bluuebunny/crossref_metadata_2025_split huggingface dataset:
Getting the most out of atlas data
Authors: Robertson M. P. , Cumming G. S. , Erasmus B. F. N. 
Published: February 2010

AbstractAim  To review some of the applications in ecology and conservation biogeography of datasets derived from atlas projects. We discuss data applications and data quality issues and suggest ways in which atlas data could be improved.Location  Southern Africa and worldwide.Methods  Atlas projects are broadly defined as collections or syntheses of original, spatially explicit data on species occurrences. We review uses of atlas datasets and discuss data quality issues using examples from atlas projects in southern Africa and worldwide.Results  Atlas projects must cope with tradeoffs between data quality and quantity, standardization of sampling methods, quantification of sampling effort, and mismatches in skills and expectations between data collectors and data users. The most useful atlases have a good measure of sampling effort; include data collected at a fine enough resolution to link to habitat variables of potential interest; have a sufficiently large sample size to work with in a multivariate context; and offer clear, quantitative indications of the quality of each record to allow for the needs of users who have specific demands for high‐quality data.Main conclusions  Atlases have an important role to play in biodiversity conservation and ideally should aim to offer reliable, high quality data that can withstand public, scientific and legal scrutiny.
Climate, climate change and range boundaries
Authors: Thomas Chris D. 
Published: February 2010

AbstractAim A major issue in ecology, biogeography, conservation biology and invasion biology is the extent to which climate, and hence climate change, contributes to the positions of species’ range boundaries. Thirty years of rapid climate warming provides an excellent opportunity to test the hypothesis that climate acts as a major constraint on range boundaries, treating anthropogenic climate change as a large‐scale experiment.Location UK and global data, and literature.Methods This article analyses the frequencies with which species have responded to climate change by shifting their range boundaries. It does not consider abundance or other changes.Results For the majority of species, boundaries shifted in a direction that is concordant with being a response to climate change; 84% of all species have expanded in a polewards direction as the climate has warmed (for the best data available), which represents an excess of 68% of species after taking account of the fact that some species may shift in this direction for non‐climatic reasons. Other data sets also show an excess of animal range boundaries expanding in the expected direction.Main conclusions Climate is likely to contribute to the majority of terrestrial and freshwater range boundaries. This generalization excludes species that are endemic to specific islands, lakes, rivers and geological outcrops, although these local endemics are not immune from the effects of climate change. The observed shifts associated with recent climate change are likely to have been brought about through both direct and indirect (changes to species’ interactions) effects of climate; indirect effects are discussed in relation to laboratory experiments and invasive species. Recent observations of range boundary shifts are consistent with the hypothesis that climate contributes to, but is not the sole determinant of, the position of the range boundaries of the majority of terrestrial animal species.
Continuous Delivery of Biomaterials to the Skin–Percutaneous Device Interface Using a Fluid Pump
Authors: Peramo Antonio , Marcelo Cynthia L. , Goldstein Steven A. , Martin David C. 
Published: February 2010

AbstractWe have developed an in vitro culture system composed of organotypic human skin explants interfaced with titanium rods attached to a fluid pump. This device was designed to mimic the process of natural mucosa delivery at the point where a rigid, permanent object penetrates living skin. Full thickness human breast skin explants discarded from surgeries were cultured at different time points at the air‐liquid interface. The skin specimens were punctured to fit at the bottom of hollow cylindrical titanium rods. Sodium lauryl sulfate (SLS) was delivered continuously to the specimens through the rods by using an attached fluid pump. Histological analysis of the skin explants as well as no‐pump controls was then performed. Our results show substantial differences between controls, where no material was pumped at the interface of rod–skin, and specimens treated with SLS, indicating that the technique of pumping the material is effective in producing observable epithelial changes. These results suggest that an adaptation of this type of device may be useful for the treatment of complications arising from the contact between tissues and percutaneous devices in vivo.
Noninvasive Activity‐based Control of an Implantable Rotary Blood Pump: Comparative Software Simulation Study
Authors: Karantonis Dean M. , Lim Einly , Mason David G. , Salamonsen Robert F. , Ayre Peter J. , Lovell Nigel H. 
Published: February 2010

AbstractA control algorithm for an implantable centrifugal rotary blood pump (RBP) based on a noninvasive indicator of the implant recipient's activity level has been proposed and evaluated in a software simulation environment. An activity level index (ALI)—derived from a noninvasive estimate of heart rate and the output of a triaxial accelerometer—forms the noninvasive indicator of metabolic energy expenditure. Pump speed is then varied linearly according to the ALI within a defined range. This ALI‐based control module operates within a hierarchical multiobjective framework, which imposes several constraints on the operating region, such as minimum flow and minimum speed amplitude thresholds. Three class IV heart failure (HF) cases of varying severity were simulated under rest and exercise conditions, and a comparison with other popular RBP control strategies was performed. Pump flow increases of 2.54, 1.94, and 1.15 L/min were achieved for the three HF cases, from rest to exercise. Compared with constant speed control, this represents a relative flow change of 30.3, 19.8, and −15.4%, respectively. Simulations of the proposed control algorithm exhibited the effective intervention of each constraint, resulting in an improved flow response and the maintenance of a safe operating condition, compared with other control modes.
REVIEW ARTICLE: The Contribution of Macrophages to Normal and Pathological Pregnancies
Authors: Nagamatsu Takeshi , Schust Danny J. 
Published: February 2010

Citation Nagamatsu T, Schust DJ. The contribution of macrophages to normal and pathological pregnancies. Am J Reprod Immunol 2010Macrophages represent one of the major leukocyte subsets in the uterine decidua. Owing to their remarkable phenotypic plasticity, decidual macrophages can participate in diverse activities during pregnancy. At baseline, decidual macrophages are characterized by an immunosuppressive phenotype and M2 polarization, supporting feto‐maternal immune tolerance. In early pregnancy, macrophage‐derived pro‐angiogenic factors prompt vascular remodeling within the uterine wall to ensure appropriate utero‐placental circulation. Upon invasion by pathogens, pattern recognition receptors on decidual macrophages help to alter the characteristics of these malleable cells toward an M1, inflammatory phenotype. Similar inflammatory characteristics are seen in those macrophages that accumulate in the lower segment of the uterus to drive cervical ripening. Disturbances in the tight control that balances macrophage function during pregnancy can trigger the development of pregnancy complications. Here, we discuss the physiologic role of uterine macrophages at different stages of pregnancy and describe their relevance in selected pregnancy disorders.
Biochemical properties of the human guanylate binding protein 5 and a tumor‐speciﬁc truncated splice variant
Authors: Wehner Mark , Herrmann Christian 
Published: February 2010

The human guanylate binding protein 5 (hGBP5) belongs to the family of interferon‐γ‐inducible large GTPases, which are well known for their high induction by pro‐inﬂammatory cytokines. The cellular role of this protein family is unclear at this point, but there are indications for antiviral and antibacterial activity of hGBP1. hGBP5 exists in three splice variants, forming two different proteins, of which the tumor‐speciﬁc one is C‐terminally truncated by 97 amino acids, and therefore lacks the CaaX motif for geranylgeranylation. Here we present biochemical data on the splice variants of hGBP5. We show that, unlike hGBP1, hGBP5a/b and hGBP5ta do not bind GMP or produce any GMP during hydrolysis despite the fact the residues involved in GMP production from hGBP1 are conserved in hGBP5. Hydrolysis of GTP is concentration‐dependent and shows weak self‐activation. Thermodynamic studies showed strongly negative entropic changes during nucleotide binding, which reﬂect structural ordering in the protein during nucleotide binding. These structural changes were also observed during changes in the oligomerization state. We observed only a minor inﬂuence of the C‐terminal truncation on hydrolysis, nucleotide binding and oligomerization of hGBP5. Based on these similarities we speculate that the missing C‐terminal part, which also carries the geranylgeranylation motif, is the reason for the dysregulation of hGBP5′s function in lymphoma cells.Structured digital abstract
MINT‐7555035, MINT‐7555053: hGBP5 a/b (uniprotkb:Q96PP8) and hGBP5 a/b (uniprotkb:Q96PP8) bind (MI:0407) by molecular sieving (MI:0071)
MINT‐7555028, MINT‐7555044: hGBP5ta (uniprotkb:Q86TM5) and hGBP5ta (uniprotkb:Q86TM5) bind (MI:0407) by molecular sieving (MI:0071)
A Qualitative Study of State‐Level Zoonotic Disease Surveillance in New England
Authors: Scotch M. , Mattocks K. , Rabinowitz P. , Brandt C. 
Published: February 2010

SummaryZoonotic diseases are infectious diseases transmittable between animals and humans and outbreaks of these diseases in animals can signify that humans are also infected (or vice versa). Thus, communication between animal and human health agencies is critical for surveillance. Understanding how these agencies conduct surveillance and share information is important for the development of successful automated zoonotic monitoring systems. Individual interviews were conducted with 13 professionals who perform animal or human zoonotic disease surveillance in one of the New England states. Questions centred on existing surveillance methods, collaborations between animal and human health agencies, and technological and data needs. The results showed that agencies routinely communicate over suspected zoonotic disease cases, yet there are barriers preventing automated electronic linking of health data of animals and humans. These include technological barriers and barriers due to sensitivity and confidentiality of information. Addressing these will facilitate the development of electronic systems for integrating animal and human zoonotic disease surveillance data.
Antistaphylococcal Activities of Telavancin Tested Alone and in Combination by Time-Kill Assay
Authors: Lin Gengrong , Pankuch Glenn A. , Ednie Lois M. , Appelbaum Peter C. 
Published: February 2010

ABSTRACT

Synergy time-kill studies against 40 methicillin-resistant
Staphylococcus aureus
(MRSA) strains of differing resistance phenotypes were conducted. Subinhibitory concentrations of telavancin were combined with sub-MIC concentrations of other antimicrobial agents that might be used in combination with telavancin to provide Gram-negative coverage. The highest incidence of synergy was found after 24 h with gentamicin (90% of strains), followed by ceftriaxone (88%), rifampin and meropenem (each 65%), cefepime (45%), and ciprofloxacin (38%) for combinations tested at or below the intermediate breakpoint for each agent.
Characterization of UDP-Glucose Dehydrogenase and UDP-Glucose Pyrophosphorylase Mutants ofProteus mirabilis: Defectiveness in Polymyxin B Resistance, Swarming, and Virulence
Authors: Jiang Sin-Sien , Lin Tzu-Yi , Wang Won-Bo , Liu Ming-Che , Hsueh Po-Ren , Liaw Shwu-Jen 
Published: February 2010

ABSTRACTProteus mirabilisis known to be highly resistant to the action of polymyxin B (PB). However, the mechanism underlying PB resistance is not clear. In this study, we used Tn5transposon mutagenesis to identify genes that may affect PB resistance inP. mirabilis. Two genes,ugdandgalU, which may encode UDP-glucose dehydrogenase (Ugd) and UDP-glucose pyrophosphorylase (GalU), respectively, were identified. Knockout mutants ofugdandgalUwere found to be extremely sensitive to PB, presumably because of alterations in lipopolysaccharide (LPS) structure and cell surface architecture in these mutants. These mutants were defective in swarming, expressed lower levels of virulence factor hemolysin, and had lower cell invasion ability. Complementation of theugdorgalUmutant with the full-lengthugdorgalUgene, respectively, led to the restoration of wild-type phenotypic traits. Interestingly, we found that the expression of Ugd and GalU was induced by PB through RppA, a putative response regulator of the bacterial two-component system that we identified previously. Mutation in eitherugdorgalUled to activation of RpoE, an extracytoplasmic function sigma factor that has been shown to be activated by protein misfolding and alterations in cell surface structure in other bacteria. Activation of RpoE or RpoE overexpression was found to cause inhibition of FlhDC and hemolysin expression. To our knowledge, this is the first report describing the roles and regulation of Ugd and GalU inP. mirabilis.
Single-Dose Pharmacokinetics of Famciclovir in Infants and Population Pharmacokinetic Analysis in Infants and Children
Authors: Blumer Jeffrey , Rodriguez Adib , Sánchez Pablo J. , Sallas William , Kaiser Guenther , Hamed Kamal 
Published: February 2010

ABSTRACT

A multicenter, open-label study evaluated the single-dose pharmacokinetics and safety of a pediatric oral famciclovir (prodrug of penciclovir) formulation in infants aged 1 to 12 months with suspicion or evidence of herpes simplex virus infection. Individualized single doses of famciclovir based on the infant's body weight ranged from 25 to 175 mg. Eighteen infants were enrolled (1 to <3 months old [
n
= 8], 3 to <6 months old [
n
= 5], and 6 to 12 months old [
n
= 5]). Seventeen infants were included in the pharmacokinetic analysis; one infant experienced immediate emesis and was excluded. Mean
C
max
and AUC
0-6
values of penciclovir in infants <6 months of age were ∼3- to 4-fold lower than those in the 6- to 12-month age group. Specifically, mean AUC
0-6
was 2.2 μg·h/ml in infants aged 1 to <3 months, 3.2 μg·h/ml in infants aged 3 to <6 months, and 8.8 μg·h/ml in infants aged 6 to 12 months. These data suggested that the dose administered to infants <6 months was less than optimal. Eight (44.4%) infants experienced at least one adverse event with gastrointestinal events reported most commonly. An updated pharmacokinetic analysis was conducted, which incorporated the data in infants from the present study and previously published data on children 1 to 12 years of age. An eight-step dosing regimen was derived that targeted exposure in infants and children 6 months to 12 years of age to match the penciclovir AUC seen in adults after a 500-mg dose of famciclovir.
Inhibitors of
Leishmania
GDP-Mannose Pyrophosphorylase Identified by High-Throughput Screening of Small-Molecule Chemical Library
Authors: Lackovic Kurt , Parisot John P. , Sleebs Nerida , Baell Jonathan B. , Debien Laurent , Watson Keith G. , Curtis Joan M. , Handman Emanuela , Street Ian P. , Kedzierski Lukasz 
Published: February 2010

ABSTRACT

The current treatment for leishmaniasis is based on chemotherapy, which relies on a handful of drugs with serious limitations, such as high cost, toxicity, and a lack of efficacy in regions of endemicity. Therefore, the development of new, effective, and affordable antileishmanial drugs is a global health priority.
Leishmania
synthesizes a range of mannose-rich glycoconjugates that are essential for parasite virulence and survival. A prerequisite for glycoconjugate biosynthesis is the conversion of monosaccharides to the activated mannose donor, GDP-mannose, the product of a reaction catalyzed by GDP-mannose pyrophosphorylase (GDP-MP). The deletion of the gene encoding GDP-MP in
Leishmania
led to a total loss of virulence, indicating that the enzyme is an ideal drug target. We developed a phosphate sensor-based high-throughput screening assay to quantify the activity of GDP-MP and screened a library containing ∼80,000 lead-like compounds for GDP-MP inhibitors. On the basis of their GDP-MP inhibitory properties and chemical structures, the activities of 20 compounds which were not toxic to mammalian cells were tested against ex vivo amastigotes and in macrophage amastigote assays. The most potent compound identified in the primary screen (compound 3), a quinoline derivative, demonstrated dose-dependent activity in both assays (50% inhibitory concentration = 21.9 μM in the macrophage assay) and was shown to be nontoxic to human fibroblasts. In order to elucidate signs of an early structure-activity relationship (SAR) for this class of compounds, we obtained and tested analogues of compound 3 and undertook limited medicinal chemistry optimization, which included the use of a number of SAR probes of the piperazinyl aryl substituent of compound 3. We have identified novel candidate compounds for the design and synthesis of antileishmanial therapeutics.
Increased Tolerance to Artemisinin in
Plasmodium falciparum
Is Mediated by a Quiescence Mechanism
Authors: Witkowski Benoit , Lelièvre Joel , López Barragán María José , Laurent Victor , Su Xin-zhuan , Berry Antoine , Benoit-Vical Françoise 
Published: February 2010

ABSTRACT

Artemisinin (ART)-based combination therapies (ACTs) are the first-line drugs—and often the last treatments—that can effectively cure
Plasmodium falciparum
infections. Unfortunately, the decreased clinical efficacy of artesunate, one of the major ART derivatives, was recently reported along the Thailand-Cambodia border. Through long-term artemisinin pressure
in vitro
, we have obtained an ART-tolerant strain that can survive extremely high doses of ART. We showed that drug pressure could induce a subpopulation of ring stages into developmental arrest, which can explain the ART tolerance in
P. falciparum
. We also observed interesting transcriptomic modifications possibly associated with the acquisition of ART tolerance. These modifications include the overexpression of heat shock and erythrocyte surface proteins and the downexpression of a cell cycle regulator and a DNA biosynthesis protein. This study highlights a new phenomenon in the
Plasmodium
response to ART that may explain the delayed clearance of parasites after artesunate treatment observed on the Thailand-Cambodia border and that provides important information for achieving a better understanding of the mechanisms of antimalarial resistance.
Upregulated Expression of B-Cell Antigen Family Tandem Repeat Proteins byLeishmaniaAmastigotes
Authors: Goto Yasuyuki , Carter Darrick , Guderian Jeffrey , Inoue Noboru , Kawazu Shin-Ichiro , Reed Steven G. 
Published: February 2010

ABSTRACTProteins with tandem repeat (TR) domains have been found in various protozoan parasites, and they are often targets of B-cell responses. Through systematic analyses of whole proteomes, we recently demonstrated that two trypanosomatid parasites,Leishmania infantumandTrypanosoma cruzi, are rich in antigenic proteins with large TR domains. However, the reason that these proteins are antigenic was unclear. Here, by performing molecular, immunological, and bioinformatic characterizations ofLeishmaniaTR proteins, we found two possible factors affecting the antigenicity of these proteins; one factor is their fundamental composition as TR proteins, and the other is regulation of their expression by parasites. Enzyme-linked immunosorbent assays (ELISAs) using recombinant proteins revealed that the copy number of the repeat affects the affinity of binding between antigens and antibodies, as expected based on thermodynamic binding kinetics. Other than containing TR domains, the TR proteins do not share characteristics, such as sequence similarity or biased cellular location predicted by the presence of a signal sequence(s) and/or a transmembrane domain(s). However, the TR proteome contained a higher percentage of proteins upregulated in amastigotes than the whole proteome, and upregulated expression of a TR protein seemed to affect its antigenicity. These results indicate thatLeishmaniaparasites actively utilize the TR protein family for parasitism in mammalian hosts.
The Yersiniabactin Transport System Is Critical for the Pathogenesis of Bubonic and Pneumonic Plague
Authors: Fetherston Jacqueline D. , Kirillina Olga , Bobrov Alexander G. , Paulley James T. , Perry Robert D. 
Published: February 2010

ABSTRACT

Iron acquisition from the host is an important step in the pathogenic process. While
Yersinia pestis
has multiple iron transporters, the yersiniabactin (Ybt) siderophore-dependent system plays a major role in iron acquisition
in vitro
and
in vivo
. In this study, we determined that the Ybt system is required for the use of iron bound by transferrin and lactoferrin and examined the importance of the Ybt system for virulence in mouse models of bubonic and pneumonic plague.
Y. pestis
mutants unable to either transport Ybt or synthesize the siderophore were both essentially avirulent via subcutaneous injection (bubonic plague model). Surprisingly, via intranasal instillation (pneumonic plague model), we saw a difference in the virulence of Ybt biosynthetic and transport mutants. Ybt biosynthetic mutants displayed an ∼24-fold-higher 50% lethal dose (LD
50
) than transport mutants. In contrast, under iron-restricted conditions
in vitro
, a Ybt transport mutant had a more severe growth defect than the Ybt biosynthetic mutant. Finally, a Δ
pgm
mutant had a greater loss of virulence than the Ybt biosynthetic mutant, indicating that the 102-kb
pgm
locus encodes a virulence factor, in addition to Ybt, that plays a role in the pathogenesis of pneumonic plague.
Intracellular Invasion by
Orientia tsutsugamushi
Is Mediated by Integrin Signaling and Actin Cytoskeleton Rearrangements
Authors: Cho Bon-A , Cho Nam-Hyuk , Seong Seung-Yong , Choi Myung-Sik , Kim Ik-Sang 
Published: February 2010

ABSTRACT

Orientia tsutsugamushi
, the causative agent of scrub typhus, is an obligate intracellular pathogen. Previously, we reported that the 56-kDa type-specific antigen (TSA56), a major outer membrane protein of
O. tsutsugamushi
, binds to fibronectin and facilitates bacterial entry into the host cell, potentially via an interaction with integrins. Here, we demonstrated that
O. tsutsugamushi
colocalizes with integrin α5β1 and activates integrin signaling effectors, including focal adhesion kinase, Src kinase, and RhoA GTPase, and also recruits signaling adaptors, such as talin and paxillin, to the site of infection. Inhibition of protein tyrosine kinases or RhoA reduced intracellular invasion. We also observed substantial actin reorganization and membrane protrusions at the sites of infection of nonphagocytic host cells. Finally, we identified a region in the extracellular domain of TSA56 that binds to fibronectin. A peptide containing this region was able to significantly reduce bacterial invasion. Taken together, these results clearly indicate that
O. tsutsugamushi
exploits integrin-mediated signaling and the actin cytoskeleton for invasion of eukaryotic host cells.