bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood group molecular genotyping
Authors: Jungbauer C.
Published: October 2011

DNA‐based typing methods of red cell antigens are applied in several fields. Genotyping is used to clarify problems in patient serology. It is also increasingly applied for routine mass‐scale typing of blood donors for minor red cell antigens and screening for donors with rare blood types. An advance in this field is the non‐invasive fetal RHD diagnostics in pregnancies of D‐negative women to determine the fetal RHD.

Reference centres for immunohaematology commonly use molecular methods to clarify problems, discrepancies or unusual results in patient serology. It is often applied in individuals with variant RhD expression to detect the contributing weak D or partial D types. Genotyping is also used to identify the individual ABO and RhD blood group in patients after mismatched transfusion. In some patients with positive direct antiglobulin test (DAT) it is necessary to type for antigens by DNA techniques. Genotyping is also helpful when reagents are not available or only weakly reactive, or to confirm weakly expressed antigens.

Blood establishments are constantly challenged with the blood supply for patients carrying irregular red cell antibodies. A high number of donors have to be typed to find compatible blood units. Increasingly, DNA‐based methods are used alongside standard serological typing. The advantages of molecular methods are the wider range of different antigens available for typing and that some DNA methods are less expensive than phenotyping. Extensive donor antigen typing leads to short response times, from request to issuing blood units. Genotyping is also used for identifying donors with extremely weak RhD expression (DEL) to prevent mistyping as RhD‐negative.

Non‐invasive fetal typing of RHD from maternal blood in pregnancies of D‐negative women is implemented in many Caucasian blood establishments. It allows that D‐negative fetuses can be identified at early stage. In these cases, no anti‐D immunoglobulin is required, which provides a more efficient use of this human blood derivate. Furthermore, in anti‐D alloimmunized women, the assay allows to accurately identify fetuses at risk for haemolytic disease.
Centralized quality control inspections for blood bags and leukocyte reduction at the Japanese Red Cross Society
Authors: Mazda Toshio
Published: October 2011

The Japanese Red Cross is now emphasizing an intense quality control procedure for testing blood bags and for leukocyte counts in blood components. The inspections and tests are described and the effects and significance these have on blood product management of the supply of safe blood are presented.
Application of quality principles in clinical transfusion laboratory practice
Authors: Roxby D. , Magrin G.
Published: October 2011

Quality systems and principles are essential aspects of high quality clinical transfusion laboratory practice. Many frameworks provide the structure for quality systems, some of which are specific to transfusion laboratory practices such as codes of practice and others are more general including ISO9001 and ISO15189. All these systems follow the same core principles incorporating quality assurance activities, quality control and continual quality improvement processes. The application of quality principles may be divided into five categories: processes, people, material, equipment and management. Specifically these categories must encompass laboratory procedures and analysis, storage and transportation of blood products, documentation of all results, selection, validation and maintenance of equipment used in these processes; the design and provision of a suitable working environment, appropriate storage and maintenance of laboratory and other records, internal and external audits and quality control. Personnel involved at any stage of clinical transfusion laboratory practice should be aware of the importance of quality principles, quality systems and quality management and their role. The strict adherence to well designed standard operating procedures and following definitive safety guidelines further enhances quality systems. Together, application of these principles ensures that all products, processes and facilities meet the required standards and specifications. If quality principles are not applied and errors are not addressed, then the consequences can be far reaching.
Changing knowledge and beliefs through an oral health pregnancy message
Authors: Bates S. Brady , Riedy Christine A.
Published: October 2011

Objectives: Pregnancy can be a critical and important period in which to intervene to improve oral health in both the mother and her child. This study examined an online approach for promoting awareness of oral health messages targeted at pregnant women, and whether this type of health messaging impacts oral health knowledge and beliefs.

Methods: The study was conducted in three parts: production and pilot testing of a brief commercial, Web site/commercial launch and testing, and dissemination and monitoring of the commercial on a video‐sharing site. The brief commercial and pre‐ and postsurveys were produced and pilot tested among a convenience sample of pregnant women (n = 13). The revised commercial and surveys were launched on a newly created Web site and monitored for activity. After 2 months, the commercial was uploaded to a popular video‐sharing Web site.

Results: Fifty‐five individuals completed both the pre‐ and postsurveys after the Web site was launched. No one responded 100 percent correctly on the presurvey; 77.4 percent responded correctly about dental visits during pregnancy, 66.0 percent about cavity prevention, and 50.9 percent about transmission of bacteria by saliva. Most respondents recalled the correct information on the posttest; 100 percent or close to 100 percent accurately responded about visiting the dentist during pregnancy and preventing cavities, while 79.2 percent responded correctly to the transmission question.

Conclusion: Social media can effectively provide dental health messages during pregnancy. This approach can play an important role in increasing awareness and improving oral health of both mother and child.
Arguments for a narrow species concept in Rubus sect. Corylifolii
Authors: Ryde Ulf
Published: October 2011

A detailed inventory of Rubus sect. Corylifolii from the province of Halland in southwestern Sweden has been performed and the chromosome number of all distinct taxa and deviating morphotypes has been determined using flow cytometry. Once putative hybrids between Corylifolii and R. caesius or R. idaeus are recognized, essentially all stands of Corylifolii in Halland can be satisfactorily identified, including six taxa with a restricted distribution. Two of the latter have been noticed before: R. sordirosanthus (H. Hyl.) Ryde, found in over 100 localities and R. cordatiformis (Neuman) Ryde (comb. nov.) in almost 80 localities, but only in restricted areas, 23 and 7 km across. The other four have even smaller distributions (1–6 km across) and occur only in 3–15 localities. Clearly, they are local species in the terminology of Weber. Such species are currently usually left undescribed, which in the case of Halland would mean that 25% of the Corylifolii would remain without a name. Such a restriction leads to a number of problems: chaos in botanical collections and provincial floras, wide‐spread species potentially being overlooked, red‐listing becoming problematic, changes in the occurrence of local species becoming impossible to follow over time, and the Corylifolii treated differently from other apomictic groups. This study shows that a proper description of all local Corylifolii species would solve these problems. It is also argued that by doing so, the total number of Swedish species would not become particularly large, still remaining much lower than in other apomictic genera, like Hieracium, Taraxacum and Ranunculus. Therefore, the four local species are here described as R. onsalaënsis Ryde, R. rugulosus Ryde, R. polybracteatus Ryde and R. soendrumensis Ryde.
Augmented Cohesive Elements for Efficient Delamination Analyses of Composite Laminates
Authors: Qiao H. , Chen W. Q. , Yang Q. D. , Lua J.
Published: October 2011

In this paper, a new type of cohesive element that employs multiple subdomain integration (MSDI) for improved cohesive stress integration accuracy of bonded plate/shell elements has been formulated. Within each subdomain, stress integration is compatible with existing schemes such as Gaussian integration (GI), Newton–Cotes integration, or the mixed Gaussian and subdomain integration (mixed GI&SDI). The numerical accuracy, efficiency, and robustness of this element when employing three integration methods for MSD cohesive stress integration have been evaluated and compared through a benchmark mode-I fracture problem of bonded double-cantilever plates. The MSDI offers at least 50% improvement of numerical accuracy as compared to the best integration method in literature and has the best numerical robustness. This significant improvement pushes the structural mesh size restriction from limiting size of 1/3–1/5 cohesive zone length to 1.5–2 times the cohesive zone length. The formulation is very easy to be implemented into any finite element programs including commercial packages. Furthermore, this formulation enables the use of dual-mesh for delamination analyses of bonded structural shells/plates, which is of practical importance because it greatly reduces the burden of mesh generation for complicated composite structures. It has also been demonstrated that using high-order shell/plate elements can improve the numerical accuracy in general because the nonlinear deformation profile permitted by this type of elements can better describe the nonlinear deformation in the crack-tip element (partially bonded elements).
Mesomechanical Modeling of Polymer/Clay Nanocomposites Using a Viscoelastic-Viscoplastic-Viscodamage Constitutive Model
Authors: Tehrani Ardeshir H. , Abu Al-Rub Rashid K.
Published: October 2011

In this study, damage evolution in a nanocomposite containing the polymethyl methacrylate polymer (PMMA) embedded with silicate nanoclay particles is simulated by using a nonlinear viscoelastic, viscoplastic, and viscodamage constitutive model. Mesomechanical two-dimensional representative volume elements (RVEs) of fully intercalated and fully exfoliated nanoclay polymer composites have been arbitrarily generated assuming a uniform dispersion of nanoclay particles with random length, aspect ratio, and orientation. Proper size of the RVE has been determined by studying the effect of the RVE size on the stress-strain response and toughness. Several simulations including different intercalated and exfoliated nanoclay weight fractions under different strain rates at room temperature have been conducted. It is concluded that the strength of exfoliated nanoclay composite is higher than intercalated one due to more distributed damage within many narrow localized zones for the case of exfoliated nanoclay polymer composite.
Correlating Microscale Thermal Conductivity of Heavily-Doped Silicon With Simultaneous Measurements of Stress
Authors: Gan Ming , Tomar Vikas
Published: October 2011

The functioning and performance of today’s integrated circuits and sensors are highly affected by the thermal properties of microscale silicon structures. Due to the well known size effect, the thermal properties of microscale silicon structures are not the same as those of the bulk silicon. Furthermore, stress/strain inside microscale silicon structures can significantly affect their thermal properties. This article presents the first thermal conductivity measurements of a microscale silicon structure under applied compressive stress at 350 K. Atomic force microscope (AFM) cantilevers made of doped single-crystal silicon were used as samples. A resistance temperature detector (RTD) heater attached to another RTD sensor was used as the heating module, which was mounted onto a nanoindentation test platform. This integrated system applied compressive load to the cantilever in the longitudinal direction while supplying heat. The thermal conductivity of the cantilevers was calculated using steady state heat conduction equation. The result shows that the measured thermal conductivity varies from 110 W/(m·K) to 140 W/(m·K) as compressive strain varies from 0.1% to 0.3%. Thermal conductivity is shown to increase with increase in compressive strain. These results match with the published simulation values. The measured thermal conductivity and stress values vary in the similar manner as a function of applied strain.
Influence of Al Particle Size and Lead Zirconate Titanate (PZT) Volume Fraction on the Dielectric Properties of PZT-Epoxy-Aluminum Composites
Authors: Banerjee S. , Cook-Chennault K. A.
Published: October 2011

Two-phase PZT-epoxy piezoelectric composites and three phase PZT-epoxy-Al composites were fabricated using a poling voltage of 0.2 kV/mm. The influence of aluminum inclusion size (nano and micron) and (lead zirconate titanate) PZT volume fraction on the dielectric properties of the three phase PZT-epoxy-aluminum composites were experimentally investigated. In general, dielectric and piezoelectric properties of the PZT-epoxy matrix were improved with the addition of aluminum particles. Composites that were comprised of micron scale aluminum inclusions demonstrated higher piezoelectric d33-strain-coefficients, and higher dielectric loss compared to composites that were comprised of nanosize aluminum inclusions. Specifically, composites comprised of micron sized aluminum particles and PZT volume fractions of 20%, 30%, and 40% had dielectric constants equal to 405.7, 661.4, and 727.8 (pC/N), respectively, while composites comprised of nanosize aluminum particles with the same PZT volume fractions, had dielectric constants equal to 233.28, 568.81, and 657.41 (pC/N), respectively. The electromechanical properties of the composites are influenced by several factors: inclusion agglomeration, contact resistance between particles, and air voids. These composites may be useful for several applications: structural health monitoring, energy harvesting, and acoustic liners.
Activity-Dependent Long-Term Depression of Electrical Synapses
Authors: Haas Julie S. , Zavala Baltazar , Landisman Carole E.
Published: October 2011

Paired bursting in coupled neurons depresses electrical synapses while their asymmetry increases after unidirectional use.
Computation-Guided Backbone Grafting of a Discontinuous Motif onto a Protein Scaffold
Authors: Azoitei Mihai L. , Correia Bruno E. , Ban Yih-En Andrew , Carrico Chris , Kalyuzhniy Oleksandr , Chen Lei , Schroeter Alexandria , Huang Po-Ssu , McLellan Jason S. , Kwong Peter D. , Baker David , Strong Roland K. , Schief William R.
Published: October 2011

A two-segment HIV epitope grafted into a scaffold protein maintains high affinity for a broadly neutralizing antibody.
Supramolecular Linear Heterojunction Composed of Graphite-Like Semiconducting Nanotubular Segments
Authors: Zhang Wei , Jin Wusong , Fukushima Takanori , Saeki Akinori , Seki Shu , Aida Takuzo
Published: October 2011

A supramolecular self-assembly approach is used to make a nanotubular heterojunction.
Watery Disks
Authors: Akeson Rachel
Published: October 2011

The Herschel Space Observatory has detected a large reservoir of water stored as ice in the disk surrounding a nearby star.
Open-Source Ecology Takes Root Across the World
Authors: Stokstad Erik
Published: October 2011

A new collaboration of volunteer research sites is running simple yet powerful experiments to shed light on global change in grasslands.
Haemophilus influenzae Type b Carriage among Young Children in Metropolitan Atlanta in the Context of Vaccine Shortage and Booster Dose Deferral
Authors: Thomas Jennifer Dolan , Jackson Michael L. , Sharma Dolly , Mair Raydel , Bach Michelle C. , Castillo Dana , Ejigiri O. Grace , Satola Sarah , Cohn Amanda C. , Jerris Robert , Jain Shabnam , Farley Monica M. , Mayer Leonard W. , Messonnier Nancy E.
Published: October 2011

Short-term deferral of the
Haemophilus influenzae
type b (Hib) vaccine booster dose during a recent U.S. Hib vaccine shortage did not result in widespread Hib carriage in Atlanta, as the Hib carriage rate was found to be 0.3% (1/342). Hib colonization was significantly more common among males and day care attendees.
Diagnostic Value of Animal-Side Antibody Assays for Rapid Detection of Mycobacterium bovis or Mycobacterium microti Infection in South American Camelids
Authors: Lyashchenko Konstantin P. , Greenwald Rena , Esfandiari Javan , Rhodes Shelley , Dean Gillian , de la Rua-Domenech Ricardo , Meylan Mireille , Vordermeier HMartin , Zanolari Patrik
Published: October 2011

Tuberculosis (TB) in South American camelids (SAC) is caused byMycobacterium bovisorMycobacterium microti. Two serological methods, rapid testing (RT) and the dual-path platform (DPP) assay, were evaluated using naturally infected SAC. The study population included 156 alpacas and 175 llamas in Great Britain, Switzerland, and the United States. TB due toM. bovis(n= 44) orM. microti(n= 8) in 35 alpacas and 17 llamas was diagnosed by gross pathology examination and culture. Control animals were from herds with no TB history. The RT and the DPP assay showed sensitivities of 71% and 74%, respectively, for alpacas, while the sensitivity for llamas was 77% for both assays. The specificity of the DPP assay (98%) was higher than that of RT (94%) for llamas; the specificities of the two assays were identical (98%) for alpacas. When the two antibody tests were combined, the parallel-testing interpretation (applied when either assay produced a positive result) enhanced the sensitivities of antibody detection to 89% for alpacas and 88% for llamas but at the cost of lower specificities (97% and 93%, respectively), whereas the serial-testing interpretation (applied when both assays produced a positive result) maximized the specificity to 100% for both SAC species, although the sensitivities were 57% for alpacas and 65% for llamas. Over 95% of the animals with evidence of TB failed to produce skin test reactions, thus confirming concerns about the validity of this method for testing SAC. The findings suggest that serological assays may offer a more accurate and practical alternative for antemortem detection of camelid TB.
“Mycobacterium tilburgii” Infection in Two Immunocompromised Children: Importance of Molecular Tools in Culture-Negative Mycobacterial Disease Diagnosis
Authors: Hartwig Nico G. , Warris Adilia , van de Vosse Esther , van der Zanden Adri G. M. , Schülin-Casonato Tanja , van Ingen Jakko , van Hest Rob
Published: October 2011

“
Mycobacterium tilburgii
” is a nontuberculous mycobacterium that cannot be cultured by current techniques. It is described as causing disseminated disease in adults. We present the first cases of disseminated disease in 2 immunocompromised children. This paper stresses the importance of molecular techniques for correct mycobacterial identification and guidance to immunological diagnosis.
Epidemiology and Antifungal Susceptibility of Bloodstream Fungal Isolates in Pediatric Patients: a Spanish Multicenter Prospective Survey
Authors: Pemán Javier , Cantón Emilia , Linares-Sicilia María José , Roselló Eva María , Borrell Nuria , Ruiz-Pérez-de-Pipaon María Teresa , Guinea Jesús , García Julio , Porras Aurelio , García-Tapia Ana María , Pérez-del-Molino Luisa , Suárez Anabel , Alcoba Julia , García-García Inmaculada
Published: October 2011

Data on fungemia epidemiology and antifungal susceptibility of isolates from children are scarce, leading frequently to pediatric empirical treatment based on available adult data. The present study was designed to update the epidemiological, mycological, and
in vitro
susceptibility data on fungal isolates from children with fungemia in Spain. All fungemia episodes were identified prospectively by blood culture over 13 months at 30 hospitals. Tests of susceptibility to amphotericin B, flucytosine, fluconazole, itraconazole, posaconazole, voriconazole, anidulafungin, caspofungin, and micafungin were performed at participant institutions by a microdilution colorimetric method. New species-specific clinical breakpoints for fluconazole, voriconazole, and echinocandins were also applied. A total of 203 episodes of fungemia in 200 children were identified. A higher proportion of fungal isolates was from general wards than intensive care units (ICU).
Candida parapsilosis
(46.8%),
Candida albicans
(36.5%),
Candida tropicalis
(5.9%),
Candida glabrata
(3.9%), and
Candida guilliermondii
(2.5%) were the leading species.
C. parapsilosis
was the predominant species except in neonates.
C. albicans
was the most frequent in neonatal ICU settings (51.9%). Intravascular catheter (79.3%), surgery (35%), prematurity (30%), and neutropenia (11%) were the most frequent predisposing factors. Most
Candida
isolates (95.1%) were susceptible to all antifungals. When the new species-specific clinical breakpoints were applied, all
C. parapsilosis
isolates were susceptible to echinocandins except one, which was micafungin resistant. This is the largest published series of fungemia episodes in the pediatric setting.
C. parapsilosis
is the most prevalent species in Spain, followed by
C. albicans
and
C. tropicalis
. Resistance to azole and echinocandin agents is extremely rare among
Candida
species. The fluconazole resistance rate in Spain has decreased in the last 10 years.
Validation of 24-Hour Flucytosine MIC Determination by Comparison with 48-Hour Determination by the Clinical and Laboratory Standards Institute M27-A3 Broth Microdilution Reference Method
Authors: Lockhart Shawn R. , Bolden Carol B. , Iqbal Naureen , Kuykendall Randall J.
Published: October 2011

Flucytosine and itraconazole are the only antifungal agents for which the Clinical Laboratory and Standards Institute recommendations include MIC breakpoint readings at 48 h only. Here we show good essential and categorical agreement between the flucytosine MIC readings at 48 and 24 h for
Candida
species.
Down-Modulation of CD8αβ Is a Fundamental Activity of Primate Lentiviral Nef Proteins
Authors: Heigele Anke , Schindler Michael , Gnanadurai Clement W. , Leonard Jolie A. , Collins Kathleen L. , Kirchhoff Frank
Published: October 2011

It is well established that the Nef proteins of human and simian immunodeficiency viruses (HIV and SIV) modulate major histocompatibility complex class I (MHC-I) cell surface expression to protect infected cells against lysis by cytotoxic T lymphocytes (CTLs). Recent data supported the observation that Nef also manipulates CTLs directly by down-modulating CD8αβ (J. A. Leonard, T. Filzen, C. C. Carter, M. Schaefer, and K. L. Collins, J. Virol. 85:6867–6881, 2011), but it remained unknown whether this Nef activity is conserved between different lineages of HIV and SIV. In this study, we examined a total of 42nefalleles from 16 different primate lentiviruses representing most major lineages of primate lentiviruses, as well as nonpandemic HIV-1 strains and the direct precursors of HIV-1 (SIVcpz and SIVgor). We found that the vast majority of thesenefalleles strongly down-modulate CD8β in human T cells. Primate lentiviral Nefs generally interacted specifically with the cytoplasmic tail of CD8β, and down-modulation of this receptor was dependent on the conserved dileucine-based motif and two adjacent acidic residues (DD/E) in the C-terminal flexible loop of SIV Nef proteins. Both of these motifs are known to be important for the interaction of HIV-1 Nef with AP-2, and they were also shown to be critical for down-modulation of CD4 and CD28, but not MHC-I, by SIV Nefs. Our results show that down-modulation of CD4, CD8β, and CD28 involves largely overlapping (but not identical) domains and is most likely dependent on conserved interactions of primate lentiviral Nefs with cellular adaptor proteins. Furthermore, our data demonstrate that Nef-mediated down-modulation of CD8αβ is a fundamental property of primate lentiviruses and suggest that direct manipulation of CD8+T cells plays a relevant role in viral immune evasion.
A Recombinant Chimeric La Crosse Virus Expressing the Surface Glycoproteins of Jamestown Canyon Virus Is Immunogenic and Protective against Challenge with either Parental Virus in Mice or Monkeys
Authors: Bennett R. S. , Gresko A. K. , Nelson J. T. , Murphy B. R. , Whitehead S. S.
Published: October 2011

La Crosse virus (LACV) and Jamestown Canyon virus (JCV), family
Bunyaviridae
, are mosquito-borne viruses that are endemic in North America and recognized as etiologic agents of encephalitis in humans. Both viruses belong to the California encephalitis virus serogroup, which causes 70 to 100 cases of encephalitis a year. As a first step in creating live attenuated viral vaccine candidates for this serogroup, we have generated a recombinant LACV expressing the attachment/fusion glycoproteins of JCV. The JCV/LACV chimeric virus contains full-length S and L segments derived from LACV. For the M segment, the open reading frame (ORF) of LACV is replaced with that derived from JCV and is flanked by the untranslated regions of LACV. The resulting chimeric virus retained the same robust growth kinetics in tissue culture as observed for either parent virus, and the virus remains highly infectious and immunogenic in mice. Although both LACV and JCV are highly neurovirulent in 21 day-old mice, with 50% lethal dose (LD
50
) values of 0.1 and 0.5 log
10
PFU, respectively, chimeric JCV/LACV is highly attenuated and does not cause disease even after intracerebral inoculation of 10
3
PFU. Parenteral vaccination of mice with 10
1
or 10
3
PFU of JCV/LACV protected against lethal challenge with LACV, JCV, and Tahyna virus (TAHV). The chimeric virus was infectious and immunogenic in rhesus monkeys and induced neutralizing antibodies to JCV, LACV, and TAHV. When vaccinated monkeys were challenged with JCV, they were protected against the development of viremia. Generation of highly attenuated yet immunogenic chimeric bunyaviruses could be an efficient general method for development of vaccines effective against these pathogenic viruses.
Targeted Entry via Somatostatin Receptors Using a Novel Modified Retrovirus Glycoprotein That Delivers Genes at Levels Comparable to Those of Wild-Type Viral Glycoproteins
Authors: Li Fang , Ryu Byoung Y. , Krueger Robin L. , Heldt Scott A. , Albritton Lorraine M.
Published: October 2011

Here we report a novel viral glycoprotein created by replacing a natural receptor-binding sequence of the ecotropic Moloney murine leukemia virus envelope glycoprotein with the peptide ligand somatostatin. This new chimeric glycoprotein, which has been named the Sst receptor binding site (Sst-RBS), gives targeted transduction based on three criteria: (i) a gain of the use of a new entry receptor not used by any known virus; (ii) targeted entry at levels comparable to gene delivery by wild-type ecotropic Moloney murine leukemia virus and vesicular stomatitis virus (VSV) G glycoproteins; and (iii) a loss of the use of the natural ecotropic virus receptor. Retroviral vectors coated with Sst-RBS gained the ability to bind and transduce human 293 cells expressing somatostatin receptors. Their infection was specific to target somatostatin receptors, since a synthetic somatostatin peptide inhibited infection in a dose-dependent manner and the ability to transduce mouse cells bearing the natural ecotropic receptor was effectively lost. Importantly, vectors coated with the Sst-RBS glycoprotein gave targeted entry of up to 1 × 10
6
transducing U/ml, a level comparable to that seen with infection of vectors coated with the parental wild-type ecotropic Moloney murine leukemia virus glycoprotein through the ecotropic receptor and approaching that of infection of VSV G-coated vectors through the VSV receptor. To our knowledge, this is the first example of a glycoprotein that gives targeted entry of retroviral vectors at levels comparable to the natural capacity of viral envelope glycoproteins.
The Oral Secretion of Infectious Scrapie Prions Occurs in Preclinical Sheep with a Range of
PRNP
Genotypes
Authors: Gough Kevin C. , Baker Claire A. , Rees Helen C. , Terry Linda A. , Spiropoulos John , Thorne Leigh , Maddison Ben C.
Published: October 2011

Preclinical sheep with the highly scrapie-susceptible VRQ/VRQ
PRNP
genotype secrete prions from the oral cavity. In order to further understand the significance of orally available prions, buccal swabs were taken from sheep with a range of
PRNP
genotypes and analyzed by serial protein misfolding cyclic amplification (sPMCA). Prions were detected in buccal swabs from scrapie-exposed sheep of genotypes linked to high (VRQ/VRQ and ARQ/VRQ) and low (ARR/VRQ and AHQ/VRQ) lymphoreticular system involvement in scrapie pathogenesis. For both groups, the level of prion detection was significantly higher than that for scrapie-resistant ARR/ARR sheep which were kept in the same farm environment and acted as sentinel controls for prions derived from the environment which might contaminate the oral cavity. In addition, sheep with no exposure to the scrapie agent did not contain any measurable prions within the oral cavity. Furthermore, prions were detected in sheep over a wide age range representing various stages of preclinical disease. These data demonstrate that orally available scrapie prions may be a common feature in sheep incubating scrapie, regardless of the
PRNP
genotype and any associated high-level accumulation of PrP
Sc
within lymphoreticular tissues. PrP
Sc
was present in buccal swabs from a large proportion of sheep with
PRNP
genotypes associated with relatively low disease penetrance, indicating that subclinical scrapie infection is likely to be a common occurrence. The significance of positive sPMCA reactions was confirmed by the transmission of infectivity in buccal swab extracts to Tg338 mice, illustrating the likely importance of orally available prions in the horizontal transmission of scrapie.
Herpes Simplex Virus Requires Poly(ADP-Ribose) Polymerase Activity for Efficient Replication and Induces Extracellular Signal-Related Kinase-Dependent Phosphorylation and ICP0-Dependent Nuclear Localization of Tankyrase 1
Authors: Li Zhuan , Yamauchi Yohei , Kamakura Maki , Murayama Tsugiya , Goshima Fumi , Kimura Hiroshi , Nishiyama Yukihiro
Published: October 2011

Tankyrase 1 is a poly(ADP-ribose) polymerase (PARP) which localizes to multiple subcellular sites, including telomeres and mitotic centrosomes. Poly(ADP-ribosyl)ation of the nuclear mitotic apparatus (NuMA) protein by tankyrase 1 during mitosis is essential for sister telomere resolution and mitotic spindle pole formation. In interphase cells, tankyrase 1 resides in the cytoplasm, and its role therein is not well understood. In this study, we found that herpes simplex virus (HSV) infection induced extensive modification of tankyrase 1 but not tankyrase 2. This modification was dependent on extracellular signal-regulated kinase (ERK) activity triggered by HSV infection. Following HSV-1 infection, tankyrase 1 was recruited to the nucleus. In the early phase of infection, tankyrase 1 colocalized with ICP0 and thereafter localized within the HSV replication compartment, which was blocked in cells infected with the HSV-1 ICP0-null mutant R7910. In the absence of infection, ICP0 interacted with tankyrase 1 and efficiently promoted its nuclear localization. HSV did not replicate efficiently in cells depleted of both tankyrases 1 and 2. Moreover, XAV939, an inhibitor of tankyrase PARP activity, decreased viral titers to 2 to 5% of control values. We concluded that HSV targets tankyrase 1 in an ICP0- and ERK-dependent manner to facilitate its replication.
Reconstitution of the Kaposi's Sarcoma-Associated Herpesvirus Nuclear Egress Complex and Formation of Nuclear Membrane Vesicles by Coexpression of ORF67 and ORF69 Gene Products
Authors: Desai Prashant J. , Pryce Erin N. , Henson Brandon W. , Luitweiler Eric M. , Cothran Jonathan
Published: October 2011

The Kaposi's sarcoma-associated herpesvirus nuclear egress complex is composed of two proteins, ORF67 and ORF69. In this study, we have recapitulated the KSHV complex by coexpression of these two proteins in insect cells using expression from recombinant baculoviruses. The proteins form a complex at the nuclear membrane as judged by live-cell analysis of protein fusions tagged with green fluorescent protein (GFP) and mCherry. Ultrastructural analysis of infected cells showed that ORF67 expression results in reduplication of the nuclear membrane. When the two proteins are expressed together, numerous virion-size nuclear membrane-derived vesicles were evident at the nuclear margins.
The emergency first aid responder system model: using community members to assist life-threatening emergencies in violent, developing areas of need
Authors: Sun Jared H , Wallis Lee A
Published: October 2011

Background

As many as 90% of all trauma-related deaths occur in developing nations, and this is expected to get worse with modernisation. The current method of creating an emergency care system by modelling after that of a Western nation is too resource-heavy for most developing countries to handle. A cheaper, more community-based model is needed to establish new emergency care systems and to support them to full maturity.

Methods

A needs assessment was undertaken in Manenberg, a township in Cape Town with high violence and injury rates. Community leaders and successfully established local services were consulted for the design of a first responder care delivery model. The resultant community-based emergency first aid responder (EFAR) system was implemented, and EFARs were tracked over time to determine skill retention and usage.

Results

The EFAR system model and training curriculum. Basic EFARs are spread throughout the community with the option of becoming stationed advanced EFARs. All EFARs are overseen by a local organisation and a professional body, and are integrated with the local ambulance response if one exists. On competency examinations, all EFARs tested averaged 28.2% before training, 77.8% after training, 71.3% 4 months after training and 71.0% 6 months after training. EFARs reported using virtually every skill taught them, and further review showed that they had done so adequately.

Conclusion

The EFAR system is a low-cost, versatile model that can be used in a developing region both to lay the foundation for an emergency care system or support a new one to maturity.
Should lymph nodes from colorectal cancer resection specimens be processed in their entirety?
Authors: Ervine Aaron , Houghton Joe , Park Richard
Published: October 2011

Aims

To quantify the benefit of processing each lymph node in its entirety in colorectal cancer specimens.

Methods

391 consecutive cases were examined retrospectively to assess how often cases were upstaged to node positive disease by examining each node in its entirety.

Results

7 out of 391 patients were upstaged by this method. However, of those patients, approximately three could have been detected by chance. Therefore, approximately 1% of cases were correctly upstaged. However, six of these seven patients also had at least one additional adverse prognostic factor, and would otherwise have been considered high risk Dukes' B cases.

Conclusions

Processing all slices of each lymph node significantly increases laboratory workload and is of minimal clinical benefit.
Mucinous tumours of the ovary
Authors: Naik Jay D , Seligmann Jenny , Perren Timothy J
Published: October 2011

Mucinous epithelial ovarian cancers (mEOC) are a relatively rare subset of ovarian cancers. Despite a relatively favourable outcome in early disease, the more frequent advanced presentation is associated with poorer response to platinum/taxane chemotherapies, and poorer survival, compared to serous ovarian cancers. We consider some of the fundamental clinico-pathological and molecular features, and existing clinical trial data regarding mEOC. Underlying molecular differences, between mEOC and serous cancers may contribute to the observed clinical differences, including an increased prevalence of K-RAS mutations in mEOC, more in keeping with gastrointestinal tumours. This observation contributes to the rationale for a trial (“mEOC”) investigating the use of “ovarian” versus “gastrointestinal” style chemotherapy. Looking to potential future approaches, we speculate upon the potential impact of emerging technologies on the future investigation and management of mEOC.
P16INK4Aoverexpression predicts lymph node metastasis in cervical carcinomas
Authors: Huang Lee-Wen , Lee Chin-Cheng
Published: October 2011

Background

The p16INK4Aprotein (p16) is a cyclin-dependent kinase inhibitor that arrests the cell cycle in the G1 phase.

Aim

To explore the potential of p16 as a predictive marker for lymph node (LN) metastasis and prognosis in cervical carcinomas.

Methods

145 patients diagnosed with FIGO stage I to IV cervical carcinoma were studied; 95 underwent LN dissection. The expression of p16 protein was studied by immunohistochemistry using tissue microarrays.

Results

Overexpression of p16 was seen in 108 of 145 (74.5%) invasive carcinomas. There was a significant correlation between p16 expression and LN metastasis (p=0.007). Patients with p16 overexpression had poorer survival than patients with p16 underexpression (59.3% vs 83.8% 5-year survival rate, log-rank p=0.015). In univariate analysis, p16 expression was a significant predictor of survival (RR 2.76, p=0.02).

Conclusions

Results suggest that p16 expression is an important predictive factor of LN metastasis in cervical cancer patients. Moreover, p16 overexpression is associated with a poor prognosis. Therefore, immunohistochemical evaluation of p16 expression is of potential value for treatment planning in cervical carcinomas.
Why is housing tenure associated with a lower risk of admission to a nursing or residential home? Wealth, health and the incentive to keep ‘my home’
Authors: McCann Mark , Grundy Emily , O'Reilly Dermot
Published: October 2011

Background

Previous research has shown that home ownership is associated with a reduced risk of admission to institutional care. The extent to which this reflects associations between wealth and health, between wealth and ability to buy in care or increased motivation to avoid admission related to policies on charging is unclear. Taking account of the value of the home, as well as housing tenure, may provide some clarification as to the relative importance of these factors.

Aims

To analyse the probability of admission to residential and nursing home care according to housing tenure and house value.

Methods

Cox regression was used to examine the association between home ownership, house value and risk of care home admissions over 6 years of follow-up among a cohort of 51 619 people aged 65 years or older drawn from the Northern Ireland Longitudinal Study, a representative sample of ≈28% of the population of Northern Ireland.

Results

4% of the cohort (2138) was admitted during follow-up. Homeowners were less likely than those who rented to be admitted to care homes (HR 0.77, 95% CI 0.70 to 0.85, after adjusting for age, sex, health, living arrangement and urban/rural differences). There was a strong association between house value/tenure and health with those in the highest valued houses having the lowest odds of less than good health or limiting long-term illness. However, there was no difference in probability of admission according to house value; HRs of 0.78 (95% CI 0.67 to 0.90) and 0.81 (95% CI 0.70 to 0.95), respectively, for the lowest and highest value houses compared with renters.

Conclusions

The requirement for people in the UK with capital resources to contribute to their care is a significant disincentive to institutional admission. This may place an additional burden on carers.
AN ANSWER TO A QUESTION ON VALUE DISTRIBUTION OF THE RIEMANN ZETA-FUNCTION
Authors: GAO RUI , LI BAO QIN
Published: October 2011

We will prove a uniqueness theorem for the Riemann zeta-function in terms of the preimages of three complex values.
Strong glucose dependence of electron current in human monocytes
Authors: Musset Boris , Cherny Vladimir V. , DeCoursey Thomas E.
Published: October 2011

Reactive oxygen species (ROS) production by human monocytes differs profoundly from that by neutrophils and eosinophils in its dependence on external media glucose. Activated granulocytes produce vast amounts of ROS, even in the absence of glucose. Human peripheral blood monocytes (PBM), in contrast, are suspected not to be able to produce any ROS if glucose is absent from the media. Here we compare ROS production by monocytes and neutrophils, measured electrophysiologically on a single-cell level. Perforated-patch-clamp measurements revealed that electron current appeared after stimulation of PBM with phorbol myristate acetate. Electron current reflects the translocation of electrons through the NADPH oxidase, the main source of ROS production. The electron current was nearly abolished by omitting glucose from the media. Furthermore, in preactivated glucose-deprived cells, electron current appeared immediately with the addition of glucose to the bath. To characterize glucose dependence of PBM further, NADPH oxidase activity was assessed as hydrogen peroxide (H2O2) production and was recorded fluorometrically. H2O2 production exhibited similar glucose dependence as did electron current. We show fundamental differences in the glucose dependence of ROS in human monocytes compared with human neutrophils.
Relief of autoinhibition of the electrogenic Na-HCO3 cotransporter NBCe1-B: role of IRBIT vs. amino-terminal truncation
Authors: Lee Seong-Ki , Boron Walter F. , Parker Mark D.
Published: October 2011

Two maneuvers known to stimulate electrogenic sodium bicarbonate cotransporter 1 (NBCe1) activity are 1) deletion from the cytosolic amino-terminus (Nt) of NBCe1-C of an 87-amino acid sequence that contains an autoinhibitory domain (AID); and 2) binding of the protein IRBIT to elements within the same 87-amino acid module in a different variant, NBCe1-B. Helpful to understanding the relationship between these two phenomena would be an appreciation of the relative magnitude of stimulation caused by each maneuver for the same NBCe1 variant. In the present study, we performed two-electrode voltage-clamp on Xenopus oocytes expressing human NBCe1-B constructs, with and without human IRBIT constructs. We find that removal of the AID stimulates NBCe1-B to the same extent as coexpression of wild-type IRBIT. The potency of wild-type IRBIT apparently is reduced by the action of endogenous oocyte protein phosphatases: a mutant IRBIT that cannot be influenced by the action of protein phosphatase-1 stimulates NBCe1-B to an extent 50% greater than can be achieved by removal of the NBCe1-B AID. Thus the stimulatory effect of IRBIT cannot be explained solely by masking of autoinhibitory determinants within the AID. Finally, we find that an NBCe1-B construct that lacks amino acid residues 2–16 of the Nt is fully autoinhibited, but cannot be stimulated by IRBIT, indicating that autoinhibitory and IRBIT-binding determinants within the cytosolic Nt are not identical.
Subcellular localization of skeletal muscle lipid droplets and PLIN family proteins OXPAT and ADRP at rest and following contraction in rat soleus muscle
Authors: MacPherson Rebecca E. K. , Herbst Eric A. F. , Reynolds Erica J. , Vandenboom Rene , Roy Brian D. , Peters Sandra J.
Published: October 2011

Skeletal muscle lipid droplet-associated proteins (PLINs) are thought to regulate lipolysis through protein-protein interactions on the lipid droplet surface. In adipocytes, PLIN2 [adipocyte differentiation-related protein (ADRP)] is found only on lipid droplets, while PLIN5 (OXPAT, expressed only in oxidative tissues) is found both on and off the lipid droplet and may be recruited to lipid droplet membranes when needed. Our purpose was to determine whether PLIN5 is recruited to lipid droplets with contraction and to investigate the myocellular location and colocalization of lipid droplets, PLIN2, and PLIN5. Rat solei were isolated, and following a 30-min equilibration period, they were assigned to one of two groups: 1) 30 min of resting incubation and 2) 30 min of stimulation ( n = 10 each). Immunofluorescence microscopy was used to determine subcellular content, distribution, and colocalization of lipid droplets, PLIN2, and PLIN5. There was a main effect for lower lipid and PLIN2 content in stimulated compared with rested muscles ( P < 0.05). Lipid droplet distribution declined exponentially from the sarcolemma to the fiber center in the rested muscles ( P = 0.001, r2= 0.99) and linearly in stimulated muscles (slope = −0.0023 ± 0.0006, P < 0.001, r2= 0.93). PLIN2 distribution declined exponentially from the sarcolemma to the fiber center in both rested and stimulated muscles ( P < 0.0001, r2= 0.99 rest; P = 0.0004, r2= 0.98 stimulated), while PLIN5 distribution declined linearly (slope = −0.0085 ± 0.0009, P < 0.0001, r2= 0.94 rest; slope=−0.0078 ± 0.0010, P = 0.0003, r2= 0.91 stimulated). PLIN5-lipid droplets colocalized at rest with no difference poststimulation ( P = 0.47; rest r2= 0.55 ± 0.02, stimulated r2= 0.58 ± 0.03). PLIN2-lipid droplets colocalized at rest with no difference poststimulation ( P = 0.48; rest r2= 0.66 ± 0.02, stimulated r2= 0.65 ± 0.02). Contrary to our hypothesis, these results show that PLIN5 is not recruited to lipid droplets with contraction in isolated skeletal muscle.
Isolated Cervical Rib Fracture: A Rare Etiology of Thoracic Outlet Syndrome
Authors: Dar Rayees Ahmad , Wani Sabiya Hamid , Mushtaque Majid
Published: October 2011

Isolated fracture of a cervical rib is a very rare entity and usually presents as a painless swelling or as thoracic outlet syndrome. We describe a case of a 45-year-old woman with history of fall two months back. She presented with symptoms of neurogenic thoracic outlet syndrome for one month. Isolated left cervical rib fracture was documented on X-ray cervical spine. Her fractured cervical rib was resected through a supraclavicular approach, and symptoms resolved completely in the postoperative period.
Peripheral Ossifying Fibroma in the Oral Cavity: MRI Findings
Authors: Chaudhari Swapnali , Umarji Hemant R.
Published: October 2011

The peripheral ossifying fibroma, a benign gingival overgrowth, occurs mainly in the anterior portion of the maxilla in young adults. The size of the lesion is usually less than 1.5 cm. We report a case of peripheral ossifying fibroma overlying the mandibular alveolar ridge of a 55-year-old female. MR scans showed a large exophytic soft tissue mass overlying mandibular alveolar ridge. The tumor revealed peripheral calcifications with slight erosion of adjacent cortical plate.
The Lyon Clinical Olfactory Test: Validation and Measurement of Hyposmia and Anosmia in Healthy and Diseased Populations
Authors: Rouby Catherine , Thomas-Danguin Thierry , Vigouroux Michel , Ciuperca Gabriela , Jiang Tao , Alexanian Jérôme , Barges Mathieu , Gallice Isabelle , Degraix Jean-Louis , Sicard Gilles
Published: October 2011

The LCOT is a self-administered test designed to assess olfactory deficits. Altogether, 525 subjects contributed to the validation. Elderly participants were well represented in this sample. In a validation study (study 1), 407 healthy and 17 anosmic volunteers between 15 and 91 years of age underwent threshold, supraliminal detection, and identification testing. Cutoff values for normosmia and hyposmia were calculated and applied in a second study in a group of patients with smell complaints and in a group of Alzheimer patients with age-matched controls. Incidence of smell deficit was estimated at 5.6% in the healthy population of study 1, and at 16% in the elderly control group of study 2. Assessment of the ability of each subtest to discriminate between groups showed that LCOT is relevant to differentiating between perception and identification deficits and between Alzheimer's and hyposmic patients.