bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue engineering for the management of chronic wounds: current concepts and future perspectives
Authors: Wong Victor W. , Gurtner Geoffrey C. 
Published: May 2012

AbstractChronic wounds constitute a significant and growing biomedical burden. With the increasing growth of populations prone to dysfunctional wound healing, there is an urgent and unmet need for novel strategies to both prevent and treat these complications. Tissue engineering offers the potential to create functional skin, and the synergistic efforts of biomedical engineers, material scientists, and molecular and cell biologists have yielded promising therapies for non‐healing wounds. However, traditional paradigms for wound healing focus largely on the role of inflammatory cells and fail to incorporate more recent research highlighting the importance of stem cells and matrix dynamics in skin repair. Approaches to chronic wound healing centred on inflammation alone are inadequate to guide the development of regenerative medicine‐based technologies. As the molecular pathways and biologic defects underlying non‐healing wounds are further elucidated, multifaceted bioengineering systems must advance in parallel to exploit this knowledge. In this viewpoint essay, we highlight the current concepts in tissue engineering for chronic wounds and speculate on areas for future research in this increasingly interdisciplinary field.
The Role of Conserved PEX3 Regions in PEX19‐Binding and Peroxisome Biogenesis
Authors: Schmidt Friederike , Dietrich Denise , Eylenstein Roy , Groemping Yvonne , Stehle Thilo , Dodt Gabriele 
Published: May 2012

AbstractThe human peroxins PEX3 and PEX19 are essential for peroxisome biogenesis. They mediate the import of membrane proteins as well as the de novo formation of peroxisomes. PEX19 binds newly synthesized peroxisomal membrane proteins post‐translationally and directs them to peroxisomes by engaging PEX3, a protein anchored in the peroxisomal membrane. After protein insertion into the lipid bilayer, PEX19 is released back to the cytosol. Crystallographic analysis provided detailed insights into the PEX3–PEX19 interaction and identified three highly conserved regions, the PEX19‐binding region, a hydrophobic groove and an acidic cluster, on the surface of PEX3. Here, we used site‐directed mutagenesis and biochemical and functional assays to determine the role of these regions in PEX19‐binding and peroxisome biogenesis. Mutations in the PEX19‐binding region reduce the affinity for PEX19 and destabilize PEX3. Furthermore, we provide evidence for a crucial function of the PEX3–PEX19 complex during de novo formation of peroxisomes in peroxisome‐deficient cells, pointing to a dual function of the PEX3–PEX19 interaction in peroxisome biogenesis. The maturation of preperoxisomes appears to require the hydrophobic groove near the base of PEX3, presumably by its involvement in peroxisomal membrane protein insertion, while the acidic cluster does not appear to be functionally relevant.
Viral load at diagnosis and influenza A H1N1 (2009) disease severity in children
Authors: Launes Cristian , Garcia‐Garcia Juan J. , Jordan Iolanda , Selva Laura , Rello Jordi , Muñoz‐Almagro Carmen 
Published: May 2012

Please cite this paper as: Launes et al. (2012) Viral load at diagnosis and influenza A H1N1 (2009) disease severity in children. Influenza and Other Respiratory Viruses 6(601), e89–e92.To assess viral load at diagnosis (VLAD) as a biomarker of novel influenza disease severity, epidemiologic and clinical data of admitted patients <18 years old with Influenza A H1N1 (2009) infection and respiratory symptoms were prospectively collected in a single pediatric tertiary hospital, from weeks 30–51 of 2009. Seventy patients were included. VLAD in children who had symptoms for ≥5 days was an accurate parameter distinguishing the patients who required mechanical ventilation (MV) from those who did not required it (area under the ROC curve: 0·73; P = 0·03). Having <4·5 log10 copies/ml with ≥5 days of symptoms was associated with a lower risk of requiring MV.
Thinking about the Gym: Greek Ideals, Newtonian Bodies and Exercise in Early Eighteenth‐Century Britain
Authors: BATCHELOR ROBERT 
Published: May 2012

AbstractRevival of Greek ideas about exercise in the British and Irish Enlightenment by doctors led to a shift in understandings about the independent mind by establishing a relation between bodily and mental health. By the late 1730s, interest shifted away from mind and body and towards the sentiments and passions, which marked gender distinctions and held together national communities. Gilbert West's writing about the Olympics in the 1740s indicated the difficulty in resolving tensions about exercise and sport producing aristocratic distinction and violent passions as against their encouragement of healthy minds and civic virtue in the nation.
National Heroics: Bullfighters, Machismo and the Cult of Celebrity
Authors: ZANARDI TARA 
Published: May 2012

AbstractBullfighting, in its newly transformed format, served as a rich source for artists in its overt performativity. Although images of bull‐related themes exist before 1700, it was not until the second half of the eighteenth century that taurine subjects became fashionable in Spanish visual culture. As the fighters achieved celebrity status, such heroics were often considered in patriotic terms. The bullfighters' bravado exemplified their bodily performance of machismo. Such machismo was regarded by many as an expression of national pride. By considering chiefly visual examples, I discuss the cult of celebrity that surrounded the bullfight during the late eighteenth century.
Heterozygote Genotypes at rs2222823 and rs2811712 SNP Loci are Associated with Cerebral Small Vessel Disease in Han Chinese Population
Authors: Li Wei , Hu Bo , Li Gui‐Lin , Zhao Xing‐Quan , Xin Bao‐Zhong , Lin Jin‐Xi , Shen Yuan , Liang Xian‐Hong , Liu Gai‐Fen , Gao Han‐Qing , Liao Xiao‐Ling , Liang Zhi‐Gang , Wang Yong‐Jun 
Published: May 2012

SUMMARY AimsWith developments of etiology of cerebral small vessel disease (CSVD) and genome‐wide association study (GWAS) of stroke, the genetic studies of CSVD are focused on genes related to blood‐brain barrier (BBB) and aging. The project aims to investigate the association between CSVD and susceptibility loci and candidate genes.MethodsAll study subjects admitted Beijing Tiantan Hospital from June 2009 to September 2010 including 197 cerebral small vessel disease patients(S), 198 large artery atherosclerosis control individuals (vascular stenotic rate ≥50% diameter reduction) (L), 200 hypertensive intracerebral hemorrhage control individuals (H) and 197 stroke‐free control individuals (C). 15 SNPs in 4 genes (MYLK, AQP4, NINJ2, and INK4/ARF) were genotyped using Multiplex Snapshot assay. Each SNP was first examined between the groups S and C in different genetic models (codominant, dominant, recessive, overdominant, and log‐additive). Permutation correction was used to adjust for multiple testing. The significant SNP loci were further analyzed in comparing S with L and H, respectively. Subgroup analysis was also performed for each risk‐factor category.ResultsAmong the 15 SNPs, rs2222823 and rs2811712 were found to be significantly associated with CSVD after multiple‐testing adjustment. The heterozygote (A/T) of rs2222823 of MYLK has an odds ratio of 0.52 (95% CI =[0.35, 0.79], P= 0.002, adjusted P= 0.031) when compared with homozygotes. The heterozygote (C/T) of rs2811712 of INK4/ARF has an odds ratio of 1.75 (95% CI =[1.13–2.71], P= 0.004, adjusted P= 0.050). The SNP rs2222823 was significant (P= 0.035) in comparing S with H. In comparing S versus L, it is significant for the subgroups of patients without diabetes (P= 0.012) and drinking (P= 0.018). rs2811712 was significant in comparing S with L for the subgroups of patients with hyperlipidemia (P= 0.029) and drinking (P= 0.04).ConclusionThe heterozygotes (T/A) at the rs2222823 SNP locus of MYLK gene decreases the risk of having cerebral small vessel disease, while the heterozygotes (C/T) at the rs2811712 SNP locus of INK4/ARF gene increases the risk, suggesting that the MYLK and INK4/ARF are the associated genes of cerebral small vessel disease in Han Chinese population.
Impact of process variables on the micromeritic and physicochemical properties of spray-dried microparticles – Part II. Physicochemical characterisation of spray-dried materials
Authors: Paluch Krzysztof J , Tajber Lidia , Amaro Maria I , Corrigan Owen I , Healy Anne Marie 
Published: May 2012

Abstract

Objectives
In this work we investigated the residual organic solvent content and physicochemical properties of spray-dried chlorothiazide sodium (CTZNa) and potassium (CTZK) salts.

Methods
The powders were characterised by thermal, X-ray diffraction, infrared and dynamic vapour sorption (DVS) analyses. Solvent levels were investigated by Karl–Fischer titration and gas chromatography.

Key findings
Spray-drying from water, methanol (MeOH) and mixes of MeOH and butyl acetate (BA) resulted in amorphous microparticles. The glass transition temperatures of CTZNa and CTZK were ∼192 and ∼159°C, respectively. These materials retained their amorphous nature when stored at 25°C in dry conditions for at least 6 months with no chemical decomposition observed. DVS determined the critical relative humidity of recrystallisation of CTZNa and CTZK to be 57% RH and 58% RH, respectively. The inlet temperature dependant oxidation of MeOH to formaldehyde was observed; the formaldehyde was seen to deposit within the amorphous matrix of spray-dried product. Spray-drying in the open blowing mode coupled with secondary drying resulted in a three-fold reduction in residual BA (below pharmacopoeial permitted daily exposure limit) compared to spray-drying in the closed mode.

Conclusions
Experiments showed that recirculation of recovered drying gas increases the risk of deposition of residual solvents in the spray-dried product.
Chronic Hepatitis C Virus Infection Breaks Tolerance and Drives Polyclonal Expansion of Autoreactive B Cells
Authors: Roughan Jill E. , Reardon Kathryn M. , Cogburn Kristin E. , Quendler Heribert , Pockros Paul J. , Law Mansun 
Published: May 2012

ABSTRACTChronic Hepatitis C virus (HCV) infection has been linked with B cell lymphoproliferative disorders and several autoimmune-related diseases. The mechanisms of how chronic viral infection affects B cell development and predisposes the patients to autoimmune manifestations are poorly understood. In this study, we established an experimental system to probe the B cell responses and characterize the antibodies from chronic-HCV-infected individuals. We identified an unusual polyclonal expansion of the IgM memory B cell subset in some patients. This B cell subset is known to be tightly regulated, and autoreactive cells are eliminated by tolerance mechanisms. Genetic analysis of the immunoglobulin (Ig) heavy chain variable gene (VH) sequences of the expanded cell population showed that the levels of somatic hypermutation (SHM) correlate with the extent of cell expansion in the patients and that the VHgenes exhibit signs of antigen-mediated selection. Functional analysis of the cloned B cell receptors demonstrated autoreactivity in some of the expanded IgM memory B cells in the patients which is not found in healthy donors. In summary, this study demonstrated that, in some patients, chronic HCV infection disrupts the tolerance mechanism that normally deletes autoreactive B cells, therefore increasing the risk of developing autoimmune antibodies. Long-term follow-up of this expanded B cell subset within the infected individuals will help determine whether these cells are predictors of more-serious clinical manifestations.
The FomA Porin from Fusobacterium nucleatum Is a Toll-Like Receptor 2 Agonist with Immune Adjuvant Activity
Authors: Toussi Deana N. , Liu Xiuping , Massari Paola 
Published: May 2012

ABSTRACTMany bacterial components selectively activate immune and nonhematopoietic target cells via Toll-like receptor (TLR) signaling; modulation of such host responses defines the immune adjuvant properties of these bacterial products. For example, the outer membrane protein porins fromNeisseria,Salmonella, andShigellaare known TLR2 agonists with established systemic and mucosal immune adjuvanticity. Early work indicated that the FomA porin fromFusobacterium nucleatumhas immune adjuvant activity in mice. Using a purified recombinant FomA, we have verified its immune stimulatory properties and have defined a role for TLR2 signaling in itsin vitroandin vivoactivity. FomA induces interleukin 8 (IL-8) secretion and NF-κB-dependent luciferase activity in HEK cells expressing TLR2, IL-6 secretion, and cell surface upregulation of CD86 and major histocompatibility complex (MHC) II in primary B cells from wild-type mice, but it fails to activate cells from TLR2 knockout mice. Accordingly, the immune adjuvant activity of FomA is also TLR2 dependent. In a mouse model of immunization with ovalbumin (OVA), FomA induces enhanced production of OVA-specific IgM and IgG, including IgG1 and IgG2b antibodies, as well as enhanced secretion of IL-10 and IL-6, consistent with a Th2-type adjuvant effect. We also observe a moderate production of anti-FomA antibodies, suggesting that FomA is also immunogenic, a quality that is also TLR2 dependent. Therefore, modulation of host immune responses by FomA may be effective for targeting general host immunity not only to pathogens (as a novel TLR2 adjuvant) but also toF. nucleatumitself (as an antigen), expanding its use as a self-adjuvanted antigen in an immunization strategy against polymicrobial infections, including those byF. nucleatum.
Prevalence of Trichomonas vaginalis and Coinfection with Chlamydia trachomatis and Neisseria gonorrhoeae in the United States as Determined by the Aptima Trichomonas vaginalis Nucleic Acid Amplification Assay
Authors: Ginocchio C. C. , Chapin K. , Smith J. S. , Aslanzadeh J. , Snook J. , Hill C. S. , Gaydos C. A. 
Published: May 2012

ABSTRACT

Our aim was to determine
Trichomonas vaginalis
prevalence using the Aptima
Trichomonas vaginalis
assay (ATV; Gen-Probe) and the prevalence of
Chlamydia trachomatis
and
Neisseria gonorrhoeae
coinfections in U.S. women undergoing screening for
C. trachomatis
/
N. gonorrhoeae
. Discarded urogenital samples from 7,593 women (18 to 89 years old) undergoing
C. trachomatis
/
N. gonorrhoeae
screening using the Aptima Combo 2 assay (Gen-Probe) in various clinical settings were tested with ATV. Overall,
T. vaginalis
,
C. trachomatis
, and
N. gonorrhoeae
prevalences were 8.7%, 6.7%, and 1.7%, respectively.
T. vaginalis
was more prevalent than
C. trachomatis
or
N. gonorrhoeae
in all age groups except the 18- to 19-year-old group. The highest
T. vaginalis
prevalence was in women ≥40 years old (>11%), while the highest
C. trachomatis
prevalence (9.2%) and
N. gonorrhoeae
prevalence (2.2%) were in women <30 years old. Coinfection prevalences were 1.3% for
C. trachomatis
/
T. vaginalis
, 0.61% for
C. trachomatis
/
N. gonorrhoeae
and
N. gonorrhoeae
/
T. vaginalis
, and 0.24% for
C. trachomatis
/
N. gonorrhoeae
/
T. vaginalis
and highest in women <30 years old.
T. vaginalis
prevalence differed by race/ethnicity, with the highest prevalence in black women (20.2%).
T. vaginalis
prevalence ranged from 5.4% in family planning clinics to 22.3% in jails. Multivariate analysis determined that ages of ≥40 years, black race, and patient locations were significantly associated with
T. vaginalis
infection.
T. vaginalis
is the most common sexually transmitted infection (STI) in women of >40 years, while
C. trachomatis
and
N. gonorrhoeae
prevalence is lowest in that age group. Higher
T. vaginalis
prevalence in women of >40 years is probably attributed to the reason for testing, i.e., symptomatic status versus routine screening in younger women. Coinfections were relatively low. High
T. vaginalis
prevalence in all age groups suggests that women screened for
C. trachomatis
/
N. gonorrhoeae
, whether asymptomatic or symptomatic, should be screened for
T. vaginalis
.
Human Papillomavirus Type 8 E6 Oncoprotein Inhibits Transcription of the PDZ Protein Syntenin-2
Authors: Lazić Daliborka , Hufbauer Martin , Zigrino Paola , Buchholz Stephanie , Kazem Siamaque , Feltkamp Mariet C. W. , Mauch Cornelia , Steger Gertrud , Pfister Herbert , Akgül Baki 
Published: May 2012

ABSTRACT

The E6 proteins from high-risk alpha human papillomavirus (HPV) types (e.g., HPV16) are characterized by the presence of a PDZ-binding motif through which they interact with a number of cellular PDZ domain-containing substrates and cooperate in their degradation. The ability of these E6 proteins to bind to PDZ domain proteins correlates with the oncogenic potential of the virus. The E6 proteins of oncogenic HPV from the genus
Betapapillomavirus
(betaPV, e.g., HPV8) do not encode a PDZ-binding motif. We found that the PDZ domain protein syntenin-2 is transcriptionally downregulated in primary human epidermal keratinocytes (PHEK) by HPV8 E6. The mRNA levels of the known HPV16 E6 PDZ protein targets Dlg, Scribble, Magi-1, Magi-3, PSD95, and Mupp1 were not changed by HPV8 E6. Decreased protein levels of syntenin-2 were observed in cell extracts from PHEK expressing HPV5, -8, -16, -20, and -38 E6 but not in HPV1 and -4 E6-positive keratinocytes. Surprisingly, HPV16 E6 also repressed transcription of syntenin-2 but with a much lower efficiency than HPV8 E6. In healthy human skin, syntenin-2 expression is localized in suprabasal epidermal layers. In organotypic skin cultures, the differentiation-dependent expression of syntenin-2 was absent in HPV8 E6- and E6E7-expressing cells. In basal cell carcinomas of the skin, syntenin-2 was not detectable, whereas in squamous cell carcinomas, expression was located in differentiated areas. Short hairpin RNA-mediated knockdown of syntenin-2 led to an inhibition of differentiation and an increase in the proliferation capacity in PHEK. These results identified syntenin-2 as the first PDZ domain protein controlled by HPV8 and HPV16 at the mRNA level.
Herpes Simplex Virus 1 Infection Activates Poly(ADP-Ribose) Polymerase and Triggers the Degradation of Poly(ADP-Ribose) Glycohydrolase
Authors: Grady Sarah L. , Hwang Jesse , Vastag Livia , Rabinowitz Joshua D. , Shenk Thomas 
Published: May 2012

ABSTRACT

Herpes simplex virus 1 infection triggers multiple changes in the metabolism of host cells, including a dramatic decrease in the levels of NAD
+
. In addition to its role as a cofactor in reduction-oxidation reactions, NAD
+
is required for certain posttranslational modifications. Members of the poly(ADP-ribose) polymerase (PARP) family of enzymes are major consumers of NAD
+
, which they utilize to form poly(ADP-ribose) (PAR) chains on protein substrates in response to DNA damage. PAR chains can subsequently be removed by the enzyme poly(ADP-ribose) glycohydrolase (PARG). We report here that the HSV-1 infection-induced drop in NAD
+
levels required viral DNA replication, was associated with an increase in protein poly(ADP-ribosyl)ation (PARylation), and was blocked by pharmacological inhibition of PARP-1/PARP-2 (PARP-1/2). Neither virus yield nor the cellular metabolic reprogramming observed during HSV-1 infection was altered by the rescue or further depletion of NAD
+
levels. Expression of the viral protein ICP0, which possesses E3 ubiquitin ligase activity, was both necessary and sufficient for the degradation of the 111-kDa PARG isoform. This work demonstrates that HSV-1 infection results in changes to NAD
+
metabolism by PARP-1/2 and PARG, and as PAR chain accumulation can induce caspase-independent apoptosis, we speculate that the decrease in PARG levels enhances the auto-PARylation-mediated inhibition of PARP, thereby avoiding premature death of the infected cell.
Suppression of the Interferon and NF-κB Responses by Severe Fever with Thrombocytopenia Syndrome Virus
Authors: Qu Bingqian , Qi Xian , Wu Xiaodong , Liang Mifang , Li Chuan , Cardona Carol J. , Xu Wayne , Tang Fenyang , Li Zhifeng , Wu Bing , Powell Kira , Wegner Marta , Li Dexin , Xing Zheng 
Published: May 2012

ABSTRACT

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease characterized by high fever, thrombocytopenia, multiorgan dysfunction, and a high fatality rate between 12 and 30%. It is caused by SFTS virus (SFTSV), a novel
Phlebovirus
in family
Bunyaviridae
. Although the viral pathogenesis remains largely unknown, hemopoietic cells appear to be targeted by the virus. In this study we report that human monocytes were susceptible to SFTSV, which replicated efficiently, as shown by an immunofluorescence assay and real-time reverse transcription-PCR. We examined host responses in the infected cells and found that antiviral interferon (IFN) and IFN-inducible proteins were induced upon infection. However, our data also indicated that downregulation of key molecules such as mitochondrial antiviral signaling protein (MAVS) or weakened activation of interferon regulatory factor (IRF) and NF-κB responses may contribute to a restricted innate immunity against the infection. NSs, the nonstructural protein encoded by the S segment, suppressed the beta interferon (IFN-β) and NF-κB promoter activities, although NF-κB activation appears to facilitate SFTSV replication in human monocytes. NSs was found to be associated with TBK1 and may inhibit the activation of downstream IRF and NF-κB signaling through this interaction. Interestingly, we demonstrated that the nucleoprotein (N), also encoded by the S segment, exhibited a suppressive effect on the activation of IFN-β and NF-κB signaling as well. Infected monocytes, mainly intact and free of apoptosis, may likely be implicated in persistent viral infection, spreading the virus to the circulation and causing primary viremia. Our findings provide the first evidence in dissecting the host responses in monocytes and understanding viral pathogenesis in humans infected with a novel deadly
Bunyavirus
.
Involvement of the Chloroplastic Isoform of tRNA Ligase in the Replication of Viroids Belonging to the Family
Avsunviroidae
Authors: Nohales María-Ángeles , Molina-Serrano Diego , Flores Ricardo , Daròs José-Antonio 
Published: May 2012

ABSTRACT

Avocado sunblotch viroid, peach latent mosaic viroid, chrysanthemum chlorotic mottle viroid, and eggplant latent viroid (ELVd), the four recognized members of the family
Avsunviroidae
, replicate through the symmetric pathway of an RNA-to-RNA rolling-circle mechanism in chloroplasts of infected cells. Viroid oligomeric transcripts of both polarities contain embedded hammerhead ribozymes that, during replication, mediate their self-cleavage to monomeric-length RNAs with 5′-hydroxyl and 2′,3′-phosphodiester termini that are subsequently circularized. We report that a recombinant version of the chloroplastic isoform of the tRNA ligase from eggplant (
Solanum melongena
L.) efficiently catalyzes
in vitro
circularization of the plus [(+)] and minus [(−)] monomeric linear replication intermediates from the four
Avsunviroidae
. We also show that while this RNA ligase specifically recognizes the genuine monomeric linear (+) ELVd replication intermediate, it does not do so with five other monomeric linear (+) ELVd RNAs with their ends mapping at different sites along the molecule, despite containing the same 5′-hydroxyl and 2′,3′-phosphodiester terminal groups. Moreover, experiments involving transient expression of a dimeric (+) ELVd transcript in
Nicotiana benthamiana
Domin plants preinoculated with a tobacco rattle virus-derived vector to induce silencing of the plant endogenous tRNA ligase show a significant reduction of ELVd circularization. In contrast, circularization of a viroid replicating in the nucleus occurring through a different pathway is unaffected. Together, these results support the conclusion that the chloroplastic isoform of the plant tRNA ligase is the host enzyme mediating circularization of both (+) and (−) monomeric linear intermediates during replication of the viroids belonging to the family
Avsunviroidae
.