroscopic analysis, including one and two dimensional (1- and 2D)-NMR, as well as high resolution-electron ionization (HR-EI)-MS.


Repetitive thinking, executive functioning, and depressive mood in the elderly.
Previous findings and the depressive-executive dysfunction hypothesis suggest that the established association between executive functioning and depression is accounted for by repetitive thinking. Investigating the association between executive functioning, repetitive thinking, and depressive mood, the present study empirically tested this mediational model in a sample of older adults, while focusing on both concrete and abstract repetitive thinking. This latter distinction is important given the potential protective role of concrete repetitive thinking, in contrast to the depletive effect of abstract repetitive thinking. A sample of 43 elderly volunteers, between 75 and 95 years of age, completed tests of executive functioning (the Stroop test, the Trail Making test, and the Fluency test), and questionnaires of repetitive thinking and depression. Positive correlations were observed between abstract repetitive thinking and depressive mood, and between concrete repetitive thinking and executive functioning; a negative correlation was observed between depressive mood and executive functioning. Further, mediational analysis evidenced that the relation between executive functioning and depressive mood was mediated by abstract repetitive thinking. The present data provide, for the first time, empirical support to the depressive-executive dysfunction hypothesis: the lack of executive resources would favor a mode of abstract repetitive thinking, which in turn would deplete mood. It suggests that clinical intervention targeting depression in the elderly should take into consideration repetitive thinking modes and the executive resources needed to disengage from rumination.


Local structural and optical properties of ZnO nanoparticles.
This study examined the local structural and optical properties of ZnO nanoparticles (NPs) with mean diameters of 4.5 and 70 nm using extended X-ray absorption fine structure (EXAFS) measurements at the Zn K edge and photoluminescence (PL) measurements. EXAFS revealed that the average bond length of atomic pairs in the NPs was shorter than that of the powder. Furthermore, a substantial amount of structural disorder existed in the NPs. From the PL measurements, we observed the direct band gap peak of 3.41 eV from the 70 nm ZnO NPs at low temperatures. This blue shift was related to the structural property changes.


Minimum exposure limits and measured relationships between the vitamin D, erythema and international commission on non-ionizing radiation protection solar ultraviolet.
The International Commission on Non-Ionizing Radiation Protection (ICNIRP) has established guidelines for exposure to ultraviolet radiation in outdoor occupational settings. Spectrally weighted ICNIRP ultraviolet exposures received by the skin or eye in an 8 h period are limited to 30 J m(-2). In this study, the time required to reach the ICNIRP exposure limit was measured daily in 10 min intervals upon a horizontal plane at a subtropical Australian latitude over a full year and compared with the effective Vitamin D dose received to one-quarter of the available skin surface area for all six Fitzpatrick skin types. The comparison of measured solar ultraviolet exposures for the full range of sky conditions in the 2009 measurement period, including a major September continental dust event, show a clear relationship between the weighted ICNIRP and the effective vitamin D dose. Our results show that the horizontal plane ICNIRP ultraviolet exposure may be used under these conditions to provide minimum guidelines for the healthy moderation of vitamin D, scalable to each of the six Fitzpatrick skin types.


Facile Synthetic Route to Atomically Thin Conductive Wires from Single-Species Molecules in One-Dimensionally Confined Space: Doped Conjugated Polymers inside Single-Walled Carbon Nanotubes.
A facile synthetic method for doped conjugated molecules by a heating process is demonstrated. Br-terminated terthiophene precursors are encapsulated in single-walled carbon nanotubes by a vapor-phase reaction, and additional heat treatment promotes the thermal condensation of the precursors. Transmission electron microscopy observations and optical measurements show the successful synthesis of sexithiophenes and their doping (oxidation) by Br dopants generated by the condensation reaction. This study provides a new strategy for the synthesis of the doped conjugated polymers from single-species molecules by only a heating process.


[Violence clusters in Pernambuco, Brazil].
To analyze the spatial distribution of homicide mortality rates among males 15 to 49 years old in the state of Pernambuco, Brazil, for the periods of 1980 to 1984 and 1995 to 1998, and to identify violence clusters. Mortality data were obtained from the Brazilian Ministry of Health's Mortality Information System. The mean homicide mortality rate was estimated for each municipality in the state for the two periods. The Moran coefficient was calculated to determine spatial autocorrelation. (The Moran coefficient ranges from -1 to +1, with a positive coefficient indicating a cluster of similar values, and a negative coefficient indicating adjacent dissimilar values.) To identify clusters of municipalities with either high or low homicide mortality rates, the local indicator of spatial association (LISA) was used. Finally, a Moran map was constructed to identify municipalities with statistically significant LISA values and to identify clusters of municipalities with either high or low homicide mortality rates. The Moran coefficient for 1980-1984 was 0.392, and for 1995-1998 it was 0.291 (P < 0.001). In the 1980-1984 period, one cluster of high homicide mortality rates was found in the Mata Sul region of the state, close to the metropolitan region of the state capital, Recife. In the 1995-1998 period, two violence clusters were identified: a predominantly urban one in the Recife metropolitan region, and the other in the state interior, in an area known as the "Marijuana Polygon" (Polígono da Maconha). This study suggests that the violence clusters are not the result of the socioeconomic conditions per se, but rather the consequence of the interaction between poor economic conditions and drug trafficking.


Clinical efficacy of 9-oxo-10, 11-dehydroageraphorone extracted from Eupatorium adenophorum against Psoroptes cuniculi in rabbits.
Animal acariasis is one of the important veterinary skin diseases. Chemical drugs have been widely used to treat and control this kind of disease. But many chemicals control could increase resistance in target species, toxicity and environmental hazards. We found that the 9-oxo-10, 11-dehydroageraphorone (euptox A) extracted from E. adenophorum has strong toxicity against P. cuniculi in vitro, but the in vivo acaricidal actions of euptox A have yet to be investigated. A 14-day experiment was performed using rabbits that were naturally infested with P. cuniculi on a farm. Rabbits were randomly divided into five groups; animals in groups A, B and C were treated in each ear topically with 4.0 ml of 2.0 and 1.0 g/L (w/v) euptox A, respectively. Animals in groups D and E were treated with ivermectin (by injection; positive controls) and glycerol with water only (by embrocation; negative controls), respectively. Each rabbit was treated twice with separate treatments on days 0 and 7. Rabbits were observed daily and detailed examinations were performed on days 0, 7 and 14, to inspect the presence or absence of mites and scabs/crusts. Seven days after the initial treatment, the mean clinical scores (presence of scabs/crusts) decreased from 3.48, 3.37, 3.43 and 3.45 to 0.37, 0.42, 0.78 and 0.38 in the ears of animals in groups A, B , C and D, respectively, which were similar to the observations recorded in the positive control rabbits. However, the clinical score for negative control rabbits did not increase significantly (P > 0.05) during the experiment, and this changed from 3.32 to 3.37 in the ears, and there were no significant differences in clinical efficacy between left and right ears. After two treatments (0 and 7 d), the rabbits in groups A, B, C and D had recovered completely 14 days after the last treatment and no recurrences of infection were observed. These results indicate that euptox A was potent compounds for the effective control of animal P. cuniculi in vivo.


Calcium and calmodulin mediation of growth hormone-releasing hormone release from the rat hypothalamus in vitro.
A major role for Ca2+ and calmodulin in stimulus-secretion coupling has been suggested for several neuropeptides; however, the cellular mechanisms of GH-releasing hormone (GHRH) release have been little investigated so far. We have used a previously validated acute rat hypothalamic explant system in order to elucidate whether Ca2+ acts as a second messenger in the regulation of GHRH release, and whether calmodulin-dependent pathways are involved. Calcium dependence of somatostatin (SRIH) release was assessed in the same experiments. Calmodulin dependence of SRIH was not investigated in detail, as it has been established previously. The calcium-entry antagonist, verapamil, antagonized K(+)-stimulated GHRH and SRIH release in a dose-dependent manner, with maximal inhibition shown at 10(-4) M. The calmodulin antagonist W7 also blocked K(+)-evoked GHRH release in a dose-dependent manner, with significant inhibition in the dose range 5 X 10(-5) M to 2 X 10(-4) M; similarly, a more specific calmodulin inhibitor, the W7 derivative 5-iodo-C8 (W8), reversed K(+)-stimulated GHRH release, showing slightly higher potency than W7. W7 also reversed GHRH release in response to the calcium-ionophore A23187, although verapamil had no effect on A23187-evoked GHRH or SRIH release. Thapsigargin, which increases the efflux of Ca2+ from calciosomes, did not affect either GHRH or SRIH release at 10(-5) M or 10(-4) M. The basal release of GHRH was clearly suppressed by W7 and W8 (10(-4) M), whereas verapamil had no effect. We conclude that calcium influx is crucial for depolarization-induced GHRH and SRIH release. Calcium entrance in response to A23187 appears to be independent of verapamil-sensitive calcium channels. The lack of effect of thapsigargin suggests that increased intracellular Ca2+ from intracellular stores is not equivalent to an increase in Ca2+ influx. Both basal and depolarization-induced release of GHRH in this system are calmodulin dependent.


Communications blackout? Do N-acylhomoserine-lactone-degrading enzymes have any role in quorum sensing?
A number of bacteria, including some significant pathogens, utilize N-acylhomoserine lactones (AHLs) as quorum sensing signals. There is considerable interest in the therapeutic potential of disrupting quorum sensing. Recently, a number of bacteria have been identified which are capable of enzymic inactivation of AHLs. These enzymes show considerable promise as 'quenchers' of quorum sensing. However, the assumption that the natural function of these enzymes is to disrupt or modulate quorum sensing has yet to be established. This review surveys the progress made to date in this field and examines what implications these findings have for our understanding of the role played by these enzymes in vivo.


Right cerebral hemisphere superiority for recognizing the internal and external features of famous faces.
Right-handed male and female subjects were asked to identify bilaterally presented famous faces from an upright display of all the faces used in the experiment, under four conditions: these involved presentation of upright external features, upright internal features, upright whole faces, and inverted whole faces. The task was one of identification in the sense of picking out presented faces from a display of all the possible faces, and did not require explicit naming of the famous people. Left visual hemifield superiorities were found for upright external features, upright internal features, and upright whole faces, which did not vary across these three conditions. Overall performance levels did vary, with whole faces better identified than internal features, which were in turn better identified than external features. The presentation of inverted whole faces led to poorer overall performance than for upright faces, and no visual hemifield asymmetry. These results show that the right cerebral hemisphere is better able than the left to recognize known faces from both internal and external features.


TGF-β-Induced Endothelial to Mesenchymal Transition in Disease and Tissue Engineering.
Endothelial to mesenchymal transition (EndMT) is a complex biological process that gives rise to cells with multipotent potential. EndMT is essential for the formation of the cardiovascular system during embryonic development. Emerging results link EndMT to the postnatal onset and progression of fibrotic diseases and cancer. Moreover, recent reports have emphasized the potential for EndMT in tissue engineering and regenerative applications by regulating the differentiation status of cells. Transforming growth factor β (TGF-β) engages in many important physiological processes and is a potent inducer of EndMT. In this review, we first summarize the mechanisms of the TGF-β signaling pathway as it relates to EndMT. Thereafter, we discuss the pivotal role of TGF-β-induced EndMT in the development of cardiovascular diseases, fibrosis, and cancer, as well as the potential application of TGF-β-induced EndMT in tissue engineering.


Molecular cloning and expression of a sixth type of alpha 2,8-sialyltransferase (ST8Sia VI) that sialylates O-glycans.
A novel member of the mouse alpha2,8-sialyltransferase (ST8Sia) family, designated ST8Sia VI, was identified by BLAST analysis of expressed sequence tags. The sequence of ST8Sia VI encodes a protein of 398 amino acids and shows 42.0 and 38.3% amino acid sequence identities to mouse alpha2,8-sialyltransferases ST8Sia I (GD3 synthase) and ST8Sia V (GD1c, GT1a, GQ1b, and GT3 synthases), respectively. The recombinant soluble form of ST8Sia VI expressed in COS-7 cells exhibited alpha2,8-sialyltransferase activity toward both glycolipids and glycoproteins that have the NeuAcalpha2,3(6)Gal sequence at the nonreducing end of their carbohydrate groups. This enzyme formed NeuAcalpha2,8NeuAc structures, but not oligosialic or polysialic acid structures. Analysis of the fetuin sialylated by ST8Sia VI indicated that ST8Sia VI prefers O-glycans to N-glycans as acceptor substrates. Substrate specificities and kinetic properties also showed that ST8Sia VI prefers O-glycans to glycolipids as acceptor substrates. ST8Sia VI also exhibited activity toward oligosaccharides such as sialyllactose and sialyllactosamine, and the structure of the minimal acceptor substrate for ST8Sia VI was determined as the NeuAcalpha2,3(6)Gal sequence. The expression of the ST8Sia VI gene was ubiquitous, and the highest expression was observed in kidney, with three major transcripts of 8.2, 3.8, and 2.7 kb. This is the first report of a mammalian alpha2,8-sialyltransferase that sialylates O-glycans preferentially.


Subclinical cardiovascular damage in patients with HCV cirrhosis before and after treatment with direct antiviral agents: a prospective study.
Cirrhosis is associated with morpho-functional cardiovascular alterations. To detect early features of cardiovascular damage in HCV-compensated cirrhotic patients using myocardial deformation indices and carotid arterial stiffness, and, further, to evaluate their short-term behaviour after HCV eradication with direct antiviral agents (DAAs). Thirty-nine consecutive patients with HCV cirrhosis, without previous cardiovascular events, were studied and matched for age, gender and cardiovascular risk factors to 39 controls without liver or cardiovascular disease. Patients and controls underwent a baseline echocardiographic evaluation including global longitudinal strain and ultrasound scan of carotid arteries. HCV-cirrhotics were reassessed by echocardiography and carotid ultrasound after obtaining sustained virological response (SVR) on DAAs. HCV-cirrhotics showed at baseline a significantly reduced global longitudinal strain compared to controls -18.1 (16.3-20.5) vs -21.2 (20.4-22.3), P < 0.001. They also had a significantly higher pulse wave velocity 8.6 (7.7-9.1) m/s vs 6.6 (6.0-7.1) m/s, P = 0.0001, and β-stiffness index 12.4 (11.1-13.5) vs 8.6 (8.0-9.2) P = 0.0001. At multiple regression analysis, diabetes and HCV cirrhosis were independent predictors of global longitudinal strain. All HCV-cirrhotic patients had SVR on DAAs. Follow-up available in 32 of 39 (82%) at 9 (8-10) months showed a significant improvement of tricuspid annular plane systolic excursion (P = 0.01) and lateral E' velocity compared to baseline (P = 0.001). HCV-cirrhotics show a significant rate of subclinical cardiac and vascular abnormalities. At a time when their survival is less linked to progression of liver disease, due to viral eradication on DAAs, cardiovascular morbidity and mortality may take a significant role.


Linear and Nonlinear Optical Properties of Triphenylamine-Indandione Chromophores: Theoretical Study of the Structure-Function Relationship under the Combined Action of Substituent and Symmetry Change.
Linear and nonlinear optical properties of experimentally synthesized triphenylamine-indandione chromophores were investigated by time-dependent density functional theory calculations. The absorption and emission spectra, as well as the static and dynamic first hyperpolarizabilities related to the combined effect of substituent introduction and symmetry breaking, were discussed in detail. Theoretical analysis indicated the uniting of indandione acceptor group(s) with a precursor (triphenylamine, TriPhA), with the molecular symmetry destroyed simultaneously, leads to an obvious change in both the peak position and intensity of the linear spectra. The same process can also substantially magnify the molecular first hyperpolarizabilities. The triphenylamine-indandione molecules exhibit efficiencies in static first hyperpolarizability relative to that of the electron-donating TriPhA component and the electron-accepting indandione moiety. The optical nonlinearity would be further expanded under the influence of a resonance effect induced by appropriate excitation. Incident light with a wavelength nearly two times the one-photon absorption is likely to cause a greater frequency dispersion response. In particular, the first hyperpolarizabilities of the title compounds can be enlarged by about 3.2 times on average by resonance enhancement at a fundamental wavelength of 1064 nm.


Effect of calcium chloride infusion on the tenderness of lambs fed a beta-adrenergic agonist.
The objective of this study was to examine the effectiveness of CaCl2 infusion in overcoming the toughness of meat associated with dietary administration of a beta- adrenergic agonist (BAA) to lambs. Thirty-two crossbred (1/2 Finnsheep X 1/4 Dorset X 1/4 Rambouillet) wether lambs were randomly assigned to receive 0 or 4 ppm BAA (L644,969; Merck, Sharpe and Dohme Research Laboratories) in a completely mixed, high-concentrate diet for 6 wk. Animals were slaughtered in two groups of 16. At each slaughter time half of each group (0 or 4 ppm BAA) was randomly assigned to CaCl2 infusion. Feeding the BAA decreased (P less than .05) fat thickness, kidney-pelvic fat, yield grade, and marbling and increased (P less than .05) dressing percentage, lean firmness, leg score, and biceps femoris weight. Weight of biceps femoris was 32.8% greater in BAA-fed lambs. Treated, but not infused, lambs were significantly less tender than control lambs after 1, 7, and 14 d of postmortem storage. At 24 h postmortem, BAA-fed lambs had higher (P less than .05) cathepsin B, calcium-dependent protease-II (CDP-II), and CDP inhibitor activities. Calcium chloride infusion increased marbling, decreased lean firmness, increased lean color score, and increased dressing percentage (P less than .05). Infusion of carcasses with CaCl2 decreased (P less than .05) shear force at all postmortem times. Infusion of carcasses with CaCl2 had no effect on cathepsins B and B + L activities, but it had a significant effect on CDP-I, CDP-II, and CDP inhibitor activities.(ABSTRACT TRUNCATED AT 250 WORDS)


Carbene-stabilized beryllium borohydride.
The reaction of N-heterocyclic carbene, L:, with BeCl(2) quantitatively yields L:BeCl(2)1 (L: = :C{N(2,6-Pr(i)(2)C(6)H(3))CH}(2)). The carbene-stabilized beryllium borohydride monomer L:Be(BH(4))(2)2 is prepared by the reaction of 1 with LiBH(4). Compound 3, prepared by the reaction of 2 with Na(2)[Fe(CO)(4)]·dioxane, represents an unusual "dual reduction" of the imidazole ring (i.e., hydroboration of the C═C backbone and hydrogenation of the C2 carbene center).


Structural investigations of the p53/p73 homologs from the tunicate species Ciona intestinalis reveal the sequence requirements for the formation of a tetramerization domain.
Most members of the p53 family of transcription factors form tetramers. Responsible for determining the oligomeric state is a short oligomerization domain consisting of one β-strand and one α-helix. With the exception of human p53 all other family members investigated so far contain a second α-helix as part of their tetramerization domain. Here we have used nuclear magnetic resonance spectroscopy to characterize the oligomerization domains of the two p53-like proteins from the tunicate Ciona intestinalis, representing the closest living relative of vertebrates. Structure determination reveals for one of the two proteins a new type of packing of this second α-helix on the core domain that was not predicted based on the sequence, while the other protein does not form a second helix despite the presence of crucial residues that are conserved in all other family members that form a second helix. By mutational analysis, we identify a proline as well as large hydrophobic residues in the hinge region between both helices as the crucial determinant for the formation of a second helix.


Feasibility of recruiting in prisons during a randomized controlled trial with people with serious mental illness.
Successful participant recruitment is vital to the feasibly of intervention research. In the behavioral and social sciences, intervention researchers face a myriad of recruitment barriers, many of which stem from working in real-world settings and among hard-to-access populations. Optimizing recruitment efforts requires being intentional about study planning and resource allocation, carefully documenting the outcomes of recruitment efforts, and developing and implementing procedures and strategies to overcome anticipated recruitment barriers. The current article presents recruitment flowcharts to illustrate (a) the multistep recruitment process and (b) the points of potential participant attrition during recruitment from a two-phase group-based intervention study conducted among individuals with serious mental illness incarcerated in a state prison system in the U.S. In addition, qualitative methods are used to examine strategies employed during the study to support recruitment efforts. Despite challenges, this study was able to achieve recruitment goals. Analyses found the majority of potential participant attrition occurred prior to informed consent, highlighting the need for studies to track recruitment efforts in more detail than is currently recommended by commonly used guidelines. Strategies to optimize recruitment efforts included maximizing recruiter availability, developing a responsive communication approach, demonstrating respect for facility procedures and operations, and ensuring peak preparedness. Careful documentation of recruitment efforts and the early deployment of recruitment strategies is vital to the feasibility of intervention studies conducted in real-world settings with hard-to-access populations. The publication of recruitment procedures and outcomes can help future researchers anticipate recruitment challenges and inform recruitment goals, timelines, and strategies.