bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in the reproductive function and developmental phenotypes in mice following intramuscular injection of an activin betaA-expressing plasmid
Authors: Kim Mi-Nyeu , Park Moon Nyeo , Jung Hoi Kyung , Cho Chunghee , Mayo Kelly E , Cho Byung-Nam 
Published: December 2008

AbstractBackgroundThe TGF-beta family protein activin has numerous reported activities with some uncertainty in the reproductive axis and development. The precise roles of activin in in vivo system were investigated using a transient gain of function model.MethodsTo this end, an expression plasmid, pCMV-rAct, with the activin betaA cDNA fused to the cytomegalovirus promoter, was introduced into muscle of the female adult mice by direct injection.ResultsActivin betaA mRNA was detected in the muscle by RT-PCR and subsequent Southern blot analysis. Activin betaA was also detected, and western blot analysis revealed a relatively high level of serum activin with correspondingly increased FSH. In the pCMV-rAct-injected female mice, estrus stage within the estrous cycle was extended. Moreover, increased numbers of corpora lutea and a thickened granulosa cell layer with a small antrum in tertiary follicles within the ovary were observed. When injected female mice were mated with males of proven fertility, a subset of embryos died in utero, and most of those that survived exhibited increased body weight.ConclusionTaken together, our data reveal that activin betaA can directly influence the estrous cycle, an integral part of the reproduction in female mice and activin betaA can also influence the embryo development as an endocrine fashion.
Evolution of a polymodal sensory response network
Authors: Srinivasan Jagan , Durak Omer , Sternberg Paul W 
Published: December 2008

Abstract

Background

Avoidance of noxious stimuli is essential for the survival of an animal in its natural habitat. Some avoidance responses require polymodal sensory neurons, which sense a range of diverse stimuli, whereas other stimuli require a unimodal sensory neuron, which senses a single stimulus. Polymodality might have evolved to help animals quickly detect and respond to diverse noxious stimuli. Nematodes inhabit diverse habitats and most nematode nervous systems are composed of a small number of neurons, despite a wide assortment in nematode sizes. Given this observation, we speculated that cellular contribution to stereotyped avoidance behaviors would also be conserved between nematode species. The ASH neuron mediates avoidance of three classes of noxious stimuli in Caenorhabditis elegans. Two species of parasitic nematodes also utilize the ASH neuron to avoid certain stimuli. We wanted to extend our knowledge of avoidance behaviors by comparing multiple stimuli in a set of free-living nematode species.

Results

We used comparative behavioral analysis and laser microsurgery to examine three avoidance behaviors in six diverse species of free-living nematodes. We found that all species tested exhibit avoidance of chemo-, mechano- and osmosensory stimuli. In C. elegans, the bilaterally symmetric polymodal ASH neurons detect all three classes of repellant. We identified the putative ASH neurons in different nematode species by their anatomical positions and showed that in all six species ablation of the ASH neurons resulted in an inability to avoid noxious stimuli. However, in the nematode Pristionchus pacificus, the ADL neuron in addition to the ASH neuron contributed to osmosensation. In the species Caenorhabditis sp. 3, only the ASH neuron was required to mediate nose touch avoidance instead of three neurons in C. elegans. These data suggest that different species can increase or decrease the contribution of additional, non-ASH sensory neurons mediating osmosensation and mechanosensation.

Conclusion

The overall conservation of ASH mediated polymodal nociception suggests that it is an ancestral evolutionarily stable feature of sensation. However, the finding that contribution from non-ASH sensory neurons mediates polymodal nociception in some nematode species suggests that even in conserved sensory behaviors, the cellular response network is dynamic over evolutionary time, perhaps shaped by adaptation of each species to its environment.
Hardwiring of fine synaptic layers in the zebrafish visual pathway
Authors: Nevin Linda M , Taylor Michael R , Baier Herwig 
Published: December 2008

Abstract
Background
Neuronal connections are often arranged in layers, which are divided into sublaminae harboring synapses with similar response properties. It is still debated how fine-grained synaptic layering is established during development. Here we investigated two stratified areas of the zebrafish visual pathway, the inner plexiform layer (IPL) of the retina and the neuropil of the optic tectum, and determined if activity is required for their organization.

Results
The IPL of 5-day-old zebrafish larvae is composed of at least nine sublaminae, comprising the connections between different types of amacrine, bipolar, and ganglion cells (ACs, BCs, GCs). These sublaminae were distinguished by their expression of cell type-specific transgenic fluorescent reporters and immunohistochemical markers, including protein kinase Cβ (PKC), parvalbumin (Parv), zrf3, and choline acetyltransferase (ChAT). In the tectum, four retinal input layers abut a laminated array of neurites of tectal cells, which differentially express PKC and Parv. We investigated whether these patterns were affected by experimental disruptions of retinal activity in developing fish. Neither elimination of light inputs by dark rearing, nor a D, L-amino-phosphono-butyrate-induced reduction in the retinal response to light onset (but not offset) altered IPL or tectal lamination. Moreover, thorough elimination of chemical synaptic transmission with Botulinum toxin B left laminar synaptic arrays intact.

Conclusion
Our results call into question a role for activity-dependent mechanisms – instructive light signals, balanced on and off BC activity, Hebbian plasticity, or a permissive role for synaptic transmission – in the synaptic stratification we examined. We propose that genetically encoded cues are sufficient to target groups of neurites to synaptic layers in this vertebrate visual system.
Comparison of temporal changes in psychological distress after hematopoietic stem cell transplantation among the underlying diseases of Japanese adult patients
Authors: Fukuo Wataru , Yoshiuchi Kazuhiro , Takimoto Yoshiyuki , Sakamoto Noriyuki , Kikuchi Hiroe , Hachizuka Maki , Inada Shuji , Nannya Yasuhito , Kumano Keiki , Takahashi Tsuyoshi , Kurokawa Mineo , Akabayashi Akira 
Published: December 2008

Abstract

Background
Although hematopoietic stem cell transplantation (HSCT) can potentially cure some hematological malignancies, patients who undergo HSCT experience psychological distress. However, there have been few studies on the short-term influence of HSCT on psychological distress.

Methods
The subjects were 71 patients with hematological malignancies who underwent HSCT: 33 with acute leukemia, 19 with chronic leukemia, nine with myelodysplastic syndrome, and 10 with malignant lymphoma. Psychological distress was assessed prior to HSCT and on the seventh day after HSCT using the Profile of Mood States (POMS).

Results
With regard to Anger-Hostility, the interaction of time (pre- and post-HSCT) and group (the four groups) was significant in male patients (p = 0.04), but not in female patients. With regard to the other subscales of POMS, there was no significant main effect or interaction in male or female patients.

Conclusion
It may be important to provide psychological support to patients throughout the period of HSCT in consideration of differences in mood changes associated with the underlying disease and patient sex in order to provide efficient psychiatric intervention for both better psychiatric and survival outcomes.
Cytomegalovirus-associated splenic infarcts in a female patient with Factor V Leiden mutation: a case report
Authors: Atzmony Lihi , Saar Nili , Chundadze Tamar , Arbel Yaron , Justo Dan , Mashav Noa 
Published: December 2008

Abstract

Introduction
Cytomegalovirus-associated thrombosis has rarely been reported in the medical literature, and if so, mainly in immunocompromized patients.

Case presentation
We report the case of a 36-year-old Caucasian woman with acute cytomegalovirus infection presenting with spontaneous splenic infarcts. Trans-esophageal echocardiography did not show any vegetations or mural thrombi. The patient was also found to be heterozygous for the Factor V Leiden mutation. Anticoagulation treatment was considered but ruled out since cytomegalovirus was the obvious trigger for thrombosis in this patient. To the best of our knowledge, this is only the third report to date of cytomegalovirus-associated splenic infarcts.

Conclusion
This case report serves as additional evidence for the role of cytomegalovirus in thrombosis.
Atypical manifestation of late onset limb girdle muscular dystrophy presenting with recurrent falling and shoulder dysfunction: a case report
Authors: Schofer Markus Dietmar , Patzer Thilo , Quante Markus 
Published: December 2008

Abstract

Introduction
Myopathies can be sub-classified into congenital, hereditary, mitochondrial, and secondary myopathies.
Congenital myopathies are usually diagnosed post partal or in early childhood. Manifestation in adolescence is uncommon and most cases occur as sporadic mutations. Therefore, there is a risk of under diagnosing this disease in middle-aged patients showing pain, dysfunction, recurrent trauma or falls, where muscle atrophy is seen as a secondary injury.

Case presentation
Our report is about a 54 year old Caucasian woman with an extended history of pain, loss of function and weakness in her right shoulder. The clinical picture showed a frozen right shoulder. The main finding was a marked limb-muscle atrophy of both delta- und biceps-muscles and a rotator cuff tear that had developed over years. Previous medical consultations attributed the atrophy to recurrent falls, shoulder dysfunction and pain. Conservative treatment (analgesics, physiotherapy, training) had failed.
The familiar anamnesis was free of any neurological diseases or other genetic diseases.
MRI showed a sub-total proximal muscular limb atrophy and a rotator cuff tear in both shoulders. An incision-biopsy of the right delta- and biceps-muscle revealed a chronical myopathy. The level of creatinkinasis was expected to be high but measurements showed values only slightly above normal. Immunohistochemistry, eventually revealed a mild form of LGMD (type 2I). Due to the pattern of symptoms and diagnostic results we described the case as atypical LGMD.

Conclusion
Our case presents a phenotype of a late onset of limb girdle muscular dystrophy syndrome associated with shoulder pain and dysfunction and recurrent falls. This kind of disease is not very common. In particular, muscle atrophy in the elderly is generally seen as a secondary injury. This case should remind us of the importance of a differential diagnosis of a late onset of muscular dystrophy-syndrome in the elderly, since an early diagnosis offers more treatment options, therefore preventing a rapid progression.
Genome-wide SNP genotyping highlights the role of natural selection in Plasmodium falciparumpopulation divergence
Authors: Neafsey Daniel E , Schaffner Stephen F , Volkman Sarah K , Park Daniel , Montgomery Philip , Milner Danny A , Lukens Amanda , Rosen David , Daniels Rachel , Houde Nathan , Cortese Joseph F , Tyndall Erin , Gates Casey , Stange-Thomann Nicole , Sarr Ousmane , Ndiaye Daouda , Ndir Omar , Mboup Soulyemane , Ferreira Marcelo U , Moraes Sandra do Lago , Dash Aditya P , Chitnis Chetan E , Wiegand Roger C , Hartl Daniel L , Birren Bruce W , Lander Eric S , Sabeti Pardis C , Wirth Dyann F 
Published: December 2008

Abstract
Background
The malaria parasite Plasmodium falciparum exhibits abundant genetic diversity, and this diversity is key to its success as a pathogen. Previous efforts to study genetic diversity in P. falciparum have begun to elucidate the demographic history of the species, as well as patterns of population structure and patterns of linkage disequilibrium within its genome. Such studies will be greatly enhanced by new genomic tools and recent large-scale efforts to map genomic variation. To that end, we have developed a high throughput single nucleotide polymorphism (SNP) genotyping platform for P. falciparum.

Results
Using an Affymetrix 3,000 SNP assay array, we found roughly half the assays (1,638) yielded high quality, 100% accurate genotyping calls for both major and minor SNP alleles. Genotype data from 76 global isolates confirm significant genetic differentiation among continental populations and varying levels of SNP diversity and linkage disequilibrium according to geographic location and local epidemiological factors. We further discovered that nonsynonymous and silent (synonymous or noncoding) SNPs differ with respect to within-population diversity, inter-population differentiation, and the degree to which allele frequencies are correlated between populations.

Conclusions
The distinct population profile of nonsynonymous variants indicates that natural selection has a significant influence on genomic diversity in P. falciparum, and that many of these changes may reflect functional variants deserving of follow-up study. Our analysis demonstrates the potential for new high-throughput genotyping technologies to enhance studies of population structure, natural selection, and ultimately enable genome-wide association studies in P. falciparum to find genes underlying key phenotypic traits.
Analysis of mammalian gene batteries reveals both stable ancestral cores and highly dynamic regulatory sequences
Authors: Ettwiller Laurence , Budd Aidan , Spitz François , Wittbrodt Joachim 
Published: December 2008

Abstract
Background
Changes in gene regulation are suspected to comprise one of the driving forces for evolution. To address the extent of cis-regulatory changes and how they impact on gene regulatory networks across eukaryotes, we systematically analyzed the evolutionary dynamics of target gene batteries controlled by 16 different transcription factors.

Results
We found that gene batteries show variable conservation within vertebrates, with slow and fast evolving modules. Hence, while a key gene battery associated with the cell cycle is conserved throughout metazoans, the POU5F1 (Oct4) and SOX2 batteries in embryonic stem cells show strong conservation within mammals, with the striking exception of rodents. Within the genes composing a given gene battery, we could identify a conserved core that likely reflects the ancestral function of the corresponding transcription factor. Interestingly, we show that the association between a transcription factor and its target genes is conserved even when we exclude conserved sequence similarities of their promoter regions from our analysis. This supports the idea that turnover, either of the transcription factor binding site or its direct neighboring sequence, is a pervasive feature of proximal regulatory sequences.

Conclusions
Our study reveals the dynamics of evolutionary changes within metazoan gene networks, including both the composition of gene batteries and the architecture of target gene promoters. This variation provides the playground required for evolutionary innovation around conserved ancestral core functions.
Reproduction Rates After Cancer Treatment: Experience From the Norwegian Radium Hospital
Authors: Cvancarova Milada , Samuelsen Sven Ove , Magelssen Henriette , Fosså Sophie Dorothea 
Published: December 2008

Purpose Most studies on postcancer reproduction are limited in patient numbers and lack of control group. We have computed 10-year first postdiagnosis cumulative reproduction rates (10-PDRs) and hazard ratios (HRs) avoiding these limitations. Patients and Methods Six thousand seventy-one patients with cancer age 15 to 45 years at diagnosis, treated from 1971 to 1997, and 30,355 controls from the general population, all born after 1950, were observed from the true (patients) or assigned (controls) date of diagnosis for a median of 10 years (range, 0 to 35). The primary focus of the study was the 10-PDR before and after 1988+ based on data from the Medical Birth Registry of Norway. Cox proportional hazards regression models were adjusted for age and calendar year at diagnosis, stratified by sex and prediagnosis parenthood. Results Across all cancer types, HRs of females were approximately 50% lower than those of the controls, the comparable percentage for male patients being approximately 30%, with some improvement after 1988+ for selected diagnoses. The highest 10-PDRs were observed in childless patients, with more favorable HRs in male than in female patients. In survivors with at least one child at diagnosis, the post-1988+ HRs improved significantly in patients with testicular and localized cervical cancer compared to pre-1988+ reproduction, with borderline improvement in localized ovarian cancer. Conclusion Postcancer reproduction is lower than that of the general population and influenced by sex, age at diagnosis, prediagnosis parenthood, and diagnostic period with more favorable rates in males than in females. Post-1988+ fertility-saving strategies may have improved the reproduction rates for select genital cancers.
Improvement of Overall Survival in Advanced Stage Mantle Cell Lymphoma
Authors: Herrmann Annina , Hoster Eva , Zwingers Thomas , Brittinger Günter , Engelhard Marianne , Meusers Peter , Reiser Marcel , Forstpointner Roswitha , Metzner Bernd , Peter Norma , Wörmann Bernhard , Trümper Lorenz , Pfreundschuh Michael , Einsele Hermann , Hiddemann Wolfgang , Unterhalt Michael , Dreyling Martin 
Published: December 2008

Purpose Mantle cell lymphomas (MCLs) represent a clinically aggressive lymphoma subtype with a poor prognosis. To explore a potential progress in outcome a historical comparison was performed using data from the Kiel Lymphoma Study Group (KLSG; 1975 to 1986) and the German Low Grade Lymphoma Study Group (GLSG; 1996 to 2004). Patients and Methods All patients with the histologically confirmed diagnosis of advanced-stage nonblastoid MCL were eligible. To minimize the potential heterogeneity of different risk profiles frequency matching was pursued. In addition, we adjusted for potential confounding variables by multiple Cox regression. Results A total of 520 patients were assessable, 150 from KLSG and 370 from GLSG studies. The median overall survival was 2.7 years for KLSG patients as compared with 4.8 years for GLSG patients (P < .0001). The 5-year survival rates were 22% in the KLSG group (95% CI, 13% to 31%) as compared with 47% for GLSG treated patients (95% CI, 38% to 55%). The hazard ratio adjusted for performance status, lactate dehydrogenase, and age was 0.44 for GLSG patients (95% CI, 0.32 to 0.59). Conclusion Median overall survival of patients with advanced nonblastoid MCL almost doubled during the past 30 years. Potential reasons for this apparent improvement in overall survival include the application of anthracycline-containing regimens and new approaches, such as antilymphoma antibodies or stem cell transplantation. Advances in general supportive care, new diagnostic tools, and general improvement of life span might have also reinforced this effect. However, our results are questioning the validity of historical comparisons which had been frequently applied in previous trials.
Phase III Study of Immediate Compared With Delayed Docetaxel After Front-Line Therapy With Gemcitabine Plus Carboplatin in Advanced Non–Small-Cell Lung Cancer
Authors: Fidias Panos M. , Dakhil Shaker R. , Lyss Alan P. , Loesch David M. , Waterhouse David M. , Bromund Jane L. , Chen Ruqin , Hristova-Kazmierski Maria , Treat Joseph , Obasaju Coleman K. , Marciniak Martin , Gill John , Schiller Joan H. 
Published: December 2008

Purpose Gemcitabine plus carboplatin (GC) is active as front-line treatment for advanced non–small-cell lung cancer (NSCLC). For patients without progression, timing of second-line chemotherapy for optimum clinical benefit remains uncertain. This phase III, randomized trial assessed the efficacy and safety of docetaxel administered either immediately after GC or at disease progression. Patients and Methods The chemotherapy-naïve patients enrolled had either stage IIIB NSCLC with pleural effusion or stage IV NSCLC. Gemcitabine (1,000 mg/m2) was administered on days 1 and 8 followed by carboplatin (area under the curve = 5) on day 1. After four 21-day cycles, patients who did not have progression were randomly assigned either to an immediate docetaxel group (docetaxel 75 mg/m2 on day 1 every 21 days, with maximum of six cycles) or to a delayed docetaxel group. The primary end point was overall survival (OS) measured from random assignment. Additional analyses included tumor response, toxicity, progression-free survival (PFS), and quality of life (QOL). Results Enrollment totaled 566 patients; 398 patients completed GC; 309 patients were randomly assigned equally to the two docetaxel treatment groups. Toxicity profiles were generally comparable for the docetaxel groups. Median PFS for immediate docetaxel (5.7 months) was significantly greater (P = .0001) than for delayed docetaxel (2.7 months). Median OS for immediate docetaxel (12.3 months) was greater than for delayed docetaxel (9.7 months), but the difference was not statistically significant (P = .0853). QOL results were not statistically different (P = .76) between docetaxel groups. Conclusion We observed a statistically significant improvement in PFS and a nonstatistically significant increase in OS when docetaxel was administered immediately after front-line GC, without increasing toxicity or decreasing QOL.
Lymphovascular Invasion Predicts Clinical Outcomes in Patients With Node-Negative Upper Tract Urothelial Carcinoma
Authors: Kikuchi Eiji , Margulis Vitaly , Karakiewicz Pierre I. , Roscigno Marco , Mikami Shuji , Lotan Yair , Remzi Mesut , Bolenz Christian , Langner Cord , Weizer Alon , Montorsi Francesco , Bensalah Karim , Koppie Theresa M. , Fernández Mario I. , Raman Jay D. , Kassouf Wassim , Wood Christopher G. , Suardi Nazareno , Oya Mototsugu , Shariat Shahrokh F. 
Published: December 2008

Purpose To assess the association of lymphovascular invasion (LVI) with cancer recurrence and survival in a large international series of patients treated with radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC). Patients and Methods Data were collected on 1,453 patients treated with RNU at 13 academic centers and combined into a relational database. Pathologic slides were rereviewed by genitourinary pathologists according to strict criteria. LVI was defined as presence of tumor cells within an endothelium-lined space. Results LVI was observed in 349 patients (24%). Proportion of LVI increased with advancing tumor stage, high tumor grade, presence of tumor necrosis, sessile tumor architecture, and presence of lymph node metastasis (all P < .001). LVI was an independent predictor of disease recurrence and survival (P < .001 for both). Addition of LVI to the base model (comprising pathologic stage, grade, and lymph node status) marginally improved its predictive accuracy for both disease recurrence and survival (1.1%, P = .03; and 1.7%, P < .001, respectively). In patients with negative lymph nodes and those in whom a lymphadenectomy was not performed (n = 1,313), addition of LVI to the base model improved the predictive accuracy of the base model for both disease recurrence and survival by 3% (P < .001 for both). In contrast, LVI was not associated with disease recurrence or survival in node-positive patients (n = 140). Conclusion LVI was an independent predictor of clinical outcomes in nonmetastatic patients who underwent RNU for UTUC. Assessment of LVI may help identify patients who could benefit from multimodal therapy after RNU. After confirmation, LVI should be included in staging of UTUC.