bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible His to Asp phosphorelay signaling in an Arabidopsis two‐component system
Authors: Urao Takeshi , Miyata Shinichi , Yamaguchi-Shinozaki Kazuko , Shinozaki Kazuo
Published: July 2002

We have so far cloned a cDNA encoding a hybrid‐type histidine kinase (ATHK1), three cDNAs encoding phosphorelay intermediates (ATHP1–3), and four cDNAs encoding response regulators (ATRR1–4) from Arabidopsis thaliana. To determine which molecules constitute a His to Asp phosphorelay pathway, we examined protein–protein interactions between them using a pairwise yeast two‐hybrid analysis, as an initial step. We detected a specific interaction between ATHK1 and ATHP1. We further examined protein–protein interactions between ATHP1–3 and other histidine kinases. We detected interactions between ETR1 and all ATHPs, and between CKI1 and ATHP1 or ATHP2. Interestingly, ERS1 could not interact with any ATHPs. We also examined protein–protein interactions between ATHP1‐3 and ATRR1‐4. The results indicated that ATHP2 could interact with ATRR4, and that ATHP3 could interact with ATRR1 or ATRR4. However, ATHP1 could not interact with any ATRRs. On the basis of these results, we discuss the possible phosphorelay networks in an Arabidopsis two‐component system.
Thermal stability of the hemagglutinin‐neuraminidase from Sendai virus evidences two folding domains
Authors: Manfrinato Maria Cristina , Bellini Tiziana , Masserini Massimo , Tomasi Maurizio , Dallocchio Franco
Published: July 2002

The domain structure of hemagglutinin‐neuraminidase from Sendai virus (cHN) was investigated by studying the thermal stability in the 20–100°C range. Differential scanning calorimetry evidences two conformational transitions. The first transition is apparently a reversible two‐state process, with T
m 48.3°C, and is shifted to 50.1°C in the presence of the substrate analogue 2,3‐dehydro‐2‐deoxy‐N‐acetyl neuraminic acid, meaning that the substrate binding domain is involved in the transition. The second transition, with apparent T
m 53.2°C, is accompanied by irreversible loss of enzymatic activity of the protein, and the presence of the substrate analogue does not affect the T
m. The data indicate that cHN is composed of two independent folding domains, and that only one domain is involved in the binding of the substrate. Our results suggest that the paramyxovirus neuraminidases have the folding properties of a two‐domain protein.
Real time NMR monitoring of local unfolding of HIV‐1 protease tethered dimer driven by autolysis
Authors: Panchal Sanjay C. , Bhavesh Neel S. , Hosur R.V.
Published: July 2002

Structural studies in proteases have been hampered because of their inherent autolytic function. However, since autolysis is known to be mediated via protein unfolding, careful monitoring of the autolytic reaction has the potential to throw light on the folding–unfolding equilibria. In this paper we describe real time nuclear magnetic resonance investigations on the tethered dimer construct of the human immunodeficiency virus‐1 protease, which have yielded insights into the relative stabilities of several residues in the protein. The residues lying along the active site (bottom, side and top of the active site) and those in helix have lower unfolding free energy values than the other parts of the protein. The residue level stability differences suggest that the protein is well suited to adjust itself in almost all the regions of its structure, as and when perturbations occur, either due to ligand binding or due to mutations.
Pesticides directly accelerate the rate of α‐synuclein fibril formation: a possible factor in Parkinson's disease
Authors: Uversky Vladimir N , Li Jie , Fink Anthony L
Published: July 2002

Parkinson's disease involves intracellular deposits of α‐synuclein in the form of Lewy bodies and Lewy neurites. The etiology of the disease is unknown, however, several epidemiological studies have implicated environmental factors, especially pesticides. Here we show that several pesticides, including rotenone, dieldrin and paraquat, induce a conformational change in α‐synuclein and significantly accelerate the rate of formation of α‐synuclein fibrils in vitro. We propose that the relatively hydrophobic pesticides preferentially bind to a partially folded intermediate conformation of α‐synuclein, accounting for the observed conformational changes, and leading to association and subsequent fibrillation. These observations suggest one possible underlying molecular basis for Parkinson's disease.
Transforming growth factor‐β negatively modulates T‐cell responses in sepsis
Authors: Ahmad Sarfraz , Choudhry Mashkoor A , Shankar Ravi , Sayeed Mohammed M
Published: July 2002

Sepsis is associated with depressed T‐cell functions and increased circulating levels of immunosuppressive agents. TGF‐β is a potential anti‐inflammatory cytokine that can modify T‐cell growth and differentiation. The up‐regulation of TGF‐β and the mechanism of its action on the T‐cells during septic injury have not been resolved. We hypothesized that in sepsis TGF‐β produced by macrophages acts on T‐cells in a paracrine manner to suppress interleukin (IL)‐2 production and proliferation. In this study, we examined the circulating TGF‐β levels in a rat model of Gram‐negative bacterial sepsis, and compared the abilities of adherent and non‐adherent splenocytes to produce TGF‐β. Additionally, we investigated the causal relationships of hrTGF‐β to concanavalin A (ConA)‐induced T‐cell responses and the intracellular mechanism of the generation of these responses in normal splenic rat T‐cells. Sepsis was induced in rats by intra‐abdominally implanting fecal pellets containing Escherichia coli (150 CFU) and Bacteroides fragilis (10 000 CFU). Adherent and non‐adherent splenocytes were isolated by differential adherence using Ficoll gradient centrifugation. T‐cells were purified by use of Nylon wool columns. We observed a 3–6‐fold increase in the circulating levels of TGF‐β in sepsis. Western blots and ELISA determinations revealed a 2.5–3‐fold increase in cell‐associated TGF‐β protein levels in adherent splenic cells. Northern analyses also showed a marked increase in TGF‐β mRNA expression in adherent cells during sepsis. On the other hand, a significant change was not observed in the TGF‐β protein and mRNA expression in non‐adherent splenocytes. Pretreatment of control rat T‐cells with hrTGF‐β decreased both ConA‐induced proliferation (by 35–40%) and IL‐2 mRNA expression (by >50%). Further, whereas incubation of control rat T‐cells with either ConA or TGF‐β for 24 h resulted in a 10–15‐fold increase in cAMP generation, the addition of hrTGF‐β along with ConA resulted in a 50–60‐fold increase in cAMP. These results suggest that in sepsis, TGF‐β produced by splenic macrophages can act in a paracrine manner on T‐cells to depress their IL‐2 mRNA expression, IL‐2 production and proliferation after up‐regulation of cAMP which can interfere with T‐cell signaling for proliferation.
Aberrant expression and function of p53 in T‐cells immortalized by HTLV‐I Tax1
Authors: Akagi Tsuyoshi , Ono Hiroaki , Tsuchida Nobuo , Shimotohno Kunitada
Published: July 2002

The expression and function of p53 tumor suppressor protein was investigated in T‐cells immortalized by the Tax1 protein of HTLV‐I. Conformationally wild‐type p53 was expressed at elevated levels in Tax1‐immortalized T‐cells by post‐transcriptional mechanisms when compared with normal T‐cells. Luciferase assays with a reporter plasmid containing p53‐binding sites revealed an impairment in the transactivating function of p53 in Tax1‐immortalized T‐cells. Our results suggest an important role for Tax1 in the aberrant expression and function of p53 observed in many HTLV‐I transformed cells.
Hydrolysis of AMPPNP by the motor domain of ncd, a kinesin‐related protein
Authors: Suzuki Yoshikazu , Shimizu Takashi , Morii Hisayuki , Tanokura Masaru
Published: July 2002

AMPPNP was found to be hydrolyzed by the motor domain of ncd (the product of a Drosophila gene, non‐claret disjunctional), a kinesin‐related protein. This hydrolysis could be monitored by 31P NMR spectroscopy and by an assay of phosphate, one of the products of the hydrolysis. The rate was ≈0.00004 s−1, 1% of the ATP turnover rate. The AMPPNP turnover was not stimulated by microtubules. Kinesin motor domain also turned over AMPPNP but at a somewhat lower rate. Although the turnover was slow, the present finding may present an important caveat, since AMPPNP has been widely used for investigations of kinesin and kinesin‐related proteins as a non‐hydrolyzable ATP analogue.
ATP synthase: a tentative structural model
Authors: Engelbrecht Siegfried , Junge Wolfgang
Published: July 2002

Adenosine triphosphate (ATP) synthase produces ATP from ADP and inorganic phosphate at the expense of proton‐ or sodium‐motive force across the respective coupling membrane in Archaea, Bacteria and Eucarya. Cation flow through the intrinsic membrane portion of this enzyme (FO, subunits ab
2
c
9–12) and substrate turnover in the headpiece (F1, subunits α
3
β
3
γ
δ
ϵ) are mechanically coupled by the rotation of subunit γ in the center of the catalytic hexagon of subunits (α
β)3 in F1. ATP synthase is the smallest rotatory engine in nature. With respect to the headpiece alone, it probably operates with three steps. Partial structures of six out of its at least eight different subunits have been published and a 3‐dimensional structure is available for the assembly (α
β)3
γ. In this article, we review the available structural data and build a tentative topological model of the holoenzyme. The rotor portion is proposed to consist of a wheel of at least nine copies of subunits c, ϵ and a portion of γ as a spoke, and another portion of γ as a crankshaft. The stator is made up from a, the transmembrane portion of b
2, δ and the catalytic hexagon of (α
β)3. As an educated guess, the model may be of heuristic value for ongoing studies on this fascinating electrochemical‐to‐mechanical‐to‐chemical transducer.
Dissecting the assembly pathway of the 20S proteasome
Authors: Zühl Frank , Seemüller Erika , Golbik Ralph , Baumeister Wolfgang
Published: July 2002

Proteasomes reach their mature active state via a complex cascade of folding, assembly and processing events. The Rhodococcus proteasome offers a means to dissect the assembly pathway and to characterize intermediates; its four subunits (α1, α2, β1, β2) assemble efficiently in vitro with any combination of α and β. Assembly studies with wild‐type and N‐terminally truncated β‐subunits in conjunction with refolding studies allowed to define the role of the propeptide which is two‐fold: It supports the initial folding of the β‐subunits and it promotes the maturation of the holoproteasomes.
Hydroxyl radicals are involved in the oxidation of isolated and cellular DNA bases by 5‐aminolevulinic acid
Authors: Douki Thierry , Onuki Janice , Medeiros Marisa H.G , Bechara Etelvino J.H , Cadet Jean , Di Mascio Paolo
Published: July 2002

5‐Aminolevulinic acid (ALA) is a heme precursor, pathological accumulation of which is associated with liver cancer. We show that the reactive oxygen species produced upon ALA metal‐catalyzed oxidation promote the formation of several radical‐induced base degradation products in isolated DNA. The distribution of modified bases is similar to that obtained upon gamma irradiation. This observation strongly suggests the involvement of hydroxyl radicals in the ALA‐mediated DNA damage. Increased levels of 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine and 5‐hydroxy‐2′‐deoxycytidine in organ DNA of rats chronically treated with ALA were observed. This is strongly suggestive of the implication of hydroxyl radicals in the ALA‐induced degradation of cellular DNA.
Useful 1O2 (1Δg) generator, 3‐(4′‐methyl‐1′‐naphthyl)‐propionic acid, 1′,4′‐endoperoxide (NEPO), for dioxygenation of squalene (a skin surface lipid) in an organic solvent and bacterial killing in aqueous medium
Authors: Nakano Minoru , Kambayashi Yasuhiro , Tatsuzawa Hidetaka , Komiyama Tomoko , Fujimori Ken
Published: July 2002

3‐(4′‐Methyl‐1′‐naphthyl)‐propionic acid, 1′,4′‐endoperoxide (NEPO) provides singlet state of oxygen (1O2, 1Δg) at 37°C in sodium phosphate buffer (pH 7.2), acetate buffer (pH 4.5), methanol or chloroform, through the retro‐Diels‐Alder reaction. The total amount of 1O2 generated by NEPO was calculated using the following equation: [1O2]=[NEPO]0[1−exp−kt], where [1O2], [NEPO]0 and k are the total amount of 1O2 produced during the time t, initial concentration of NEPO and the first‐order reaction rate constant, respectively. When squalene was exposed to 1O2 which was generated thermolytically from NEPO, it was oxidized to three hydroperoxides, mono‐, di‐ and tri‐hydroperoxides, in amounts proportional to the dose of NEPO. The oxidizability of squalene was much more extensive compared with unsaturated phospholipids. Additionally, when wild‐type E. coli and lycopene‐producing mutant E. coli were exposed to NEPO‐derived 1O2, there was significant loss of viability of wild‐type E. coli but no significant loss of viability in lycopene‐producing strain, suggesting that lycopene by scavenging 1O2 protected E. coli against 1O2 toxicity.
Density‐ and proliferation status‐dependent expression of T‐cadherin, a novel lipoprotein‐binding glycoprotein: a function in negative regulation of smooth muscle cell growth?
Authors: Kuzmenko Yelena S , Kern Frances , Bochkov Valery N , Tkachuk Vsevolod A , Resink Thérèse J
Published: July 2002

The atypical low density lipoprotein (LDL) binding proteins (M
r 105 and 130 kDa; p105 and p130) in human aortic medial membranes and cultured human and rat aortic smooth muscle cells (SMC) have recently been identified as the cell adhesion glycoprotein T‐cadherin. Although cadherins are generally recognized to be important regulators of morphogenesis, the function of T‐cadherin in the vasculature is poorly understood. This study has examined the relationship between expression of T‐cadherin and the density and proliferation status of SMC. T‐cadherin (p105 and p130) levels in SMC lysates were measured on Western blots using ligand‐binding techniques. T‐cadherin expression was dependent upon cell density, and maximal levels were achieved at confluency. T‐cadherin levels were reversibly modulated by switching cultures between serum‐free (upmodulation) and serum‐containing (downmodulation) conditions. Platelet‐derived growth factor (PDGF)‐BB, epidermal growth factor (EGF) or insulin‐like growth factor (IGF) elicited a dose‐ and time‐dependent downmodulation that was reversible after transfer of SMC to growth factor‐free medium. Our results support the hypothesis that T‐cadherin may function as a negative determinant of cell growth.
Characterization of the active site of a hydrogen sensor from Alcaligenes eutrophus
Authors: Pierik Antonio J , Schmelz Milena , Lenz Oliver , Friedrich Bärbel , Albracht Simon P.J
Published: July 2002

A third hydrogenase was recently identified in the proteobacterium Alcaligenes eutrophus as a constituent of a novel H2‐sensing multicomponent regulatory system. This regulatory hydrogenase (RH) has been overexpressed in cells deficient in both the NAD+‐reducing [NiFe]‐hydrogenase and the membrane‐bound [NiFe]‐hydrogenase. EPR, FTIR and activity studies of membrane‐free extracts revealed that the RH has an active site much like that of standard [NiFe]‐hydrogenases, i.e. a Ni‐Fe site with two CN− groups and one CO molecule. Its catalytic power is low, but the RH is always active, insensitive to oxygen, and occurs in only two redox states.
Distinct mechanisms of antibody‐mediated enzymatic reactivation in β‐galactosidase molecular sensors
Authors: Feliu J.X , Ramı́rez E , Villaverde A
Published: July 2002

The antibody‐mediated reactivation of engineered Escherichia coli β‐galactosidases [Benito et al. (1996) J. Biol. Chem. 271, 21251–21256] has been thoughtfully investigated in three recombinant molecular sensors. Proteins M278VP1, JX772A and JX795A display the highly antigenic G‐H loop peptide segment of foot‐and‐mouth disease virus VP1 protein, accommodated in different solvent‐exposed loops of the assembled tetramer. These chimaeric enzymes exhibit a significant increase in enzymatic activity upon binding of either monoclonal antibodies or sera directed against the inserted viral peptide. In JX772A but not in M278VP1, the Fab 3E5 antibody fragment promotes reactivation to the same extent as the complete antibody. On the other hand, M278VP1 K
m is reduced by more than 50% in the presence of activating serum, this parameter remains invariable in JX772A and it is only slightly modified in JX795A. In these last two proteins, significant k
cat variations can account for the increased enzymatic activity. Alternative reactivation mechanisms in the different β‐galactosidase probes are discussed in the context of the bacterial enzyme structure and its tolerance to antibody‐induced conformational modifications.
Primary structure of a visual pigment in bullfrog green rods
Authors: Hisatomi Osamu , Takahashi Yusuke , Taniguchi Yuki , Tsukahara Yasuo , Tokunaga Fumio
Published: July 2002

In frog retina there are special rod photoreceptor cells (‘green rods’) with physiological properties similar to those of typical vertebrate rods (‘red rods’). A cDNA fragment encoding the putative green rod visual pigment was isolated from a retinal cDNA library of the bullfrog, Rana catesbeiana. Its deduced amino acid sequence has more than 65% identity with those of blue‐sensitive cone pigments such as chicken blue and goldfish blue. Antisera raised against its C‐terminal amino acid sequence recognized green rods. It is concluded that bullfrog green rods contain a visual pigment which is closely related to the blue‐sensitive cone pigments of other non‐mammalian vertebrates.
Antigen recognition by conformational selection
Authors: Berger Christine , Weber-Bornhauser Susanne , Eggenberger Jolanda , Hanes Jozef , Plückthun Andreas , Bosshard Hans Rudolf
Published: July 2002

Conformational adaptation between antigen and antibody can modulate the antibody specificity. The phenomenon has often been proposed to result from an ‘induced fit’, which implies that the binding reaction induces a conformational change in the antigen and the antibody. Thus, an ‘induced fit’ requires initial complex formation followed by a conformational change in the complex. However, an antibody may select those antigen molecules that happen to be in a fitting conformational state. This leads to the same end result as an induced fit. Here, we demonstrate conformational selection by a single chain antibody fragment, raised against a random coil variant of the leucine zipper domain of transcription factor GCN4, when it cross‐reacts with the wild‐type dimeric leucine zipper. Kinetic and equilibrium data show that the single chain antibody fragment fragment selects monomeric peptides from the population in equilibrium with the leucine zipper dimer.
Defective regulation of Ca2+/calmodulin‐dependent protein kinase II in γ‐irradiated ataxia telangiectasia fibroblasts
Authors: Famulski Konrad S , Paterson Malcolm C
Published: July 2002

Recent indirect evidence suggests that a Ca2+/calmodulin‐dependent pathway, which may involve calmodulin‐dependent protein kinase II (CaMKII), mediates the S‐phase delay manifested by γ‐ray‐exposed human fibroblasts. This pathway is severely impaired in ataxia telangiectasia (A‐T) cells [Mirzayans et al. (1995) Oncogene 11, 1597]. To extend these findings, we assayed CaMKII activity in irradiated normal and A‐T fibroblasts. The radiation treatment induced the autonomous activity of the kinase in normal cells. In contrast, this activity was not elevated in either (i) normal cells pretreated with the selective CaMKII antagonist KN‐62 or (ii) γ‐irradiated A‐T cells. Moreover, A‐T fibroblasts, unlike normal cells, failed to mobilize intracellular Ca2+ upon mitogenic stimulation. These findings identify a novel role for CaMKII in radiation‐induced signal transduction and suggest its involvement in effecting the S‐phase delay. The data also implicate ATM, the product of the gene responsible for A‐T, as a key mediator of both intracellular Ca2+ mobilization and CaMKII activation in response not only to genotoxic stress but also to physiological stimuli.
Thrombin‐induced association of SHP‐2 with multiple tyrosine‐phosphorylated proteins in human platelets
Authors: Edmead C.E , Crosby D.A , Southcott M , Poole A.W
Published: July 2002

SH2 domain containing phosphatase‐2 (SHP‐2) has an important regulatory role in a variety of cell types. However, little is known concerning its function in platelets. We show here that, in thrombin‐stimulated human platelets, SHP‐2 undergoes a time‐dependent association with platelet endothelial cell adhesion molecule‐1 (PECAM‐1) and four low molecular weight phosphoproteins which are attenuated by the Src kinase inhibitor PP1. The low molecular weight proteins, which may be transmembrane proteins, are shown to bind exclusively to the N‐terminal SH2 domain of SHP‐2 and are therefore possible activators of the phosphatase. In addition, SHP‐2 phosphatase activity is shown to be increased following thrombin stimulation or cross‐linking of PECAM.
Crystal structure of streptokinase β‐domain
Authors: Wang Xiaoqiang , Tang Jordan , Hunter Bret , Zhang Xuejun C.
Published: July 2002

Streptokinase, a 47 kDa secreted protein of hemolytic strains of streptococci, is a human plasminogen activator and contains three structural domains linked by flexible loops. We describe here the crystal structure of the isolated streptokinase middle (SKβ) domain determined at 2.4 Å resolution. Among the functionally important structural features is a putative binding site for a kringle domain of plasminogen located at the tip of a fully exposed hairpin loop. The distribution of genetically conserved residues of SKβ is strongly correlated with their functions. The extensive interface of the SKβ dimer suggests that such dimers may also exist in solution for free SKβ.
Domain interactions in antibody Fv and scFv fragments: effects on unfolding kinetics and equilibria
Authors: Jäger Marcus , Plückthun Andreas
Published: July 2002

The equilibrium denaturation and unfolding kinetics of the domains VL and VH have been compared with those of the Fv and single‐chain Fv (scFv) fragment of an engineered variant of the antibody McPC603 in the presence and absence of the antigen phosphorylcholine. The scFv fragment is significantly more stable than the isolated constituting domains. Antigen binding stabilizes the heterodimeric assembly even further. Domain dissociation and domain unfolding are coupled processes, giving rise to a highly cooperative unfolding transition. For the Fv fragment, cooperative unfolding is only observed in the presence of antigen. At low protein concentrations and in the absence of antigen, the Fv fragment is significantly destabilized, leading to quantitative domain dissociation before significant domain unfolding takes place. The kinetic unfolding of VH, VL and the scFv fragment is monophasic. Unfolding of the scFv fragment is much slower, when extrapolated to zero denaturant, than either of the isolated domains, suggesting that the higher thermodynamic stability of the scFv fragment is at least partially due to a high‐energy transition state for unfolding. These studies emphasize the enormous importance of mutual domain stabilization in engineering stable antibodies.
Effect of temperature on kinesin‐driven microtubule gliding and kinesin ATPase activity
Authors: Böhm Konrad J. , Stracke Roland , Baum Marina , Zieren Martin , Unger Eberhard
Published: July 2002

DeCuevas et al. [J. Cell Biol. 116 (1992) 957–965] demonstrated by circular dichroism spectroscopy for the kinesin stalk fragment that shifting temperature from 25 to 30°C caused a conformational transition. To gain insight into functional consequences of such a transition, we studied the temperature dependence of a full‐length kinesin by measuring both the velocity of microtubule gliding across kinesin‐coated surfaces and microtubule‐promoted kinesin ATPase activity in solution. The corresponding Arrhenius plots revealed distinct breaks at 27°C, corroborating the temperature‐dependent conformational transition for a motility‐competent full‐length kinesin. Microtubules were found to glide up to 45°C; at higher temperatures, kinesin was irreversibly damaged.
Validation of the Arizona Governor's Quality Award criteria: a test of the Baldrige criteria
Authors: Pannirselvam Gertrude P , Siferd Sue P , Ruch William A
Published: July 2002

Tens of thousands of firms have used the Malcolm Baldrige National Quality Award (MBNQA) criteria to improve the quality of their products and processes. Because the MBNQA data are confidential, there has been no published assessment of the validity and reliability of these criteria for evaluating the quality management practices of an organization. In this research, we analyze data from the Arizona Governor's Quality Award (AGQA) in order to check the validity of the model used to evaluate organizational quality. The criteria for the AGQA closely parallel the MBNQA criteria. Hence, the conclusions drawn from this study provide a basis for generalization to the MBNQA criteria. In the literature review, the MBNQA criteria are compared to two other instruments that have been developed and tested for measuring quality management. The MBNQA criteria are found to be more comprehensive and less prescriptive than the other two. In our research, we examine content validity, construct validity, and predictive validity of the AGQA. Finally, we present our conclusions and implications for researchers and managers.
The prediction of stress fractures using a ‘stressed volume’ concept
Authors: Taylor David , Kuiper Jan‐Herman
Published: July 2002

This paper addresses an anomaly which exists in the current literature regarding stress fractures. Analysis of the data on fatigue strength of bone samples in vitro would conclude that these fractures should never occur at the strain levels known to occur in vivo. This anomaly can be resolved by including in the analysis the effect of stressed volume, whereby larger volumes of material are expected to have worse fatigue properties. A Weibull analysis was used to predict the probability of failure, Pf; this was an upperbound prediction because it did not include the effects of remodelling and adaptation. Combining this analysis with a finite element model of the human tibia, we predicted a Pf value of 21% after five weeks of strenuous exercise, which is comparable with reported incidences in military personnel. The high incidence of stress fractures in the cannon bone of racehorses could also be predicted (Pf = 62%, compared to 70% experimentally). The approach can be used to investigate the effect of variables in the exercise regime such as the distance run per day and the use of improved footwear. It can also predict the increased risk of stress fractures in elderly people. The results suggest certain simple rules which may be of clinical value in designing exercise regimes and in understanding the risk factors for this type of injury. © 2001 Orthopaedic Research Society. Punlished by Elsevier Science Ltd. All rights reserved.
Responses to maternal separation : mechanisms and mediators
Authors: Kuhn Cynthia M. , Schanberg Saul M.
Published: July 2002

Clinical studies indicate the predominance of psychosocial factors (nurturing environment) in the genesis of the Maternal Deprivation Syndrome. Consequences of disrupting mother‐infant interactions range from marked suppression of certain neuroendocrine and physiological systems after short periods of maternal deprivation to retardation of growth and behavioral development after chronic periods. We have shown that maternal separation initiates a complex adaptive biobehavioral response in preweaning rat pups that includes (1) a decrease in the synthesis of ornithine decarboxylase, an obligatory enzyme for normal cell growth and development, (2) a reduction in DNA synthesis, an index of cell multiplication, (3) abnormal patterns of neuroendocrine secretion, and (4) a suppression of cell responses to growth hormone, prolactin and insulin, three major trophic hormones. This unique pattern of adaptation to maternal separation is not related to food or temperature changes but results from a lack of a specific type of tactile stimulation of the pup by the mother. Recently, we have shown that in the absence of “nurturing touch” the brain initiates the suppression of ornithine decarboxylase gene transcription by interfering with the cell's ability to transduce the activating signal induced by the growth promoting hormones. Studies indicate that central endorphinergic pathways may mediate this action. This is accomplished by the downregulation of specific Immediate Early Genes (c‐myc and max) that normally promote the synthesis of this critical growth‐regulatory enzyme. These studies of short‐term maternal separation not only demonstrated that maternal care is a critical regulator of pup physiology and biobehavioral development but that there are marked similarities between this animal model of maternal separation and the delay in growth and development observed in children with the deprivation syndrome or in touch‐deprived premature human neonates. Our identification of a specific type of nurturing touch as a neonatal growth requirement led us to test supplemental tactile stimulation in isolated very‐premature human babies. The result of our intervention with massage was dramatic. Infants not only showed marked gains in weight and behavioral development, but also a significant enhancement in sympatho‐adrenal maturation. We suggest that animal models of maternal deprivation can be used to understand the integrative processing of appropriate sensory input, CNS function and end‐organ physiology required to maintain normal development.
Has there been a decrease in the prevalence of mood disorders in HIV-seropositive individuals since the introduction of combination therapy?
Authors: Alciati A. , Starace F. , Scaramelli B. , Campaniello M. , Adriani B. , Mellado C. , Cargnel A.
Published: July 2002

Purpose.

The aim of this study was to assess the prevalence of current mood disorders in HIV-seropositive patients treated with combined antiretroviral drug therapy including or not protease inhibitors.

Subjects and methods.

A random sample of 90 subjects consecutively attending, between February 1 and July 31, 1998, the outpatient unit of the Second Department of Infectious Diseases of the ‘L. Sacco’ Hospital in Milan was assessed by means of the Structured Clinical Interview for DSMIII-R (SCID) and the Zung Self-Rating Depression Scale (ZSDS).

Results.

Twenty-three-point-three percent of the subjects were classified in CDC stage A, 32.3% in CDC stage B and 44.4% in CDC stage C. A DSMIII-R psychiatric diagnosis of current mood disorder was found in 4.4% of the recruited sample (dysthymia: 2.2%; adjustment disorder with depressed mood: 2.2%).

Conclusions.

Direct and indirect effect of new combination therapies, epidemiological changes in social groups affected by HIV and possible modifications in social perception of people with HIV infection may explain, at least in part, the decreased prevalence of current mood disorders observed in our study as compared to prevalence rates reported in the pre-HAART era.
Quality of life of the mentally ill. Reliability of the Swedish version of the Lancashire Quality of Life profile
Authors: Hansson L , Svensson B , Björkman T
Published: July 2002

There has been a growing interest in the quality of life (QoL) of the mentally ill, subsequently a number of instruments to measure QoL have been developed. One of the measures of QoL which has received considerable attention is the Lancashire QoL Profile (LQOLP). The present study investigated test-retest reliability and internal consistency in the Swedish translation of the LQOLP using a cross-sectional sample of 29 inpatients. The results showed that test-retest reliability of subjective life satisfaction in the nine life domains covered by the LQOLP was satisfactory in seven of the domains, and acceptable in two (social relations and religion). Test-retest reliability for total subjective satisfaction score, global well-being, and an interviewer rated QoL were all on a satisfactory level (r > 0.80). The internal consistency and homogeneity of the total subjective QoL scale and the nine life domain subscales was satisfactory except for the social relations scale, where it was somewhat low.
The development and validation of a Spanish version of the quality of life in depression scale (QLDS)
Authors: Cervera-Enguix S. , Ramírez N. , Girala N. , McKenna S.P.
Published: July 2002

Objective:

The adaptation of the Quality of Life in Depression Scale, the QLDS, into Spanish.

Methods:

The original UK version of the QLDS was considered by two translation panels, who produced a Spanish translation. Priority was given to conceptual rather than semantic equivalence. This version was then field-tested with 15 depressed patients. The final stage of the research involved a postal survey of 62 patients, who were asked to complete the measure on two occasions.

Results:

The Spanish QLDS was found to be appropriate and acceptable by depressed patients. The questionnaire's test-retest reliability and internal consistency were both high, and QLDS scores correlated as predicted with scores on sections of the Nottingham Health Profile. The measure was sensitive to different levels of depression as assessed by the Hospital Anxiety and Depression Scale.

Conclusion:

The Spanish version of the QLDS is suitable for use in clinical trials and for monitoring individual patients in routine clinical practice.
One step forward, two steps back: women in the post-communist states
Authors: LaFont Suzanne
Published: July 2002

The role and status of women in the post-communist countries has been and continues to be varied and full of contradictions. This article discusses the historical, social, economic, and political dynamics affecting the lives of women during the transition from communism to democracy. It argues that democracy, rather than diminishing gender discrimination, has widened the gender gap through declines in women's political representation and increases in women's unemployment and underemployment. Recently, however, the proliferation of women's organizations and the growth of women's studies programs suggests a more optimistic outlook for the future.
Body Composition in Patients With Psoriatic Arthritis and Changes During Interleukin‐12/Interleukin‐23 Inhibition
Authors: Paccou Julien , Bavière Wallis , Sornay‐Rendu Elisabeth , Szulc Pawel , Ramdane Nassima , Cortet Bernard , Chapurlat Roland , Flipo René‐Marc
Published: May 2021

Objective

Little is known about body composition in patients with psoriatic arthritis (PsA). Our objective was to compare body composition parameters in PsA patients and healthy controls and then investigate the effects of ustekinumab (UST) on body composition in patients with PsA.

Methods

At baseline, 30 PsA patients were compared cross‐sectionally with 60 healthy controls without PsA, matched for age, sex, menopausal status, and body mass index (BMI). Thirty active PsA patients treated with UST were included in a 6‐month open follow‐up study. Body composition parameters were measured at baseline and 6 months of treatment.

Results

Body composition parameters were different in PsA patients compared to healthy controls; in PsA patients, total and appendicular lean mass were lower (P = 0.013 and P = 0.010, respectively), whereas total fat mass was higher (P < 0.001). In 30% of the PsA patients, skeletal muscle mass was below the cutoff for low muscle quantity (men 7.26 kg/m2, women 5.5 kg/m2), whereas no such change was observed in the control group. After 6 months of treatment with UST, there was no significant change in BMI in 18 of the PsA patients. Total lean mass decreased slightly (P = 0.046), whereas fat mass tended to increase, but not significantly. No significant changes in appendicular lean mass and skeletal muscle mass index were observed.

Conclusion

In this study, we found that PsA patients had higher fat mass and lower lean mass than healthy controls. At 6‐months of treatment, total lean mass decreased slightly, whereas fat mass tended to increase, but not significantly.
Nurse‐Led Consultation for Patients With Rheumatoid Arthritis at Low Disease Activity: A Randomized Noninferiority Trial
Authors: Kwok Suet‐Kei , Tang Lai‐Man , Tsang Hoi‐Lun , Chung Ho‐Yin , Chung Man‐Ho , Ho Carmen T. K. , Lau Chak‐Sing , Cheung Tommy T.
Published: May 2021

Objective

To determine the effectiveness of nurse‐led consultations in patients with stable rheumatoid arthritis (RA) in Hong Kong.

Methods

The present work was a single‐center, randomized, open‐label, noninferiority trial. Patients who had rheumatoid arthritis (RA) with low disease activity (LDA) were randomized at a 1:1 ratio to attend a nurse‐led consultation or rheumatologist follow‐up visit for 2 years. The primary end point was the proportion of patients whose RA remained at LDA. Secondary end points included the proportion of patients with RA in disease remission and the scores recorded on the Leeds Satisfaction Questionnaire at 2 years, changes from baseline on the Disease Activity Score in 28 joints using the C‐reactive protein level (DAS28‐CRP), modified Sharp/van der Heijde score (SHS), Health Assessment Questionnaire disability index (HAQ DI), Short Form 36 (SF‐36) physical component score, and 19‐item Compliance Questionnaire for Rheumatology (CQR‐19) score.

Results

Among 280 patients who were randomized equally to either attend nurse‐led consultations or rheumatologist follow‐up visits, 267 patients completed the study. In the nurse‐led consultation and rheumatologist follow‐up groups, 92.1% and 91.4% patients, respectively, remained at LDA at 2 years. The 95% confidence intervals (95% CIs) of the adjusted treatment difference were within the predefined noninferiority margin in both the intention‐to‐treat analysis (95% CI 5.75, 7.15) and the per‐protocol analysis (95% CI 1.67, 7.47). Although the changes in DAS28‐CRP score over 2 years were significantly different between the 2 treatment groups (P < 0.001), there were no significant changes from baseline in SHS, HAQ DI, SF‐36 physical component scores, and CQR‐19 scores. At the end of the study, more patients expressed satisfaction with nurse‐led consultations.

Conclusion

Nurse‐led consultations were not inferior to rheumatologist follow‐up visits in patients with stable RA.
Metacarpophalangeal Joint Impairment in Hand Osteoarthritis and Its Association With Mechanical Factors: Results From the Digital Cohort Osteoarthritis Design Hand Osteoarthritis Cohort
Authors: Kouki Inès , Tuffet Sophie , Crema Michel D. , Rousseau Alexandra , Richette Pascal , Dougados Maxime , Berenbaum Francis , Sellam Jérémie , Courties Alice
Published: May 2021

Objective

To determine the prevalence, distribution, and characteristics associated with radiographic metacarpophalangeal (MCP) joint osteoarthritis (OA).

Methods

This was a cross‐sectional study of baseline data from the Digital Cohort Osteoarthritis Design, a French monocentric cohort including patients with symptomatic hand OA. We evaluated the prevalence of radiographic MCP joint OA, defined as ≥2 MCP joints with a Kellgren/Lawrence score of ≥2. We compared the prevalence of MCP joint OA in the dominant and nondominant hands. Associations between radiographic MCP joint OA and patient characteristics were studied using univariable and multivariable logistic regression.

Results

Radiographic MCP joint OA was present in 138 of the 425 patients (32.5%) but was not severe. Patients with MCP joint OA had a mean age of 69.2 ± 6.9 years, a body mass index of 25 ± 4.2 kg/m2, and 86.2% were women. MCP joint OA was more frequent in the dominant hand and predominated at the first and second MCP joints. In the multivariable analysis, MCP joint OA was associated with older age (odds ratio [OR] 1.05 [95% confidence interval (95% CI) 1.01, 1.10] for each year), manual occupation (OR 3.74 [95% CI 1.21, 11.54]), scaphotrapezial OA (OR 2.18 [95% CI 1.27, 3.72]), and a high number of proximal interphalangeal joints with radiographic OA. MCP joint OA was not associated with metabolic syndrome or hand OA symptoms.

Conclusion

In this cross‐sectional study using a hospital‐based hand OA cohort, radiographic MCP joint OA was frequent and associated with structural hand OA features rather than with symptom severity. Our results suggest that the involvement of MCP joints in hand OA is predominantly related to mechanical rather than systemic factors in this population.
Innovations in Biomaterial Design toward Successful RNA Interference Therapy for Cancer Treatment
Authors: Ward Deidra M. , Shodeinde Aaliyah B. , Peppas Nicholas A.
Published: May 2021

Gene regulation using RNA interference (RNAi) therapy has been developed as one of the frontiers in cancer treatment. The ability to tailor the expression of genes by delivering synthetic oligonucleotides to tumor cells has transformed the way scientists think about treating cancer. However, its clinical application has been limited due to the need to deliver synthetic RNAi oligonucleotides efficiently and effectively to target cells. Advances in nanotechnology and biomaterials have begun to address the limitations to RNAi therapeutic delivery, increasing the likelihood of RNAi therapeutics for cancer treatment in clinical settings. Herein, innovations in the design of nanocarriers for the delivery of oligonucleotides for successful RNAi therapy are discussed.
Using fall‐seeded cover crop mixtures to enhance agroecosystem services: A review
Authors: Lavergne Stéphanie , Vanasse Anne , Thivierge Marie‐Noëlle , Halde Caroline
Published: May 2021

The intensification of agriculture has resulted in the loss of species diversity in agroecosystems. Crop diversification not only improves ecosystem functions but increases agroecosystem resilience to climate change. Cover crops (CC) are used in the crop rotation to increase plant diversity and provide continuous living roots and soil cover. Previous studies have focused mainly on pure stands of CC and on binary mixtures. In recent years, there has been a growing interest in multispecies mixtures (>2 species). Here, we review reports from the literature to document the effectiveness of fall‐seeded CC mixtures to provide agroecosystem services such as weed suppression, N cycling, soil organic C storage, and crop productivity. We cover both organic and conventional field crop systems in North America and Europe. We found, for both systems, that fall‐seeded CC mixtures increased many agroecosystem services compared with a control without CC; however, they had inconsistent effects in comparison with a pure stand. The capacity of mixtures to enhance a given agroecosystem service was found to be dependent on the species functional group. Legume‐based mixtures increased soil N and C contents along with crop yield, whereas nonlegume mixtures improved N recycling and weed suppression. Differences in the functional groups within CC mixtures could lead to trade‐offs among agroecosystem services. Future research should focus on what drives species‐specific contributions to productivity and other ecosystem services when CC are seeded in mixtures. More long‐term research is needed to provide better insights into the stability of the ecosystem services provided by CC mixtures.
Cotton yield response to soil applied potassium across the U. S. Cotton Belt
Authors: Lewis Katie , Morgan Gaylon , Frame William Hunter , Fromme Daniel , Dodds Darrin M. , Edmisten Keith L. , Robertson Bill , Boman Randy , Cutts Trey , Delaney Dennis P. , Burke Joseph Alan , Nichols Robert L.
Published: May 2021

Across the U.S. Cotton Belt, potassium (K) deficiency symptoms in cotton (Gossypium hirsutum L.) have become more common over the past decade. In 2015–2017, an experiment was conducted in Alabama, Arkansas, Louisiana, Mississippi, North Carolina, Oklahoma, South Carolina, two regions in Texas, and Virginia for a total of 23 site‐years. The objectives were (a) to quantify soil K levels at‐depth in representative soils where cotton is commonly grown in major cotton production regions with observed K deficiencies; and (b) to evaluate the effects of application method and K rates on cotton lint yield, loan value, and return on fertilizer investment. Granular and liquid potassium chloride were broadcast or injected, respectively, 2–4 wk prior to planting at 0, 45, 90, 135, and 180 kg K2O ha−1. Locations other than Texas and Oklahoma generally had soil K levels <less than 150 mg kg−1, the Mehlich III critical K level, and thus, a yield response to applied K fertilizer was expected. However, among the 23 site‐years, a treatment effect was determined at 5 site‐years. Two of those, Williamson County, Texas, and Virginia endured severe moisture stress and resulted in low yields (<526 kg lint ha−1). A positive lint yield response to knife‐injected 0–0–15 was determined in 2015 at the Lubbock County, Texas, location—a location with high yield (>1,653 kg lint ha−1). Inconsistent yield responses among locations indicate that K dynamics in the soil–cotton plant system are not well understood and deserve continued investigation.
Double‐Exchange‐Induced in situ Conductivity in Nickel‐Based Oxyhydroxides: An Effective Descriptor for Electrocatalytic Oxygen Evolution
Authors: Tian Bailin , Shin Hyeyoung , Liu Shengtang , Fei Muchun , Mu Zhangyan , Liu Cheng , Pan Yanghang , Sun Yamei , Goddard William A. , Ding Mengning
Published: May 2021

Motivated by in silico predictions that Co, Rh, and Ir dopants would lead to low overpotentials to improve OER activity of Ni‐based hydroxides, we report here an experimental confirmation on the altered OER activities for a series of metals (Mo, W, Fe, Ru, Co, Rh, Ir) doped into γ‐NiOOH. The in situ electrical conductivity for metal doped γ‐NiOOH correlates well with the trend in enhanced OER activities. Density functional theory (DFT) calculations were used to rationalize the in situ conductivity of the key intermediate states of metal doped γ‐NiOOH during OER. The simultaneous increase of OER activity with intermediate conductivity was later rationalized by their intrinsic connections to the double exchange (DE) interaction between adjacent metal ions with various d orbital occupancies, serving as an indicator for the key metal‐oxo radical character, and an effective descriptor for the mechanistic evaluation and theoretical guidance in design and screening of efficient OER catalysts.
Size‐Dependent Selectivity of Electrochemical CO2 Reduction on Converted In2O3 Nanocrystals
Authors: Huang Yang , Mao Xinnan , Yuan Guotao , Zhang Duo , Pan Binbin , Deng Jun , Shi Yunru , Han Na , Li Chaoran , Zhang Liang , Wang Lu , He Lin , Li Youyong , Li Yanguang
Published: May 2021

The size modulation of catalyst particles represents a useful dimension to tune catalytic performances by impacting not only their surface areas but also local electronic structures. It, however, has remained inadequately explored and poorly elucidated. Here, we report the interesting size‐dependent selectivity of electrochemical CO2 reduction on In2O3 nanocrystals. 5‐nm nanoparticles and 15‐nm nanocubes with focused size distribution are prepared via a facile solvothermal reaction in oleylamine by carefully controlling a set of experimental parameters. They serve as the precatalysts, and are reduced to In nanocrystals while largely inherit the original size feature during electrochemical CO2 reduction. Catalyst derived from 15‐nm nanocubes exhibits greater formate selectivity (>95 %) at lower overpotential and negligible side reactions compared to bulk‐like samples (indium foil and 200‐nm cubes) as well as the catalyst derived from smaller 5‐nm nanoparticles. This unique size dependence is rationalized as a result of the competition among different reaction pathways by our theoretical computations. Smaller is not always better in the catalyst design.