bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring pyrethroid resistance in field collected Blattella germanica Linn. (Dictyoptera: Blattellidae) in Indonesia
Authors: AHMAD Intan ,   SRIWAHJUNINGSIH, ASTARI Sita , PUTRA Ramadhani Eka , PERMANA Agus Dana
Published: March 2009

The German cockroach, Blattella germanica, is a major and the most common pest in public areas in Indonesia. Although intensive control measures have been carried out to control the populations of this pest, results have been far from successful, which is believed to be because of its resistance to insecticides. A standard World Health Organization (WHO) glass jar test was carried out to determine the resistance level of this insect to pyrethroid insecticides, the most commonly used insecticides for cockroach control in Indonesia. A susceptible S1 strain collected from Tembagapura Papua was compared with four strains collected from Bandung, West Java: strain S2, from a local restaurant; strain S3, from the Bandung train station; and strains S4 and S5, from two different hotels. All strains showed low resistance to the pyrethroid, except the S5 strain, which had a Resistance Ratio (RR)50 of 95 for permethrin. The addition of piperonyl butoxide (PBO) suggests that the detoxifying enzyme mixed function oxidases (MFO) played an important role in the development of resistance to permethrin in the S5 strain, suggested by the high Synergist Ratio (SR) of 70.4. However, the low level of resistance to cypermethrin was not affected by PBO, suggesting that other mechanisms of pyrethroid resistance are involved. Our study is the first report of German cockroach resistance to permethrin in Indonesia, and the findings can be used in formulating potential strategies for cockroach resistance management.
Molecular cloning and expression pattern of 14‐3‐3ζ from the malaria vector, Anopheles sinensis
Authors: JO Yong Hun , NOH Mi Young , KANG Se Won , KIM Dong Hyun , OH Seung Han , LEE Yong Seok , BANG In Seok , SEO Sook Jae , KIM Iksoo , HAN Yeon Soo
Published: March 2009

14‐3‐3 proteins are known to play a pivotal role in cell survival, apoptosis and signal transduction. The 14‐3‐3ζ isoform has been cloned and characterized from many eukaryotic organisms, including the fruit fly and silkworm. However, no study on mosquito 14‐3‐3 has been reported to date. In an attempt to investigate the function of 14‐3‐3 in midgut epithelial cells undergoing apoptosis, a cDNA library was generated from the malaria vector, Anopheles sinensis, which was treated with apoptosis‐inducing Actinomycin‐D. We were able to identify and obtain A. sinensis 14‐3‐3ζ cDNA (Ansi14‐3‐3ζ) from expressed sequence tags (EST) analysis after conducting massive sequencing of the A. sinensis cDNA library. Ansi14‐3‐3ζ has very high homology to 14‐3‐3 homologs of various insects, such as Anopheles gambiae (100%), Aedes aegypti (100%), Drosophila melanogaster (96%), Bombyx mori (93%), Apis mellifera (93%) and Mus musculus (81%), indicating that mosquito 14‐3‐3ζ is a highly conserved gene in diverse organisms. Analysis of temporal expression patterns showed that Ansi14‐3‐3ζ mRNA is highly expressed in egg, early pupae and adult stages and is also expressed, although at low levels, in fourth instar larvae and late pupae. In response to two immune elicitors (lipopolysaccharide and laminarin), no striking induction of 14‐3‐3ζ mRNA was observed in A. sinensis. Further studies of the precise biological function, inducibility and subcellular distribution of 14‐3‐3ζ are required in Plasmodium invasion‐induced apoptotic midgut cells in A. sinensis in the context of the Time Bomb model.
Ultraviolet Light (254 nm) Inactivation of Listeria monocytogenes on Frankfurters That Contain Potassium Lactate and Sodium Diacetate
Authors: Sommers C.H. , Cooke P.H. , Fan X. , Sites J.E.
Published: March 2009

ABSTRACT:  Listeria monocytogenes, a psychrotrophic foodborne pathogen, is an occasional postprocess contaminant on ready‐to‐eat meat (RTE) products including frankfurters. Ultraviolet C light (UVC) is an FDA‐approved technology for the decontamination of food surfaces. In this study, the ability of UVC to inactivate L. monocytogenes on frankfurters that contained potassium lactate (PL) and sodium diacetate (SDA), either before or after packaging, was investigated. UVC irradiation of frankfurters that were surface‐inoculated with L. monocytogenes resulted in a 1.31, 1.49, and 1.93 log reduction at doses of 1, 2, and 4 J/cm2, respectively. UVC treatment had no effect on frankfurter color or texture at UVC doses up to 4 J/cm2. Frankfurter meat treated with UVC doses up to 16 J/cm2 did not increase mutagenesis in bacterial or human cells, either with or without exogenous metabolic activation. UVC treatment of single‐layer frankfurter packs at a dose of 2 J/cm2 resulted in a 0.97 (± 0.14) log reduction of L. monocytogenes. Following 8 wk of refrigerated storage L. monocytogenes levels decreased by only 0.65 log in non‐UVC‐treated frankfurter packs compared with 2.5 log in the UVC‐treated packs. Because the numbers of L. monocytogenes associated with contaminations of ready‐to‐eat meats are typically very low, the use of UVC in combination with potassium lactate and sodium diacetate has the potential to reduce the number of frankfurter recalls and foodborne illness outbreaks.
Aroma Evaluation of Transgenic, Thaumatin II‐Producing Cucumber Fruits
Authors: Zawirska‐Wojtasiak R. , Gośliński M. , Szwacka M. , Gajc‐Wolska J. , Mildner‐Szkudlarz S.
Published: March 2009

ABSTRACT: Fruits of transgenic cucumber lines expressing preprothaumatin II gene were evaluated concerning their aroma. Four homozygous lines, that is, 210 06, 212 01, 224 09, and 225 03 with different levels of transgene expression were selected. Recipient line cv. Borszczagowski, which was formed by inbred line ofCucumis sativusL., was used as a control. The experiment was carried out in a greenhouse and an outdoor experimental plot. The aroma of cucumber fruits was evaluated by GC/MS, as well as GC/MS/TOF in the distillates and by SPME. Irrespective of the isolation/separation technique used, the differences between aroma compounds in transgenic cucumbers and the control were quantitative, and not qualitative. Modified samples showed higher concentrations of volatiles, particularly of the main cucumber fruits odorant (E, Z)‐2,6 nonadienal. Transgenic expression of the thaumatin II gene resulted not only in a sweeter taste of fruits in comparison with the control, but also higher aroma acceptability. This was shown by sensory profile analysis. Also electronic nose measurements differentiated between transgenic lines and the control.
Noninvasive Markers of Airway Inflammation in Asthma
Authors: Wedes Samuel H. , Khatri Sumita B. , Zhang Renliang , Wu Weijia , Comhair Suzy A. A. , Wenzel Sally , Teague William G. , Israel Elliot , Erzurum Serpil C. , Hazen Stanley L.
Published: March 2009

Background: Although airway inflammation plays a major role in the pathophysiology of asthma, quantitative markers of airway nflammation are limited in clinical practice.

Objective: To determine if the levels of noninvasive markers of eosinophil‐catalyzed oxidation, lipid peroxidation, and nitric oxide (NO) production are associated with asthma.

Methods: Participants were enrolled from academic medical centers participating in the Severe Asthma Research Program. Clinical characteristics, laboratory data, pulmonary function tests, and the levels of the following noninvasive markers were obtained: urinary bromotyrosine (BrTyr), a marker of eosinophil‐catalyzed oxidation, urinary F2‐isoprostanes (F2‐lsoPs), markers of lipid peroxidation, and exhaled NO, a marker of airway inflammation.

Results: Fifty‐seven asthmatic participants and 38 healthy participants were enrolled. BrTyr, F2‐lsoPs, and exhaled NO were each significantly increased in asthmatic participants versus controls (p < 0.01). An elevated level (greater than the median) of any marker was associated with a significant 3‐ to 6‐fold greater odds of having asthma. Participants with two or more elevated marker levels showed an 18‐fold greater odds of having asthma. Relationships were also noted with airflow obstruction and bronchodilator response.

Conclusion: The findings from this pilot study indicate that urinary levels of BrTyr and F2‐lsoPs, in addition to exhaled NO levels, are associated with asthma.
On the influence of oil prices on economic activity and other macroeconomic and financial variables*
Authors: Lescaroux François , Mignon Valérie
Published: March 2009

The aim of this paper is to investigate the links between oil prices and various macroeconomic and financial variables for a large set of countries, including both oil‐importing and oil‐exporting countries. Both short‐run and long‐run interactions are analysed through the implementation of Granger‐causality tests, evaluation of cross correlations between the cyclical components of the series in order to identify lead/lag relationships and cointegration analysis. Our results highlight the existence of various relationships between oil prices and macroeconomic variables and, especially, an important link between oil and share prices on the short run. Turning to the long run, numerous long‐term relationships are detected, the Granger‐causality generally running from oil prices to the other variables. An important conclusion is relating to the key role played by the oil market on stock markets.
Acute visual loss after spinal surgery
Authors: Hoff Jana Midelfart , Varhaug Pål , Midelfart Anna , Lund‐Johansen Morten
Published: March 2009

Purpose:  To report visual loss after prone spinal surgery.

Methods:  Computed tomography scan, fundus photography, optical coherence tomography (OCT).

Results:  A 56‐year‐old man demonstrated loss of vision in the left eye after cervical spinal surgery. Clinical examination revealed loss of vision to finger counting, severe visual field defect and blurred neural rim area around the optic disc in the left eye. Six weeks later, visual acuity in the left eye was 6/9 and there was inferior visual field defect. Six months after the surgery, significant reduction of retinal nerve fibre layer thickness around the optic nerve head was measured with OCT, consistent with the visual field defect.

Conclusion:  Ischemic optic neuropathy is the most common cause of visual loss after spine surgery and special emphasis should be given to protect the eye against possible pressure during the surgery.
Pancytopenia in a cat with visceral leishmaniasis
Authors: Marcos Ricardo , Santos Marta , Malhão Fernanda , Pereira Rui , Fernandes Ana Cristina , Montenegro Luís , Roccabianca Paola
Published: March 2009

Abstract: A 4‐year‐old, domestic shorthair, female spayed cat was presented for decreased appetite and depression. Severe pancytopenia with erythrocyte autoagglutination was found. The cat was seronegative for feline immunodeficiency and leukemia viruses. Immune‐mediated hemolytic anemia was suspected but no response to treatment with a blood transfusion, enrofloxacin, and prednisone was observed. Blood and bone marrow smears obtained 11 days later contained Leishmania amastigotes in the cytoplasm of neutrophils and macrophages, respectively. Serologic and PCR testing of peripheral blood confirmed infection with Leishmania infantum. Despite treatment, the cat worsened clinically and was euthanized. At necropsy, visceral dissemination of the parasite was confirmed. The findings in this case indicate that visceral leishmaniasis should be considered as a differential diagnoses in cats with pancytopenia in areas endemic for Leishmania. In addition, amastigotes may be observed in peripheral blood neutrophils.
Anticoagulant‐dependent in vitro hemagglutination in a cat
Authors: Schaefer Deanna M.W. , Priest Heather , Stokol Tracy , Goldstein Richard E. , Belcher Nicole
Published: March 2009

Abstract:A 17‐year‐old domestic shorthaired cat was presented to the Cornell University Hospital for Animals for recheck of hyperthyroidism previously treated with radioiodine. Marked agglutination was noted in a blood sample collected into EDTA for a CBC; no other clinical or hematologic evidence of hemolysis was observed and none developed despite persistent agglutination in additional EDTA samples collected over a 2‐month period. Blood drawn into heparin and sodium citrate tubes did not have grossly or microscopically detectable agglutination, unless EDTA was added. Plasma from the cat induced agglutination of washed RBCs from a control cat in the presence of EDTA but not in the presence of heparin. Flow cytometric analysis of samples created by mixing plasma from the patient with washed RBCs from a control cat showed immunoglobulin coating of the control RBCs, predominantly by IgM. These findings suggested an anticoagulant‐dependent antibody‐mediated mechanism for the agglutination. EDTA‐dependent hemagglutination has not been reported previously in cats, although rare cases have been described in humans. The phenomenon needs to be recognized as an in vitro occurrence in order to prevent erroneous diagnosis of immune‐mediated hemolytic anemia.
Mechanism Maps for Frictional Attachment Between Fibrillar Surfaces
Authors: McMeeking Robert M. , Ma Lifeng , Arzt Eduard
Published: March 2009

The mechanics of frictional attachment between surfaces with pillars, inspired by the head fixation system of dragonflies, is analyzed. The system consists of two surfaces of interdigitating pillars held together through friction, as by the densely packed bristles of two brushes when pressed together. The adhesive strength of the system is promoted by high elastic modulus, high friction coefficient, large aspect ratio, and dense packing of the fibers. However, the design is limited by the compressive buckling, the compressive indentation or cracking of the contacting pillars, yielding in shear or similar mechanisms that limit the achievable friction stress, and tensile failure of the pillars upon pull-out. Maps, which summarize the strength of the adhesive system and the failure limits and illustrate the trade-off among the design parameters, are presented. Case studies for steel, nylon, and ceramic pillars show that useful strength can be achieved in such attachments; when buckling during assembly and contact failure can be avoided, adhesive performance as high as 30% of the tensile strength of the pillar material may be possible.
Symmetrical Solutions for Edge-Loaded Annular Elastic Membranes
Authors: Yu Weiwei , Karr Dale G.
Published: March 2009

The Föppl–Hencky nonlinear membrane theory is employed to study the axisymmetric deformation of annular elastic membranes. The general solutions for displacements and stresses are established for arbitrary edge boundary conditions. New exact solution results are developed for central loading and edge forcing conditions. Both positive and negative radial stress solutions are found. Comparisons are made for special cases to previously known solutions with excellent agreement.
Compression of Viscoplastic Material Between Rotating Plates
Authors: Alexandrov Sergei , Jeng Yeau-Ren
Published: March 2009

An analysis is conducted of the two-dimensional flow of Bingham solids between two rotating plates. The maximum friction law is adopted at the plate surface. An asymptotic analysis of the solution is performed in the vicinity of the friction surface. Its results are used in a numerical procedure to obtain an accurate approximation of the solution near the friction surface. The through thickness distribution of velocities, the equivalent strain rate, and stresses is illustrated. Qualitative features of the solution are emphasized. The results are compared with the solution for rate-independent materials.
Suppressing Flutter Vibrations by Parametric Inertia Excitation
Authors: Dohnal Fadi , Tondl Aleš
Published: March 2009

A theoretical study of a slender engineering structure with lateral and angular deflections is investigated under the action of flow-induced vibrations. This aero-elastic instability excites and couples the system’s bending and torsion modes. Semiactive means due to open-loop parametric excitation are introduced to stabilize this self-excitation mechanism. The parametric excitation mechanism is modeled by time-harmonic variation in the concentrated mass and/or moment of inertia. The conditions for full suppression of the self-excited vibrations are determined analytically and compared with numerical results of an example system. For the first time, example systems are presented for which parametric antiresonance is established at the parametric combination frequency of the sum type.
Kinematic Measurements from YouTube Videos
Authors: Ruiz Michael J.
Published: March 2009

Video analysis of motion has been in use now for some time.1–3 However, some teachers may not have video equipment or may be looking for innovative ways to engage students with interesting applications at no cost. The recent advent of YouTube offers opportunities for students to measure kinematic properties of real-life events using their computers. This paper provides examples such as measuring the average speed of a winning horse at the Kentucky Derby, plotting speed versus time from watching the speedometer of a high-performance bike, and determining acceleration for circular motion of amusement park rides.
Circadian Control of the NAD
+
Salvage Pathway by CLOCK-SIRT1
Authors: Nakahata Yasukazu , Sahar Saurabh , Astarita Giuseppe , Kaluzova Milota , Sassone-Corsi Paolo
Published: March 2009

Circadian Oscillations

The 24-hour day-night cycle plays an important role in mammalian physiology and behavior and, as most travelers are well aware, there is an intimate link between our in-built circadian clocks and metabolic rhythms. This link is in part forged by the protein deacetylase SIRT1, which regulates the clock's molecular circuitry. SIRT1 uses as a cofactor the cellular metabolite NAD
+
, which is synthesized through a salvage pathway that includes the enzyme nicotinamide phosphoribosyltransferase (NAMPT) (see the Perspective by

Wijnen

).

Ramsey
et al.

(p.
651
; published online 19 March) and

Nakahata
et al.

(p.
654
, published online 12 March) now show that NAMPT and NAD
+
levels oscillate during the daily 24-hour cycle and that this oscillation is regulated by the circadian clock. Furthermore, the oscillations in NAD
+
modulate the activity of SIRT1 feeding back into the circadian clock.
Steroid profiles of professional soccer players: an international comparative study
Authors: Strahm E , Sottas P-E , Schweizer C , Saugy M , Dvorak J , Saudan C
Published: March 2009

Background and objectives:

Urinary steroid profiling is used in doping controls to detect testosterone abuse. A testosterone over epitestosterone (T/E) ratio exceeding 4.0 is considered as suspicious of testosterone administration, irrespectively of individual heterogeneous factors such as the athlete’s ethnicity. A deletion polymorphism in the UGT2B17 gene was demonstrated to account for a significant part of the interindividual variability in the T/E between Caucasians and Asians. Here, the variability of urinary steroid profiles was examined in a widely heterogeneous cohort of professional soccer players.

Method:

The steroid profile of 57 Africans, 32 Asians, 50 Caucasians and 32 Hispanics was determined by gas chromatography–mass spectrometry.

Results:

Significant differences have been observed between all ethnic groups. After estimation of the prevalence of the UGT2B17 deletion/deletion genotype (African: 22%; Asian: 81%; Caucasian: 10%; Hispanic: 7%), ethnic-specific thresholds were developed for a specificity of 99% for the T/E (African: 5.6; Asian: 3.8; Caucasian: 5.7; Hispanic: 5.8). Finally, another polymorphism could be hypothesised in Asians based on specific concentration ratio of 5α-/5β-androstane-3α,17β-diol in urine.

Conclusion:

These results demonstrate that a unique and non-specific threshold to evidence testosterone misuse is not fit for purpose. An athlete’s endocrinological passport consisting of a longitudinal follow-up together with the ethnicity and/or the genotype would strongly enhance the detection of testosterone abuse. Finally, additional genotyping studies should be undertaken to determine whether the remaining unexplained disparities have an environmental or a genetic origin.
SELF-CONSISTENT DISTRIBUTIONS FOR CHARGED PARTICLE BEAM IN MAGNETIC FIELD
Authors: DRIVOTIN OLEG I. , OVSYANNIKOV DMITRI A.
Published: March 2009

The problem of constructing self-consistent stationary particle distributions in four-dimensional phase space is considered for an azimuthally symmetric charged particle beam in a longitudinal magnetic field. In the general case of a longitudinally nonuniform beam, it is assumed that the magnetic field and the radius of the beam cross-section can slowly vary in the axial direction. The simplest case of a longitudinally uniform beam is studied in more detail. The approach applied here is to analyze the particle density in the space of integrals of motion. The relations between this density, the phase density, and the density in the configuration space are obtained. The set of admissible values of integrals of motion for a radially confined beam is examined. The construction of new self-consistent distributions consists in the specifying of some function defined on this set. Wide classes of new distributions are found. In particular cases, some of these distributions are identical to those known before, for example, the Kapchinsky-Vladimirsky distribution.
INVESTIGATION AND OPTIMIZATION OF LOW-ENERGY HEAVY-ION BEAM DYNAMICS IN PERIODIC AXISYMMETRICAL STRUCTURES WITH DC FOCUSING
Authors: DYUBKOV VYACHESLAV SERGEEVICH , MASUNOV EDUARD SERGEEVICH
Published: March 2009

It is well-known that nonsynchronous harmonics of a RF field can focus particles. In order to focus ultra-low energy beam particles, a spatially periodic electrostatic field can be used, too. In this case the transverse focusing is provided by a periodic array of electrostatic lenses. This article is dedicated to questions of two high-current low-energy beam focusing types used in an injector-buncher of an ion linear accelerator, an application of a spatially periodic electrostatic focusing being examined for the first time. A two-dimensional nonlinear motion equation is derived in the Hamiltonian form in a smooth approximation. It allows us to study a correlation between the longitudinal and transverse ion beam dynamics at low energies. An investigation of the phase and transverse beam dynamics stability conditions in the initial part of the linac are given consideration. Conditions of the beam dynamics stability are found and analyzed. An approach to the field optimization problem is described. A method of the geometric parameter choice is worked out for a realization of the required field distributions in each structure. To verify the results of the beam dynamics stability analysis and optimized structure parameter choice, numerical simulations of low-energy heavy-ion beams are carried out.
PARAMETRIC OPTIMIZATION METHODS FOR THE TOKAMAK PLASMA CONTROL PROBLEM
Authors: ZAVADSKY SERGEY V. , OVSYANNIKOV DMITRI A. , CHUNG SHENG-LUEN
Published: March 2009

Mathematical models of the structural parametric optimization of plasma dynamics are discussed. Optimization approach to plasma dynamic is based on the consideration of trajectory ensemble. This ensemble describes transient process in tokamak subject to the initial data and external disturbances. In the framework of this approach the optimization of dynamics of the trajectory ensemble in ITER tokamak is given. The trajectories of this ensemble are perturbed at the initial point set and the set of external disturbances.
SOME H-OPTIMIZATION PROBLEMS FOR THE ITER PLASMA CONTROL SYSTEM
Authors: ZHABKO NATALIA A.
Published: March 2009

Some ideas concerning the application of methods of H-optimization theory in practice are discussed in this work. The problem of plasma current and shape stabilization system synthesis in tokamak ITER is considered as an application of discussed ideas.
PATH INTEGRAL APPROACH TO A DAMPED AND DRIVEN OSCILLATOR COUPLED WITH ANOTHER ONE
Authors: THRAPSANIOTIS E. G.
Published: March 2009

We approach the case of two coupled oscillators where the first one may correspond to a photonic field, while the second one is damped and driven. We model the oscillator's damping via a bath and consider the relevant master equation. We use perturbation theory to handle it. We then path integrate over the effective Hamiltonian of the two oscillators and derive the path integrated density matrix. We suppose that initially both of the oscillators are in coherent states and study the quadrature squeezing effect of the second oscillator.
VORTEX CREEP PERPENDICULAR TO THE c-AXIS IN CRYSTALLINE AND GRAIN-ORIENTED YBCO SUPERCONDUCTOR
Authors: OBAIDAT I. M. , GHARAIBEH M. , ALBISS B. A. , HASAN (QASEER) M. K.
Published: March 2009

Magnetization measurements were carried out on crystalline and grain-oriented YBa 2 Cu 3 O 7-δ samples. We have measured the creep of magnetic flux lines along the a-axis (perpendicular to the c-axis) of the crystalline sample and perpendicular to the c-axis of a c-axis-grain-oriented polycrystalline sample. The measurements were done at 4.2 K and for magnetic fields in the range 1 kOe < H < 10 kOe . The magnetization M was found to decrease linearly with ln t in both samples for all the applied magnetic fields. With the initial increase of the applied magnetic field, the vortex pinning potential, Up, was found to decrease sharply in the grain-oriented sample, followed by a slow (almost linear) rate of decrease. In the crystalline sample, the rate of decrease of Up was found to be slow and linear for all applied magnetic fields.
THERMODYNAMICS OF NONCOMMUTATIVE DE SITTER SPACE–TIME
Authors: VAKILI B. , KHOSRAVI N. , SEPANGI H. R.
Published: March 2009

We study the effects of noncommutativity of space–time geometry on the thermodynamical properties of the de Sitter horizon. We show that noncommutativity results in modifications in temperature, entropy and vacuum energy and that these modifications are of order of the Planck scale, suggesting that the size of the noncommutative parameter should be close to that of the Planck. In an alternative way to deal with noncommutativity, we obtain a quantization rule for the entropy. Since noncommutativity in space–time geometry modifies the Heisenberg algebra and introduces the general uncertainty principle, we also investigate the above problem in this framework.
CONFORMAL MOTIONS IN PLANE SYMMETRIC STATIC SPACE–TIMES
Authors: SAIFULLAH K. , SHAIR-E-YAZDAN
Published: March 2009

In this paper, conformal motions are studied in plane symmetric static space–times. The general solution of conformal Killing equations and the general form of the conformal Killing vector for these space–times are presented. All possibilities for the existence of conformal motions in these space–times are exhausted.
QUANTUM INTERFERENCE EFFECTS IN SLOWLY ROTATING NUT SPACE–TIME
Authors: MOROZOVA V. S. , AHMEDOV B. J.
Published: March 2009

General relativistic quantum interference effects in a slowly rotating NUT space–time, such as the Sagnac effect and the phase shift effect of interfering particles in a neutron interferometer, are considered. It was found that in the case of the Sagnac effect, the influence of the NUT parameter is becoming important due to the fact that the angular velocity of the locally nonrotating observer must be larger than the one in the Kerr space–time. In the case of neutron interferometry, it is found that due to the presence of the NUT parameter, an additional term in the phase shift of interfering particles emerges. This term can be, in principle, detected by a sensitive interferometer and the derived results could be further used in experiments to detect the gravitomagnetic charge. Finally, as an example, we apply the obtained results to the calculation of the UCN (ultra-cold neutrons) energy level modification in a slowly rotating NUT space–time.
Functional role of J domain of cysteine string protein in Ca2+-dependent secretion from acinar cells
Authors: Weng Ning , Baumler Megan D. , Thomas Diana D. H. , Falkowski Michelle A. , Swayne Leigh Anne , Braun Janice E. A. , Groblewski Guy E.
Published: March 2009

The heat shock protein 70 family members Hsc70 and Hsp70 are known to play a protective role against the onset of experimental pancreatitis, yet their molecular function in acini is unclear. Cysteine string protein (CSP-α) is a zymogen granule (ZG) membrane protein characterized by an NH2-terminal “J domain” and a central palmitoylated string of cysteine residues. The J domain functions as a cochaperone by modulating the activity of Hsc70/Hsp70 family members. A role for CSP-α in regulating digestive enzyme exocytosis from pancreas was investigated by introducing CSP-α truncations into isolated acini following their permeabilization with Perfringolysin O. Incubation of acini with CSP-α1-82, containing the J domain, significantly augmented Ca2+-stimulated amylase secretion. Effects of CSP-α1-82were concentration dependent, with a maximum 80% increase occurring at 200 μg/ml of protein. Although CSP-α1-82had no effects on basal secretion measured in the presence of ≤10 nM free Ca2+, it did significantly augment GTP-γS-induced secretion under basal Ca2+conditions by ∼25%. Mutation of the J domain to abolish its cochaperone activity failed to augment Ca2+-stimulated secretion, implicating the CSP-α/Hsc70 cochaperone system as a regulatory component of the secretory pathway. CSP-α physically associates with vesicle-associated membrane protein 8 (VAMP 8) on ZGs, and the CSP-α-VAMP 8 interaction was dependent on amino acids 83-112 of CSP-α. Immunofluorescence analysis of acinar lobules or purified ZGs confirmed the CSP-α colocalization with VAMP 8. These data establish a role for CSP-α in regulating digestive enzyme secretion and suggest that CSP-α and Hsc70 modulate specific soluble N-ethylmaleimide-sensitive attachment receptor interactions necessary for exocytosis.
Cigarette smoke-induced emphysema in A/J mice is associated with pulmonary oxidative stress, apoptosis of lung cells, and global alterations in gene expression
Authors: Rangasamy Tirumalai , Misra Vikas , Zhen Lijie , Tankersley Clarke G. , Tuder Rubin M. , Biswal Shyam
Published: March 2009

Cigarette smoking is the major risk factor for developing chronic obstructive pulmonary disease, the fourth leading cause of deaths in the United States. Despite recent advances, the molecular mechanisms involved in the initiation and progression of this disease remain elusive. We used Affymetrix Gene Chip arrays to determine the temporal alterations in global gene expression during the progression of pulmonary emphysema in A/J mice. Chronic cigarette smoke (CS) exposure caused pulmonary emphysema in A/J mice, which was associated with pronounced bronchoalveolar inflammation, enhanced oxidative stress, and increased apoptosis of alveolar septal cells. Microarray analysis revealed the upregulation of 1,190, 715, 260, and 246 genes and the downregulation of 1,840, 730, 442, and 236 genes in the lungs of mice exposed to CS for 5 h, 8 days, and 1.5 and 6 mo, respectively. Most of the genes belong to the functional categories of phase I genes, Nrf2-regulated antioxidant and phase II genes, phase III detoxification genes, and others including immune/inflammatory response genes. Induction of the genes encoding multiple phase I enzymes was markedly higher in the emphysematous lungs, whereas reduced expression of various cytoprotective genes constituting ubiquitin-proteasome complex, cell survival pathways, solute carriers and transporters, transcription factors, and Nrf2-regulated antioxidant and phase II-responsive genes was noted. Our data indicate that the progression of CS-induced emphysema is associated with a steady decline in the expression of various genes involved in multiple pathways in the lungs of A/J mice. Many of the genes discovered in this study could rationally play an important role in the susceptibility to CS-induced emphysema.
CNV and nervous system diseases – what’s new?
Authors: Gu W. , Lupski J.R.
Published: March 2009

Several new genomic disorders caused by copy number variation (CNV) of genes whose dosage is critical for the physiological function of the nervous system have been recently identified. Dup(7)(q11.23) patients carry duplications of the genomic region deleted in Williams-Beuren syndrome, they are characterized by prominent speech delay. The phenotypes of Potocki-Lupski syndrome and MECP2 duplication syndrome were neuropsychologically examined in detail, which revealed autism as an endophenotype and a prominent behavioral feature of these disorders. Tandem duplication of LMNB1 was reported to cause adult-onset autosomal dominant leukodystrophy. PAFAH1B1/LIS1 and YWHAE, which were deleted in isolated lissencephaly (PAFAH1B1/LIS1 alone) and Miller-Dieker syndrome (both genes), were found to be duplicated in patients with developmental delay. Finally, two novel microdeletion syndromes affecting 17q21.31 and 15q13.3, as well as their reciprocal duplications, were also identified. In this review, we provide an overview of the phenotypic manifestation of these syndromes and the rearrangements causing them.
Molecular and clinical characterization of de novo and familial cases with microduplication 3q29: guidelines for copy number variation case reporting
Authors: Goobie S. , Knijnenburg J. , FitzPatrick D. , Sharkey F.H. , Lionel A.C. , Marshall C.R. , Azam T. , Shago M. , Chong K. , Mendoza-Londono R. , den Hollander N.S. , Ruivenkamp C. , Maher E. , Tanke H.J. , Szuhai K. , Wintle R.F. , Scherer S.W.
Published: March 2009

Microdeletions of 3q29 have previously been reported, but the postulated reciprocal microduplication has only recently been observed. Here, cases from four families, two ascertained in Toronto (Canada) and one each from Edinburgh (UK) and Leiden (Netherlands), carrying microduplications of 3q29 are presented. These families have been characterized by cytogenetic and molecular techniques, and all individuals have been further characterized with genome-wide, high density single nucleotide polymorphism (SNP) arrays run at a single centre (The Centre for Applied Genomics, Toronto). In addition to polymorphic copy-number variants (CNV), all carry duplications of 3q29 ranging in size from 1.9 to 2.4 Mb, encompassing multiple genes and defining a minimum region of overlap of about 1.6 Mb bounded by clusters of segmental duplications that is remarkably similar in location to previously reported 3q29 microdeletions. Consistent with other reports, the phenotype is variable, although developmental delay and significant ophthalmological findings were recurrent, suggesting that dosage sensitivity of genes located within 3q29 is important for eye and CNS development. We also consider CNVs found elsewhere in the genome for their contribution to the phenotype. We conclude by providing preliminary guidelines for management and anticipatory care of families with this microduplication, thereby establishing a standard for CNV reporting.
Putatively benign copy number variants in subjects with idiopathic autism spectrum disorder and/or intellectual disability
Authors: Qiao Y. , Harvard C. , Riendeau N. , Fawcett C. , Liu X. , Holden J.J.A. , Lewis M.E.S. , Rajcan-Separovic E.
Published: March 2009

Putatively benign copy number variants (bCNVs) can be broadly defined as DNA copy number gains or losses that do not lead to a recognizable clinical phenotype. Detection of bCNVs in genomes of clinically healthy individuals is increasing with the widespread use of whole genome arrays of different resolutions and the use of sequence comparison methods. However, the role of bCNVs in human disease susceptibility and phenotype diversity is mostly unknown. In order to explore a potential role of bCNVs in the susceptibility to and/or pathogenesis of human neurodevelopmental disorders we examined the frequency and type of common bCNVs (detected in ≥2 independent control studies) amongst 221 subjects with an autism spectrum disorder (ASD) and/or intellectual disability (ID) in comparison to 40 controls using three array platforms of increasing resolution (Spectral Genomics (1 Mb), Agilent (0.03 Mb) and NimbleGen (0.01 Mb)). We determined that the number of bCNVs/subject, type and frequency of most common bCNVs were similar for both the test and control cohorts when the same array platform was used. The comparison of the ‘load’ of bCNVs (i.e. number/subject) to a standardized metric of phenotypic features (see de Vries et al., 2001) in 91 ASD subjects revealed that a phenotype score ≥4 is significantly more common (P < 0.05) in persons with an ASD having one or more bCNVs via 1 Mb array-CGH, whereas individuals without any recognizable bCNVs are significantly more likely to have a less complex phenotype and a score ≤3. Finally, we report 14 CNVs found amongst our ASD and ID cohorts that are infrequent in neurodevelopmentally normal controls and are of familial origin, thus comprising rare CNVs of unknown significance. Two of these rare familial bCNVs revealed variation in size when transmitted from parent to child, indicating genomic instability. The ongoing discovery and correlation of the pathogenic versus putatively benign underpinnings of the human genome, its inherent variability and potential gene, positional and epigenetic influences will continue to improve our understanding of genome plasticity and its influences on human neurodevelopmental disorders.
Benign and pathogenic copy number variation on the short arm of chromosome 4
Authors: Hannes F. , Vermeesch J.R.
Published: March 2009

The terminal deletion of the short arm of chromosome 4 causing the Wolf-Hirschhorn syndrome is one of the first pathogenic copy number variations (CNVs) ever described. Since this first discovery, a large number of 4p CNVs causing variable phenotypes have been described. Here, we present an overview on those benign and pathogenic visible and submicroscopic 4p imbalances. Interestingly, some CNVs can be, dependent on their copy number state, both benign and pathogenic. In addition, we show how the collection of both phenotypes and genotypes of 4p terminal deletions is leading towards the genetic dissection of the Wolf-Hirschhorn syndrome.
Diseases associated with the low copy number of the C4B gene encoding C4, the fourth component of complement
Authors: Szilágyi Á. , Füst G.
Published: March 2009

In this review article, earlier and recent work of the research group on the copy number polymorphism of the C4B gene are summarized. In a study performed in 1991 a sharp decrease was found among healthy elderly (>60 years old) people as compared to healthy young (<45 years old) people in the frequency of the individuals with a low copy number of the C4B gene (one of the two genes (C4A and C4B) encoding the C4 complement protein). This observation indicated that subjects with a low C4B copy number are selected out from the population of healthy individuals due to their increased morbidity/mortality of some disease(s). In accordance with this assumption a marked accumulation of low C4B copy number carriers was found in patients with acute myocardial infarction (AMI) and stroke as compared to age-matched healthy subjects. In addition it was demonstrated that AMI patients who carry a low copy number of the C4B gene have a highly significantly increased risk for short-term (1 year) post-AMI mortality as compared to non-carriers. These relationships, which were first revealed more than 15 years ago by our group, have been recently supported by new data obtained using up-to-date genotyping methods worked out by our group in two Caucasian populations, Hungarian and Icelandic. In addition, we proved that this relationship concerns only recent smokers. These findings indicate that there is strong connection between low copy number of the C4B gene on one hand and cardiovascular disease morbidity and mortality on the other. Hypotheses and the results of recent studies aiming to elucidate the mechanism of this association as well as other diseases connected with the low C4B copy number are discussed.
Copy number variation of Fc gamma receptor genes and disease predisposition
Authors: Fanciulli M. , Vyse T.J. , Aitman T.J.
Published: March 2009

Naturally occurring variation in gene copy number is increasingly recognized as a major source of inter-individual differences in phenotype and is an important susceptibility factor for genetically complex diseases. Several studies provide evidence of copy number variation at genes involved in inflammation and immunity highlighting their possible contribution to the inter-individual variation observed in immune responses. This review will explore copy number variation at the Fc gamma receptor cluster and its relevance in the pathogenesis of common human diseases.
Chromosome copy number variation and breast cancer risk
Authors: Tchatchou S. , Burwinkel B.
Published: March 2009

Breast cancer is the most frequent cancer among women. It is caused by genetic and environmental factors. Whereas mutations in high-penetrance susceptibility genes have been identified in familial breast cancer and several single nucleotide polymorphisms (SNPs) have been shown to be associated with both familial and sporadic breast cancer risk, the impact of genomic copy number variants (CNVs) on breast cancer risk has so far poorly been studied. An example of a CNV affecting the tumor suppressor gene MTUS1 that has been shown to be associated with familial breast cancer risk is given. Moreover, we discuss CNVs affecting detoxification genes like GSTM1 and GSTT1 whose association with breast cancer risk is controversial. Finally, the potential of array-based genome-wide CNV association studies is discussed.
Predisposition to colorectal cancer: exploiting copy number variation to identify novel predisposing genes and mechanisms
Authors: Venkatachalam R. , Ligtenberg M.J.L. , Hoogerbrugge N. , Geurts van Kessel A. , Kuiper R.P.
Published: March 2009

Although cancer is mostly regarded as an acquired disease, familial predisposition plays a significant role in many cancer types. Thus far, several high penetrant cancer predisposing genes have been identified. As yet, however, these genes explain only a fraction of the familial and/or hereditary cases of cancer. This has led to the exploration of the human genome for novel cancer predisposing genes. The identification of such genes will not only increase our understanding of cancer predisposition and development, but will also have direct implications for genetic counseling and personalized management of the patients and their family members. Here we provide an inventory of currently known molecular mechanisms related to familial colorectal cancer development and an outline of copy number analysis-based strategies to identify new predisposing genes. Finally, we discuss a novel copy number-associated epigenetic mechanism underlying the predisposition to colorectal cancer.
Sulfotransferase gene copy number variation: pharmacogenetics and function
Authors: Hebbring S.J. , Moyer A.M. , Weinshilboum R.M.
Published: March 2009

Pharmacogenetics is the study of the role of inheritance in variation to drug response. Drug response phenotypes can vary from adverse drug reactions at one end of the spectrum to equally serious lack of the desired effect of drug therapy at the other. Many of the current important examples of pharmacogenetics involve inherited variation in drug metabolism. Sulfate conjugation catalyzed by cytosolic sulfotransferase (SULT) enzymes, particularly SULT1A1, is a major pathway for drug metabolism in humans. Pharmacogenetic studies of SULT1A1 began over a quarter of a century ago and have advanced from biochemical genetic experiments to include cDNA and gene cloning, gene resequencing, and functional studies of the effects of single nucleotide polymorphisms (SNPs). SNP genotyping, in turn, led to the discovery of functionally important copy number variations (CNVs) in the SULT1A1 gene. This review will briefly describe the evolution of our understanding of SULT1A1 pharmacogenetics and CNV, as well as challenges involved in utilizing both SNP and CNV data in an attempt to predict SULT1A1 function. SULT1A1 represents one example of the potential importance of CNV for the evolving disciplines of pharmacogenetics and pharmacogenomics.
Human subtelomeric copy number variations
Authors: Riethman H.
Published: March 2009

Copy number variation is a defining characteristic of human subtelomeres. Human subtelomeric segmental duplication regions (‘Subtelomeric Repeats’) comprise about 25% of the most distal 500 kb and 80% of the most distal 100 kb in human DNA. Huge allelic disparities seen in subtelomeric DNA sequence content and organization are postulated to have an impact on the dosage of transcripts embedded within the duplicated sequences, on the transcription of genes in adjacent single copy DNA regions, and on the chromatin structures mediating telomere functions including chromosome stability. In addition to the complex duplicon substructure and huge allelic variations in extended subtelomere regions, both copy number variation and alternative sequence organizations for DNA characterize the sequences immediately adjacent to terminal (TTAGGG)n tracts (‘subterminal DNA’). The structural variation in subterminal DNA is likely to have important consequences for expression of subterminal transcripts such as a newly-discovered gene family encoding actin-interacting proteins and a non-coding telomeric repeat containing RNA (TERRA) transcript family critical for telomere integrity. Major immediate challenges include discovering the full extent and nature of subtelomeric structural and copy number variation in humans, and developing methods for tracking individual allelic variants in the context of total genomic DNA.
Expression divergence and copy number variation in the human genome
Authors: Auer H.
Published: March 2009

DNA copy number variation (CNV) was recently discovered as a significant part of human genetic variation. This variation affects genes as well as intergenic regions. Herein, current insight into the effects of CNV on gene expression is summarized. The consequences of intergenic CNVs are poorly understood. For CNV affecting genes, a dosage compensation mechanism seems to be applied on a subset of genes only, while others show augmented expression caused by increasing copy number. For the latter case, extensive literature reports a positive correlation between gene copy number and gene expression. Recent advances in techniques for genome-wide measurements of CNV and gene expression are described. These advances will soon allow the generation of comprehensive maps of these two phenomena, which will contribute to our understanding of the mechanisms underlying how CNV affects gene expression.
CNV discovery using SNP genotyping arrays
Authors: Yau C. , Holmes C.C.
Published: March 2009

Genome-wide single nucleotide polymorphism (SNP) genotyping platforms have made an important contribution to population genetics and genetic epidemiology. Recently there has been a realisation that these SNP platforms can also be used for typing copy number variants (CNVs). This allows for ‘generalised’ genotyping of both SNPs and CNVs simultaneously on a common sample set, with advantages in terms of cost and unified analysis. In this article we review various statistical approaches to calling CNVs from SNP data. We highlight three tiers of algorithms depending on the level of information used.