bluuebunny/crossref_metadata_2025 huggingface dataset:
Complete Genome Sequence and Comparative Genome Analysis of Enteropathogenic
Escherichia coli
O127:H6 Strain E2348/69
Authors: Iguchi Atsushi , Thomson Nicholas R. , Ogura Yoshitoshi , Saunders David , Ooka Tadasuke , Henderson Ian R. , Harris David , Asadulghani M. , Kurokawa Ken , Dean Paul , Kenny Brendan , Quail Michael A. , Thurston Scott , Dougan Gordon , Hayashi Tetsuya , Parkhill Julian , Frankel Gad
Published: October 2008

Enteropathogenic
Escherichia coli
(EPEC) was the first pathovar of
E. coli
to be implicated in human disease; however, no EPEC strain has been fully sequenced until now. Strain E2348/69 (serotype O127:H6 belonging to
E. coli
phylogroup B2) has been used worldwide as a prototype strain to study EPEC biology, genetics, and virulence. Studies of E2348/69 led to the discovery of the locus of enterocyte effacement-encoded type III secretion system (T3SS) and its cognate effectors, which play a vital role in attaching and effacing lesion formation on gut epithelial cells. In this study, we determined the complete genomic sequence of E2348/69 and performed genomic comparisons with other important
E. coli
strains. We identified 424 E2348/69-specific genes, most of which are carried on mobile genetic elements, and a number of genetic traits specifically conserved in phylogroup B2 strains irrespective of their pathotypes, including the absence of the ETT2-related T3SS, which is present in
E. coli
strains belonging to all other phylogroups. The genome analysis revealed the entire gene repertoire related to E2348/69 virulence. Interestingly, E2348/69 contains only 21 intact T3SS effector genes, all of which are carried on prophages and integrative elements, compared to over 50 effector genes in enterohemorrhagic
E. coli
O157. As E2348/69 is the most-studied pathogenic
E. coli
strain, this study provides a genomic context for the vast amount of existing experimental data. The unexpected simplicity of the E2348/69 T3SS provides the first opportunity to fully dissect the entire virulence strategy of attaching and effacing pathogens in the genomic context.
Genomic Characterization of
Ralstonia solanacearum
Phage φRSB1, a T7-Like Wide-Host-Range Phage
Authors: Kawasaki Takeru , Shimizu Mio , Satsuma Hideki , Fujiwara Akiko , Fujie Makoto , Usami Shoji , Yamada Takashi
Published: October 2008

φRSΒ1 is a wide-host-range, T7-like bacteriophage that infects and efficiently lyses the phytopathogenic bacterium
Ralstonia solanacearum
. The φRSB1 genome comprises 43,079 bp of double-stranded DNA (61.7% G+C) with 325-bp terminal repeats and contains 47 open reading frames. Strong activity of tandem early promoters and wide specificity of phage promoters of φRSB1 were demonstrated.
The Type 4 Pili of EnterohemorrhagicEscherichia coliO157:H7 Are Multipurpose Structures with Pathogenic Attributes
Authors: Xicohtencatl-Cortes Juan , Monteiro-Neto Valério , Saldaña Zeus , Ledesma Maria A. , Puente Jose Luís , Girón Jorge A.
Published: October 2008

EnterohemorrhagicEscherichia coli(EHEC) O157:H7 produces long bundles of polar type 4 pili (T4P) called HCP (forhemorrhagiccolipili) that form physical bridges between bacteria associating with human and animal epithelial cells. Here, we sought to further investigate whether HCP possessed other pathogenicity attributes associated with T4P production. Comparative studies performed with wild-type EHEC EDL933 and an isogenichcpAmutant revealed that HCP play different roles in the biology of this organism. We found that in addition to promoting bacterial attachment to host cells, HCP mediate (i) invasion of epithelial cells, (ii) hemagglutination of rabbit erythrocytes, (iii) interbacterial connections conducive to biofilm formation, (iv) specific binding to host extracellular matrix proteins laminin and fibronectin but not collagen, and (v) twitching motility. Nonadherent laboratoryE. colistrain HB101 complemented withhcpABCgenes on plasmid pJX22, which specifies for HCP overproduction in EDL933, became hyperadherent and invasive and produced a thick biofilm, suggesting that the presence of HCP confers HB101(pJX22) new attributes otherwise not exhibited by HB101. Analogous to other bacteria in which T4P are involved in the pathogenesis of several infectious diseases, our data strongly suggest that HCP display multiple functions that may contribute to EHEC colonization of different hosts and to virulence, survival, and transmission of this food-borne pathogen.
Distinct Sensory Pathways in
Vibrio cholerae
El Tor and Classical Biotypes Modulate Cyclic Dimeric GMP Levels To Control Biofilm Formation
Authors: Hammer Brian K. , Bassler Bonnie L.
Published: October 2008

Quorum sensing (QS), or cell-cell communication in bacteria, is achieved through the production and subsequent response to the accumulation of extracellular signal molecules called autoinducers (AIs). To identify AI-regulated target genes in
Vibrio cholerae
El Tor (
V. cholerae
El
), the strain responsible for the current cholera pandemic, luciferase expression was assayed in an AI
−
strain carrying a random
lux
transcriptional reporter library in the presence and absence of exogenously added AIs. Twenty-three genes were identified and shown to require the QS transcription factor, HapR, for their regulation. Several of the QS-dependent target genes, annotated as encoding hypothetical proteins, in fact encode HD-GYP proteins, phosphodiesterases that degrade the intracellular second messenger cyclic dimeric GMP (c-di-GMP), which is important for controlling biofilm formation. Indeed, overexpression of a representative QS-activated HD-GYP protein in
V. cholerae
El
reduced the intracellular concentration of c-di-GMP, which in turn decreased exopolysaccharide production and biofilm formation. The
V. cholerae
classical biotype (
V. cholerae
Cl
), which caused previous cholera pandemics and is HapR
−
, controls c-di-GMP levels and biofilm formation by the VieA signaling pathway. We show that the VieA pathway is dispensable for biofilm formation in
V. cholerae
El
but that restoring HapR in
V. cholerae
Cl
reestablishes QS-dependent repression of exopolysaccharide production. Thus, different pandemic strains of
V. cholerae
modulate c-di-GMP levels and control biofilm formation in response to distinct sensory pathways.
The Complete Genome Sequence of
Bacillus anthracis
Ames “Ancestor”
Authors: Ravel Jacques , Jiang Lingxia , Stanley Scott T. , Wilson Mark R. , Decker R. Scott , Read Timothy D. , Worsham Patricia , Keim Paul S. , Salzberg Steven L. , Fraser-Liggett Claire M. , Rasko David A.
Published: October 2008

The pathogenic bacterium
Bacillus anthracis
has become the subject of intense study as a result of its use in a bioterrorism attack in the United States in September and October 2001. Previous studies suggested that
B. anthracis
Ames Ancestor, the original Ames fully virulent plasmid-containing isolate, was the ideal reference. This study describes the complete genome sequence of that original isolate, derived from a sample kept in cold storage since 1981.
The Complete Genome Sequence ofHelicobacter pyloriStrain G27
Authors: Baltrus David A. , Amieva Manuel R. , Covacci Antonello , Lowe Todd M. , Merrell D. Scott , Ottemann Karen M. , Stein Markus , Salama Nina R. , Guillemin Karen
Published: October 2008

Helicobacter pyloriis a gram-negative pathogen that colonizes the stomachs of over half the world's population and causes a spectrum of gastric diseases including gastritis, ulcers, and gastric carcinoma. TheH. pylorispecies exhibits unusually high levels of genetic variation between strains. Here we announce the complete genome sequence ofH. pyloristrain G27, which has been used extensively inH. pyloriresearch.
Monoclonality and oligoclonality of T cell receptorβgene in angioimmunoblastic T cell lymphoma
Authors: Shah Z H , Harris S , Smith J L , Hodges E
Published: October 2008

Angioimmunoblastic T cell lymphoma (AILT) is an aggressive T cell lymphoma with an incidence of approximately 1–2% of all non-Hodgkin lymphoma. The detection of clonal T cell receptor (TCR) gene rearrangements helps in the diagnosis of T cell malignancies such as AILT, where morphological and immunohistological investigations are not always sufficient to reach a definitive diagnosis. TCR β (TCRB) and TCR γ (TCRG) gene rearrangements were analysed from 17 WHO-defined cases of AILT by PCR for the presence of TCR clonality.TCRBgene rearrangements were sequenced to identify molecular signature(s) common among this patient group. Monoclonal and oligoclonalTCRBandTCRGgene rearrangements were detected in all cases. BV17S1 was slightly over-represented compared to the use of other Vβgene segments; however, no preferential usage of J gene segment(s) was detected. The results of this study emphasise that TCR clonality and oligoclonality is a diagnostic feature of AILT and that BV17S1 is over-represented with no other common molecular findings.
Medication-induced upper gastrointestinal tract injury
Authors: Chen Z , Scudiere J R , Montgomery E
Published: October 2008

Medication-induced upper gastrointestinal (GI) tract injuries are probably fairly common, yet these injuries are rarely documented in pathology reports. Since these injuries often manifest as non-specific histological changes, making a definitive diagnosis of medication-induced injury can be challenging. Three types of evidence can assist in the establishment of a diagnosis: specific histological patterns, the presence of medication fragments in tissue, and clinical data. Histological patterns may reflect specific tissue responses to medication effects or medication toxicity. Morphological clues of medication use such as pill fragments and crystal deposition may be visible within the tissue itself. Clinical data, including medication history, endoscopic findings, and predisposing conditions can alert the pathologist to situations where medication-induced injury should merit a high ranking on the differential diagnosis list. Except for rare cases where characteristic histological changes can be diagnostic, clinical correlation is essential when diagnosing medication-induced injuries. In this review, key features of the most commonly encountered medication-induced upper GI tract injuries are briefly discussed, and a practical guide to assist the practicing pathologist in the recognition and diagnosis of these injuries is provided.
Inflammatory bowel disease unclassified and indeterminate colitis: the role of the pathologist
Authors: Geboes K , Van Eyken P
Published: October 2008

Analysis of multiple biopsies allows a correct diagnosis of inflammatory bowel diseases in 66–75% of newly diagnosed patients. Additional endoscopic and clinical data allow a final diagnosis in more than 90%. Errors or lack of diagnosis are more frequent (up to 7%) in patients with severe inflammatory activity. The terminology for cases without a definite diagnosis is unclear. “Unclassified” and “uncertain” colitis have been proposed as well as “indeterminate colitis”. The latter term has become widely used but with a variety of definitions. The common feature of all definitions is that the aetiology and type of colitis can not be identified properly. Pathologists stress the need for colectomy specimens for the diagnosis, while paediatricians, surgeons and gastroenterologists stress the fact that the colitis can not be classified irrespective of the diagnostic tools used. A correct diagnosis is however essential for treatment. For the pathologist who has to provide such a diagnosis, it is important to know the normal histology and the features associated with various forms of colitis and clinical conditions. This paper describes an algorithm for a diagnosis of colitis with a focus on indeterminate colitis.
Prevalence ofDientamoeba fragilisamong patients consulting complementary medicine practitioners in the British Isles: Figure 1
Authors: Schuster H , Jackson R S
Published: October 2008

A high prevalence ofDientamoeba fragilisis reported in faecal samples collected from patients attending complementary medicine practitioners in the British Isles. Specimens were collected directly after passing into sodium acetate–acetic acid–formalin (SAF). During two observation periods in 2002–04 and 2005–07, aD fragilisprevalence of 14.6% (n = 543) and 16.9% (n = 421), respectively, was recorded. These results confirm a surprisingly high prevalence ofD fragilisamong a selected population. Clinical information was only available for half of the patients withD fragilis; 50% of requests with clinical information reported gastrointestinal symptoms. For further work on its pathogenic role and prevalence among patients with gastrointestinal symptoms, immediate collection in SAF should be considered the optimal sampling modality for UK based laboratories.
Impact of reporting rules of biopsy Gleason score for prostate cancer
Authors: Kuroiwa K , Uchino H , Yokomizo A , Naito S
Published: October 2008

Aims:

To investigate how the biopsy Gleason score (GS) and the clinical risk classification have been changed by the reporting rules.

Methods:

565 prostate biopsy specimens were reassessed. Each Gleason pattern, 1 to 5, was interpreted according to the modified Gleason grading system proposed by the International Society of Urological Pathology. The GS for each case was assigned by the previous reporting rules in the institute (OLD rules), applying the overall-scoring, and ignoring a pattern occupying less than 5% and the tertiary pattern. The GS was also assigned according to the NEW rules, applying the highest-core scoring and reflecting a pattern occupying less than 5% and the tertiary pattern.

Results:

GS upgrading by the NEW rules was observed in 195 (35%) patients. Of these, 179 (92%) patients were upgraded only by applying the highest-core scoring. Of 198 patients with GS 6 by the OLD rules, 22 (11%) were upgraded to GS 3+4. Of 172 patients with GS 3+4 by the OLD rules, 59 (34%) and 28 (16%), respectively, were upgraded to GS 4+3 and ⩾8. Of 108 patients with GS 4+3 by the OLD rules, 63 (58%) were upgraded to GS ⩾8. As a result, the distribution of D’Amico’s clinical risk classification (low, intermediate and high risk) was changed from 26%, 43% and 31% to 23%, 35% and 41%, respectively.

Conclusions:

Clinicians should be aware that the reporting rules, especially the highest-core scoring, contribute to a significant upward shift of the biopsy GS and risk classification.
Darbepoetin-α prevents progressive left ventricular dysfunction and remodeling in nonanemic dogs with heart failure
Authors: Rastogi Sharad , Imai Makoto , Sharov Victor G. , Mishra Sudhish , Sabbah Hani N.
Published: October 2008

In anemic patients with heart failure (HF), erythropoietin-type drugs can elicit clinical improvement. This study examined the effects of chronic monotherapy with darbepoetin-α (DARB) on left ventricular (LV) function and remodeling in nonanemic dogs with advanced HF. HF [LV ejection fraction (EF) ∼25%] was produced in 14 dogs by intracoronary microembolizations. Dogs were randomized to once a week subcutaneous injection of DARB (1.0 μg/kg, n = 7) or to no therapy (HF, n = 7). All procedures were performed during cardiac catheterization under general anesthesia and under sterile conditions. LV end-diastolic volume (EDV), end-systolic volume (ESV), and EF were measured before the initiation of therapy and at the end of 3 mo of therapy. mRNA and protein expression of caspase-3, hypoxia inducible factor-1α, and the bone marrow-derived stem cell marker c-Kit were determined in LV tissue. In HF dogs, EDV and ESV increased and EF decreased after 3 mo of followup. Treatment with DARB prevented the increase in EDV, decreased ESV, and increased EF. DARB therapy also normalized the expression of HIF-1α and active caspase-3 and enhanced the expression of c-Kit. We conclude that chronic monotherapy with DARB prevents progressive LV dysfunction and dilation in nonanemic dogs with advanced HF. These results suggest that DARB elicits beneficial effects in HF that are independent of the presence of anemia.
Neuronal nitric oxide synthase-derived hydrogen peroxide is a major endothelium-dependent relaxing factor
Authors: Capettini L. S. A. , Cortes S. F. , Gomes M. A. , Silva G. A. B. , Pesquero J. L. , Lopes M. J. , Teixeira M. M. , Lemos V. S.
Published: October 2008

Endothelium-dependent vasorelaxation in large vessels is mainly attributed to Nω-nitro-l-arginine methyl ester (l-NAME)-sensitive endothelial nitric oxide (NO) synthase (eNOS)-derived NO production. Endothelium-derived hyperpolarizing factor (EDHF) is the component of endothelium-dependent relaxations that resists full blockade of NO synthases (NOS) and cyclooxygenases. H2O2 has been proposed as an EDHF in resistance vessels. In this work we propose that in mice aorta neuronal (n)NOS-derived H2O2 accounts for a large proportion of endothelium-dependent ACh-induced relaxation. In mice aorta rings, ACh-induced relaxation was inhibited by l-NAME and Nω-nitro-l-arginine (l-NNA), two nonselective inhibitors of NOS, and attenuated by selective inhibition of nNOS with l-ArgNO2-L-Dbu-NH2 2TFA (L-ArgNO2-L-Dbu) and 1-(2-trifluoromethylphehyl)imidazole (TRIM). The relaxation induced by ACh was associated with enhanced H2O2 production in endothelial cells that was prevented by the addition of l-NAME, l-NNA, L-ArgNO2-L-Dbu, TRIM, and removal of the endothelium. The addition of catalase, an enzyme that degrades H2O2, reduced ACh-dependent relaxation and abolished ACh-induced H2O2 production. RT-PCR experiments showed the presence of mRNA for eNOS and nNOS but not inducible NOS in mice aorta. The constitutive expression of nNOS was confirmed by Western blot analysis in endothelium-containing vessels but not in endothelium-denuded vessels. Immunohistochemistry data confirmed the localization of nNOS in the vascular endothelium. Antisense knockdown of nNOS decreased both ACh-dependent relaxation and ACh-induced H2O2 production. Antisense knockdown of eNOS decreased ACh-induced relaxation but not H2O2 production. Residual relaxation in eNOS knockdown mouse aorta was further inhibited by the selective inhibition of nNOS with L-ArgNO2-L-Dbu. In conclusion, these results show that nNOS is constitutively expressed in the endothelium of mouse aorta and that nNOS-derived H2O2 is a major endothelium-dependent relaxing factor. Hence, in the mouse aorta, the effects of nonselective NOS inhibitors cannot be solely ascribed to NO release and action without considering the coparticipation of H2O2 in mediating vasodilatation.
Limited functional and metabolic improvements in hypertrophic and healthy rat heart overexpressing the skeletal muscle isoform of SERCA1 by adenoviral gene transfer in vivo
Authors: O'Donnell J. Michael , Fields Aaron , Xu Xianyao , Chowdhury Shamim A. K. , Geenen David L. , Bi Jian
Published: October 2008

Adenoviral gene transfer of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a to the hypertrophic heart in vivo has been consistently reported to lead to enhanced myocardial contractility. It is unknown if the faster skeletal muscle isoform, SERCA1, expressed in the whole heart in early failure, leads to similar improvements and whether metabolic requirements are maintained during an adrenergic challenge. In this study, Ad.cmv.SERCA1 was delivered in vivo to aortic banded and sham-operated Sprague-Dawley rat hearts. The total SERCA content increased 34%. At 48–72 h posttransfer, echocardiograms were acquired, hearts were excised and retrograded perfused, and hemodynamics were measured parallel to NMR measures of the phosphocreatine (PCr)-to-ATP ratio (PCr/ATP) and energy substrate selection at basal and high workloads (isoproterenol). In the Langendorff mode, the rate-pressure product was enhanced 27% with SERCA1 in hypertrophic hearts and 10% in shams. The adrenergic response to isoproterenol was significantly potentiated in both groups with SERCA1.31P NMR analysis of PCr/ATP revealed that the ratio remained low in the hypertrophic group with SERCA1 overexpression and was not further compromised with adrenergic challenge.13C NMR analysis revealed fat and carbohydrate oxidation were unaffected at basal with SERCA1 expression; however, there was a shift from fats to carbohydrates at higher workloads with SERCA1 in both groups. Transport of NADH-reducing equivalents into the mitochondria via the α-ketoglutamate-malate transporter was not affected by either SERCA1 overexpression or adrenergic challenge in both groups. Echocardiograms revealed an important distinction between in vivo versus ex vivo data. In contrast to previous SERCA2a studies, the echocardiogram data revealed that SERCA1 expression compromised function (fractional shortening) in the hypertrophic group. Shams were unaffected. While our ex vivo findings support much of the earlier cardiomyocyte and transgenic data, the in vivo data challenge previous reports of improved cardiac function in heart failure models after SERCA intervention.
Prolonged treatment of porcine pulmonary artery with nitric oxide decreases cGMP sensitivity and cGMP-dependent protein kinase specific activity
Authors: Perkins William J. , Warner David O. , Jones Keith A.
Published: October 2008

A cultured porcine pulmonary artery (PA) model was used to examine the effects of prolonged nitric oxide (NO) treatment on the response to acutely applied NO, cGMP analog, or atrial natriuretic peptide (ANP). Twenty-four-hour treatment with the NO donor ( Z)-1-[ N-(2-aminoethyl)- N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO) resulted in >10-fold decrease in the response to acutely applied DETA-NO. In parallel with this, the relaxant response to acutely applied cGMP analog, β-phenyl-1, N2-etheno-8-bromoguanosine-3′,5′-cyclic monophosphorothioate, Sp isomer (Sp-8-Br-PET-cGMPS), and ANP decreased. The reduction in ANP responsiveness in PA was not associated with a reduction in cGMP levels evoked by 10−6M ANP. Twenty-four hours in culture and treatment with DETA-NO decreased total cGMP-dependent protein kinase (cGKI) mRNA level compared with that in freshly prepared PA (1.05 ± 0.12, 0.42 ± 0.08, and 0.11 ± 0.01 amol/μg, respectively). Total cGKI protein levels were decreased to a lesser extent by 24 h in culture and further decreased by 24-h DETA-NO treatment compared with that in freshly prepared PA (361 ± 33, 272 ± 20, and 238 ± 25 ng/mg total protein, respectively). Maximal cGMP-stimulated phosphotransferase activity was reduced in 24-h cultured and DETA-NO-treated PA (986 ± 84, 815 ± 81, and 549 ± 78 pmol Pi·min−1·mg soluble protein−1), but the cGMP concentration resulting in 50% of maximal phosphotransferase activity was not. cGKI specific activity (maximal cGMP-activated phosphotransferase activity/ng cGKI) was significantly reduced in PA treated with DETA-NO for 24 h compared with freshly prepared and 24-h cultured PA (1.95 ± 0.22, 2.64 ± 0.25, and 2.85 ± 0.28 pmol Pi·min−1·ng cGKI−1, respectively). We conclude that prolonged NO treatment induces decreased acute NO responsiveness in PA in part by decreasing cGMP sensitivity. It does so by decreasing both cGKI expression and cGKI specific activity.
Airway epithelial-derived factor relaxes pulmonary vascular smooth muscle
Authors: Farah Omar R. , Li Dongge , McIntyre Brendan A. S. , Pan Jingyi , Belik Jaques
Published: October 2008

The factors controlling the pulmonary vascular resistance under physiological conditions are poorly understood. We have previously reported on an apparent cross talk between the airway and adjacent pulmonary arterial bed where a factor likely derived from the bronchial epithelial cells reduced the magnitude of agonist-stimulated force in the vascular smooth muscle. The main purpose of this investigation was to evaluate whether bronchial epithelial cells release a pulmonary arterial smooth muscle relaxant factor. Conditioned media from SPOC-1 or BEAS-2B, a rat- and a human-derived bronchial epithelial cell line, respectively, were utilized. This media significantly relaxed precontracted adult but not fetal pulmonary arterial muscle in an oxygen tension-dependent manner. This response was mediated via soluble guanylate cyclase, involving AKT/PI3-kinase and neuronal nitric oxide synthase. Airway epithelial cell-conditioned media increased AKT phosphorylation in pulmonary smooth muscle cells (SMC) and reduced intracellular calcium change following ATP stimulation to a significantly greater extent than observed for bronchial SMC. The present data strongly support the evidence for bronchial epithelial cells releasing a stable and soluble factor capable of inducing pulmonary arterial SMC relaxation. We speculate that under physiological conditions, the maintenance of a low pulmonary vascular resistance, postnatally, is in part modulated by the airway epithelium.
Lung alveolar integrity is compromised by telomere shortening in telomerase-null mice
Authors: Lee Jooeun , Reddy Raghava , Barsky Lora , Scholes Jessica , Chen Hui , Shi Wei , Driscoll Barbara
Published: October 2008

Shortened telomeres are a normal consequence of cell division. However, telomere shortening past a critical point results in cellular senescence and death. To determine the effect of telomere shortening on lung, four generations of B6.Cg- Terc tm1Rdp mice, null for the terc component of telomerase, the holoenzyme that maintains telomeres, were bred and analyzed. Generational inbreeding of terc−/− mice caused sequential shortening of telomeres. Lung histology from the generation with the shortest telomeres ( terc−/− F4) showed alveolar wall thinning and increased alveolar size. Morphometric analysis confirmed a significant increase in mean linear intercept (MLI). terc−/− F4 lung showed normal elastin deposition but had significantly decreased collagen content. Both airway and alveolar epithelial type 1 cells (AEC1) appeared normal by immunohistochemistry, and the percentage of alveolar epithelial type 2 cells (AEC2) per total cell number was similar to wild type. However, because of a decrease in distal lung cellularity, the absolute number of AEC2 in terc−/− F4 lung was significantly reduced. In contrast to wild type, terc−/− F4 distal lung epithelium from normoxia-maintained mice exhibited DNA damage by terminal deoxynucleotidyltransferase (TdT)-mediated dUTP nick end labeling (TUNEL) and 8-oxoguanine immunohistochemistry. Western blotting of freshly isolated AEC2 lysates for stress signaling kinases confirmed that the stress-activated protein kinase (SAPK)/c-Jun NH2-terminal kinase (JNK) stress response pathway is stimulated in telomerase-null AEC2 even under normoxic conditions. Expression of downstream apoptotic/stress markers, including caspase-3, caspase-6, Bax, and HSP-25, was also observed in telomerase-null, but not wild-type, AEC2. TUNEL analysis of freshly isolated normoxic AEC2 showed that DNA strand breaks, essentially absent in wild-type cells, increased with each successive terc−/− generation and correlated strongly with telomere length ( R2 = 0.9631). Thus lung alveolar integrity, particularly in the distal epithelial compartment, depends on proper telomere maintenance.
Emerging pulmonary vasculature lacks fate specification
Authors: Schwarz Margaret A. , Caldwell Lauren , Cafasso Danielle , Zheng Haihua
Published: October 2008

Lung morphogenesis requires precise coordination between branching morphogenesis and vascularization to generate distal airways capable of supporting respiration at the cell-cell interface. The specific origins and types of blood vessels that initially form in the lung, however, remain obscure. Herein, we definitively show that during the early phases of lung development [i.e., embryonic day ( E) 11.5], functional vessels, replete with blood flow, are restricted to the mesenchyme, distal to the epithelium. However, by day E14.5, and in response to epithelial-derived VEGF signals, functional vessels extend from the mesenchyme to the epithelial interface. Moreover, these vessels reside adjacent to multipotent mesenchymal stromal cells that likely play a regulatory role in this process. As well as and distinct from the systemic vasculature, immunostaining for EphrinB2 and EphB4 revealed that arterial and venous identity is not distinguishable in emergent pulmonary vasculature. Collectively, this study provides evidence that lung vascularization initially originates in the mesenchyme, distal to the epithelium, and that arterial-venous specification does not exist in the early lung. At a mechanistic level, we show that basilar epithelial VEGF prompts endothelial cells to move toward the epithelium where they undergo morphogenesis during the proliferative, canalicular stage. Thus our findings challenge existing notions of vascular origin and identity during development.
Loss of Bmx Nonreceptor Tyrosine Kinase Prevents Pressure Overload–Induced Cardiac Hypertrophy
Authors: Mitchell-Jordan Scherise A. , Holopainen Tanja , Ren Shuxun , Wang Sujing , Warburton Sarah , Zhang Michael J. , Alitalo Kari , Wang Yibin , Vondriska Thomas M.
Published: November 2008

Bmx nonreceptor tyrosine kinase has an established role in endothelial and lymphocyte signaling; however, its role in the heart is unknown. To determine whether Bmx participates in cardiac growth, we subjected mice deficient in the molecule (Bmx knockout mice) to transverse aortic constriction (TAC). In comparison with wild-type mice, which progressively developed massive hypertrophy following TAC, Bmx knockout mice were resistant to TAC-induced cardiac growth at the organ and cell level. Loss of Bmx preserved cardiac ejection fraction and decreased mortality following TAC. These findings are the first to demonstrate a necessary role for the Tec family of tyrosine kinases in the heart and reveal a novel regulator (Bmx) of pressure overload–induced hypertrophic growth.
Was There Doctrinal Dissemination in Early Yahweh Religion?
Authors:   Noll
Published: October 2008

Recent research on scribal practice demonstrates that the scrolls of the Jewish canon were produced by a tiny elite class who did not attempt to disseminate the contents of the scrolls to the largely illiterate Hebrew-speaking peoples. However, the Bible contains a number of passages that describe or command dissemination of their contents (e.g., Deut. 31:10-13), as well as stories about individuals who try to influence common religious belief and practice (e.g., 1 Kigs 18:17-40). These biblical commandments and stories frequently persuade researchers that something like a "doctrinal dissemination" must have been common among pre-Hellenistic Yahwists. Recent research by anthropologists observing processes of religious dissemination is pertinent to this question, calls common assumptions about dissemination into question, and supports the recent conclusions about Hebrew scribal practice.
Mosaic Disability and Identity in Exodus 4:10; 6:12, 30
Authors: Junior Nyasha , Schipper Jeremy
Published: October 2008

In the book of Exodus, Moses describes himself as having a speech difficulty at three different points (4:10; 6:12, 30). These descriptions occur at points in the narrative in which his complex relationship to the Egyptians or Hebrews is at issue. Informed by the burgeoning field of disability studies, this article explores the construction of Moses' identity in the book of Exodus in order to show that his references to his disability provide more than simply an excuse to avoid his divine commission. While his disability may function as an excuse, Moses' emphasis on his disability allows him to circumvent questions about his group identity.
Modern Day Moabites: The Bible and the Debate About Same-Sex Marriage
Authors: Stahlberg Lesleigh Cushing
Published: October 2008

With the debate about same-sex marriage raging in the United States, this paper asks whether the canonical scriptures of Judaism and Christianity offer any justification for blessing same-sex unions. It looks to the ways that the Bible is used by proponents and opponents of same-sex marriage. It analyzes the hermeneutics of the religious left and the religious right, particularly as they grapple with the "clobber texts" of Lev. 18:22 and 20:13. It then turns to the biblical book of Ruth, which critic J. Hillis Miller describes as having "been alienated from itself, translated from itself" through new uses. The paper puts the book of Ruth to yet another new use/misprision, using it as a prooftext to support same-sex marriage. The book has already been upheld by lesbian readers of scripture because of the intimate relationship between the protagonists, Ruth and Naomi, but this paper "misreads" the text differently. Ruth describes how a marriage made between an Israelite and a Moabite brings about the line of King David, one of the most important figures in the Bible and the man from whose line the Messiah is expected to come. The biblical law, however, is unequivocal: Moabites are not permitted to enter into the community of Israel. Juxtaposing the levitical laws (ostensibly) prohibiting homosexuality with those banning Moabites from Israel, this paper argues that the religious left could hold up the book of Ruth as a biblical model for allowing marriage that seems explicitly forbidden by biblical law.
The Mappe and the Bible: Nation, Empire and the Collective Memory of Jonah
Authors: Staffell Simon
Published: October 2008

This article uses the work of the English cartographer John Speed as a way to explore the role of the collective memory of Jonah in social and political discourses during the sixteenth and seventeenth centuries. The paper engages with debates concerning nationalism during the early modern period. Collective memory theory is also used to consider how Jonah became a reified site of memory. By placing Speed's writing alongside the works of his forebears and examining the function of the Jonah text within three sermons, the evolving collective memory of the biblical text, and its imagined attachment to national identity, is traced. It is suggested that Speed's cartographic selectivity in depicting biblical narratives can be seen in relation to the nascent nationalist and imperialist worldviews and ideologies of sixteenth and seventeenth century England.
Zum periphrastischen Infinitiv in Genesis viii 5
Authors: Gzella Holger
Published: October 2008

The astonishing use of the double infinitive absolute with the verb, attested only in Gen. viii 5, has not yet been explained satisfactorily. The present paper argues that this construction is neither a variant form of the periphrastic participle, nor that serves as a pluperfect. Instead, the two infinitives provide an adverbial modification for the main verb by specifically marking durativity and/or iterativity. However, precisely the combination with appears to be special. The past tense indicator, itself being semantically void here, has been employed instead of a full verb, even though such a full verb would normally be expected with this expression, in order to retrieve a piece of information given in Gen. viii 3 and move it from the background to the foreground. It is thus the information structure which conditions the author's decision to explicitly mark the durative Aktionsart.
Awe, Wordlessness and Calamity—A Short Note on Amos v 13
Authors: Goff Matthew
Published: October 2008

Amos v 13 describes a person who perceives God's retribution against social injustice. The word, which may refer to silence, moaning or mourning, signifies that the man is shocked to the point of wordlessness in response to divine violence.
,,JHWH, Gott meiner Rettung!&ldquo Beobachtungen und Erwägungen zur Struktur von Psalm lxxxviii
Authors: Weber Beat
Published: October 2008

Psalm lxxxviii consists of two cantos, four stanzas, ten strophes, and twenty bicola. Two bicola consistently form a strophe, and two, sometimes three strophes form larger units, or stanzas. Two stanzas make up the psalm's first half (a canto), and two stanzas make up its second half (a second canto). The psalm-halves, which contribute to the alternating structure of the whole (ABA'B'), correspond and complete one another (a diptych).The speaker reviews the past and reports on his persistent suffering and prayer. Verses 3, 11, and 15 are to be understood as quotable coordinated “prayers within a prayer”. Along with the recurrent apostrophes of God (verses 2, 10, and 14), they actualize the whole: despite darkness and the lack of a reply, they keep the direct address to YHWH as the “God of my salvation” (2a) alive.
Constructing Meaning in the Face of Suffering: Theodicy in Lamentations
Authors: Boase Elizabeth
Published: October 2008

This article explores the existence of theodic elements within the book of Lamentations. Drawing on the typology outlined by A. Laato and J. C. de Moor (Theodicy in the World of the Bible [Leiden, 2003]) it is identified that Lamentations explores both retributive and educative theodicy within its poems. Other theodic solutions are not, however, present. Although these theodic solutions are present, it cannot be argued that Lamentations constitutes a theodicy as such. Rather, the poems raise and in turn subvert a range of possible theodic assertions in response to the existential crisis which emerged in the wake of the fall of Jerusalem in 586 BCE.
Through a Glass Darkly: Zechariah's Unprocessed Visionary Experience
Authors: Tiemeyer Lena-Sofia
Published: October 2008

This article proposes a new interpretation of Zechariah's vision report. Zechariah's vision report has the distinct quality of an unprocessed description of a visionary experience without much ideological reflection and it attempts to impose ideological meanings onto a multivalent experience. This statement is suggested primarily by the often confused quality of the account, in combination with its interpretative openness. It is further supported by the existence of later textual additions (e.g. Zech. i 14-17; ii 10-17; iii 8b, 10; iv 6b-10a) which serve to accredit Zechariah's originally pristine report with religious and political significance.
Additional Observations Relating to the Legal Significance of Psalm ciii 12
Authors: Pickut William
Published: October 2008

Distinctions in morpho-syntax and meaning between Ps. ciii 12 and the Aramaic quittance formulae must be taken into account, in order to avoid a misappropriation of Mr. Gregory's observations. Legally speaking, the psalm presents God as one who grants pardon for sin, but He cannot be shown to have actually relinquished the grounds for litigation.
Greek Deuteronomy's “Fever and Chills” and Their Magical Afterlife
Authors: Lincicum David
Published: October 2008

The Greek text of Deut. xxviii 22 preserves the earliest reference in a Jewish context to “fever and chills”, a pair that repeatedly surfaces in later incantations. This provided both a scriptural justification for some Greek curses and contributed to the “magical Wirkungsgeschichte” of Deuteronomy itself.
The Role of the Secondary Characters in the Story of the Anointing of Saul (I Samuel ix-x)
Authors: Jacobs Jonathan
Published: October 2008

In this article I address the roles of the secondary characters in the story of the anointing of Saul as king (I Sam. ix-x). This story contains more than the usual number of secondary characters in a biblical narrative, with some of them playing strange or unusual roles. Through literary analysis of the story's structure and its key words, it becomes clear that the secondary characters play a central role in the story. The hidden message of the story, arising from the chiastic structure of this unit, the molding of the main character, and the molding of the secondary characters surrounding him, is that the king of Israel does not come to be chosen by chance; his selection is guided by God. This message is important for the reader, but the development of the story shows that Saul himself learns the same lesson over the course of the events.
“Bēl Bows, Nabû Stoops!” The Prophecy of Isaiah xlvi 1-2 as a Reflection of Babylonian “Processional Omens”
Authors: Schaudig Hanspeter
Published: October 2008

This article argues that Isa xlvi 1-2 represents a prophecy given on the occasion of the Babylonian New Year's festival. It is based on the condition and “behaviour” of the Babylonian cult statues carried in procession. This prophecy is not only directly dependent upon a group of Babylonian omens, called “processional omens”, but also follows the Babylonian custom of divining portents from the condition and movement of the statue of Marduk at the New Year's festival.
Psalm cxlv: David's Song of Praise
Authors:   Booij
Published: October 2008

In Psalm cxlv the Taw-verse makes an inclusion with the title. This is the more remarkable since only this psalm has in its title the word tehillā. As “a song of praise of David”, Psalm cxlv recalls the books of Chronicles, especially in showing David's part in the praise of God. The text complies with the cultic situation in David's time as portrayed in Chronicles. So Psalm cxlv appears to be a text written ex persona Davidis. As such, it was meant to be an introduction to Psalms cxlvi-cl.
“No Future for the Proud Exultant Ones” The Exilic Book of the Four Prophets (Hos., Am., Mic., Zeph.) as a Concept Opposed to the Deuteronomistic History
Authors: Wöhrle Jakob
Published: October 2008

In the research of the last years, the existence of a collection comprising the four prophetic books of Hosea, Amos, Micah and Zephaniah as a precursor of the Book of the Twelve has often been presumed. However, the intention of this collection has been defined inadequately, since the passages assigned to the redactors of this collection differ greatly from each other in their individual content. But compared with the Deuteronomistic History, the intent of this Book of the Four becomes evident. It presents a history of prophecy relying on the history described in the books of Kings but with its own interpretation. Not only cultic, but also social offences led to the divine wrath, and social criteria will determine the future of the people. Thus, the exilic Book of the Four can be understood as a concept opposed to the Deuteronomistic History.
Der Mensch lebt nicht vom Brot allein, sondern …
Authors: Kiss Jenö
Published: October 2008

The aim of this study is, on the one side, to inquire into the meaning of the expression in Deut. viii 3b. Because this expression appears only once in the Old Testament, this study investigates the genitival construction in Num. xxx 13; Deut. xxiii 24; Jer. xvii 16, and Ps. lxxxix 35, and the expression in Num. xxx 3; Judg. xi 36; Isa. xlv 23; and lv 11. One may conclude that these expressions bear signs of a juridical language, with the connotation of ‘self commitment’. Accordingly, in Deut. viii 3b denotes the self commitment of YHWH. Secondly, the study explores the meaning of the expression. Following the lead of Deut. viii 16-18, it arrives at the conclusion that “bread alone” denotes food detached from YHWH, acquired by one's own efforts, in contrast to the manna, the symbol of the provision of God. According to the final clause of Deut. viii 3b, YHWH teaches his people that, when there is food and wealth, they recognise his covenantal love, the sole foundation of Israel's life.
Understanding Amos vi 12 in Light of his other Rhetorical Questions
Authors: Allen Spencer
Published: October 2008

The MT of Amos vi 12a comprises a pair of rhetorical questions: “Do horses run on the rock(s)? Or does one plow with oxen?” An analysis of Amos' other pairs of rhetorical questions, which demonstrate a high degree of semantic and structural parallelism, suggests that the MT is corrupt. Four criteria are accordingly derived from these other rhetorical questions to evaluate the numerous proposed solutions for vi 12a. Alan Cooper's emendation is identified as most consistent with Amos' general usage: “Do horses run on crags? Or does the wild ox plow in the valley?”
The Cult at Kiriath Yearim: Implications from the Biblical Record
Authors: Leuchter Mark
Published: October 2008

Kiriath Yearim typically appears as little more than a geographical setting throughout the narratives and poetry of the Bible, and in some cases it is alluded to in such veiled terms that interpreters have often times not even noticed the allusion. This is understandable when we consider the principle events that take place in or around the city within the Biblical narrative: the conquest under Joshua, the fall of the Elides, the capture and the eventual return of the Ark from the Philistines, and the momentous installation of the Ark in Jerusalem under David. In all of these cases, attention is commanded by the dramatic circumstances and personalities involved as part of a larger historical yarn. Yet in each of these episodes, the circumstances involving Kiriath Yearim involve brief and subtle but concrete references to the city's cultic dimensions and point to its position as a major cult center in pre-Monarchic Israel. Additional passages from the prophetic corpus provide greater detail regarding a once-flourishing cult at Kiriath Yearim that had withered in subsequent eras, but which still occupied a position in the nation's religious consciousness and memory and which became an important theme in the prophetic discourse of the 8th through 6th centuries BCE.
A “Transubstantiated” Humanity: The Relationship between the Divine Image and the Presence of God in Genesis i 26f
Authors: Herring Stephen
Published: October 2008

Since the 1960's the consensus in Old Testament research regarding humanity's role as image of God has been along the lines of a functional or propagandistic interpretation. Thus, humanity represents the deity by functioning like him: they rule over the earth by his command and in his stead. This interpretation, however, often overlooks the ontological worldview of the ancient Near East where the distinction between object and referent was not as clear as it is today. The image functioned to make present the referent, be it god or king. In this way, the priestly conception of humanity as divine image is more than mere function but concerns the manifestation of divine presence as well.
Traces of Aramaic Dialectal Variation in Late Biblical Hebrew
Authors: Pat-El Na'ama
Published: October 2008

This paper discusses some uses of the particle lmh in Late Biblical Hebrew and suggests that its varying uses reflect an Aramaic calque which can best be explained in light of the different syntax of this particle in East and West Aramaic dialects.
The Divine Title ‘The High One’, in the Song of Hannah
Authors: Labuschagne Casper
Published: October 2008

Staying close to MT, the problematic in 1 Sam. ii 10 should be read a synonym of. This particular form of the epithet was deliberately chosen to pun upon the name Eli.
Do not Weep in Bethel: An Emendation Suggested for Micah i 10
Authors: Baruchi-Unna Amitai
Published: October 2008

A new emendation is suggested, according to which Micah i 10 should be translated as follows: In Gath tell it not. Do not weep in Bethel at all. Ophrah roll yourself in dust.