bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription factor AP2‐Sp and its target genes in malarial sporozoites
Authors: Yuda Masao , Iwanaga Shiroh , Shigenobu Shuji , Kato Tomomi , Kaneko Izumi 
Published: December 2009

SummaryThe malarial sporozoite is the stage that infects the liver, and genes expressed in this stage are potential targets for vaccine development. Here, we demonstrate that specific gene expression in this stage is regulated by an AP2‐related transcription factor, designated AP2‐Sp (APETALA2 in sporozoites), that is expressed from the late oocyst to the salivary gland sporozoite. Disruption of the AP2‐Sp gene did not affect parasite replication in the erythrocyte but resulted in loss of sporozoite formation. The electrophoretic mobility‐shift assay showed that the DNA‐binding domain of AP2‐Sp recognizes specific eight‐base sequences, beginning with TGCATG, which are present in the proximal promoter region of all known sporozoite‐specific genes. Promoter assays demonstrated that these sequences act as cis‐acting elements and are critical for the expression of sporozoite‐specific genes with different expression profiles. In transgenic parasites that express endogenous AP2‐O (APETALA2 in ookinetes), but whose AP2 domain had been swapped with that of AP2‐Sp, several target genes of AP2‐Sp were induced in the ookinete stage. These results indicate that AP2‐Sp is a major transcription factor that regulates gene expression in the sporozoite stage.
Activation of the l,d‐transpeptidation peptidoglycan cross‐linking pathway by a metallo‐d,d‐carboxypeptidase in Enterococcus faecium
Authors: Sacco Emmanuelle , Hugonnet Jean‐Emmanuel , Josseaume Nathalie , Cremniter Julie , Dubost Lionel , Marie Arul , Patin Delphine , Blanot Didier , Rice Louis B. , Mainardi Jean‐Luc , Arthur Michel 
Published: December 2009

SummaryBypass of the penicillin‐binding proteins by an l,d‐transpeptidase (Ldtfm) confers cross‐resistance to β‐lactam and glycopeptide antibiotics in mutants of Enterococcus faecium selected in vitro. Ldtfm is produced by the parental strain D344S although it insignificantly contributes to peptidoglycan cross‐linking as pentapeptide stems cannot be used as acyl donors by this enzyme. Here we show that production of the tetrapeptide substrate of Ldtfm is controlled by a two‐component regulatory system (DdcRS) and a metallo‐d,d‐carboxypeptidase (DdcY). The locus was silent in D344S and its activation was due to amino acid substitutions in DdcS or DdcR that led to production of DdcY and hydrolysis of the C‐terminal d‐Ala residue of the cytoplasmic peptidoglycan precursor UDP‐MurNAc‐pentapeptide. The T161A and T161M substitutions affected a position of DdcS known to be essential for the phosphatase activity of related sensor kinases. Complete elimination of UDP‐MurNAc‐pentapeptide, which was required specifically for resistance to glycopeptides, involved substitutions in DdcY that increased the catalytic efficiency of the enzyme (E127K) and affected its interaction with the cell envelope (I14N). The ddc locus displays striking similarities with portions of the van vancomycin resistance gene clusters, suggesting possible routes of emergence of cross‐resistance to glycopeptides and β‐lactams in natural conditions.
Some reassembly required
Authors: Cate Jamie H. D. 
Published: December 2009

SummaryCells invest a significant amount of their energy synthesizing proteins, and a large portion of the energy expenditure goes into making ribosomes, the RNA‐protein machines at the centre of translation. When ribosomes are damaged in a cell, i.e. during stressful conditions, cells must first recognize the damage and then mount a response. Remme et al. show that instead of having to rebuild ribosomes from scratch, bacteria can repair ribosomes by replacing damaged proteins in situ, thereby saving significant time and energy. Given the central role of translation, such repair mechanisms might be widespread in nature.
Conformational flexibility of σ70 in anti‐terminator loading
Authors: DeHaseth Pieter L. , Gott Jonatha M. 
Published: December 2009

SummaryIn promoter DNA, the preferred distance of the −10 and −35 elements for interacting with RNA polymerase‐bound σ70 is 17 bp. However, the Devi et al. paper in this issue of Molecular Microbiology demonstrates that when the C‐terminal domain of σ70, including the 3.2 linker, is not attached to the core enzyme, distances between 0 and 3 bp can be accommodated. This attests to the great flexibility of the 3.2 linker. The particularly stable complex with the 2 bp separation may lend itself to structural studies of an early elongation complex containing σ70.
Hereditary cutaneous mucinosis in shar pei dogs is associated with increased hyaluronan synthase‐2 mRNA transcription by cultured dermal fibroblasts
Authors: Zanna Giordana , Docampo María J. , Fondevila Dolors , Bardagí Mar , Bassols Anna , Ferrer Lluís 
Published: December 2009

AbstractShar pei dogs are known for the distinctive feature of thick, wrinkled skin as a consequence of high dermal mucin content. Excessive dermal deposition of mucinous substance leading to severe skin folding, and/or to the more severe vesicular form characterized by dermal vesicles or bullae, is highly prevalent in this breed and is known as idiopathic mucinosis. Hyaluronic acid (HA) is the main component that accumulates in the dermis, and high levels of HA have also been detected in the serum of shar pei dogs. In this study, the cellular and molecular mechanisms underlying cutaneous mucinosis of shar pei dogs were investigated. Thirteen shar pei dogs and four control dogs of other breeds were included. In primary dermal fibroblast cultures, transcription of the family of hyaluronan synthases (HAS) involved in HA synthesis, and of hyaluronidases (HYAL) involved in HA degradation, were studied by reverse transcriptase polymerase chain reaction. The location of HA in cell cultures was studied by immunofluorescence and confocal laser microscopy. Dermal fibroblasts transcribed HAS2, HAS3, HYAL1 and HYAL2, but no amplification for HAS1 was found. A higher transcription of HAS2 was demonstrated in shar pei dogs compared with control dogs. By confocal microscopy, HA was detected as a more diffuse and intense network‐like pattern of green fluorescence in the fibroblast cells of shar pei dogs in comparison with control dogs. Together, these results provide additional evidence that hereditary cutaneous mucinosis in shar pei dogs may be a consequence of over‐transcription or increased activity of HAS2.
The keratinocyte in epidermal renewal and defence
Authors: Suter Maja M. , Schulze Katja , Bergman Wilhelmina , Welle Monika , Roosje Petra , Müller Eliane J. 
Published: December 2009

AbstractTraditionally, keratinocytes have been considered inert constituents of the multilayered epidermis. Today’s understanding has fundamentally changed. The keratinocyte is now recognized as an active player in epidermal renewal with key functions in the skin’s immune defence. Under homeostatic conditions, keratinocyte progenitor cells are believed to divide symmetrically or asymmetrically, that is they continue to proliferate or go on to terminally differentiate and build up the overlaying epidermis. The fine‐tuned process of epidermal renewal relies on an extraordinary network of signalling cascades which are governed by keratinocyte–receptor interactions with the environment through paracrine and autocrine circuits. Opposing this coordinated homeostatic process are signals of wounding and inflammation. They alter the fate of the keratinocyte and its response to the environment through changes in adhesion molecules and surface receptors, in addition to triggering an immediate inflammatory keratinocyte response in terms of secretion of cytokines, chemokines and antimicrobial peptides. If uncontrolled, the fundamental changes imposed by wounding and inflammation upon the homeostatic programme can lead to severe skin lesions including chronic inflammatory disorders. This review will describe the current knowledge of the regulatory signalling network which allows the keratinocyte to actively impact both epidermal homeostasis and the inflammatory response.
Multicentric, controlled clinical study to evaluate effectiveness and safety of miltefosine and allopurinol for canine leishmaniosis
Authors: Miró Guadalupe , Oliva Gaetano , Cruz Israel , Cañavate Carmen , Mortarino Michele , Vischer Claudia , Bianciardi Paolo 
Published: December 2009

AbstractThe aim of this trial was to evaluate the effectiveness and safety of miltefosine–allopurinol combination therapy vs. the current reference combination therapy, meglumine antimoniate–allopurinol, for canine leishmaniosis. Dogs included in the study exhibited clinical signs of the disease, were positive by PCR and serologically positive by immunofluorescent antibody test for leishmaniosis, and negative for ehrlichiosis. Dogs were divided into two groups: Group 1 was treated with 2 mg/kg of miltefosine orally once daily for 28 days and 10 mg/kg of allopurinol orally twice daily for 7 months; Group 2 was treated with 50 mg/kg of meglumine antimoniate sub‐cutaneously twice daily for 28 days and allopurinol (same dose as Group 1) for 7 months. Dogs were examined according to the following schedule: pre‐inclusion, Day 0 (D0), D14, D28, D84, D140 and D196. At each visit, blood, urine and bone marrow samples were collected. Parameters monitored included haematology, biochemistry, protein electrophoresis, serology, urinary protein/creatinine ratio and RTQ‐PCR performed on bone marrow aspirates. A significant reduction in total clinical score and parasite load was observed in both groups over the 7‐month study period (P < 0.0001), with no significant difference between groups (P = 0.3). The safety of miltefosine–allopurinol combination therapy was confirmed by lack of effect on renal and hepatic parameters and adverse reactions. Miltefosine, in combination with allopurinol, offers a safe, convenient and effective alternative treatment option for canine leishmaniosis compared to the reference therapy.
The molecular logic of pemphigus and impetigo: the desmoglein story
Authors: Amagai Masayuki 
Published: December 2009

AbstractDesmosomes are intercellular adhesive junctions of epithelial cells that contain two major transmembrane components, desmogleins (Dsg) and desmocollins; these are both cadherin‐type cell–cell adhesion molecules. Pemphigus is an autoimmune blistering disease caused by IgG autoantibodies that target Dsg1 and Dsg3 in pemphigus foliaceus and pemphigus vulgaris respectively. Bullous impetigo is a common and highly contagious superficial skin infection caused by Staphylococcus aureus. Staphylococcal scalded skin syndrome (SSSS) is a generalized form of bullous impetigo. The blisters in bullous impetigo and SSSS are induced by exfoliative toxin that specifically cleaves Dsg1. Clinical and microscopic localization of blisters in pemphigus, bullous impetigo and SSSS are logically explained at the molecular level by the desmoglein compensation theory; the similarity of lesions among these diseases is underscored by a similar pathogenesis.
Intradermal testing of horses with and without insect bite hypersensitivity in the Netherlands using an extract of nativeCulicoidesspecies
Authors: Sloet van Oldruitenborgh‐Oosterbaan Marianne M. , Van Poppel Miriam , De Raat Inge J. , Van Den Boom Robin , Savelkoul Huub F.J. 
Published: December 2009

AbstractIntradermal tests using aCulicoides nubeculosusextract have proven unreliable for diagnosis of equine insect bite hypersensitivity (IBH) in the Netherlands. The aim of this study was to evaluate the diagnostic value of an extract derived from the Dutch speciesC. obsoletusandC. pulicaris. Thirteen pairs of horses were tested, each pair consisting of one horse with IBH and the other a healthy control. Each horse was injected intradermally with 0.1 mL of three concentrations ofCulicoideswhole body extract (1 : 1000 w/v, 1 : 10,000 w/v and 1 : 25,000 w/v), histamine solution (0.01 mg/mL, positive control) and phosphate‐buffered saline (negative control). Skin responses were evaluated after 30 min and at 1, 4 and 24 h. At all time points the absolute wheal diameter elicited byCulicoidesextract 1 : 1000 w/v was significantly larger (P < 0.01) in the IBH horses than in the control horses. Using the 1 : 10,000 w/v extract the difference was significant at 1, 4 and 24 h and using the 1 : 25,000 w/v extract only at 24 h. The relative wheal diameter was greater in IBH than in control horses at all concentrations and time points except at 0.5 h for the 1 : 10,000 w/v and 1 : 25,000 w/v concentrations. At the 1 : 1000 w/v concentration, the sensitivity and specificity was 92% using the relative wheal diameter. These results indicate that intradermal testing using 1 : 1000 w/v concentrationCulicoidesextracts relevant to the locality provides useful support for a clinical diagnosis of equine insect hypersensitivity.
Flea and tick control in the 21st century: challenges and opportunities
Authors: Dryden Michael Wayne 
Published: December 2009

AbstractHistorically, veterinarians have told their clients that one flea is all that is necessary to produce and maintain the clinical signs of flea allergy dermatitis (FAD). Newer adulticides, such as fipronil, imidacloprid, nitenpyram and selamectin, have had a positive clinical effect on dogs and cats with FAD. However, data on flea feeding and the effect of these products on flea feeding bring into question the once perceived dogma of the single flea bite concept. Current data would indicate that the primary role of these insecticides in managing FAD is in rapidly reducing flea numbers and reducing flea feeding rather than preventing flea bites. Controlling tick infestations is important not only because ticks are nuisance parasites of dogs and cats, but also because they are vectors of a variety of bacterial and protozoal diseases. Achieving satisfactory tick control is often difficult due to unrealistic expectations of pet owners, to residual acaricidal properties of products that are often less than 100% and because of constant re‐infestation pressure. Some of the most important factors veterinarians must be aware of are regional changes in tick distributions, our inability to control wildlife tick hosts and expectation differences between flea and tick control. These factors probably cause most real and perceived product failures.
Levels of house dust mite‐specific serum immunoglobulin E (IgE) in different cat populations using a monoclonal based anti‐IgE enzyme‐linked immunosorbent assay
Authors: Bexley Jennifer , Hogg Janice E. , Hammerberg Bruce , Halliwell Richard E.W. 
Published: December 2009

AbstractLevels of serum immunoglobulin E (IgE) specific for the house dust mites (HDMs)Dermatophagoides farinae(DF) andDermatophagoides pteronyssinus(DP) in 58 cats with clinical signs suggestive of atopic dermatitis (allergic dermatitis cats), 52 cats with no history of allergic or immunological disease (nonallergic cats) and 26 specific pathogen‐free (SPF) cats were measured using a monoclonal anti‐IgE enzyme‐linked immunosorbent assay. Reactivity to both native and reduced HDM allergens was compared. SPF cats had significantly lower levels of HDM‐specific serum IgE than cats with allergic dermatitis and nonallergic cats. The difference in levels of HDM‐specific IgE in the serum of cats with allergic dermatitis and nonallergic cats was significant for native DF allergen, but not for native DP allergen or reduced HDM allergens. The results suggest that DF in its native form may be a significant allergen in cats with allergic dermatitis. The clinical relevance of these reactions, however, remains to be proven.
Increased transepidermal water loss and decreased ceramide content in lesional and non‐lesional skin of dogs with atopic dermatitis
Authors: Shimada Kenichiro , Yoon Ji‐Seon , Yoshihara Toru , Iwasaki Toshiroh , Nishifuji Koji 
Published: December 2009

AbstractThis study evaluated changes in transepidermal water loss (TEWL), skin hydration and intercorneal lipid content in dogs with atopic dermatitis (AD). TEWL and skin hydration were measured in the inguinal skin of 10 dogs with AD and 30 normal dogs. TEWL was significantly higher in both lesional skin (94.3 ± 38.8 g/m2/h) and non‐lesional skin (28.8 ± 9.5) of dogs with AD than healthy controls (12.3 ± 2.3) (P < 0.05). Water content in the lesional skin of dogs with AD (15.8 ± 7.0 AU) was significantly lower than that of controls (24.2 ± 8.8) (P < 0.05), whereas no significant differences were recognized in water content between non‐lesional skin of dogs with AD and controls. To compare the lipid content between lesional and non‐lesional skin of dogs with AD and controls, intercorneal lipids, extracted from the stratum corneum, were quantified by thin‐layer chromatography. The relative amounts of ceramides in the lesional skin (24.4 ± 5.6%) and non‐lesional skin (25.6 ± 3.8%) of dogs with AD were significantly lower than those in controls (31.4 ± 6.9%) (P < 0.05). Conversely, no significant differences were recognized in the relative amounts of cholesterols and free fatty acids (FFA) between dogs with AD and controls. Moreover, there are statistical correlations between TEWL and the relative amounts of ceramides, but not those of cholesterols and FFA, in both lesional and non‐lesional skin of dogs with AD. These results strongly suggest that decreased ceramide content accelerates TEWL in dogs with AD, similar to the situation seen in the corresponding human disease.
Defining the complex epithelia that comprise the canine claw with molecular markers of differentiation
Authors: Bowden Paul E. , Henderson Hayley , Reilly John D. 
Published: December 2009

AbstractCanine claws are complex epithelial structures resembling the mammalian hair fibre, and human nail plate, in terms of tissue‐specific differentiation. They are composed of several distinct epithelial cell lineages undergoing either hard or soft keratinization. The claw plate has three distinct regions: stratum externum, stratum medium (SM) and stratum internum and the underside and tip are cushioned by a soft keratinizing epithelium, the sole. We have examined keratin expression in the canine claw and associated epithelia. Digits from German shepherd dogs were decalcified, processed and sectioned by sledge microtome. Sections were stained with haematoxylin and eosin or treated with specific antibodies to various keratins (immunohistochemistry). Proteins were extracted from claw components and analysed by SDS‐PAGE and Western blotting. The keratinized canine claw plate expressed hair‐specific keratins (type I, K25‐K38 and type II, K71‐K86) but only the inner region of the SM contained K6‐ and K16‐positive tubules, soft epithelia running through the hard keratinized claw plate. The soft keratinaceous sole epithelium expressed keratins K5, K6, K14, K16 and K17 and contained cells with abundant envelopes. The canine claw had two slippage zones, the inner claw bed, between the claw plate and ungula process, which expressed K17 and the region between the inner and outer claw sheath, equivalent to the hair follicle companion layer, which expressed K6, K77, K16 and K17. In conclusion, several different cell types have been defined in the canine claw presenting a complex mechanism of cellular differentiation.
The histamine H4receptor as a new target for treatment of canine inflammatory skin diseases
Authors: Roßbach Kristine , Stark Holger , Sander Kerstin , Leurs Rob , Kietzmann Manfred , Bäumer Wolfgang 
Published: December 2009

AbstractHistamine is a well known mediator of allergic skin diseases and, with the discovery of the histamine H4receptor, the role of histamine is re‐evaluated. There are only limited published data elucidating the role of the histamine H4receptor in dogs. Twelve beagles intradermally injected with histamine (0.25 μmol and 2.5 μmol/site) reacted with a classical wheal and flare reaction. None of the dogs showed signs of pruritus. The dogs reacted with a wheal and flare reaction after intradermal injection of histamine H4receptor agonist/H3receptor antagonist clobenpropit (0.1 μmol) and selective histamine H4receptor agonist VUF 8430 (1.5 μmol). Again, no scratching occurred in any of the dogs. The highly selective histamine H4receptor antagonist JNJ 7777120 reduced the histamine‐induced wheal reaction in nine out of 12 dogs. To determine whether canine mast cells are susceptible to histamine H4receptor‐mediated reactions, effects of clobenpropit and VUF 8430 were tested in canine mastocytoma cells (C2). Incubation with histamine H4receptor agonists (up to 10 μmol/L) induced a distinct calcium2+influx. C2 cells also responded with enhanced chemotaxis when stimulated with histamine, VUF 8430 and clobenpropit. Neither VUF 8430, nor clobenpropit (up to 10 μmol/L) led to a modulation of histamine concentration in supernatants of canine mastocytoma cells, whereas mastoparan, used as a positive control, enhanced histamine concentration in supernatants. For treatment of allergic skin diseases in dogs, a combination of H1R and H4R antagonists might be advantageous.
Relationship of serum cholesterol levels to atopy in the US population
Authors: Fessler M. B. , Jaramillo R. , Crockett P. W. , Zeldin D. C. 
Published: December 2009

To cite this article: Fessler MB, Jaramillo R, Crockett PW, Zeldin DC. Relationship of serum cholesterol levels to atopy in the US population. Allergy 2010; 65: 859–864.AbstractBackground:  Cholesterol promotes Th2 immunity and allergic inflammation in rodents; whether this occurs in humans is unclear. Reports of both direct and inverse associations between serum cholesterol and atopy in different populations suggest that race and/or other demographic variables may modify these relationships.Aims of the study:  To determine the relationships between levels of three serum cholesterol measures [total cholesterol (TC), high density lipoprotein‐cholesterol (HDL‐C), and non‐HDL‐C] and atopy in a sample representative of the US population.Methods:  Cross‐sectional study of 6854 participants aged ≥6 years from the 2005–2006 National Health and Nutrition Examination Survey.Results:  In the overall population, adjusted odds ratios (AORs) per two‐standard deviation increase in TC and non‐HDL‐C for biochemical atopy (defined as ≥1 allergen‐specific IgE to 19 allergens) were 1.17 [95% confidence interval (CI), 1.00–1.38] and 1.19 (95% CI, 1.03–1.39), respectively. Interactions by race were noted for the two relationships (interaction P = 0.004 and P = 0.009, respectively) with non‐Hispanic Whites (NHWs) having direct relationships [TC: AOR 1.27 (95% CI, 1.03–1.57); non‐HDL‐C: AOR 1.27 (95% CI, 1.03–1.56)] and non‐Hispanic Blacks (NHBs) inverse relationships [TC: AOR 0.77 (95% CI, 0.62–0.95); non‐HDL‐C: AOR 0.86 (95% CI, 0.69–1.08)]. The adjusted HDL‐C–atopy relationship was nonsignificant for NHWs and inverse for NHBs [AOR 0.77 (95% CI, 0.61–0.96)]. Relationships were independent of body mass index and serum C‐reactive protein and unmodified by corticosteroid or statin usage. Results were similar using current hay fever/allergy as the atopy outcome.Conclusions:  There are marked inter‐racial differences in the relationship between serum cholesterol and atopy in the US population.