bluuebunny/crossref_metadata_2025_split huggingface dataset:
K+ channel types targeted by synthetic OSK1, a toxin fromOrthochirus scrobiculosusscorpion venom
Authors: MOUHAT Stéphanie , VISAN Violeta , ANANTHAKRISHNAN S. , WULFF Heike , ANDREOTTI Nicolas , GRISSMER Stephan , DARBON Hervé , DE WAARD Michel , SABATIER Jean-Marc 
Published: December 2004

OSK1 (α-KTx3.7) is a 38-residue toxin cross-linked by three disulphide bridges that was initially isolated from the venom of the Asian scorpion Orthochirus scrobiculosus. OSK1 and several structural analogues were produced by solid-phase chemical synthesis, and were tested for lethality in mice and for their efficacy in blocking a series of 14 voltage-gated and Ca2+-activated K+ channels in vitro. In the present paper, we report that OSK1 is lethal in mice by intracerebroventricular injection, with a LD50 (50% lethal dose) value of 2 μg/kg. OSK1 blocks Kv1.1, Kv1.2, Kv1.3 channels potently and KCa3.1 channel moderately, with IC50 values of 0.6, 5.4, 0.014 and 225 nM respectively. Structural analogues of OSK1, in which we mutated positions 16 (Glu16→Lys) and/or 20 (Lys20→Asp) to amino acid residues that are conserved in all other members of the α-KTx3 toxin family except OSK1, were also produced and tested. Among the OSK1 analogues, [K16,D20]-OSK1 (OSK1 with Glu16→Lys and Lys20→Asp mutations) shows an increased potency on Kv1.3 channel, with an IC50 value of 0.003 nM, without loss of activity on KCa3.1 channel. These data suggest that OSK1 or [K16,D20]-OSK1 could serve as leads for the design and production of new immunosuppressive drugs.
An overview of interactions between micronutrients and of micronutrients with drugs, genes and immune mechanisms
Authors: Thurnham David I. 
Published: December 2004

AbstractThe objective of the present review is to examine critically the consequences of interactions that micronutrients undergo with nutrients and non-nutrients (mainly prescribed medicines) in diets and lifestyle factors (smoking, tea and alcohol consumption). In addition, the review describes recent work on interactions between nutrients and genes, the influence of gene polymorphisms on micronutrients, the impact of immune responses on micronutrients and specific interactions of antioxidant micronutrients in disease processes to minimise potential pro-oxidant damage.
The key role of nutrition in controlling human population dynamics
Authors: Duncan C.J , Scott S 
Published: December 2004

AbstractThe early hominids and their successors, the nomadic hunter–gatherers, were evolutionarily adapted to an omnivorous diet. Their food was well balanced nutritionally and they acquired adequate supplies with relatively little expenditure of energy. The complete change to a fixed agricultural lifestyle (the Neolithic revolution) took place only some 12 000 years ago and was the most momentous event in human history. Being tied to the land that they worked led eventually to the city states and the great civilisations of history, which brought with them wars and epidemics of infectious diseases. Much more serious were the insidious effects of the new cereal-based diet which persisted until the twentieth century. Not only was it labour intensive, but also for the bulk of the population it was often deficient in vitamins, minerals and energy, particularly at certain times of the year. Time-series analysis reveals a regular short wavelength oscillation in the grain supply that persisted for at least 350 years and dominated the population dynamics of pre-industrial England. In addition to reducing fertility, it acted primarily via its effects on the nutrition of the pregnant woman. Malnutrition during one of the critical trimesters of pregnancy could have far-reaching effects not only on the health of the fetus and neonate but also on the illnesses of later, adult life. These consequences were insidiously and inevitably carried forward to the subsequent generations. Girls who were born with a low birth weight produced daughters and granddaughters of low birth weight, irrespective of their nutrition during childhood. These intergenerational, knock-on effects established a vicious circle from which there was little chance of escape.
Molecular diagnosis of basal cell carcinoma and other basaloid cell neoplasms of the skin by the quantification of Gli1 transcript levels
Authors: Hatta Naohito , Hirano Takashi , Kimura Tetsunori , Hashimoto Ken , Mehregan Darius R. , Ansai Shinichi , Takehara Kazuhiko , Takata Minoru 
Published: December 2004

Background:  Distinguishing basal cell carcinoma (BCC) from other benign and malignant skin tumors is sometimes a difficult task for the pathologists. Because the activation of hedgehog signals and the up‐regulation of its critical transcriptional factor Gli1 are well documented in BCC, a molecular technique measuring Gli1 transcripts may aide the diagnosis.Methods:  Gli1 transcript levels were measured by real‐time quantitative reverse transcriptase polymerase chain reaction (RT‐PCR) using RNA extracted from formalin‐fixed, paraffin‐embedded tissues of 68 cases of various skin tumors. Hematoxylin and eosin‐stained pathology slides were independently reviewed by three expert dermatopathologists.Results:  The histological diagnoses were unambiguous in 53 tumors. The tumors included BCC (21), squamous cell carcinoma (13), seborrheic keratoses (8), trichoepithelioma (5), eccrine poroma/porocarcinoma (4), and sebaceous epithelioma/carcinoma (2). In these unambiguous cases, all BCC and trichoepithelioma tumors showed high expression of Gli1mRNA, while the expression was virtually absent in other tumors. The diagnosis was discordant among three pathologists in the remaining 15 tumors. Histological diagnoses included BCC, BCC with sebaceous differentiation, sebaceoma/sebaceous epithelioma, trichoblastoma, trichoepithelioma, basaloid follicular harmartoma, basosquamous carcinoma, etc. Six of them showed high Gli1 transcript levels.Conclusions:  Quantification of Gli1 transcripts by RT‐PCR is helpful in discriminating BCC and trichoepithelioma from other skin tumors.
Biphasic sarcomatoid basal cell carcinoma (carcinosarcoma): four cases with immunohistochemistry and review of the literature
Authors: Bigby S. M. , Charlton A. , Miller M. V. , Zwi L. J. , Oliver G. F. 
Published: December 2004

Background:  Biphasic sarcomatoid carcinoma (BSC), or carcinosarcoma, is an uncommon biphasic neoplasm that has been reported in diverse anatomical sites. The tumor is composed of a malignant epithelial component intimately associated with a malignant mesenchymal component, which may be homologous or heterologous. Twenty‐three cases of primary cutaneous BSC have been reported in the English literature. In only eight of these cases was basal cell carcinoma the epithelial component.Methods:  We report a further four cases of primary cutaneous biphasic basal cell carcinoma, and include the clinical, histological and immunohistochemical features.Results:  The four cases showed basal cell carcinoma associated with a pleomorphic sarcomatous stroma. In addition, myofibroblastic differentiation and foci of osteoid were present in one case, and leiomyosarcomatous areas in another. The epithelial components were positive for several epithelial markers. The mesenchymal components were positive for vimentin and CD99, and negative for epithelial markers. p53 was positive with equal intensity in both epithelial and mesenchymal components. A significantly worse outcome was observed in patients with tumors measuring 40 mm or more at excision.Conclusions:  The sarcomatous component of the tumor is best regarded as a metaplastic transformation of the carcinomatous component. These tumors are potentially aggressive if incompletely excised, and complete resection is recommended.
A Critical Examination of the Handbook of Industrial, Work and Organizational Psychology by N. Anderson, D.S. Ones, H.K. Sinangil and C. Viswesvaran (eds)*
Authors: Gorriti Mikel 
Published: December 2004

Books reviewed:N. Anderson, D.S. Ones, H.K. Sinangil and C. Viswesvaran, Handbook of Industrial, Work and Organizational Psychology
The Transmembrane Helix of the
Escherichia coli
Division Protein FtsI Localizes to the Septal Ring
Authors: Wissel Mark C. , Wendt Jennifer L. , Mitchell Calista J. , Weiss David S. 
Published: December 2004

ABSTRACT

FtsI (also called PBP3) of
Escherichia coli
is a transpeptidase required for synthesis of peptidoglycan in the division septum and is one of about a dozen division proteins that localize to the septal ring. FtsI comprises a short amino-terminal cytoplasmic domain, a single transmembrane helix (TMH), and a large periplasmic domain that encodes the catalytic (transpeptidase) activity. We show here that a 26-amino-acid fragment of FtsI is sufficient to direct green fluorescent protein to the septal ring in cells depleted of wild-type FtsI. This fragment extends from W22 to V47 and corresponds to the TMH. This is a remarkable finding because it is usual for a TMH to target a protein to a site more specific than the membrane. Alanine-scanning mutagenesis of the TMH identified several residues important for septal localization. These residues cluster on one side of an alpha-helix, which we propose interacts directly with another division protein to recruit FtsI to the septal ring.
Fate of Predator and Prey Proteins during Growth of
Bdellovibrio bacteriovorus
on
Escherichia coli
and
Pseudomonas syringae
Prey
Authors: Barel Gilli , Sirota Alexandra , Volpin Hanne , Jurkevitch Edouard 
Published: December 2004

ABSTRACT

A two-dimensional electrophoretic analysis of protein distribution followed by identification of selected proteins by mass spectrometry was performed on fresh bdellovibrio cultures containing attack phase cells of the predatory bacterium
Bdellovibrio bacteriovorus
strain 109J-1 and the remains of an
Escherichia coli
or a
Pseudomonas syringae
pv.
tomato
prey. Cleavage of the peptidoglycan-associated outer membrane proteins (OMPs) OmpA in
E. coli
and OprF in
P. syringae
occurred in both prey. The tryptic peptides obtained from the cleavage products of OmpA and OprF were all located within the 19-kDa pronase-resistant N-terminal parts of the corresponding proteins. The predator cell fraction was separated from the prey ghosts in fresh bdellovibrio cultures by centrifugation on a Percoll-sucrose cushion. Proteins from each fraction were separated by two-dimensional electrophoresis and identified by mass spectrometric analysis. As no prey OMP could be detected in the predator cell fraction, it was concluded that prey OMPs are not transferred to the predator, as had been suggested previously. However, a protein from the predator was found bound to ghost cell envelopes. This protein may correspond to a protein earlier suggested to be associated with the prey outer or cytoplasmic membranes. Along with recently described polypeptides from
B. bacteriovorus
strains 100 and 114, it forms a new family of putative outer membrane proteins.
New Temperature-Sensitive Alleles of
ftsZ
in
Escherichia coli
Authors: Addinall Stephen G. , Small Elaine , Whitaker Duncan , Sturrock Shane , Donachie William D. , Khattar Medhat M. 
Published: December 2004

ABSTRACT

We isolated five new temperature-sensitive alleles of the essential cell division gene
ftsZ
in
Escherichia coli
, using P1-mediated, localized mutagenesis. The five resulting single amino acid changes (Gly
109
→Ser
109
for
ftsZ6460
, Ala
129
→Thr
129
for
ftsZ972
, Val
157
→Met
157
for
ftsZ2066
, Pro
203
→Leu
203
for
ftsZ9124
, and Ala
239
→Val
239
for
ftsZ2863
) are distributed throughout the FtsZ core region, and all confer a lethal cell division block at the nonpermissive temperature of 42°C. In each case the division block is associated with loss of Z-ring formation such that fewer than 2% of cells show Z rings at 42°C. The
ftsZ9124
and
ftsZ6460
mutations are of particular interest since both result in abnormal Z-ring formation at 30°C and therefore cause significant defects in FtsZ polymerization, even at the permissive temperature. Neither purified FtsZ9124 nor purified FtsZ6460 exhibited polymerization when it was assayed by light scattering or electron microscopy, even in the presence of calcium or DEAE-dextran. Hence, both mutations also cause defects in FtsZ polymerization in vitro. Interestingly, FtsZ9124 has detectable GTPase activity, although the activity is significantly reduced compared to that of the wild-type FtsZ protein. We demonstrate here that unlike expression of
ftsZ84
, multicopy expression of the
ftsZ6460
,
ftsZ972
, and
ftsZ9124
alleles does not complement the respective lethalities at the nonpermissive temperature. In addition, all five new mutant FtsZ proteins are stable at 42°C. Therefore, the novel isolates carrying single
ftsZ
(Ts) point mutations, which are the only such strains obtained since isolation of the classical
ftsZ84
mutation, offer significant opportunities for further genetic characterization of FtsZ and its role in cell division.
Depolymerization of β-1,6-N-Acetyl-d-Glucosamine Disrupts the Integrity of Diverse Bacterial Biofilms
Authors: Itoh Yoshikane , Wang Xin , Hinnebusch B. Joseph , Preston James F. , Romeo Tony 
Published: December 2004

ABSTRACTPolymeric β-1,6-N-acetyl-d-glucosamine (poly-β-1,6-GlcNAc) has been implicated as anEscherichia coliandStaphylococcus epidermidisbiofilm adhesin, the formation of which requires thepgaABCDandicaABCDloci, respectively. Enzymatic hydrolysis of poly-β-1,6-GlcNAc, demonstrated for the first time by chromatography and mass spectrometry, disrupts biofilm formation by these species and byYersinia pestisandPseudomonas fluorescens, which possesspgaABCDhomologues.
Natural Isolates of
Salmonella enterica
Serovar Dublin Carry a Single
nadA
Missense Mutation
Authors: Bergthorsson Ulfar , Roth John R. 
Published: December 2004

ABSTRACT

Nicotinic acid is required by most isolates of
Salmonella enterica
(serovar Dublin), a pathogen of cattle. A single
nadA
missense mutation causes the nutritional requirement of all serovar Dublin isolates tested. Models for persistence of this allele are tested and discussed.
ThepbgPEoperon inPhotorhabdus luminescensIs Required for Pathogenicity and Symbiosis
Authors: Bennett H. P. J. , Clarke D. J. 
Published: December 2004

ABSTRACTPhotorhabdusis a genus of gram-negativeEnterobacteriaceaethat is pathogenic to insect larvae while also maintaining a mutualistic relationship with nematodes from the familyHeterorhabditis, where the bacteria occupy the gut of the infective juvenile (IJ) stage of the nematode. In this study we describe the identification and characterization of a mutation in thepbgE1gene ofPhotorhabdus luminescensTT01, predicted to be the fifth gene in thepbgPEoperon. We show that this mutant, BMM305, is strongly attenuated in virulence against larvae of the greater wax moth,Galleria mellonella, and we report that BMM305 is more sensitive to the cationic antimicrobial peptide, polymyxin B, and growth in mildly acidic pH than the parental strain ofP. luminescens. Moreover, we also show that the lipopolysaccharide (LPS) present on the surface of BMM305 does not appear to contain any O antigen. Complementation studies reveal that the increased sensitivity to polymyxin B and growth in mildly acidic pH can be rescued by the intransexpression ofpbgE1, while the defects in O-antigen assembly and pathogenicity require the intransexpression ofpbgE1and the downstream genespbgE2andpbgE3. Finally, we show that BMM305 is defective in symbiosis as this mutant is unable to colonize the gut of the IJ stage of the nematode. Therefore, we conclude that thepbgPEoperon is required for both pathogenicity and symbiosis inP. luminescens.
The Epstein-Barr Virus Replication Protein BBLF2/3 Provides an Origin-Tethering Function through Interaction with the Zinc Finger DNA Binding Protein ZBRK1 and the KAP-1 Corepressor
Authors: Liao Gangling , Huang Jian , Fixman Elizabeth D. , Hayward S. Diane 
Published: December 2004

ABSTRACTHerpesviruses encode a set of core proteins essential for lytic replication of their genomes. Three of these proteins form a tripartite helix-primase complex that, in the case of Epstein-Barr virus (EBV), consists of the helicase BBLF4, the primase BSLF1, and the linker protein BBLF2/3. BBLF2/3 and its homologs in the other herpesviruses remain relatively poorly characterized. To better understand the contribution to replication made by BBLF2/3, a yeast two-hybrid screen was performed with BBLF2/3 as the bait protein. This screen identified as interactors a number of cell replication-related proteins such as DNA polymerase beta and subunits of DNA polymerase delta along with the EBV-encoded DNase BGLF5. The screen also identified the DNA binding zinc finger protein ZBRK1 and the ZBRK1 corepressor KAP-1 as BBLF2/3 interactors. Interaction between BBLF2/3 and ZBRK1 and KAP-1 was confirmed in coimmunoprecipitation assays. A binding site for ZBRK1 in the EBV oriLyt enhancer was identified by electrophoretic mobility shift assay. ZBRK1, KAP-1, and the ZBRK1 binding protein BRCA1 were shown by indirect immunofluorescence to be present in replication compartments in lytically induced D98-HR1 cells, and additionally, chromatin immunoprecipitation assays determined that these proteins associated with oriLyt DNA. Replication of an oriLyt plasmid and a variant oriLyt (ΔZBRK1) plasmid was examined in lytically induced D98-HR1 cells. Exogenous ZBRK1, KAP-1, or BRCA1 increased the efficiency of oriLyt replication, while deletion of the ZBRK1 binding site impaired replication. These experiments identify ZBRK1 as another cell protein that, through BBLF2/3, provides a tethering point on oriLyt for the EBV replication complex. The data also suggest that BBLF2/3 may serve as a contact interface for cell proteins involved in replication of EBV oriLyt.
Study of Poligar Violence in Late 18th Century Tamil Country in South India
Authors: Seylon Raman N. 
Published: December 2004

AbstractThis paper is written in an effort to understand the nature and the causes behind the brutal acts of violence unleashed by the poligar military households of South India. It particularly focuses on the poligar rajah Kattabomma Nayakar, who has, since the early 1950s, assumed the role of an ancestor figure of Tamil nationalism. I have relied mainly on colonial archival materials and a few folkloric accounts as my sources and used the anthropological insights of F. G. Baily, Victor Turner, and Steward Gordon in their studies of the political conflicts. In this paper, I do not so much question the reliability and accuracy of the colonial materials. However, I examine their interpretations and the motivations that many historians seem to have overlooked. This is particularly so in the case of poligar led violence as its true causes are often misrepresented and misunderstood in colonial records. We could even say that there is a vested colonial interest in misunderstanding these acts of violence, which are often used as citations to justify the subsequent colonial policies directed not only against the poligars but also against the entire the civil population of the Tamil country. In this paper, I argue that the poligars such as Kattabomma Nayakar were rebels with a cause. They saw themselves indulging in most cases in activities that stood within the bounds of the poligars' traditional mode of conduct. Further, I will also demonstrate how the political violence is intimately linked with political mobility and state formation in pre modern South India. A wider applicability of the results of this study to other parts of South Asia is useful in illuminating the causes and the nature of the political conflicts in various cross cultural settings.
CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma
Authors: Trudel Suzanne , Li Zhi Hua , Wei Ellen , Wiesmann Marion , Chang Hong , Chen Christine , Reece Donna , Heise Carla , Stewart A. Keith 
Published: December 2004

Abstract
The t(4;14) translocation that occurs uniquely in a subset (15%) of patients with multiple myeloma (MM) results in the ectopic expression of the receptor tyrosine kinase (RTK), fibroblast growth factor receptor 3 (FGFR3). Inhibition of activated FGFR3 in MM cells induces apoptosis, validating FGFR3 as a therapeutic target in t(4;14) MM and encouraging the clinical development of FGFR3 inhibitors for the treatment of these patients, who have a poor prognosis. We describe here the characterization of a novel, small-molecule inhibitor of class III, IV, and V RTKs, CHIR-258, as an inhibitor of FGFR3. CHIR-258 potently inhibits FGFR3 with an inhibitory concentration of 50% (IC50) of 5 nM in in vitro kinase assays and selectively inhibited the growth of B9 cells and human myeloma cell lines expressing wild-type (WT) or activated mutant FGFR3. In responsive cell lines, CHIR-258 induced cytostatic and cytotoxic effects. Importantly, addition of interleukin 6 (IL-6) or insulin growth factor 1 (IGF-1) or coculture on stroma did not confer resistance to CHIR-258. In primary myeloma cells from t(4;14) patients, CHIR-258 inhibited downstream extracellular signal-regulated kinase (ERK) 1/2 phosphorylation with an associated cytotoxic response. Finally, therapeutic efficacy of CHIR-258 was demonstrated in a xenograft mouse model of FGFR3 MM. These studies support the clinical evaluation of CHIR-258 in MM.
Decision-Making About Tamoxifen in Women at High Risk for Breast Cancer: Clinical and Psychological Factors
Authors: Bober Sharon L. , Hoke Lizbeth A. , Duda Rosemary B. , Regan Meredith M. , Tung Nadine M. 
Published: December 2004

Purpose To explore the health-related and psychological factors that influence decision making about tamoxifen (Nolvadex; AstraZeneca, Waltham, MA) chemoprevention in women at increased risk for developing breast cancer. Methods This study involves the assessment of 129 women eligible to take tamoxifen following cancer-risk counseling. Treatment decision and decision satisfaction were measured at 2 and 4 months following counseling. Health-related factors included physician recommendation, personal and family-related health history, and concern about side effects. Psychological factors included breast cancer–related anxiety, risk perception, and depression. Results At 2 months’ follow-up, 44% of participants declined tamoxifen treatment. This number increased to 49% at 4 months. Personal and family health history were not related to the decision, but history of abnormal biopsy did predict tamoxifen use. Physician recommendation was highly correlated with treatment decision. Concern about side effects was related to the decision to decline treatment. Breast cancer–related anxiety and heightened risk perception were associated with the decision to take tamoxifen. However, anxiety and psychological distress were also negatively related to treatment satisfaction. Conclusion Decision-making about tamoxifen is complex, and many eligible women decline treatment or remain undecided. Findings call for further educational follow-up with high-risk women after they undergo initial counseling. Factors related to misperceptions of risk and side effects, as well as psychological distress, may be particularly important targets for intervention.