bluuebunny/crossref_metadata_2025 huggingface dataset:
Early postnatal appearance of enhanced noradrenaline content in the brain of vasopressin‐deficient brattleboro rat; normal adrenoceptor densities and aberrant influences of vasopressin treatment
Authors: Boer G.J. , Feenstra M.G.P. , Botterblom M.J.A. , Korse V. , Te Riele P.
Published: July 2002

The course of postnatal development of noradrenaline (NA) and its unconjugated free metabolite 3‐methoxy‐4‐hydroxyphenylglycol (MHPG), as well as the influence on early chronic vasopressin treatment, were investigated in various brain regions of the hereditary vasopressin‐deficient (homozygous di/di) Brattleboro rat. In addition, the densities of the adrenergic receptor subtypes were measured in adult brain.

Brain NA levels of di/di pups appeared enhanced already at 7 days of age when compared with data of heterozygous (+/di) controls. This was also seen in areas not known to receive a vasopressinergic input, e.g. the frontal cortex. Levels of MHPG also differed between genotypes, but changes were slight and either a decrease or increase, depending on age and region tested. Saturation analyses of α1‐, α2‐, and β‐adrenoceptor binding on crude membrane preparations of some brain regions revealed no differences in adulthood.

Chronic treatment with vasopressin between 6 and 13 days of age reduced the enhanced NA brain levels throughout the brain of the di/di Brattleboro pups. The known vasopressin‐mediated enhancement of NA turnover in adult brain was also measurable in +/di pups of this neonatal period (MHPG/NA ratios), indicating the early maturation of the interaction of vasopressinergic and NAergic systems. However, the dose‐response in the di/di Brattleboro rat was biphasic with a decrease at a low dose of vasopressin.

Since changes were found throughout the brain, it was concluded that vasopressin deficiency had altered the maturation of NA neurons of the locus coeruleus which may be due to the absence of a presumed inhibitory control of vasopressin on synthesis and storage mechanisms at the perikaryal level.
Brain large neutral amino acids and catecholamines in parenterally nourished preterm rabbits
Authors: Lopez Suzanne M. , Rassin David K.
Published: July 2002

Total parenteral nutrition (TPN) has been adapted as a standard for providing nutrition to ill term and preterm infants. The availability of tyrosine in amino acid preparations utilized for TPN is limited and may potentiate a tyrosine‐deficient state. Phenlyalanine hydroxylase activity, responsible for catalyzing tyrosine synthesis, has been suggested to be decreased in fetal and neonatal animals. Parenterally nourished premature rabbits (n=16) and suckled rabbits (n=19) were studied in order to compare growth parameters and amino acids in the plasma and brain, as well as whole brain catecholamine concentrations. Influx velocities into the brain of amino acids were also determined in these two groups.

The preterm rabbit's average birth weight (42.6±6.0) was less than that of term rabbits (56.7±8.7, P<0.005). Significantly lower concentrations of the catecholamine precursor tyrosine were found in both the plasma and brain of the parenterally nourished animals compared to the suckled animals. Tyrosine is reduced in the brain in TPN‐supported animals reflecting both low tyrosine intake and increased plasma concentrations of large neutral amino acids that compete for uptake at the blood‐brain barrier. However, no difference was observed between the two groups in their brain catecholamine concentrations.

The seven‐day parenterally nourished rabbit appears to be tyrosine‐deficient but no evident effects on brain catecholamine concentrations were seen. The effects and impact of a tyrosine‐deficient state might better be evaluated by regional evaluation of catecholaminergic areas of the brain or over a longer period of parenteral nutrition.
TYROSINE PHOSPHORYLATION INDUCED BY INTEGRIN‐MEDIATED ADHESION OF RETINAL NEURONS TO LAMININ
Authors: Malosio Maria Luisa , Curtis Ivan De
Published: July 2002

Integrin α6β1 is a laminin receptor involved in adhesion and neurite extension of retinal neurons on laminin. The present study was carried out to understand some of the intracellular mechanisms which allow integrin‐mediated neurite extension on laminin in primary neuronal cultures. Both integrin‐mediated adhesion to laminin and antibody‐induced integrin clustering resulted in the increased tyrosine phosphorylation of a 120 kDa polypeptide which was identified as the focal adhesion kinase. The kinetics of phosphorylation and dephopsphorylation of this kinase were dramatically different in neurons plated on laminin, than in neurons in which the receptors were clustered with anti‐integrin antibodies. To look at possible interactions of the focal adhesion kinase with integrins, we made use of sucrose velocity gradients, which have allowed the identification of a large complex containing the α6β1 laminin receptor. Analysis of the gradients showed that the focal adhesion kinase was not associated with the integrin receptors under these experimental conditions, while about 26% of the c‐Src kinase codistributed with the integrin receptor complex, and showed a molecular size and a distribution similar to that of a 59 kDa phosphoprotein co‐migrating with the α6β1 receptor. Our results suggest that integrin‐induced tyrosine phosphorylation is an early intracellular event during neuronal adhesion, and that the integrin‐mediated increase in tyrosine phosphorylation of the focal adhesion kinase is not sufficient per se for the induction of neurite outgrowth. Furthermore, our data indicate that Src kinase may be involved in integrin‐mediated neuronal interactions with laminin.
Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP)
Authors: Stracke Jan O. , Fosang Amanda J. , Last Karena , Mercuri Francesca A. , Pendás Alberto M. , Llano Elena , Perris Roberto , Di Cesare Paul E. , Murphy Gillian , Knäuper Vera
Published: July 2002

Matrix metalloproteinase (MMP)‐19 and MMP‐20 (enamelysin) are two recently discovered members of the MMP family. These enzymes are involved in the degradation of the various components of the extracellular matrix (ECM) during development, haemostasis and pathological conditions. Whereas MMP‐19 mRNA is found widely expressed in body tissues, including the synovium of normal and rheumatoid arthritic patients, MMP‐20 expression is restricted to the enamel organ. In this study we investigated the ability of MMP‐19 and MMP‐20 to cleave two of the macromolecules characterising the cartilage ECM, namely aggrecan and the cartilage oligomeric matrix protein (COMP). Both MMPs hydrolysed aggrecan efficiently at the well‐described MMP cleavage site between residues Asn341 and Phe342, as shown by Western blotting using neo‐epitope antibodies. Furthermore, the two enzymes cleaved COMP in a distinctive manner, generating a major proteolytic product of 60 kDa. Our results suggest that MMP‐19 may participate in the degradation of aggrecan and COMP in arthritic disease, whereas MMP‐20, due to its unique expression pattern, may primarily be involved in the turnover of these molecules during tooth development.
The chromosomal protein HMG‐D binds to the TAR and RBE RNA of HIV‐1
Authors: Arimondo Paola B. , Gelus Nathalie , Hamy François , Payet Dominique , Travers Andrew , Bailly Christian
Published: July 2002

The high mobility group protein HMG‐D is known to bind preferentially to DNA of irregular structures with little or no sequence specificity. Upon binding to DNA, this HMG‐box protein widens the minor groove of the double helix and induces a significant bending of the helix. We show here that HMG‐D can strongly bind to double‐stranded RNA. Electrophoretic mobility shift assays show that HMG‐D100 interacts with the transactivation response region (TAR) RNA from HIV‐1. Strong interaction with a high affinity Rev protein binding element (RBE) RNA was also characterized. Gel shift experiments performed with several TAR RNA constructs lacking the lateral pyrimidine bulge or with modified apical loop regions indicate that the protein does not recognize the single‐strand domains of the RNA but apparently interacts directly with the double‐stranded stem regions. No protein–RNA complexes could be detected when using single‐stranded oligoribonucleotides. HMG‐D protein could bind to the wide minor groove of the A‐form TAR RNA. The comparison of the amino acid sequence of HMG‐D with that of known RNA binding proteins suggests that the interaction of the protein with a double‐stranded RNA implicates the basic region of HMG‐D as well as its HMG‐box domain. From the in vitro data reported here, we propose a novel functional role for proteins of the HMG‐1 family. The results suggest that architectural HMG proteins can be recruited by double‐stranded RNA for the development of HIV‐1 in the host cell.
MAIL, a novel nuclear IκB protein that potentiates LPS‐induced IL‐6 production
Authors: Kitamura Hiroshi , Kanehira Katsushi , Okita Keisuke , Morimatsu Masami , Saito Masayuki
Published: July 2002

We have identified and characterized a novel member of the ankyrin‐repeat family named ‘molecule possessing ankyrin‐repeats induced by lipopolysaccharide’ (MAIL). The C‐terminal portion of MAIL shared high sequence homology with the IκB family. Intraperitoneal injection of lipopolysaccharide (LPS) into mice rapidly (<0.5 h) induced MAIL mRNA in various tissues, particularly in the spleen, lymph node, and lung. Ectopically expressed MAIL was localized in the nucleus, and remarkably potentiated the LPS‐induced mRNA expression and secretion of interleukin (IL)‐6 in Swiss 3T3 cells. These findings indicate that MAIL is one of the nuclear IκB proteins and an activator of IL‐6 production.
Regulation of the G1 to S transition by the ubiquitin pathway
Authors: DeSalle Lauren M , Pagano Michele
Published: July 2002

This year the most prestigious prize in medical sciences, the Lasker Award, has been presented to the three scientists who discovered the ubiquitin pathway: Aaron Ciechanover, Avram Hershko, and Alexander Varshavsky [Nature Med. 6 (2000) 1073–1081]. During a time when the scientific community was focused on understanding how proteins were synthesized, they intently pursued the novel idea that cells were programmed to selectively destroy proteins. Their work led to the identification of an elaborate system of protein degradation targeting a myriad of cellular substrates. A small protein called ubiquitin is at the center of this process. Although the ubiquitin pathway was first described in the early 1980s, it has only more recently advanced to the forefront of basic research as a significant regulatory network within the cell. The field continues to grow as new ubiquitination enzymes and novel functions of this system are identified. Scientists are focused on elucidating the mechanisms by which cells deploy the ubiquitin pathway to control levels of selected proteins, such as cell cycle regulatory proteins, transcription factors and signaling molecules. Accelerated or decelerated rates of degradation of particular substrates participate in the genesis of many human diseases. Thus, understanding the mechanisms that confer specificity to the ubiquitin system will allow the development of novel therapeutic approaches to target aberrations in this pathway underlying tumorigenesis and other human pathologies.
Tyrosine‐1290 of tetanus neurotoxin plays a key role in its binding to gangliosides and functional binding to neurones
Authors: Sutton J.Mark , Chow-Worn Oliver , Spaven Lindsey , Silman Nigel J , Hallis Bassam , Shone Clifford C
Published: July 2002

Tetanus toxin acts by blocking the release of glycine from inhibitory neurones within the spinal cord. An initial stage in the toxin's action is binding to acceptors on the nerve surface and polysialogangliosides are a component of these acceptor moieties. Using site‐directed mutagenesis, we identify tyrosine‐1290 of tetanus toxin as a key residue that is involved in ganglioside binding. This residue, which is located at the centre of a shallow pocket on the β‐trefoil domain of the tetanus Hc fragment, is also shown to play a key role in the functional binding of tetanus toxin to spinal cord neurones leading to the inhibition of neurotransmitter release.
Transthyretin amyloidosis: a tale of weak interactions
Authors: Saraiva Maria João Mascarenhas
Published: July 2002

Over 70 transthyretin (TTR) mutations have been associated with hereditary amyloidoses, which are all autosomal dominant disorders with adult age of onset. TTR is the main constituent of amyloid that deposits preferentially in peripheral nerve giving rise to familial amyloid polyneuropathy (FAP), or in the heart leading to familial amyloid cardiomyopathy. Since the beginning of this decade the central question of these types of amyloidoses has been why TTR is an amyloidogenic protein with clinically heterogeneous pathogenic consequences. As a result of amino acid substitutions, conformational changes occur in the molecule, leading to weaker subunit interactions of the tetrameric structure as revealed by X‐ray studies of some amyloidogenic mutants. Modified soluble tetramers exposing cryptic epitopes seem to circulate in FAP patients as evidenced by antibody probes recognizing specifically TTR amyloid fibrils, but what triggers dissociation into monomeric and oligomeric intermediates of amyloid fibrils is largely unknown. Avoiding tetramer dissociation and disrupting amyloid fibrils are possible avenues of therapeutic intervention based on current molecular knowledge of TTR amyloidogenesis and fibril structure.
Non‐invasive visualization of sperm mitochondria behavior in transgenic mice with introduced green fluorescent protein (GFP)
Authors: Shitara Hiroshi , Kaneda Hideki , Sato Akitsugu , Iwasaki Kuniko , Hayashi Jun-Ichi , Taya Choji , Yonekawa Hiromichi
Published: July 2002

Using high sensitive polymerase chain reaction (PCR), we previously demonstrated that selective elimination of sperm mitochondrial DNA occurred during early embryogenesis in mouse. To analyze the process morphologically in more detail, a non‐invasive, real‐time observation of sperm mitochondria was used. Transgenic mice that express green fluorescent protein (GFP) exclusively in mitochondria (mtGFP‐tg mice) were generated. The fluorescence in mtGFP‐tg mice was strong and stable enough to carry out repeated observations under confocal laser scanning microscopy. In these mtGFP‐tg mice it was revealed that the sperm mitochondria were selectively eliminated from egg cytoplasm during the two‐cell stage of early embryogenesis. Therefore, mtGFP‐tg mice should contribute to studies on sequential or repeated analysis of mitochondria.
Structural classification of CDR‐H3 in antibodies
Authors: Shirai Hiroki , Kidera Akinori , Nakamura Haruki
Published: July 2002

Large varieties in the lengths and the amino acid sequences of the third complementarity determining region of the antibody heavy chain (CDR‐H3) have made it difficult to establish a relationship between the sequences and the tertiary structures, in contrast to the other CDRs, which are classified by their canonical structures. A total of 55 CDR‐H3 segments from well determined crystal structures were analyzed, and we have derived several remarkable rules, which could partly govern the CDR‐H3 conformation dependence on the sequence. Since the rules are physically reasonable, they are expected to be applicable to structural modeling and design of antibodies.
Biomarker evidence of DNA oxidation in lung cancer patients: association of urinary 8‐hydroxy‐2′‐deoxyguanosine excretion with radiotherapy, chemotherapy, and response to treatment
Authors: Erhola Marina , Toyokuni Shinya , Okada Kunihiko , Tanaka Tomoyuki , Hiai Hiroshi , Ochi Hirotomo , Uchida Koji , Osawa Toshihiko , Nieminen Markku M , Alho Hannu , Kellokumpu-Lehtinen Pirkko
Published: July 2002

Ratios of urinary 8‐hydroxy‐2′‐deoxyguanosine to urinary creatinine (8‐OHdG/creatinine) have been considered as a good biological indicator of DNA oxidation. Urinary 8‐OHdG/creatinine levels of lung cancer patients were evaluated by enzyme‐linked immunosorbent assay using a monoclonal antibody N45.1 during radiotherapy and chemotherapy. An increase in urinary 8‐OHdG/creatinine was found in non‐small‐cell carcinoma (non‐SCC) patients during the course of radiotherapy. SCC patients showed higher levels of urinary 8‐OHdG/creatinine than the controls. Furthermore, SCC patients with complete or partial response to the chemotherapy showed a significant decrease in urinary 8‐OHdG/creatinine while patients with no change or progressive disease showed an increase.
The effect of melittin on proliferation and death of thymocytes
Authors: Shaposhnikova V.V , Egorova M.V , Kudryavtsev A.A , Levitman M.Kh , Korystov Yu.N
Published: July 2002

The effect of melittin, an activator of phospholipase A2, on proliferation and death of rat thymocytes in a broad concentration range was studied. Cell proliferation was estimated by the accumulation of colchicin metaphases, necrotic death was determined from lysis and staining of cells with trypan blue, and apoptosis was assessed from the type of DNA fragmentation, the amount of fragmented DNA, and the percentage of cells with subdiploid DNA. It was shown that low melittin concentrations (below 5 μg/ml) stimulate thymocyte proliferation. At high melittin concentrations, thymocytes die by the primary necrosis type. Throughout the concentration range studied, melittin does not produce apoptosis in thymocytes. Conversely, high melittin concentrations even inhibit thymocyte apoptosis in the control and after irradiation. An inhibitor of RNA synthesis actinomycin D does not affect thymocyte death in the presence of melittin. It is concluded that the activation of phospholipase A2 can induce necrosis but not apoptosis and thus is not a necessary step in the signaling cascade that initiates apoptosis in thymocytes.
Identification of a novel nuclear speckle‐type protein, SPOP
Authors: Nagai Yasuo , Kojima Tatsuya , Muro Yoshinao , Hachiya Takahisa , Nishizawa Yuji , Wakabayashi Takashi , Hagiwara Masatoshi
Published: July 2002

A novel antigen recognized by serum from a scleroderma patient was identified by expression cloning from the HeLa cell cDNA library. The cloned cDNA encoded a 374‐amino acid protein with a relative molecular mass of 47 000 and a predicted amino acid sequence 62.7% identical to the hypothetical protein of Caenorhabditis elegans, T16H12.5. The deduced amino acid sequence had a typical POZ domain and an unidentified region conserved during evolution. No zinc finger or RNA recognition motifs were found in this clone. The 2 kbp mRNA encoding the novel clone SPOP (speckle‐type POZ protein) was found to be expressed in all human tissues examined. HA‐tagged SPOP, transfected and overexpressed in COS7 cells, exhibited a discrete speckled pattern in the nuclei and was co‐localized with the splicing factor, snRNP B′/B. Deletion analysis revealed that both the POZ domain and the evolutionarily conserved region at the amino‐terminus are required for the nuclear speckled accumulation of SPOP.
Ribozyme processed tRNA transcripts with unfriendly internal promoter for T7 RNA polymerase: production and activity
Authors: Fechter Pierre , Rudinger Joëlle , Giegé Richard , Théobald-Dietrich Anne
Published: July 2002

A limitation for a universal use of T7 RNA polymerase for in vitro tRNA transcription lies in the nature of the often unfavorable 5′‐terminal sequence of the gene to be transcribed. To overcome this drawback, a hammerhead ribozyme sequence was introduced between a strong T7 RNA polymerase promoter and the tDNA sequence. Transcription of this construct gives rise to a ‘transzyme’ molecule, the autocatalytic activity of which liberates a 5′‐OH tRNA transcript starting with the proper nucleotide. The method was optimized for transcription of yeast tRNATyr, starting with 5′‐C1, and operates as well for yeast tRNAAsp with 5′‐U1. Although the tRNAs produced by the transzyme method are not phosphorylated, they are fully active in aminoacylation with k
cat and K
m parameters quasi identical to those of their phosphorylated counterparts.
A mammalian sperm cytosolic phospholipase C activity generates inositol trisphosphate and causes Ca2+ release in sea urchin egg homogenates
Authors: Jones Keith T , Cruttwell Caroline , Parrington John , Swann Karl
Published: July 2002

Injection of sperm extracts triggers Ca2+ oscillations in mammalian eggs similar to those seen at fertilisation. Here, we show that addition of sperm extracts to sea urchin egg homogenates causes Ca2+ release and inositol 1,4,5‐trisphosphate (InsP3) production. Furthermore depleting homogenates of phosphatidylinositol lipids using a phosphatidylinositol‐specific phospholipase C blocked the sperm extract from causing InsP3 production and a Ca2+ rise. A response could be recovered by the addition of phosphatidylinositol 4,5‐bisphosphate to either sperm extracts or egg homogenates. These data indicate that sperm extracts contain an InsP3‐generating phospholipase C which may play a role in Ca2+ release at fertilisation.
Caspase‐3 inhibits growth in Saccharomyces cerevisiae without causing cell death1
Authors: Wright Michael E. , Han David K. , Carter Lauren , Fields Stanley , Schwartz Stephen M. , Hockenbery David M.
Published: July 2002

Caspase‐3, a member of the caspase family of cell death proteases, cleaves cytoplasmic and nuclear substrates and promotes apoptotic cell death in mammalian cells. Although yeast homologs of apoptotic genes have not been identified, some components of apoptotic pathways retain function in yeast. Here we show that the expression of caspase‐3 delays cell growth in Saccharomyces cerevesiae without causing cell death. Mutation of the caspase‐3 QACRG active site abolished effects on yeast growth. Co‐expression of caspase inhibitors alleviated growth inhibition in yeast as did the tripeptide caspase inhibitor ZVAD‐fmk. These results suggest that substrates for caspase‐3 are present in S. cerevesiae and may participate in the normal cell growth and division processes.
Effect of mutations in the β1‐thyroid hormone receptor on the inhibition of T3 binding by desethylamiodarone
Authors: van Beeren H.C. , Bakker O. , Chatterjee V.K.K. , Wiersinga W.M.
Published: July 2002

Desethylamiodarone (DEA) acts as a competitive inhibitor of triiodothyronine (T3) binding to the α1‐thyroid hormone receptor (TRα1) but as a non‐competitive inhibitor with respect to TRβ1. To gain insight into the position of the binding site of desethylamiodarone on TRβ1 we investigated the naturally occurring mutants Y321C, R429Q, P453A, P453T and the artificial mutants L421R and E457A in the ligand binding domain of human TRβ1. The IC50 values (in μM) of DEA for P453A (50±11) and P453T (55±16) mutant TRβ1 are not different from that for the wild type TRβ1 (56±15), but the IC50 values of R429Q (32±7; P<0.001) and E457A (17±3; P<0.001) are significantly lower than of the wild type. Scatchard plots and Langmuir analyses indicate a non‐competitive nature of the inhibition by DEA of T3 binding to all four mutant TRβ1s tested. Mutants P453A and P453T do not influence overall electrostatic potential, and also do not influence the affinity for DEA compared to wild type. Mutant E457A causes a change from a negatively charged amino acid to a hydrophobic amino acid, enhancing the affinity for DEA. Mutant R429Q, located in helix 11, causes an electrostatic potential change from positive to uncharged, also resulting in greater affinity for DEA. We therefore postulate that amino acids R429 and E457 are at or close to the binding site for DEA, and that DEA does not bind in the T3 binding pocket itself, in line with the non‐competitive nature of the inhibition of T3 binding to TRβ1 by DEA.
Overexpression of poly(A)‐binding protein down‐regulates the translation or the abundance of its own mRNA
Authors: Hornstein Eran , Harel Hila , Levy Galit , Meyuhas Oded
Published: July 2002

Poly(A)‐binding protein (PABP) mRNA is subject to autoregulation through a 61 nucleotides long A‐rich sequence in its 5′ untranslated region (UTR). Here, we show that this mode of regulation is exerted in a cell type‐specific manner. Thus, overexpression of PABP in mouse NIH 3T3 fibroblasts represses the translation of the respective endogenous mRNA or that of a chimeric mRNA containing just the 5′ UTR of PABP mRNA. In contrast, ectopic expression of PABP in human embryonic kidney 293 cells down‐regulates the abundance of the endogenous PABP mRNA, rather than affecting its translational efficiency. Transfection experiments with chimeric constructs suggest that the lack of translational autoregulation of endogenous PABP mRNA in these cells appears to reflect the presence of an overriding regulatory element outside the A‐rich region.
Wide distribution of short interspersed elements among eukaryotic genomes
Authors: Borodulina Olga R. , Kramerov Dmitri A.
Published: July 2002

Most short interspersed elements (SINEs) in eukaryotic genomes originate from tRNA and have internal promoters for RNA polymerase III. The promoter contains two boxes (A and B) spaced by ∼33 bp. We used oligonucleotide primers specific to these boxes to detect SINEs in the genomic DNA by polymerase chain reaction (PCR). Appropriate DNA fragments were revealed by PCR in 30 out of 35 eukaryotic species suggesting the wide distribution of SINEs. The PCR products were used for hybridization screening of genomic libraries which resulted in identification of four novel SINE families. The application of this approach is illustrated by discovery of a SINE family in the genome of the bat Myotis daubentoni. Members of this SINE family termed VES have an additional B‐like box, a putative polyadenylation signal and RNA polymerase III terminator.
Biological activities of granzyme K are conserved in the mouse and account for residual Z‐Lys‐SBzl activity in granzyme A‐deficient mice
Authors: Wilharm Elke , Tschopp Jürg , Jenne Dieter E.
Published: July 2002

Tryptase‐like activities of T and NK cells contribute to the induction of target cell apoptosis, but only granzyme A (GzmA) has been shown to exhibit Z‐Lys‐SBzl esterase activity in murine T cells. GzmA‐deficient mice exhibit residual Z‐Lys‐SBzl hydrolyzing activity and almost normal levels of lymphocyte‐mediated cytotoxicity. Here we report the cloning and biochemical characterization of recombinant mouse granzyme K (GzmK). The purified murine protein shows Z‐Lys‐SBzl hydrolyzing activity and is inhibited by bikunin, the light chain of inter‐α‐trypsin inhibitor, like the human homolog. We conclude that GzmK expressed by GzmA‐deficient T cells accounts for the remaining Z‐Lys‐SBzl activity. Functional similarities between GzmA and GzmK may explain the subtle immunological deficits observed in GzmA‐deficient mice.
Novel variation of lipid A structures in strains of different Yersinia species1
Authors: Aussel Laurent , Thérisod Hélène , Karibian Doris , Perry Malcolm B , Bruneteau Maud , Caroff Martine
Published: July 2002

The Yersinia genus includes human and animal pathogens (plague, enterocolitis). The fine structures of the endotoxin lipids A of seven strains of Yersinia enterocolitica, Yersinia ruckeri and Yersinia pestis were determined and compared using mass spectrometry. These lipids differed in secondary acylation at C‐2′: this was dodecanoic acid (C12) for two strains of Y. enterocolitica and Y. ruckeri, tetradecanoic acid (C14) in two other Y. enterocolitica and hexadecenoic acid (C16:1) in Y. pestis. The enterocolitica lipids having a mass identical to that of Escherichia coli were found to be structurally different. The results supported the idea of a relation between membrane fluidity and environmental adaptability in Yersinia.
Osteoprotegerin ameliorates sciatic nerve crush induced bone loss
Authors: Bateman Ted A. , Dunstan Colin R. , Lacey David L. , Ferguson Virginia L. , Ayers Reed A. , Simske Steven J.
Published: July 2002

This study examines the ability of osteoprotegerin (OPG) to prevent the local bone resorption caused by sciatic nerve damage. Sixty‐five 18‐week‐old male mice were assigned to one of six groups (n = 10–11/group). A baseline control group was sacrificed on day zero of the 10‐day study. The remaining groups were placebo sham operated, placebo nerve crush (Plac NC) operated, 0.1 mg/kg/day OPG + nerve crush (LOW), 0.3 mg/kg/day OPG + nerve crush (MED), and 1.0 mg/kg/day OPG + nerve crush (HI). Nerve crush or sham operations were performed on the right leg. The left leg served as a contralateral control to the nerve crushed (ipsilateral) leg. The difference in mass between the right and left femur and tibia was examined. Additionally, quantitative histomorphometry was performed on the right and left femur and tibia diaphyses. Nerve crush resulted in a significant loss of bone mass in the ipsilateral side compared to the contralateral side. Bone mass for the ipsilateral bones of the Plac NC group were significantly reduced by 3.8% in the femur and 3.5% in the tibia compared to the contralateral limb. The percent diminution was reduced for OPG treated mice compared to the Plac NC group for both the femur and tibia. In the femur, the percent reduction of ipsilateral bone mass was reduced to 1.0% (LOW), 1.3% (MED) and 1.6% (HI) compared to the contralateral limb. In the tibia, loss of bone mass in the ipsilateral limb was reduced to 1.4% (LOW), 1.4% (MED), and 2.4% (HI) compared to the contralateral. OPG also decreased the amount of tibial endocortical resorption compared to the Plac NC group. In summary, OPG mitigated bone loss caused by damage to the sciatic nerve. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Smooth muscle actin expression by human articular chondrocytes and their contraction of a collagen—glycosaminoglycan matrix in vitro
Authors: Kinner B. , Spector M.
Published: July 2002

Recent studies have demonstrated that human articular chondrocytes can express the gene for a contractile muscle actin, α‐smooth muscle actin (SMA), in situ. One objective of this work was to evaluate the SMA‐content of isolated human articular chondrocytes using Western blot analysis and to correlate the amount of SMA in the cells with passage number and the number of days in culture. A second objective was to determine if articular cartilage‐derived cells expressing the gene for SMA in vitro also continue to express type II collagen. A final aim of the current study was to determine if SMA‐containing cartilage‐derived cells were capable of contracting a collagen–glycosaminoglycan analog of extracellular matrix in vitro. Articular chondrocytes were isolated from 13 patients undergoing total joint arthroplasty. Cells were serially passaged through passage 7. Samples were allocated for Western blot analysis of SMA. Cells in monolayer culture were also stained immunohistochemically for SMA and type II collagen. Cells from passage 3 and 7 were seeded into a porous type I collagen–glycosaminoglycan matrix and the diameter of the scaffolds measured every other day for 21 days. Immunohistochemistry of the articular cartilage samples revealed SMA in the articular chondrocytes in situ with a greater percentage of cells staining positive in the superficial half (60 ± 1.2%; mean ± SEM) of the cartilage than in the basal half (28 ± 1.3%). There was an increasing amount of SMA in the cells in monolayer culture with passage number and a meaningful correlation of the SMA content with the days in culture (linear regression analysis; R2 = 0.72). Double staining for SMA and type II collagen showed that type II collagen‐expressing cells in monolayer could also express SMA. SMA‐containing cells were found to contract the collagen–glycosaminoglycan matrix, with the cells containing more SMA (passage 7 cells) displaying more matrix contraction than those with a lesser amount of SMA (passage 3 cells). The results indicate that control of the expression of SMA may be important when employing articular chondrocytes, expanded in monolayer culture, for implantation alone or in a cell‐seeded matrix for cartilage repair procedures. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Neurochemical coding in the myenteric plexus of the upper gastrointestinal tract of hibernating hamsters
Authors: Shochina M. , Belai A. , Toole L. , Knight G. , Burnstock G.
Published: July 2002

As part of our investigation of the plasticity of autonomic nerves in physiological and pathological conditions, we have examined the effect of hibernation on the neurochemical content of myenteric nerves and nerve cell bodies of the upper gastrointestinal tract of the non‐seasonal hibernator, the golden hamster. Age matched hamsters kept at room temperature and those kept at 5°C but failed to hibernate, were used as controls. Possible changes in nerve fibers and nerve cell bodies containing the general neuronal marker, protein gene product 9.5, the peptides, vasoactive intestinal polypeptide, substance P (SP) and calcitonin gene‐related peptide (CGRP), the catecholamine synthesizing enzyme tyrosine hydroxylase and the enzyme responsible for synthesizing nitric oxide, nitric oxide synthase, were examined in the oesophagus, proventriculus and proximal and distal stomach of the golden hamsters using immunohistochemical techniques. The results of the present study revealed a significant increase in the number of nerve cell bodies and density of nerve fibers containing SP‐immunoreactivity and increased number of CGRP‐immunoreactive cell bodies but not the other markers examined in the proximal stomach and proventriculus. In contrast, there was no change in the distribution of any of the neuroactive substances examined in the myenteric plexus of the oesophagus and distal stomach. It is suggested that the change in the environment of the hibernating hamsters perturbs the normal digestive physiology in the proximal stomach and proventriculus that is reflected by the selective changes in SP‐ and CGRP‐containing enteric nerves; these changes may be part of protective reflex mechanisms to the environmental changes resulting from hibernation, where upgrading of nerve cell bodies expessing CGRP and SP has occurred.
Assessment and treatment of dysthymia. The development of the Cornell dysthymia rating scale
Authors: Cohen J
Published: July 2002

The understanding and classification of persistently depressed mood has undergone many changes since the term ‘dysthymia’ was first used nearly 150 years ago. Originally it was applied to both melancholia and mania; later it was applied to depressive personality. The Diagnostic and Statistical Manual (DSM)-III in 1980 and in subsequent updates classified dysthymia as a mood disorder, characterized by a frequently insidious onset and a course that is chronic and unremitting. The assessment of clinical response in the pharmacologic treatment of dysthymia has been more difficult than that for major depression. The Hamilton Rating Scale for Depression, among others, is oriented towards episodic rather than chronic states of depression. A new rating scale, the Cornell Dysthymia Rating Scale, has been developed to better assess milder symptomatology in chronically depressed patients. Early studies suggest its utility, but further validation of the scale is needed in patients with dysthymia and without major depression.
Plasmonic Supercrystals with a Layered Structure Studied by a Combined TEM‐SAXS‐XCCA Approach
Authors: Schulz Florian , Westermeier Fabian , Dallari Francesco , Markmann Verena , Lange Holger , Grübel Gerhard , Lehmkühler Felix
Published: August 2020

Supercrystals composed of plasmonic nanoparticles constitute a promising material platform for tailored light‐matter interactions. The optimization of their optical properties requires precise syntheses and a detailed structural characterization that addresses not only the basic geometrical parameters but also the degree of order. Herein, plasmonic supercrystals with a well‐defined layered structure are studied by a combined transmission electron microscopy, small‐angle X‐ray scattering and X‐ray cross‐correlation analysis (TEM‐SAXS‐XCCA) approach. It is demonstrated that scanning small‐angle x‐ray scattering (SAXS) data can unambiguously be assigned to the number of crystalline layers by comparison with complementary transmission electron microscopy (TEM) experiments on the same regions of interest. A small but significant increase of the lattice constant with increasing number of layers and a high degree of orientational order irrespective of the number of layers is found. This points to specifics of the supercrystal formation mechanism that could be utilized to improve the control of self‐assembly for supercrystal geometries with subnanometer precision.
Cloaking Dynamics on Lubricant‐Infused Surfaces
Authors: Günay Ahmet Alperen , Sett Soumyadip , Ge Qiaoyu , Zhang TieJun , Miljkovic Nenad
Published: August 2020

Lubricant‐infused surfaces (SLIPSs/LISs) enable omniphobicity by reducing droplet pinning through creation of an atomically smooth liquid–liquid interface. Although SLIPSs/LISs provide efficient omniphobicity, the need for lubricant adds additional barriers to heat and mass transport and affects three‐phase contact line dynamics. Here, evaporation dynamics of microscale water droplets on SLIPSs/LISs are investigated using steady and transient methods. Although steady results demonstrate that evaporation on SLIPSs/LISs is identical to solid functional surfaces having equivalent apparent contact angle, transient measurements show significant increases in evaporation timescale. To understand the inconsistency, high‐speed optical imaging is used to study the evaporating droplet free interface. Focal plane shift imaging enables the study of cloaking dynamics by tracking satellite microdroplet motion on the cloaked oil layer to characterize critical timescales. By decoupling the effect of substrate material and working fluid via experiments on both microstructured copper oxide and nanostructured boehmite with water and ethanol, it is demonstrated that lubricant cloaking cannot be predicted purely by thermodynamic considerations. Rather, coalescence dynamics, droplet formation, and surface interactions play important roles on establishing cloaking. The outcomes of this work shed light onto the physics of lubricant cloaking, and provide a powerful experimental platform to characterize droplet interfacial phenomena.
Construction of Porous ZnS@Co3S4@NiO Nanosheets Hybrid Materials for High‐Performance Pseudocapacitor Electrode by Morphology Reshaping
Authors: Yi Tingfeng , Li Ying , Qi Siyu , Peng Panpan , Zhu Yanrong , Xie Ying
Published: August 2020

Designing electrode materials with high reversible capacitance is the key to developing high‐performance pseudocapacitors. In this work, a novel ternary hybrid material, porous ZnS@Co3S4@NiO nanosheets are successfully constructed through a morphology reshaping enabled by a hydrothermal method followed by calcination. From a macroscopic view, the introduction of NiO changes the nanorod morphology of ZnS@Co3S4, and forms a porous nanosheet structure. The porous architecture with an increased specific surface area can promote the transport of ions and electrons, accelerate the diffusion of the electrolyte, and offer more active sites for electrochemical reactions. These advantages enhance the electrochemical properties of ZnS@Co3S4@NiO nanosheets when used as electrode materials for supercapacitors. ZnS@Co3S4@NiO nanosheets deliver an initial capacitance of 1418.7 F g−1, and it also reaches 1550.9 F g−1 with a capacitance retention rate of 109.3% at 5 A g−1, after 5000 cycles. However, ZnS@Co3S4 nanorods only deliver an initial capacitance of 708.7 F g−1, and maintain 716.4 F g−1 with a capacitance retention rate of 101.1% after 5000 cycles. These results show that the ZnS@Co3S4@NiO nanosheets are a promising electrode material for high‐performance pseudocapacitor electrode, and morphology reshaping is an effective strategy to design high‐performance pseudocapacitive materials.
Rational Modulation of Carbon Fibers for High‐Performance Zinc–Iodine Batteries
Authors: He Yulong , Liu Miaomiao , Zhang Jintao
Published: August 2020

Zinc–iodine batteries (ZIBs) are regarded as promising energy storage devices due to their high performance and low cost. Nevertheless, their wide application is mainly limited by the preparation of iodine‐based cathode and dendrite‐free zinc anode. Flexible carbon fibers have attracted tremendous attention, due to their iodine encapsulation properties. This characteristic is a result of their porous structure, large surface area, and excellent intrinsic properties. With the development of carbon fibers for loading iodine, the surface properties can be rationally modulated via heteroatom doping and combination with various polymers can enhance battery performance. In this review, recent research advances on the functionalization of carbon fibers for ZIBs are summarized, with special focus on the pore size of carbon fibers, the species, and content of doping elements, and the selection of targeted polymers toward the loading of iodine. Finally, the prospects and future challenges of ZIBs based on carbon fibers are presented. The review aims to provide the basic guides for designing advanced iodine‐based electrode materials on the basis of carbon fibers with both compositional advantages and microporous structure to achieve high‐performance ZIBs.
Multifunctional Geometric Metasurfaces Based on Tri‐Spectral Meta‐Atoms with Completely Independent Phase Modulations at Three Wavelengths
Authors: Xie Rensheng , Zhai Guohua , Gao Jianjun , Zhang Dajun , Wang Xiong , An Sensong , Zheng Bowen , Zhang Hualiang , Ding Jun
Published: August 2020

Metasurface has drawn much attention due to its unprecedented wave‐front manipulation abilities with an ultrathin flat profile. However, the metasurface as a diffractive device usually suffers from chromatic aberrations, which greatly hinders the design freedom at different wavelengths. In this work, it is demonstrated that this limitation can be overcome by a multifunctional metasurface with completely independent phase modulations at three arbitrarily wavelengths. Specifically, a novel single‐layer tri‐spectral meta‐atom composed of three alternatively arranged slot and metallic resonators is proposed to operate at three distinct wavelengths, where 2π geometric phase modulations under the circularly polarized incidence can be achieved independently by rotating the corresponding resonators. As proof of concept demonstrations, a tri‐wavelength vortex beam generator and a meta‐hologram are designed to verify the proposed method. First, a vortex beam generator with arbitrary topological charge numbers at three wavelengths is designed and verified through theoretical calculation and full‐wave simulation. Moreover, a meta‐hologram generated by the computer‐generated holography is designed to display three frequency selective holographic images on the same image plane. The tri‐wavelength meta‐hologram is validated through theoretical calculation, full‐wave simulation, and experiment. The experimental results agree very well with the numerical ones, demonstrating the attractive capabilities of multifunctionalities at three wavelengths.
Screening Cancer Immunotherapy: When Engineering Approaches Meet Artificial Intelligence
Authors: Zhou Xingwu , Qu Moyuan , Tebon Peyton , Jiang Xing , Wang Canran , Xue Yumeng , Zhu Jixiang , Zhang Shiming , Oklu Rahmi , Sengupta Shiladitya , Sun Wujin , Khademhosseini Ali
Published: August 2020

Immunotherapy is a class of promising anticancer treatments that has recently gained attention due to surging numbers of FDA approvals and extensive preclinical studies demonstrating efficacy. Nevertheless, further clinical implementation has been limited by high variability in patient response to different immunotherapeutic agents. These treatments currently do not have reliable predictors of efficacy and may lead to side effects. The future development of additional immunotherapy options and the prediction of patient‐specific response to treatment require advanced screening platforms associated with accurate and rapid data interpretation. Advanced engineering approaches ranging from sequencing and gene editing, to tumor organoids engineering, bioprinted tissues, and organs‐on‐a‐chip systems facilitate the screening of cancer immunotherapies by recreating the intrinsic and extrinsic features of a tumor and its microenvironment. High‐throughput platform development and progress in artificial intelligence can also improve the efficiency and accuracy of screening methods. Here, these engineering approaches in screening cancer immunotherapies are highlighted, and a discussion of the future perspectives and challenges associated with these emerging fields to further advance the clinical use of state‐of‐the‐art cancer immunotherapies are provided.
Giant Field‐Induced Strain with Low Hysteresis and Boosted Energy Storage Performance under Low Electric Field in (Bi0.5Na0.5)TiO3‐Based Grain Orientation‐Controlled Ceramics
Authors: Bai Wangfeng , Zhao Xinyu , Ding Yuqin , Wang Leijie , Zheng Peng , Hao Jigong , Zhai Jiwei
Published: August 2020

Lead‐free dielectrics with both excellent strain behavior and superior energy‐storage feature are crucial toward providing desired performance for smart electrical devices, especially under harsh environmental conditions. Herein, it is demonstrated that giant strain response of ≈0.51% with small hysteresis of ≈29% and large recoverable energy density (≈1.6 J cm−3) under low electric field (120 kV cm−1), together with excellent stabilities against temperature, frequency, and cycling, can be simultaneously achieved in oriented (with 79.4% 〈00l〉 texture) (Bi0.5Na0.5)TiO3–BaTiO3–NaNbO3 (BNT–BT–NN) ceramics through integrating crystallographic texturing and domain engineering. Besides, a fast discharge rate of <0.1 µs along with good thermal endurance in a wide temperature range can also be acquired. It is uncovered by piezoelectric force microscopy measurements that the formation of oriented microstructure greatly promotes the domain switching and mobility, producing the considerably easy ergodic relaxor to ferroelectric phase transition with concurrently improved strain and energy storage properties in grain orientation controlled BNT–BT–NN ceramics. This study offers a feasible and propagable guidance, i.e., crystallographic texturing and domain engineering, to develop new lead‐free dielectrics for both actuators and capacitors.
Valence Engineering via In Situ Carbon Reduction on Octahedron Sites Mn3O4 for Ultra‐Long Cycle Life Aqueous Zn‐Ion Battery
Authors: Tan Qiuyang , Li Xueting , Zhang Bao , Chen Xu , Tian Yawen , Wan Houzhao , Zhang Lishang , Miao Ling , Wang Cong , Gan Yi , Jiang Jianjun , Wang Yi , Wang Hao
Published: August 2020

In recent years, rechargeable aqueous zinc‐ion batteries (ZIBs) have received much attention. However, the disproportionation effect of Mn2+ seriously affects the capacity retention of ZIBs during cycling. Here, the capacity retention of the Mn3O4 cathode is improved by effective valence engineering. The valence engineering of Mn3O4 is caused by bulk oxygen defects, which are in situ derived from the Mn‐metal organic framework during carbonization. Bulk oxygen defects can change the (MnO6) octahedral structure, which improves structural stability and inhibits the dissolution of Mn2+. The ZIB assembled from bulk oxygen defects Mn3O4@C nanorod arrays (Od‐Mn3O4@C NA/CC) exhibits an ultra‐long cycle life, reaching 84.1 mAh g−1 after 12 000 cycles at 5 A g−1 (up to 95.7% of the initial capacity). Furthermore, the battery has a high specific capacity of 396.2 mAh g−1 at 0.2 A g−1. Ex situ characterization results show that initial Mn3O4 is converted to ramsdellite MnO2 for insertion and extraction of H+ and Zn2+. First‐principles calculations show that the charge density of Mn3+ increases greatly, which improves the conductivity. In addition, the flexible quasi‐solid‐state ZIB is successfully assembled using Od‐Mn3O4 @ C NA/CC. Valence engineering induced by bulk oxygen defects can help develop advanced cathodes for aqueous ZIB.