bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of sphingolipid induced apoptosis by caspase inhibitors indicates that sphingosine acts in an earlier part of the apoptotic pathway than ceramide
Authors: Sweeney Elizabeth A , Inokuchi Jin-ichi , Igarashi Yasuyuki
Published: July 2002

Caspases are specific proteases involved in apoptosis, and their inhibition by specific peptide inhibitors can inhibit apoptosis. With these inhibitors we examined the relationship of caspases and sphingolipids involved in the induction of apoptosis of human leukemic HL60 cells. We have previously shown that sphingosine (Sph) and its methylated derivative dimethylsphingosine (DMS) effectively induce apoptosis in HL60 cells. Using these lipids as well as ceramide analogues we found both similarities and differences in the caspase involvement in apoptosis induced by the two distinct lipid types. The wide‐spectrum caspase inhibitor Z‐VAD‐FMK and Z‐DEVD‐FMK, an inhibitor of the downstream caspases 3 (CPP32, Yama) and 7, both inhibited apoptosis induced by all the lipids tested. Z‐AAD‐FMK which inhibits the serine protease Granzyme B, inhibited Sph/DMS induced apoptosis, but little or no effect on ceramide induced apoptosis. Granzyme B shares a substrate sequence preference with upstream caspases capable of activating themselves and other caspases downstream. Z‐IETD‐FMK, which inhibits caspase 8/FLICE also inhibited Sph/DMS induced apoptosis with no inhibition of apoptosis induced by either ceramide. Together, these data indicate that Sph/DMS act independently from ceramide in the apoptosis pathway and further suggest that Sph/DMS act earlier in the pathway than ceramide and are involved upstream of even the early proteases, whereas the point of action for ceramide is downstream of the early proteases but upstream from the late caspases.
The dipyridyls paraquat and diquat attenuate the interaction of G‐actin with thymosin β4
Authors: Huff Thomas , Cappelletti Graziella , Hannappel Ewald
Published: July 2002

β‐Thymosins sequester G‐actin and preserve a pool of monomers of actin which constitute an important prerequisite for cellular function of the microfilament system. To study the influence of paraquat binding to G‐actin on the interaction of G‐actin with thymosin β4 we determined the apparent dissociation constant of the G‐actin‐thymosin β4 complex in the absence or presence of paraquat using an ultrafiltration assay. Paraquat (1,1′‐dimethyl‐4,4′‐dipyridylium dichloride) attenuates this interaction in a concentration‐ and time‐dependent manner. When exposed to 10 mM paraquat, the apparent dissociation constant increased 10–85‐fold within 15 min to 24 h. After incubation for 24 h even a paraquat concentration as low as 100 μM increased the dissociation constant of the G‐actin‐thymosin β4 complex from 0.66 μM to 0.82 μM (P<0.05). Diquat (1,1′‐ethylene‐2,2′‐dipyridylium dibromide) similarly weakens the interaction of G‐actin and β‐thymosins. In none of the experiments was oxidation of the methionine residue or any other modification of thymosin β4 detected. Therefore we conclude that the dipyridyls paraquat and diquat directly interact with G‐actin and thereby impede the interaction between G‐actin and thymosin β4.
Direct evidence of nitric oxide production from bovine aortic endothelial cells using new fluorescence indicators: diaminofluoresceins
Authors: Nakatsubo Naoki , Kojima Hirotatsu , Kikuchi Kazuya , Nagoshi Hiroshi , Hirata Yasunobu , Maeda Daisuke , Imai Yasuyuki , Irimura Tatsuro , Nagano Tetsuo
Published: July 2002

The measurement of nitric oxide (NO) is important for direct examination of the regulatory roles of NO in various biological systems. Diaminofluoresceins (DAFs), new fluorescence indicators for NO, were applied to detect the release of NO from bovine aortic endothelial cells (ECs). DAFs react with NO to yield the corresponding green‐fluorescent triazolofluoresceins, which provide the advantages of specificity, sensitivity and a simple protocol for the direct detection of NO. Using these DAFs, we could detect the generation of NO not only from inducible NO synthase expressed in macrophages, but also from constitutive NO synthase expressed in ECs.
Characterisation of an Arabidopsis cDNA encoding a thylakoid lumen protein related to a novel `pentapeptide repeat' family of proteins
Authors: Kieselbach Thomas , Mant Alexandra , Robinson Colin , Schroder Wolfgang P
Published: July 2002

We have cloned an Arabidopsis cDNA encoding a novel thylakoid lumen protein, P17.4, that has been previously isolated from lumen extracts of spinach chloroplasts. The protein is synthesised with a bipartite presequence containing a Sec‐type lumen‐targeting signal peptide and the precursor protein is imported into the lumen of pea chloroplasts. The encoded protein is homologous to an Anabaena protein that is essential for correct glycolipid localisation, and is also related to at least 16 unassigned open reading frames in Synechocystis. This family of proteins is characterised by the presence of numerous pentapeptide repeats with the consensus structure AXLXX, and its members are predicted to be located in the cytosol, plasma membrane and periplasm/lumen. P17.4 is therefore the first higher plant member of an extended family of putative cyanobacterial proteins that may serve important roles in lipid transport or assembly.
Structure and mRNA expression of a bovine trp homologue related to mammalian trp2 transcripts
Authors: Wissenbach Ulrich , Schroth Gregor , Philipp Stephan , Flockerzi Veit
Published: July 2002

Mammalian homologues of the transient receptor potential (trp) gene product fromDrosophila melanogasterfunction as Ca2+‐selective or non‐selective cation channels. Complementary DNA was isolated from a bovine testis cDNA library which encodes bovine trp2 (btrp2), a protein of 432 amino acid residues comprising four predicted transmembrane segments. Btrp2 mRNA is expressed in bovine testis, spleen and liver but not in brain, heart, adrenal gland or retina. In bovine testis expression of btrp2 mRNA is restricted to spermatocytes but is not present in spermatogonia, Leydig or Sertoli cells suggesting that btrp2 may contribute to the formation of ion channels in sperm cells.
Re‐expression of C/EBPα induces CYP2B6, CYP2C9 and CYP2D6 genes in HepG2 cells
Authors: Jover Ramiro , Bort Roque , Gómez-Lechón M.José , Castell José V
Published: July 2002

Cytochrome P450 (CYP) activity is very low or even absent in human hepatomas, a phenomenon that is accompanied by low levels of some liver transcription factors, notably C/EBPα. To investigate a possible link between this transcription factor and hepatic CYP expression, we have stably transfected HepG2 cells with a C/EBPα vector containing a Zn‐inducible metallothionein promoter. Expression of functional C/EBPα up to liver levels concomitantly increased the mRNAs of several members of the CYP2 family (2B6, 2C9 and 2D6), suggesting that this transcription factor may play a relevant role in controlling the hepatic expression of CYP enzymes.
Characterization of the Ca2+‐dependent and ‐independent interactions between calmodulin and its binding domain of inducible nitric oxide synthase
Authors: Yuan Tao , Vogel Hans J , Sutherland Cindy , Walsh Michael P
Published: July 2002

Most interactions of calmodulin (CaM) with its target proteins are Ca2+‐dependent, but a few Ca2+‐independent CaM‐target protein interactions have been identified. One example is the inducible isoform of nitric oxide synthase (iNOS) expressed in macrophages. We describe here the characterization of the Ca2+‐independent interaction between CaM and a synthetic peptide corresponding to the CaM‐binding domain of murine macrophage iNOS using circular dichroism (CD) spectroscopy. The CD spectrum of free iNOS peptide indicated a β‐sheet conformation. The interaction of iNOS peptide with apo‐CaM in the absence of Ca2+ resulted in the peptide acquiring a type II β‐turn structure. This is in contrast to the situation in the presence of Ca2+ in which case the peptide acquired an α‐helical conformation upon interaction with CaM, i.e. similar to the Ca2+‐dependent interactions of CaM with numerous targets such as myosin light chain kinase (MLCK). Consistent with this similar structural change, iNOS peptide inhibited the Ca2+‐CaM‐dependent activation of smooth muscle MLCK by competing with MLCK for binding to Ca2+‐CaM. The K
d of Ca2+‐CaM for iNOS peptide was calculated from competition assays to be 0.3 nM. These results indicate that the structure of the CaM‐binding domain of iNOS is quite different when bound to apo‐CaM than Ca2+‐CaM.
Cysteine‐string proteins regulate exocytosis of insulin independent from transmembrane ion fluxes
Authors: Zhang Hui , Kelley William L. , Chamberlain Luke H. , Burgoyne Robert D. , Wollheim Claes B. , Lang Jochen
Published: July 2002

Cysteine‐string proteins (Csps) are vesicle proteins involved in exocytosis of synaptic vesicles in Drosophila and modulation of presynaptic calcium influx. As both the contribution of calcium channel regulation to the role of Csp in exocytosis and a function of Csp outside the nervous system are unknown, we studied its function in endocrine exocytosis from large dense core vesicles (LDCVs) using insulin‐secreting pancreatic β‐cells. Csps were expressed in primary and derived β‐cell lines on insulin‐containing LDCVs. Suppression of Csp expression reduced not only depolarisation induced insulin release but also exocytosis in permeabilised cells directly stimulated by Ca2+. Thus, Csp is a secretory granule protein and is required for endocrine exocytosis independent of the modulation of transmembrane calcium fluxes.
Biophysical interaction between phospholamban and protein phosphatase 1 regulatory subunit GM
Authors: Berrebi-Bertrand Isabelle , Souchet Michel , Camelin Jean-Claude , Laville Marie-Paule , Calmels Thierry , Bril Antoine
Published: July 2002

Regulation of the sarco(endo)plasmic reticulum Ca2+‐ATPase (SERCA 2a) depends on the phosphorylation state of phospholamban (PLB). When PLB is phosphorylated, its inhibitory effect towards SERCA 2a is relieved, leading to an enhanced myocardial performance. This process is reversed by a sarcoplasmic reticulum (SR)‐associated type 1 protein phosphatase (PP1) composed of a catalytic subunit PP1C and a regulatory subunit GM. Human GM and PLB have been produced in an in vitro transcription/translation system and used for co‐immunoprecipitation and biosensor experiments. The detected interaction between the two partners suggests that cardiac PP1 is targeted to PLB via GM and we believe that this process occurs with the identified transmembrane domains of the two proteins. Thus, the interaction between PLB and GM may represent a specific way to modulate the SR function in human cardiac muscle.
Superoxide induces apoptosis in cardiomyocytes, but proliferation and expression of transforming growth factor‐β1 in cardiac fibroblasts
Authors: Li Pei-Feng , Dietz Rainer , von Harsdorf Rüdiger
Published: July 2002

Cardiomyocyte apoptosis and cardiac fibroblast proliferation are characteristic features of failing myocardium. Here we investigated the effect of superoxide on the cell fate of cardiomyocytes and cardiac fibroblasts. Cultured rat cardiomyocytes or cardiac fibroblasts were treated with superoxide. In response to superoxide stimulation cardiomyocytes underwent apoptosis as revealed by the increase in histone associated DNA fragmentation and positive to in situ nick end‐labeling. In contrast, cardiac fibroblasts were stimulated to proliferate as demonstrated by the increase in DNA synthesis detected by [3H]thymidine incorporation and in cell number. Additionally, Northern blot analysis showed that transforming growth factor‐β1, a key factor responsible for myocardial fibrosis, was upregulated in cardiac fibroblasts in response to superoxide stimulation. These data suggest that superoxide can induce such divergent effects as apoptosis in cardiomyocytes and cell growth in cardiac fibroblasts, indicating that it may be a potential factor involved in the pathogenesis of heart failure.
Human histamine H2 receptor gene: multiple transcription initiation and tissue‐specific expression1
Authors: Murakami Hideaki , Sun-Wada Ge-Hong , Matsumoto Makiko , Nishi Tsuyoshi , Wada Yoh , Futai Masamitsu
Published: July 2002

We have characterized the genomic structure of 12.3 kb of the 5′‐flanking region of the human histamine H2 receptor gene. The multiple transcription initiation sites of the human histamine H2 receptor gene were mapped utilizing the 5′‐end cap structure of mRNA. We found that a 85 bp segment (−610–−525 bp) immediately upstream of the initiation site exhibits a strong promoter activity in the gastric adenocarcinoma, MNK45, expressing human histamine H2 receptor. A 4.8 kb transcript of the human histamine H2 receptor gene was found in the placenta, spinal cord, lymph node and bone marrow in addition to the previously reported tissues including the heart, brain and stomach, whereas a 1.8 kb transcript was observed in almost all tissues examined. 3′‐rapid amplification of cDNA ends revealed the corresponding length of the 3′‐untranslated region. These results suggest that the 3′‐untranslated region may be involved in the differential expression.
Fourier‐transform resonance Raman spectra of cation carotenoid in photosystem II reaction centres
Authors: Pascal Andrew , Telfer Alison , Barber James , Robert Bruno
Published: July 2002

Resonance Raman spectra of the cation form of a redox‐active carotenoid in photosystem II are presented. These results have implications for the nature of the carotenoid radical and in particular the localisation of the hole on this molecule.
Role of the 14‐3‐3 proteins in the regulation of H+‐ATPase activity in the plasma membrane of suspension‐cultured sugar beet cells under cold stress
Authors: Chelysheva Vera V , Smolenskaya Irina N , Trofimova Marina C , Babakov Alexei V , Muromtsev Georgii S
Published: July 2002

All higher plants possess highly specific binding sites for fusicoccin, a metabolite of the fungus Fusicoccum amygdali Del. These sites are harboured in the plasma membranes and formed by a 14‐3‐3 protein dimer associated with the C‐terminal autoinhibitory domain of H+‐ATPase. We considered the fusicoccin binding to plasma membranes to be an indicator of complexation between the 14‐3‐3 dimer and H+‐ATPase, we assessed the effect of cold stress on the interaction of these proteins in suspension‐cultured sugar beet cells and protoplasts derived from these cells. In both objects, upon lowering the temperature to 0–4°C, a portion of the cytoplasmic 14‐3‐3 proteins became associated with the plasma membrane, which showed an increasing amount of ATPase/14‐3‐3 complexes and enhanced ATPase activity. Association between ATPase and 14‐3‐3 resulted in a several‐fold rise in the H+ efflux from protoplasts and intact cells. We suppose that regulation of the H+ pumping under changing external conditions may be based on the interaction between H+‐ATPase and the 14‐3‐3 proteins.
Histidine modification and mutagenesis point to the involvement of a large conformational change in the mechanism of action of phage lambda lysozyme
Authors: Evrard Christine , Fastrez Jacques , Soumillion Patrice
Published: July 2002

Phage lambda lysozyme (λL) is structurally related to other known lysozymes but its mechanism of action is different from the classical lysozyme mechanism, acting as a transglycosidase rather than a hydrolase. As two conformations have been revealed by the crystal structure, we investigated the effect of mutating and modifying a histidine located near to or far from the active site in the respective closed and open conformations. Whereas its asparagine mutation has little or no effect on activity, its N‐carbethoxylation inactivates the enzyme. This provide further evidence for the involvement of the closed conformation and for the need of conformational mobility in λL function.
Somatostatin receptor subtype 1 modulates basal inhibition of growth hormone release in somatotrophs
Authors: Kreienkamp Hans-Jürgen , Akgün Ercan , Baumeister Hans , Meyerhof Wolfgang , Richter Dietmar
Published: July 2002

Somatostatin (SST) inhibits the secretion of many peptide hormones including growth hormone (GH). The various functions of SST are mediated through at least five different receptor subtypes (SSTR1–5), their precise physiological roles have not been solved yet. Here we report on studies concerning the functional role of SSTR1 in the modulation of GH release from somatotrophs. Primary cell cultures from pituitaries of wild‐type SSTR1 mice exposed to the SSTR1 selective somatostatin analog CH‐275 show reduction of basal levels of GH secretion whereas somatotrophs isolated from SSTR1 null mutant mice did not respond to the agonist‐mediated effect. This suggests that SSTR1 is involved in modulating basal GH levels in primary pituitary cell cultures and, together with SSTR2, may control the secretion of GH in the body.
Progress toward an explicit mechanistic model for the light‐driven pump, bacteriorhodopsin
Authors: Lanyi Janos K
Published: July 2002

Recent crystallographic information about the structure of bacteriorhodopsin and some of its photointermediates, together with a large amount of spectroscopic and mutational data, suggest a mechanistic model for how this protein couples light energy to the translocation of protons across the membrane. Now nearing completion, this detailed molecular model will describe the nature of the steric and electrostatic conflicts at the photoisomerized retinal, as well as the means by which it induces proton transfers in the two half‐channels leading to the two membrane surfaces, thereby causing unidirectional, uphill transport.
The opinion of Brazilian women regarding vaginal labor and cesarean section
Authors: Osis M.J.D. , Pádua K.S. , Duarte G.A. , Souza T.R. , Faúndes A.
Published: July 2002

Objectives: The opinions of Brazilian women regarding vaginal delivery and cesarean sections was studied. Methods: Six hundred and fifty‐six women who had given birth in seven hospitals in São Paulo and Pernambuco, using the Public Health Service, were interviewed. The opinions of women who had delivered only by cesarean section was compared with those of women who had had at least one vaginal delivery. Results: Significantly more women who had experienced at least one vaginal delivery considered this to be the best way of giving birth (90.4% vs. 75.9% among C‐section‐only women). Similar proportions in both groups (45.5% and 42.8%) stated that vaginal labor is better because it causes less pain and suffering for the woman. Significantly more women who had experienced a vaginal labor (47.1% vs. 30.3%) reported that it had no disadvantage. More women who had only had cesarean sections referred not having contractions/pain as an advantage of this method (56.7% vs. 41.7%). Conclusions: Apparently, pain and women's perception of pain were the characteristics which differentiated women with history of vaginal delivery from those with cesarean sections in the sample studied. However, the opinion that vaginal delivery is better than cesarean section was expressed independently of the recognition that pain could be its main disadvantage.
Serum vitamin K level and bone mineral density in post‐menopausal women
Authors: Kanai T. , Takagi T. , Masuhiro K. , Nakamura M. , Iwata M. , Saji F.
Published: July 2002

Objective: Vitamin K is known to influence bone metabolism by facilitating the synthesis of osteocalcin (BGP). The bone mineral density decreases drastically after menopause. We investigated the relationship of bone mineral density, vitamin K levels and other biological parameters of bone metabolism in post‐menopausal women. Methods: Serum levels of vitamin K, BGP and other markers of bone metabolism were measured in 71 post‐menopausal women (19 with reduced bone mineral density and 52 with normal bone density), and 24 women with climacteric symptoms receiving hormone replacement therapy (HRT), (6 with reduced bone mineral density and 18 with normal density). Results: In the first group, women with reduced bone mineral density showed lower levels of vitamin K1 and K2 than those with normal bone mineral density. In the other group, the level of BGP decreased but levels of vitamin K showed no increase during HRT. Conclusion: The present findings suggested that vitamin K was related to post‐menopausal bone mineral loss.
Great grand multiparity: is it a risk?
Authors: Abu‐Heija A.T , El Chalabi H
Published: July 2002

Objective: To compare antenatal and intrapartum complications incidence among women delivering for the 10th time or more and to compare this with those of low parity (para 2–5). Methods: The records of (154) women of great grand multipara (para>10) were reviewed and compared with (308) women (para 2–5) delivered during the same period. Antepartum as well as intrapartum complications were compared, all occurring between 16 April 1994 and 15 January 1995. Results: Great grand multiparous women are older. The incidence of diabetes mellitus, chronic hypertension and preterm labor are similar to those with low parity, while they have higher incidences of pre‐eclampsia (7.1% vs. 2.6%) and intrauterine fetal death (5.2 vs. 1.3%) P<0.025. There were no differences in the incidences of placental abruption, placenta previa, malpresentation, postpartum hemorrhage and operative delivery between the two groups. Great grand multipara also have a higher incidence of macrosomia (12% vs.12%) P<0.0001. Conclusion: Great grand multiparous woman are at increased risk of having pre‐eclampsia, intrauterine fetal death and macrosomia.
The presence of smooth muscle actin in fibroblasts in the torn human rotator cuff
Authors: Premdas J. , Tang J.‐B. , Warner J. P. , Murray M. Meaney , Spector M.
Published: July 2002

The rotator cuff frequently sustains athletic and occupational injury, often resulting in chronic pain and disability. However, despite the high incidence of such shoulder problems, the pathophysiology of rotator cuff injury and healing has not yet been fully elucidated. The notable finding of this study was the presence of a contractile actin isoform, α‐smooth muscle actin (SMA), in nonvascular cells in all of the seven torn human rotator cuff specimens evaluated immunohistochemically. Up to 95% of cells in any one region, and over 95% of elongated cells found in association with crimped collagen, contained SMA. Most of the cells staining positive for SMA in these sections had morphological features of the fibroblast, though a small number were chondrocyte‐like. Treatment of cells growing out from human rotator cuff explants with TGF‐β1 significantly increased the amount of SMA evaluated by Western blot analysis. PDGF‐BB and IFN‐γ had no effect on the cell content of SMA. This is the first documentation of the presence of SMA‐positive cells in the human rotator cuff tendon. SMA has been found in a number of other healing connective tissues including skin, ligament, meniscus, cartilage, and other types of tendon. Of importance are previous findings that SMA‐positive cells can contract a collagen‐glycosaminoglycan analog of extracellular matrix in vitro. The results of the present study thus suggest that SMA‐containing cells could contribute to the retraction of the torn ends of a ruptured rotator cuff and play an important role in healing. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Early anchoring collagen fibers at the bone—tendon interface are conducted by woven bone formation: light microscope and scanning electron microscope observation using a canine model
Authors: Oguma Hiroshi , Murakami Gen , Takahashi‐Iwanaga Hiromi , Aoki Mitsuhiro , Ishii Seiichi
Published: July 2002

To clarify the early process of recovery at the bone‐tendon interface, we used light microscopy and SEM to examine the process of anchoring of collagen fibers to bone in a canine model.

At two weeks, tendon, scar tissue, woven bone and lamellar bone were present at the insertion site. SEM revealed anchoring of collagen fibril bundles of the scar to the woven bone. By 4 weeks, the number of anchoring fibers had increased and a parallel arrangement of fibers was observed. SEM demonstrated deep penetration of fibers into the woven bone layer. In addition, the fibers were observed to project into and intermingle with the scar tissue. By 6 weeks, the anchoring fibers had developed fully and were distributed densely over the interface. SEM also revealed that the collagen fibril bundles in the scar tissue had connected with the collagen fibrils of the woven bone by way of the anchoring bundles. The woven bone was identifiable throughout the early stages of recovery as the interface between soft tissue and hard tissue. Throughout all experimental periods, no staining was observed at the interface of the tendon and bone by Saffranin‐O. The formation of woven bone was important during early recovery of the tendonbone interface prior to the completion of fibrocartilage‐mediated insertion. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Occurrence and clinical correlates of psychiatric co-morbidity in delusional disorder
Authors: Maina G. , Albert U. , Badà A. , Bogetto F.
Published: July 2002

The present study investigated the occurrence and the clinical correlates of psychiatric co-morbidity in a sample of 64 patients with delusional disorder (DD). Subjects were evaluated with a semi-structured interview for the collection of demographic and clinical features of the disorder; co-morbid axis 1 disorders were determined according to the clinical interview using DSM-IV by Othmer and Othmer. Delusional disorder subjects with and without co-morbid diagnoses were compared to investigate whether the presence of another psychiatric disorder influenced the clinical features of the illness.

Seventy-two percent of the subjects had at least one additional lifetime psychiatric diagnosis. High lifetime co-morbidity was found with affective disorders, whose onset generally had been subsequent to the onset of DD. Patients with at least one co-morbid disorder (N = 46) had an earlier age at onset, presented for the first psychiatric consultation at an earlier age, and were younger at index evaluation for this study with respect to patients without co-morbidity (N = 18). Types of DD differed significantly according to the presence/absence of lifetime co-morbid disorders: DD patients with co-morbidity were in most cases persecutory type (54.4%) while DD patients without co-morbidity were mixed type (66.7%).

Our data indicate that there is a considerable proportion of patients whose DDr is strictly connected with other co-occurring psychiatric disorders (mainly affective disorders), which exert an influence on the phenomenology of the illness.
Partial left ventriculectomy: sunrise or sunset?
Authors: Starling Randall C. , McCarthy Patrick M.
Published: July 2002

Partial left ventriculectomy (PLV) was proposed as an alternative to cardiac transplantation for patients with advanced heart failure. Patients with dilated cardiomyopathy that were considered eligible candidates for cardiac transplantation were offered the option of surgical ventriculectomy or to continue waiting for a donor organ. Sixty‐two patients underwent PLV between May 1996 and December 1998, mean age 54 years, 47 males, mean ejection fraction 13.5%, mean peak oxygen consumption 10.8 ml/kg/min, 39% NYHA class III and 61% NYHA IV. Perioperative mortality 3.2%, 10/62 (16%) required implant of a left ventricular assist device (LVAD) due to shock, most in the early post‐operative period. Survival at 1 and 2 years was 78% and 68%. Event free survival (freedom from death, LVAD, or return of NYHA class IV failure) was 50% and 37% at 1 and 2 years. Event free survivors experienced improvement in NYHA class (3.7 to 2.2) and increased oxygen consumption (11.7 to 16.0 ml/kg/min). Based on these data PLV has a significant early failure rate and a 2 year event free survival rate of only 37%. PLV does not yield outcomes equivalent to cardiac transplantation based on current selection criteria and requires further investigation to determine its role in the treatment of advanced heart failure.
Stereoselective Preparation of C‐Aryl Glycosides via Visible‐Light‐Induced Nickel‐Catalyzed Reductive Cross‐Coupling of Glycosyl Chlorides and Aryl Bromides
Authors: Mou Ze‐Dong , Wang Jia‐Xi , Zhang Xia , Niu Dawen
Published: May 2021

A nickel‐catalyzed cross‐coupling reaction of glycosyl chlorides with aryl bromides has been developed. The reaction proceeds smoothly under visible‐light irradiation and features the use of bench‐stable glycosyl chlorides, allowing the highly stereoselective synthesis of C‐aryl glycosides.

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Chemical Characterization of a Volatile Dubnium Compound, DbOCl3
Authors: Chiera Nadine M. , Sato Tetsuya K. , Eichler Robert , Tomitsuka Tomohiro , Asai Masato , Adachi Sadia , Dressler Rugard , Hirose Kentaro , Inoue Hiroki , Ito Yuta , Kashihara Ayuna , Makii Hiroyuki , Nishio Katsuhisa , Sakama Minoru , Shirai Kaori , Suzuki Hayato , Tokoi Katsuyuki , Tsukada Kazuaki , Watanabe Eisuke , Nagame Yuichiro
Published: May 2021

The formation and the chemical characterization of single atoms of dubnium (Db, element 105), in the form of its volatile oxychloride, was investigated using the on‐line gas phase chromatography technique, in the temperature range 350–600 °C. Under the exactly same chemical conditions, comparative studies with the lighter homologues of Group 5 in the Periodic Table clearly indicate the volatility sequence being NbOCl3 > TaOCl3 ≥ DbOCl3. From the obtained experimental results, thermochemical data for DbOCl3 were derived. The present study delivers reliable experimental information for theoretical calculations on chemical properties of transactinides.
High‐Spin Imido Cobalt Complexes with Imidyl Radical Character**
Authors: Reckziegel Alexander , Kour Manjinder , Battistella Beatrice , Mebs Stefan , Beuthert Katrin , Berger Robert , Werncke C. Gunnar
Published: May 2021

We report on the synthesis of a variety of trigonal imido cobalt complexes [Co(NAryl)L2]−, (L=N(Dipp)SiMe3), Dipp=2,6‐diisopropylphenyl) with very long Co−NAryl bonds of around 1.75 Å. Their electronic structure was interrogated using a variety of physical and spectroscopic methods such as EPR or X‐Ray absorption spectroscopy which leads to their description as highly unusual imidyl cobalt complexes. Computational analyses corroborate these findings and further reveal that the high‐spin state is responsible for the imidyl character. Exchange of the Dipp substituent on the imide by the smaller mesityl function (2,4,6‐trimethylphenyl) effectuates the unexpected Me3Si shift from the ancillary ligand set to the imidyl nitrogen, revealing a highly reactive, nucleophilic character of the imidyl unit.
A Mortise‐and‐Tenon Joint Inspired Mechanically Interlocked Network
Authors: Zhao Dong , Zhang Zhaoming , Zhao Jun , Liu Kai , Liu Yuhang , Li Guangfeng , Zhang Xinhai , Bai Ruixue , Yang Xue , Yan Xuzhou
Published: May 2021

Mortise‐and‐tenon joints have been widely used for thousands of years in wooden architectures in virtue of their artistic and functional performance. However, imitation of similar structural and mechanical design philosophy to construct mechanically adaptive materials at the molecular level is a challenge. Herein, we report a mortise‐and‐tenon joint inspired mechanically interlocked network (MIN), in which the [2]rotaxane crosslink not only mimics the joint in structure, but also reproduces its function in modifying mechanical properties of the MIN. Benefiting from the hierarchical energy dissipative ability along with the controllable intramolecular movement of the mechanically interlocked crosslink, the resultant MIN simultaneously exhibits notable mechanical adaptivity and structural stability in a single system, as manifested by decent stiffness, strength, toughness, and deformation recovery capacity.
Enantioselective Total Synthesis and Structural Revision of Dysiherbol A
Authors: Baars Julian , Grimm Isabelle , Blunk Dirk , Neudörfl Jörg‐Martin , Schmalz Hans‐Günther
Published: May 2021

A 12‐step total synthesis of the natural product dysiherbol A, a strongly anti‐inflammatory and anti‐tumor avarane meroterpene isolated from the marine sponge Dysidea sp., was elaborated. As key steps, the synthesis features an enantioselective Cu‐catalyzed 1,4‐addition/enolate‐trapping opening move, an Au‐catalyzed double cyclization to build up the tetracyclic core‐carbon skeleton, and a late installation of the C5‐bridgehead methyl group via proton‐induced cyclopropane opening associated with spontaneous cyclic ether formation. The obtained pentacyclic compound (corresponding to an anhydride of the originally suggested structure for dysiherbol A) showed identical spectroscopic data as the natural product, but an opposite molecular rotation. CD‐spectroscopic measurements finally confirmed that both the constitution and the absolute configuration of the originally proposed structure of (+)‐dysiherbol A need to be revised.
Molecular properties prediction, synthesis, and antimicrobial activity of bis(azolyl)sulfonamidoacetamides
Authors: P Siva sankar , K Narendra babu , Rekha Tamatam , Padmaja Adivireddy , Padmavathi Venkatapuram
Published: May 2021

A library of bis(azolyl)sulfonamidoacetamides was prepared by the reaction of azolylsulfonylamines with azolylchloroacetamides in the presence of pyridine/4‐(dimethylamino)pyridine (DMAP) under ultrasonication. The reaction proceeded well with DMAP, resulting in a higher yield of the products. The antimicrobial activity of the compounds indicated that N‐{5‐[N‐(2‐{[4‐(4‐chloro‐1H‐pyrrol‐2‐yl)‐1H‐imidazol‐2‐yl)amino}‐2‐oxoethyl)sulfamoyl]‐4‐phenylthiazol‐2‐yl}benzamide (22a), N‐{5‐[N‐(2‐{[4‐(4‐chloro‐1H‐pyrrol‐2‐yl)‐1H‐imidazol‐2‐yl]amino}‐2‐oxoethyl)sulfamoyl]‐4‐(4‐chlorophenyl)thiazol‐2‐yl}benzamide (22c), and N‐{5‐[N‐(2‐{[4‐(4‐chloro‐1H‐pyrrol‐2‐yl)‐1H‐imidazol‐2‐yl]amino}‐2‐oxoethyl)sulfamoyl]‐4‐(4‐chloro‐phenyl)‐1H‐imidazol‐2‐yl}benzamide (24c) exhibited a low minimal inhibitory concentration (MIC) against Bacillus subtilis, equal to the standard drug, chloramphenicol. Compounds 22c and 24c also showed low MICs against Aspergillus niger, equal to the standard drug, ketoconazole. The molecular properties of the synthesized molecules were studied to identify druglikeness properties of the target compounds. On the basis of molecular properties prediction, 19a, 19b, 20b, 20c, 21a–c, 22b, 22c, and 23a–c can be treated as drug candidates.
Surface Modulation of Iron‐doped MoS2 Nanosheets by Phytic Acid for Enhanced Water Oxidation
Authors: Zhao Min , Song Yanhui , Wang Jingkun , Wei Bingwei , Wang Chengqiang , Sha Wenbo , Cao Hailiang , Liu Peizhi , Du Xiaoqiang , Guo Junjie
Published: May 2021

Surface modulation and heteroatom doping are important approaches for boosting the electrocatalytic performances of MoS2 nanosheets. As a molecular electrocatalyst, the natural organic phytic acid (PA) offer attractive intermediate for oxygen evolution reaction (OER). Here, a surface modulation strategy is demonstrated through the decoration of PA onto the basal plane of iron (Fe)‐doped MoS2 nanosheets supported on nickel foam (NF) for boosted OER activity. Experimental results indicate that the PA modification and Fe doping could effectively boost the charge transfer and mass transport during the OER process. Specially, PA2‐Fe−MoS2 grown on NF (PA2‐Fe−MoS2/NF) exhibits excellent OER activity (218 mV@20 mA cm−2) and durability, even superior to RuO2 and many other previously reported OER catalysts. This natural organic molecule modification provides a facile strategy to designing low‐cost and efficient electrocatalytic materials.
Effect of Topology on Photodynamic Sterilization of Porphyrinic Metal‐Organic Frameworks
Authors: Liu Yao‐Yao , Chen Li‐Jian , Zhao Xu , Yan Xiu‐Ping
Published: May 2021

Porphyrinic metal‐organic frameworks (MOFs) are promising photosensitizers due to the lack of self‐aggregation of porphyrin in aqueous solution. However, how the topology of porphyrinic MOFs affects the generation of singlet oxygen (1O2) is unclear. Here, the effect of the topology of porphyrinic MOFs on their photodynamic performance is reported. Four porphyrinic zirconium MOFs (MOF‐525, MOF‐545, PCN‐223 and PCN‐224 with different topologies: ftw, csq, shp and she, respectively) were selected to study the influence of topology on the photodynamic antibacterial performance. The 1O2 generation and the photodynamic antibacterial performance followed an decreasing order of MOF‐545>MOF‐525>PCN‐224>PCN‐223. The results reveal that the pore size, the distance between porphyrin, and the number of porphyrin per Zr6O8 cluster in MOFs greatly affected 1O2 generation. This work provides guidance for designing new MOFs for efficient photodynamic sterilization.
Enantiopure Polyradical Tetrahedral Pd12L6 Cages
Authors: Rajasekar Prabhakaran , Swain Abinash , Rajaraman Gopalan , Boomishankar Ramamoorthy
Published: May 2021

The synthesis of cages with a polyradical framework remains a challenging task. Herein is reported an enantiomeric pair of quinoid‐bridged polyradical tetrahedral palladium(II) cages that are stabilized by an unusual dianionic diradical form (dhbq..2−). These cages have been characterized by electron paramagnetic resonance and UV‐visible spectroscopy, squid magnetometry and mass spectrometry. Single‐crystal‐derived X‐ray investigations of the iso‐structural cages built on fluoranilate linkers confirm the tetrahedral structure of the obtained radical cages. Theoretical calculations showed that the diradical state of the dhbq anions is more stable than the usual monoradical state. A weak ferromagnetic exchange between adjacent radical centers was observed in DFT studies.
Radicals and Anions of Siloles and Germoles
Authors: Reinhold Crispin R. W. , Schmidtmann Marc , Tumanskii Boris , Müller Thomas
Published: May 2021

The synthesis of persistent sila‐ and germacyclopentadienyl (silolyl‐ and germolyl‐) radicals by careful stoichiometric reduction of the corresponding halides with potassium is reported. The radicals were characterized by EPR spectroscopy and trapping reactions. The reduction of tris(trimethylsilyl)silyl‐substituted halides was successful while smaller substituents (i. e., t‐Butyl, Ph) gave the corresponding dimers. The EPR spectroscopic parameter of the synthesized tetrolyl radicals indicate only small spin delocalization to the butadiene unit due to cross‐hyperconjugation. Silolyl‐ and germolyl anions are unavoidable byproducts and are isolated in the form of their potassium salts and characterized by X‐ray crystallography. The comparison of the molecular structures of two closely related potassium silolides provided an example for different coordination of the potassium cation to the silolyl anion (η1 vs. η5 coordination) that triggers the switch between delocalized and localized states.
Externally Regulated Specific Molecular Recognition Driven Pathway Selectivity in Supramolecular Polymerization
Authors: Chakraborty Anwesha , Manna Rabindra Nath , Paul Ankan , Ghosh Suhrit
Published: May 2021

This article reveals 4‐dimethylaminopyridine (DMAP) regulated pathway selectivity in the supramolecular polymerization of a naphthalene‐diimide derivative (NDI‐1), appended with a carboxylic acid group. In decane, NDI‐1 produces ill‐defined aggregate (Agg‐1) due to different H‐bonding motifs of the −COOH group. With one mole equivalent DMAP, the NDI‐1/DMAP complex introduces new nucleation condition and exhibits a cooperative supramolecular polymerization producing J‐aggregated fibrillar nanostructure (Agg‐2). With 10 % DMAP and fast cooling (10 K/min), similar nucleation and open chain H‐bonding with the free monomer in an anti‐parallel arrangement produces identical J‐aggregate (Agg‐2a). With 2.5 % DMAP and slow cooling (1 K/min), a distinct nucleation and supramolecular polymerization pathway emerge leading to the thermodynamically controlled Agg‐3 with face‐to‐face stacking and 2D‐morphology. Slow cooling with 5–10 % DMAP produces a mixture of Agg‐2a and Agg‐3. Computational modelling studies provide valuable insights into the internal order and the pathway complexity.
How corporate social responsibility can incentivize top managers: A commitment to sustainability as an agency intervention
Authors: Greiner Michael , Sun Jing
Published: May 2021

Over the past few years, scholarly interest in corporate social responsibility (CSR) has been increasing. However, research on the relationship between CSR and firm performance has revealed a complicated relationship. In this paper, we argue that part of the basis for the generally positive relationship between CSR and firm performance might come from a reduction in agency costs. Relying on behavioral agency theory, we construct a model in which CSR moderates the impact of the agency problem on specific firm outcomes, including firm performance, the use of stock options, and goodwill. Based on panel data of publicly traded U.S. firms from 1999 to 2013, we find support for that model. These findings suggest the role of CSR in improving corporate governance efficiency through mitigating agency problems inside the firm.
Catalysis in Supramolecular Systems: the Case of Gel Phases
Authors: Rizzo Carla , Marullo Salvatore , Billeci Floriana , D'Anna Francesca
Published: May 2021

Supramolecular gels are a fascinating class of materials, originated by the self‐assembly of low molecular weight molecules. Underpinned by non‐covalent interactions, they find application in a diverse range of fields. Among these, supramolecular gels can be considered as organized, non‐conventional reaction media, able to influence reactivity in a radically different way, compared with what happens in solution. This short review will focus on this aspect, covering literature from 2010 onwards, addressing the application of supramolecular gels as reaction media. In particular, in the first section we explore organocatalytic reactions in gel phase, with wide synthetic relevance, such as aldol and Mannich reactions as well as Friedel Crafts or ester hydrolysis processes. Subsequently, focus is laid on metal‐catalysed reactions, among which relevance is given to widely used reactions like cross‐coupling and click reactions. Then, the final sections describe the use of supramolecular gels as reaction media for photo‐ and biocatalysed processes.
Genome‐wide identification of age‐related CpG sites for age estimation from blood DNA of Han Chinese individuals
Authors: Xiao Chao , Yi Shaohua , Huang Daixin
Published: May 2021

Age‐related CpG (AR‐CpG) sites are currently the most promising molecular markers for forensic age estimation. However, the AR‐CpG sites of Han Chinese population remains to be systematically characterized. In this study, we performed genome‐wide methylation analyses on 42 whole blood DNA from healthy Han Chinese volunteers (aged from 18 to 62 years) using the Illumina MethylationEPIC BeadChip microarray. As expected, both known and novel AR‐CpG sites were identified. Considering the sex difference in aging rate, we then separately selected AR‐CpG candidates and built pyrosequencing‐based multiple linear regression models for age estimation of males and females. The model constructed from the male sample group (n = 167, aged from 1.50 to 85.71 years) explained 95.22% of variation in age using five AR‐CpG sites (chr6:11044864 ELOVL2, chr1:207997068 C1orf132, cg19283806 CCDC102B, cg17740900, and chr10:73740306 CHST3) and yielded a mean absolute error (MAE) of 2.79 years. The model constructed from the female sample group (n = 141, aged from 3.33 to 80.38 years) explained 94.90% of variation in age with six AR‐CpG sites (chr6:11044867 ELOVL2, chr1:207997060 C1orf132, chr2:106015757 FHL2, cg26947034, chr16: 67184108 B3GNT9, and chr20:44658203 SLC12A5) and yielded an MAE of 2.53 years. Besides, the estimated age was highly correlated with the actual age (R > 0.97). The robustness of these AR‐CpG markers was demonstrated by 10‐fold cross‐validations. In conclusion, we updated the AR‐CpG sites of Han Chinese population and provided two sets of AR‐CpG sites for accurate age estimation.
The hypoglycemic effect of freeze‐dried fermented mulberry mixed with soybean on type 2 diabetes mellitus
Authors: Long Xiao‐Shan , Liao Sen‐Tai , Li Er‐Na , Pang Dao‐Rui , Li Qian , Liu Shu‐Cheng , Hu Teng‐Gen , Zou Yu‐Xiao
Published: May 2021

Mulberry has significant hypoglycemic effect and can be used as an auxiliary food for people with type 2 diabetes. However, it is rich in carbohydrate and cannot be consumed directly by diabetic patients. In the study, we fermented the mulberry to reduce the content of glucose and fructose, and added the soybean to reduce the loss of probiotics during fermentation and then determined its hypoglycemic effect. We induced type 2 diabetes mellitus (T2DM) mice by streptozotocin and measured its blood glucose, serum biochemistry, hepatic and pancreatic histopathology, and the diversity of the gut microbiota. After 5 weeks of oral DFMS administration, the glucose tolerance was improved significantly in T2DM mice. Furthermore, there were also significant increases in superoxide dismutase activity and glutathione concentration, and marked reductions in the concentrations of malondialdehyde and free fatty acids. Moreover, DFMS also prevented histopathological changes and the increases in the activities of alanine transaminase and aspartate transaminase. DFMS treatment also markedly increased the richness of the gut microbial community. The abundance of Bacteroidetes was increased, and those of Proteobacteria, Escherichia‐Shigella, and Lactobacillus were reduced. In summary, DFMS has a clear hypoglycemic effect in mice with T2DM.
A multiple agency view of venture capital investment duration: The roles of institutions, foreignness, and alliances
Authors: Sethuram Shyamala , Taussig Markus , Gaur Ajai
Published: May 2021

Research Summary

Venture capital firms (VCs) must simultaneously manage a range of relationships with investors, investees, prospective buyers, and co‐investors who frequently exert divergent influences on when investments should be exited. The greater weight of one particular relationship can lead a VC to exit an investment earlier than would maximize returns for that investment. In this study, we utilize a global sample to examine how VC firms' investment duration decisions are shaped by firm‐specific and environmental factors. Our findings suggest that VCs are less patient and exit faster when they have less experience, invest in more institutionally challenged host countries, or are foreign and invested in an emerging economy. Importantly, while co‐investing with other VCs increases patience in advanced economies, this effect disappears in emerging economies.

Managerial Summary

Agency theory explains why firms commonly capitalize on information advantages created by conditions of uncertainty to prioritize their own private interests over those shared with partners. This article introduces a framework, based on multiple agency theory, to examine the factors shaping the duration of venture capital firms' investments. Our findings, based on a sample of deals across 33 countries, suggest greater patience when host country market institutions are more advanced and venture capitalists themselves have more experience. In emerging economies only, we find that patience is increased by being local or from a foreign country with similarly challenging institutions. Importantly, while co‐investing with other venture capitalists increases patience in advanced economies, this effect disappears in emerging economies.