bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clear‐cell dermal duct tumour: another distinctive, previously underrecognized cutaneous adnexal neoplasm
Authors: Rütten A , Hantschke M , Angulo J , Requena L 
Published: December 2007

Aims:  To describe 13 examples of clear cell dermal duct tumour, a neoplasm previously underrecognized in the literature.Methods and results:  Thirteen examples of a neoplasm that we have named clear‐cell dermal duct tumour were studied histopathologically and immunohistochemically. Histopathologically, all lesions consisted of mostly dermal neoplasms mainly composed of multiple solid aggregations of clear cells involving the dermis. Although the neoplasms were mostly solid, ductal structures were identified in all cases. Immunohistochemically, neoplastic cells were immunoreactive for MNF116 and AE1/AE3 cytokeratins, but not for CAM5.2 or cytokeratin 7. Epithelial membrane antigen, carcinoembryonic antigen and glial cystic disease fibrillary protein 15 decorated the ductal structures, but neoplastic cells were negative. In contrast to some other clear cell neoplasms of the skin, which may be associated with diabetes mellitus, none of our cases of clear cell dermal duct tumour developed in a diabetic patient.Conclusions:  We consider these neoplasms to be clear cell dermal duct tumours for the following reasons: (i) the neoplasms were mostly composed of multiple solid aggregations of epithelial clear cells; (ii) neoplastic aggregations mostly involved the dermis; (iii) in some cases, neoplastic aggregations of conventional poroid cells were intermingled with the aggregations of clear cells; (iv) ductal structures were identified within some neoplastic aggregations; (iv) small areas of necrosis en masse were seen in some neoplastic aggregations; and (v) the stroma of the neoplasm was scant.
Expression of c‐FLIP is primarily detected in diffuse large B‐cell lymphoma and Hodgkin’s lymphoma and correlates with lack of caspase 8 activation
Authors: Van Houdt I S , Muris J J , Hesselink A T , Kramer D , Cillessen S A G M , Moesbergen L M , Vos W , Hooijberg E , Meijer C J L M , Kummer J A , Oudejans J J 
Published: December 2007

Aims:  Inhibition of apoptosis is important in the pathogenesis of lymphomas. c‐FLIP, a regulator of caspase 8‐mediated apoptosis, plays an important role in protecting normal B and T cells from apoptosis and possibly also in lymphomas. Because of contradictory reports about immunohistochemical detection of c‐FLIP expression, the aim was to test the specificity of four antibodies in c‐FLIP‐transfected cells and subsequently to investigate expression of c‐FLIP in different types of lymphoma.Methods and results:  Two of four antibodies were specific. In primary lymphomas c‐FLIP expression was restricted to Hodgkin’s lymphomas (> 90%) and diffuse large B‐cell lymphomas (44%). Burkitt lymphomas and indolent B‐cell lymphomas were negative in all cases. No expression was detected in primary T‐cell lymphomas, although expression was observed in one relapsed ALK+ anaplastic large cell lymphoma. Expression of c‐FLIP was inversely correlated with caspase 8 activation.Conclusions:  c‐FLIP is important in escape of B cells from apoptosis during normal follicle centre cell reaction and may thus be an important early event in the development of B‐cell‐derived lymphomas. Moreover, non‐specific staining of frequently used antibodies might explain discrepancies in different reports of c‐FLIP expression.
Goblet cell carcinoid of the appendix: a specific type of carcinoma
Authors: Van Eeden S , Offerhaus G J A , Hart A A M , Boerrigter L , Nederlof P M , Porter E , Van Velthuysen M‐L F 
Published: December 2007

Aims:  Goblet cell carcinoid is a poorly understood tumour of the appendix. The aim of this study was to determine whether it should be regarded as a separate entity or as a variant of classical carcinoid.Methods and results:  The immunohistochemical expression pattern of 21 markers and the mutation status of KRas codon 12 were determined in 16 goblet cell carcinoids and compared with 14 classical carcinoids, 19 colonic adenocarcinomas and 10 appendiceal mucinous cystadeno (carcino)mas. The results were subjected to a stepwise linear discriminant analysis.Goblet cell carcinoids were significantly different from the control groups. The most important markers for discriminating between the groups were CEA (classical carcinoid versus all others), KRas mutation (present in all mucinous cystadeno (carcino)mas), β‐catenin (goblet cell carcinoid versus left sided colonic adenocarcinoma) and chromogranin (goblet cell carcinoid versus right sided colonic adenocarcinoma). Expression of Math1 and HD5 was similar in goblet cell carcinoid and colonic adenocarcinoma but absent in classical carcinoid.Conclusion:  The results suggest that goblet cell carcinoids should be regarded as a separate entity. The formerly used term ‘crypt cell carcinoma’ may be more appropriate because it reflects the more aggressive clinical behaviour of these tumours as well as their greater similarity to adenocarcinomas rather than to carcinoids.
The expression of Wilms’ tumour‐1 and Ca125 in invasive micropapillary carcinoma of the breast
Authors: Lee A H S , Paish E C , Marchio C , Sapino A , Schmitt F C , Ellis I O , Reis‐Filho J S 
Published: December 2007

Aim:  Metastases from ovarian serous papillary carcinoma to the breast and primary invasive micropapillary carcinoma of the breast are histologically similar. The distinction is clinically important to ensure appropriate management. Wilms’ tumour‐1 (WT1) and Ca125 are frequently expressed in serous papillary carcinomas, and uncommonly in unselected mammary carcinomas. One previous study found Ca125 expression in 69% of invasive micropapillary carcinomas. The aim was to assess the frequency of expression of WT1 and Ca125 in invasive micropapillary carcinoma.Methods and results:  Twenty‐five of 34 invasive micropapillary carcinomas showed no nuclear expression of WT1. The remaining nine tumours showed weak to moderate immunoreactivity in 1–10% of nuclei. Six of these nine tumours also contained ductal carcinoma in situ, which expressed WT1 in five of the six. Membranous or cytoplasmic expression of Ca125 was found in seven tumours.Conclusion:  Nuclear WT1 expression is present in a minority of invasive micropapillary carcinomas and, when present, expression is focal. The frequency of expression of Ca125 was similar to the results in unselected mammary carcinoma. Thus, these markers are useful members of the immunohistochemical panel for the distinction of mammary invasive micropapillary carcinoma from ovarian serous papillary carcinoma.
Differential expression of matrix metalloproteinase (MMP)‐2, MMP‐9 and tissue inhibitor of metalloproteinase (TIMP)‐1 and TIMP‐2 in non‐melanoma skin cancer: implications for tumour progression
Authors: O’Grady A , Dunne C , O’Kelly P , Murphy G M , Leader M , Kay E 
Published: December 2007

Aims:  To investigate the expression of matrix metalloproteinase (MMP)‐2, MMP‐9, and tissue inhibitor of metalloproteinase (TIMP)‐1 and TIMP‐2 in non‐melanoma skin cancer (NMSC) and to compare their expression between different tumour types and with clinicopathological factors.Methods and results:  A study of 11 normal skin, 29 Bowen’s disease (BD), 40 squamous cell carcinoma (SCC) and 38 basal cell carcinoma (BCC) samples for MMP‐2, MMP‐9, TIMP‐1 and TIMP‐2 expression was carried out using immunohistochemistry and in situ hybridization. The expression of all metalloproteinases was greater in tumours than in normal skin. MMP‐2 and MMP‐9 expression was more extensive in the stroma of SCC than of BCC or BD. TIMP‐1 expression was greater in the stroma of BCC than of SCC or BD and TIMP‐2 expression was greater in the stroma of SCC than of BD. There was a correlation between increased metalloproteinase expression and depth of lesion (MMP‐2 and TIMP‐2), inflammation (MMP‐2, MMP‐9, TIMP‐1 and TIMP‐2) and microvessel density (MMP‐2, MMP‐9 and TIMP‐2).Conclusions:  MMP‐2, MMP‐9, TIMP‐1 and TIMP‐2 play an important role in the pathogenesis of non‐melanoma skin cancer, but differ significantly in their expression levels between the tumour types examined. The immunoexpression of these proteins may be useful indicators of cutaneous cancer invasion and progression.
Evaluation of oestrogen receptor expression in breast cancer by quantification of mRNA
Authors: Potemski P , Pluciennik E , Bednarek A K , Kusinska R , Kubiak R , Kordek R 
Published: December 2007

Aims:  cDNA microarrays have subclassified breast carcinomas into molecular subtypes with oestrogen receptor‐α (ER) gene expression as a main marker. The aim was to compare ER expression in 97 patients with operable breast cancer estimated by real‐time reverse transcriptase‐polymerase chain reaction (real‐time RT‐PCR) and by routine immunohistochemistry, and to determine which method was reliable for molecular subtyping in relation to basal‐type keratins and HER2 gene expression.Methods and results:  Frozen tumour samples were analysed by real‐time RT‐PCR for the expression of ER, HER2, keratin 5 and keratin 17 genes. In a group of 27 tumours with a low level of ER mRNA (<1.00), there were eight ER+ cases as assessed by immunohistochemistry, and of 70 cases with a high level of ER mRNA (≥1.00), 26 were ER− by immunohistochemistry (P = 0.003). Lack of prognostic relevance of ER mRNA level was demonstrated, whereas assessment by immunohistochemistry was related to clinical outcome. Expression of basal keratins and HER2 genes differed significantly between ER+ and ER− tumours based on immunohistochemistry, but not on mRNA level.Conclusions:  These results throw doubt on the assessment of ER mRNA as a key factor in the molecular distinction between breast tumours.
Immunohistochemical expression patterns of AP2α and AP2γ in the developing fetal human breast
Authors: Friedrichs N , Steiner S , Buettner R , Knoepfle G 
Published: December 2007

Aims:  AP2α (TFAP2A) and AP2γ (TFAP2G) transcription factors have been implicated in the control of proliferation, differentiation and apoptosis of normal breast epithelium and in breast cancer. The aim of this study was to provide a comprehensive analysis of the expression patterns of TFAP2A and TFAP2G in the developing fetal breast anlage with other relevant markers.Methods and results:  Sixty fetal and one infant human breast specimens from 14 weeks of gestational age to 5 months old were examined. The primary breast outgrowth/nipple showed TFAP2A expression by the basal cells (week 14), followed later by cytokeratin (CK) 5 co‐expression (week 17). Sprouting of the secondary outgrowths was characterized by HER‐2+ invading cells. Preliminary ductal buds were lined by TFAP2G/HER‐1‐expressing myoepithelial precursors (week 19). Maturation of TFAP2A/CK18+ epithelia and TFAP2G/smooth muscle actin‐positive myoepithelia proceeded in a distal‐to‐proximal manner beginning in the terminal end buds (week 22). CK5+ progenitor cells and CK5/TFAP2A or CK5/TFAP2G co‐expressing intermediary glandular or myoepithelial cells were found in the terminal end buds of neonatal fetal breast tissue.Conclusions:  AP2 transcription factors may play decisive pacemaker roles in initiating and coordinating budding and branching processes during formation of the fetal breast anlage, possibly via modulation of an epidermal growth factor receptor.
Can multiscale models of species’ distribution be generalized from region to region? A case study of the koala
Authors: McAlpine C. A. , Rhodes J. R. , Bowen M. E. , Lunney D. , Callaghan J. G. , Mitchell D. L. , Possingham H. P. 
Published: December 2007

SummaryWhile various studies have evaluated the habitat requirements for wildlife in fragmented forest landscapes at multiple spatial scales, few have considered whether there is regional variation in the most important factors. This is a conundrum for managers of any species with a broad geographical range: to what extent should studies in one region inform decisions in another?We addressed this question using a case study of the koala,Phascolarctos cinereus, in three biogeographically different fragmented forested landscapes in eastern Australia. Mixed‐effect logistic models were applied to predict koala occurrence from explanatory variables captured at four spatial scales: the individual tree, the stand (<1 ha), the patch (1–100 ha) and the landscape (100–1000 ha).We used model averaging to account for model and parameter uncertainty, and tested the cross‐regional discrimination ability of the models.We discovered that multiscale models of koala distribution cannot be readily generalized from region to region, and that specific conservation actions for each region, rather than the entire geographical range, are more appropriate. We found a strong justification for adopting a hierarchical landscape approach to koala conservation across its range. However, cross‐regional differences in habitat relationships occurred within this hierarchy. Exceptions were landscape context, which showed a consistently strong effect and high rank in all regions, and the presence of individual preferred tree species of the genusEucalyptus, which showed modest consistency in its interaction with large‐diameter trees across the regions. In contrast, the remaining habitat variables, including patch size (a key management factor), showed moderate to strong cross‐regional variation attributed to the interaction of edaphic factors, landscape history and contemporary land‐use patterns.Synthesis and applications. Adopting a uniform conservation programme over a large geographical area is attractive to policy‐makers and conservation planners. However, our study confirms the lack of generality of species distribution models over large areas. Consequently, we argue against adopting a uniform conservation programme for species with a large geographical range.
Modelling the habitat requirements of leopardPanthera pardusin west and central Asia
Authors: Gavashelishvili Alexander , Lukarevskiy Victor 
Published: December 2007

SummaryTop predators are seen as keystone species of ecosystems. Knowledge of their habitat requirements is important for their conservation and the stability of the wildlife communities that depend on them. The goal of our study was to model the habitat of leopardPanthera pardusin west and central Asia, where it is endangered, and analyse the connectivity between different known populations in the Caucasus to enable more effective conservation management strategies to be implemented.Presence and absence data for the species were evaluated from the Caucasus, Middle East and central Asia. Habitat variables related to climate, terrain, land cover and human disturbance were used to construct a predictive model of leopard habitat selection by employing a geographic information system (GIS) and logistic regression.Our model suggested that leopards in west and central Asia avoid deserts, areas with long‐duration snow cover and areas that are near urban development. Our research also provides an algorithm for sample data management, which could be used in modelling habitats for similar species.Synthesis and applications. This model provides a tool to improve search effectiveness for leopard in the Caucasus, Middle East and central Asia as well as for the conservation and management of the species. The model can predict the probable distribution of leopards and the corridors between various known populations. Connectivity patterns can be used to facilitate corridor planning for leopard conservation, especially in the Caucasus, where the leopard is a top priority conservation species. Also, as top predators are often associated with high biodiversity, the leopard habitat model could help to identify biodiversity hotspots. The protection of biodiversity hotspots is seen as the most effective way to conserve biodiversity globally.
Mutations in two global regulators lower individual mortality in Escherichia coli
Authors: Fontaine Fanette , Stewart Eric J. , Lindner Ariel B. , Taddei François 
Published: December 2007

SummaryThere has been considerable investigation into the survival of bacterial cells under stress conditions, but little is known about the causes of mortality in the absence of exogenous stress. That there is a basal frequency of cell death in such populations may reflect that it is either impossible to avoid all lethal events, or alternatively, that it is too costly. Here, through a genetic screen in the model organism Escherichia coli, we identify two mutants with lower frequencies of mortality: rssB and fliA. Intriguingly, these two genes both affect the levels of different sigma factors within the cell. The rssB mutant displays enhanced resistance to multiple external stresses, possibly indicating that the cell gains its increased vitality through elevated resistance to spontaneous, endogenous stresses. The loss of fliA does not result in elevated stress resistance; rather, its survival is apparently due to a decreased physical stress linked to the insertion of the flagellum through the membrane and energy saved through the loss of the motor proteins. The identification of these two mutants implies that reducing mortality is not impossible; rather, due to its cost, it is subject to trade‐offs with other traits that contribute to the competitive success of the organism.
The large subunit of Leishmania topoisomerase I functions as the ‘molecular steer’ in type IB topoisomerase
Authors: BoseDasgupta Somdeb , Ganguly Agneyo , Das Benu Brata , Roy Amit , Khalkho Neeta V. M. , Majumder Hemanta K. 
Published: December 2007

SummaryKinetoplastid topoisomerase IB is an unusual bisubunit enzyme where reconstitution of the large (LdTOPIL or L) and small (LdTOPIS or S) subunits shows functional activity. It is yet to be deciphered whether one subunit or both navigate the heterodimer to its cellular DNA targets. Tethering a specific DNA‐binding protein to topoisomerase I alters its site specificity. The chimeric constructs UMSBP–LdTOPIL/S or U–L/S (fusion of UMSBP to the N‐terminus of L and reconstituted with S) and LdTOPIL/UMSBP–LdTOPIS or L/U–S (fusion of UMSBP to the N‐terminus of S and reconstituted with L) exhibit relaxation activity. Only U–L/S shows altered site specificity and enhanced DNA‐binding affinity for the universal minicircle sequence (UMS) containing substrate. This proves that L alone serves as the ‘molecular steer’ for this heterodimer. Reconstituted U–L/S also induces cleavage close to UMS and causes minicircle linearization. The differential properties of the reconstituted chimeras U–L/S and L/U–S reveal the structural and functional asymmetry between the heterodimer. Therefore this study helps in a better understanding of the mechanistic details underlying topoisomerization by this bi‐subunit enzyme.
LeuX tRNA‐dependent and ‐independent mechanisms of Escherichia coli pathogenesis in acute cystitis
Authors: Hannan Thomas J. , Mysorekar Indira U. , Chen Swaine L. , Walker Jennifer N. , Jones Jennifer M. , Pinkner Jerome S. , Hultgren Scott J. , Seed Patrick C. 
Published: December 2007

SummaryUropathogenic Escherichia coli (UPEC) contain multiple horizontally acquired pathogenicity‐associated islands (PAI) implicated in the pathogenesis of urinary tract infection. In a murine model of cystitis, type 1 pili‐mediated bladder epithelial invasion and intracellular proliferation are key events associated with UPEC virulence. In this study, we examined the mechanisms by which a conserved PAI contributes to UPEC pathogenesis in acute cystitis. In the human UPEC strain UTI89, spontaneous excision of PAI IIUTI89 disrupts the adjacent leuX tRNA locus. Loss of wild‐type leuX‐encoded tRNA5Leu significantly delayed, but did not eliminate, FimB recombinase‐mediated phase variation of type 1 pili. FimX, an additional FimB‐like, leuX‐independent recombinase, was also found to mediate type 1 pili phase variation. However, whereas FimX activity is relatively slow in vitro, it is rapid in vivo as a non‐piliated strain lacking the other fim recombinases rapidly expressed type 1 pili upon experimental infection. Finally, we found that disruption of leuX, but not loss of PAI IIUTI89 genes, reduced bladder epithelial invasion and intracellular proliferation, independent of type 1 piliation. These findings indicate that the predominant mechanism for preservation of PAI IIUTI89 during the establishment of acute cystitis is maintenance of wild‐type leuX, and not PAI IIUTI89 gene content.
The disulphide isomerase DsbC cooperates with the oxidase DsbA in a DsbD‐independent manner
Authors: Vertommen Didier , Depuydt Matthieu , Pan Jonathan , Leverrier Pauline , Knoops Laurent , Szikora Jean‐Pierre , Messens Joris , Bardwell James C. A. , Collet Jean‐Francois 
Published: December 2007

SummaryIn Escherichia coli, DsbA introduces disulphide bonds into secreted proteins. DsbA is recycled by DsbB, which generates disulphides from quinone reduction. DsbA is not known to have any proofreading activity and can form incorrect disulphides in proteins with multiple cysteines. These incorrect disulphides are thought to be corrected by a protein disulphide isomerase, DsbC, which is kept in the reduced and active configuration by DsbD. The DsbC/DsbD isomerization pathway is considered to be isolated from the DsbA/DsbB pathway. We show that the DsbC and DsbA pathways are more intimately connected than previously thought. dsbA‐dsbC‐ mutants have a number of phenotypes not exhibited by either dsbA‐, dsbC‐ or dsbA‐dsbD‐ mutations: they exhibit an increased permeability of the outer membrane, are resistant to the lambdoid phage Φ80, and are unable to assemble the maltoporin LamB. Using differential two‐dimensional liquid chromatographic tandem mass spectrometry/mass spectrometry analysis, we estimated the abundance of about 130 secreted proteins in various dsb‐ strains. dsbA‐dsbC‐ mutants exhibit unique changes at the protein level that are not exhibited by dsbA‐dsbD‐ mutants. Our data indicate that DsbC can assist DsbA in a DsbD‐independent manner to oxidatively fold envelope proteins. The view that DsbC's function is limited to the disulphide isomerization pathway should therefore be reinterpreted.
The Gup1 homologue of Trypanosoma brucei is a GPI glycosylphosphatidylinositol remodelase
Authors: Jaquenoud Malika , Pagac Martin , Signorell Aita , Benghezal Mohammed , Jelk Jennifer , Bütikofer Peter , Conzelmann Andreas 
Published: December 2007

SummaryGlycosylphosphatidylinositol (GPI) lipids of Trypanosoma brucei undergo lipid remodelling, whereby longer fatty acids on the glycerol are replaced by myristate (C14:0). A similar process occurs on GPI proteins of Saccharomyces cerevisiae where Per1p first deacylates, Gup1p subsequently reacylates the anchor lipid, thus replacing a shorter fatty acid by C26:0. Heterologous expression of the GUP1 homologue of T. brucei in gup1Δ yeast cells partially normalizes the gup1Δ phenotype and restores the transfer of labelled fatty acids from Coenzyme A to lyso‐GPI proteins in a newly developed microsomal assay. In this assay, the Gup1p from T. brucei (tbGup1p) strongly prefers C14:0 and C12:0 over C16:0 and C18:0, whereas yeast Gup1p strongly prefers C16:0 and C18:0. This acyl specificity of tbGup1p closely matches the reported specificity of the reacylation of free lyso‐GPI lipids in microsomes of T. brucei. Depletion of tbGup1p in trypanosomes by RNAi drastically reduces the rate of myristate incorporation into the sn‐2 position of lyso‐GPI lipids. Thus, tbGup1p is involved in the addition of myristate to sn‐2 during GPI remodelling in T. brucei and can account for the fatty acid specificity of this process. tbGup1p can act on GPI proteins as well as on GPI lipids.