bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rotavirus NSP4 is secreted from infected cells as an oligomeric lipoprotein and binds to glycosaminoglycans on the surface of non-infected cells
Authors: Didsbury Alicia , Wang Carol , Verdon Daniel , Sewell Mary A , McIntosh Julie D , Taylor John A 
Published: December 2011

Abstract

Background
Nonstructural glycoprotein 4 (NSP4) encoded by rotavirus is the only viral protein currently believed to function as an enterotoxin. NSP4 is synthesized as an intracellular transmembrane glycoprotein and as such is essential for virus assembly. Infection of polarized Caco-2 cells with rotavirus also results in the secretion of glycosylated NSP4 apparently in a soluble form despite retention of its transmembrane domain. We have examined the structure, solubility and cell-binding properties of this secreted form of NSP4 to further understand the biochemical basis for its enterotoxic function. We show here that NSP4 is secreted as discrete detergent-sensitive oligomers in a complex with phospholipids and demonstrate that this secreted form of NSP4 can bind to glycosaminoglycans present on the surface of a range of different cell types.

Methods
NSP4 was purified from the medium of infected cells after ultracentrifugation and ultrafiltration by successive lectin-affinity and ion exchange chromatography. Oligomerisation of NSP4 was examined by density gradient centrifugation and chemical crosslinking and the lipid content was assessed by analytical thin layer chromatography and flame ionization detection. Binding of NSP4 to various cell lines was measured using a flow cytometric-based assay.

Results
Secreted NSP4 formed oligomers that contained phospholipid but dissociated to a dimeric species in the presence of non-ionic detergent. The purified glycoprotein binds to the surface of various non-infected cells of distinct lineage. Binding of NSP4 to HT-29, a cell line of intestinal origin, is saturable and independent of divalent cations. Complementary biochemical approaches reveal that NSP4 binds to sulfated glycosaminoglycans on the plasma membrane.

Conclusion
Our study is the first to analyze an authentic (i.e. non-recombinant) form of NSP4 that is secreted from virus-infected cells. Despite retention of the transmembrane domain, secreted NSP4 remains soluble in an aqueous environment as an oligomeric lipoprotein that can bind to various cell types via an interaction with glycosaminoglycans. This broad cellular tropism exhibited by NSP4 may have implications for the pathophysiology of rotavirus disease.
Radiotherapy and "new" drugs-new side effects?
Authors: Niyazi Maximilian , Maihoefer Cornelius , Krause Mechthild , Rödel Claus , Budach Wilfried , Belka Claus 
Published: December 2011

AbstractBackground and purposeTargeted drugs have augmented the cancer treatment armamentarium. Based on the molecular specificity, it was initially believed that these drugs had significantly less side effects. However, currently it is accepted that all of these agents have their specific side effects. Based on the given multimodal approach, special emphasis has to be placed on putative interactions of conventional cytostatic drugs, targeted agents and other modalities. The interaction of targeted drugs with radiation harbours special risks, since the awareness for interactions and even synergistic toxicities is lacking. At present, only limited is data available regarding combinations of targeted drugs and radiotherapy. This review gives an overview on the current knowledge on such combined treatments.Materials and methodsUsing the following MESH headings and combinations of these terms pubmed database was searched: Radiotherapy AND cetuximab/trastuzumab/panitumumab/nimotuzumab, bevacizumab, sunitinib/sorafenib/lapatinib/gefitinib/erlotinib/sirolimus, thalidomide/lenalidomide as well as erythropoietin. For citation crosscheck the ISI web of science database was used employing the same search terms.ResultsSeveral classes of targeted substances may be distinguished: Small molecules including kinase inhibitors and specific inhibitors, antibodies, and anti-angiogenic agents. Combination of these agents with radiotherapy may lead to specific toxicities or negatively influence the efficacy of RT. Though there is only little information on the interaction of molecular targeted radiation and radiotherapy in clinical settings, several critical incidents are reported.ConclusionsThe addition of molecular targeted drugs to conventional radiotherapy outside of approved regimens or clinical trials warrants a careful consideration especially when used in conjunction in hypo-fractionated regimens. Clinical trials are urgently needed in order to address the open question in regard to efficacy, early and late toxicity.
Treatment with gefitinib after erlotinib-induced liver injury: a case report
Authors: Nakatomi Katsumi , Nakamura Yoichi , Tetsuya Iida , Kohno Shigeru 
Published: December 2011

Abstract

Introduction
Gefitinib and erlotinib have minor differences in their chemical structures, and thus it remains unclear whether the hepatotoxicity induced by one compound is affected by the other. The case of a patient who developed erlotinib-induced liver injury and was then treated with gefitinib without hepatic toxicity or disease progression is presented.

Case presentation
A 31-year-old Japanese woman, who never smoked and who was diagnosed as having lung adenocarcinoma with carcinomatous meningitis, was treated with erlotinib. She developed erlotinib-induced liver injury after four weeks of treatment. The treatment was stopped right away, but the symptoms of meningitis re-appeared immediately. Gefitinib treatment was started and continued without recurrence of drug-induced liver injury.

Conclusion
Gefitinib appears to be a potential treatment option after erlotinib-induced liver injury.
Professional liability insurance in Obstetrics and Gynaecology: estimate of the level of knowledge about malpractice insurance policies and definition of an informative tool for the management of the professional activity
Authors: Scurria Serena , Asmundo Alessio , Crinò Claudio , Gualniera Patrizia 
Published: December 2011

Abstract

Background
In recent years, due to the increasingly hostile environment in the medical malpractice field and related lawsuits in Italy, physicians began informing themselves regarding their comprehensive medical malpractice coverage.

Methods
In order to estimate the level of knowledge of medical professionals on liability insurance coverage for healthcare malpractice, a sample of 60 hospital health professionals of the obstetrics and gynaecology area of Messina (Sicily, Italy) were recluted. A survey was administered to evaluate their knowledge as to the meaning of professional liability insurance coverage but above all on the most frequent policy forms ("loss occurrence", "claims made" and "I-II risk"). Professionals were classified according to age and professional title and descriptive statistics were calculated for all the professional groups and answers.

Results
Most of the surveyed professionals were unaware or had very bad knowledge of the professional liability insurance coverage negotiated by the general manager, so most of the personnel believed it useful to subscribe individual "private" policies. Several subjects declared they were aware of the possibility of obtaining an extended coverage for gross negligence and substantially all the surveyed had never seen the loss occurrence and claims made form of the policy. Moreover, the sample was practically unaware of the related issues about insurance coverage for damages related to breaches on informed consent. The results revealed the relative lack of knowledge--among the operators in the field of obstetrics and gynaecology--of the effective coverage provided by the policies signed by the hospital managers for damages in medical malpractice. The authors thus proposed a useful information tool to help professionals working in obstetrics and gynaecology regarding aspects of insurance coverage provided on the basis of Italian civil law.

Conclusion
Italy must introduce a compulsory insurance system which could absorb, through a mechanism of "distribution of risk", the malpractice litigation and its costs. This will provide compensation in accidental cases where it wouldn't be possible to demonstrate carelessness, imprudence and/or lack of skill.
Dependence of NMDA/GSK-3β Mediated Metaplasticity on TRPM2 Channels at Hippocampal CA3-CA1 Synapses
Authors: Xie Yu-Feng , Belrose Jillian C , Lei Gang , Tymianski Michael , Mori Yasuo , MacDonald John F , Jackson Michael F 
Published: December 2011

Abstract

Transient receptor potential melastatin 2 (TRPM2) is a calcium permeable non-selective cation channel that functions as a sensor of cellular redox status. Highly expressed within the CNS, we have previously demonstrated the functional expression of these channels in CA1 pyramidal neurons of the hippocampus. Although implicated in oxidative stress-induced neuronal cell death, and potentially in neurodegenerative disease, the physiological role of TRPM2 in the central nervous system is unknown. Interestingly, we have shown that the activation of these channels may be sensitized by co-incident NMDA receptor activation, suggesting a potential contribution of TRPM2 to synaptic transmission. Using hippocampal cultures and slices from TRPM2 null mice we demonstrate that the loss of these channels selectively impairs NMDAR-dependent long-term depression (LTD) while sparing long-term
potentiation. Impaired LTD resulted from an inhibition of GSK-3β, through increased phosphorylation, and a reduction in the expression of PSD95 and AMPARs. Notably, LTD could
be rescued in TRPM2 null mice by recruitment of GSK-3β signaling following dopamine D2 receptor stimulation. We propose that TRPM2 channels play a key role in hippocampal synaptic plasticity.
A genome-wide linkage study of mammographic density, a risk factor for breast cancer
Authors: Greenwood Celia MT , Paterson Andrew D , Linton Linda , Andrulis Irene L , Apicella Carmel , Dimitromanolakis Apostolos , Kriukov Valentina , Martin Lisa J , Salleh Ayesha , Samiltchuk Elena , Parekh Rashmi V , Southey Melissa C , John Esther M , Hopper John L , Boyd Norman F , Rommens Johanna M 
Published: December 2011

Abstract
Introduction
Mammographic breast density is a highly heritable (h2 > 0.6) and strong risk factor for breast cancer. We conducted a genome-wide linkage study to identify loci influencing mammographic breast density (MD).

Methods
Epidemiological data were assembled on 1,415 families from the Australia, Northern California and Ontario sites of the Breast Cancer Family Registry, and additional families recruited in Australia and Ontario. Families consisted of sister pairs with age-matched mammograms and data on factors known to influence MD. Single nucleotide polymorphism (SNP) genotyping was performed on 3,952 individuals using the Illumina Infinium 6K linkage panel.

Results
Using a variance components method, genome-wide linkage analysis was performed using quantitative traits obtained by adjusting MD measurements for known covariates. Our primary trait was formed by fitting a linear model to the square root of the percentage of the breast area that was dense (PMD), adjusting for age at mammogram, number of live births, menopausal status, weight, height, weight squared, and menopausal hormone therapy. The maximum logarithm of odds (LOD) score from the genome-wide scan was on chromosome 7p14.1-p13 (LOD = 2.69; 63.5 cM) for covariate-adjusted PMD, with a 1-LOD interval spanning 8.6 cM. A similar signal was seen for the covariate adjusted area of the breast that was dense (DA) phenotype. Simulations showed that the complete sample had adequate power to detect LOD scores of 3 or 3.5 for a locus accounting for 20% of phenotypic variance. A modest peak initially seen on chromosome 7q32.3-q34 increased in strength when only the 513 families with at least two sisters below 50 years of age were included in the analysis (LOD 3.2; 140.7 cM, 1-LOD interval spanning 9.6 cM). In a subgroup analysis, we also found a LOD score of 3.3 for DA phenotype on chromosome 12.11.22-q13.11 (60.8 cM, 1-LOD interval spanning 9.3 cM), overlapping a region identified in a previous study.

Conclusions
The suggestive peaks and the larger linkage signal seen in the subset of pedigrees with younger participants highlight regions of interest for further study to identify genes that determine MD, with the goal of understanding mammographic density and its involvement in susceptibility to breast cancer.
Role of IFN-γ in the establishment of anterior chamber-associated immune deviation (ACAID)-induced CD8+ T regulatory cells
Authors: Paunicka Kathryn , Chen Peter W , Niederkorn Jerry Y 
Published: December 2011

ABSTRACT
Introduction of alloantigens into the AC induces a form of immune tolerance known as ACAID, which induces antigen-specific CD8+ Tregs, contributing to ocular immune privilege by down-regulating immune responses. Recent evidence suggests IFN-γ is needed for the suppressive function of CD8+ ACAID Tregs. This study tested the hypothesis that IFN-γ is needed for alloantigen-specific ACAID CD8+ Tregs to execute their suppressive function but is not required for the establishment of ACAID CD8+ Tregs. To address this hypothesis, ACAID was induced by injecting BALB/c spleen cells into the AC of WT C57BL/6 mice, IFN-γ−/− C57BL/6 mice, or anti-IFN-γ-treated WT C57BL/6 mice. LAT assays using C57BL/6 APCs as stimulators, CD4+ T cells from C57BL/6 mice previously immunized toward BALB/c alloantigens as effector cells, and IFN-γ-competent, IFN-γ−/−, or IFN-γR−/− CD8+ Tregs were used to evaluate the suppressive function of CD8+ ACAID Tregs in response to IFN-γ. IFN-γ−/− mice or mice treated with anti-IFN-γ antibody prior to AC injection of alloantigen failed to develop ACAID. The suppressive function of IFN-γ−/− ACAID CD8+ Tregs was restored through the administration of exogenous IFN-γ. This suppressive responsiveness toward IFN-γ was CD8+ Treg-intrinsic, as CD8+ Tregs from IFN-γR−/− mice, which were primed in the AC with alloantigens, were not able to suppress alloantigen-specific DTH responses. These results indicate that IFN-γ is not needed for the induction of CD8+ ACAID Tregs but is required for ACAID Tregs to exert the suppression of allospecific DTH responses.
Hearing with an atympanic ear: good vibration and poor sound-pressure detection in the royal python,Python regius
Authors: Christensen Christian Bech , Christensen-Dalsgaard Jakob , Brandt Christian , Madsen Peter Teglberg 
Published: December 2011

SUMMARYSnakes lack both an outer ear and a tympanic middle ear, which in most tetrapods provide impedance matching between the air and inner ear fluids and hence improve pressure hearing in air. Snakes would therefore be expected to have very poor pressure hearing and generally be insensitive to airborne sound, whereas the connection of the middle ear bone to the jaw bones in snakes should confer acute sensitivity to substrate vibrations. Some studies have nevertheless claimed that snakes are quite sensitive to both vibration and sound pressure. Here we test the two hypotheses that: (1) snakes are sensitive to sound pressure and (2) snakes are sensitive to vibrations, but cannot hear the sound pressure per se. Vibration and sound-pressure sensitivities were quantified by measuring brainstem evoked potentials in 11 royal pythons, Python regius. Vibrograms and audiograms showed greatest sensitivity at low frequencies of 80–160 Hz, with sensitivities of –54 dB re. 1 m s–2 and 78 dB re. 20 μPa, respectively. To investigate whether pythons detect sound pressure or sound-induced head vibrations, we measured the sound-induced head vibrations in three dimensions when snakes were exposed to sound pressure at threshold levels. In general, head vibrations induced by threshold-level sound pressure were equal to or greater than those induced by threshold-level vibrations, and therefore sound-pressure sensitivity can be explained by sound-induced head vibration. From this we conclude that pythons, and possibly all snakes, lost effective pressure hearing with the complete reduction of a functional outer and middle ear, but have an acute vibration sensitivity that may be used for communication and detection of predators and prey.
Localization of the bioadhesive precursors of the sandcastle worm, Phragmatopoma californica (Fewkes)
Authors: Wang Ching Shuen , Stewart Russell J. 
Published: December 2011

SUMMARY
The marine sandcastle worm bonds mineral particles together into underwater composite dwellings with a proteinaceous glue. The products of at least four distinct secretory cell types are co-secreted from the building organ to form the glue. Prominent hetereogeneous granules contain dense sub-granules of Mg and the (polyphospho)proteins Pc3A and B, as well as at least two polybasic proteins, Pc1 and Pc4, as revealed by immunolabeling with specific antibodies against synthetic peptides. Equally prominent homogeneous granules comprise at least two polybasic proteins, Pc2 and Pc5, localized by immunolabeling with anti-synthetic peptide antibodies. The components of the sub-micrometer granule types are unknown, though positive staining with a redox-sensitive dye suggests the contents include o-dihydroxy-phenylalanine (dopa). Quantitative PCR and in situ hybridization demonstrated that a tyrosinase-like enzyme with a signal peptide was highly expressed in both the heterogeneous and homogeneous granules. The contents of the granules are poorly mixed in the secreted mixture that forms the glue. Subsequent covalent cross-linking of the glue may be catalyzed by the co-secreted tyrosinase. The first three parapodia of the sandcastle worm also contain at least two distinct secretory tissues. The Pc4 protein was immunolocalized to the anterior secretory cells and the tryosinase-like gene was expressed in the posterior secretory cells, which suggests these proteins may have multiple roles.
Dosing of 3-Factor Prothrombin Complex Concentrate for International Normalized Ratio Reversal
Authors: Baggs Jennifer H , Patanwala Asad E , Williams Evan M , Erstad Brian L 
Published: December 2011

BACKGROUND: Three-factor prothrombin complex concentrate (PCC) is commonly used for reversal of international normalized ratio (INR) in patients who are bleeding or require emergency surgery. However, there is little information regarding the optimal dosing strategy for achieving adequate INR reversal. OBJECTIVE: To determine whether patients with higher initial INR levels are less likely to achieve adequate INR reversal after receiving 3-factor PCC. METHODS: A retrospective cohort study was conducted in a tertiary care medical center in the US. Patients who received 3-factor PCC were grouped into 2 categories based on degree of INR reversal after PCC infusion: (1) adequate reversal (final INR ≤1.5) or (2) inadequate reversal (final INR >1.5). Initial INR was compared between the 2 groups using the Wilcoxon rank-sum test. A multivariate logistic regression analysis was used to adjust for confounders and determine predictors of adequate INR reversal. RESULTS: Fifty patients met criteria for inclusion in the final analyses. Of these, 58% achieved adequate reversal after PCC. There were no significant differences in patient demographics or in vitamin K or fresh frozen plasma (FFP) use between the 2 groups. Median PCC dose was also similar between the adequate and inadequate reversal groups (25.2 vs 24.5 units/kg, respectively; p = 0.2). The group that did not achieve adequate reversal had a significantly higher initial INR (3.5 vs 2.5, p = 0.012) prior to PCC administration. In the multivariate logistic regression analysis, initial INR was a significant predictor of adequate INR reversal (ie, reversal less likely as INR increases) after adjusting for PCC dose and concurrent use of vitamin K or FFP (OR = 0.38; 95% CI 0.17 to 0.87; p = 0.02). CONCLUSIONS: Patients with a higher initial INR are less likely to achieve adequate INR reversal after receiving 3-factor PCC and may require higher doses than were used in the study.
Maine Nursery and Landscape Industry Perspectives on Invasive Plant Issues
Authors: Coats Vanessa C. , Stack Lois Berg , Rumpho Mary E. 
Published: December 2011

AbstractA survey of the Maine landscape and nursery industry was conducted to identify industry views on invasive plant issues, attitudes towards potential regulation, and to estimate the potential economic costs of banning the sale of specific invasive plant species in Maine. Analysis of the 190 surveys returned (19% of 980 mailed) revealed that 76% of industry member respondents were genuinely concerned about invasive plant issues, and the same percentage felt the horticulture industry is responsible for educating customers about invasive plants. Industry members (68%) did not feel compelled to sell invasive plants merely on the basis of customer attraction to the plant, or due to competition with a neighboring business that sells the invasive plant. Self-reporting of sales indicated that Norway maple ($96K), burningbush ($68K), and Japanese barberry ($44K) constituted the largest portion of annual industry revenue (maximum values reported for 2006 to 2008) derived from the sale of seven identified invasive plants. Industry self-regulation was the most favored form of regulation, although the industry likely would not be significantly affected by legislated state-wide bans of at least purple loosestrife and oriental bittersweet. Bans on other popular invasive plants, including burningbush, Japanese barberry, and Norway maple likely would have a relatively small, short-term impact on the horticulture industry until alternative plants with similar properties were identified. The results of this survey demonstrated a need for identifying which plants are truly invasive or potentially invasive in Maine, as well as a need for open discussion of invasive plant issues among all interested parties in Maine.
Intergenerational Transmission, Attitudes, and Post-Traumatic Stress Disorder in Times of War: A Comparison between Elderly People and Their Adult Offspring after the Second Lebanon War (2006) and Casting Lead Operation (2008)
Authors: Ron Pnina 
Published: December 2011

Background: While the effects of war on individuals, age groups, and communities have been thoroughly studied, there has been relatively little mention in the literature regarding its differential effects on adult children and their elderly parents and grandparents. Methods: Three hundred thirty-eight participants (167 elderly parents and 171 adult offspring) living in the northern and southern regions of Israel, were interviewed after the Second Lebanon War (2006) and the Casting Lead Operation (2008). (A military operation took place at the Israeli southern border as a reaction to the 7 years of missiles bombing from the Gaza strip to the Israeli civilians.) The participants were sampled by a cluster sampling. Findings: Elderly population experiences higher levels of PTSD symptoms than their adult children do. Women experience higher levels of PTSD symptoms than men and Israeli Arabs and Druze more than Israeli Jews. Conclusions: A policy should be enacted among the local authorities and the governmental offices that would ensure accessibility to and the ability to provide proper care for the elderly population during times of war or terror events. In addition, it is important to setup local teams in every local community to deal with the level of mental and emotional preparedness of the home front and its inhabitants, in case the latter should again become part of the human casualties of the wars and terrorist events that occur in Israel.