bluuebunny/crossref_metadata_2025 huggingface dataset:
Incomplete B Cell Tolerance to Cartilage Oligomeric Matrix Protein in Mice
Authors: Geng Hui , Nandakumar Kutty Selva , Xiong Li , Jie Rui , Dong Jiahui , Holmdahl Rikard
Published: June 2013

Objective

Cartilage oligomeric matrix protein (COMP) is a major noncollagenous component of cartilage and is used as a biomarker in rheumatoid arthritis and experimental arthritis. Injection of COMP leads to severe inflammatory joint disease, and antibodies play a critical role in mediating arthritis. The arthritogenicity of COMP might be due to the lack of self tolerance. This study was undertaken to determine the status of COMP‐specific B cell tolerance using COMP‐deficient mice.

Methods

Arthritis development and antibody responses were compared between COMP‐sufficient and COMP‐deficient littermates after immunization with rat COMP. Serum anti‐COMP antibody levels were measured using a panel of recombinant mouse COMP proteins, and antibody‐secreting cells were enumerated by enzyme‐linked immunospot assays. A novel sandwich enzyme‐linked immunosorbent assay was developed to assess COMP molecules in serum.

Results

COMP‐sufficient mice, but not COMP‐deficient mice, developed severe arthritis following immunization with rat COMP. However, anti‐COMP antibody titers to native COMP and recombinant protein domains covering the entire mouse COMP sequence, except the less immunodominant type 3 repeat domains, were decreased in COMP‐sufficient mice compared to COMP‐deficient mice. In addition, COMP‐sufficient mice had fewer B cells secreting COMP‐reactive antibodies. Detectable levels of full‐length COMP in arthritic COMP‐sufficient B10.Q NCF‐1*/* and healthy mice suggested systemic availability of COMP to the immune system.

Conclusion

The lack of arthritis, together with high levels of COMP‐specific antibodies, in COMP‐deficient mice indicates that susceptibility to arthritis is COMP specific and that endogenous expression of COMP in wild‐type mice tolerizes B cells in vivo.
Letter to the Editor
Authors: Wu Beilei , de Leon Alexander R.
Published: June 2013

Regarding Paper

“Sample size determination in clinical trials with multiple co‐primary endpoints including mixed continuous and binary variables”

by T. Sozu, T. Sugimoto, and T. Hamasaki

Biometrical Journal (2012) 54(5): 716–729

Article: http://dx.doi.org/10.1002/bimj.201100221

Authors' Reply: http://dx.doi.org/10.1002/bimj.201300032

This paper recently introduced a methodology for calculating the sample size in clinical trials with multiple mixed binary and continuous co‐primary endpoints modeled by the so‐called conditional grouped continuous model (CGCM). The purpose of this note is to clarify certain aspects of the methodology and propose an alternative approach based on latent means tests for the binary endpoints. We demonstrate that our approach is more powerful, yielding smaller sample sizes at powers comparable to those used in the paper.
Generation of Free Oligosaccharides from Bacterial Protein N‐Linked Glycosylation Systems
Authors: Dwivedi Ritika , Nothaft Harald , Reiz Bela , Whittal Randy M. , Szymanski Christine M.
Published: June 2013

All Campylobacter species are capable of N‐glycosylating their proteins and releasing the same oligosaccharides into the periplasm as free oligosaccharides (fOS). Previously, analysis of fOS production in Campylobacter required fOS derivatization or large culture volumes and several chromatography steps prior to fOS analysis. In this study, label‐free fOS extraction and purification methods were developed and coupled with quantitative analysis techniques. Our method follows three simple steps: (1) fOS extraction from the periplasmic space, (2) fOS purification using silica gel chromatography followed by porous graphitized carbon purification and (3) fOS analysis and accurate quantitation using a combination of thin‐layer chromatography, mass spectrometry, NMR, and high performance anion exchange chromatography with pulsed amperometric detection. We applied our techniques to analyze fOS from C. jejuni, C. lari, C. rectus, and C. fetus fetus that produce different fOS structures. We accurately quantified fOS in Campylobacter species that ranged from 7.80 (±0.84) to 49.82 (±0.46) nmoles per gram of wet cell pellet and determined that the C. jejuni fOS comprises 2.5% of the dry cell weight. In addition, a novel di‐phosphorylated fOS species was identified in C. lari. This method provides a sensitive and quantitative method to investigate the genesis, biology and breakdown of fOS in the bacterial N‐glycosylation systems. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 772–783, 2013.
A personal perspective on chemistry‐driven RNA research
Authors: Micura Ronald , Kreutz Christoph , Breuker Kathrin
Published: June 2013

In this mini review, we discuss how our understanding of ribonucleic acid (RNA) properties becomes significantly deepened when a broad range of modern chemical and biophysical methods is applied. We span our perspective from RNA solid‐phase synthesis and site‐specific labeling to single‐molecule fluorescence‐resonance‐energy‐transfer imaging and NMR spectroscopy approaches to explore the dynamics of RNA over a broad timescale. We then move on to Fourier‐transform‐ion‐cyclotron‐resonance mass spectrometry (FT‐ICR‐MS) as a powerful technique for RNA sequencing and modification analysis. The novel methodological developments are discussed for selected biological systems that include the thiamine‐pyrophosphate riboswitch, HIV and ribosomal A‐site RNA, and transfer RNA. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 1114–1123, 2013.
One set system for the synthesis and purification of glycosaminoglycan oligosaccharides reconstructed using a hyaluronidase‐immobilized column
Authors: Suto Shinichiro , Kakizaki Ikuko , Nakamura Toshiya , Endo Masahiko
Published: June 2013

Using the transglycosylation reaction as a reverse reaction for the hydrolysis of hyaluronidase, new artificial oligosaccharides may be synthesized by reconstructing natural glycosaminoglycans (GAGs) according to preliminary planned arrangements. However, as some problems have been associated with the method, including the low yields of reaction products and complicated processes of separation and purification, improvements in this method were investigated. Transglycosylation reactions were carried out using bovine testicular hyaluronidase‐immobilized resin packed in a column. For the transglycosylation reaction, pyridylaminated (PA) GAG hexasaccharides, which were the minimum size for hydrolysis sensitivity and the transglycosylation reaction, were used as acceptors, whereas large size GAGs were used as donors. The reaction mixture was pooled after incubation in the hyaluronidase‐immobilized resin column and was then introduced into continuously joined HPLC columns constructed from three steps: the first step of ion‐exchange HPLC for concentrating newly synthesized GAG oligosaccharides as reaction products, the second step of reverse phase HPLC for separating PA oligosaccharides from non‐PA oligosaccharides, and the third step of size fractionation HPLC for fractionating newly synthesized oligosaccharides. Newly synthesized oligosaccharides were obtained by one complete cycle of the transglycosylation reaction and separation. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 189–196, 2014.
Insight into the redox partner interaction mechanism in cytochrome P450BM‐3 using molecular dynamics simulations
Authors: Verma Rajni , Schwaneberg Ulrich , Roccatano Danilo
Published: June 2013

Flavocytochrome P450BM‐3 is a soluble bacterial reductase composed of two flavin (FAD/FMN) and one HEME domains. In this article, we have performed molecular dynamics simulations on both the isolated FMN and HEME domains and their crystallographic complex, with the aim to study their binding modes and to garner insight into the interdomain electron transfer (ET) mechanism. The results evidenced an interdomain conformational rearrangement that reduces the average distance between the FMN and HEME cofactors from 1.81 nm, in the crystal structure, to an average value of 1.41 ± 0.09 nm along the simulation. This modification is in agreement with previously proposed hypotheses suggesting that the crystallographic FMN/HEME complex is not in the optimal arrangement for favorable ET rate under physiological conditions. The calculation of the transfer rate along the simulation, using the Pathways Path method, demonstrated the occurrence of seven ET pathways between the two redox centers, with three of them providing ET rates (KET) comparable with the experimental one. The sampled ET pathways comprise the amino acids N319, L322, F390, K391, P392, F393, A399, C400, and Q403 of the HEME domain and M490 of the FMN domain. The values of KET closer to the experiment were found along the pathways FMN(C7) → F390 → K391 → P392 → HEME(Fe) and FMN(C8) → M490 → F393 → HEME(Fe). Finally, the analysis of the collective modes of the protein complex evidences a clear correlation of the first two essential modes with the activation of the most effective ET pathways along the trajectory. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 197–209, 2014.
Partial hepatectomy for ruptured hepatocellular carcinoma
Authors: Yang T , Sun Y F , Zhang J , Lau W Y , Lai E C H , Lu J H , Shen F , Wu M C
Published: June 2013

Background

Improvements in surgical technique and perioperative care have made partial hepatectomy a safe and effective treatment for hepatocellular carcinoma (HCC), even in the event of spontaneous HCC rupture.

Methods

A consecutive cohort of patients who underwent partial hepatectomy for HCC between 2000 and 2009 was divided into a ruptured group and a non-ruptured group. Patients with ruptured HCC were further divided into emergency and staged hepatectomy subgroups. Mortality and morbidity, overall survival and recurrence-free survival (RFS) were compared. Prognostic factors for overall survival and RFS were identified by univariable and multivariable analyses.

Results

A total of 1233 patients underwent partial hepatectomy for HCC, of whom 143 had a ruptured tumour. The morbidity and mortality rates were similar in the ruptured and non-ruptured groups, as well as in the emergency and staged subgroups. In univariable analyses, overall survival and RFS were lower in the ruptured group than in the non-ruptured group (both P < 0·001), and also in the emergency subgroup compared with the staged subgroup (P = 0·016 and P = 0·025 respectively). In multivariable analysis, spontaneous rupture independently predicted poor overall survival after hepatectomy (hazard ratio 1·54, 95 per cent confidence interval 1·24 to 1·93) and RFS (HR 1·75, 1·39 to 2·22). Overall survival and RFS after hepatectomy for ruptured HCC in the emergency and staged subgroups were not significantly different in multivariable analyses.

Conclusion

Spontaneous rupture predicted poor long-term survival after hepatectomy for HCC, but surgical treatment seems possible, safe and appropriate in selected patients.
Systematic review and meta-analysis of hypothermic machine perfusion versus static cold storage of kidney allografts on transplant outcomes
Authors: O'Callaghan J M , Morgan R D , Knight S R , Morris P J
Published: June 2013

Background

Adequate preservation of renal allografts for transplantation is important for maintaining and improving transplant outcomes. There are two prevalent methods: hypothermic machine perfusion and static cold storage. The preferred method of storage, however, remains controversial. The objective was to review systematically the evidence comparing outcomes from these two modalities.

Methods

A literature search was performed using MEDLINE, Embase, the Cochrane Library, the Transplant Library and the International Clinical Trials Registry Platform. The final date for searches was 30 November 2012. Studies were assessed for methodological quality. Summary effects were calculated as relative risk (RR) with 95 per cent confidence interval (c.i.). Randomized clinical trials (RCTs) and non-RCTs were included, but evaluated separately. Results from RCTs alone were used for meta-analysis.

Results

Eighteen studies met the inclusion criteria, including seven RCTs (1475 kidneys) and 11 non-RCTs (728 kidneys). The overall risk of delayed graft function was lower with hypothermic machine perfusion than static cold storage (RR 0·81, 95 per cent c.i. 0·71 to 0·92; P = 0·002). There was no difference in the rate of primary non-function (RR 1·15, 0·46 to 2·90; P = 0·767). There was a faster initial fall in the level of serum creatinine with hypothermic machine perfusion in two RCTs, but not in another. There was no relationship between rates of acute rejection or patient survival and the method of preservation.

Conclusion

Data from the included studies suggest that hypothermic machine perfusion reduces delayed graft function compared with static cold storage. There was no difference in primary non-function, acute rejection, long-term renal function or patient survival. A difference in renal graft survival is uncertain.
Proximal margin length with transhiatal gastrectomy for Siewert type II and III adenocarcinomas of the oesophagogastric junction
Authors: Mine S , Sano T , Hiki N , Yamada K , Kosuga T , Nunobe S , Yamaguchi T
Published: June 2013

Background

A gross proximal oesophageal margin greater than 5 cm is considered to be necessary for curative surgery of adenocarcinoma of the oesophagogastric junction. This study investigated whether a shorter proximal margin might suffice in the context of total gastrectomy for Siewert type II and III tumours.

Methods

The gross proximal margin was measured on stretched specimens just after resection. Relationships between gross proximal margin lengths and clinicopathological features were investigated in patients with Siewert type II and III adenocarcinoma of the oesophagogastric junction treated by R0–1 surgical resection. For survival analyses, only patients who had undergone R0 resection for pathological (p) T2–4 N0–3 M0 tumour via a transhiatal approach were evaluated.

Results

Of the 140 patients, 120 had a total gastrectomy. Two patients (1·4 per cent) had histologically positive proximal margins and another two (1·4 per cent) developed anastomotic recurrence. Of 100 patients with pT2–4 N0–3 M0 tumours who underwent gastrectomy via a transhiatal approach, those with gross proximal margins larger than 20 mm appeared to have better survival than those with shorter margins (P = 0·027). Multivariable analysis demonstrated that a gross proximal margin of 20 mm or less was an independent prognostic factor (hazard ratio (HR) 3·56, 95 per cent confidence interval 1·39 to 9·14; P = 0·008), as was pathological node status (HR 1·76, 1·08 to 2·86; P = 0·024).

Conclusion

Gross proximal margin lengths of more than 20 mm in resected specimens seem satisfactory for patients with type II and III adenocarcinoma of the oesophagogastric junction treated by transhiatal gastrectomy.
Surgical delay is a critical determinant of survival in perforated peptic ulcer
Authors: Buck D L , Vester-Andersen M , Møller M H
Published: June 2013

Background

Morbidity and mortality following perforated peptic ulcer (PPU) remain substantial. Surgical delay is a well established negative prognostic factor, but evidence derives from studies with a high risk of bias. The aim of the present nationwide cohort study was to evaluate the adjusted effect of hourly surgical delay on survival after PPU.

Methods

This was a cohort study including all Danish patients treated surgically for PPU between 1 February 2003 and 31 August 2009. Medically treated patients and those with a malignant ulcer were excluded. The associations between surgical delay and 30-day survival are presented as crude and adjusted relative risks (RRs) with 95 per cent confidence intervals (c.i.).

Results

A total of 2668 patients were included. Their median age was 70·9 (range 16·2–104·2) years and 55·4 per cent (1478 of 2668) were female. Some 67·5 per cent of the patients (1800 of 2668) had at least one of six co-morbid diseases and 45·6 per cent had an American Society of Anesthesiologists fitness grade of III or more. A total of 708 patients (26·5 per cent) died within 30 days of surgery. Every hour of delay from admission to surgery was associated with an adjusted 2·4 per cent decreased probability of survival compared with the previous hour (adjusted RR 1·024, 95 per cent c.i. 1·011 to 1·037).

Conclusion

Limiting surgical delay in patients with PPU seems of paramount importance.
Raised haematocrit concentration and the risk of death and vascular complications after major surgery
Authors: Musallam K M , Porter J B , Sfeir P M , Tamim H M , Richards T , Lotta L A , Peyvandi F , Jamali F R
Published: June 2013

Background

Preoperative anaemia is associated with adverse postoperative outcomes. Data on raised preoperative haematocrit concentration are limited. This study aimed to evaluate the effect of raised haematocrit on 30-day postoperative mortality and vascular events in patients undergoing major surgery.

Methods

This was a cohort study using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database. Thirty-day mortality and vascular events, demographics and perioperative risk factors were obtained for adults undergoing major surgery. The adjusted effect of raised (over 0·50) compared with normal (0·41–0·50, American Medical Association reference range) preoperative haematocrit concentration on postoperative outcomes was assessed. Separate sex-specific analyses were also conducted, using haematocrit concentration thresholds commonly used in the diagnosis and management of apparent or absolute erythrocytosis.

Results

Some 3961 (2·0 per cent) of 197 469 patients had a raised haematocrit concentration before surgery. After adjustment, the 30-day postoperative mortality rate was higher in patients with raised haematocrit than in those without (odds ratio (OR) 2·23, 95 per cent confidence interval 1·77 to 2·80). Thirty-day rates of deep vein thrombosis (OR 1·95, 1·44 to 2·64) and pulmonary embolism (OR 1·79, 1·17 to 2·73), but not myocardial infarction or stroke, were also higher in patients with a raised haematocrit concentration. The effect on mortality was noted beyond the haematocrit thresholds of 0·48 in women and 0·52 in men; the effect estimates were considerably higher for values exceeding 0·54. Values between 0·41 and 0·45 were not associated with increased mortality risk. Similar observations were noted for venous thrombosis, although with apparent sex differences.

Conclusion

A raised haematocrit concentration was associated with an increased risk of 30-day mortality and venous thrombosis following major surgery.
Venous thromboembolism
Authors: Stansby G , Berridge D
Published: June 2013

Extended treatment
PTEN expression is consistent in colorectal cancer primaries and metastases and associates with patient survival
Authors: Atreya Chloe E. , Sangale Zaina , Xu Nafei , Matli Mary R. , Tikishvili Eliso , Welbourn William , Stone Steven , Shokat Kevan M. , Warren Robert S.
Published: June 2013

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) negatively regulates the phosphoinositide‐3‐kinase (PI3K) signaling pathway. In colorectal cancer (CRC), observed frequencies of loss of PTEN expression, concordant expression in primary tumors and metastases, and the association of PTEN status with outcome vary markedly by detection method. We determined the degree to which PTEN expression is consistent in 70 matched human CRC primaries and liver metastases using a validated immunohistochemistry assay. We found loss of PTEN expression in 12.3% of assessable CRC primaries and 10.3% of assessable liver metastases. PTEN expression (positive or negative) was concordant in 98% of matched colorectal primaries and liver metastases. Next we related PTEN status to mutations in RAS and PI3K pathway genes (KRAS, NRAS, BRAF, and PIK3CA) and to overall survival (OS). PTEN expression was not significantly associated with the presence or absence of mutations in RAS or PI3K pathway genes. The median OS of patients whose tumors did not express PTEN was 9 months, compared to 49 months for patients whose tumors did express PTEN (HR = 6.25, 95% confidence intervals (CI) (1.98, 15.42), P = 0.0017). The association of absent PTEN expression with increased risk of death remained significant in multivariate analysis (HR = 6.31, 95% CI (2.03, 17.93), P = 0.0023). In summary, PTEN expression was consistent in matched CRC primaries and in liver metastases. Therefore, future investigations of PTEN in metastatic CRC can use primary tumor tissue. In patients with liver‐only metastases, loss of PTEN expression predicted poor OS.
Tryptamine and dimethyltryptamine inhibit indoleamine 2,3 dioxygenase and increase the tumor‐reactive effect of peripheral blood mononuclear cells
Authors: Tourino Melissa Cavalheiro , de Oliveira Edson Mendes , Bellé Luziane Potrich , Knebel Franciele Hinterholz , Albuquerque Renata Chaves , Dörr Felipe Augusto , Okada Sabrina Sayori , Migliorini Silene , Soares Irene Silva , Campa Ana
Published: June 2013

Indoleamine 2,3‐dioxygenase (IDO) is an interferon‐γ (IFN‐γ)–induced tryptophan‐degrading enzyme, producing kynurenine (KYN) that participates in the mechanism of tumor immune tolerance. Thus, IDO inhibition has been considered a strategy for anticancer therapy. The aim of this study was to identify whether the metabolites originated from the competitive routes of tryptophan metabolism, such as the serotonergic or N, N‐dimethyltryptamine (DMT) pathways, have inhibitory effects on recombinant human IDO (rhIDO) activity. Serotonin and melatonin had no effect; on the other hand, tryptamine (TRY) and DMT modulated the activity of rhIDO as classical non‐competitive inhibitors, with Ki values of 156 and 506 μM, respectively. This inhibitory effect was also observed on constitutively expressed or IFN‐γ–induced IDO in the A172 human glioma cell line. TRY and DMT increased the cytotoxic activity of peripheral blood mononuclear cells (PBMCs) in co‐culture assays. We conclude that the IDO inhibition by TRY and DMT contributed to a more effective tumor‐reactive response by the PBMCs. Copyright © 2013 John Wiley & Sons, Ltd.
Chain Growth by CO Insertion in the Fischer–Tropsch Reaction
Authors: van Santen Rutger A. , Markvoort Albert J.
Published: June 2013

The molecular kinetics of the mechanism of chain growth through CO insertion of the Fischer–Tropsch reaction is analyzed. The maximum chain growth within the CO insertion chain growth model is predicted if the rate of CO activation to give the C1 species that initiates chain growth balances the rate of chain growth termination. The overall rate of chain growth, determined by the elementary rates of CO insertion, hydrogen‐transfer reaction steps, and CO bond cleavage, has to be fast compared to the rate of methanation and the rate of chain growth termination, which gives an oxygenate or hydrocarbon product. However, estimates of rate constants based on quantum‐chemical data predict low chain growth within this CO insertion mechanism, which is mainly caused by the relatively slow rate of CO insertion into the growing chain compared to the rate of product desorption. Such a high barrier for CO insertion is consistent with oxygenate formation through the carbide mechanism pathway. A comparison of the derived expressions for CO consumption shows that the rate of chain growth is limiting within the mechanism of chain growth through CO insertion, whereas within the carbide mechanism it is rate controlled by the rate of CO to CHx monomer formation.
Hydrogen Transfer Processes Mediated by Supported Iridium Oxide Nanoparticles
Authors: Hammond Ceri , Schümperli Martin T. , Conrad Sabrina , Hermans Ive
Published: June 2013

Homogeneous iridium catalysts have demonstrated exceptional catalytic activity for a number of hydrogen transfer reactions. Herein, we demonstrate the synthesis of a heterogeneous iridium catalyst supported on nanoparticulate cerium oxide and investigate its application for the aerobic oxidation of benzyl alcohol and the Meerwein–Ponndorf–Verley transfer hydrogenation of cyclohexanone. Along with the optimisation of the activity of the catalyst, the kinetic parameters have been examined to unravel the elementary reaction steps mediated by this catalyst and further rationalise the observed structure–activity relationships. Both spectroscopic and catalytic investigations suggest that iridium oxide nanoparticles, most likely Ir2O3, mediate these reactions via the formation of metal hydroxide species, which are subsequently reoxidised with either a molecular oxygen or a ketone. In contrast to many other metal‐ or metal oxide‐based catalysts, this catalyst can perform the selective oxidation of alcohols in the absence of a base, at mild temperatures and at a low metal loading.
Mechanistic Insight into the Staudinger Reaction Catalyzed by N‐Heterocyclic Carbenes
Authors: Hans Morgan , Wouters Johan , Demonceau Albert , Delaude Lionel
Published: June 2013

Four zwitterions were prepared by treating 1,3‐dimesitylimidazolin‐2‐ylidene (SIMes) or 1,3‐dimesitylimidazol‐2‐ylidene (IMes) with either N‐tosyl benzaldimine or diphenylketene. They were isolated in high yields and characterized by IR and NMR spectroscopy. The molecular structures of three of them were determined by using X‐ray crystallography and their thermal stability was monitored by using thermogravimetric analysis. The imidazol(in)ium‐2‐amides were rather labile white solids that did not show any tendency to tautomerize into the corresponding 1,2,2‐triaminoethene derivatives. They displayed a mediocre catalytic activity in the Staudinger reaction of N‐tosyl benzaldimine with diphenylketene. In contrast, the imidazol(in)ium‐2‐enolates were orange‐red crystalline materials that remained stable over extended periods of time. Despite their greater stability, these zwitterions turned out to be efficient promoters for the model cycloaddition under scrutiny. As a matter of fact, their catalytic activity matched those recorded with the free carbenes. Altogether, these results provide strong experimental insight into the mechanism of the Staudinger reaction catalyzed by N‐heterocyclic carbenes. They also highlight the superior catalytic activity of the imidazole‐based carbene IMes compared with its saturated analogue SIMes in the reaction under consideration.
Solvent Responsive Magnetic Dynamics of a Dinuclear Dysprosium Single‐Molecule Magnet
Authors: Ren Min , Bao Song‐Song , Hoshino Norihisa , Akutagawa Tomoyuki , Wang Bingwu , Ding Yu‐Chen , Wei Shiqiang , Zheng Li‐Min
Published: June 2013

A new dysprosium(III) phosphonate dimer {Dy(notpH4)(NO3)(H2O)}2⋅8 H2O (1) [notpH6=1,4,7‐triazacyclononane‐1,4,7‐triyl‐tris(methylenephosphonic acid)] that contains two equivalent DyIII ions with a three‐capped trigonal prism environment is reported. Complex 1 can be transformed into {Dy(notpH4)(NO3)(H2O)}2 (2) in a reversible manner by desorption and absorption of solvent water at ambient temperature. This process is accompanied by a large dielectric response. Magnetic studies reveal that both 1 and 2 show thermally activated magnetization relaxation as expected for single‐molecule magnets. Moreover, the magnetic dynamics of the two compounds can be manipulated by controlling the number of solvent molecules at room temperature.
A New Dynamic Covalent Bond of SeN: Towards Controlled Self‐Assembly and Disassembly
Authors: Yi Yu , Xu Huaping , Wang Lu , Cao Wei , Zhang Xi
Published: June 2013

A new kind of SeN dynamic covalent bond has been found that can form between the Se atom of a phenylselenyl halogen species and the N atom of a pyridine derivative, such as polystyrene‐b‐poly(4‐vinylpyridine). This SeN dynamic covalent bond can be reversibly and rapidly formed or cleaved under acidic or basic conditions, respectively. Furthermore, the bond can be dynamically cleaved by heating or treatment with stronger electron‐donating pyridine derivatives. The multiple responses of SeN bond to external stimuli has enriched the existing family of dynamic covalent bonds. It can be used for controlled and reversible self‐assembly and disassembly, which may find potential applications in a number of areas, including self‐healing materials and responsive assemblies.
Energy, Equipment and Cost Savings by Using a Membrane Unit in an Amine‐Based Absorption Process for CO2 Removal
Authors: Song Shankui , Esche Erik , Stünkel Steffen , Brinkmann Torsten , Wind Jan , Shishatskiy Sergey , Wozny Günter
Published: June 2013

A hybrid system consisting of a membrane unit and an amine‐based process for CO2 removal in the oxidative coupling of methane is investigated experimentally and in simulations. Absorption processes with two different absorbents for removing 90 % of CO2 from the feed stream are regarded as benchmarks and compared to the membrane process with respect to potential energy, equipment, and cost reductions. The results show that a membrane unit using polyimide could assist with CO2 capture and lead to a reduction of the consumed energy per kilogram of CO2 by 40 % and also reduce the size of the absorption columns. Alternative processes with a two‐step membrane cascade to enhance the recovery of product ethylene are also discussed.
Steady‐state nuclear actin levels are determined by export competent actin pool
Authors: Skarp Kari‐Pekka , Huet Guillaume , Vartiainen Maria K.
Published: June 2013

A number of studies in the last decade have irrevocably promoted actin into a fully fledged member of the nuclear compartment, where it, among other crucial tasks, facilitates transcription and chromatin remodeling. Changes in nuclear actin levels have been linked to different cellular processes: decreased nuclear actin to quiescence and increased nuclear actin to differentiation. Importin 9 and exportin 6 transport factors are responsible for the continuous nucleocytoplasmic shuttling of actin, but the mechanisms, which result in modulated actin levels, have not been characterized. We find that in cells growing under normal growth conditions, the levels of nuclear actin vary considerably from cell to cell. To understand the basis for this, we have extensively quantified several cellular parameters while at the same time recording the import and export rates of green fluorescent protein (GFP)‐tagged actin. Surprisingly, our dataset shows that the ratio of nuclear to cytoplasmic fluorescence intensity, but not nuclear shape, size, cytoplasm size, or their ratio, correlates negatively with both import and export rate of actin. This suggests that high‐nuclear actin content is maintained by both diminished import and export. The high nuclear actin containing cells still show high mobility of actin, but it is not export competent, suggesting increased binding of actin to nuclear complexes. Creation of such export incompetent actin pool would ensure enough actin is retained in the nucleus and make it available for the various nuclear functions described for actin. © 2013 Wiley Periodicals, Inc.
Gelsolin: The tail of a molecular gymnast
Authors: Nag Shalini , Larsson Mårten , Robinson Robert C. , Burtnick Leslie D.
Published: June 2013

Gelsolin superfamily members are Ca2+‐dependent, multidomain regulators of the actin cytoskeleton. Calcium binding activates gelsolin by inducing molecular gymnastics (large‐scale conformational changes) that expose actin interaction surfaces by releasing a series of latches. A specialized tail latch has distinguished gelsolin within the superfamily. Active gelsolin exhibits actin filament severing and capping, and actin monomer sequestering activities. Here, we analyze a combination of sequence, structural, biophysical and biochemical data to assess whether the molecular plasticity, regulation and actin‐related properties of gelsolin are also present in other superfamily members. We conclude that all members of the superfamily will be able to transition between a compact conformation and a more open form, and that most of these open forms will interact with actin. Supervillin, which lacks the severing domain 1 and the F‐actin binding‐site on domain 2, is the clear exception. Eight calcium‐binding sites are absolutely conserved in gelsolin, adseverin, advillin and villin, and compromised to increasing degrees in CapG, villin‐like protein, supervillin and flightless I. Advillin, villin and supervillin each contain a potential tail latch, which is absent from CapG, adseverin and flightless I, and ambiguous in villin‐like protein. Thus, calcium regulation will vary across the superfamily. Potential novel isoforms of the superfamily suggest complex regulation at the gene, transcript and protein levels. We review animal, clinical and cellular data that illuminate how the regulation of molecular flexibility in gelsolin‐like proteins permits cells to exploit the force generated from actin polymerization to drive processes such as cell movement in health and disease. © 2013 Wiley Periodicals, Inc.
Computed tomographic colonography for colorectal cancer screening
Authors: Hassan Cesare , Pooler B. Dustin , Kim David H. , Rinaldi Antonio , Repici Alessandro , Pickhardt Perry J.
Published: June 2013

BACKGROUND

The objective of this study was to determine whether age, sex, a positive family history of colorectal cancer, and body mass index (BMI) are important predictors of advanced neoplasia in the setting of screening computed tomographic colonography (CTC).

METHODS

Consecutive patients who were referred for first‐time screening CTC from 2004 to 2011 at a single medical center were enrolled. Results at pathology were recorded for all patients who underwent polypectomy. Logistic regression was used to identify significant predictor variables for advanced neoplasia (any adenoma ≥10 mm or with villous component, high‐grade dysplasia, or adenocarcinoma). Odds ratios (ORs) were used to express associations between the study variables (age, sex, BMI, and a positive family history of colorectal cancer) and advanced neoplasia.

RESULTS

In total, 7620 patients underwent CTC screening. Of these, 276 patients (3.6%; 95% confidence interval [CI], 3.2%‐4.1%) ultimately were diagnosed with advanced neoplasia. At multivariate analysis, age (mean OR per 10‐year increase, 1.8; 95% CI, 1.6‐2.0) and being a man (OR, 1.7; 95% CI, 1.3‐2.2) were independent predictors of advanced neoplasia, whereas BMI and a positive family history of colorectal cancer were not. The number needed to screen to detect 1 case of advanced neoplasia varied from 51 among women aged ≤55 years to 10 among men aged >65 years. The number of post‐CTC colonoscopies needed to detect 1 case of advanced neoplasia varied from 2 to 4.

CONCLUSIONS

Age and sex were identified as important independent predictors of advanced neoplasia risk in individuals undergoing screening CTC, whereas BMI and a positive family history of colorectal cancer were not. These results have implications for appropriate patient selection. Cancer 2013;119:2549–2554. © 2013 American Cancer Society.
The remote sensing image enhancement based on nonsubsampled contourlet transform and unsharp masking
Authors: Pu Xiaoting , Jia Zhenhong , Wang Liejun , Hu Yingjie , Yang Jie
Published: June 2013

To restrain pseudo‐Gibbs phenomenon, low contrast and blurred phenomenon in the process of image enhancement, a new method based on the nonsubsampled contourlet transform and the unsharp masking is proposed in this paper. The proposed method utilizes the shift‐invariance of nonsubsampled contourlet transform to restrain the pseudo‐Gibbs phenomenon, and then enhance details of the image by unsharp masking. We achieved an increase in image definition by 54.5%, the mean increased by 15.6%, whereas the standard deviation increased by 54.5% compared with the unsharp masking method. To the noisy image, we achieved an increase in image definition by 35.4%, the mean increased by 2.2%, whereas the standard deviation increased by 34.9% compared with the unsharp masking method. Copyright © 2013 John Wiley & Sons, Ltd.
Active contours driven by normalized local image fitting energy
Authors: Peng Yali , Liu Fang , Liu Shigang
Published: June 2013

In this paper, a new local region‐based active contour model that is driven by normalized local image fitting energy is proposed. By considering the local image fitting energy to extract the local image information, our model can effectively and efficiently segment images with intensity inhomogeneities. In addition, to keep the smoothness of the level set function, the time‐consuming reinitialization step widely adopted in traditional level set methods can be avoided by introducing a Gaussian filtering process. Experimental results on synthetic and real images demonstrate that the proposed model has much less CPU time and sensitivity to the initial contour than the well‐known local binary fitting model. Copyright © 2013 John Wiley & Sons, Ltd.
Improvement of growth habit and optical properties of rapidly grown KDP crystal by adding diethylene triamine pentacetate acid in growth solution
Authors: Zhu Shengjun , Wang Shenglai , Ding Jianxu , Liu Guangxia , Xu Xinguang
Published: June 2013

By altering the concentration of a new additive ‐ diethylene triamine pentacetate acid (DTPA) in the growth solution, a series of KDP crystals were obtained by the “point seed” rapid growth method. The growth rates up to about 20 mm/day. Effects of DTPA on the growth habit and optical properties of these as‐grown KDP crystals were investigated. The results reveal that, with the increase of DTPA concentration in growth solution, the contents of impurity metal ions incorporated into crystal and aspect ratio of crystal morphology were both decreased gradually, while the UV transmittance of crystal was enhanced continually. In the presence of moderate concentration of DTPA (100–200 ppm), the solution stability was increased and optical properties of crystal (including optical homogeneity, light scattering and laser damage threshold) were all improved. However excessive doping (>500 ppm) has opposite effects. The impact mechanism was also analyzed combining with the structure of KDP crystal and chemical characteristics of DTPA molecular.
How the development of handedness could contribute to the development of language
Authors: Michel George F. , Babik Iryna , Nelson Eliza L. , Campbell Julie M. , Marcinowski Emily C.
Published: June 2013

We propose a developmental process which may link the development of handedness with the development of hemispheric specialization for speech processing. Using Arbib's proposed sequence of sensorimotor development of manual skills and gestures (that he considers to be the basis of speech gestures and proto‐language), we show how the development of hand‐use preferences in proto‐reaching skills concatenate into object acquisition skills and eventually into role‐differentiated bimanual manipulation skills (that reflect interhemispheric communication and coordination). These latter sensorimotor skills might facilitate the development of speech processing via their influence on the development of tool‐using and object management abilities. © 2013 Wiley Periodicals, Inc. Dev Psychobiol 55: 608–620, 2013.
Age and sex differences in reward behavior in adolescent and adult rats
Authors: Hammerslag Lindsey R. , Gulley Joshua M.
Published: June 2013

Compared to adults, adolescents are at heightened risk for drug abuse and dependence. One of the factors contributing to this vulnerability may be age‐dependent differences in reward processing, with adolescents approaching reward through stimulus‐directed, rather than goal‐directed, processes. However, the empirical evidence for this in rodent models of adolescence, particularly those that investigate both sexes, is limited. To address this, male and female rats that were adolescents (P30) or adults (P98) at the start of the experiment were trained in a Pavlovian approach (PA) task and were subsequently tested for the effects of reward devaluation, extinction, and re‐acquisition. We found significant interactions between age and sex: females had enhanced acquisition of PA and poorer extinction, relative to males, while adolescents and females were less sensitive to reward devaluation than male adults. These results suggest that females and adolescents exhibit reward behavior that is more stimulus‐directed, rather than goal‐directed. © 2013 Wiley Periodicals, Inc. Dev Psychobiol 56: 611–621, 2014.
Motherless quail mothers display impaired maternal behavior and produce more fearful and less socially motivated offspring
Authors: Pittet Florent , Le Bot Océane , Houdelier Cécilia , Richard‐Yris Marie‐Annick , Lumineau Sophie
Published: June 2013

Early maternal deprivation impairs the behavioral development of young individuals. Recently, strong differences between mothered and maternally deprived chicks have been reported concerning their emotionality, sociality, and spatial skills. Here we investigated long‐term and cross‐generational impacts of maternal deprivation by comparing the characteristics of the non‐reproductive and the maternal behavior of 22 mothered and 22 non‐mothered adult female Japanese quail (Coturnix c. japonica) and by comparing the behavior of their respective fostered chicks. We reveal that non‐brooded mothers were more fearful and less competent in spatial tasks and expressed impaired maternal care, characterized by more aggression towards chicks, higher activity rates, and more abnormal pacing during the first days of the care period. Chicks' behavior was clearly affected by maternal care inducing strong differences in their fearfulness and social motivation. Our results show both long‐term and cross‐generational impacts of early maternal deprivation in precocial birds. © 2013 Wiley Periodicals, Inc. Dev Psychobiol 56: 622–634, 2014.
Habenular commissure formation in zebrafish is regulated by the pineal gland–specific gene unc119c
Authors: Toyama Reiko , Kim Mi Ha , Rebbert Martha L. , Gonzales John , Burgess Harold , Dawid Igor B.
Published: June 2013

Background: The zebrafish pineal gland (epiphysis) is a site of melatonin production, contains photoreceptor cells, and functions as a circadian clock pacemaker. Since it is located on the surface of the forebrain, it is accessible for manipulation and, therefore, is a useful model system to analyze pineal gland function and development. We previously analyzed the pineal transcriptome during development and showed that many genes exhibit a highly dynamic expression pattern in the pineal gland. Results: Among genes preferentially expressed in the zebrafish pineal gland, we identified a tissue‐specific form of the unc119 gene family, unc119c, which is highly preferentially expressed in the pineal gland during day and night at all stages examined from embryo to adult. When expression of unc119c was inhibited, the formation of the habenular commissure (HC) was specifically compromised. The Unc119c interacting factors Arl3l1 and Arl3l2 as well as Wnt4a also proved indispensible for HC formation. Conclusions: We suggest that Unc119c, together with Arl3l1/2, plays an important role in modulating Wnt4a production and secretion during HC formation in the forebrain of the zebrafish embryo. Developmental Dynamics 242:1033–1042, 2013. © 2013 Wiley Periodicals, Inc.
CD73 expression on extracellular vesicles derived from CD4+CD25+Foxp3+ T cells contributes to their regulatory function
Authors: Smyth Lesley Ann , Ratnasothy Kulachelvy , Tsang Julia Y. S. , Boardman Dominic , Warley Alice , Lechler Robert , Lombardi Giovanna
Published: June 2013

CD4+CD25+Foxp3+ Treg cells maintain immunological tolerance. In this study, the possibility that Treg cells control immune responses via the production of secreted membrane vesicles, such as exosomes, was investigated. Exosomes are released by many cell types, including T cells, and have regulatory functions. Indeed, TCR activation of both freshly isolated Treg cells and an antigen‐specific Treg‐cell line resulted in the production of exosomes as defined morphologically by EM and by the presence of tetraspanin molecules LAMP‐1/CD63 and CD81. Expression of the ecto‐5‐nucleotide enzyme CD73 by Treg cells has been shown to contribute to their suppressive function by converting extracellular adenosine‐5‐monophosphate to adenosine, which, following interaction with adenosine receptors expressed on target cells, leads to immune modulation. CD73 was evident on Treg cell derived exosomes, accordingly when these exosomes were incubated in the presence of adenosine‐5‐monophosphate production of adenosine was observed. Most importantly, CD73 present on Treg cell derived exosomes was essential for their suppressive function hitherto exosomes derived from a CD73‐negative CD4+ T‐cell line did not have such capabilities. Overall our findings demonstrate that CD73‐expressing exosomes produced by Treg cells following activation contribute to their suppressive activity through the production of adenosine.
Nucleoprotein‐specific nonneutralizing antibodies speed up LCMV elimination independently of complement and FcγR
Authors: Straub Tobias , Schweier Oliver , Bruns Michael , Nimmerjahn Falk , Waisman Ari , Pircher Hanspeter
Published: June 2013

CD8+ T cells have an essential role in controlling lymphocytic choriomeningitis virus (LCMV) infection in mice. Here, we examined the contribution of humoral immunity, including nonneutralizing antibodies (Abs), in this infection induced by low virus inoculation doses. Mice with impaired humoral immunity readily terminated infection with the slowly replicating LCMV strain Armstrong but showed delayed virus elimination after inoculation with the faster replicating LCMV strain WE and failed to clear the rapidly replicating LCMV strain Docile, which is in contrast to the results obtained with wild‐type mice. Thus, the requirement for adaptive humoral immunity to control the infection was dependent on the replication speed of the LCMV strains used. Ab transfers further showed that LCMV‐specific IgG Abs isolated from LCMV immune serum accelerated virus elimination. These Abs were mainly directed against the viral nucleoprotein (NP) and completely lacked virus neutralizing activity. Moreover, mAbs specific for the LCMV NP were also able to decrease viral titers after transfer into infected hosts. Intriguingly, neither C3 nor Fcγ receptors were required for the antiviral activity of the transferred Abs. In conclusion, our study suggests that rapidly generated nonneutralizing Abs specific for the viral NP speed up virus elimination and thereby may counteract T‐cell exhaustion.
Non‐neutralizing antibodies protect from chronic LCMV infection independently of activating FcγR or complement
Authors: Richter Kirsten , Oxenius Annette
Published: June 2013

Chronic viral infections lead to CD8+ T cell exhaustion, characterized by impaired cytokine secretion. The presence of the immune‐regulatory cytokine IL‐10 promotes chronic lymphocytic choriomeningitis virus (LCMV) Clone 13 infection in mice, whereas the absence of IL‐10/IL‐10R signaling early during infection results in viral clearance and higher percentages and numbers of antiviral, cytokine‐producing T cells. However, it is currently unclear which cell populations and effector molecules are crucial to protect against chronic infection. In this study, we demonstrate that antiviral, LCMV‐binding, non‐neutralizing antibodies are needed, in addition to CD4+ and CD8+ T cells, to clear a high‐dose LCMV infection in mice, in the absence of IL‐10. The interaction between CD4+ T cells and B cells in B‐cell follicles via CD40/CD40L, in addition to class switch and/or somatic hypermutation, is crucial for viral control in the absence of IL‐10. Interestingly, transfer of LCMV‐binding non‐neutralizing antibodies protected recipients from chronic infection. In addition, viral clearance in the absence of IL‐10R signaling was independent of activating Fcγ receptors and complement. These data highlight that non‐neutralizing antibodies effectively contribute to the control of LCMV infection when present prior to infection, suggesting that the induction of neutralizing antibodies is not implicitly necessary for the generation of successful vaccines.