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Background: Symmetrical alopecia is a common symptom of endocrine and autoimmune diseases, which are rarely manifested with pruritus. Increased levels of stress in primates have been presented with increased levels of pruritus and alopecia appearance. Methods: A pruritic and alopecic disease was investigated in a group of tufted capuchin monkeys (N = 12), but due to ethical reasons, four random animals were further investigated by numerous diagnostic methods. The impact of food and enclosure enrichment was assessed and observed over a 2‐year period. Results: Histopathology of four random tufted capuchin monkeys revealed lymphocytic perifolliculitis, with an appearance of a "swarm of bees" which was suggestive of alopecia areata. Etiological classification of pruritus excluded dermatological, systemic, and neurological causes, making it behavioral. Enclosure and food enrichment had a beneficial impact on pruritus (12/12) and alopecia (10/12). Conclusion: The findings were suggestive of alopecia areata, while the pruritus was considered behavioral in origin. Alopecia and pruritus improved upon enclosure and food enrichment. [ABSTRACT FROM AUTHOR]

The number of structural studies of peptoids has grown dramatically over the past 20 years. To date, over 100 high‐resolution structures have been reported for peptoids, which are typically defined as N‐substituted glycine oligomers. We have collected these structures and standardized their sequence representations to facilitate structural analysis as the dataset continues to grow. These structures are presented online as The Peptoid Data Bank (databank.peptoids.org), which also provides persistent links to the published structural data. This review analyzes the present collection of structures and finds extensive support for grouping side chains by their chemistry at the position adjacent to the backbone nitrogen. Groups of side chains with similar chemistry at this position show similar influences on the conformational preferences of the backbone. We also observe a relationship between the side chain and backbone conformations for many monomers that has not previously attracted significant discussion: the values of the χ1 and ϕ dihedrals are correlated. We outline a general design strategy for attaining a specific backbone conformation based on the patterns seen in the collected structures. [ABSTRACT FROM AUTHOR]

Background: A growing proportion of transplant donors and recipients have a history of COVID‐19 infection. This study sought to characterize clinical practice after recipient or donor COVID‐19 infection. Methods: An online survey was distributed to heart transplant clinicians through a professional society message board and social media. Responses were collected between September 29 and November 5, 2021. Results: There were 222 health care professionals (68% transplant cardiologists, 22% transplant surgeons, 10% other) across diverse geographic regions who completed the survey. While there was significant variation in donor acceptance, as it relates to past and current COVID‐19 infection, the respondents were fairly cautious: 28% would not typically accept a donor with a history of COVID‐19 regardless of the infection course and > 80% would not accept donors who had evidence of myocardial dysfunction during past COVID‐19 infection, or who died of COVID‐19 or its complications. The timing of candidate reactivation on the waiting list after COVID‐19 infection also varied and often diverged from scenarios addressed by social guidelines. Eighty‐one percent of the respondents felt COVID‐19 vaccine should be mandatory before transplant, but this rate varied by geographic region. Conclusion: Our results reflect evolving experience of the heart transplant field at a time of lack of high‐quality evidence. In the absence of longer‐term outcome data for donors and transplant candidates with history of COVID‐19 infection, clinicians remain cautious; however, this approach will likely need to be refined as an increasing proportion of the population will continue to be infected with COVID‐19. [ABSTRACT FROM AUTHOR]

The morphological changes of phosphonate polypeptoid electrolyte membranes, poly‐N‐(2‐ethyl)hexylglycine‐block‐poly‐N‐phosphonomethylglycine (pNehm‐b‐pNpmn), in hydrated and dry states were characterized by cryogenic transmission electron microscopy (cryo‐TEM) and cryogenic electron tomography (cryo‐ET). The analysis of 3D tomograms revealed that the pNeh9‐b‐pNpm9 thin films absorbed a large amount of water, resulting in the formation of membranes that were nearly flat and giant multicompartment vesicles dispersed in the water phase. A simple lamellar phase appeared when the films were dried. In contrast, pNeh18‐b‐pNpm18 thin films absorbed little water and formed small highly curved unilamellar and multilamellar vesicles. Water was located mainly outside the closely‐packed vesicles. When water was removed by drying, the walls of adjacent vesicles collapsed to form honeycomb‐like capsules. The changes in domain size reflected changes in chain conformations. The pNpm9 blocks were saturated by water and fully extended, while pNpm18 blocks were neither saturated by water nor fully extended. In addition, the thicknesses of hydrophobic blocks in the hydrated films of both pNeh9‐b‐pNpm9 and pNeh18‐b‐pNpm18 were smaller than those in the dry films, reflecting an increase of the average distance between the neighboring junctions of polypeptoid molecules. [ABSTRACT FROM AUTHOR]

Peptoids belong to a class of sequence‐controlled polymers comprising of N‐alkylglycine. This study focuses on using tandem mass spectrometry techniques to characterize the fragmentation patterns of a set of singly and doubly protonated peptoids consisting of one basic residue placed at different positions. The singly protonated peptoids fragment by producing predominately high‐abundant C‐terminal ions called Y‐ions and low‐abundant N‐terminal ions called B‐ions. Computational studies suggest that the proton affinity (PA) of the C‐terminal fragments is generally higher than that of the N‐terminal fragments, and the PA of the former increases as the fragments are elongated. The B‐ions are likely formed upon dissociating the proton‐activated amide bonds via an oxazolone structure, and the Y‐ions are produced subsequently by abstracting a proton from the newly formed B‐ions, which is energetically favored. The doubly protonated peptoids prefer to fragment closest to either the N‐ or the C‐terminus and produce corresponding B/Y‐ion pairs. The basic residue seems to dictate the preferred fragmentation site, which may be the result of minimizing the repulsion between the two charges. Water and terminal neutral losses are a facile process accompanying the peptoid fragmentation in both charge states. The patterns appear to be highly influenced by the location of the basic residue. [ABSTRACT FROM AUTHOR]

Background: Sympathetic reinnervation after heart transplantation (HTX) is a known phenomenon, which has an impact on patient heart rate variability and exercise capacity. The impact of reinnervation on myocardial structure has not been evaluated yet.Propose: To evaluate the feasibility of simultaneous imaging of cardiac reinnervation and cardiac structure using a hybrid PET/MRI system.Study Type: Prospective / pilot study.Subjects: Ten patients, 4-21 years after cardiac transplantation.Field Strength/sequence: 3 T hybrid PET/MRI system. Cine SSFP, T1 mapping (modified Look-Locker inversion recovery sequence) pre/postcontrast as well as dynamic [11 C]meta-hydroxyephedrine ([11 C]mHED) PET.Assessment: All MRI and PET parameters were evaluated by experienced readers using dedicated postprocessing software packages for cardiac MRI and PET. For all parameters a 16-segment model for the left ventricle was applied.Statistical Tests: Mann-Whitney U-test; Spearman correlations.Results: Thirty-six of 160 myocardial segments showed evidence of reinnervation by PET. On a segment-based analysis, mean native T1 relaxation times were nonsignificantly altered in segments with evidence of reinnervation (1305 ± 151 msec vs. 1270 ± 112 msec; P = 0.1), whereas mean extracellular volume (ECV) was significantly higher in segments with evidence of reinnervation (35.8 ± 11% vs. 30.9 ± 7%; P = 0.019). There were no significant differences in wall motion (WM) and wall thickening (WT) between segments with or without reinnervation (mean WM: 7.6 ± 4 mm vs. group B: 9.3 ± 7 mm [P = 0.13]; WT: 79 ± 63% vs. 94 ± 74% [P = 0.27]) under resting conditions.Data Conclusion: The assessment of cardiac reinnervation using a hybrid PET/MRI system is feasible. Segments with evidence of reinnervation by PET showed nonsignificantly higher T1 relaxation times and a significantly higher ECV, suggesting a higher percentage of diffuse fibrosis in these segments, without impairment of rest WM and WT.Level Of Evidence: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:1326-1335. [ABSTRACT FROM AUTHOR]

Conformational control in peptoids, N-substituted glycines, is crucial for the design and synthesis of biologically-active compounds and atomically-defined nanomaterials. While there are a growing number of structural studies in solution, most have been performed with conformationallyconstrained short sequences (e.g., sterically-hindered sidechains or macrocyclization). Thus, the inherent degree of heterogeneity of unconstrained peptoids in solution remains largely unstudied. Here, we explored the folding landscape of a series of simple peptoid tetramers in aqueous solution by NMR spectroscopy. By incorporating specific 13C-probes into the backbone using bromoacetic acid-2-13C as a submonomer, we developed a new technique for sequential backbone assignment of peptoids based on the 1,n-Adequate pulse sequence. Unexpectedly, two of the tetramers, containing an N-(2-aminoethyl)glycine residue (Nae), had preferred conformations. NMR and molecular dynamics studies on one of the tetramers showed that the preferred conformer (52%) had a transcis-trans configuration about the three amide bonds. Moreover, >80% of the ensemble contained a cis amide bond at the central amide. The backbone dihedral angles observed fall directly within the expected minima in the peptoid Ramachandran plot. Analysis of this compound against similar peptoid analogs suggests that the commonly used Nae monomer plays a key role in the stabilization of peptoid structure via a side-chain-to-main-chain interaction. This discovery may offer a simple, synthetically high-yielding approach to control peptoid structure, and suggests that peptoids have strong intrinsic conformational preferences in solution. These findings should facilitate the predictive design of folded peptoid structures, and accelerate application in areas ranging from drug discovery to biomimetic nanoscience. [ABSTRACT FROM AUTHOR]

Like polypeptides, peptoids, or N-substituted glycine oligomers, have intrinsic conformational preferences due to their amide backbones and close spacing of side chain substituents. However, the conformations that peptoids adopt are distinct from polypeptides due to several structural differences: the peptoid backbone is composed of tertiary amide bonds that have trans and cis conformers similar in energy, they lack a backbone hydrogen bond donor, and have an Nsubstituent. To better understand how these differences manifest in actual peptoid structures, we analyzed 46 high quality, experimentally determined peptoid structures reported in the literature to extract their backbone conformational preferences. One hundred thirty-two monomer dihedral angle pairs were compared to the calculated energy landscape for the peptoid Ramachandran plot, and were found to fall within the expected minima. Interestingly, only two regions of the backbone dihedral angles ϕ and ψ were found to be populated that are mirror images of each other. Furthermore, these two conformers are present in both cis and trans forms. Thus, there are four primary conformers that are sufficient to describe almost all known backbone conformations for peptoid oligomers, despite conformational constraints imposed by a variety of side chains, macrocyclization, or crystal packing forces. Because these conformers are predominant in peptoid structure, and are distinct from those found in protein secondary structures, we propose a simple naming system to aid in the description and classification of peptoid structure. [ABSTRACT FROM AUTHOR]

Interleukin (IL)‐33 is a member of the IL‐1 family and is able to act cardioprotective. The aim of this study was to investigate the regulation of IL‐33 by 3‐hydroxy‐3‐methylglutaryl‐coenzyme‐A (HMG‐CoA) reductase inhibitors (statins) and bisphosphonates (BPs) in human cardiac tissue. The lipophilic fluvastatin, simvastatin, atorvastatin, and lovastatin as well as the nitrogenous BPs alendronate and ibandronate, but not hydrophilic pravastatin increased IL‐33 mRNA and intracellular IL‐33 protein levels in both human adult cardiac myocytes (HACM) and fibroblasts (HACF). Additionally, fluvastatin reduced soluble ST2 secretion from HACM. IL‐33 was also up‐regulated by the general inhibitor of prenylation perillic acid, a RhoA kinase inhibitor Y‐27632, and by latrunculin B, but statin‐induced IL‐33 expression was inhibited by mevalonate, geranylgeranyl pyrophosphate (GGPP) and RhoA activator U‐46619. The IL‐33 promoter was 2.3‐fold more accessible in statin‐treated HACM compared to untreated cells (P = 0.037). In explanted hearts of statin‐treated patients IL‐33 protein was up‐regulated as compared with the hearts of non‐statin‐treated patients (P = 0.048). As IL‐33 was previously shown to exert cardioprotective effects, one could speculate that such up‐regulation of IL‐33 expression in human cardiac cells, which might happen mainly through protein geranylgeranylation, could be a novel mechanism contributing to known cardioprotective effects of statins and BPs. [ABSTRACT FROM AUTHOR]

Hydrophobicity has proven to be an extremely useful parameter in small molecule drug discovery programmes given that it can be used as a predictive tool to enable rational design. For larger molecules, including peptoids, where folding is possible, the situation is more complicated and the average hydrophobicity (as determined by RP-HPLC retention time) may not always provide an effective predictive tool for rational design. Herein, we report the first ever application of partitioning experiments to determine the log D values for a series of peptoids. By comparing log D and average hydrophobicities we highlight the potential advantage of employing the former as a predictive tool in the rational design of biologically active peptoids. [ABSTRACT FROM AUTHOR]

A novel approach to sequentially degrade peptoid N-terminal N-(substituted)glycine residues on the solid-phase using very mild conditions is reported. This method relies on the treatment of resin-bound, bromoacetylated peptoids with silver perchlorate in THF, leading to an intramolecular cyclization reaction to liberate the terminal residue as a N-substituted morpholine-2,5-dione, resulting in a truncated peptoid upon hydrolysis and a silver bromide byproduct. Side-chain functional group tolerance is explored and reaction kinetics are determined. In a series of pentapeptoids possessing variable, non-nucleophilic side-chains at the second position (R²), we demonstrate that sequential N-terminal degradation of the first two residues proceeds in 87% and 74% conversions on average, respectively. We further demonstrate that the degradation reaction is selective for peptoids, and represents substantial progress toward a mild, iterative sequencing method for peptoid oligomers. [ABSTRACT FROM AUTHOR]

Background: In patients with advanced refractory heart failure (HF) cardiac transplantation (HTX), conservative medical management and the implantation of a ventricular assist device (VAD) represent valuable options. The determination of the best therapeutic destination strategy for the individual patient remains a challenge. The aim of this study was to assess the clinical outcome in advanced refractory HF patients either managed conservatively receiving optimal contemporary medical therapy ('conservative'), or who who underwent pulsatile flow VAD ('pVAD') or continuous-flow VAD ('contVAD') implantation. Materials and methods: A total of 118 patients with INTERMACS profile >1 at baseline, who died, or fully completed a 24-month follow-up free from HTX were included into this retrospective analysis. All-cause mortality at 24 months was assessed and compared between the three groups. Results: Fifty (42%) patients were managed conservatively, 25 (21%) received a pVAD and 43 (36%) a contVAD. NT-proBNP values were comparable between the three groups (median 4402 (IQR 2730-13390) pg/mL, 3580 (1602-6312) pg/mL and 3693 (2679-8065) pg/mL, P = 0·256). Mean survival was 18·6 (95% CI 16·2-21·0) months for patients managed conservatively, 7·0 (3·9-10·0) for pVAD and 20·5 (18·2-22·8) for contVAD (overall log-rank test P < 0·001). Conservatively managed patients spent a mean of 22·4 (95% CI 22·1-22·8), pVAD 17·7 (15·4-20·1) and contVAD 21·6 (21·2-22·1) months out of hospital (conservative vs. pVAD P < 0·001; conservative vs. contVAD P = 0·015; pVAD vs. contVAD P < 0·001). Conclusions: In accordance with the literature, contVAD resulted in a significantly better clinical outcome than pVAD implantation. However, conservative management with current optimal medical therapy appears to remain a valuable option for patients with advanced HF. [ABSTRACT FROM AUTHOR]

Background and Purpose: Valproic acid (VPA), a widely used epilepsy and bipolar disorder treatment, provides acute protection against haemorrhagic shock-induced mortality in a range of in vivo models through an unknown mechanism. In the liver, this effect occurs with a concomitant protection against a decrease in GSK3β-Ser(9) phosphorylation. Here, we developed an in vitro model to investigate this protective effect of VPA and define a molecular mechanism.Experimental Approach: The human hepatocarcinoma cell line (Huh7) was exposed to conditions occurring during haemorrhagic shock (hypoxia, hypercapnia and hypothermia) to investigate the changes in GSK3β-Ser(9) phosphorylation for a 4 h period following treatment with VPA, related congeners, PPAR agonists, antagonists and siRNA.Key Results: Huh7 cells undergoing combined hypoxia, hypercapnia, and hypothermia reproduced the reduced GSK3β-Ser(9) phosphorylation shown in vivo during haemorrhagic shock, and this change was blocked by VPA. The protective effect occurred through upstream PTEN and Akt signalling, and prevented downstream β-catenin degradation while increasing histone 2/3 acetylation. This effect was reproduced by several VPA-related compounds with known PPARγ agonist activity, independent of histone deacetylase (HDAC) inhibitory activity. Specific pharmacological inhibition (by T0070907) or knockdown of PPARγ blocked the protective effect of VPA against these signalling changes and apoptosis. In addition, specific activation of PPARγ using ciglitazone reproduced the changes induced by VPA in haemorrhagic shock-like conditions.Conclusion and Implications: Changes in GSK3β-Ser(9) phosphorylation in in vivo haemorrhagic shock models can be modelled in vitro, and this has identified a role for PPARγ activation in the protective role of VPA. [ABSTRACT FROM AUTHOR]

Background: Cutaneous bullous mastocytosis (CBM) is a rare disease characterised by erythroderma, bullae formation on trunk, scalp and extremities which evolve to erosions. Objective: To describe a rare variant of cutaneous mastocytosis and treatment options. Animal: A 7‐month‐old Yorkshire terrier puppy with erythroderma and bullae formation. Methods: Clinical examination (including haematological, biochemical and radiographic), skin biopsy, histopathological and immunohistochemical evaluation. Conclusion and clinical relevance: The case fulfills the criteria of CBM, representing a rare entity that is reported to be associated with spontaneous regression. However, in severe cases treatment with systemic corticosteroids, H1 and H2 antihistamines, and masitinib can be performed. [ABSTRACT FROM AUTHOR]

Peptoids are positional isomers of peptides: peptoid sidechains are attached to backbone nitrogens rather than α-carbons. Peptoids constitute a class of sequence-specific polymers resistant to biological degradation and potentially as diverse, structurally and functionally, as proteins. While molecular simulation of proteins is commonplace, relatively few tools are available for peptoid simulation. Here, we present a first-generation atomistic forcefield for peptoids. Our forcefield is based on the peptide forcefield CHARMM22, with key parameters tuned to match both experimental data and quantum mechanical calculations for two model peptoids (dimethylacetamide and a sarcosine dipeptoid). We used this forcefield to demonstrate that solvation of a dipeptoid substantially modifies the conformations it can access. We also simulated a crystal structure of a peptoid homotrimer, H-( N-2-phenylethyl glycine)3-OH, and we show that experimentally observed structural and dynamical features of the crystal are accurately described by our forcefield. The forcefield presented here provides a starting point for future development of peptoid-specific simulation methods within CHARMM. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A domestic ferret was submitted for sterilisation because of right testis enlargement. Oestradiol and cortisol concentrations were within normal physiological ranges, but testosterone was below and progesterone above normal. Microscopically, the right testis, with the exception of a small part of the epididymis, was replaced with neoplastic tissue. The tumour was composed of streams and bundles of closely packed spindle to ovoid cells forming whorls around collagen and capillaries, and separated by a collagenous matrix. In some areas, cells were loosely arranged and separated by a pale myxomatous matrix. The left testis showed atrophy. The majority of neoplastic cells expressed vimentin and S-100 protein, while expression of collagen IV was moderate and there was no expression of glial fibrillary acid protein. On the basis of macroscopical and histopathological findings, and supported by immunohistochemical reactivity, the diagnosis of benign peripheral nerve sheath tumour was made. This is the first report of benign peripheral nerve sheath tumour in ferret testis. [ABSTRACT FROM AUTHOR]

Epailly E, Albanell J, Andreassen A, Bara C, Campistol JM, Delgado JF, Eisen H, Fiane AE, Mohacsi P, Schubert S, Sebbag L, Turazza FM, Valantine H, Zuckermann A, Potena L. Proliferation signal inhibitors and post-transplant malignancies in heart transplantation: practical clinical management questions. Clin Transplant 2011: 25: E475-E486. © 2011 John Wiley & Sons A/S. Abstract: Although malignancy is a major threat to long-term survival of heart transplant (HT) recipients, clear strategies to manage immunosuppression in these patients are lacking. Several lines of evidences support the hypothesis of an anticancer effect of proliferation signal inhibitors (PSIs: mammalian target of rapamycin [mTOR] inhibitors) in HT recipients. This property may arise from PSI's ability to replace immunosuppressive therapies that promote cancer progression, such as calcineurin inhibitors or azathioprine, and/or through their direct biological actions in preventing tumor development and progression. Given the lack of randomized studies specifically exploring these issues in the transplant setting, a collaborative group reviewed current literature and personal clinical experience to reach a consensus aimed to provide practical guidance for the clinical conduct in HT recipients with malignancy, or at high risk of malignancy, with a special focus on advice relevant to potential role of PSIs. [ABSTRACT FROM AUTHOR]

Peptoid oligomers were initially developed as part of a larger basic research effort to accelerate the drug-discovery process in the biotech/biopharma industry. Their ease of synthesis, stability, and structural similarity to polypeptides made them ideal candidates for the combinatorial discovery of novel peptidomimetic drug candidates. Diverse libraries of short peptoid oligomers provided one of the first demonstrations in the mid-1990s that high-affinity ligands to pharmaceutically relevant receptors could be discovered from combinatorial libraries of synthetic compounds. The solid-phase submonomer method of peptoid synthesis was so efficient and general that it soon became possible to explore the properties of longer polypeptoid chains in a variety of areas beyond drug discovery (e.g., diagnostics, drug delivery, and materials science). Exploration into protein-mimetic materials soon followed, with the fundamental goal of folding a non-natural sequence-specific heteropolymer into defined secondary or tertiary structures. This effort first yielded the peptoid helix and much later the peptoid sheet, both of which are secondary-structure mimetics that are close relatives to their natural counterparts. These crucial discoveries have brought us closer to building proteinlike structure and function from a non-natural polymer and have provided great insight into the rules governing polymer and protein folding. The accessibility of peptoid synthesis to chemists and nonchemists alike, along with a lack of information-rich non-natural polymers available to study, has led to a rapid growth in the field of peptoid science by many new investigators. This work provides an overview of the initial discovery and early developments in the peptoid field. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 545-555, 2011. [ABSTRACT FROM AUTHOR]

Sequence-specific polymers are proving to be a powerful approach to assembly and manipulation of matter on the nanometer scale. This has been most impressive in the case of DNA, and progress has been made toward templating inorganic nanoparticles using DNA nanostructures. One obstacle to this progress is that inorganic nanomaterials are often incompatible with DNA assembly conditions, which involve aqueous solutions high in either or both monovalent and divalent salt. Synthetic oligopeptide ligands have been shown by others to improve nanoparticle stability in high concentrations of monovalent salt. Ligands that are peptoids, or sequence-specific N-functional glycine oligomers, allow precise and flexible control over the arrangement of binding groups, steric spacers, charge, and other functionality. We have synthesized short peptoids that can prevent the aggregation of gold nanoparticles in high-salt environments including divalent salt, and allow coadsorption of a single DNA molecule. This degree of precision and versatility is likely to prove essential in bottom-up assembly of nanostructures and in biomedical applications of nanomaterials. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 669-678, 2011. [ABSTRACT FROM AUTHOR]

The design and synthesis of protein-like polymers is a fundamental challenge in materials science. A means to achieve this goal is to create synthetic polymers of defined sequence where all relevant folding information is incorporated into a single polymer strand. We present here the aqueous self-assembly of peptoid polymers (N-substituted glycines) into ultrathin, two-dimensional highly ordered nanosheets, where all folding information is encoded into a single chain. The sequence designs enforce a two-fold amphiphilic periodicity. Two sequences were considered: one with charged residues alternately positive and negative (alternating patterning), and one with charges segregated in positive and negative halves of the molecule (block patterning). Sheets form between pH 5 and 10 with the optimal conditions being pH 6 for the alternating sequence and pH 8 for the block sequence. Once assembled, the nanosheets remain stable between pH 6 and 10 with observed degradation beginning to occur below pH 6. The alternating charge nanosheets remain stable up to concentrations of 20% acetonitrile, whereas the block pattern displayed greater robustness remaining stable up to 30% acetonitrile. These observations are consistent with expectations based on considerations of the molecules' electrostatic interactions. This study represents an important step in the construction of abiotic materials founded on biological informatic and folding principles. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 586-595, 2011. [ABSTRACT FROM AUTHOR]

(Echocardiography 2010;27:1151-1155) [ABSTRACT FROM AUTHOR]

Information about several topics discusses at the international forum for red blood cell transfusion is presented. It discusses local protocol and guidelines for blood transfusion in elective cardiac surgery patients. It also summarized the experience of various centres in for red blood cell transfusions in patients undergoing elective cardiac surgery.

Background Solid organ transplant recipients have a high risk of developing nonmelanoma skin cancers (NMSC). We describe the characteristics and incidence of skin tumors in an Austrian population of heart transplant recipients (HTR). Methods Three hundred and twenty-two HTR out of 970 who had received their organ between December 1984 and July 2003 were analyzed for NMSC. Factors associated with tumor development including the different immunosuppressive (IS) modalities were evaluated. Besides triple combination immunosuppressive therapy, all allograft recipients had received induction therapy either with antithymocyte globulin, OKT3 or monoclonal anti-IL-2 receptor antibodies. Results Median post-transplant follow-up for all patients was 74.18 months (minimum: 2.6, maximum: 224.8). The median time from transplantation until the excision of the first NMSC was 79.57 months (minimum: 2.69, maximum: 192.8). A total of 263 NMSC were excised in 73 patients. The cumulative incidence of developing a skin tumor increased from 7.3% after 5 years to 26.9% after 10 years and to 56.5% after 15 years. Older age at transplantation ( P < 0.0001) and the presence of pre-cancerous skin conditions ( P < 0.0001) were associated with an increased occurrence of NMSC. No significant difference in NMSC incidence was found when the different IS therapies were compared. Conclusions The cumulative incidence of NMSC in our cohort of HTR is comparable to published data on HTR adjusted according to the geographic location. Transplant patients with clinical evidence of pre-cancerous skin conditions have a higher degree of susceptibility for the development of NMSC and require particular dermatologic care. [ABSTRACT FROM AUTHOR]

Cholesterol (or other higher sterols such as ergosterol and phytosterols) is universally present in large amounts (20–40 mol%) in eukaryotic plasma membranes, whereas it is universally absent in the membranes of prokaryotes. Cholesterol has a unique ability to increase lipid order in fluid membranes while maintaining fluidity and diffusion rates. Cholesterol imparts low permeability barriers to lipid membranes and provides for large mechanical coherence. A short topical review is given of these special properties of cholesterol in relation to the structure of membranes, with results drawn from a variety of theoretical and experimental studies. Particular focus is put on cholesterol's ability to promote a special membrane phase, the liquidordered phase, which is unique for cholesterol (and other higher sterols like ergosterol) and absent in membranes containing the cholesterol precursor lanosterol. Cholesterol's role in the formation of special membrane domains and so-called rafts is discussed. [ABSTRACT FROM AUTHOR]

Summary A vaccine inducing protective immunity to a spirochaete-induced colitis of pigs predominantly stimulates expansion of CD8+ cells in vivo and in antigen-stimulated lymphocyte cultures. CD8+ cells, however, are rarely considered necessary for protection against extracellular bacterial pathogens. In the present study, pigs recovering from colitis resulting from experimental infection with Brachyspira (Serpulina) hyodysenteriae had increased percentages of peripheral blood CD4– CD8+ (αα-expressing) cells compared with non-infected pigs. CD8αα+ cells proliferated in antigen-stimulated cultures of peripheral blood mononuclear cells from B. hyodysenteriae-vaccinated pigs. Proliferating CD8αα+ cells consisted of CD4–, CD4+ and γδ T-cell receptor-positive cells. CD4– CD8αβ+ cells from vaccinated or infected pigs did not proliferate upon in vitro antigen stimulation. Of the CD8αα cells that had proliferated, flow cytometric analysis indicated that the majority of the CD4+ CD8+ cells were large (i.e. lymphoblasts) whereas the CD4– CD8+ cells were predominantly small. Addition of monoclonal antibodies (mAb) specific for either porcine major histocompatibility complex (MHC) class I or class II antigens diminished B. hyodysenteriae-specific proliferative responses whereas addition of mAb to porcine MHC II, but not porcine MHC I, reduced the CD8αα response. In vitro depletion of CD4+ cells by flow cytometric cell sorting diminished, but did not completely abrogate, the proliferative response of cells from vaccinated pigs to B. hyodysenteriae antigen stimulation. These results suggest that CD8αα cells are involved in recovery and possibly protection from a spirochaete-induced colitis of pigs; yet, this... [ABSTRACT FROM AUTHOR]

Cryogenic transmission electron microscopy (cryo‐TEM) combined with single particle analysis (SPA) is an emerging imaging approach for soft materials. However, the accuracy of SPA‐reconstructed nanostructures, particularly those formed by synthetic polymers, remains uncertain due to potential packing heterogeneity of the nanostructures. In this study, the combination of molecular dynamics (MD) simulations and image simulations is utilized to validate the accuracy of cryo‐TEM 3D reconstructions of self‐assembled polypeptoid fibril nanostructures. Using CryoSPARC software, image simulations, 2D classifications, ab initio reconstructions, and homogenous refinements are performed. By comparing the results with atomic models, the recovery of molecular details is assessed, heterogeneous structures are identified, and the influence of extraction location on the reconstructions is evaluated. These findings confirm the fidelity of single particle analysis in accurately resolving complex structural characteristics and heterogeneous structures, exhibiting its potential as a valuable tool for detailed structural analysis of synthetic polymers and soft materials. [ABSTRACT FROM AUTHOR]

APC ) gene, responsible for familial adenomatous polyposis (FAP) were analyzed in 15 patients with FAP-associated papillary thyroid carcinomas: 13 had the mutation between codons 778 and 1309 (exon 15), 1 at codon 593 (exon 14), and 1 at codon 140 (exon 3). Therefore APC gene mutations clustered in the genomic area associated with congenital hypertrophy of the retinal pigment epithelium (CHRPE) (codons 463–1387). Ocular patches were documented in 12 patients. In particular, 4 of the 15 patients, all women with a mean age of 23.5 (range 20–32), were found during the study of 15 consecutive kindreds who had undergone systematic screening for extracolonic manifestations. Three of them belonged to the same kindred and were asymptomatic. These four patients were also screened for loss of heterozygosity of APC in the thyroid tumoral tissue. No biallelic inactivation of the APC gene was found. In contrast, three of these four patients had activation of the ret-PTC oncogene. In particular, there was activation of the ret-PTC1 isoform, a chimeric gene resulting from fusion of a gene named H4 with the RET gene. On histologic examination, three of the four patients showed Hashimoto-like lymphocytic infiltration. Present data suggest that: (1) the incidence of FAP-associated thyroid cancer probably has been underestimated in the past; (2) intensive screening could detect a larger than expected number of thyroid carcinomas; (3) systematic screening is recommended in patients with ocular patches and genetic mutation in exon 15; (4) Hashimoto-like findings do not exclude carcinoma but are a frequent accompanying finding; (5) despite frequent multicentricity and early lymph node involvement, FAP-associated thyroid tumors seem to have an excellent prognosis, in particular those showing ret-PTC activation. [ABSTRACT FROM AUTHOR]

Functional and phenotypic properties of porcine peripheral blood CD4/CD8 double-positive (DP) lymphocytes were examined. In cross-sectional and longitudinal studies involving a total of 103 pigs, this lymphocyte population was found to increase gradually in proportion with age, comprising < 2% of the total peripheral blood lymphocyte pool in 1-week-old swine and reaching 30-55% by 3 years of age. CD4/CD8 DP lymphocytes were able to proliferate in response to stimulation with recall viral antigen. Furthermore, these cells mostly expressed high levels of the surface antigen recognized by monoclonal antibody (mAb) 4B4 (4B4hi), which is specific for the human β1 integrin. The CD4+4B4hi lymphocytes from pseudorabies virus-immune swine, proliferated in response to stimulation with the homologous virus, while CD4+4B4hi lymphocytes did not. Stimulation of CD4 single-positive (SP) cells with recall viral antigen, but not with mitogen, resulted in the generation of lymphoblasts which were predominantly of CD4/CD8 DP phenotype, suggesting a role for recall antigen in the generation of this lymphocyte subset. More than half of the CD4+ lymphocytes from palatine tonsils of 6-month-old swine were CD4/CD8 DP, while in the lymph nodes CD4/CD8 DP cells accounted for only one-third or less of CD4+ cells. In contrast, CD4/CD8 DP lymphocytes were absent from the palatine tonsils of 3-day-old swine, which only contained CD4 SP cells. Together, these results indicate that porcine CD4/CD8 DP lymphocytes, exhibit properties of mature antigen-experienced cells, and are inducible by stimulation with recall antigen. These data are consistent with the hypothesis that this population in swine includes memory/effector T cells. [ABSTRACT FROM AUTHOR]

The present study describes the distribution of CD4/CD8 double-positive (DP) T cells in lymph nodes and mucosa-associated lymphoid tissues of pigs at 6–7 months of age. Proportions of lymphocytes isolated from peripheral, bronchial and mesenteric lymph nodes expressing CD4 and/ or CD8 molecules were similar and ranged from 10-13% CD4/CD8 DP cells, 25-27% CD4 single-positive (SP) cells, and 27-32% CD8 SP cells. Mucosa-associated lymphoid tissues had significantly smaller proportions of CD4+ and/or CD8+ T cells than lymph nodes and CD4/CD8 DP cells accounted for a larger proportion of the total CD4+ lymphocytes than in lymph nodes. Compared to the lymph nodes, the predominant CD4+ and/or CD8+ T-cell subset in tonsils was the CD4/CD8 DP population (18%), because of both a higher proportion of these cells and a lower proportion of CD4 SP (12%) and CD8 SP (14%) lymphocyte subsets. Jejunal Peyer's patches were comprised of 12% CD4 SP, 28% CD8 SP and 10% CD4/CD8 DP lymphocytes. In contrast, the mid-section of the continuous Peyer's patch in the ileum contained 7% CD4 SP, 8% CD8 SP and 4% CD4/CD8 DP lymphocytes. The distribution of T lymphocytes in porcine mucosal lymphoid aggregates agrees with the reported correlation between high and low rates of lymphocyte entry into these tissues and the abundance or scarcity of T cells, respectively. Defining the role of CD4/CD8 DP lymphocytes and their unique distribution in mucosa-associated lymphoid tissues in the pig may reveal novel T-cell-mediated regulatory pathways. [ABSTRACT FROM AUTHOR]

The self‐assembly of block copolymers has captured the interest of scientists for many decades because it can induce ordered structures and help to imitate complex structures found in nature. In contrast to proteins, nature's most functional hierarchical structures, conventional polymers are disperse in their length distribution. Here, we synthesized hydrophilic and hydrophobic polypeptoids via solid‐phase synthesis (uniform) and ring‐opening polymerization (disperse). Differential scanning calorimetry measurements showed that the uniform hydrophobic peptoids converge to a maximum of the melting temperature at a much lower chain length than their disperse analogs, showing that not only the chain length but also the dispersity has a considerable impact on the thermal properties of those homopolymers. These homopolymers were then coupled to yield amphiphilic block copolypeptoids. SAXS and AFM measurements confirm that the dispersity plays a major role in microphase separation of these macromolecules, and it appears that uniform hydrophobic blocks form more ordered structures. [ABSTRACT FROM AUTHOR]

There is a growing interest in new methods to generate bio‐inspired, chemically diverse, sequence‐defined synthetic polymers. Solid‐phase submonomer approaches offer facile access to these types of materials, since they take advantage of readily available synthons. Submonomer approaches to date have been applied to peptidomimetics with oligo‐amide backbones. Here we extend the approach to a phosphorous‐containing backbone, where N‐substituted phosphoramidate oligomers are constructed from a set of amine submonomers, diphenyl H‐phosphonate, and cyclohexane diol. The key chemical steps in chain elongation are a chain extension reaction based on H‐phosphonate (P III) chemistry, and a side chain attachment step based on the Atherton‐Todd reaction. Cheap, stable chemical reagents are used without heating, all reaction times are 30 minutes or less and open to air, and no main‐chain protecting groups are required. Phosphoramitoid tetramers and pentamers displaying a variety of side chain functionalities were synthesized by a three‐step solid‐phase submonomer method, typically with >85% crude purities. [ABSTRACT FROM AUTHOR]