Search

Thousands of interactions assemble proteins into modules that impart spatial and functional organization to the cellular proteome. Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. The first, BioPlex 3.0, results from affinity purification of 10,128 human proteins-half the proteome-in 293T cells and includes 118,162 interactions among 14,586 proteins. The second results from 5,522 immunoprecipitations in HCT116 cells. These networks model the interactome whose structure encodes protein function, localization, and complex membership. Comparison across cell lines validates thousands of interactions and reveals extensive customization. Whereas shared interactions reside in core complexes and involve essential proteins, cell-specific interactions link these complexes, "rewiring" subnetworks within each cell's interactome. Interactions covary among proteins of shared function as the proteome remodels to produce each cell's phenotype. Viewable interactively online through BioPlexExplorer, these networks define principles of proteome organization and enable unknown protein characterization., Competing Interests: Declaration of interests J.W.H. is a founder and scientific advisory board member of Caraway Therapeutics and a Founding Scientific Advisor for Interline Therapeutics., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We describe the synthesis and characterization of a new trinuclear Ni(ii) Schiff base complex of formula [Ni3(L)2(NCS)2(OAc)2(CH3OH)2] (1) where HL is the 1 : 1 condensation product of 2-picolylamine and o-vanillin. The crystal structure of complex 1 shows that the two terminal Ni(ii) ions are connected to the central one through a phenoxido- and a syn-syn acetato bridge, giving rise to a very bent configuration in the Ni3-core. Magnetic susceptibility measurements show the presence of a weak antiferromagnetic coupling with J = -3.22(2) cm-1. We also report a magneto-structural correlation, performed with all the magnetically characterized Ni(ii) trimers with similar bridges, showing a linear dependence between the J value and the dihedral angle (θ) between the planes containing the Ni-O-Ni and the carboxylate bridges. The super-exchange interaction is investigated by extensive density functional calculations within the broken symmetry approximation which show good agreement with the experimental data. The analysis of the spin density distribution and the shape of the magnetically active single occupied molecular orbitals (SOMO) provide a mechanism of exchange coupling through the bridging groups.

We report a comprehensive proteogenomics analysis, including whole-genome sequencing, RNA sequencing, and proteomics and phosphoproteomics profiling, of 218 tumors across 7 histological types of childhood brain cancer: low-grade glioma (n = 93), ependymoma (32), high-grade glioma (25), medulloblastoma (22), ganglioglioma (18), craniopharyngioma (16), and atypical teratoid rhabdoid tumor (12). Proteomics data identify common biological themes that span histological boundaries, suggesting that treatments used for one histological type may be applied effectively to other tumors sharing similar proteomics features. Immune landscape characterization reveals diverse tumor microenvironments across and within diagnoses. Proteomics data further reveal functional effects of somatic mutations and copy number variations (CNVs) not evident in transcriptomics data. Kinase-substrate association and co-expression network analysis identify important biological mechanisms of tumorigenesis. This is the first large-scale proteogenomics analysis across traditional histological boundaries to uncover foundational pediatric brain tumor biology and inform rational treatment selection., Competing Interests: Declaration of Interests E.E.S. serves as chief executive officer for Sema4 and has an equity interest in this company., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Protein abundance profiling using isobaric labeling is a well-established quantitative mass spectrometry technique. However, ratio distortion resulting from coisolated and cofragmented ions, commonly referred to as interference, remains a drawback of this strategy. Tribrid mass spectrometers, such as the Orbitrap Fusion and the Orbitrap Fusion Lumos with a triple mass analyzer configuration, facilitate methods (namely, SPS-MS3) that can help alleviate interference. However, few standards are available to measure interference and thereby aid in method development. Here we introduce the TKO6 standard that assesses ion interference and is designed specifically for data acquired at low (unit) mass resolution. We use TKO6 to compare interference in MS2- versus MS3-based quantitation methods, data acquisition methods of different lengths, and ion-trap-based tandem mass tag reporter ion analysis (IT-MS3) with conventional Orbitrap-based analysis (OT-MS3). We show that the TKO6 standard is a valuable tool for assessing quantification accuracy in isobaric-tag-based analyses.

Introduction: Given the high prevalence of smoking among Veterans and the economic, social, and clinical implications, it is important to understand the factors that contribute to smoking in order to focus efforts to mitigate these factors and improve smoking cessation efforts among Veterans. The availability of research on smoking in Veterans compared with civilians is limited given the military-specific differences in their life course. We aimed to identify military-specific factors combined with sociodemographic factors for ever smoking and current smoking among Veterans to inform future interventions., Materials and Methods: We used data from the 2010 National Survey of Veterans, the most current, to analyze the association of sociodemographic and military-specific factors with ever versus never smoking, and current versus past smoking using multiple variable logistic regression models (IRB#4125)., Results: Among 8,618 respondents, the proportions of current, past, and never smokers were 17%, 48%, and 34%, respectively. Sociodemographic factors associated with ever smoking were female gender, educational attainment of less than a bachelor's degree, and being divorced/separated/widowed. Military-specific factors associated with ever smoking were exposure to dead/dying/wounded soldiers during service, and past, current, and unsure enrollment in Veterans Affairs healthcare. Never smoking was associated with Hispanic ethnicity, income over $75,000, and reporting fair or poor health. Military factors associated with never smoking were presence of a service-connected disability and military service July 1964 or earlier (i.e., pre-Vietnam). Among 5,652 ever smokers, sociodemographic factors associated with current smoking were age less than 65, being non-Hispanic black, educational attainment of less than a bachelor's degree, being divorced/separated/widowed, never married, and having no insurance. Factors associated with reduced likelihood of current smoking compared with past smoking included income >$41,000 and reporting fair or poor health. Military-specific variables associated with reduced likelihood of current smoking were service era of May 1975 or later (i.e., post-Vietnam) and 5 or more years of service., Conclusion: Military-specific variables are associated with smoking behaviors among Veterans. Findings from this study that exposure to dead/dying/wounded soldiers, service era, duration of service, service-connected disability status, and enrollment in VA care all influence smoking in Veterans, can inform prevention and cessation efforts in part by encouraging alternative healthy habits or cessation techniques in subgroups of Veterans with particular military backgrounds. By assessing risk factors in this unique population future research can leverage these findings to determine mechanisms that help explain these associations. Identifying factors associated with smoking offers insights for smoking cessation and prevention interventions given the military experiences and increased smoking incidence among Veterans.

Background: Systematic reviews (SRs) depend on comprehensive searches for evidence to provide balanced, accurate results. Requesting published and unpublished studies from pharmaceutical manufacturers has been proposed as a method to engage industry stakeholders and potentially reduce reporting bias. The Drug Effectiveness Review Project (DERP) has been requesting such evidence since 2003; the purpose of this study was to retrospectively evaluate the type and impact of the evidence received., Methods: Data from "dossiers" submitted by pharmaceutical manufacturers for a set of 40 SRs conducted for DERP from July 2006 to June 2015 were retrospectively evaluated. Characteristics of data submitted in dossiers, including numbers, types, and characteristics of studies submitted and then included in DERP SRs, were abstracted. Time trends, study quality, publication status, and whether the submission represented a unique study or supplemental data to a published study were assessed. The impact of this evidence on SR conclusions was assessed using dual review. Differences were resolved through a consensus., Results: Over 9 years, 160 dossiers were received, relating to 40 DERP SRs. Out of 7360 studies/datasets submitted, 2.2% (160) were included in a SR. The ratio of submitted-to-included increased over time. Most were unique studies (23% were supplemental data sets), and almost 42% of the studies were unpublished. The majority of the studies were rated fair quality, with 7.3% rated good and 14% rated poor quality by the original SR authors. Considering all literature search sources, 7.2% of all studies included in the 40 SRs came from a dossier, and 16% of dossier studies were included in a meta-analysis. The dossier studies resulted in changes to conclusions in 42% of the SRs. Out of 46 unpublished unique studies included in a SR, 25 (54%) influenced the conclusions in favor of the manufacturers drug, 8% favored a competitor drug, and 40% favored neither. In 92% of cases favoring the manufacturer's drug, the dossier study was the only evidence for that drug in a specific population or outcome., Conclusions: In SRs conducted for DERP, few studies submitted by pharmaceutical manufacturers were ultimately included in a SR. The included data helped to reduce reporting and publication bias by filling important gaps and in some cases led to altered conclusions.

Bioremediation of wastewater is gaining popularity over chemical treatment due to the greener aspect. The volume of literature containing algal biodegradation is small. Especially, removal of toxic materials like phenol from coke-oven wastewater using fast-growing cyanobacteria was not tried. The current study, therefore, targeted at bioremediation of phenol from wastewater using Leptolyngbya sp., a cyanobacterial strain, as a finishing step. Furthermore, the growth of the strain was studied under different conditions, varying phenol concentration 50-150 mg/L, pH 5-11, inoculum size 2-10% to assess its ability to produce lipid. The strain was initially grown in BG-11 as a reference medium and later in phenolic solution. The strain was found to sustain 150 mg/L concentration of phenol. SEM study had shown the clear difference in the structure of cyanobacterial strain when grown in pure BG-11 medium and phenolic solution. Maximum removal of phenol (98.5 ± 0.14%) was achieved with an initial concentration 100 mg/L, 5% inoculum size at pH 11, while the maximum amount of dry biomass (0.38 ± 0.02 g/L) was obtained at pH 7, initial phenol concentration of 50 mg/L, and 5% inoculum size. Highest lipid yield was achieved at pH 11, initial phenol concentration of 100 mg/L, and 5% inoculum size. Coke-oven wastewater collected from secondary clarifier of effluent treatment plant was also treated with the said strain and the removal of different pollutants was observed. The study suggests the utilization of such potential cyanobacterial strain in treating industrial effluent containing phenol., Competing Interests: Compliance with ethical standardsOn behalf of all authors, the corresponding author states that there is no conflict of interest.

Purpose: The current standard of care for surgically eligible stage I non-small cell lung cancer (NSCLC) is surgical resection, but emerging data suggest that stereotactic body radiation therapy (SBRT) is potentially as effective as surgery. However, specialist views of the current evidence about SBRT and how they would incorporate a randomized controlled trial (RCT) into practice is unclear. We sought to understand specialist opinions about evidence regarding treatment of stage I NSCLC and how this translates into practice and clinical trial implementation., Methods and Materials: We used a 28-item, web-based survey that invited all participating providers from the American Society for Radiation Oncology, American Thoracic Society Thoracic Oncology Assembly, and the International Association for the Study of Lung Cancer to share opinions regarding practice beliefs, treatment of stage I NSCLC, and a clinical trial scenario., Results: A total of 959 surveys were completed; 64% were from radiation oncologists (ROs) and 49% were from outside the United States. The majority of ROs (80%) reported that current evidence indicates that SBRT has the same or a better benefit compared with surgery for surgically eligible patients with stage I NSCLC; 28% of non-radiation oncologists (NROs) indicated the same ( P  < .01). Almost all ROs (94%), compared with 62% of NROs, would permit surgically eligible patients to enroll in an RCT of SBRT versus surgery ( P  < .01). Most ROs (82%) and NROs (87%) believed that changing practice in thoracic surgery would be somewhat difficult, very difficult, or impossible (P = .066) even if an RCT showed better survival with SBRT., Conclusions: NROs believe that SBRT is much less effective than surgery, contrary to ROs, who believe that they are similar. Most would support an RCT, but NROs would do so less. Changes in surgical practice may be challenging even if an RCT shows better mortality and quality of life with SBRT. These results are helpful in the creation and dissemination of RCTs that are designed to understand this question.

Mass spectrometry (MS) has become an accessible tool for whole proteome quantitation with the ability to characterize protein expression across thousands of proteins within a single experiment. A subset of MS quantification methods (e.g., SILAC and label-free) monitor the relative intensity of intact peptides, where thousands of measurements can be made from a single mass spectrum. An alternative approach, isobaric labeling, enables precise quantification of multiple samples simultaneously through unique and sample specific mass reporter ions. Consequently, in a single scan, the quantitative signal comes from a limited number of spectral features (≤11). The signal observed for these features is constrained by automatic gain control, forcing codependence of concurrent signals. The study of constrained outcomes primarily belongs to the field of compositional data analysis. We show experimentally that isobaric tag proteomics data are inherently compositional and highlight the implications for data analysis and interpretation. We present a new statistical model and accompanying software that improves estimation accuracy and the ability to detect changes in protein abundance. Finally, we demonstrate a unique compositional effect on proteins with infinite changes. We conclude that many infinite changes will appear small and that the magnitude of these estimates is highly dependent on experimental design.

Prolyl hydroxylation is a very common post-translational modification and plays many roles in eukaryotes such as collagen stabilization, hypoxia sensing, and controlling protein transcription and translation. There is a growing body of evidence that suggests that prokaryotes contain prolyl 4-hydroxylases (P4Hs) homologous to the hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) enzymes that act on elongation factor Tu (EFTu) and are likely involved in the regulation of bacterial translation. Recent biochemical and structural studies with a PHD from Pseudomonas putida (PPHD) determined that it forms a complex with EFTu and hydroxylates a prolyl residue of EFTu. Moreover, while animal, plant, and viral P4Hs act on peptidyl proline, most prokaryotic P4Hs have been known to target free l-proline; the exceptions include PPHD and a P4H from Bacillus anthracis (BaP4H) that modifies collagen-like proline-rich peptides. Here we use biophysical and mass spectrometric methods to demonstrate that BaP4H recognizes full-length BaEFTu and a BaEFTu 9-mer peptide for site-specific proline hydroxylation. Using size-exclusion chromatography coupled small-angle X-ray scattering (SEC-SAXS) and binding studies, we determined that BaP4H forms a 1:1 heterodimeric complex with BaEFTu. The SEC-SAXS studies reveal dissociation of BaP4H dimeric subunits upon interaction with BaEFTu. While BaP4H is unusual within bacteria in that it is structurally and functionally similar to the animal PHDs and collagen P4Hs, respectively, this work provides further evidence of its promiscuous substrate recognition. It is possible that the enzyme might have evolved to hydroxylate a universally conserved protein in prokaryotes, similar to the PHDs, and implies a functional role in B. anthracis.

Objective: It is important to identify separate publications that report outcomes from the same underlying clinical trial, in order to avoid over-counting these as independent pieces of evidence., Methods: We created positive and negative training sets (comprised of pairs of articles reporting on the same condition and intervention) that were, or were not, linked to the same clinicaltrials.gov trial registry number. Features were extracted from MEDLINE and PubMed metadata; pairwise similarity scores were modeled using logistic regression., Results: Article pairs from the same trial were identified with high accuracy (F1 score=0.843). We also created a clustering tool, Aggregator, that takes as input a PubMed user query for RCTs on a given topic, and returns article clusters predicted to arise from the same clinical trial., Discussion: Although painstaking examination of full-text may be needed to be conclusive, metadata are surprisingly accurate in predicting when two articles derive from the same underlying clinical trial., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Ultrasound at 5.0 MHz was noted to be chondro-inductive, with improved SOX-9 gene and COL2A1 protein expression in constructs that allowed for cell-to-cell contact. To achieve tissue-engineered cartilage using macroporous scaffolds, it is hypothesized that a combination of ultrasound at 5.0 MHz and transforming growth factor-β3 induces human mesenchymal stem cell differentiation to chondrocytes. Expression of miR-145 was used as a metric to qualitatively assess the efficacy of human mesenchymal stem cell conversion. Our results suggest that in group 1 (no transforming growth factor-β3, no ultrasound), as anticipated, human mesenchymal stem cells were not efficiently differentiated into chondrocytes, judging by the lack of decrease in the level of miR-145 expression. Human mesenchymal stem cells differentiated into chondrocytes in group 2 (transforming growth factor-β3, no ultrasound) and group 3 (transforming growth factor-β3, ultrasound) with group 3 having a 2-fold lower miR-145 when compared to group 2 at day 7, indicating a higher conversion to chondrocytes. Transforming growth factor-β3-induced chondrogenesis with and without ultrasound stimulation for 14 days in the ultrasound-assisted bioreactor was compared and followed by additional culture in the absence of growth factors. The combination of growth factor and ultrasound stimulation (group 3) resulted in enhanced COL2A1, SOX-9, and ACAN protein expression when compared to growth factor alone (group 2). No COL10A1 protein expression was noted. Enhanced cell proliferation and glycosaminoglycan deposition was noted with the combination of growth factor and ultrasound stimulation. These results suggest that ultrasound at 5.0 MHz could be used to induce chondrogenic differentiation of mesenchymal stem cells for cartilage tissue engineering.

Chondrocyte-seeded scaffolds were cultured in an ultrasound (US)-assisted bioreactor, which supplied the cells with acoustic energy around resonance frequencies (~5.0 MHz). Polyurethane-polycarbonate (BM), chitosan (CS) and chitosan-n-butanol (CSB) based scaffolds with varying porosities were chosen and the following US regimen was employed: 15 kPa and 60 kPa, 5 min per application and 6 applications per day for 21 days. Non-stimulated scaffolds served as control. For BM scaffolds, US stimulation significantly impacted cell proliferation and depth-independent cell population density compared to controls. The highest COL2A1/COL1A1 ratios and ACAN mRNA were noted on US-treated BM scaffolds compared to controls. A similar trend was noted on US-treated cell-seeded CS and CSB scaffolds, though COL2A1/COL1A1 ratios were significantly lower compared to BM scaffolds. Expression of Sox-9 was also elevated under US and paralleled the COL2A1/COL1A1 ratio. As an original contribution, a simplified mathematical model based on Biot theory was developed to understand the propagation of the incident US wave through the scaffolds and the model analysis was connected to cellular responses. Scaffold architecture influenced the distribution of US field, with the US field being the least attenuated in BM scaffolds, thus coupling more mechanical energy into cells, and leading to increased cellular activity., (Published by Elsevier Ltd.)

Objective: To evaluate the comparative benefits and harms in both mother and child of antidepressant treatment for depression in pregnant or postpartum women., Data Sources: MEDLINE, the Cochrane Library, CINAHL, Scopus, ClinicalTrials.gov (inception to July 2013), manufacturers, and reference lists., Methods of Study Selection: Two reviewers independently selected studies of pregnant women with depression comparing antidepressants with each other, placebo or no treatment, or nondrug treatments. Studies making comparisons among women taking antidepressants for any reason and those not taking antidepressants (depression status unknown) were used to fill gaps in the evidence., Tabulation, Integration, and Results: Dual study data extraction and quality assessment were used. Six randomized controlled trials and 15 observational studies provided evidence. Low-strength evidence suggested neonates of pregnant women with depression taking selective serotonin reuptake inhibitors had higher risk of respiratory distress than did neonates of untreated women (13.9% compared with 7.8%; P<.001) but no difference in risk of neonatal convulsions (0.14% compared with 0.11%; P=.64) or preterm birth (17% compared with 10%; P=.07). Indirect evidence from studies of pregnant women receiving antidepressants for mixed or unreported reasons compared with pregnant women not taking antidepressants (depression status unknown) suggested future research should focus on congenital anomalies and autism spectrum and attention deficit disorders in the child. In postpartum depression, low-strength evidence suggested symptom response was not improved when sertraline was added to psychotherapy or when cognitive-behavioral therapy was added to paroxetine. Evidence was insufficient for other outcomes, including depression symptoms, functional capacity, breastfeeding, and infant and child development. A serious limitation is the lack of study populations of exclusively depressed pregnant and postpartum women., Conclusion: Evidence about the comparative benefits and harms of pharmacologic treatment of depression in pregnant and postpartum women was largely inadequate to allow informed decisions about treatment. Considering the prevalence of depression, filling this gap is essential.

Objectives: To evaluate the benefits and harms of pharmacological therapy for depression in women during pregnancy or the postpartum period., Data Sources: Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE, Scopus, ClinicalTrials.gov, and Scientific Information Packets from pharmaceutical manufacturers. Databases were searched from their inception to July 2013.., Review Methods: We included studies comparing pharmacological treatments for depression during or after pregnancy with each other, with nonpharmacological treatments, or with usual care or no treatment. Outcomes included both maternal and infant or child benefits and harms. Dual review was used for study inclusion, data abstraction, and quality assessment. We assessed study quality using methods of the Drug Effectiveness Review Project. We graded the strength of the body of evidence according to the methods of the Effective Health Care Program. Direct evidence comprised studies that compared interventions of interest in the population of interest (i.e., depressed women) and measured the outcomes of interest. Studies comparing groups of depressed women with control groups with no evidence of depression were considered indirect., Results: We included 15 observational studies that provided direct evidence on benefits and harms of antidepressants for depression during pregnancy. We included six randomized controlled trials and two observational studies of antidepressant treatment for depression in postpartum women. Studies of depressed pregnant women primarily compared antidepressant treatment with no treatment, and studies of postpartum women also compared antidepressants alone with combination antidepressant-nonpharmacological treatments. This evidence was insufficient to draw conclusions on the comparative benefits or harms of antidepressants for the outcomes of maternal depression symptoms, functional capacity, breastfeeding, mother-infant dyad interactions, and infant and child development for either pregnant or postpartum women with depression. Low-strength evidence suggests that neonates of women with depression taking selective serotonin reuptake inhibitors (SSRIs) during pregnancy had higher risk of respiratory distress than neonates of untreated women but that risk of preterm birth or neonatal convulsions does not differ between these groups. Direct evidence on the risk of major malformations and neonatal development with exposure to antidepressants in utero was insufficient to draw conclusions. For postpartum women with depression, evidence was insufficient to evaluate the full range of benefits and harms of treatment. Low-strength evidence was unable to show a benefit of adding brief psychotherapy or cognitive behavioral therapy to SSRIs., To address gaps in the direct evidence, we included an additional 109 observational studies of pregnant women receiving antidepressants for mixed or unreported reasons compared with pregnant women not taking antidepressants whose depression status was unknown. Signals from this indirect evidence suggest that future research should focus on the comparative risk of congenital anomalies and neonatal motor developmental delays. Although the absolute increased risk of autism spectrum disorder or attention-deficit hyperactivity disorder in the child associated with antidepressant use for depression in pregnancy may be very small, this issue also merits attention in future research. Future research should compare available treatments in groups of women with depression and have adequate sample sizes. Investigations should also take into account potential confounding, including age, race, parity, other exposures (e.g., alcohol, smoking, and other potential teratogens), and the impact of dose, severity of depression, timing of diagnosis, or prior depressive episodes., Conclusions: Evidence about the comparative benefits and harms of pharmacological treatment of depression in pregnant and postpartum women was largely inadequate to allow well-informed decisions about treatment. For pregnant women, this was mainly because comparison groups were not exclusively depressed women. For postpartum women, the lack of evidence arose chiefly from a scarcity of studies. These are major limitations, as depression is known to be associated with serious adverse outcomes. Given the prevalence of depression and its impact on the lives of pregnant women, new mothers, and children, new research to fill this informational gap is essential., Competing Interests: None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report., (This publication is in the public domain.)

The need for tissue-engineered constructs as replacement tissue continues to grow as the average age of the world's population increases. However, additional research is required before the efficient production of laboratory-created tissue can be realized. The multitude of parameters that affect cell growth and proliferation is particularly daunting considering that optimized conditions are likely to change as a function of growth. Thus, a generalized research platform is needed in order for quantitative studies to be conducted. In this article, an ultrasonic bioreactor is described for use in studying the response of cells to ultrasonic stimulation. The work is focused on chondrocytes with a long-term view of generating tissue-engineered articular cartilage. Aspects of ultrasound (US) that would negatively affect cells, including temperature and cavitation, are shown to be insignificant for the US protocols used and which cover a wide range of frequencies and pressure amplitudes. The bioreactor is shown to have a positive influence on several factors, including cell proliferation, viability, and gene expression of select chondrocytic markers. Most importantly, we show that a total of 138 unique proteins are differentially expressed on exposure to ultrasonic stimulation, using mass-spectroscopy coupled proteomic analyses. We anticipate that this work will serve as the basis for additional research which will elucidate many of the mechanisms associated with cell response to ultrasonic stimulation.

Four new dicyanamide (dca) bridged multinuclear Zn(II)-Schiff-base complexes, {[Zn2L(1)(μ1,5-dca)dca]·CH3OH}2 (1), [Zn2L(2)(μ1,5-dca)dca]n (2), [Zn3L(3)2(μ1,5-dca)2]n (3), and [(ZnL(4))2Zn(μ1,5-dca)dca]n (4), have been synthesized using four different Schiff bases L(1)H2 = N,N(/)-bis(3-methoxysalicylidenimino)-1,3-diaminopentane, L(2)H2 = N,N'-bis(5-bromo-3-methoxysalicylidenimino)-1,3-diaminopropane, L(3)H2 = N,N'-bis(5-bromosalicylidenimino)-1,3-diaminopropane, and L(4)H2 = N,N'-bis(5-chlorosalicylidenimino)-1,3-diaminopropane and NaN(CN)2 in order to extend the metal-ligand assembly. The directional properties of linear end-to-end bridging dca ligands have resulted in different metal ion connectivities leading to unique variety of templates in each of the complexes. All the ligands and complexes have been characterized by microanalytical and spectroscopic techniques. The structures of the complexes have been conclusively determined by single crystal X-ray diffraction studies. Thermogravimetric analyses have been performed to investigate the thermal stability of the metal-organic frameworks. Finally, the photoluminescence properties of the complexes as well as their respective ligands have been investigated with a comparative approach.

Surfaces that preferentially bind human serum albumin (HSA) were generated by grafting albumin-binding linear peptide (LP1) onto silicon surfaces. The research aim was to evaluate the adsorption pattern of proteins and the adhesion of platelets from platelet-poor plasma and platelet-rich plasma, respectively, by albumin-binding surfaces under physiological shear rate (96 and 319 s(-1)) conditions. Bound proteins were quantified using enzyme-linked immunosorbent assays (ELISAs) and two-dimensional gel electrophoresis. A ratio of ∼1000:100:1 of adsorbed HSA, human immunoglobulin (HIgG) and human fibrinogen (HFib) was noted, respectively, on LP1-functionalized surfaces, and a ratio of ∼5:2:1 of the same was noted on control surfaces, as confirmed by ELISAs. The surface-adsorbed von Willebrand factor was undetectable by sensitive ELISAs. The amount of adhered platelets correlated with the ratio of adsorbed HSA/HFib. Platelet morphology was more rounded on LP1-functionalized surfaces when compared to control surfaces. The platelet adhesion response on albumin-binding surfaces can be explained by the reduction in the co-adsorption of other plasma proteins in a surface environment where there is an excess of albumin molecules, coupled with restrictions in the conformational transitions of other surface-adsorbed proteins into hemostatically active forms.

The response of biomaterial surfaces when exposed to blood is in part dependent upon the nature and composition of the adsorbed layer of proteins. Surfaces passivated with albumin have been shown to reduce platelet adhesion and activation. In an attempt to develop surfaces that can selectively and specifically bind albumin, silicon-based surfaces were functionalized with linear peptides and chemical ligands that displayed an affinity for albumin. Peptide functionalized surfaces were observed to preferentially bind albumin when compared to human immunoglobulin and human fibrinogen, which possess low densities of surface adsorbed platelets. The platelet morphology was noted to be discoid on the peptide modified surface. Both the unmodified control and SCL functionalized surfaces had high densities of surface adhered platelets with spread out morphology. The peptide and SCL functionalized surfaces were noted to have no impact on PTT and PT clotting times, indicating that the extrinsic and intrinsic pathways were unperturbed by the surfaces generated.

Both pulsed- and square-wave, low-intensity ultrasound (US) signals have been reported to impact chondrocyte function and biosynthetic activity. In this study, a low-intensity diffuse ultrasound (LIDUS) signal at 5.0 MHz (0.14 mW/cm(2)) was employed to stimulate bovine chondrocytes seeded in three-dimensional (3D) chitosan-based matrices. While the duration of application was constant at 51 s, US was applied once, twice, four times and eight times/day, and the impacts of US on the biosynthetic activity of chondrocytes and the expression of chondrocyte-specific genes were evaluated. When stimulated with continuous US for predetermined time intervals, chondrocytes had higher levels of type II collagen, aggrecan, L-Sox5 and Sox9 mRNA expression when compared to controls; however, under the same conditions, the expression of MMP-3 was downregulated. Interestingly, both Sox5 and Sox9 genes coordinately responded to changes in US stimulation and generally mirrored the response of collagen type II transcript to changes in US stimulation. RT-PCR analysis revealed that US stimulation increased the gene expression of cell-surface integrins α5 and β1. The expression of integrins α2 was downregulated by US treatment, suggesting that multiple integrin subunits may be involved in the regulation of chondrocytic function in response to US stimuli. The enhancement in the abundance of the mRNA transcripts upon US stimulation was observed to correlate with the protein expression of collagen type I, collagen type II, and integrins α5 and β1. In conclusion, the US stimulation regimen employed was shown to modulate the proliferative capacity, biosynthetic activity and integrin mRNA expression of articular chondrocytes maintained in 3D matrices., (Copyright © 2011 John Wiley & Sons, Ltd.)

Surface modification strategies that take advantage of the passivation effects of albumin are important in the development of biomaterial surfaces. In this study, linear peptides (LP1, LP2) and a small chemical ligand (SCL) with albumin binding affinities were grafted onto silane functionalized silicon substrates. Surfaces were characterized with contact angle and ellipsometric measurements, and densities of immobilized ligands were assessed spectroscopically. Ellipsometrically measured thickness correlated with the predicted molecular lengths of grafted moieties. Contact angle analysis indicated that the LP1 and LP2 functionalized surfaces were hydrophilic compared to SCL functionalized and control surfaces. Adsorption of albumin from human serum was evaluated and quantified via specific enzyme-linked immunosorbent assays and 2D gel electrophoresis. The following trend was noted for surface adsorbed albumin: LP1 > LP2 > SCL > C, with LP1 derivatized surfaces having ~2.450 μg/cm(2) of bound albumin. LP1 derivatized surfaces possessed the least number of adsorbed platelets with rounded platelet morphology when compared to control surface.

Two new Cu(II) linear trinuclear Schiff base complexes, [Cu3(L)2(CH3COO)2] (1) and [Cu3(L)2(CF3COO)2] (2), have been prepared using a symmetrical Schiff base ligand H2L [where H2L = N,N'-bis(2-hydroxyacetophenone)propylenediimine]. Both of the complexes have been characterized by elemental analyses, Fourier transform IR, UV/vis, and electron paramagnetic resonance spectroscopy. Single-crystal X-ray structures show that the adjacent Cu(II) ions are linked by double phenoxo bridges and a mu(2)-eta(1):eta(1) carboxylato bridge. In each complex, the central copper atom is located in an inversion center with distorted octahedral coordination geometry, while the terminal copper atoms have square-pyramidal geometry. Cryomagnetic susceptibility measurements over a wide range of temperature exhibit a distinct antiferromagnetic interaction of J = -36.5 and -72.3 cm(-1) for 1 and 2, respectively. Density functional theory calculations (B3LYP functional) and continuous-shape measurement (CShM) studies have been performed on the trinuclear unit to provide a qualitative theoretical interpretation of the antiferromagnetic behavior shown by the complexes.

An unusual early, childhood presentation in a case with reputured non-coronary sinus of Valsalva aneurysm with Gerbode defect and severe pulmonary hypertension is described. The reasons for early rupture are discussed and anatomically important relations of membranous septum, fibroskeleton of heart and conduction system are schematically elucidated. Associated severe tricuspid and aortic regurgitation are explained to be secondary effects following the rupture of aneurysm. A technique of surgical correction of this rare association of anomalies using single PTFE patch is illustrated, cautiously safeguarding the closely related conduction system. Regurgitant aortic and tricuspid valves were also successfully repaired. In retrospect, early repair before rupture of aneurysm and onset of severe pulmonary hypertension may be more beneficial, which would also prevent the leakage of semilunar and atrioventricular valves.