bluuebunny/crossref_metadata_2025 huggingface dataset:
Triangulating the provenance of African elephants using mitochondrial DNA
Authors: Ishida Yasuko , Georgiadis Nicholas J. , Hondo Tomoko , Roca Alfred L.
Published: August 2012

African elephant mitochondrial (mt) DNA follows a distinctive evolutionary trajectory. As females do not migrate between elephant herds, mtDNA exhibits low geographic dispersal. We therefore examined the effectiveness of mtDNA for assigning the provenance of African elephants (or their ivory). For 653 savanna and forest elephants from 22 localities in 13 countries, 4258 bp of mtDNA was sequenced. We detected eight mtDNA subclades, of which seven had regionally restricted distributions. Among 108 unique haplotypes identified, 72% were found at only one locality and 84% were country specific, while 44% of individuals carried a haplotype detected only at their sampling locality. We combined 316 bp of our control region sequences with those generated by previous trans‐national surveys of African elephants. Among 101 unique control region haplotypes detected in African elephants across 81 locations in 22 countries, 62% were present in only a single country. Applying our mtDNA results to a previous microsatellite‐based assignment study would improve estimates of the provenance of elephants in 115 of 122 mis‐assigned cases. Nuclear partitioning followed species boundaries and not mtDNA subclade boundaries. For taxa such as elephants in which nuclear and mtDNA markers differ in phylogeography, combining the two markers can triangulate the origins of confiscated wildlife products.
Manikin‐Ship: Value‐added relatedness in Vietnamese museums, 1996–2005
Authors: Jonsson Hjorleifur
Published: August 2012

Objects are telling of identity and difference, through possession, exchange, and display, but this dynamic must be historicised and socially situated. In this article, I focus on the signification of ethnicity in Vietnamese museums, particularly on an apparent distinction between historically ‘hot’ and ‘cold’ matter. The earliest displays responded to the previous hegemony of French colonial significations. Subsequent national exhibits consistently enable Vietnam through assemblies of objects and images, but suggest—when examined over time—fundamentally different configurations of the nation, ethnicity, gender, and historicity. Object assemblies, where a centrepiece signifies the surrounding objects, indicate repeated prospecting for new social assemblages, most recently situating Vietnam in post‐Cold War networks through the Southeast Asian kinship implied in the nation’s ethnic diversity.
Identifying Areas of High Risk of Human Exposure to Coccidioidomycosis in Texas Using Serology Data from Dogs
Authors: Gautam R. , Srinath I. , Clavijo A. , Szonyi B. , Bani‐Yaghoub M. , Park S. , Ivanek R.
Published: August 2012

Coccidioidomycosis or Valley Fever (VF) is an emerging soil‐borne fungal zoonosis affecting humans and animals. Most non‐human cases of VF are found in dogs, which we hypothesize may serve as sentinels for estimating the human exposure risk. The objective of this study is to use the spatial and temporal distribution and clusters of dogs seropositive for VF to define the geographic area in Texas where VF is endemic, and thus presents a higher risk of exposure to humans. The included specimens were seropositive dogs tested at a major diagnostic laboratory between 1999 and 2009. Data were aggregated by zip code and smoothed by empirical Bayesian estimation to develop an isopleth map of VF seropositive rates using kriging. Clusters of seropositive dogs were identified using the spatial scan test. Both the isopleth map and the scan test identified an area with a high rate of VF‐seropositive dogs in the western and southwestern parts of Texas (relative risk = 31). This location overlapped an area that was previously identified as a potential endemic region based on human surveys. Together, these data suggest that dogs may serve as sentinels for estimating the risk of human exposure to VF.
Antiviral Immune Responses of Bats: A Review
Authors: Baker M. L. , Schountz T. , Wang L.‐F.
Published: August 2012

Despite being the second most species‐rich and abundant group of mammals, bats are also among the least studied, with a particular paucity of information in the area of bat immunology. Although bats have a long history of association with rabies, the emergence and re‐emergence of a number of viruses from bats that impact human and animal health has resulted in a resurgence of interest in bat immunology. Understanding how bats coexist with viruses in the absence of disease is essential if we are to begin to develop therapeutics to target viruses in humans and susceptible livestock and companion animals. Here, we review the current status of knowledge in the field of bat antiviral immunology including both adaptive and innate mechanisms of immune defence and highlight the need for further investigations in this area. Because data in this field are so limited, our discussion is based on both scientific discoveries and theoretical predictions. It is hoped that by provoking original, speculative or even controversial ideas or theories, this review may stimulate further research in this important field. Efforts to understand the immune systems of bats have been greatly facilitated in recent years by the availability of partial genome sequences from two species of bats, a megabat, Pteropus vampyrus, and a microbat, Myotis lucifugus, allowing the rapid identification of immune genes. Although bats appear to share most features of the immune system with other mammals, several studies have reported qualitative and quantitative differences in the immune responses of bats. These observations warrant further investigation to determine whether such differences are associated with the asymptomatic nature of viral infections in bats.
Hantavirus Infection among Wild Small Mammals in Vellore, South India
Authors: Chandy S. , Ulrich R. G. , Schlegel M. , Petraityte R. , Sasnauskas K. , Prakash D. J. , Balraj V. , Abraham P. , Sridharan G.
Published: August 2012

Wild indigenous small mammals including 83 rodents (bandicoot and black rats, and house mice) and a shrew captured from multiple sites in Vellore, south India, were tested for serological and molecular evidence of hantavirus infection. Indirect immunofluorescence assay (IFA) using Hantaan virus (HTNV) antigen indicated hantavirus‐reactive antibodies in 16 (19.3%) of 83 rodents (bandicoot and black rats). Western blot (WB) using Thailand virus (THAIV) antigen confirmed hantavirus‐reactive antibodies in nine of the 16 HTNV IFA‐positive rodents. Reverse transcription polymerase chain reaction (RT‐PCR) of lung and kidney tissue of captured mammals resulted in the detection of partial S segment sequence in a bandicoot rat. This study complements our earlier reports on hantavirus epidemiology in south India and documents first laboratory evidence for rodent‐associated hantaviruses in south India.
A novel enzyme‐dependent melatonin metabolite in humans
Authors: Li Chaoyue , Li Guangming , Tan Dun‐Xian , Li Feng , Ma Xiaochao
Published: August 2012

Exogenous melatonin is widely used in humans for multiple pharmacologic purposes. The metabolic pathways of melatonin reflect the fate and functions of melatonin in vivo. This study was designed to re‐profile melatonin metabolism in humans using a metabolomic approach. In the urine of healthy subjects treated with 10 mg melatonin, sulfate‐ or glucuronide‐conjugated metabolites of melatonin were detected, including 6‐hydroxymelatonin sulfate, 6‐hydroxymelatonin glucuronide, N‐acetylserotonin glucuronide, N‐acetylserotonin sulfate, and an unknown sulfated metabolite (X). The molecular weight of metabolite X was 14 Da smaller than 6‐hydroxymelatonin sulfate, but 16 Da larger than N‐acetylserotonin sulfate. Further studies suggest that metabolite X was produced via O‐demethylation, 6‐hydroxylation, and sulfation. The antioxidant products of melatonin, N(1)‐acetyl‐N(2)‐formyl‐5‐methoxykynuramine and N(1)‐acetyl‐5‐methoxy‐kynuramine, were not detected in human urine. In summary, this study provided a global view of melatonin metabolism in humans and extended our knowledge of enzyme‐dependent pathways of melatonin metabolism.
Long‐term Aβ exposure augments mCa2+‐independent mROS‐mediated depletion of cardiolipin for the shift of a lethal transient mitochondrial permeability transition to its permanent mode in NARP cybrids: a protective targeting of melatonin
Authors: Hsiao Chia‐Wei , Peng Tsung‐I. , Peng Alexander C. , Reiter Russel J. , Tanaka Masashi , Lai Yiu‐Kay , Jou Mei‐Jie
Published: August 2012

Mitochondrial dysfunction is a hallmark of amyloid β‐peptide (Aβ)‐induced neurodegeneration of Alzheimer's disease (AD). This study investigated whether mtDNA T8993G mutation‐induced complex V inhibition, clinically associated with neurological muscle weakness, ataxia, and retinitis pigmentosa (NARP), is a potential risk factor for AD and the pathological link for long‐term exposure of Aβ‐induced mitochondrial toxicity and apoptosis in NARP cybrids. Using noninvasive fluorescence probe–coupled laser scanning imaging microscopy and NARP cybrids harboring 98% mutant genes along with its parental 143B osteosarcoma cells, we demonstrated that Aβ‐augmented mitochondrial Ca2+ (mCa2+)‐independent mitochondrial reactive oxygen species (mROS) formation for a cardiolipin (CL, a major mitochondrial protective phospholipid)‐dependent lethal modulation of the mitochondrial permeability transition (MPT). Aβ augmented not only the amount but also the propagation rate of mROS‐induced mROS formation to significantly depolarize mitochondrial membrane potential (∆Ψm) and reduce mCa2+ stress. Aβ‐augmented mROS oxidized and depleted CL, thereby enhances mitochondrial fission and movement retardation, which promoted the NARP‐augmented lethal transient‐MPT (t‐MPT) to switch to its irreversible mode of permanent‐MPT (p‐MPT). Interestingly, melatonin, a multiple mitochondrial protector, markedly reduced Aβ‐augmented mROS formation and therefore significantly reduced mROS‐mediated depolarization of ∆Ψm, fission of mitochondria and retardation of mitochondrial movement to stabilize CL and hence the MPT. In the presence of melatonin, Aβ‐promoted p‐MPT was reversed to a protective t‐MPT, which preserved ∆Ψm and lowered elevated mCa2+ to sublethal levels for an enhanced mCa2+‐dependent O2 consumption. Thus, melatonin may potentially rescue AD patients associated with NARP symptoms.
High levels of melatonin generated during the brewing process
Authors: Garcia‐Moreno H. , Calvo J. R. , Maldonado M. D.
Published: August 2012

Beer is a beverage consumed worldwide. It is produced from cereals (barley or wheat) and contains a wide array of bioactive phytochemicals and nutraceutical compounds. Specifically, high melatonin concentrations have been found in beer. Beers with high alcohol content are those that present the greatest concentrations of melatonin and vice versa. In this study, gel filtration chromatography and ELISA were combined for melatonin determination. We brewed beer to determine, for the first time, the beer production steps in which melatonin appears. We conclude that the barley, which is malted and ground in the early process, and the yeast, during the second fermentation, are the largest contributors to the enrichment of the beer with melatonin.
Highly selective inhibition of butyrylcholinesterase by a novel melatonin–tacrine heterodimers
Authors: Zawadzka Anna , Łozińska Iwona , Molęda Zuzanna , Panasiewicz Mirosława , Czarnocki Zbigniew
Published: August 2012

Novel inhibitors of cholinesterases, especially butyrylcholinesterase (BuChE), were obtained by coupling melatonin–tacrine heterodimers via the carbamate bond. Compounds 14a‐i possessed potent cholinesterase inhibitory activity (with IC50 values as low as 1.18 nm for acetylcholinesterase (AChE) and 0.24 nm for butyrylcholinesterase (BuChE)). These heterodimers exhibit selectivity toward BuChE, being from 4‐ to 256‐fold more active toward BuChE than AChE, but still acting as better AChE inhibitors than tacrine 4.
An approach to identify, from DCE MRI, significant subvolumes of tumors related to outcomes in advanced head‐and‐neck cancera)
Authors: Wang Peng , Popovtzer Aron , Eisbruch Avraham , Cao Yue
Published: August 2012

Purpose:

To develop and investigate a method to identify, from dynamic contrast enhanced (DCE) MRI, significant subvolumes of tumors related to treatment outcomes.

Methods:

A method, called global‐initiated regularized local fuzzy clustering, was proposed to identify subvolumes of head‐and‐neck cancers (HNC) from heterogeneous distributions of tumor blood volume (BV) and blood flow (BF) for assessment of therapy response. BV and BF images, derived from DCE MRI, of 14 patients with advanced HNC were obtained before treatment and 2 weeks after the start of 7‐week chemoradiation therapy (chemo‐RT). The delineated subvolumes of tumors with low BV or BF before and during treatment were evaluated for their associations with local failure (LF). Receiver operating characteristic (ROC) analysis was used to assess performance of the method for prediction of local failure of HNC.

Results:

The sizes of the subvolumes of primary tumors with low BV, delineated by our method before and week 2 during treatment, were significantly greater in the patients with LF than with local control (LC) (p = 0.02 for pre‐RT and 0.01 for week 2). While the total primary tumor volumes were reduced from baseline to week 2 during therapy to a similar extent for both the patients with LF and LC, the percentage decreases in the subvolumes of the primary tumors with low BV in the same time interval were significantly smaller for the patients with LF than those with LC (p < 0.05). ROC analysis shows that for any given sensitivity, the subvolume of the tumor with low BV week 2 during treatment has greater specificity for prediction of local failure than the pretreatment total tumor volume, the percentage change in the tumor volume week 2 during treatment, or the change in the averaged BV values of the entire tumor week 2 during therapy.

Conclusions:

We developed a method to identify the significant subvolumes of primary tumors related to local failure. Large poorly perfused subvolumes of primary or nodal HNC before treatment and persisting during the early course of chemo‐RT have the potential for prediction of local or regional failure, and could be candidates for local dose intensification.
Magnitude of speed of sound aberration corrections for ultrasound image guided radiotherapy for prostate and other anatomical sites
Authors: Fontanarosa Davide , van der Meer Skadi , Bloemen‐van Gurp Esther , Stroian Gabriela , Verhaegen Frank
Published: August 2012

Purpose:

The purpose of this work is to assess the magnitude of speed of sound (SOS) aberrations in three‐dimensional ultrasound (US) imaging systems in image guided radiotherapy. The discrepancy between the fixed SOS value of 1540 m/s assumed by US systems in human soft tissues and its actual nonhomogeneous distribution in patients produces small but systematic errors of up to a few millimeters in the positions of scanned structures.

Methods:

A correction, provided by a previously published density‐based algorithm, was applied to a set of five prostate, five liver, and five breast cancer patients. The shifts of the centroids of target structures and the change in shape were evaluated.

Results:

After the correction the prostate cases showed shifts up to 3.6 mm toward the US probe, which may explain largely the reported positioning discrepancies in the literature on US systems versus other imaging modalities. Liver cases showed the largest changes in volume of the organ, up to almost 9%, and shifts of the centroids up to more than 6 mm either away or toward the US probe. Breast images showed systematic small shifts of the centroids toward the US probe with a maximum magnitude of 1.3 mm.

Conclusions:

The applied correction in prostate and liver cancer patients shows positioning errors of several mm due to SOS aberration; the errors are smaller in breast cancer cases, but possibly becoming more important when breast tissue thickness increases.
Dosimetric aspects of inverse‐planned modulated‐arc total‐body irradiation
Authors: Held Mareike , Kirby Neil , Morin Olivier , Pouliot Jean
Published: August 2012

Purpose:

To develop optimal beam parameters and to verify the dosimetric aspects of the recently developed modulated‐arc total‐body irradiation (MATBI) technique, which delivers an inverse‐planned dose to the entire body using gantry rotation.

Methods:

The patient is positioned prone and supine underneath the gantry at about 2 m source‐to‐surface distance (SSD). Then, up to 28 beams irradiate the patient from different gantry angles. Based on full‐body computed‐tomography (CT) images of the patient, the weight of each beam is optimized, using inverse planning, to create a uniform body dose. This study investigates how to best simulate patients and the ideal beam setup parameters, such as field size, number of beams, and beam geometry, for treatment time and dose homogeneity. In addition, three anthropomorphic water phantoms were constructed and utilized to verify the accuracy of dose delivery, with both diode array and ion chamber measurements. Furthermore, to improve the accuracy of the new technique, a beam model is created specifically for the extended‐SSD positioning for MATBI.

Results:

Low dose CT scans can be utilized for dose calculations without affecting the accuracy. The largest field size of 40 × 40 cm2 was found to deliver the most uniform dose in the least amount of time. Moreover, a higher number of beams improves dose homogeneity. The average dose discrepancy between ion chamber measurements and extended‐SSD beam model calculations was 1.2%, with the largest discrepancy being 3.2%. This average dose discrepancy was 1.4% with the standard beam model for delivery at isocenter.

Conclusions:

The optimum beam setup parameters, regarding dose uniformity and treatment duration, are laid out for modulated‐arc TBI. In addition, the presented dose measurements show that these treatments can be delivered accurately. These measurements also indicated that a new beam model did not significantly improve the accuracy of dose calculations. The optimum beam setup parameters along with the measurements performed to ensure accurate dose delivery serve as a useful guide for the clinical implementation of MATBI.
Modular Biological Complexity
Authors: Koch Christof
Published: August 2012

Understanding how vast numbers of heterogeneous components behave in biological systems requires consideration of their interactions as modules.
How Low Can You Go? Physical Production Mechanism of Elephant Infrasonic Vocalizations
Authors: Herbst Christian T. , Stoeger Angela S. , Frey Roland , Lohscheller Jörg , Titze Ingo R. , Gumpenberger Michaela , Fitch W. Tecumseh
Published: August 2012

The Song of the Elephant

In mammals, vocal sound production generally occurs in one of two ways, either through muscular control—as when a cat purrs or, more commonly, by air passing through the vocal folds—which occurs in humans and facilitates production of extremely high frequency bat calls. Over the past 20 years, it has been recognized that elephants can communicate through extremely low frequency infrasonic sounds. Taking advantage of a natural death of an elephant in a zoo,

Herbst
et al.

(p.
595
) examined the biomechanics of elephant sound production in an excised elephant larynx. Self-sustained vocal-fold vibrations, without the presence of any neural control, were used to produce infrasonic elephant sounds, using the same mechanism as singing in humans and echolocation in bats.
Aerial Photographs Reveal Late–20th-Century Dynamic Ice Loss in Northwestern Greenland
Authors: Kjær Kurt H. , Khan Shfaqat A. , Korsgaard Niels J. , Wahr John , Bamber Jonathan L. , Hurkmans Ruud , van den Broeke Michiel , Timm Lars H. , Kjeldsen Kristian K. , Bjørk Anders A. , Larsen Nicolaj K. , Jørgensen Lars Tyge , Færch-Jensen Anders , Willerslev Eske
Published: August 2012

A Picture of Disappearing Ice

Global warming is accelerating the loss of ice sheet mass by melting, sublimation, and erosion of their margins. In order to provide a better context for understanding contemporary losses, a longer record of the recent past is needed.

Kjær
et al.

(p.
569
) extend the record of thinning along the northwest margin of the Greenland Ice Sheet back to the mid-1980s, by using archived aerial photographs in conjunction with a digital elevation model and comparing their results to more recent data. Northwestern Greenland has experienced two dynamic ice loss events in the past three decades. Local ice loss appears to be caused by a combination of predictable surface processes that operate over decadal time scales and ones that involve the rapid movement of ice over periods of 3 to 5 years that exhibit strong regional differences.
Cuckoos Combat Socially Transmitted Defenses of Reed Warbler Hosts with a Plumage Polymorphism
Authors: Thorogood Rose , Davies Nicholas B.
Published: August 2012

Learning to Recognize a Cuckoo

Species that are parasitized by cuckoos have evolved several strategies for trying to avoid having their nests hijacked—one of the most obvious being outright attacking, or mobbing, of cuckoos that enter the area. However, cuckoos are not without evolved defenses—most common cuckoo females look remarkably similar to a small hawk, and this mimicry deters mobbing.
Thorogood and Davies
(p.
578
; see the Perspective by

Mappes and Lindström

) show that social learning in parasitized birds can thwart this protective mimicry. When hosts observe mimics being mobbed, they are more likely to mob them, themselves, later. However, the hosts will only mob the color morph that they observed being mobbed. This specificity may have allowed for the evolution and maintenance of two female morphs within common cuckoos.
Non-Centrosymmetric Cylindrical Micelles by Unidirectional Growth
Authors: Rupar Paul A. , Chabanne Laurent , Winnik Mitchell A. , Manners Ian
Published: August 2012

Unidirectional Growth

Block copolymers, in which two dissimilar polymers are covalently joined together, can be designed to form micelles in solution and can be used as self-assembling injectable gels for tissue engineering or wound healing. One challenge is to find ways to create asymmetrical structures, because normally, block addition would occur at both ends of the polymer chain.

Rupar
et al.

(p.
559
; see the Perspective by

Pochan

) devised a route to link together three diblock copolymers with a capping approach. Protecting one end during growth gave rise to asymmetrical structures.
How Did the Cuckoo Get Its Polymorphic Plumage?
Authors: Mappes Johanna , Lindström Leena
Published: August 2012

As reed warblers learn to avoid the threat from cuckoos resembling sparrow hawks, they remain under threat from differently colored cuckoos.
NIH Basics
Authors: Collins Francis S.
Published: August 2012

“When everybody gets to one side of the boat, it usually tips over.” that saying may have originated on Wall Street, but it also stands as a warning to those charting the future of U.S. biomedical research. If the United States focuses too much of its investment on one part of the research continuum, the entire enterprise may sink.
Dreams Meet Realities at AIDS Conference
Authors: Cohen Jon
Published: August 2012

The 19th International AIDS Conference, held in Washington, D.C., from 22 to 27 July, marked the meeting's return to the United States for the first time in 22 years.
Multicellularity Driven by Bacteria
Authors: Carpenter Jennifer
Published: August 2012

Bacteria can prompt single-celled choanoflagellates to divide into multicellular versions of themselves, biologists reported last week at the 71st annual meeting of the Society for Developmental Biology.
NASA's Spacefaring Science Chief Sets a New Course for Mars
Authors: Bhattacharjee Yudhijit
Published: August 2012

Science
spoke to John Grunsfeld, head of NASA's Science Mission Directorate, days before what he calls the science event of the decade: the 5 August (PDT) landing of Curiosity on the martian surface.
Fighting Polio in Pakistan
Authors: Roberts Leslie
Published: August 2012

Pakistan's 18-year struggle shows why it is so hard to eradicate polio from its last few strongholds.
Daily Quality Control in CD3+and CD4+T Cell Estimation by the FACSCount System at a Tertiary Care Center in South India
Authors: Ramalingam Veena V. , Mani Monika , Sundaresan Vijayanand C. , Karunaiya Ramesh J. , Sachithanandham Jaiprasath , Kannangai Rajesh
Published: August 2012

CD4+T cell count estimations are subject to high variations; hence, in this study, the previous day's tested samples were included routinely as the internal quality controls. The percentages of variation of the 2-day values were analyzed for 280 observations and the mean variation for CD4+and CD3+T cell counts ranged from 5.21% to 9.66%. This method is a good internal quality control (IQC) procedure for the estimation of CD3+and CD4+T cell counts in resource-poor settings.
The DBA/1 Strain Is a Novel Mouse Model for Experimental Borrelia burgdorferi Infection
Authors: Campfield Brian T. , Nolder Christi L. , Davis Amy , Hirsch Raphael , Nowalk Andrew J.
Published: August 2012

Lyme arthritis, caused byBorrelia burgdorferi, has similarities to rheumatoid arthritis and its experimental murine model, collagen-induced arthritis (CIA). Currently, no common strain exists for examination of arthritis models of Lyme arthritis and CIA, which are typically studied in C3H/HeJ and DBA/1 mice, respectively. The aim of this study was to define the characteristics ofBorrelia burgdorferiinfection and arthritis in the DBA/1 murine strain. Murine Lyme arthritis was induced in C3H/HeJ and DBA/1 mice by subcutaneous infection withB. burgdorferi. Tibiotarsal joints were measured during infection, and mice were sacrificed for histologic, microbiologic, and serologic analysis on days 14 and 42 postinfection. All bladder cultures obtained from C3H/HeJ and DBA/1 mice at 14 days postinfection grewBorrelia. There was no significant difference in spirochetal burdens in hearts and tibiotarsal joints at days 14 and 42 postinfection. Tibiotarsal joint swelling and histologic scoring were not significantly different between the two strains. Serologic analysis revealed increased IgG2a production in C3H/HeJ mice compared to DBA/1 mice. Analysis of 2-dimensional immunoblots revealed several specific antigens (LA7, BBA03, BBA64, BBA73, OspA, and VlsE) which were not recognized by DBA/1 sera. We conclude that the DBA/1 murine strain is a suitable model for the study of Lyme arthritis and experimentalB. burgdorferiinfection, allowing direct comparison between Lyme arthritis and collagen-induced arthritis. The specificity of the humoral immune response differs between the two strains, further study of which may reveal important findings about how individual strains respond toB. burgdorferiinfection.
Safety and Immunogenicity of a Meningococcal Quadrivalent Conjugate Vaccine in Five- to Eight-Year-Old Saudi Arabian Children Previously Vaccinated with Two Doses of a Meningococcal Quadrivalent Polysaccharide Vaccine
Authors: Khalil Mohamed , Al-Mazrou Yagob , Findlow Helen , Chadha Helen , Bosch Castells Valerie , Johnson David R. , Borrow Ray
Published: August 2012

Saudi Arabian children respond poorly to 2 doses of meningococcal quadrivalent polysaccharide vaccine (MPSV4) when given before 2 years of age. This study examined whether such children were able to respond to 1 dose of quadrivalent meningococcal diphtheria toxoid conjugate vaccine (MCV4) when they were older. Saudi Arabian children 5 to 8 years of age who had previously been vaccinated with 2 doses of MPSV4 when they were under 2 years of age (termed the prior-MPSV4 group) were enrolled in a controlled, open-label, multicenter study. In the prior-MPSV4 group, children (n= 153) received 1 dose of MCV4, as did a group of age-matched meningococcal vaccine-naïve children (n= 85). Blood samples collected prevaccination and 28 days postvaccination were measured for serogroup-specific serum bactericidal antibody (SBA) levels in the presence of baby rabbit complement (rSBA) and for IgG antibody levels. Vaccine tolerability and safety were also evaluated. For all of the measured serogroups (A, C, Y, and W-135), the meningococcal vaccine-naïve participants achieved higher postvaccination rSBA geometric mean titers (GMTs) than did those in the prior-MPSV4 group. This was statistically significant for serogroup C (512 versus 167). Percentages of participants with postvaccination titers of ≥8 and with ≥4-fold increases in prevaccination to postvaccination titers appeared to be quite similar in the 2 groups. No worrisome safety signals were detected. MCV4 induced robust immune responses and was well tolerated in Saudi Arabian children who previously received 2 doses of MPSV4 as well as in those who were previously meningococcal vaccine naïve.
Activation-Induced FoxP3 Expression Regulates Cytokine Production in Conventional T Cells Stimulated with Autologous Dendritic Cells
Authors: Cavatorta Derek J. , Erb Hollis N. , Felippe M. Julia
Published: August 2012

A defining feature of dendritic cells (DCs) is their ability to induce the proliferation of autologous T cells in the absence of foreign antigen—a process termed the “autologous mixed leukocyte reaction” (AMLR). We report that equine monocyte-derived DCs, but not macrophages, are potent inducers of the AMLR. The response is contact dependent and major histocompatibility complex class II dependent and primarily involves CD3+CD4+CD8−T cells. Upon stimulation with DCs or the mitogen concanavalin A, a subset of the proliferating T cells expresses the regulatory T-cell (Treg) transcription factor FoxP3. Although many of these FoxP3+T cells are capable of producing the effector cytokines interleukin-4 (IL-4) and gamma interferon (IFN-γ), they are more likely to produce IL-10 and less likely to produce IFN-γ than equivalent FoxP3−cells. Therefore, FoxP3 expression is an inherent component of equine T cell activation and is associated with a more immunosuppressive cytokine profile. These results confirm that FoxP3 expression in the horse, in contrast to the mouse, is regulated similarly to FOXP3 expression in humans and provide evidence that FoxP3 expression by conventional T cells may help regulate the developing immune response.
Multiplex Assay Detection of Immunoglobulin G Antibodies That Recognize Babesia microti Antigens
Authors: Priest Jeffrey W. , Moss Delynn M. , Won Kimberly , Todd Charles W. , Henderson Leslie , Jones Cara C. , Wilson Marianna
Published: August 2012

Human babesiosis, a blood-borne infection caused by several species of
Babesia
, including
B. microti
, is an emerging disease that is endemic in the Northeast, upper Midwest, and Pacific Northwest regions of the United States. Risk factors for babesiosis include exposure to the infected tick vector and blood transfusions from infected donors. In this work, we cloned and expressed two of the immunodominant antigens from
B. microti
and used them in a multiplex bead format assay (MBA) to detect parasite-specific IgG responses in human sera. The MBA using recombinant
B. microti
secreted antigen 1 (BmSA1) protein was more specific (100%) and slightly more sensitive (98.7%) than the assay using a truncated recombinant BMN1-17 construct (97.6% and 97.4%, respectively). Although some antibody reactivity was observed among sera from confirmed-malaria patients, only one
Plasmodium falciparum
sample was simultaneously positive for IgG antibodies to both antigens. Neither antigen reacted with sera from babesiosis patients who were infected with
Babesia
species other than
B. microti
. Both positive and negative MBA results were reproducible between assays and between instruments. Additional studies of these recombinant antigens and of the multiplex bead assay using blood samples from clinically defined babesiosis patients and from blood donors are needed to more clearly define their usefulness as a blood screening assay.
The Absence of PspA or Presence of Antibody to PspA Facilitates the Complement-Dependent Phagocytosis of PneumococciIn Vitro
Authors: Ren Bing , Li Jie , Genschmer Kristopher , Hollingshead Susan K. , Briles David E.
Published: August 2012

Pneumococcal surface protein A (PspA) is a surface molecule on pneumococci that is required for full virulence in mouse models of infection. PspA has been reported to inhibit complement deposition on the pneumococcal surface. It has been assumed that this decreased complement deposition results in the inefficient phagocytosis of wild-type pneumococci. However, an effect of PspA on phagocytosis had not been shown. Our present studies demonstrated that a loss of PspA by capsular type 3 strains WU2 and A66.1 led to enhanced complement-dependent phagocytosis of the pneumococci by the mouse macrophage cell line J774A.1. This observation was made using human complement as well as mouse complement. Since this enhanced phagocytosis could be blocked by antibody to complement receptor CR3 on J774A.1, it was concluded that PspA's effect on phagocytosis was due to its effect on the amount of deposited complement, which in turn helped opsonize the pneumococci for phagocytosis. Since these studies included new independent mutants lacking PspA, the results provide solid confirmation of the previously reported effects of PspA on pneumococcal virulence and complement deposition. Finally, we showed that antibody to PspA, which is also known to enhance complement deposition, also enhances the phagocytosis of pneumococci in a largely complement-dependent manner.
Dexamethasone Downregulates the Systemic Cytokine Response in Patients with Community-Acquired Pneumonia
Authors: Remmelts Hilde H. F. , Meijvis Sabine C. A. , Biesma Douwe H. , van Velzen-Blad Heleen , Voorn G. Paul , Grutters Jan C. , Bos Willem Jan W. , Rijkers Ger T.
Published: August 2012

The influence of adjunctive corticosteroids on the cytokine response in community-acquired pneumonia (CAP) is largely unknown. In this study, we analyzed the effect of dexamethasone on the cytokine response in patients with CAP and evaluated whether this effect is dependent on the causative microorganism. We hypothesized that dexamethasone has a larger effect on the cytokine response in patients with pneumococcal pneumonia than in patients with pneumonia caused by an atypical bacterium. A total of 304 hospitalized, nonimmunocompromised patients with CAP were randomized to an adjunctive 4-day course of 5 mg dexamethasone once a day (
n
= 151) or a placebo (
n
= 153). Serum concentrations of interleukin-1 receptor antagonist (IL-1Ra), IL-6, IL-8, IL-10, IL-17, tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), macrophage inflammatory protein-1 alpha (MIP-1α), and monocyte chemotactic protein-1 (MCP-1) were measured on days 0, 1, 2, and 4 and at a control visit. Overall, the concentrations of IL-6 (
P
< 0.01), IL-8 (
P
< 0.01), MCP-1 (
P
< 0.01), and TNF-α (
P
< 0.01) were significantly lower on day 2 in the dexamethasone group than in the placebo group. In patients with pneumococcal pneumonia (
n
= 72), both treatment groups showed a rapid decrease of cytokine concentrations; only the concentration of TNF-α (
P
= 0.05) was significantly lower in the dexamethasone group on day 2. In patients with CAP caused by an atypical pathogen (
Legionella pneumophila
,
Chlamydophila
species,
Coxiella burnetii
, or
Mycoplasma pneumoniae
;
n
= 58), IL-1Ra (
P
< 0.01), IL-6 (
P
< 0.01), and MCP-1 (
P
= 0.03) decreased more rapidly in the dexamethasone group than in the placebo group. In conclusion, dexamethasone downregulates the cytokine response during CAP. This effect seems to be dependent on the causative microorganism. This study provides insight into which patients with CAP might benefit most from adjunctive dexamethasone.
Comparative Analysis of Two Broad-Range PCR Assays for Pathogen Detection in Positive-Blood-Culture Bottles: PCR–High-Resolution Melting Analysis versus PCR-Mass Spectrometry
Authors: Jeng Kevin , Gaydos Charlotte A. , Blyn Lawrence B. , Yang Samuel , Won Helen , Matthews Heather , Toleno Donna , Hsieh Yu-Hsiang , Carroll Karen C. , Hardick Justin , Masek Billy , Kecojevic Alexander , Sampath Rangarajan , Peterson Stephen , Rothman Richard E.
Published: August 2012

Detection of pathogens in bloodstream infections is important for directing antimicrobial treatment, but current culture-based approaches can be problematic. Broad-range PCR assays which target conserved genomic motifs for postamplification amplicon analysis permit detection of sepsis-causing pathogens. Comparison of different broad-range assays is important for informing future implementation strategies. In this study, we compared positive-blood-culture bottles processed by PCR coupled to high-resolution melting curve analysis (PCR/HRMA) and PCR coupled to electrospray ionization-mass spectrometry (PCR/ESI-MS) to microbiology culture results. Genus-level concordance was 90% (confidence interval [CI], 80 to 96%) for PCR/HRMA and 94% (CI, 85 to 98%) for PCR/ESI-MS. Species-level concordance was 90% (CI, 80 to 96%) for PCR/HRMA and 86% (CI, 75 to 93%) for PCR/ESI-MS. Unlike PCR/HRMA, PCR/ESI-MS was able to resolve polymicrobial samples. Our results demonstrated that the two assays have similar overall concordance rates but may have different roles as potential adjunctive tests with standard blood culture, since each method has different capabilities, advantages, and disadvantages.
Isolation and Identification of Kroppenstedtia eburnea Isolates from Multiple Patient Samples
Authors: Barker Adam P. , Simmon Keith E. , Cohen Sam , Slechta E. Susan , Fisher Mark A. , Schlaberg Robert
Published: August 2012

No clinical isolates have been reported for the recently described thermoactinomycete
Kroppenstedtia eburnea
. Between 2006 and 2011, we obtained 14 clinical isolates from patients in 9 U.S. states. Here we report growth characteristics, 16S rRNA gene sequencing, matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry-based identification, and antimicrobial susceptibility profiles of this recently described organism.
Aspergillus tanneri sp. nov., a New Pathogen That Causes Invasive Disease Refractory to Antifungal Therapy
Authors: Sugui Janyce A. , Peterson Stephen W. , Clark Lily P. , Nardone Glenn , Folio Les , Riedlinger Gregory , Zerbe Christa S. , Shea Yvonne , Henderson Christina M. , Zelazny Adrian M. , Holland Steven M. , Kwon-Chung Kyung J.
Published: August 2012

The most common cause of invasive aspergillosis (IA) in patients with chronic granulomatous disease (CGD) is
Aspergillus fumigatus
followed by
A. nidulans
; other aspergilli rarely cause the disease. Here we review two clinical cases of fatal IA in CGD patients and describe a new etiologic agent of IA refractory to antifungal therapy. Unlike typical IA caused by
A. fumigatus
, the disease caused by the new species was chronic and spread from the lung to multiple adjacent organs. Mycological characteristics and the phylogenetic relationship with other aspergilli based on the sequence analysis of
Mcm7
,
RPB2
, and
Tsr1
indicated that the new species, which we named as
A. tanneri
, belongs to
Aspergillus
section
Circumdati
. The species has a higher amphotericin B, voriconazole, and itraconazole MIC and causes more chronic infection in CGD mice than
A. fumigatus
. This is the first report documenting IA in CGD patients caused by a species belonging to the
Aspergillus
section
Circumdati
that is inherently resistant to azoles and amphotericin B. Unlike the results seen with many members of
Aspergillus
section
Circumdati
, ochratoxin was not detected in filtrates of cultures grown in various media. Our phenotypic and genetic characterization of the new species and the case reports will assist future diagnosis of infection caused by
A. tanneri
and lead to more appropriate patient management.
Applying a Real-Time PCR Assay for Histoplasma capsulatum to Clinically Relevant Formalin-Fixed Paraffin-Embedded Human Tissue
Authors: Koepsell Scott A. , Hinrichs Steven H. , Iwen Peter C.
Published: August 2012

A real-time PCR assay to detect
Histoplasma capsulatum
in formalin-fixed, paraffin-embedded (FFPE) tissue is described. The assay had an analytical sensitivity of 6 pg/μl of fungal DNA, analytical specificity of 100%, and clinical sensitivity of 88.9%. This proof-of-concept study may aid in the diagnosis of histoplasmosis from FFPE tissue.
Performance Assessment of the DR. TBDR/NTM IVD Kit for Direct Detection of Mycobacterium tuberculosis Isolates, Including Rifampin-Resistant Isolates, and Nontuberculous Mycobacteria
Authors: Lee Meng-Rui , Cheng Aristine , Huang Yu-Tsung , Liu Chia-Ying , Chung Kuei-Pin , Wang Hao-Chien , Liang Sheng-Kai , Liao Chun-Hsing , Yu Chong-Jen , Hsueh Po-Ren
Published: August 2012

We evaluated the performance of the DR. TBDR/NTM IVD kit, which was designed to detect
Mycobacterium tuberculosis
, rifampin-resistant
M. tuberculosis
, and nontuberculous mycobacteria, for detecting 110 positive and 50 negative cultures in
Mycobacterium
Growth Indicator Tubes. The accuracy rate of this kit for identification of
Mycobacterium
species was 95.5% (105/110).
Detection and Serotyping of Lyophilized Nonculturable Pneumococcal Isolates
Authors: Modak Joyanta K. , Steinhoff Mark C. , Zaman K. , Islam Maksuda , El Arifeen Shams , Saha Samir K.
Published: August 2012

One hundred fifty-two nonculturable lyophilized carriage pneumococcal isolates from a vaccine trial were subjected to PCR for serotyping, and 149 (98%) were successfully classified as vaccine or nonvaccine types, which were similar to viable isolates. The methodology will be useful for analysis of this and other studies where stored pneumococcal isolates fail to grow.
Human Endogenous Retrovirus K Gag Coassembles with HIV-1 Gag and Reduces the Release Efficiency and Infectivity of HIV-1
Authors: Monde Kazuaki , Contreras-Galindo Rafael , Kaplan Mark H. , Markovitz David M. , Ono Akira
Published: August 2012

Human endogenous retroviruses (HERVs), which are remnants of ancestral retroviruses integrated into the human genome, are defective in viral replication. Because activation of HERV-K and coexpression of this virus with HIV-1 have been observed during HIV-1 infection, it is conceivable that HERV-K could affect HIV-1 replication, either by competition or by cooperation, in cells expressing both viruses. In this study, we found that the release efficiency of HIV-1 Gag was 3-fold reduced upon overexpression of HERV-K
CON
Gag. In addition, we observed that in cells expressing Gag proteins of both viruses, HERV-K
CON
Gag colocalized with HIV-1 Gag at the plasma membrane. Furthermore, HERV-K
CON
Gag was found to coassemble with HIV-1 Gag, as demonstrated by (i) processing of HERV-K
CON
Gag by HIV-1 protease in virions, (ii) coimmunoprecipitation of virion-associated HERV-K
CON
Gag with HIV-1 Gag, and (iii) rescue of a late-domain-defective HERV-K
CON
Gag by wild-type (WT) HIV-1 Gag. Myristylation-deficient HERV-K
CON
Gag localized to nuclei, suggesting cryptic nuclear trafficking of HERV-K Gag. Notably, unlike WT HERV-K
CON
Gag, HIV-1 Gag failed to rescue myristylation-deficient HERV-K
CON
Gag to the plasma membrane. Efficient colocalization and coassembly of HIV-1 Gag and HERV-K Gag also required nucleocapsid (NC). These results provide evidence that HIV-1 Gag heteromultimerizes with HERV-K Gag at the plasma membrane, presumably through NC-RNA interaction. Intriguingly, HERV-K Gag overexpression reduced not only HIV-1 release efficiency but also HIV-1 infectivity in a myristylation- and NC-dependent manner. Altogether, these results indicate that Gag proteins of endogenous retroviruses can coassemble with HIV-1 Gag and modulate the late phase of HIV-1 replication.
YB-1 Functions as a Porter To Lead Influenza Virus Ribonucleoprotein Complexes to Microtubules
Authors: Kawaguchi Atsushi , Matsumoto Ken , Nagata Kyosuke
Published: August 2012

De novo
-synthesized RNAs are under the regulation of multiple posttranscriptional processes by a variety of RNA-binding proteins. The influenza virus genome consists of single-stranded RNAs and exists as viral ribonucleoprotein (vRNP) complexes. After the replication of vRNP in the nucleus, it is exported to the cytoplasm and then reaches the budding site beneath the cell surface in a process mediated by Rab11a-positive recycling endosomes along microtubules. However, the regulatory mechanisms of the postreplicational processes of vRNP are largely unknown. Here we identified, as a novel vRNP-interacting protein, Y-box-binding protein 1 (YB-1), a cellular protein that is involved in regulation of cellular transcription and translation. YB-1 translocated to the nucleus from the cytoplasm and accumulated in PML nuclear bodies in response to influenza virus infection. vRNP assembled into the exporting complexes with YB-1 at PML nuclear bodies. After nuclear export, using YB-1 knockdown cells and
in vitro
reconstituted systems, YB-1 was shown to be required for the interaction of vRNP exported from the nucleus with microtubules around the microtubule-organizing center (MTOC), where Rab11a-positive recycling endosomes were located. Further, we also found that YB-1 overexpression stimulates the production of progeny virions in an Rab11a-dependent manner. Taking these findings together, we propose that YB-1 is a porter that leads vRNP to microtubules from the nucleus and puts it into the vesicular trafficking system.
Identification of Transmembrane Protein 134 as a Novel LMP1-Binding Protein by Using Bimolecular Fluorescence Complementation and an Enhanced Retroviral Mutagen
Authors: Talaty Pooja , Emery Amanda , Holthusen Kirsten , Everly David N.
Published: August 2012

Latent membrane protein 1 (LMP1) of Epstein-Barr virus induces constitutive signaling in infected cells. LMP1 signaling requires oligomerization of LMP1 via its transmembrane domain, localization to lipid rafts in the membrane, and association of the LMP1 cytoplasmic domain to adaptor proteins, such as the tumor necrosis factor receptor-associated factors (TRAFs). Protein complementation is a novel technique to examine protein-protein interaction through the assembly of functional fluorescent proteins or enzymes from inactive fragments. A previous study in our lab demonstrated the use of bimolecular fluorescence complementation (BiFC) to study the assembly of the LMP1 signaling complexes within the plasma membrane of mammalian cells. In the present study, LMP1 was used as bait in a genome-wide BiFC screen with an enhanced retroviral mutagen to identify new LMP1-binding proteins. Our screen identified a novel LMP1-binding protein, transmembrane protein 134 (Tmem134). Tmem134 is a candidate oncogene that is amplified in breast cancer cell lines. Binding, colocalization, and cofractionation between LMP1 and Tmem134 were confirmed. Finally, Tmem134 affected LMP1-induced NF-κB induction. Together, these data suggest that BiFC is a unique and novel platform to identify proteins recruited to the LMP1-signaling complex.