bluuebunny/crossref_metadata_2025 huggingface dataset:
SATB1 dictates expression of multiple genes including IL-5 involved in human T helper cell differentiation
Authors: Ahlfors Helena , Limaye Amita , Elo Laura L. , Tuomela Soile , Burute Mithila , Gottimukkala Kamal Vishnu P. , Notani Dimple , Rasool Omid , Galande Sanjeev , Lahesmaa Riitta
Published: June 2010

Special AT-rich binding protein 1 (SATB1) is a global chromatin organizer and a transcription factor regulated by interleukin-4 (IL-4) during the early T helper 2 (Th2) cell differentiation. Here we show that SATB1 controls multiple IL-4 target genes involved in human Th cell polarization or function. Among the genes regulated by SATB1 is that encoding the cytokine IL-5, which is predominantly produced by Th2 cells and plays a key role in the development of eosinophilia in asthma. We demonstrate that, during the early Th2 cell differentiation, IL-5 expression is repressed through direct binding of SATB1 to the IL-5 promoter. Furthermore, SATB1 knockdown-induced up-regulation of IL-5 is partly counteracted by down-regulating GATA3 expression using RNAi in polarizing Th2 cells. Our results suggest that a competitive mechanism involving SATB1 and GATA3 regulates IL-5 transcription, and provide new mechanistic insights into the stringent regulation of IL-5 expression during human Th2 cell differentiation.
Phosphatidylinositol 3-kinase-δ inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals
Authors: Herman Sarah E. M. , Gordon Amber L. , Wagner Amy J. , Heerema Nyla A. , Zhao Weiqiang , Flynn Joseph M. , Jones Jeffrey , Andritsos Leslie , Puri Kamal D. , Lannutti Brian J. , Giese Neill A. , Zhang Xiaoli , Wei Lai , Byrd John C. , Johnson Amy J.
Published: June 2010

Targeted therapy with imatinib in chronic myeloid leukemia (CML) prompted a new treatment paradigm. Unlike CML, chronic lymphocytic leukemia (CLL) lacks an aberrant fusion protein kinase but instead displays increased phosphatidylinositol 3-kinase (PI3K) activity. To date, PI3K inhibitor development has been limited because of the requirement of this pathway for many essential cellular functions. Identification of the hematopoietic-selective isoform PI3K-δ unlocks a new therapeutic potential for B-cell malignancies. Herein, we demonstrate that PI3K has increased enzymatic activity and that PI3K-δ is expressed in CLL cells. A PI3K-δ selective inhibitor CAL-101 promoted apoptosis in primary CLL cells ex vivo in a dose- and time-dependent fashion that was independent of common prognostic markers. CAL-101–mediated cytotoxicity was caspase dependent and was not diminished by coculture on stromal cells. In addition, CAL-101 abrogated protection from spontaneous apoptosis induced by B cell–activating factors CD40L, TNF-α, and fibronectin. In contrast to malignant cells, CAL-101 does not promote apoptosis in normal T cells or natural killer cells, nor does it diminish antibody-dependent cellular cytotoxicity. However, CAL-101 did decrease activated T-cell production of various inflammatory and antiapoptotic cytokines. Collectively, these studies provide rationale for the clinical development of CAL-101 as a first-in-class targeted therapy for CLL and related B-cell lymphoproliferative disorders.
A mutant allele of the Swi/Snf member BAF250a determines the pool size of fetal liver hemopoietic stem cell populations
Authors: Krosl Jana , Mamo Aline , Chagraoui Jalila , Wilhelm Brian T. , Girard Simon , Louis Isabelle , Lessard Julie , Perreault Claude , Sauvageau Guy
Published: June 2010

It is believed that hemopoietic stem cells (HSC), which colonize the fetal liver (FL) rapidly, expand to establish a supply of HSCs adequate for maintenance of hemopoiesis throughout life. Accordingly, FL HSCs are actively cycling as opposed to their predominantly quiescent bone marrow counterparts, suggesting that the FL microenvironment provides unique signals that support HSC proliferation and self-renewal. We now report the generation and characterization of mice with a mutant allele of Baf250a lacking exons 2 and 3. Baf250aE2E3/E2E3 mice are viable until E19.5, but do not survive beyond birth. Most interestingly, FL HSC numbers are markedly higher in these mice than in control littermates, thus raising the possibility that Baf250a determines the HSC pool size in vivo. Limit dilution experiments indicate that the activity of Baf250aE2E3/E2E3 HSC is equivalent to that of the wild-type counterparts. The Baf250aE2E3/E2E3 FL-derived stroma, in contrast, exhibits a hemopoiesis-supporting potential superior to the developmentally matched controls. To our knowledge, this demonstration is the first that a mechanism operating in a cell nonautonomous manner canexpand the pool size of the fetal HSC populations.
Intrinsic response of thoracic propriospinal neurons to axotomy
Authors: Siebert Justin R , Middelton Frank A , Stelzner Dennis J
Published: June 2010

Background

Central nervous system axons lack a robust regenerative response following spinal cord injury (SCI) and regeneration is usually abortive. Supraspinal pathways, which are the most commonly studied for their regenerative potential, demonstrate a limited regenerative ability. On the other hand, propriospinal (PS) neurons, with axons intrinsic to the spinal cord, have shown a greater regenerative response than their supraspinal counterparts, but remain relatively understudied in regards to spinal cord injury.

Results

Utilizing laser microdissection, gene-microarray, qRT-PCR, and immunohistochemistry, we focused on the intrinsic post-axotomy response of specifically labelled thoracic propriospinal neurons at periods from 3-days to 1-month following T9 spinal cord injury. We found a strong and early (3-days post injury, p.i) upregulation in the expression of genes involved in the immune/inflammatory response that returned towards normal by 1-week p.i. In addition, several regeneration associated and cell survival/neuroprotective genes were significantly up-regulated at the earliest p.i. period studied. Significant upregulation of several growth factor receptor genes (GFRa1, Ret, Lifr) also occurred only during the initial period examined. The expression of a number of pro-apoptotic genes up-regulated at 3-days p.i. suggest that changes in gene expression after this period may have resulted from analyzing surviving TPS neurons after the cell death of the remainder of the axotomized TPS neuronal population.

Conclusions

Taken collectively these data demonstrate that thoracic propriospinal (TPS) neurons mount a very dynamic response following low thoracic axotomy that includes a strong regenerative response, but also results in the cell death of many axotomized TPS neurons in the first week after spinal cord injury. These data also suggest that the immune/inflammatory response may have an important role in mediating the early strong regenerative response, as well as the apoptotic response, since expression of all of three classes of gene are up-regulated only during the initial period examined, 3-days post-SCI. The up-regulation in the expression of genes for several growth factor receptors during the first week post-SCI also suggest that administration of these factors may protect TPS neurons from cell death and maintain a regenerative response, but only if given during the early period after injury.
Prevalence of alternative splicing choices in Arabidopsis thaliana
Authors: English Adam C , Patel Ketan S , Loraine Ann E
Published: June 2010

Background

Around 14% of protein-coding genes of Arabidopsis thaliana genes from the TAIR9 genome release are annotated as producing multiple transcript variants through alternative splicing. However, for most alternatively spliced genes in Arabidopsis, the relative expression level of individual splicing variants is unknown.

Results

We investigated prevalence of alternative splicing (AS) events in Arabidopsis thaliana using ESTs. We found that for most AS events with ample EST coverage, the majority of overlapping ESTs strongly supported one major splicing choice, with less than 10% of ESTs supporting the minor form. Analysis of ESTs also revealed a small but noteworthy subset of genes for which alternative choices appeared with about equal prevalence, suggesting that for these genes the variant splicing forms co-occur in the same cell types. Of the AS events in which both forms were about equally prevalent, more than 80% affected untranslated regions or involved small changes to the encoded protein sequence.

Conclusions

Currently available evidence from ESTs indicates that alternative splicing in Arabidopsis occurs and affects many genes, but for most genes with documented alternative splicing, one AS choice predominates. To aid investigation of the role AS may play in modulating function of Arabidopsis genes, we provide an on-line resource (ArabiTag) that supports searching AS events by gene, by EST library keyword search, and by relative prevalence of minor and major forms.
No association between variation in the NR4A1 gene locus and metabolic traits in white subjects at increased risk for type 2 diabetes
Authors: Müssig Karsten , Machicao Fausto , Machann Jürgen , Schick Fritz , Claussen Claus D , Stefan Norbert , Fritsche Andreas , Häring Hans-Ulrich , Staiger Harald
Published: June 2010

Background

The nuclear receptor NR4A1 is implicated in metabolic regulation in insulin-sensitive tissues, such as liver, adipose tissue, and skeletal muscle. Functional loss of NR4A1 results in insulin resistance and enhanced intramuscular and hepatic lipid content. Therefore, we investigated in a cohort of white European subjects at increased risk for type 2 diabetes whether genetic variation within the NR4A1 gene locus contributes to prediabetic phenotypes, such as insulin resistance, ectopic fat distribution, or β-cell dysfunction.

Methods

We genotyped 1495 subjects (989 women, 506 men) for five single nucleotide polymorphisms (SNPs) tagging 100% of common variants (MAF = 0.05) within the NR4A1 gene locus with an r2 = 0.8. All subjects underwent an oral glucose tolerance test (OGTT), a subset additionally had a hyperinsulinemic-euglycemic clamp (n = 506). Ectopic hepatic (n = 296) and intramyocellular (n = 264) lipids were determined by magnetic resonance spectroscopy. Peak aerobic capacity, a surrogate parameter for oxidative capacity of skeletal muscle, was measured by an incremental exercise test on a motorized treadmill (n = 270).

Results

After appropriate adjustment and Bonferroni correction for multiple comparisons, none of the five SNPs was reliably associated with insulin sensitivity, ectopic fat distribution, peak aerobic capacity, or indices of insulin secretion (all p ≥ 0.05).

Conclusions

Our data suggest that common genetic variation within the NR4A1 gene locus may not play a major role in the development of prediabetic phenotypes in our white European population.
Hypoxia increases the metastatic ability of breast cancer cells via upregulation of CXCR4
Authors: Cronin Patricia A , Wang Jiang H , Redmond H Paul
Published: June 2010

Background

Chemokine SDF1α and its unique receptor CXCR4 have been implicated in organ-specific metastases of many cancers including breast cancer. Hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. We hypothesized that hypoxia would upregulate CXCR4 expression and lead to increased chemotactic responsiveness to its specific ligand SDF1α.

Methods

Three breast cancer cell lines MDA-MB-231, MCF7 and 4T1 were subjected to 48 hrs of hypoxia or normoxia. Cell surface receptor expression was evaluated using flow cytometry. An extracellular matrix invasion assay and microporous migration assay was used to assess chemotactic response and metastatic ability.

Results

CXCR4 surface expression was significantly increased in the two human breast cancer cell lines, MDA-MB-231 and MCF7, following exposure to hypoxia. This upregulation of CXCR4 cell surface expression corresponded to a significant increase in migration and invasion in response to SDF1-αin vitro. The increase in metastatic potential of both the normoxic and the hypoxic treated breast cancer cell lines was attenuated by neutralization of CXCR4 with a CXCR4 neutralizing mAb, MAB172 or a CXCR4 antagonist, AMD3100, showing the relationship between CXCR4 overexpression and increased chemotactic responsiveness.

Conclusions

CXCR4 expression can be modulated by the tissue microenvironment such as hypoxia. Upregulation of CXCR4 is associated with increased migratory and invasive potential and this effect can be abrogated by CXCR4 inhibition. Chemokine receptor CXCR4 is a potential therapeutic target in the adjuvant treatment of breast cancer.
TRPM3 channel stimulated by pregnenolone sulphate in synovial fibroblasts and negatively coupled to hyaluronan
Authors: Ciurtin Coziana , Majeed Yasser , Naylor Jacqueline , Sukumar Piruthivi , English Anne A , Emery Paul , Beech David J
Published: June 2010

Background

Calcium-permeable channels are known to have roles in many mammalian cell types but the expression and contribution of such ion channels in synovial cells is mostly unknown. The objective of this study was to investigate the potential relevance of Transient Receptor Potential Melastatin 3 (TRPM3) channel to fibroblast-like synoviocytes (FLSs) of patients with rheumatoid arthritis.

Methods

The study used RT-PCR and immunofluorescence to detect mRNA and protein. Intracellular calcium measurement detected channel activity in a FLS cell-line and primary cultures of FLSs from patients with rheumatoid arthritis. Enzyme-linked immunosorbent assays measured hyaluronan.

Results

Endogenous expression of TRPM3 was detected. Previously reported stimulators of TRPM3 sphingosine and pregnenolone sulphate evoked sustained elevation of intracellular calcium in FLSs. The FLS cell-line showed an initial transient response to sphingosine which may be explained by TRPV4 channels but was not observed in FLSs from patients. Blocking antibody targeted to TRPM3 inhibited sustained sphingosine and pregnenolone sulphate responses. Secretion of hyaluronan, which contributes adversely in rheumatoid arthritis, was suppressed by pregnenolone sulphate in FLSs from patients and the effect was blocked by anti-TRPM3 antibody.

Conclusions

The data suggest that FLSs of patients with rheumatoid arthritis express TRPM3-containing ion channels that couple negatively to hyaluronan secretion and can be stimulated by pharmacological concentrations of pregnenolone sulphate.
Debate: Limitations on universality: the "right to health" and the necessity of legal nationality
Authors: Kingston Lindsey N , Cohen Elizabeth F , Morley Christopher P
Published: June 2010

Background

The "right to health," including access to basic healthcare, has been recognized as a universal human right through a number of international agreements. Attempts to protect this ideal, however, have relied on states as the guarantor of rights and have subsequently ignored stateless individuals, or those lacking legal nationality in any nation-state. While a legal nationality alone is not sufficient to guarantee that a right to healthcare is accessible, an absence of any legal nationality is almost certainly an obstacle in most cases. There are millions of so-called stateless individuals around the globe who are, in effect, denied medical citizenship in their countries of residence. A central motivating factor for this essay is the fact that statelessness as a concept is largely absent from the medical literature. The goal for this discussion, therefore, is primarily to illustrate the need for further monitoring of health access issues by the medical community, and for a great deal more research into the effects of statelessness upon access to healthcare. This is important both as a theoretical issue, in light of the recognition by many of healthcare as a universal right, as well as an empirical fact that requires further exploration and amelioration.

Discussion

Most discussions of the human right to health assume that every human being has legal nationality, but in reality there are at least 11 to 12 million stateless individuals worldwide who are often unable to access basic healthcare. The examples of the Roma in Europe, the hill tribes of Thailand, and many Palestinians in Israel highlight the negative health impacts associated with statelessness.

Stateless individuals often face an inability to access the most basic healthcare, much less the "highest attainable standard of health" outlined by international agreements. Rather than presuming nationality, statelessness must be recognized by the medical community. Additionally, it is imperative that stateless populations be recognized, the health of these populations be tracked, and more research conducted to further elaborate upon the connection between statelessness and access to healthcare services, and hence a universal right to health.
Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors
Authors: Chlenski Alexandre , Guerrero Lisa J , Peddinti Radhika , Spitz Jared A , Leonhardt Payton T , Yang Qiwei , Tian Yufeng , Salwen Helen R , Cohn Susan L
Published: June 2010

Background

New, more effective strategies are needed to treat highly aggressive neuroblastoma. Our laboratory has previously shown that full-length Secreted Protein Acidic and Rich in Cysteine (SPARC) and a SPARC peptide corresponding to the follistatin domain of the protein (FS-E) potently block angiogenesis and inhibit the growth of neuroblastoma tumors in preclinical models. Peptide FS-E is structurally complex and difficult to produce, limiting its potential as a therapeutic in the clinic.

Results

In this study, we synthesized two smaller and structurally more simple SPARC peptides, FSEN and FSEC, that respectively correspond to the N-and C-terminal loops of peptide FS-E. We show that both peptides FSEN and FSEC have anti-angiogenic activity in vitro and in vivo, although FSEC is more potent. Peptide FSEC also significantly inhibited the growth of neuroblastoma xenografts. Histologic examination demonstrated characteristic features of tumor angiogenesis with structurally abnormal, tortuous blood vessels in control neuroblastoma xenografts. In contrast, the blood vessels observed in tumors, treated with SPARC peptides, were thin walled and structurally more normal. Using a novel method to quantitatively assess blood vessel abnormality we demonstrated that both SPARC peptides induced changes in blood vessel architecture that are consistent with blood vessel normalization.

Conclusion

Our results demonstrate that SPARC peptide FSEC has potent anti-angiogenic and anti-tumorigenic effects in neuroblastoma. Its simple structure and ease of production indicate that it may have clinical utility in the treatment of high-risk neuroblastoma and other types of pediatric and adult cancers, which depend on angiogenesis.
Primary appendiceal mucinous adenocarcinoma alongside with situs inversus totalis: a unique clinical case
Authors: Petrou Athanasios , Papalambros Alexandros , Katsoulas Nikolaos , Bramis Konstantinos , Evangelou Konstantinos , Felekouras Evaggelos
Published: June 2010

Introduction

Mucinous adenocarcinoma is a rare neoplasm of the gastrointestinal tract and one of the three major histological subtypes of the primary appendiceal adenocarcinoma. The most common type of presentation is that of acute appendicitis and the diagnosis is usually occurred after appendectomy. The accurate preoperative diagnosis and management of the above condition represents a real challenge when uncommon anatomic anomalies such intestinal malrotation and situs inversus take place. Situs inversus totalis with an incidence of 0.01% is an uncommon condition caused by a single autosomal recessive gene of incomplete penetration in which the major visceral organs are mirrored from their normal positions.

Case presentation

We present an unusual case of a 59 years old, previously healthy man presented with a left lower quadrant abdominal pain, accompanied with low fever, leukocytosis, anorexia and constipation. A chest radiograph demonstrated dextrocardia with a right side positioned stomach bubble. Both preoperative US and CT scan of the abdomen and pelvis declared situs inversus, with a characteristic thickening in its wall, appendix situated in the left lower quadrant of the abdomen. These findings reached to the diagnosis of acute appendicitis with situs inversus and a standard appendicectomy was performed. Pathologic evaluation established primary mucinous adenocarcinoma of the appendix and three months afterwards the patient underwent a subsequent extended left hemicolectomy.

Conclusion

In conclusion, the occurrence of primary appendiceal mucinous adenocarcinoma along with situs inversus, definitely accounts as a unique clinical case. Even synchronous manifestation of primary mucinous adenocarcinoma of the appendix and situs inversus totalis represents an unusual anatomo-pathological entity, all physicians should be familiar having the knowledge to make an appropriate and accurate diagnosis that will lead to prompt and correct treatment.
Thermal discomfort with cold extremities in relation to age, gender, and body mass index in a random sample of a Swiss urban population
Authors: Mozaffarieh Maneli , Fontana Gasio Paola , Schötzau Andreas , Orgül Selim , Flammer Josef , Kräuchi Kurt
Published: June 2010

Background

The aim of this epidemiological study was to investigate the relationship of thermal discomfort with cold extremities (TDCE) to age, gender, and body mass index (BMI) in a Swiss urban population.

Methods

In a random population sample of Basel city, 2,800 subjects aged 20-40 years were asked to complete a questionnaire evaluating the extent of cold extremities. Values of cold extremities were based on questionnaire-derived scores. The correlation of age, gender, and BMI to TDCE was analyzed using multiple regression analysis.

Results

A total of 1,001 women (72.3% response rate) and 809 men (60% response rate) returned a completed questionnaire. Statistical analyses revealed the following findings: Younger subjects suffered more intensely from cold extremities than the elderly, and women suffered more than men (particularly younger women). Slimmer subjects suffered significantly more often from cold extremities than subjects with higher BMIs.

Conclusions

Thermal discomfort with cold extremities (a relevant symptom of primary vascular dysregulation) occurs at highest intensity in younger, slimmer women and at lowest intensity in elderly, stouter men.
Producing infectious enterovirus type 71 in a rapid strategy
Authors: Han Jian-Feng , Cao Rui-Yuan , Tian Xue , Yu Man , Qin E-De , Qin Cheng-Feng
Published: June 2010

Background

Enterovirus 71 (EV71) is an etiologic agent of hand-foot-and-mouth disease (HFMD), and recent HFMD epidemics worldwide have been associated with a severe form of brainstem encephalitis associated with pulmonary edema and high case-fatality rates. EV71 contains a positive-sense single-stranded genome RNA of approximately 7400 bp in length which encodes a polyprotein with a single open reading frame (ORF), which is flanked by untranslated regions at both the 5' and 3' ends.

Results

A long distance RT-PCR assay was developed to amplify the full length genome cDNA of EV71 by using specific primes carrying a SP6 promoter. Then the in vitro synthesized RNA transcripts from the RT-PCR amplicons were then transfected into RD cells to produce the rescued virus. The rescued virus was further characterized by RT-PCR and indirect fluorescent-antibody (IFA) assay in comparison with the wild type virus. The rescued viruses were infectious on RD cells and neurovirulent when intracerebrally injected into suckling mice.

Conclusions

Thus, we established a rapid method to produce the infectious full length cDNA of EV71 directly from RNA preparations and specific mutations can be easily engineered into the rescued enterovirus genome by this method.
Pathogenesis and antigenic characterization of a new East European subtype 3 porcine reproductive and respiratory syndrome virus isolate
Authors: Karniychuk Uladzimir U , Geldhof Marc , Vanhee Merijn , Van Doorsselaere Jan , Saveleva Tamara A , Nauwynck Hans J
Published: June 2010

Background

Porcine reproductive and respiratory syndrome virus (PRRSV) is divided into a European and North American genotype. East European PRRSV isolates have been found to be of the European genotype, but form different subtypes. In the present study, PRRSV was isolated from a Belarusian farm with reproductive and respiratory failure and designated "Lena". Analyses revealed that Lena is a new East European subtype 3 PRRSV isolate. The main purpose of this investigation was to study the pathogenesis and antigenic characteristics of PRRSV (Lena).

Results

Obvious clinical and virological differences were observed between the animals inoculated with a recent European subtype 1 PRRSV isolate (Belgium A) and animals inoculated with PRRSV (Lena). Three out of six pigs inoculated with PRRSV (Belgium A) had anorexia and low fever at 3, 4 and 5 days post-inoculation (dpi). High fever, anorexia and depression were prominent signs in most pigs inoculated with PRRSV (Lena) between 2 and 28 dpi. Four pigs out of ten died during the experiment. Arcanobacterium pyogenes was isolated from lungs of one animal that died, and Streptococcus suis was isolated from lungs of one animal that was euthanized. The difference in viral titres in sera from PRRSV (Belgium A) and PRRSV (Lena)-infected pigs was statistically significant (p < 0.05) at 7, 10, 14 and 21 dpi. The highest viral titres in sera ranged from 104.8 to 106.1 TCID50/ml for PRRSV (Lena) whereas they ranged from 103.1 to 104.8 TCID50/ml for PRRSV (Belgium A).

The replication of PRRSV (Lena) was further studied in depth. Viral titres ranged from 102.5 TCID50/100 mg to 105.6 TCID50/100 mg in nasal secretions between 3 and 14 dpi and from 102.8 TCID50/100 mg to 104.6 TCID50/100 mg in tonsillar scrapings between 3 and 21 dpi. High viral titres were detected in lungs (102.3-107.7 TCID50/g tissue), tonsils (102.0-106.2 TCID50/g tissue) and inguinal lymph nodes (102.2-106.6 TCID50/g tissue) until 35, 28 and 35 dpi, respectively.

To examine the antigenic heterogeneity between the East European subtype 3 isolate Lena, the European subtype 1 strain Lelystad and the North American strain US5, sets of monospecific polyclonal antisera were tested in immunoperoxidase monolayer assays (IPMAs) with homologous and heterologous viral antigens. Heterologous antibody titres were significantly lower than homologous titres (p = 0.01-0.03) for antisera against PRRSV (Lena) at all sampling time points. For antisera against PRRSV (Lelystad) and PRRSV (US5), heterologous antibody titres were significantly lower than homologous titres at 14 and 21 dpi (p = 0.01-0.03) and at 10 and 14 dpi (p = 0.04), respectively.

Conclusions

Lena is a highly pathogenic East European subtype 3 PRRSV, which differs from European subtype 1 Lelystad and North American US5 strains at both the genetic and antigenic level.
View and review on viral oncology research
Authors: Bergonzini Valeria , Salata Cristiano , Calistri Arianna , Parolin Cristina , Palù Giorgio
Published: June 2010

To date, almost one and a half million cases of cancer are diagnosed every year in the US and nearly 560,000 Americans are expected to die of cancer in the current year, more than 1,500 people a day (data from the American Cancer Society athttp://www.cancer.org/). According to the World Health Organization (WHO), roughly 20% of all cancers worldwide results from chronic infections; in particular, up to 15% of human cancers is characterized by a viral aetiology with higher incidence in Developing Countries. The link between viruses and cancer was one of the pivotal discoveries in cancer research during the past Century. Indeed, the infectious nature of specific tumors has important implications in terms of their prevention, diagnosis, and therapy. In the 21stCentury, the research on viral oncology field continues to be vigorous, with new significant and original studies on viral oncogenesis and translational research from basic virology to treatment of cancer. This review will cover different viral oncology aspects, starting from the history of viral oncology and moving to the peculiar features of oncogenic RNA and DNA viruses, with a special focus on human pathogens.
Affect School for chronic benign pain patients showed improved alexithymia assessments with TAS-20
Authors: Melin Eva O , Thulesius Hans O , Persson Bengt A
Published: June 2010

Background

Alexithymia is a disturbance associated with psychosomatic disorders, pain syndromes, and a variety of psychiatric disorders. The Affect School (AS) based on Tomkins Affect Theory is a therapy focusing on innate affects and their physiological expressions, feelings, emotions and scripts. In this pilot study we tried the AS-intervention method in patients with chronic benign pain.

Methods

The AS-intervention, with 8 weekly group sessions and 10 individual sessions, was offered to 59 patients with chronic non-malignant pain at a pain rehabilitation clinic in Sweden 2004-2005. Pre and post intervention assessments were done with the Hospital Anxiety and Depression scale (HAD), the Toronto Alexithymia Scale-20 (TAS-20), the Visual Analogue Scale for pain assessment (VAS-pain), the European Quality of Life health barometer (EQoL) and the Stress and Crisis Inventory-93 (SCI-93). After the group sessions we used Bergdahl's Questionnaire for assessing changes in interpersonal relations, general well-being and evaluation of AS.

Results

The AS intervention was completed by 54 out of 59 (92%) patients. Significant reductions in total TAS-20 post-test scores (p = 0.0006) as well as TAS-20 DIF and DDF factors (Difficulties Identifying Feelings, and Difficulties Describing Feelings) were seen (p = 0.0001, and p = 0.0008) while the EOT factor (Externally Oriented Thinking) did not change. Improvements of HAD-depression scores (p = 0.04), EQoL (p = 0.02) and self-assessed changes in relations to others (p < 0.001) were also seen. After Bonferroni Correction for Multiple Analyses the TAS-20 test score reduction was still significant as well as Bergdahl's test after group sessions. The HAD, EQoL, SCI-93, and VAS-pain scores were not significantly changed. The AS-intervention was ranked high by the participants.

Conclusions

This pilot study involving 59 patients with chronic benign pain indicates that the alexithymia DIF and DDF, as well as depression, social relations and quality of life may be improved by the Affect School therapeutic intervention.
Successful medical management of emphysematous gastritis with concomitant portal venous air: a case report
Authors: Paul Manju , John Savio , Menon Madhav C , Golewale Nazar H , Weiss Stan L , Murthy Uma K
Published: June 2010

Introduction

The causes of diffuse abdominal pain following pelvic surgery are numerous. We present a rare case of acute abdominal pain in a woman in the post-partum period.

Case presentation

A 25-year-old Caucasian woman with neurofibromatosis type 1 presented to our hospital with diffuse abdominal pain immediately after a cesarean section. The patient was acutely ill and toxic with a fever of 38.8°C, a pulse of 120 beats per minute and a distended abdomen with absent bowel sounds. A computed tomography scan showed air in the wall of the stomach and portal venous system. The patient was successfully treated with intravenous antibiotics, bowel rest and total parenteral nutrition.

Conclusion

It is rare for a case of emphysematous gastritis associated with portal venous air to be treated successfully without surgery. To the best of our knowledge, to date there has been no reported association of emphysematous gastritis with neurofibromatosis.
The case for longer sweeps in vibrator acquisition
Authors: Gibson John , Lin Forest , Egreteau Alexandre , Meunier Julien , Lansley Malcolm
Published: June 2010

There is growing interest in the oil and gas industry to improve the quality of subsurface imaging and reservoir characterization through improved spatial sampling and wide-azimuth coverage of seismic acquisition designs.
Accurate detection of resistivity anomalies using the symmetry attribute and inversion of marine CSEM data
Authors: Dell'Aversana Paolo
Published: June 2010

Sea-bed logging (SBL) or the marine controlled-source electromagnetic (CSEM) method has been widely used for hydrocarbon exploration and provided encouraging results over the past few years.
Introduction to this special section: Borehole geophysics
Authors: Chopra Satinder , Hardage Bob
Published: June 2010

Borehole geophysics is essential for exploration, assessment, and production of Earth's resources, in addition to carrying out fundamental studies on the Earth itself. Borehole-based technology encompasses activities ranging from coring to measurements such as logging, VSP, crosswell profiling, and passive seismic monitoring. Each of these disciplines has grown into an established branch of borehole geophysics. The idea behind all these measurements has been to obtain useful information about the geological environment that helps evaluate subsurface zones of interest.
3D VSP technology now a standard high-resolution reservoir-imaging technique: Part 2, interpretation and value
Authors: Müller Klaus W. , Soroka William L. , Paulsson Björn , Marmash Samer , Al Baloushi Mariam , Al Jeelani Omar
Published: June 2010

This second part of an article about a large 3D VSP survey in Abu Dhabi describes the interpretation effort which quantifies the value that a 3D VSP seismic image can bring when supplementing even a 640-fold, high-resolution surface seismic volume.
From Estrogen-Centric to Aging and Oxidative Stress: A Revised Perspective of the Pathogenesis of Osteoporosis
Authors: Manolagas Stavros C.
Published: June 2010

Estrogen deficiency has been considered the seminal mechanism of osteoporosis in both women and men, but epidemiological evidence in humans and recent mechanistic studies in rodents indicate that aging and the associated increase in reactive oxygen species (ROS) are the proximal culprits. ROS greatly influence the generation and survival of osteoclasts, osteoblasts, and osteocytes. Moreover, oxidative defense by the FoxO transcription factors is indispensable for skeletal homeostasis at any age. Loss of estrogens or androgens decreases defense against oxidative stress in bone, and this accounts for the increased bone resorption associated with the acute loss of these hormones. ROS-activated FoxOs in early mesenchymal progenitors also divert ß-catenin away from Wnt signaling, leading to decreased osteoblastogenesis. This latter mechanism may be implicated in the pathogenesis of type 1 and 2 diabetes and ROS-mediated adverse effects of diabetes on bone formation. Attenuation of Wnt signaling by the activation of peroxisome proliferator-activated receptor γ by ligands generated from lipid oxidation also contributes to the age-dependent decrease in bone formation, suggesting a mechanistic explanation for the link between atherosclerosis and osteoporosis. Additionally, increased glucocorticoid production and sensitivity with advancing age decrease skeletal hydration and thereby increase skeletal fragility by attenuating the volume of the bone vasculature and interstitial fluid. This emerging evidence provides a paradigm shift from the “estrogen-centric” account of the pathogenesis of involutional osteoporosis to one in which age-related mechanisms intrinsic to bone and oxidative stress are protagonists and age-related changes in other organs and tissues, such as ovaries, accentuate them.
AFRICAN AMERICAN ENGLISH IN URBAN SEATTLE: ACCOMMODATION AND INTRASPEAKER VARIATION IN THE PACIFIC NORTHWEST
Authors: SCANLON MICHAEL , WASSINK ALICIA BECKFORD
Published: June 2010

This study considers intraspeaker (style-related) variation and its links to both identity and authenticity in African American English (AAE) speech. It presents a case study of intraspeaker variation in one African American woman from Seattle, Washington, who maintains deep network connections with both African American and white speakers. We examine her variation in two showcase variables (ay-monophthongization; merger of pin-pen), drawing from data collected in conversations with speakers of different ethnicities, to examine the envelope of variation exhibited by this speaker. While her use of core AAE features is not categorical or high-frequency, she does display quantitative shifts in core AAE features that signal responses to interlocutor familiarity, interlocutor speech, and interlocutor ethnicity. The study supports the conclusion that higher-status African Americans can signal an authentic identity with low-frequency but stylized use of AAE forms and argues for a broader concept of AAE competence that takes into account the range of stylistic variation a speaker displays.
Functional Optimization Through Semilocal Approximate Minimization
Authors: Cervellera Cristiano , Macciò Danilo , Muselli Marco
Published: June 2010

An approach based on semilocal approximation is introduced for the solution of a general class of operations research problems, such as Markovian decision problems, multistage optimal control, and maximum-likelihood estimation. Because it is extremely hard to derive analytical solutions that minimize the cost in most instances of the problem, we must look for approximate solutions. Here, it is shown that good solutions can be obtained with a moderate computational effort by exploiting properties of semilocal approximation through kernel models and efficient sampling of the state space. The convergence of the proposed method, called semilocal approximate minimization (SLAM), is discussed, and the consistency of the solution is derived. Simulation results show the efficiency of SLAM, also through its application to a classic operations research problem, i.e., inventory forecasting.
Power comparisons of significance tests of location using scores, ranks, and modular ranks
Authors: Zimmerman Donald W.
Published: June 2010

The Type I error probability and the power of the independent samples t test, performed directly on the ranks of scores in combined samples in place of the original scores, are known to be the same as those of the non‐parametric Wilcoxon–Mann–Whitney (WMW) test. In the present study, simulations revealed that these probabilities remain essentially unchanged when the number of ranks is reduced by assigning the same rank to multiple ordered scores. For example, if 200 ranks are reduced to as few as 20, or 10, or 5 ranks by replacing sequences of consecutive ranks by a single number, the Type I error probability and power stay about the same. Significance tests performed on these modular ranks consistently reproduce familiar findings about the comparative power of the t test and the WMW tests for normal and various non‐normal distributions. Similar results are obtained for modular ranks used in comparing the one‐sample t test and the Wilcoxon signed ranks test.
Development of an efficient synthetic strategy for bioactive alkaloids possessing a spirocyclic ring system
Authors: Honda Toshio
Published: June 2010

Efficient synthetic strategies for several bioactive alkaloids bearing a spirocyclic ring system have been developed. By application of an intramolecular aromatic oxidation of a phenolic intermediate, derived from l-tyrosine and glycine, with hypervalent iodine reagents, TAN1251A, isolated fromPenicillium thomiiRA-89, was synthesized in an optically pure form. Similarly, a novel synthetic path to TAN1251C and TAN1251D was established by employing an l-tyrosine dimer as a common starting material. Moreover, an enamide-phenol oxidative coupling reaction was applied to the synthesis of spirocyclic isoquinoline alkaloids, stepharine and annosqualine. Finally, stereoselective syntheses of securinine and viroallosecurinine in optically active forms were established by using a tandem ring-closing metathesis (RCM) of the enyne as a key reaction.
Differential Replication of Two Chloroplast Genome Forms in Heteroplasmic Chlamydomonas reinhardtii Gametes Contributes to Alternative Inheritance Patterns
Authors: Nishimura Yoshiki , Stern David B
Published: June 2010

Two mechanisms for chloroplast DNA replication have been revealed through the study of an unusual heteroplasmic strain of the green alga Chlamydomonas reinhardtii. Heteroplasmy is a state in which more than one genome type occurs in a mitochondrion or chloroplast. The Chlamydomonas strain spa19 bears two distinct chloroplast genomes, termed PS+ and PS−. PS+ genomes predominate and are stably maintained in vegetative cells, despite their lack of known replication origins. In sexual crosses with spa19 as the mating type plus parent, however, PS+ genomes are transmitted in only ∼25% of tetrads, whereas the PS− genomes are faithfully inherited in all progeny. In this research, we have explored the mechanism underlying this biased uniparental inheritance. We show that the relative reduction and dilution of PS+ vs. PS− genomes takes place during gametogenesis. Bromodeoxyuridine labeling, followed by immunoprecipitation and PCR, was used to compare replication activities of PS+ and PS− genomes. We found that the replication of PS+ genomes is specifically suppressed during gametogenesis and germination of zygospores, a phenomenon that also was observed when spa19 cells were treated with rifampicin, an inhibitor of the chloroplast RNA polymerase. Furthermore, when bromodeoxyuridine incorporation was compared at 11 sites within the chloroplast genome between vegetative cells, gametes, and rifampicin-treated cells by quantitative PCR, we found that incorporation was often reduced at the same sites in gametes that were also sensitive to rifampicin treatment. We conclude that a transcription-mediated form of DNA replication priming, which may be downregulated during gametogenesis, is indispensable for robust maintenance of PS+ genomes. These results highlight the potential for chloroplast genome copy number regulation through alternative replication strategies.
The stability of African savannas: insights from the indirect estimation of the parameters of a dynamic model
Authors: Higgins Steven I. , Scheiter Simon , Sankaran Mahesh
Published: June 2010

Savannas are characterized by a competitive tension between grasses and trees, and theoretical models illustrate how this competitive tension is influenced by resource availability, competition for these resources, and disturbances. How this universe of theoretical possibilities translates into the real world is, however, poorly understood. In this paper we indirectly parameterize a theoretical model of savanna dynamics with the aim of gaining insights as to how the grass–tree balance changes across a broad biogeographical gradient. We use data on the abundance of trees in African savannas and Markov chain Monte Carlo methods to estimate the model parameters. The analysis shows that grasses and trees can coexist over a broad range of rainfall regimes. Further, our results indicate that savannas may be regulated by either asymptotically stable dynamics (in the absence of fire) or by stable limit cycles (in the presence of fire). Rainfall does not influence which of these two classes of dynamics occurs. We conclude that, even though fire might not be necessary for grass–tree coexistence, it nonetheless is an important modifier of grass : tree ratios.
Montane meadow change during drought varies with background hydrologic regime and plant functional group
Authors: Debinski Diane M. , Wickham Hadley , Kindscher Kelly , Caruthers Jennet C. , Germino Matthew
Published: June 2010

Climate change models for many ecosystems predict more extreme climatic events in the future, including exacerbated drought conditions. Here we assess the effects of drought by quantifying temporal variation in community composition of a complex montane meadow landscape characterized by a hydrological gradient. The meadows occur in two regions of the Greater Yellowstone Ecosystem (Gallatin and Teton) and were classified into six categories (M1–M6, designating hydric to xeric) based upon Satellite pour l'Observation de la Terre (SPOT) satellite imagery. Both regions have similar plant communities, but patch sizes of meadows are much smaller in the Gallatin region. We measured changes in the percent cover of bare ground and plants by species and functional groups during five years between 1997 and 2007. We hypothesized that drought effects would not be manifested evenly across the hydrological gradient, but rather would be observed as hotspots of change in some areas and minimally evident in others. We also expected varying responses by plant functional groups (forbs vs. woody plants). Forbs, which typically use water from relatively shallow soils compared to woody plants, were expected to decrease in cover in mesic meadows, but increase in hydric meadows. Woody plants, such as Artemisia, were expected to increase, especially in mesic meadows. We identified several important trends in our meadow plant communities during this period of drought: (1) bare ground increased significantly in xeric meadows of both regions (Gallatin M6 and Teton M5) and in mesic (M3) meadows of the Teton, (2) forbs decreased significantly in the mesic and xeric meadows in both regions, (3) forbs increased in hydric (M1) meadows of the Gallatin region, and (4) woody species showed increases in M2 and M5 meadows of the Teton region and in M3 meadows of the Gallatin region. The woody response was dominated by changes in Artemisia spp. and Chrysothamnus viscidiflorus. Thus, our results supported our expectations that community change was not uniform across the landscape, but instead could be predicted based upon functional group responses to the spatial and temporal patterns of water availability, which are largely a function of plant water use and the hydrological gradient.