bluuebunny/crossref_metadata_2025 huggingface dataset:
Heating Up Circadian Rhythms
Authors: Gough Nancy R.
Published: July 2007

In addition to light, temperature can affect circadian cycles of behavioral activity. Kaushik
et al
. found that fruit flies undergo phase shifts in their circadian behavior in response to pulses of elevated temperature--37°C, but not 30°C--during the early part of the "night" (dark period). Light pulses during the dark period caused both delays and advances in the circadian cycle depending on when the light was applied. Coimmunoprecipitation experiments revealed that in head extracts from the flies, the 37°C heat pulse or light promoted an interaction between the cryptochrome CRY, which is the light sensor for the circadian clock, and the transcriptional regulators TIM (Timeless) and PER (Period), which form a heterodimer and are part of the feedback loop that controls the circadian cycle (see the
Drosophila
Circadian Pathway). The 37°C heat pulse was only effective at promoting the interaction or delaying the circadian cycle when applied early in the dark period [Zeitgeber time 15 (ZT15), where ZT0 is the number of hours elapsed since dawn]. The heat- or light-induced phase shifts were lost in loss-of-function

cry
b

flies, confirming that CRY is important for responding to either heat or light. A PER mutant called

per
L

exhibited more extreme phase shift changes in response to heat and light, including both delays and advances in the cycle depending on when the pulse of heat or light was applied, and also exhibited phase shift changes in response to 30°C temperature pulses. The interaction between CRY and PER and TIM detected by coimmunoprecipitation was promoted even when the mutant flies were exposed to the 30°C heat pulse. The authors suggest that the

Per
L

mutation or heat trigger a conformational change in TIM that promotes its interaction with CRY, thereby altering the circadian cycle.

R. Kaushik, P. Nawathean, A. Busza, A. Murad, P. Emery, M. Rosbash, PER-TIM interactions with the photoreceptor cryptochrome mediate circadian temperature responses in
Drosophila
.
PLoS Biol.
5
, e146 (2007).
[PubMed]
Bone Morphogenetic Protein Clips Angiogenic Role of Prolactin
Authors: Ray L. Bryan
Published: July 2007

The process of angiogenesis is critical during development and is a process that allows invasion of other tissues by cancer cells. Bone morphogenetic protein 1 (BMP1)-like proteins are proteases that help orchestrate morphogenesis. BMP1-like proteases promote deposition of extracellular matrix by cleaving precursors of structural proteins like procollagens. BMP1 also has antiangiogenic effects by releasing an antiangiogenic portion of the membrane proteoglycan perlecan. BMPs can also activate latent ligands of the transforming growth factor-β (TGF-β) superfamily. Ge
et al
. now report that BMP1 also appears to be an important factor in producing antiangiogenic fragments of growth hormone (GH) and prolactin (PRL). Although best known for their systemic endocrine actions, GH and PRL are also secreted locally by endothelial cells, producing paracrine or autocrine effects. The full-length hormones are angiogenic, but both can be cleaved to form N-terminal fragments that are antiangiogenic. The cleaved form of PRL is also implicated in postpartum cardiomyopathy in humans. Ge
et al
. fished for BMP1 substrates by screening for proteins associated with a modified form of BMP1 (which bound but did not cleave or release substrates) in a phage-display assay and found placental lactogen, a hormone related to GH and PRL. They showed that BMP1 could cleave PRL and GH to small ~17-kD fragments. They expressed truncated PRL that corresponded to the 17-kD fragment and showed that it had antiangiogenic activity in a chick chorioallantoic membrane assay and antagonized the proliferative effect of basic fibroblast growth factor on endothelial cells in culture. Mouse embryo fibroblasts lacking two genes encoding BMP1-like proteases no longer produced detectable amounts of the PRL cleavage product. The authors note that these results, along with evidence that BMP1 mRNA is highly expressed in endothelial cells associated with tumors, indicate that BMP1-like proteases may be key factors in regulation of angiogenesis.

G. Ge, C. A. Fernández, M. A. Moses, D. S. Greenspan, Bone morphogenetic protein 1 processes prolactin to a 17-kDa antiangiogenic factor.
Proc. Natl. Acad. Sci. U.S.A
.
104
, 10010-10015 (2007).
[Abstract]
[Full Text]
GPCRs Signaling Directly Through Src-Family Kinases
Authors: McGarrigle Deirdre , Huang Xin-Yun
Published: July 2007

A wide range of extracellular signals are transduced by G protein–coupled receptors (GPCRs). When activated by ligands, GPCRs can activate associated heterotrimeric guanine nucleotide–binding proteins (G proteins), which in turn act on various effectors. Increasing evidence indicates that GPCRs also signal independently of heterotrimeric G proteins. Several GPCRs directly interact with Src-family kinases. Here, we discuss the evidence for direct interaction and activation of Src-family kinases by GPCRs and data that suggest that agonist dosage provides a mechanism by which GPCRs can switch between G protein–dependent and G protein–independent signaling.
Open versus closed kinetic chain exercises for patellar chondromalacia
Authors: Bakhtiary A H , Fatemi E
Published: July 2007

Subject:

Conservative treatment of patellar chondromalacia has been the subject of several studies. One recommended treatment is a strengthening exercise of the quadriceps muscle, which may be performed in closed or open kinetic chains. This study was designed to compare the effect of straight leg raise (SLR) and semi-squat exercises on the treatment of patellar chondromalacia, which has not been done to date.

Material and methods:

32 female university students with a diagnosis of patellar chondromalacia were randomly assigned to two experimental groups: SLR and semi-squat exercise. Before starting exercise protocols, Q angle, maximal isometric voluntary contraction force (MIVCF) of quadriceps, crepitation, circumference of thigh 5 and 10 cm above the patella and patellofemoral pain according to the visual analogue scale (VAS) were assessed. Both groups then followed a 3-week programme of quadriceps muscle strengthening exercises (SLR or semi-squat) starting with 20 exercises twice a day and increasing each session by 5 exercises every 2 days. All measurements were repeated at the end of each week and then again 2 weeks after the 3-week exercise programme.

Results:

Reduced Q angle (mean differences (SD) 0.8 (0.3), p = 0.016) and crepitation (19.9 (8.5), p = 0.04), and an increase in the MIVCF of the quadriceps (15.8 (5.6), p = 0.01) and thigh circumference (1.5 (0.3), p = 0.001) were found in semi-squat group compared with SLR group. However, patellofemoral pain was decreased significantly in both groups.

Conclusion:

The results of this study indicate that semi-squat exercises (closed kinetic chain) are more effective than SLR exercise (open kinetic chain) in the treatment of patellar chondromalacia. More studies are needed to investigate the long-term effect of these types of exercise.
Identification of stress-induced genes from the drought-tolerant plant Prosopis juliflora (Swartz) DC. through analysis of expressed sequence tags
Authors: George Suja , Venkataraman Gayatri , Parida Ajay
Published: July 2007

Abiotic stresses such as cold, salinity, drought, wounding, and heavy metal contamination adversely affect crop productivity throughout the world. Prosopis juliflora is a phreatophyte that can tolerate severe adverse environmental conditions such as drought, salinity, and heavy metal contamination. As a first step towards the characterization of genes that contribute to combating abiotic stress, construction and analysis of a cDNA library of P. juliflora genes is reported here. Random expressed sequence tag (EST) sequencing of 1750 clones produced 1467 high-quality reads. These clones were classified into functional categories, and BLAST comparisons revealed that 114 clones were homologous to genes implicated in stress response(s) and included heat shock proteins, metallothioneins, lipid transfer proteins, and late embryogenesis abundant proteins. Of the ESTs analyzed, 26% showed homology to previously uncharacterized genes in the databases. Fifty-two clones from this category were selected for reverse Northern analysis: 21 were shown to be upregulated and 16 downregulated. The results obtained by reverse Northern analysis were confirmed by Northern analysis. Clustering of the 1467 ESTs produced a total of 295 contigs encompassing 790 ESTs, resulting in a 54.2% redundancy. Two of the abundant genes coding for a nonspecific lipid transfer protein and late embryogenesis abundant protein were sequenced completely. Northern analysis (after polyethylene glycol stress) of the 2 genes was carried out. The implications of the analyzed genes in abiotic stress tolerance are also discussed.
DNA sequence and haplotype variation in two candidate genes for dilated cardiomyopathy in the turkey Meleagris gallopavo
Authors: Lin Kuan-chin , Xu Jun , Kamara Davida , Geng Tuoyu , Gyenai Kwaku , Reed Kent M. , Smith Edward J.
Published: July 2007

Determining variation in genes is fundamental to understanding their function in the disease state. Cardiac troponin T (cTnT) and phospholamban (PLN) genes have been implicated in dilated cardiomyopathy (DCM) in human and model species. To investigate the role of these 2 candidate genes in DCM in the turkey Meleagris gallopavo, understanding sequence variants and map position distribution is necessary. To this end, a total of 1854 and 1771 bp of cTnT and PLN gene sequences, respectively, were scanned for single nucleotide polymorphisms (SNPs) in a randomly bred population. A total of 15 SNPs was identified in the cTnT and PLN genomic sequences. Nine haplotypes, 5 in cTnT and 4 in PLN, were identified. Observed heterozygosities (0.02–0.39) in the turkey population were low for both genes. Within each gene, 1 SNP corresponding to a restriction enzyme site was identified and used to develop a PCR–restriction fragment length polymorphism (RFLP) genotyping assay. The PLN gene was genetically mapped to turkey chromosome 2, equivalent to Gallus gallus chromosome 3, and cTnT mapped to a turkey microchromosome. Although limited because of the relatively small sample size of 55 birds, the data from this SNP analysis of PLN and cTnT provide a foundation from which to evaluate the function of cTnT and PLN in the turkey. Information about the distribution of the SNPs and haplotypes will facilitate future association and linkage studies.
Tissue culture triggers chromosome alterations, amplification, and transposition of repeat sequences in Allium fistulosum
Authors: Gernand Dorota , Golczyk Hieronim , Rutten Twan , Ilnicki Tomasz , Houben Andreas , Joachimiak Andrzej J.
Published: July 2007

Structural alterations in nuclei and chromosomes of cells derived from callus culture of Allium fistulosum have been studied with fluorescent in situ hybridization (FISH) using 5S ribosomal DNA (rDNA), 45S rDNA, and 375-bp repeat probes. A high frequency of chromosome abnormalities was found to be caused by the loss of telomere-located 375-bp repeats, chromosome fusion, and subsequent breakage–fusion–bridge cycles. Products of chromosome fusions and monocentric and regularly shaped chromosomes showed additional 375-bp repeat and 45S rDNA clusters at unusual sites, suggesting dynamic copy-number changes and transposition of these repeats. Southern hybridization revealed no differences in the 375-bp repeat and 45S rDNA repeat array order or the degree of methylation between DNA isolated from leaves or tissue-culture cells. In addition, protruding, spike-like structures positive for 375-bp repeats were identified on the surface of different-sized nuclei. Transmission electron microscopy analysis revealed the accumulation of densely packed chromatin within spike-like structures. Because root calyptra cells showed similar structures, it is likely that heterochromatic spike-like structures are a feature of nondividing cells at the onset of programmed cell death.
Molecular characterization of vernalization response genes in Canadian spring wheat
Authors: Iqbal Muhammad , Navabi Alireza , Yang Rong-Cai , Salmon Donald F. , Spaner Dean
Published: July 2007

Vernalization response (Vrn) genes play a major role in determining the flowering/maturity times of spring-sown wheat. We characterized a representative set of 40 western Canadian adapted spring wheat cultivars/lines for 3 Vrn loci. The 40 genotypes were screened, along with 4 genotypes of known Vrn genes, using previously published genome-specific polymerase chain reaction primers designed for detecting the presence or absence of dominant or recessive alleles of the major Vrn loci: Vrn-A1, Vrn-B1, and Vrn-D1. The dominant promoter duplication allele Vrn-A1a was present in 34 of 40 cultivars/lines, whereas the promoter deletion allele Vrn-A1b was present in only 1 of the western Canadian cultivars ( Triticum aestivum L. ‘Rescue’) and 2 of its derivative chromosomal substitution lines. The intron deletion allele Vrn-A1c was not present in any line tested. Only 4 of the western Canadian spring wheat cultivars tested here carry the recessive vrn-A1 allele. The dominant allele of Vrn-B1 was detected in 20 cultivars/lines. Fourteen cultivars/lines had dominant alleles of Vrn-A1a and Vrn-B1 in combination. All cultivars/lines carried the recessive allele for Vrn-D1. The predominance of the dominant allele Vrn-A1a in Canadian spring wheat appears to be due to the allele's vernalization insensitivity, which confers earliness under nonvernalizing growing conditions. Wheat breeders in western Canada have incorporated the Vrn-A1a allele into spring wheats mainly by selecting for early genotypes for a short growing season, thereby avoiding early and late season frosts. For the development of early maturing cultivars with high yield potential, different combinations of Vrn alleles may be incorporated into spring wheat breeding programs in western Canada.
Probucol promotes endogenous antioxidant reserve and confers protection against reperfusion injuryThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.
Authors: Singla Dinender K. , Kaur Kuljeet , Sharma Anita K. , Dhingra Sanjiv , Singal Pawan K.
Published: July 2007

The present study examines whether a subchronic probucol treatment of rats offers protection against ischemia–reperfusion (IR) injury in isolated perfused hearts. Sprague–Dawley rats were treated every second day per week with probucol (cumulative dose 120 mg/kg body mass, i.p.) for 4 weeks. In the probucol group, baseline myocardial antioxidant enzyme, glutathione peroxidase (GSHPx), activity was increased (p < 0.05), whereas superoxide dismutase (SOD) and catalase (CAT) activities were not changed. Baseline oxidative stress, as indicated by the myocardial lipid peroxidation, was less (p < 0.05) in the probucol group. Isolated hearts were subjected to 60 min global I and 20 min R. Recovery of the contractile function in globally ischemic hearts upon reperfusion was 36% in untreated group and 74% in the probucol group. After IR, GSHPx and CAT activities were significantly (p < 0.05) higher in the probucol group compared with the control group, whereas SOD did not change. Lipid peroxidation owing to IR was significantly less in the probocol group. These data suggest that probucol treatment improves endogenous antioxidant reserve and protects against increased oxidative stress following IR injury.
Differential effects of losartan and candesartan on vasoconstrictor responses in the ratThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.
Authors: Nossaman Bobby D. , Baber Syed R. , Nazim Mohammed M. , Detrolio John D. , Kadowitz Philip J.
Published: July 2007

Losartan has been reported to have inhibitory effects on thromboxane (TP) receptor-mediated responses. In the present study, the effects of 2 nonpeptide angiotensin II (AT1) receptor antagonists, losartan and candesartan, on responses to angiotensin II, the thromboxane A2mimic, U46619, and norepinephrine were investigated and compared in the pulmonary and systemic vascular beds of the intact-chest rat. In this study, intravenous injections of angiotensin II, U46619, and norepinephrine produced dose-related increases in pulmonary and systemic arterial pressure. Losartan and candesartan, in the doses studied, decreased or abolished responses to angiotensin II. Losartan, but not candesartan, and only in a higher dose, produced small, but statistically significant, reductions in pressor responses to U46619 and to norepinephrine in the pulmonary and systemic vascular beds. Furthermore, losartan significantly reduced arachidonic acid-induced platelet aggregation, whereas candesartan had no effect. Pressor responses to angiotensin II were not changed by thromboxane and alpha-adrenergic receptor antagonists, or by cyclooxygenase and NO synthase inhibitors. These results show that losartan and candesartan are potent selective AT1receptor antagonists in the pulmonary and systemic vascular beds and that losartan can attenuate thromboxane and alpha-adrenergic responses when administered at a high dose, whereas candesartan in the highest dose studied had no effect on responses to U46619 or to norepinephrine. The present data show that the effects of losartan and candesartan on vasoconstrictor responses are different and that pulmonary and systemic pressor responses to angiotensin II are not modulated or mediated by the release of cyclooxygenase products, activation of TP receptors, or the release of NO in the anesthetized rat.
Hydrogen peroxide causes cardiac dysfunction independent from its effects on matrix metalloproteinase-2 activationThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.
Authors: León Hernando , Bautista-López Norma , Sawicka Jolanta , Schulz Richard
Published: July 2007

Hydrogen peroxide (H2O2) causes cardiac dysfunction through multiple mechanisms. As oxidative stress can activate matrix metalloproteinases (MMPs) and, in particular, MMP-2 activity is associated with oxidative stress injury in the heart, we hypothesized that MMP-2 activation by H2O2in isolated rat hearts contributes to cardiac dysfunction in this model. Isolated working rat hearts were perfused at 37 °C with a recirculating Krebs–Henseleit buffer ± 5 mmol/L pyruvate, known to protect hearts from oxidative stress. H2O2(300 µmol/L) was added as a single bolus after 20 min of equilibration, and cardiac function was monitored for 60 min. MMPs activities in both the heart and perfusate samples were assessed by gelatin zymography. Tissue high energy phosphates were analysed by HPLC. The actions of 2 MMP inhibitors, doxycycline (75 µmol/L) or Ro 31-9790 (3 µmol/L), were also assessed. H2O2at 300 µmol/L produced a rapid decline in cardiac mechanical function, which was maximal at 5 min. A peak in perfusate MMP-2 activity was also observed at 5 min. The deleterious effect of H2O2on cardiac function was abolished by pyruvate but not by the MMPs inhibitors. This study suggests that in intact hearts, H2O2induces contractile dysfunction independent of MMPs activation.
Ral-GTPase interacts with the β1 subunit of Na+/K+-ATPase and is activated upon inhibition of the Na+/K+pumpThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.
Authors: Bhullar Rajinder P. , Clough Richard R. , Kanungo Juddy , Elsaraj Sherif M. , Grujic Ognjen
Published: July 2007

Na+/K+-ATPase functions as both an ion pump and a signal transducer. Cardiac glycosides partially inhibit Na+/K+-ATPase, causing activation of multiple interrelated growth pathways via the Na+/K+-ATPase/c-Src/epidermal growth factor receptor complex. Such pathways include Ras/MEK/ERK and Ral/RalGDS cascades, which can lead to cardiac hypertrophy. In search of novel Ral-GTPase binding proteins, we used RalB as the bait to screen a human testes cDNA expression library using the yeast 2-hybrid system. The results demonstrated that 1 of the RalB interacting clones represented the C-terminal region of the β1 subunit of Na+/K+-ATPase. Further analysis using the yeast 2-hybrid system and full-length β1 subunit of Na+/K+-ATPase confirmed the interaction with RalA and RalB. In vitro binding and pull-down assays demonstrated that the β1 subunit of Na+/K+-ATPase interacts directly with RalA and RalB. Ral-GTP pull-down assays demonstrated that short-term ouabain treatment of A7r5 cells, a rat aorta smooth muscle cell line, caused activation of Ral GTPase. Maximal activation was observed 10 min after ouabain treatment. Ouabain-mediated Ral activation was inhibited upon the stimulation of Na+/K+-ATPase activity by Ang II. We propose that Ral GTPase is involved in the signal transducing function of Na+/K+-ATPase and provides a possible molecular mechanism connecting Ral to cardiac hypertrophy during diseased conditions.
Insulin withdrawal induces apoptosis via a free radical-mediated mechanismThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.
Authors: Ricci Craig , Pastukh Viktor , Mozaffari Mahmood , Schaffer Stephen W.
Published: July 2007

Diabetes is characterized by chronic hyperglycemia as well as insulin deficiency or resistance. However, the majority of research has focused on the consequences of hyperglycemia in development of diabetic complications, whereas the effects of insulin deficiency or resistance, independent of hyperglycemia, have received little attention. Since insulin is a well known cytoprotective factor, we hypothesized that its removal could significantly impact cell survival. To examine this possibility, cultured neonatal cardiomyocytes were subjected to insulin withdrawal and examined for apoptosis. Insulin deficient cells succumbed to apoptosis, an effect associated with impaired PI3-kinase/Akt signaling and reduction in the Bcl-2 to Bax ratio. Perhaps more importantly, superoxide generation was altered in cells subjected to insulin withdrawal. Removal of insulin caused a significant increase in reactive oxygen species production and resulted in oxidative mitochondrial DNA damage the latter effect is associated with impaired expression of mitochondrially encoded proteins that make up the electron transport chain. Significantly, the effects of insulin withdrawal could be mitigated by treatment with the antioxidant, Tiron. Collectively, these data demonstrate that insulin deficiency leads to apoptosis and suggest a role for oxidative mitochondrial DNA damage in this cascade.
LOW TEMPERATURE ELECTROLUMINESCENCE OF GREEN AND DEEP GREEN GaInN/GaN LIGHT EMITTING DIODES
Authors: Li Y. , Zhao W. , Xia Y. , Zhu M. , Senawiratne J. , Detchprohm T. , Wetzel C.
Published: July 2007

Electroluminescence of GaInN/GaN multiple-quantum-well (QW) light-emitting diodes emitting in the green spectral region is analyzed at variable low temperature. Spectra are dominated by QW emission at RT throughout 7.7 K. Below 150 K, donor-acceptor pair recombination appears that must be assigned to residual impurities in either the barriers or the p-layers. The current-voltage behavior reveals shunt paths that carry up to several mA at low bias voltages. Below 20 K those paths are frozen out, but the device still emits predominantly from the QW. The peak energy exhibits a blue shift from RT to 158 K followed by a red shift from 158 K to 7.7 K. The deeper binding energy at low temperatures can hardly be affect by the injection current indicating that saturation of low-density states cannot be responsible for the transition between red and blue shifts.
SPATIAL SPECTRAL ANALYSIS IN HIGH BRIGHTNESS GaInN/GaN LIGHT EMITTING DIODES
Authors: Detchprohm T. , Xia Y. , Senawiratne J. , Li Y. , Zhu M. , Zhao W. , Xi Y. , Schubert E. F. , Wetzel C.
Published: July 2007

We analyze GaInN based light emitting diodes emitting in the range of 400-550nm using a new intensity-quantitative spectroscopic cathodoluminescence mapping method. Spectroscopic information of arbitrary sample locations is generated from sequences of quantitative image scans. From the temperature dependence of the intensity, we derive thermal activation energies of the dominant loss processes. Those compare well with the hole binding energies in the piezoelectric and quantized quantum well structures.
TERAHERTZ SENSING OF MATERIALS
Authors: Xuan G. , Ghosh S. , Kim S. , Lv P-C. , Buma T. , Weng B. , Barner K. , Kolodzey J.
Published: July 2007

Biomolecules such as DNA and proteins exhibit a wealth of modes in the Terahertz (THz) range from the rotational, vibrational and stretching modes of biomolecules. Many materials such as drywall that are opaque to human eyes are transparent to THz. Therefore, it can be used as a powerful tool for biomolecular sensing, biomedical analysis and through-the-wall imaging. Experiments were carried out to study the absorption of various materials including DNA and see-through imaging of drywall using FTIR spectrometer and Time Domain Spectroscopy (TDS) system.
NON-VOLATILE HIGH SPEED & LOW POWER CHARGE TRAPPING DEVICES
Authors: Kim Moon Kyung , Tiwari Sandip
Published: July 2007

We report the operational characteristics of ultra-small-scaled SONOS (below 50 nm gate width and length) and SiO 2/ SiO 2 structural devices with 0.5 um gate width and length where trapping occurs in a very narrow region. The experimental work summarizes the memory characteristics of retention time, endurance cycles, and speed in SONOS and SiO 2/ SiO 2 structures. Silicon nitride has many defects to hold electrons as charge storage media in SONOS memory. Defects are also incorporated during growth and deposition in device processing. Our experiments show that the interface between two oxides, one grown and one deposited, provides a remarkable media for electron storage with a smaller gate stack and thus lower operating voltage. The exponential dependence of the time on the voltage is reflected in the characteristic energy. It is ~0.44 eV for the write process and ~0.47 eV for the erase process in SiO 2/ SiO 2 structural device which is somewhat more efficient than those of SONOS structure memory.
HYBRID NANOMATERIALS FOR MULTI-SPECTRAL INFRARED PHOTODETECTION
Authors: STIFF-ROBERTS ADRIENNE D.
Published: July 2007

Quantum dot infrared photodetectors (QDIPs) using quantum dots (QDs) grown by strained-layer epitaxy have demonstrated low dark current, multi-spectral response, high operating temperature, and infrared (IR) imaging. However, achieving near room-temperature, multi-spectral operation is a challenge due to randomness in QD properties. The ability to control dopant incorporation is important since charge carrier occupation influences dark current and IR spectral response. In this work, dopant incorporation is investigated in two classes of QDs; epitaxial InAs/GaAs QDs and CdSe colloidal QDs (CQDs) embedded in MEH-PPV conducting polymers. The long-term goal of this work is to combine these hybrid nanomaterials in a single device heterostructure to enable multi-spectral IR photodetection. Two important results towards this goal are discussed. First, by temperature-dependent dark current-voltage and polarization-dependent Fourier transform IR spectroscopy measurements in InAs/GaAs QDIPs featuring different doping schemes, we have provided experimental evidence for the important contribution of thermally-activated, defect-assisted, sequential resonant tunneling. Second, the enhanced quantum confinement and electron localization in the conduction band of CdSe / MEH-PPV nanocomposites enable intraband transitions in the mid-IR at room temperature. Further, by controlling the semiconductor substrate material, doping type, and doping level on which these nanocomposites are deposited, the intraband IR response can be tuned.
DEVELOPMENT AND VALIDATION OF PERFORMANCE MEASURES FOR WORLD CLASS MANUFACTURING PRACTICES IN INDIA
Authors: DIGALWAR ABHIJEET K. , SANGWAN KULDIP SINGH
Published: July 2007

This paper aims to develop and validate performance measures for world class manufacturing (WCM) in Indian context that could be used by managers/ practitioners in assessing and improving their manufacturing performance. Using a thorough synthesis of the world class manufacturing literature, sixteen performance measures — top management commitment, knowledge management, employee training, innovation and technology, employee empowerment, environmental health and safety, supplier management, production planning and control, quality, flexibility, speed, cost, customer involvement, customer satisfaction, customer services and company growth — of world class manufacturing and their 89 variables have been developed. Using the data obtained from a survey of manufacturing industries in India, the identified performance measures were subjected to appropriate statistical tests to establish reliability and validity. Statistical computing package SPSS 11.5 for Windows was used for reliability and validity analysis. The validated instrument of world class manufacturing measures developed here may be used by manufacturing organizations to prioritise their management efforts to assess and implement WCM. The validated results are in Indian context, however, the instrument developed can be used in global context.
Biogenesis and Function of Multivesicular Bodies
Authors: Piper Robert C. , Katzmann David J.
Published: July 2007

The two major cellular sites for membrane protein degradation are the proteasome and the lysosome. Ubiquitin attachment is a sorting signal for both degradation routes. For lysosomal degradation, ubiquitination triggers the sorting of cargo proteins into the lumen of late endosomal multivesicular bodies (MVBs)/endosomes. MVB formation occurs when a portion of the limiting membrane of an endosome invaginates and buds into its own lumen. Intralumenal vesicles are degraded when MVBs fuse to lysosomes. The proper delivery of proteins to the MVB interior relies on specific ubiquitination of cargo, recognition and sorting of ubiquitinated cargo to endosomal subdomains, and the formation and scission of cargo-filled intralumenal vesicles. Over the past five years, a number of proteins that may directly participate in these aspects of MVB function and biogenesis have been identified. However, major questions remain as to exactly what these proteins do at the molecular level and how they may accomplish these tasks.
The Effectiveness of Correctional Rehabilitation: A Review of Systematic Reviews
Authors: Lipsey Mark W. , Cullen Francis T.
Published: July 2007

The effects of correctional interventions on recidivism have important public safety implications when offenders are released from probation or prison. Hundreds of studies have been conducted on those effects, some investigating punitive approaches and some investigating rehabilitation treatments. Systematic reviews (meta-analyses) of those studies, while varying greatly in coverage and technique, display remarkable consistency in their overall findings. Supervision and sanctions, at best, show modest mean reductions in recidivism and, in some instances, have the opposite effect and increase reoffense rates. The mean recidivism effects found in studies of rehabilitation treatment, by comparison, are consistently positive and relatively large. There is, however, considerable variability in those effects associated with the type of treatment, how well it is implemented, and the nature of the offenders to whom it is applied. The specific sources of that variability have not been well explored, but some principles for effective treatment have emerged. The rehabilitation treatments generally found effective in research do not characterize current correctional practice, and bridging the gap between research and practice remains a significant challenge.
Cyclosporin inhibition of collagen remodeling is mediated by gelsolin
Authors: Chan Matthew W. C. , Arora Pamela D. , McCulloch Christopher A.
Published: July 2007

Cyclosporin A (CsA) inhibits collagen remodeling by interfering with the collagen-binding step of phagocytosis. In rapidly remodeling connective tissues such as human periodontium this interference manifests as marked tissue overgrowth and loss of function. Previous data have shown that CsA inhibits integrin-induced release of Ca2+ from internal stores, which is required for the binding step of collagen phagocytosis. Because gelsolin is a Ca2+-dependent actin-severing protein that mediates collagen phagocytosis, we determined whether gelsolin is a CsA target. Compared with vehicle controls, CsA treatment of wild-type mice increased collagen accumulation by 60% in periodontal tissues; equivalent increases were seen in vehicle-treated gelsolin-null mice. Collagen degradation by phagocytosis in cultured gelsolin wild-type fibroblasts was blocked by CsA, comparable to levels of vehicle-treated gelsolin-null fibroblasts. In wild-type cells treated with CsA, collagen binding was similar to that of gelsolin-null fibroblasts transfected with a gelsolin-severing mutant and treated with vehicle. CsA blocked collagen-induced Ca2+ fluxes subjacent to bound collagen beads, gelsolin recruitment, and actin assembly at bead sites. CsA reduced gelsolin-dependent severing of actin in wild-type cells to levels similar to those in gelsolin-null fibroblasts. We conclude that CsA-induced accumulation of collagen in the extracellular matrix involves disruption of the actin-severing properties of gelsolin, thereby inhibiting the binding step of collagen phagocytosis.
Activation of aconitase in mouse fast-twitch skeletal muscle during contraction-mediated oxidative stress
Authors: Zhang Shi-Jin , Sandström Marie E. , Lanner Johanna T. , Thorell Anders , Westerblad Håkan , Katz Abram
Published: July 2007

Aconitase is a mitochondrial enzyme that converts citrate to isocitrate in the tricarboxylic acid cycle and is inactivated by reactive oxygen species (ROS). We investigated the effect of exercise/contraction, which is associated with elevated ROS production, on aconitase activity in skeletal muscle. Humans cycled at 75% of maximal workload, followed by six 60-s bouts at 125% of maximum workload. Biopsies were taken from the thigh muscle at rest and after the submaximal and supramaximal workloads. Isolated mouse extensor digitorum longus (EDL; fast twitch) and soleus (slow twitch) muscles were stimulated to perform repeated contractions for 10 min. Muscles were analyzed for enzyme activities and glutathione status. Exercise did not affect aconitase activity in human muscle despite increased oxidative stress, as judged by elevated levels of oxidized glutathione. Similarly, repeated contractions did not alter aconitase activity in soleus muscle. In contrast, repeated contractions significantly increased aconitase activity in EDL muscle by ∼50%, despite increased ROS production. This increase was not associated with a change in the amount of immunoreactive aconitase (Western blot) but was markedly inhibited by cyclosporin A, an inhibitor of the protein phosphatase calcineurin. Immunoprecipitation experiments demonstrated that aconitase was phosphorylated on serine residues. Aconitase in cell-free extracts was inactivated by the addition of the ROS hydrogen peroxide. In conclusion, the results suggest that aconitase activity can be regulated by at least two mechanisms: oxidation/reduction and phosphorylation/dephosphorylation. During contraction, a ROS-mediated inactivation of aconitase can be overcome, possibly by dephosphorylation of the enzyme. The dual-control system may be important in maintaining aerobic ATP production during muscle contraction.
The effect of insulin on net lipid oxidation predicts worsening of insulin resistance and development of type 2 diabetes mellitus
Authors: Koska Juraj , Ortega Emilio , Bogardus Clifton , Krakoff Jonathan , Bunt Joy C.
Published: July 2007

Suppression of lipid oxidation (Lox) by insulin is impaired in obesity and type 2 diabetes mellitus (T2DM). Here we tested whether high Lox represents a primary or acquired characteristic in the pathogenesis of T2DM. Hood-indirect calorimetry was performed under postabsorptive conditions and during a two-step hyperinsulinemic euglycemic clamp (insulin infusion rates in mU·m−2·min−1: 40 low and 400 high) in 465 Pima Indians: 317 with normal glucose tolerance (NGT), 117 with impaired glucose tolerance (IGT), and 31 with T2DM. The predictive effect of net lipid oxidation (Lox) on development of T2DM was assessed in 296 subjects (51 of whom developed T2DM), whereas the predictive effect of Lox on followup changes in insulin-mediated glucose disposal (M) and acute insulin response (AIR) was studied in 190 subjects with NGT at baseline. Cross-sectionally, after adjustment for age, sex, body fat (BF), and M low, Lox low was increased in T2DM compared with NGT and IGT subjects ( P < 0.05). Prospectively, after adjustment for followup duration, age, sex, BF, M, and AIR, increased clamp Lox predicted T2DM [hazard rate ratios (95% CI): Lox low, 1.5 (1.1, 2.0), P < 0.01; Lox high, 1.3 (1.0, 1.8), P = 0.05]. High Lox low at baseline was also associated with subsequent worsening of M low ( P = 0.04). These data indicate that the inability of insulin to suppress Lox may represent an early risk marker for insulin resistance and T2DM that is independent of adiposity, acute insulin secretion, and insulin action on glucose uptake.
Zinc dyshomeostasis in rats with aldosteronism. Response to spironolactone
Authors: Thomas Manesh , Vidal Alex , Bhattacharya Syamal K. , Ahokas Robert A. , Sun Yao , Gerling Ivan C. , Weber Karl T.
Published: July 2007

Zinc is a structural constituent of many proteins, including Cu/Zn superoxide dismutase (SOD), an endogenous antioxidant enzyme. Hypozincemia has been found in patients hospitalized with congestive heart failure, where neurohormonal activation, including the renin-angiotensin-aldosterone system (RAAS), is expected and oxidative stress is present. This study was undertaken to elucidate potential pathophysiological mechanisms involved in Zn dyshomeostasis in aldosteronism. In rats receiving aldosterone/salt treatment (ALDOST) alone for 1 and 4 wk or in combination with spironolactone (Spiro), an ALDO receptor antagonist, we monitored 24-h urinary and fecal Zn excretion and tissue Zn levels in heart, liver, and skeletal muscle, together with tissue metallothionein (MT)-I, a Zn2+-binding protein, and Cu/Zn-SOD activities in plasma and tissues. When compared with unoperated, untreated, age-/sex-matched controls, urinary and, in particular, fecal Zn losses were markedly increased ( P < 0.05) at days 7 and 28 of ALDOST, leading to hypozincemia and a fall ( P < 0.05) in plasma Cu/Zn-SOD activity. Microscopic scars and perivascular fibrosis of intramural coronary arteries first appeared in the right and left ventricles at week 4 of ALDOST and were accompanied by increased ( P < 0.05) tissue Zn, MT-I, and Cu/Zn-SOD activity, which were not found in uninjured liver or skeletal muscle. Spiro cotreatment prevented cardiac injury and Zn redistribution to the heart. Thus increased urinary and fecal Zn losses, together with their preferential translocation to sites of cardiac injury, where MT-I overexpression and increased Cu/Zn-SOD activity appeared, contribute to Zn dyshomeostasis in rats with aldosteronism, which were each prevented by Spiro. These findings may shed light on Zn dyshomeostasis found in patients with decompensated heart failure.
Reduced central blood volume and cardiac output and increased vascular resistance during static handgrip exercise in postural tachycardia syndrome
Authors: Stewart Julian M. , Taneja Indu , Medow Marvin S.
Published: July 2007

Postural tachycardia syndrome (POTS) is characterized by exercise intolerance and sympathoactivation. To examine whether abnormal cardiac output and central blood volume changes occur during exercise in POTS, we studied 29 patients with POTS (17–29 yr) and 12 healthy subjects (18–27 yr) using impedance and venous occlusion plethysmography to assess regional blood volumes and flows during supine static handgrip to evoke the exercise pressor reflex. POTS was subgrouped into normal and low-flow groups based on calf blood flow. We examined autonomic effects with variability techniques. During handgrip, systolic blood pressure increased from 112 ± 4 to 139 ± 9 mmHg in control, from 119 ± 6 to 143 ± 9 in normal-flow POTS, but only from 117 ± 4 to 128 ± 6 in low-flow POTS. Heart rate increased from 63 ± 6 to 82 ± 4 beats/min in control, 76 ± 3 to 92 ± 6 beats/min in normal-flow POTS, and 88 ± 4 to 100 ± 6 beats/min in low-flow POTS. Heart rate variability and coherence markedly decreased in low-flow POTS, indicating uncoupling of baroreflex heart rate regulation. The increase in central blood volume with handgrip was absent in low-flow POTS and blunted in normal-flow POTS associated with abnormal splanchnic emptying. Cardiac output increased in control, was unchanged in low-flow POTS, and was attenuated in normal-flow POTS. Total peripheral resistance was increased compared with control in all POTS. The exercise pressor reflex was attenuated in low-flow POTS. While increased cardiac output and central blood volume characterizes controls, increased peripheral resistance with blunted or eliminated in central blood volume increments characterizes POTS and may contribute to exercise intolerance.
Effects of acetazolamide on aerobic exercise capacity and pulmonary hemodynamics at high altitudes
Authors: Faoro Vitalie , Huez Sandrine , Giltaire Sébastien , Pavelescu Adriana , van Osta Aurélie , Moraine Jean-Jacques , Guenard Hervé , Martinot Jean-Benoît , Naeije Robert
Published: July 2007

Aerobic exercise capacity is decreased at altitude because of combined decreases in arterial oxygenation and in cardiac output. Hypoxic pulmonary vasoconstriction could limit cardiac output in hypoxia. We tested the hypothesis that acetazolamide could improve exercise capacity at altitude by an increased arterial oxygenation and an inhibition of hypoxic pulmonary vasoconstriction. Resting and exercise pulmonary artery pressure (Ppa) and flow (Q) (Doppler echocardiography) and exercise capacity (cardiopulmonary exercise test) were determined at sea level, 10 days after arrival on the Bolivian altiplano, at Huayna Potosi (4,700 m), and again after the intake of 250 mg acetazolamide vs. a placebo three times a day for 24 h. Acetazolamide and placebo were administered double-blind and in a random sequence. Altitude shifted Ppa/Q plots to higher pressures and decreased maximum O2consumption (V̇o2max). Acetazolamide had no effect on Ppa/Q plots but increased arterial O2saturation at rest from 84 ± 5 to 90 ± 3% ( P < 0.05) and at exercise from 79 ± 6 to 83 ± 4% ( P < 0.05), and O2consumption at the anaerobic threshold (V-slope method) from 21 ± 5 to 25 ± 5 ml·min−1·kg−1( P < 0.01). However, acetazolamide did not affect V̇o2max(from 31 ± 6 to 29 ± 7 ml·kg−1·min−1), and the maximum respiratory exchange ratio decreased from 1.2 ± 0.06 to 1.05 ± 0.03 ( P < 0.001). We conclude that acetazolamide does not affect maximum exercise capacity or pulmonary hemodynamics at high altitudes. Associated changes in the respiratory exchange ratio may be due to altered CO2production kinetics.
Trial-by-Trial Transformation of Error Into Sensorimotor Adaptation Changes With Environmental Dynamics
Authors: Fine Michael S. , Thoroughman Kurt A.
Published: July 2007

Humans can rapidly change their motor output to make goal-directed reaching movements in a new environment. Theories that describe this adaptive process have long presumed that adaptive steps scale proportionally with error. Here we show that while performing a novel reaching task, participants did not adopt a fixed learning rule, but instead modified their adaptive response based on the statistical properties of the movement environment. We found that as the directional bias of the force distribution shifted from strongly biased to unbiased, participants transitioned from an adaptive process that scaled proportionally with error to one that adapted to the direction, but not magnitude, of error. Participants also modified their response as the likelihood of the perturbation changed; as the likelihood decreased from 80 to 20% of trials, participants adopted an increasingly disproportional strategy. We propose that people can rapidly switch between learning processes within minutes of experiencing a novel environment.
Voltage Imaging Reveals the CA1 Region at the CA2 Border as a Focus for Epileptiform Discharges and Long-Term Potentiation in Hippocampal Slices
Authors: Chang Payne Y. , Taylor Portia E. , Jackson Meyer B.
Published: July 2007

Voltage-sensitive-dye imaging was used to study the initiation and propagation of epileptiform activity in transverse hippocampal slices. A portion of the slices tested generated epileptiform discharges in response to electrical shocks under normal physiological conditions. The fraction of slices showing epileptiform responses increased from 44 to 86% when bathing [K+] increased from 3.2 to 4 mM. Regardless of stimulation site in the dentate gyrus and hippocampus, discharges generally initiated in the CA3 region. After onset, discharges abruptly appeared in the CA1 region, right at the CA2 border. This spread from the CA3 region to the CA1 region was saltatory, occurring before detectable activity in the intervening CA2 and CA3 regions. Discharges did eventually propagate smoothly through the intervening CA3 region into the CA2 region, but on a slower timescale. The surge in the CA1 region did not spread back into the CA2 region, but spread through the CA1 region toward the subiculum. Tetanic stimulation, theta bursts, and GABAAreceptor antagonists failed to alter this characteristic pattern, but did reduce the latency of discharge onset. The part of the CA1 region at the CA2 border, where epileptic responses emerged with relatively short latency, also expressed stronger long-term potentiation (LTP) than the rest of the CA1 region. The CA2 region, where discharges had long latencies and low amplitudes, expressed weaker LTP. Thus the CA1 region at the CA2 border has unique properties, which make this part of the hippocampus an important locus for both epileptiform activity and plasticity.
Dual GABAergic Synaptic Response of Fast Excitation and Slow Inhibition in the Medial Habenula of Rat Epithalamus
Authors: Kim Uhnoh , Chung Lee-yup
Published: July 2007

We report here a novel action of GABAergic synapses in regulating tonic firing in the mammalian brain. By using gramicidin-perforated patch recording in rat brain slices, we show that cells of the medial habenula of the epithalamus generate tonic firing in basal conditions. The GABAergic input onto these cells at postnatal days 18–25 generates a combinatorial activation of fast excitation and slow inhibition. The fast excitation, mediated by γ-aminobutyric acid type A receptors (GABAARs), is alone capable of triggering robust action potentials to increase cell firing. This excitatory influence of GABAergic input results from the Cl− homeostasis that maintains intracellular Cl− at high levels. The GABAA excitation is often followed by a slow inhibition mediated by GABABRs that suppresses tonic firing. Interestingly, in a subpopulation of the cells, the GABAB inhibition exhibits a remarkably low threshold for synaptic activation in that low-strength GABAergic input often activates selectively the GABAB slow inhibition, whereas the GABAA excitation requires further increases in stimulus strength. Our study demonstrates that the dual activation of GABAergic excitation and inhibition through GABAARs and GABABRs generates distinct temporal patterns of cell firing that alter the cellular output in an activity-dependent manner.