Striving to establish a care relationship-Mission possible or impossible?-Triad encounters between patients, relatives and nurses.
When patients, relatives and nurses meet, they form a triad that can ensure a good care relationship. However, hospital environments are often stressful and limited time can negatively affect the care relationship, thus decreasing patient satisfaction. To explain the care relationship in triad encounters between patients, relatives and nurses at a department of medicine for older people. A qualitative explorative study with an ethnographic approach guided by a sociocultural perspective. Participatory observations and informal field conversations with patients, relatives and nurses were carried out from October 2015-September 2016 and analysed together with field notes using ethnographic analysis. The result identifies a process where patients, relatives and nurses use different strategies for navigating before, during and after a triad encounter. The process is based on the following categories: orienting in time and space, contributing to a care relationship and forming a new point of view. The result indicates that nurses, who are aware of the process and understand how to navigate between the different perspectives in triad encounters, can acknowledge both the patient's and relatives' stories, thus facilitating their ability to understand the information provided, ensure a quality care relationship and strengthen the patient's position in the health-care setting, therefore making the mission to establish a care relationship possible.


Chlorella-gold nanorods hydrogels generating photosynthesis-derived oxygen and mild heat for the treatment of hypoxic breast cancer.
Hypoxic tumors are rarely cured because their low oxygen environment restricts the cytotoxicity of many chemotherapeutics by blocking the production of intracellular reactive oxygen species. Inspired by the highly efficient production of oxygen as a waste product of chlorella photosynthesis, we developed an in situ rapidly gelling BSA-PEG-based hydrogel depot system that contains chlorella and gold nanorods, namely Chlorella AuNRs BSA-Gel. The entrapped chlorella in our gel efficiently generated a high level of oxygen and oxygenated hemoglobin via photosynthesis in response to 660-nm light in vitro and in vivo, respectively. The incorporated gold nanorods showed excellent performance in precisely increasing the surrounding temperature to 41-42 °C responding to 808-nm near-infrared laser, which presumably played a supporting role in expanding the tumor vasculature and thereby facilitating the delivery of doxorubicin and oxygen to hypoxic tumors of mice. Our results showed that a combined therapy of Chlorella AuNRs BSA-Gel plus Dox followed by irradiation at 660 nm and 808 nm significantly abolished 4 T1 breast cancer cell-xenografted tumors of BALB/C mice. We believe that our oxygen-generating and mild heat-emitting hydrogel should be considered to be a valid prototype of a local depot system for treatment of hypoxic tumors.


Molecular Characterization of a Novel Putative Partitivirus Infecting Cytospora sacchari, a Plant Pathogenic Fungus.
Three double-stranded RNAs (dsRNAs), approximately 1.85, 1.65 and 1.27 kb in size, were detected in an isolate of Cytospora sacchari from Iran. Partial nucleotide sequence revealed a 1,284 bp segment containing one ORF that potentially encodes a 405 aa protein. This protein contains conserved motifs related to RNA dependent RNA polymerases (RdRp) that showed similarity to RdRps of partitiviruses. The results indicate that these dsRNAs represent a novel Partitivirus that we tentatively designate Cytospora sacchari partitivirus (CsPV). Treatment of the fungal strain by cyclohexamide and also hyphal tip culture had no effect on removing the putative virus. Phylogenetic analysis of putative RdRp of CsPV and other partitiviruses places CsPV as a member of the genus Partitivirus in the family Partitiviridae, and clustering with Aspergillus ochraceous virus 1.


Clickable Photoaffinity Ligands for Metabotropic Glutamate Receptor 5 Based on Select Acetylenic Negative Allosteric Modulators.
G protein-coupled receptors (GPCRs) represent the largest class of current drug targets. In particular, small-molecule allosteric modulators offer substantial potential for selectively "tuning" GPCR activity. However, there remains a critical need for experimental strategies that unambiguously determine direct allosteric ligand-GPCR interactions, to facilitate both chemical biology studies and rational structure-based drug design. We now report the development and use of first-in-class clickable allosteric photoprobes for a GPCR based on metabotropic glutamate receptor 5 (mGlu5) negative allosteric modulator (NAM) chemotypes. Select acetylenic mGlu5 NAM lead compounds were rationally modified to contain either a benzophenone or an aryl azide as a photoreactive functional group, enabling irreversible covalent attachment to mGlu5 via photoactivation. Additionally, a terminal alkyne or an aliphatic azide was incorporated as a click chemistry handle, allowing chemoselective attachment of fluorescent moieties to the irreversibly mGlu5-bound probe via tandem photoaffinity labeling-bioorthogonal conjugation. These clickable photoprobes retained submicromolar affinity for mGlu5 and negative cooperativity with glutamate, interacted with the "common allosteric-binding site," displayed slow binding kinetics, and could irreversibly label mGlu5 following UV exposure. We depleted the number of functional mGlu5 receptors using an irreversibly bound NAM to elucidate and delineate orthosteric agonist affinity and efficacy. Finally, successful conjugation of fluorescent dyes via click chemistry was demonstrated for each photoprobe. In the future, these clickable photoprobes are expected to aid our understanding of the structural basis of mGlu5 allosteric modulation. Furthermore, tandem photoaffinity labeling-bioorthogonal conjugation is expected to be a broadly applicable experimental strategy across the entire GPCR superfamily.


A brief assessment of learning for orphaned and abandoned children in low and middle income countries.
Assessment of children's learning and performance in low and middle income countries has been critiqued as lacking a gold standard, an appropriate norm reference group, and demonstrated applicability of assessment tasks to the context. This study was designed to examine the performance of three nonverbal and one adapted verbal measure of children's problem solving, memory, motivation, and attention across five culturally diverse sites. The goal was to evaluate the tests as indicators of individual differences affected by life events and care circumstances for vulnerable children. We conclude that the measures can be successfully employed with fidelity in non-standard settings in LMICs, and are associated with child age and educational experience across the settings. The tests can be useful in evaluating variability in vulnerable child outcomes.


Haplotype analysis discriminates genetic risk for DR3-associated endocrine autoimmunity and helps define extreme risk for Addison's disease.
Multiple autoimmune disorders (e.g. Addison's disease, type 1 diabetes, celiac disease) are associated with HLA-DR3, but it is likely that alleles of additional genes in linkage disequilibrium with HLA-DRB1 contribute to disease. The objective of the study was to characterize major histocompatability complex (MHC) haplotypes conferring extreme risk for autoimmune Addison's disease (AD). Eighty-six 21-hydroxylase autoantibody-positive, nonautoimmune polyendocrine syndrome type 1, Caucasian individuals collected from 1992 to 2009 with clinical AD from 68 families (12 multiplex and 56 simplex) were genotyped for HLA-DRB1, HLA-DQB1, MICA, HLA-B, and HLA-A as well as high density MHC single-nucleotide polymorphism (SNP) analysis for 34. AD and genotype were measured. Ninety-seven percent of the multiplex individuals had both HLA-DR3 and HLA-B8 vs. 60% of simplex AD patients (P = 9.72 × 10(-4)) and 13% of general population controls (P = 3.00 × 10(-19)). The genotype DR3/DR4 with B8 was present in 85% of AD multiplex patients, 24% of simplex patients, and 1.5% of control individuals (P = 4.92 × 10(-191)). The DR3-B8 haplotype of AD patients had HLA-A1 less often (47%) than controls (81%, P = 7.00 × 10(-5)) and type 1 diabetes patients (73%, P = 1.93 × 10(-3)). Analysis of 1228 SNPs across the MHC for individuals with AD revealed a shorter conserved haplotype (3.8) with the loss of the extended conserved 3.8.1 haplotype approximately halfway between HLA-B and HLA-A. Extreme risk for AD, especially in multiplex families, is associated with haplotypic DR3 variants, in particular a portion (3.8) but not all of the conserved 3.8.1 haplotype.


Prenatal exposure to cigarette smoke and benign breast disease.
Experimental studies have indicated that cigarette smoke contains potential human breast toxins and that the toxic influence during the prenatal period is greater than that of later life. The study sample includes 810 women whose mothers enrolled in the Collaborative Perinatal Project between 1959 and 1966 in Boston and Providence. These women have been followed from gestation until middle-age. Information on maternal smoking during pregnancy was prospectively collected during prenatal visits. We identified 146 women who had been told by a health professional that they had benign breast disease. Log-binomial regression models with Generalized Estimating Equation methods were employed to quantify the association between maternal smoking and benign breast disease among offspring. There was a positive association between maternal smoking during pregnancy and the risk of benign breast disease among offspring. In particular, women whose mother smoked 1 pack or more per day were 1.7 times more likely to develop benign breast disease (relative risk = 1.7 [95% confidence interval = 1.2-2.5]) in comparison with women whose mother never smoked during pregnancy. The association was independent of women's age, race, education, age at menarche, parity, obesity, birth weight, and maternal age at pregnancy. Exposure to heavy cigarette smoking during the prenatal period was associated with an increased risk of benign breast disease in adulthood.


A network analysis of food flows within the United States of America.
The world food system is globalized and interconnected, in which trade plays an increasingly important role in facilitating food availability. We present a novel application of network analysis to domestic food flows within the USA, a country with global importance as a major agricultural producer and trade power. We find normal node degree distributions and Weibull node strength and betweenness centrality distributions. An unassortative network structure with high clustering coefficients exists. These network properties indicate that the USA food flow network is highly social and well-mixed. However, a power law relationship between node betweenness centrality and node degree indicates potential network vulnerability to the disturbance of key nodes. We perform an equality analysis which serves as a benchmark for global food trade, where the Gini coefficient = 0.579, Lorenz asymmetry coefficient = 0.966, and Hoover index = 0.442. These findings shed insight into trade network scaling and proxy free trade and equitable network architectures.


Driving through dense fog: a study of the effects and control of sustainable public procurement of electric cars.
Governments are large buyers of vehicles, thus contributing to pollution. To promote sustainability, policies have been shaped to replace government-owned fossil fuel cars with electric cars. Public procurement is seen as a strategic tool for the government to transition. This study identifies a research gap due to a lack of studies on how stakeholders at different levels identify and calculate the sustainability effects of public procurement of cars. Our approach uses a multilevel perspective to explore how various stakeholders perceive and assess the effects of sustainable public procurement. The data were obtained through a qualitative research design with documents and semi-structured interviews with stakeholders in Norway ranging from government agencies, public procurement officers, car suppliers, and end-users. (End-users in this setting are the ones who ultimately use the vehicles). The study's findings are two-fold. First, it contributes to understanding that perceived effects of sustainable public procurement vary from the stakeholders' perspectives and that public procurement initiatives perceive to have cultural effects in addition to innovation, environmental, economic, and social impacts. Second, it contributes to understanding the importance of feedback mechanisms in public procurement to align the assessment of the effects. A better understanding of how effects are identified, and improved feedback mechanisms could help government representatives control the procurement system and accomplish the intended effects.


Progesterone and adipoQ receptor 11 links ras signaling to cardiac development in zebrafish.
Progesterone and adipoQ receptor (PAQR) 10 and PAQR11 are 2 highly homologous genes involved in compartmentalized Ras signaling in the Golgi apparatus. The aim of this study was to investigate the physiological functions of PAQR10 and PAQR11. We used zebrafish as a model system to analyze the potential function of PAQR10/PAQR11. The expression profiles of PAQR10 and PAQR11 in zebrafish embryos are overlapping in many areas, but only PAQR11 is expressed in the developing heart. Knockdown of PAQR11 but not PAQR10 in zebrafish embryos causes cardiac developmental defects, including dilation of cardiac chambers, abnormal heart looping, disruption of atrioventricular cushion formation, heart edema, and blood regurgitation. PAQR11 knockdown markedly reduces the number and proliferation rate of cardiomyocytes and alters the morphology of myocardial cells during early heart development. The cardiac defects caused by PAQR11 knockdown can be phenocopied by MEK inhibitors and a dominant negative Ras. Furthermore, constitutively active Ras and especially a Golgi-localized but not a plasma membrane-localized Ras are able to rescue the cardiac defects caused by PAQR11 knockdown. This study not only provides in vivo evidence that PAQR11 plays a critical role in heart morphogenesis but also pinpoints the importance of compartmentalized Ras signaling during development.


Exploring global retailers' corporate social responsibility performance.
Retailers serve as the main interface between business and society. This study explores the Corporate Social Responsibility priorities and performance of the largest 23 global retailers. This set of global retailers, who have a major impact on society, were studied in terms of social, environmental and sustainability practices and strategy, and there performance was analysed and evaluated. The study uses a four-dimensional Social, Economic, Environmental, Supply Chain model for sustainability performance evaluation. We rely on data collected from annual reports, and find that global retailers have addressed the business-society interface in relatively balanced ways for the different dimensions of CSR. Further, our findings indicate that global retailers in different regions have different CSR priorities. In particular, the data indicates that the US retailers place a lower priority on supply chain sustainability performance, followed by the Australians, while European retailers place a higher priority. The study concludes that while global retailers all pay attention to the same dimensions of CSR and do so differently in the different regions, the variation and lack of significant progress indicates that there is a role for stronger government regulation. This study contributes to the literature by shifting the analysis from country to a global level, is more objective in relying on reported data rather than interviews or surveys and provides a new analytical tool.


Flow cytometry crossmatch reactivity with pronase-treated T cells induced by non-HLA autoantibodies in human immunodeficiency virus-infected patients.
Pronase treatment is used in the flow cytometry crossmatch (FCXM) to prevent nonspecific antibody binding on B cells. However, we have observed unexpected positive results with pronase-treated T cells in human immunodeficiency virus (HIV)-infected patients. In this study, 25 HIV-infected patients without HLA antibodies were tested with pronase-treated and nontreated cells. HIV-positive sera were pretreated with reducing agents and preabsorbed with pronase-treated and nontreated T or B cells before crossmatching. All patients displayed FCXM reactivity with pronase-treated T cells but not with nontreated T cells. None of the patients exhibited FCXM reactivity with pronase-treated and nontreated B cells. These patients displayed FCXM reactivity with pronase-treated CD4+ and CD8+ T cells but not with their nontreated counterparts. Preabsorption with pronase-treated T cells reduced the T cell FCXM reactivity. Preabsorption with pronase-treated B cells or nontreated T and B cells did not have any effect on the T cell FCXM reactivity. Pretreatment with reducing agents did not affect the T cell FCXM reactivity. 15 of 21 HIV-infected kidney allograft recipients with pronase-treated T cell FCXM reactivity display long-term graft survival (1193±631days). These data indicate that HIV-infected patients have nondeleterious autoantibodies recognizing cryptic epitopes exposed by pronase on T cells.


Are We Overdoing Pediatric Lower Gastrointestinal Endoscopy?
Lower gastrointestinal endoscopy (LGIE)/colonoscopy is frequently performed for rectal bleeding, recurrent abdominal pain, and the diagnosis of inflammatory bowel disease (IBD). Although these are common indications, the causes of isolated rectal bleeding and recurrent abdominal pain in the otherwise well child have not been described. A retrospective analysis of patients who had had an LGIE/colonoscopy from January 2001 to December 2010 was performed. The following data were collected: demographic data, indication, distance reached, macroscopic findings, microscopic findings, diagnosis, additional procedures, and complications. There were a total of 999 colonoscopies. The colonoscopy was normal in 390 of 999 (39%). The commonest indication for colonoscopy was a diagnosis of suspected IBD, 449 of 999 (45%). IBD was confirmed in 282 of 449 (63%), but colonoscopy was normal in 143 of 449 (32%) of suspected IBD. Colonoscopy was performed for rectal bleeding in 197 of 999 (20%) of whom 141 of 197 (72%) were normal. There were 46 (5%) colonoscopies performed for recurrent abdominal pain, which were all normal. Our completion rate to the cecum and beyond was 521 of 999 (52%). Our perforation rate during the 10 years was 0.2%. Colonoscopy is a safe procedure in pediatrics; however, 39% of colonoscopies in this series were normal. Many of these could have been avoided by eliminating colonoscopy in patients with recurrent abdominal pain in the absence of other clinical features, conservative management with laxatives for those with fresh blood per rectum typical of anal fissures, and fecal calprotectin screening before endoscopy in patients with suspected IBD.


Effect of indoor nitrogen dioxide on lung function in urban environment.
High levels of indoor NO2 are associated with increased asthma symptoms and decreased expiratory peak flows in children. We investigated the association of exposure to domestic indoor NO2, objectively measured in winter and spring, with respiratory symptoms and lung function in a sample of adolescents from a southern Mediterranean area. From a large school population sample (n=2150) participating in an epidemiological survey in the urban area of the City of Palermo (southern Italy), a sub-sample of 303 adolescents was selected which furnished an enriched sample for cases of current asthma. All subjects were evaluated by a health questionnaire, skin prick tests and spirometry. One-week indoor NO2 monitoring of their homes was performed by diffusive sampling during spring and again during winter. We found that about 25% of subjects were exposed to indoor NO2 levels higher than the 40µg/m(3) World Health Organization limit, during both spring and winter. Moreover, subjects exposed to the highest indoor NO2 concentrations had increased frequency of current asthma (p=0.005), wheeze episodes in the last 12 months (p<0.001), chronic phlegm (p=0.013), and rhinoconjunctivitis (p=0.008). Finally, subjects with a personal history of wheeze ever had poorer respiratory function (FEF25-75%, p=0.01) when exposed to higher indoor NO2 concentrations. Home exposure to high indoor NO2 levels frequently occurs in adolescents living in a southern Mediterranean urban area and is significantly associated with the risks for increased frequency of both respiratory symptoms and reduced lung function.


An Updated Review of the Therapeutic Management of Keratoacanthomas.
Keratoacanthomas are fast-growing cutaneous neoplasms that can be difficult to distinguish from squamous cell carcinoma, both clinically and histologically. The uncertain behavior of these neoplasms creates a challenge in management, and treatment choice often varies significantly between cases. The objective of this review is to discuss the most common and up-to-date treatment modalities used in the management of keratoacanthomas. A literature search was performed using PubMed to access and review relevant keratoacanthoma treatment modalities published within the last 40 years. Keywords searched included "keratoacanthoma," "Grzybowski syndrome," "Ferguson-Smith syndrome," "Witten-Zac syndrome," and "Muir-Torre" syndrome. Our search resulted in 3,408 articles, of which 67 articles were ultimately included in this review. Although surgical removal with excision or Mohs micrographic surgery remains the standard of therapy, there are many alternative therapeutic modalities that can be utilized.


High-level carbapenem resistance in a Citrobacter freundii clinical isolate is due to a combination of KPC-2 production and decreased porin expression.
An imipenem-resistant isolate of Citrobacter freundii ZJ163 (MIC 256 microg ml(-1)) isolated from a Chinese hospital was investigated. The C. freundii ZJ163 isolate exhibited high-level resistance to carbapenems, penicillins, cephalosporins, cefoxitin, aztreonam, quinolones and aminoglycosides. Isoelectric focusing (IEF) demonstrated three beta-lactamases with pIs of 5.4 (TEM-1), 6.7 (KPC-2) and 7.9 (CTX-M-14). Two different transconjugants (types A and B) were obtained by conjugation studies. The type A transconjugant exhibited reduced susceptibility or resistance to penicillins, cephalosporins and aztreonam, but was susceptible to carbapenems, quinolones and aminoglycosides. The antimicrobial susceptibility patterns of the type B transconjugant were similar to that of type A, except for its significantly reduced carbapenem susceptibility (imipenem MIC 2 microg ml(-1)). IEF, specific PCRs and DNA sequence analysis indicated that the type A transconjugant produced CTX-M-14 beta-lactamase with a pI of 7.9, that the type B transconjugant produced KPC-2 beta-lactamase with a pI of 6.7 and that the beta-lactamase with a pI of 5.4 was TEM-1. PCR analysis and sequencing confirmed the presence of the ampC gene in the chromosomal DNA from C. freundii ZJ163, although no activity of AmpC beta-lactamase was detected by IEF. Urea/SDS-PAGE analysis of outer-membrane proteins revealed that the levels of the 41 and 38 kDa porins were decreased in C. freundii ZJ163. It was concluded that production of KPC-2 combined with decreased expression of porins contributes to high-level resistance to carbapenems in C. freundii ZJ163.


Visualizing myosin's power stroke in muscle contraction.
The long-standing swinging crossbridge or lever arm hypothesis for the motor action of myosin heads finds support in recent results from 3-D tomograms of insect flight muscle (IFM) fast frozen during active contraction and from both fluorescence polarization and X-ray diffraction during rapid stretches or releases of isometrically contracting fibers. The latter provide direct evidence for lever arm movements synchronous with force changes. Rebuilding the atomic model of nucleotide-free subfragment 1 (S1) to fit fast-frozen, active IFM crossbridges suggests a two-stage power stroke in which the catalytic domain rolls on actin from weak to strong binding; this is followed by a 5-nm lever arm swing of the light chain domain, which gives a total interaction distance of approx. 12 nm. Comparison of S1 crystal structures with in situ myosin heads suggests that actin binding may be necessary in order to view the full repertoire of myosin motor action. The differing positions of the catalytic domains of actin-attached myosin heads in contracting IFM suggest that both the actin-myosin binding energy and the hydrolysis of ATP may be used to cock the crossbridge and drive the power stroke.


Efficient generation of neural stem cell-like cells from rat adipose derived stem cells after lentiviral transduction with green fluorescent protein.
Neural stem cells (NSCs) can be isolated from nervous tissues or derived from embryonic stem cells. However, their procurement for clinical applications is limited, and there is a need for alternative types of cell that have NSCs properties. In the present study, the differentiation potential of rat adipose-derived stem cells (ADSCs) was evaluated by infecting these cells with a lentiviral vector-encoding green fluorescent protein (GFP). ADSCs transduced with lentivirus were able to generate NSC-like cells, without any effects on their growth, phenotype, and normal differentiation potential. NSC-like cells derived from ADSCs formed neurospheres and expressed high levels of the neural progenitor marker nestin. In the absence of selected growth factors, these neurospheres differentiated into neurons expressing NeuN and MAP2 and GFAP-expressing glia, as determined by immunocytochemistry, Western blotting, and quantitative real-time polymerase chain reaction. These results demonstrate that ADSCs can be induced to generate neurospheres that have NSC-like properties and may thus constitute a potential source of cells in stem cell therapy for neurological disorders.


Physical activity and depressive symptoms after breast cancer: Cross-sectional and longitudinal relationships.
The objective of this study was to examine the cross-sectional and longitudinal relationships between moderate-to-vigorous intensity physical activity (MVPA) and depressive symptoms in women after treatment for breast cancer. Accelerometer data on MVPA and self-report data on frequency of depressive symptoms were collected five times at ∼ 3-month intervals from women (Mage at Time 1 = 55.01 ± 10.96 years) who had completed treatment for breast cancer 3 months prior to study inception. Data were analyzed using latent growth modeling with structured residuals. Levels of MVPA decreased, on average, by .52 min every 3 months (p < .001), whereas the frequency of depressive symptoms was stable. MVPA was inversely and significantly related cross-sectionally with depressive symptoms, but not longitudinally. Also, there was no evidence of a bidirectional predictive relationship between MVPA and depressive symptoms. Although higher levels of MVPA were associated with less frequent depressive symptoms cross-sectionally in women after treatment for breast cancer, MVPA did not predict frequency of depressive symptoms or vice versa. Common etiologic or shared risk factors underpinning the cross-sectional relationships between depressive symptoms and MVPA should be studied across the transition from treatment to survivorship. (PsycINFO Database Record


Vergisson 4: a left-handed Neandertal.
Handedness is an important marker for lateralization of humans in the modern and fossil record. For the most part, Neandertals and their ancestors are strongly right-handed. We describe a single tooth from a Neandertal level at Vergisson 4 (Vg 4-83). This left upper central incisor shows all the features typical of Neandertal incisors. It also exhibits a predominance of left-handed striations. Striations on the incisor's labial surface were mapped at 20x magnification using Photoshop. Angulations of the striations were determined from their deviation from the maximum mesio-distal line and were analyzed using NIH's freeware, Image J. Of the 60 labial surface striations, Vg 4-83 shows a strong predominance of left-handed striations (46; 76.7%), which are statistically significantly different (p < .001 with a two-tailed chi2 test) from the small number (3) of right-handed striations. The identification of another left-handed Neandertal adds to our understanding about handedness variation in this fossil hominin. Given the high frequency of right-handed Neandertals, the 90: 10 modern ratio is still preserved in this group.


Genetic and proteomic evidence for roles of Drosophila SUMO in cell cycle control, Ras signaling, and early pattern formation.
SUMO is a protein modifier that is vital for multicellular development. Here we present the first system-wide analysis, combining multiple approaches, to correlate the sumoylated proteome (SUMO-ome) in a multicellular organism with the developmental roles of SUMO. Using mass-spectrometry-based protein identification, we found over 140 largely novel SUMO conjugates in the early Drosophila embryo. Enriched functional groups include proteins involved in Ras signaling, cell cycle, and pattern formation. In support of the functional significance of these findings, sumo germline clone embryos exhibited phenotypes indicative of defects in these same three processes. Our cell culture and immunolocalization studies further substantiate roles for SUMO in Ras signaling and cell cycle regulation. For example, we found that SUMO is required for efficient Ras-mediated MAP kinase activation upstream or at the level of Ras activation. We further found that SUMO is dynamically localized during mitosis to the condensed chromosomes, and later also to the midbody. Polo kinase, a SUMO substrate found in our screen, partially colocalizes with SUMO at both sites. These studies show that SUMO coordinates multiple regulatory processes during oogenesis and early embryogenesis. In addition, our database of sumoylated proteins provides a valuable resource for those studying the roles of SUMO in development.


Microbial Communities across Global Marine Basins Show Important Compositional Similarities by Depth.
The environmental surveys following the 2010 Deepwater Horizon (DWH) spill identified a variety of hydrocarbon-degrading microorganisms, and laboratory studies with field-collected water samples then demonstrated faster-than-expected hydrocarbon biodegradation rates at 5°C. Knowledge about microbial community composition, diversity, and functional metabolic capabilities aids in understanding and predicting petroleum biodegradation by microbial communities in situ and is therefore an important component of the petroleum spill response decision-making process. This study investigates the taxonomic composition of microbial communities in six different global basins where petroleum and gas activities occur. Shallow-water communities were strikingly similar across basins, while deep-water communities tended to show subclusters by basin, with communities from the epipelagic, mesopelagic, and bathypelagic zones sometimes appearing within the same cluster. Microbial taxa that were enriched in the water column in the Gulf of Mexico following the DWH spill were found across marine basins. Several hydrocarbon-degrading genera (e.g., Actinobacteria, Pseudomonas, and Rhodobacteriacea) were common across all basins. Other genera such as Pseudoalteromonas and Oleibacter were highly enriched in specific basins.IMPORTANCE Marine microbial communities are a vital component of global carbon cycling, and numerous studies have shown that populations of petroleum-degrading bacteria are ubiquitous in the oceans. Few studies have attempted to distinguish all of the taxa that might contribute to petroleum biodegradation (including, e.g., heterotrophic and nondesignated microbes that respond positively to petroleum and microbes that grow on petroleum as the sole carbon source). This study quantifies the subpopulations of microorganisms that are expected to be involved in petroleum hydrocarbon biodegradation, which is important information during the decision-making process in the event of a petroleum spill accident.


Concomitant Assessment of Monocyte HLA-DR Expression and Ex Vivo TNF-α Release as Markers of Adverse Outcome after Various Injuries-Insights from the REALISM Study.
Intensive care unit (ICU) patients develop an altered host immune response after severe injuries. This response may evolve towards a state of persistent immunosuppression that is associated with adverse clinical outcomes. The expression of human leukocyte antigen DR on circulating monocytes (mHLA-DR) and ex vivo release of tumor necrosis factor α (TNF-α) by lipopolysaccharide-stimulated whole blood are two related biomarkers offered to characterize this phenomenon. The purpose of this study was to concomitantly evaluate the association between mHLA-DR and TNF-α release and adverse clinical outcome (i.e., death or secondary infection) after severe trauma, sepsis or surgery in a cohort of 353 ICU patients. mHLA-DR and TNF-α release was similarly and significantly reduced in patients whatever the type of injury. Persistent decreases in both markers at days 5-7 (post-admission) were significantly associated with adverse outcomes. Overall, mHLA-DR (measured by flow cytometry) appears to be a more robust and standardized parameter. Each marker can be used individually as a surrogate of immunosuppression, depending on center facilities. Combining these two parameters could be of interest to identify the most immunosuppressed patients presenting with a high risk of worsening. This last aspect deserves further exploration.


Giant, accordioned sperm acrosomes of the greater bulldog bat, Noctilio leporinus.
Sperm of the greater bulldog bat Noctilio leporinus display an architecture that is totally unique among mammalian spermatozoa. The sperm head of Noctilio is extraordinarily large and flat and lies eccentrically with respect to the sperm tail. The major portion of the atypically large acrosome lies anterior to the nucleus and is shaped into a dozen accordionlike folds that run parallel to the long axis of the sperm. The ridge of each fold is shaped into approximately 60 minute, evenly spaced rises that extend along the entire length of the fold. We speculate that acrosome ridges may serve to strengthen the sperm head during transport.


New beta 2-adrenergic agonist aerosols.
The beta 2-adrenergic agonists are reviewed in terms of their dose-response characteristics, and two newer agents, fenoterol hydrobromide and bitolterol mesylate aerosols, are reviewed in relation to older agents. The fenoterol aerosol contains a more potent beta 2-adrenergic agonist dose per puff than the other aerosols but, when given in equipotent doses, offers no advantage over available agents. Bitolterol mesylate is a prodrug that is hydrolyzed to the active beta 2-adrenergic agonist colterol by lung esterases. Bitolterol demonstrates an improved bronchoselectivity in animals, but there are insufficient comparative data in humans. Tachycardia is the dose-limiting toxicity for all beta 2-adrenergic agonists. Currently available data do not suggest an important improvement in duration of action for the newer agents over terbutaline or albuterol. Aerosol administration improves bronchoselectivity of all the agents. Optimal use of beta 2-adrenergic agonist aerosols requires understanding of the variable dose-response characteristics. The type of delivery system and patient technique are important variables in determining the dose delivered. Tube-spacer devices attached to aerosol canisters can significantly improve delivery of the beta 2-adrenergic agonists to the lungs in patients unable to synchronize actuation and inspiration. They provide minimal to no improvement in patients who can perform the appropriate technique. Aerosol administration is the route of choice for beta 2-adrenergic agonists for prophylaxis of exercise-induced bronchospasm; albuterol and terbutaline provide a prolonged duration of action with excellent beta 2-adrenergic selectivity. Patients should be carefully instructed in the optimal use of metered-dose inhalers, and some patients may benefit from use of tube-spacers.


Protein phosphorylation in neurodegeneration: friend or foe?
Protein misfolding and aggregation is a common hallmark in neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and fronto-temporal dementia (FTD). In these disorders, the misfolding and aggregation of specific proteins occurs alongside neuronal degeneration in somewhat specific brain areas, depending on the disorder and the stage of the disease. However, we still do not fully understand the mechanisms governing protein aggregation, and whether this constitutes a protective or detrimental process. In PD, alpha-synuclein (aSyn) forms protein aggregates, known as Lewy bodies, and is phosphorylated at serine 129. Other residues have also been shown to be phosphorylated, but the significance of phosphorylation in the biology and pathophysiology of the protein is still controversial. In AD and in FTD, hyperphosphorylation of tau protein causes its misfolding and aggregation. Again, our understanding of the precise consequences of tau phosphorylation in the biology and pathophysiology of the protein is still limited. Through the use of a variety of model organisms and technical approaches, we are now gaining stronger insight into the effects of phosphorylation in the behavior of these proteins. In this review, we cover recent findings in the field and discuss how targeting phosphorylation events might be used for therapeutic intervention in these devastating diseases of the nervous system.


The Bacillus subtilis extracytoplasmic function σ factor σ(V) is induced by lysozyme and provides resistance to lysozyme.
Bacteria encounter numerous environmental stresses which can delay or inhibit their growth. Many bacteria utilize alternative σ factors to regulate subsets of genes required to overcome different extracellular assaults. The largest group of these alternative σ factors are the extracytoplasmic function (ECF) σ factors. In this paper, we demonstrate that the expression of the ECF σ factor σ(V) in Bacillus subtilis is induced specifically by lysozyme but not other cell wall-damaging agents. A mutation in sigV results in increased sensitivity to lysozyme killing, suggesting that σ(V) is required for lysozyme resistance. Using reverse transcription (RT)-PCR, we show that the previously uncharacterized gene yrhL (here referred to as oatA for O-acetyltransferase) is in a four-gene operon which includes sigV and rsiV. In quantitative RT-PCR experiments, the expression of oatA is induced by lysozyme stress. Lysozyme induction of oatA is dependent upon σ(V). Overexpression of oatA in a sigV mutant restores lysozyme resistance to wild-type levels. This suggests that OatA is required for σ(V)-dependent resistance to lysozyme. We also tested the ability of lysozyme to induce the other ECF σ factors and found that only the expression of sigV is lysozyme inducible. However, we found that the other ECF σ factors contributed to lysozyme resistance. We found that sigX and sigM mutations alone had very little effect on lysozyme resistance but when combined with a sigV mutation resulted in significantly greater lysozyme sensitivity than the sigV mutation alone. This suggests that sigV, sigX, and sigM may act synergistically to control lysozyme resistance. In addition, we show that two ECF σ factor-regulated genes, dltA and pbpX, are required for lysozyme resistance. Thus, we have identified three independent mechanisms which B. subtilis utilizes to avoid killing by lysozyme.


[The abortion from bioethics: autonomy of woman and physician?].
In this reflection on abortion, we will analyze from the bioethics viewpoint the concept of autonomy, in accordance with the liberal individual model and personal ambitions to be applied to the woman's and the doctor's decision making and the society in general. Now that the abortion liberalization is being proposed in Spain through a law that intends to substitute the decriminalization of certain assumptions that have been in effect since 1985, it is necessary to analyze in deep the ethical aspects beyond the legal and social approaches. Bioethics and Law must join together, since both have the same aim: the promotion of human life respect and its basic rights; safeguard -as long as possible-, the values within an interpersonal relationship that lead to fulfill a woman's life having an unwanted pregnancy, as well as that of the fetus and the doctor; and always trying to protect the rights of those who are the weakest: the woman and the fetus, without disregarding everyone's duties with them.


Relationship of motility to flow of contents in the human small intestine.
To measure simultaneously motility and flow of intestinal contents, a multilumen polyvinyl tube was passed by mouth in 10 healthy volunteers. Motility was recorded at five sites, spanning 100 cm of tube, to allow recognition of migrating motor complexes during fasting and during their disruption by food. Loci were designated as jejunal, ileal, and terminal ileal, as judged by length of tube in the intestine and by fluoroscopy. Flow of intestinal contents was measured by indicator (phenolsulfonphthalein) dilution over a 20-cm segment; flow was related to motility at the perfusion site. A liquid test meal of 400 ml and 600 kcal, containing polyethylene glycol 4000, was eaten after 6 h of fasting. During fasting, flow of intestinal contents was intermittent at all levels and varied with the presence of or absence of the activity front ("phase 3" of the migrating motor complex). The activity-front periods contributed 50% of total flow, but occupied less than one-third of the total recording time. Flow corrected for time was significantly greater with the presence of activity front than with phases 1 or 2 of the migrating motor complex (p less than 0.001). In addition, of 45 increments in flow of greater than 0.75 ml . min-1, the majority (82%) were associated with an activity front. The flow rate increased promptly after a meal and fluctuated markedly during the postprandial period in most studies. By the time migrating motor complex had returned, more than 90% of meal marker (polyethylene glycol) was accounted for in intestinal aspirates. In contrast, only 56%-73% of marker was recovered postprandially in those studies in which the migrating motor complex had not returned by the time the study was terminated. Thus, flow of intestinal content is largely intermittent during fasting, peaks of flow being associated with passage of the activity front of the migrating motor complex; on the other hand, half the fasting flow is unassociated with the activity front. Reappearance of the migrating motor complex at any level after a liquid test meal signals clearing of the liquid meal from the more proximal intestine.


Double hits with bioactive nanozyme based on cobalt-doped nanoglass for acute and diabetic wound therapies through anti-inflammatory and pro-angiogenic functions.
Regeneration of pathological wounds, such as diabetic ulcers, poses a significant challenge in clinical settings, despite the widespread use of drugs. To overcome clinical side effects and complications, drug-free therapeutics need to be developed to promote angiogenesis while overcoming inflammation to restore regenerative events. This study presents a novel bioactive nanozyme based on cobalt-doped nanoglass (namely, CoNZ), which exhibits high enzymatic/catalytic activity while releasing therapeutic ions. Cobalt oxide "Co3O4" tiny crystallites produced in situ through a chemical reaction with H2O2 within CoNZ nanoparticles play a crucial role in scavenging ROS. Results showed that CoNZ-treatment to full-thickness skin wounds in mice significantly accelerated the healing process, promoting neovascularization, matrix deposition, and epithelial lining while reducing pro-inflammatory signs. Notably, CoNZ was highly effective in treating pathological wounds (streptozotocin-induced diabetic wounds). Rapid scavenging of ROS by CoNZ and down-regulation of pro-inflammatory markers while up-regulating tissue healing signs with proliferative cells and activated angiogenic factors contributed to the observed healing events. In vitro experiments involving CoNZ-cultures with macrophages and endothelial cells exposed to high glucose and ROS-generating conditions further confirmed the effectiveness of CoNZ. CoNZ-promoted angiogenesis was attributed to the release of cobalt ions, as evidenced by the comparable effects of CoNZ-extracted ionic medium in enhancing endothelial migration and tubule formation via activated HIF-1α. Finally, we compared the in vivo efficacy of CoNZ with the clinically-available drug deferoxamine. Results demonstrated that CoNZ was as effective as the drug in closing the diabetic wound, indicating the potential of CoNZ as a novel drug-free therapeutic approach.


Decay of correlations between cross-polarized electromagnetic waves in a two-dimensional random medium.
The problem of multiple scattering of polarized light in a two-dimensional medium composed of fiberlike inhomogeneities is studied. The attenuation lengths for the density matrix elements are calculated. For a highly absorbing medium it is found that, as the sample thickness increases, the intensity of waves polarized along the fibers decays faster than the other density matrix elements. With further increase in the sample thickness, the off-diagonal elements which are responsible for correlations between the cross-polarized waves disappear. In the asymptotic limit of very thick samples the scattered light proves to be polarized perpendicular to the fibers. The difference in the attenuation lengths between the density matrix elements results in a nonmonotonic depth dependence of the degree of polarization. In the opposite case of a weakly absorbing medium, the off-diagonal element of the density matrix and, correspondingly, the correlations between the cross-polarized fields are shown to decay faster than the intensity of waves polarized along and perpendicular to the fibers.


Persistent poliovirus infection of human fetal brain cells.
It has been suggested that poliovirus (PV), the causative agent of poliomyelitis, could persist in surviving patients. We have previously shown that PV can persistently infect some human cell lines in vitro, particularly neuroblastoma cell lines. We report here an ex vivo model in which PV can persistently infect primary cultures of human fetal brain cells. Two mutations involving capsid residues 142 of VP2 and 95 of VP1 were repeatedly selected during the persistent infections. These residues are located in capsid regions known to be involved in interactions between PV and its receptor. During the first week after infection, viral antigens were found in cells of both the neuronal and glial lineages. In contrast, 2 weeks after infection, viral antigens were detected almost exclusively in cells of the neuronal lineage. They were detected predominantly in cells expressing a marker of early commitment to the neuronal lineage, MAP-5, particularly in neuroblasts. Viral antigens were also found in immature progenitors expressing a neuroepithelium marker, nestin, and in cells expressing a marker of postmitotic neurons, MAP-2. The presence of viral antigens in postmitotic neurons suggests that PV can persist in neurons of patients who have survived poliomyelitis.


A computer-based method of selecting clones for a full-length cDNA project: simultaneous collection of negligibly redundant and variant cDNAs.
We describe a computer-based method that selects representative clones for full-length sequencing in a full-length cDNA project. Our method classifies end sequences using two kinds of criteria, grouping, and clustering. Grouping places together variant cDNAs, family genes, and cDNAs with sequencing errors. Clustering separates those cDNA clones into distinct clusters. The full-length sequences of the clones selected by grouping are determined preferentially, and then the sequences selected by clustering are determined. Grouping reduced the number of rice cDNA clones for full-length sequencing to 21% and mouse cDNA clones to 25%. Rice full-length sequences selected by grouping showed a 1.07-fold redundancy. Mouse full-length sequences showed a 1.04-fold redundancy, which can be reduced by approximately 30% from the selection using our previous method. To estimate the coverage of unique genes, we used FANTOM (Functional Annotation of RIKEN Mouse cDNA Clones) clusters (). Grouping covered almost all unique genes (93% of FANTOM clusters), and clustering covered all genes. Therefore, our method is useful for the selection of appropriate representative clones for full-length sequencing, thereby greatly reducing the cost, labor, and time necessary for this process.


Pulmonary Aspects of COVID-19.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory virus that gains entry via angiotensin-converting enzyme 2 (ACE2) within airway epithelium. Patients exhibit a spectrum of respiratory symptoms from asymptomatic to respiratory failure. Patient factors including obesity, tobacco use, and black race are all associated with increased ACE2 expression and may contribute to increased complications. Consolidation and ground-glass opacities on chest imaging are typical but not specific for coronavirus disease 2019 (COVID-19). Venous thromboembolism occurs infrequently when prophylactic anticoagulation is provided. However, capillary microthrombosis is nearly ubiquitous, suggesting that it contributes to hypoxemia. Remdesivir and glucocorticoids may benefit some hospitalized patients. Many of those afflicted remain symptomatic two weeks following diagnosis and continue to require health care. Total lung capacity, diffusion capacity, and maximal oxygen consumption may be reduced for months in some survivors. Lung transplant offers chronically critically ill patients new hope, and this option may have increasing potential for outpatients with COVID-19-associated fibrosis.


The human amyloid-beta precursor protein770 mutation V717F generates peptides longer than amyloid-beta-(40-42) and flocculent amyloid aggregates.
One of the familial forms of Alzheimer's disease (AD) encodes the amyloid-beta precursor protein (AbetaPP) substitution mutation V717F. This mutation is relevant to AD research, since it has been utilized to generate transgenic mice models to study AD pathology and therapeutic interventions. Amyloid beta (Abeta) peptides were obtained from the cerebral tissue of three familial AD subjects carrying the AbetaPP V717F mutation. A combination of ultracentrifugation, size-exclusion, and reverse-phase high performance liquid chromatography, tryptic and cyanogen bromide hydrolysis, amino acid analysis, and matrix-assisted laser desorption ionization and surface-enhanced laser desorption ionization mass spectrometry was used to characterize the familial AD mutant Abeta peptides. The AbetaPP V717F mutation, located 4-6 residues beyond the wild-type AbetaPP gamma-secretase cleavage site, yielded longer Abeta peptides with C termini between residues 43 and 54. In the cerebral cortex these peptides aggregated into thin water- and SDS-insoluble amyloid bundles that condensed into flocculent spherical plaques. In the leptomeningeal arteries the amyloid was deposited in moderate amounts and was primarily composed of the shorter and more soluble Abeta species ending at residues 40, 42, and 44. The single V717F mutation in AbetaPP results in distinctive and drastic changes in the length and tertiary structure of Abeta peptides, which appear to be responsible for the earlier clinical manifestations of dementia and death of these patients.


The Pathologist Pipeline: Implications of Changes for Programs and Post-Sophomore Fellowships-Program Directors' Section Perspective.
A shortage of physicians in the United States has been long projected. Because of predictions of retirement among the aging pathology workforce, there is an anticipated shortage of pathologist as well. To address the pathology workforce shortage among pathologists, the Association of Pathology Chairs assembled a subcommittee of the Association of Pathology Chairs Advocacy Committee to explore ways to identify the strengths, weaknesses, opportunities, and threats to the pathology workforce. One opportunity to encourage strong candidates to pursue pathology as a career is to explore possibility to revisit advanced credit for the post-sophomore fellowship. A survey that was designed to understand the post-sophomore fellowship training better was distributed on the listserv of the Program Directors Section of the Association of Pathology Chairs. A review of the literature on post-sophomore fellowship programs is presented in light of the findings from this survey. Many post-sophomore fellowship programs are run similar to a first-year resident experience, although programs show great diversity in curriculum, including some programs that focus on research. Post-sophomore fellowships attract medical students to the area of pathology and tend to end up in academic and research positions. A second survey of program directors served as an opinion poll of challenging issues that affect residency training. From the second opinion poll, most program directors feel that residents can use additional training to improve the outcome of our future pathologists.


Effects of high hydrostatic pressure on coastal bacterial community abundance and diversity.
Hydrostatic pressure is an important parameter influencing the distribution of microbial life in the ocean. In this study, the response of marine bacterial populations from surface waters to pressures representative of those under deep-sea conditions was examined. Southern California coastal seawater collected 5 m below the sea surface was incubated in microcosms, using a range of temperatures (16 to 3°C) and hydrostatic pressure conditions (0.1 to 80 MPa). Cell abundance decreased in response to pressure, while diversity increased. The morphology of the community also changed with pressurization to a predominant morphotype of small cocci. The pressure-induced community changes included an increase in the relative abundance of Alphaproteobacteria, Gammaproteobacteria, Actinobacteria, and Flavobacteria largely at the expense of Epsilonproteobacteria. Culturable high-pressure-surviving bacteria were obtained and found to be phylogenetically similar to isolates from cold and/or deep-sea environments. These results provide novel insights into the response of surface water bacteria to changes in hydrostatic pressure.


Health costs of women with chronic overlapping pain conditions by opioid and complementary and integrative health use.
To estimate differences in average annual health care expenditures of adult women with chronic overlapping pain conditions (COPCs) by pain treatment modality as follows: (1) no long-term opioid or complementary and integrative health (CIH) use; (2) CIH only use; (3) long-term opioid only use; and (4) long-term opioid and CIH use. Cross-sectional Medical Expenditure Panel Survey data (2012-2016). We estimated differences between average annual expenditures of adult women with COPCs by their use of long-term opioids and CIH modalities. Generalized linear regression with a log link function was used to estimate adjusted marginal effects in annual expenditures. The distribution family was chosen based on Modified Park Tests. We controlled for pain severity, patient demographic characteristics, physical limitations, comorbidities, mental health, insurance status, physical therapy use, and census region. We also employed propensity-score based marginal mean weighting through stratification to balance our treatment groups on observed covariates. We identified adult women (>17 years) with one or more self-reported COPC using 3-digit International Classification of Diseases (ICD)-9/10-Clinical Modification (CM) codes (N = 9169) and categorized their use of CIH and long-term opioids. Compared to women without long-term opioid or CIH use, CIH only use was significantly associated with lower inpatient expenditures (-$947 [-$1699, -$196]; p-value < 0.01), higher office-based expenditures ($1345 [$944, $1746]; p-value < 0.001), and higher patient out-of-pocket expenditures ($628 [$409, $848]; p-value < 0.001). Long-term opioid use, alone or in combination with CIH, was significantly associated with higher expenditures (p-value < 0.05) in total and across all utilization categories compared to women without any long-term opioid or CIH use. Our results indicate that CIH treatment approaches for chronic pain have the potential to be utilized without increasing overall costs. Future research should further examine the role of CIH modalities in achieving cost-effective pain management that reduces avoidable opioid use.


Acquired immunodeficiency syndrome in children: report of the Centers for Disease Control National Surveillance, 1982 to 1985.
Since national surveillance for acquired immunodeficiency syndrome (AIDS) began in 1981, the Centers for Disease Control (CDC) has received reports of more than 20,000 cases of AIDS in the United States. As of December 31, 1985, 307 of these cases had been diagnosed in children younger than 13 years of age. The number of cases is increasing rapidly. The number of cases reported in 1985 more than doubled those reported in 1984. The major risk factors in children for acquiring infection with the causative agent, human immunodeficiency virus (HIV), were having a mother known to be infected and/or at increased risk for infection and receiving a transfusion of blood or blood products. Of the 307 children with AIDS, 73% were reported from one of four states: New York, New Jersey, Florida, and California. Most AIDS cases in children occur in black or Hispanic infants and toddlers. The estimated incubation period for AIDS in children has increased each surveillance year, with the longest incubation exceeding 7 years. The prognosis for children with AIDS is poor and infants less than 1 year of age have the shortest survival time following diagnosis. Continued national surveillance for AIDS is mandatory for establishing effective prevention programs to control the spread of the disease. The CDC encourages all health care personnel to report cases of AIDS to their public health departments.


Using in vivo biotinylated ubiquitin to describe a mitotic exit ubiquitome from human cells.
Mitotic division requires highly regulated morphological and biochemical changes to the cell. Upon commitment to exit mitosis, cells begin to remove mitotic regulators in a temporally and spatially controlled manner to bring about the changes that reestablish interphase. Ubiquitin-dependent pathways target these regulators to generate polyubiquitin-tagged substrates for degradation by the 26S proteasome. However, the lack of cell-based assays to investigate in vivo ubiquitination limits our knowledge of the identity of substrates of ubiquitin-mediated regulation in mitosis. Here we report an in vivo ubiquitin tagging system used in human cells that allows efficient purification of ubiquitin conjugates from synchronized cell populations. Coupling purification with mass spectrometry, we have identified a series of mitotic regulators targeted for polyubiquitination in mitotic exit. We show that some are new substrates of the anaphase-promoting complex/cyclosome and validate KIFC1 and RacGAP1/Cyk4 as two such targets involved respectively in timely mitotic spindle disassembly and cell spreading. We conclude that in vivo biotin tagging of ubiquitin can provide valuable information about the role of ubiquitin-mediated regulation in processes required for rebuilding interphase cells.


Has large-scale named-entity network analysis been resting on a flawed assumption?
The assumption that a name uniquely identifies an entity introduces two types of errors: splitting treats one entity as two or more (because of name variants); lumping treats multiple entities as if they were one (because of shared names). Here we investigate the extent to which splitting and lumping affect commonly-used measures of large-scale named-entity networks within two disambiguated bibliographic datasets: one for co-author names in biomedicine (PubMed, 2003-2007); the other for co-inventor names in U.S. patents (USPTO, 2003-2007). In both cases, we find that splitting has relatively little effect, whereas lumping has a dramatic effect on network measures. For example, in the biomedical co-authorship network, lumping (based on last name and both initials) drives several measures down: the global clustering coefficient by a factor of 4 (from 0.265 to 0.066); degree assortativity by a factor of ∼13 (from 0.763 to 0.06); and average shortest path by a factor of 1.3 (from 5.9 to 4.5). These results can be explained in part by the fact that lumping artificially creates many intransitive relationships and high-degree vertices. This effect of lumping is much less dramatic but persists with measures that give less weight to high-degree vertices, such as the mean local clustering coefficient and log-based degree assortativity. Furthermore, the log-log distribution of collaborator counts follows a much straighter line (power law) with splitting and lumping errors than without, particularly at the low and the high counts. This suggests that part of the power law often observed for collaborator counts in science and technology reflects an artifact: name ambiguity.


Hb Westmead: an alpha 2-globin gene mutation detected by polymerase chain reaction and Stu I cleavage.
Hb Westmead or alpha 2 122(H5)His----Gln beta 2 is one of the most common hemoglobin variants in Guangxi, a province in Southern China. The alpha 2-globin DNA sequence of a carrier for this variant was selectively amplified by the polymerase chain reaction and analyzed with the restriction enzyme Stu I. We found that this mutant globin was encoded at the alpha 2 locus and that the CAC----CAG mutation at codon 122 created a new Stu I restriction site. It is easy to detect this mutation by these methods.


[Tetraspanins and syndecans: Partners in crime for 'dealing' exosomes?]
Exosomes are small extracellular vesicles derived from endosomal compartments. The molecular mechanisms supporting the biology of exosomes, from their biogenesis to their internalization by target cells, rely on 'dedicated' membrane proteins. These mechanisms of action need to be further clarified. This will help to better understand how exosome composition and heterogeneity are established. This would also help to rationalize their use as source of biomarkers and therapeutic tools. Here we discuss how syndecans and tetraspanins, two families of membrane scaffold proteins, cooperate to regulate different steps of exosome biology.


Assessment of the efficacy and potential complications of transjugular liver biopsy in canine cadavers.
Transjugular liver biopsy (TJLB) is used in humans at risk of bleeding. There are no reports of its use in veterinary medicine. To assess the efficacy and potential complications of TJLB in canine cadavers, and compare with samples obtained via needle liver biopsy (NLB) and surgical liver biopsy (SLB). Twenty-five medium and large breed canine cadavers. Prospective study. TJLBs were procured through the right jugular vein. After biopsy, intravenous contrast and gross inspection were used to assess the biopsy site. Minor and major complications were recorded. NLBs and SLBs were then obtained. Histopathology was performed, and TJLB and NLB were compared for number of complete portal tracts (CPTs), length, and fragmentation. Pathologic process and autolysis were assessed in all samples. All TJLBs yielded liver tissue. The proportion of minor complications was 12/25 (48%), and major complications 16/25 (64%); 13/16 (81%) of the major complications were liver capsule perforation. In 21/25 (84%), the histopathology in the SLB was reflected in the TJLBs. For cases with minimal autolysis, median number of CPTs in TJLBs was 7.5, compared with 4 in NLBs (P = .018). Median length of TJLB specimen was 28 mm compared to 22 mm in NLBs (P = .007). Fragmentation rate was median of 1.25 for TJLB compared to 1.50 in NLBs (P = .11). TJLB is technically feasible and achieves comparable results to NLB and SLB. The number of complications, in particular liver capsule perforation, was greater than expected. Further studies are indicated before clinical use is recommended.


Control of dispersion state of silsesquioxane nanofillers for stabilization of polystyrene thin films.
The influence of the dispersion states of the nanofillers on the dewetting behavior of the polymer thin film was investigated. Polyhedral oligomeric silsesquioxanes (POSS) with various substituents were added into polystyrene (PS) thin films as the nanofillers. The dewetting rate of the films drastically changed with the surface substituents of POSS additives. Neutron reflectivity measurements indicated that the difference of the dewetting rate was associated with the dispersion state of POSS additives in the films. POSS with phenethyl groups (PhPOSS), which homogeneously dispersed into the films, resulted in the decrease of the glass transition temperature of PS and the enhancement of the dewetting of the films. POSS with a fluoroalkyl group (CpPOSS-R f) segregated to the film surface and showed the retardation of the dewetting by the decrease of the surface energy of the film. POSS with hydroxyl groups (CpPOSS-2OH) segregated to the film surface and film-substrate interface and led to the elimination of the dewetting, suggesting the importance of the interfacial segregation for the inhibition of dewetting. These results revealed the strong relationship between the dispersion state of the nanofillers and the dewetting of the nanofilled films.


Helper and suppressor T-cells regulating killer cells of EB virus infected cells.
Using an in-vitro human lymphocyte system, a study was performed to determine whether helper T-cells and suppressor T-cells control the generation of killer cells against autologous B-cells transformed by Epstein-Barr (EB) virus. When T-cells were treated with mitomycin C and reacted in the presence of macrophages with target cells bearing HLA-DR, helper T-cells were induced but suppressor T-cells were not. In contrast, when T-cells were reacted in the absence of macrophages to target cells lacking HLA-DR, suppressor T-cells but not helper T-cells were induced. The culture supernatant of the T-cells which showed suppressor activity also suppressed the generation of killer cells. The thus-induced suppressor T-cells also suppressed the HLA incompatible allogeneic killer cells which were directed against autologous B-cells transformed by EB virus and also autologous killer cells directed against allogeneic target cells. These observations indicated that there is no HLA restriction between the suppressor T-cells and the killer cells and the suppression is antigen nonspecific.


The use of microarrays to study autoimmunity.
As with the development of any novel and potentially powerful technology, the prospect of revealing new information that may dramatically change our understanding of biological processes can generate much excitement. Such is true for the emerging genomic approaches that make possible high-density assays using microarray platforms. Indeed, it is difficult, if not impossible, to imagine any area of biology that could not be affected by the wide range of potential applications of microarray technology. Numerous examples, such as those from the field of oncology, provide striking evidence of the power of microarrays to bring about extraordinary advances in molecularly defining important disease phenotypes that were otherwise unrecognized using conventional approaches such as histology. However, only a few studies in autoimmunity are available to date. Very recent work in alopecia areata, multiple sclerosis, systemic lupus erythematosus, and Sjögren's syndrome illustrates the potential for gaining new insights into the pathophysiology of these complex autoimmune disorders on a global, molecular scale. These new insights are likely to significantly improve our understanding of disease processes, diagnosis, identification of new therapeutic targets, and identification of patients most likely to benefit from specific and tailored therapies.


Parent and Friend Emotion Socialization in Early Adolescence: Their Unique and Interactive Contributions to Emotion Regulation Ability.
During early adolescence, parental influence diminishes, whereas friends' influence increases in shaping emotion regulation abilities. However, it is unclear how parents and friends jointly contribute to emotion regulation abilities and how their joint effects vary by gender. This study examines fathers, mothers, and friends as simultaneous emotional socializers and considers the young adolescents' gender. The analysis drew on 438 young Chinese adolescents (55.7% girls, Mage = 11.39, SD = 1.28) who participated in a longitudinal survey over one year. Results showed that parental and friend emotion socialization have both distinct and joint effects. Friends' responses provided a unique contribution to emotion regulation abilities across gender, whereas parents' responses displayed unique contributions among girls. In predicting girls' emotion regulation abilities, mothers' supportive responses explained the additional variance beyond friends' responses, whereas fathers' unsupportive responses moderated the predictive power of friends' responses. These findings clarify emotion-related socialization theories and emphasize the importance of gender specific prevention programs focusing on emotion socialization from both parents and friends in early adolescence.


HIV and co-infections.
Despite significant reductions in morbidity and mortality secondary to availability of effective combination anti-retroviral therapy (cART), human immunodeficiency virus (HIV) infection still accounts for 1.5 million deaths annually. The majority of deaths occur in sub-Saharan Africa where rates of opportunistic co-infections are disproportionately high. In this review, we discuss the immunopathogenesis of five common infections that cause significant morbidity in HIV-infected patients globally. These include co-infection with Mycobacterium tuberculosis, Cryptococcus neoformans, hepatitis B virus, hepatitis C virus, and Plasmodium falciparum. Specifically, we review the natural history of each co-infection in the setting of HIV, the specific immune defects induced by HIV, the effects of cART on the immune response to the co-infection, the pathogenesis of immune restoration disease (IRD) associated with each infection, and advances in the areas of prevention of each co-infection via vaccination. Finally, we discuss the opportunities and gaps in knowledge for future research.


Information-Theoretic Evidence for Predictive Coding in the Face-Processing System.
Predictive coding suggests that the brain infers the causes of its sensations by combining sensory evidence with internal predictions based on available prior knowledge. However, the neurophysiological correlates of (pre)activated prior knowledge serving these predictions are still unknown. Based on the idea that such preactivated prior knowledge must be maintained until needed, we measured the amount of maintained information in neural signals via the active information storage (AIS) measure. AIS was calculated on whole-brain beamformer-reconstructed source time courses from MEG recordings of 52 human subjects during the baseline of a Mooney face/house detection task. Preactivation of prior knowledge for faces showed as α-band-related and β-band-related AIS increases in content-specific areas; these AIS increases were behaviorally relevant in the brain's fusiform face area. Further, AIS allowed decoding of the cued category on a trial-by-trial basis. Our results support accounts indicating that activated prior knowledge and the corresponding predictions are signaled in low-frequency activity (<30 Hz).SIGNIFICANCE STATEMENT Our perception is not only determined by the information our eyes/retina and other sensory organs receive from the outside world, but strongly depends also on information already present in our brains, such as prior knowledge about specific situations or objects. A currently popular theory in neuroscience, predictive coding theory, suggests that this prior knowledge is used by the brain to form internal predictions about upcoming sensory information. However, neurophysiological evidence for this hypothesis is rare, mostly because this kind of evidence requires strong a priori assumptions about the specific predictions the brain makes and the brain areas involved. Using a novel, assumption-free approach, we find that face-related prior knowledge and the derived predictions are represented in low-frequency brain activity.


Responding to threat: hemispheric asymmetries and interhemispheric division of input.
This investigation examined how hemispheric asymmetry and interhemispheric processing contribute to attentional biases toward emotional information. Participants (n = 88) named the color of lateralized squares presented concurrently with neutral, positive, or threatening words. A left-hemisphere advantage in color naming was reduced when distractors were emotional, suggesting right-hemisphere priming by emotional stimuli. Furthermore, the advantage of dividing the word and color across visual fields was increased for emotion words when they were frequently presented, indicating a strategic use of interhemispheric division of labor to reduce the distracting effect of emotional words. Finally, participants with high levels of anxious apprehension were most likely to make use of this interhemispheric processing strategy, supporting a processing efficiency theory of cognitive function in anxiety.


Strategies of reducing the carcinogenic risk of cytostatic agents on the basis of bioassay evaluation.
This article described strategies that can be used to reduce the carcinogenic risk of cytostatic chemotherapy and summarizes our recent experimental results. Reduction of neoplasms caused by the carcinogenic potency inherent in cytostatic agents can be obtained. (A) by chemical modifications such as: (1) exchanging a chlorine atom in N, N'-bis-(2-chloroethyl)-N-nitrosourea (BCNU) in the chloroethyl group at N'-position for a hydroxyl group to form the less carcinogenic analog N-(2-chloroethyl)-N'-(2-hydroxyethyl)-N-nitrosourea (HECNU); (2) linking chlorambucil to the steroid prednisolone to obtain a conjugate (prednimustine) with distinctly lower carcinogenic potential than chlorambucil; (3) progressive ring halogenation of phenyl-triazenes to generate agents with decreased long-term toxic risk; (B) by replacing cyclophosphamide within the carcinogenic drug combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) by vincristine to form the combination VMF which has no detectable carcinogenic potential; (C) by coadministration of cyclophosphamide and mesna to achieve a dose-related reduction of cyclophosphamide-induced urinary bladder carcinomas; (D) by administration of dinaline, a compound which reduces the spontaneous incidence of malignant tumors in rats. These examples demonstrate that the carcinogenic risk of single agents and drug combinations used for antineoplastic chemotherapy has successfully been reduced, as assessed in long-term bioassays. Such strategies should be considered in the treatment of patients with long life expectancy following cytotoxic chemotherapy.


Minocycline prevents osmotic demyelination associated with aquaresis.
Overly rapid correction of chronic hyponatremia can cause osmotic demyelination syndrome (ODS). Minocycline protects ODS associated with overly rapid correction of chronic hyponatremia with hypertonic saline infusion in rats. In clinical practice, inadvertent rapid correction frequently occurs due to water diuresis, when vasopressin action suddenly ceases. In addition, vasopressin receptor antagonists have been applied to treat hyponatremia. Here the susceptibility to and pathology of ODS were evaluated using rat models developed to represent rapid correction of chronic hyponatremia in the clinical setting. The protective effect of minocycline against ODS was assessed. Chronic hyponatremia was rapidly corrected by 1 (T1) or 10 mg/kg (T10) of tolvaptan, removal of desmopressin infusion pumps (RP), or administration of hypertonic saline. The severity of neurological impairment in the T1 group was significantly milder than in other groups and brain hemorrhage was found only in the T10 and desmopressin infusion removal groups. Minocycline inhibited demyelination in the T1 group. Further, immunohistochemistry showed loss of aquaporin-4 (AQP4) in astrocytes before demyelination developed. Interestingly, serum AQP4 levels were associated with neurological impairments. Thus, minocycline can prevent ODS caused by overly rapid correction of hyponatremia due to water diuresis associated with vasopressin action suppression. Increased serum AQP4 levels may be a predictive marker for ODS.


Congenital hypofibrinogenemia: characterization of two missense mutations affecting fibrinogen assembly and secretion.
Congenital hypofibrinogenemia is a rare bleeding disorder characterized by abnormally low levels of fibrinogen in plasma, generally due to heterozygous mutations in one of the three fibrinogen genes (FGA, FGB, and FGG, coding for Aalpha, Bbeta, and gamma chain, respectively). Hypofibrinogenemic patients are usually asymptomatic, whereas individuals bearing similar mutations in the homozygous or compound heterozygous state develop a severe bleeding disorder: afibrinogenemia. The mutational spectrum of these quantitative fibrinogen disorders includes large deletions, point mutations causing premature termination codons, and missense mutations affecting fibrinogen assembly or secretion, distributed throughout the 50-kb fibrinogen gene cluster. In this study, we report the mutational screening of two unrelated hypofibrinogenemic patients leading to the identification of two missense mutations, one hitherto unknown (alphaCys45Phe), and one previously described (gammaAsn345Ser). The involvement of alphaCys45Phe and gammaAsn345Ser in the pathogenesis of hypofibrinogenemia was investigated by in-vitro expression experiments. Both mutations were demonstrated to cause a severe impairment of intracellular fibrinogen processing, either by affecting half-molecule dimerization (alphaCys45Phe) or by hampering hexamer secretion (gammaAsn345Ser).


Sampling Variation of RAD-Seq Data from Diploid and Tetraploid Potato (Solanum tuberosum L.).
The new sequencing technology enables identification of genome-wide sequence-based variants at a population level and a competitively low cost. The sequence variant-based molecular markers have motivated enormous interest in population and quantitative genetic analyses. Generation of the sequence data involves a sophisticated experimental process embedded with rich non-biological variation. Statistically, the sequencing process indeed involves sampling DNA fragments from an individual sequence. Adequate knowledge of sampling variation of the sequence data generation is one of the key statistical properties for any downstream analysis of the data and for implementing statistically appropriate methods. This paper reports a thorough investigation on modeling the sampling variation of the sequence data from the optimized RAD-seq (Restriction sit associated DNA sequencing) experiments with two parents and their offspring of diploid and autotetraploid potato (Solanum tuberosum L.). The analysis shows significant dispersion in sampling variation of the sequence data over that expected under multinomial distribution as widely assumed in the literature and provides statistical methods for modeling the variation and calculating the model parameters, which may be easily implemented in real sequence datasets. The optimized design of RAD-seq experiments enabled effective control of presentation of undesirable chloroplast DNA and RNA genes in the sequence data generated.


Women's Knowledge of and Support for Abortion Restrictions in Texas: Findings from a Statewide Representative Survey.
States have passed numerous laws restricting abortion, and Texas passed some of the most restrictive legislation between 2011 and 2013. Information about women's awareness of and support for the laws' provisions could inform future debates regarding abortion legislation. Between December 2014 and January 2015, some 779 women aged 18-49 participated in an online, statewide representative survey about recent abortion laws in Texas. Poisson regression analysis was used to assess correlates of support for a law that would make obtaining an abortion more difficult. Women's knowledge of specific abortion restrictions in Texas and reasons for supporting these laws were also assessed. Overall, 31% of respondents would support a law making it more difficult to obtain an abortion. Foreign-born Latinas were more likely than whites to support such a law (prevalence ratio, 1.5), and conservative Republicans were more likely than moderates and Independents to do so (2.3). Thirty-six percent of respondents were not very aware of recent Texas laws, and 19% had never heard of them. Among women with any awareness of the laws, 19% supported the requirements; 42% of these individuals said this was because such laws would make abortion safer. Many Texas women of reproductive age are unaware of statewide abortion restrictions, and some support these requirements because of misperceptions about the safety of abortion. Advocates and policymakers should address these knowledge gaps in efforts to protect access to legal abortion.


Waiting times in emergency department after using the emergency severity index triage tool.
Hospital emergency departments (EDs) are as barometers of the health care system. Crowded EDs threaten delivery of timely care. Prolonged ED wait times reduce the quality of care and increase adverse and sometimes irreversible events. The purpose of this study was to determine the patients' waiting time at Namazi and Shahid Faghihi hospitals in Shiraz, Iran. This analytical cross-sectional study was conducted in two phases from December 2012 to May 2013. First, the researcher attended the EDs of the two hospitals and recorded the information of 900 patients who entered the ED, including arrival time, level of triage, and time of first visit by physician. Then, among patients admitted to the ED units, 273 were followed and waiting times for the first physician order in the referral unit and the commencement of clinical interventions (defined as check time by the nurse) were recorded. The median waiting time from arrival to first visit by physician for the 900 patients included in the study was 8 (5-14) minutes [median (interquartile range)]. For the patients admitted to referral units, waiting time was 84 (43-145) minutes for the physician order and 85 (45-147) minutes for the commencement of first clinical intervention; 75% of the patients in triage level I, 84.6% in triage level II, and 95.6% in triage level III were visited within the target time limit. Waiting time for commencement of clinical action in patients admitted to the EDs was considerably high for patients with higher priorities; so, rapid care of critically ill patients, identified during the triage process, should be emphasized.


Socioeconomic status and determinants of hemostatic function in healthy women.
Hemostatic factors are reported to be associated with coronary heart disease (CHD). Socioeconomic status (SES) is 1 of the determinants of the hemostatic profile, but the factors underlying this association are not well known. Our aim was to examine determinants of the socioeconomic differences in hemostatic profile. Between 1991 and 1994, we studied 300 healthy women, aged 30 to 65 years, who were representative of women living in the greater Stockholm area. Fibrinogen, factor VII mass concentration (FVII:Ag), activated factor VII (FVIIa), von Willebrand factor (vWF), and plasminogen activator inhibitor-1 (PAI-1) were measured. Educational attainment was used as a measure of SES. Low educational level and an unfavorable hemostatic profile were both associated with older age, unhealthful life style, psychosocial stress, atherogenic biochemical factors, and hypertension. Levels of hemostatic factors increased with lower educational attainment. Independently of age, the differences between the lowest (mandatory) and highest (college/university) education in FVII:Ag levels were 41 microg/L (95% confidence interval [CI], 15 to 66 microg/L, P=0.001), 0.26 g/L (95% CI, 0.10 to 0.42 g/L, P=0.001) in fibrinogen levels, and 0.11 U/mL (95% CI, 0.09 to 0.12 U/mL, P=0.03) in levels of vWF. The corresponding differences in FVIIa and PAI-1 were not statistically significant. With further adjustment for menopausal status, family history of CHD, marital status, psychosocial stress, lifestyle patterns, biochemical factors, and hypertension, statistically significant differences between mandatory and college/university education were observed in FVII:Ag (difference=34 microg/L; 95% CI, 2 to 65 microg/L, P=0.05) but not in fibrinogen (difference=0.03 g/L; 95% CI, -0.13 to 0.19 g/L, P=0.92) or in vWF (difference=0.06 U/mL; 95% CI, -0.10 to 0.22 U/mL, P=0.45). An educational gradient was most consistent and statistically significant for FVII:Ag, fibrinogen, and vWF. Age, psychosocial stress, unhealthful life style, atherogenic biochemical factors, and hypertension mediated the association of low educational level with elevated levels of fibrinogen and vWF. Psychosocial stress and unhealthful life style were the most important contributing factors. There was an independent association between education and FVII:Ag, which could not be explained by any of these factors.


FT-IR microscopic characterization of normal and malignant human colonic tissues.
Fourier-transform infrared spectroscopy (FT-IR) employs a unique approach to optical diagnosis of tissue pathology based on the characteristic molecular vibrational spectra of the tissue. In this study, we report infrared absorption spectra of formalin fixed, paraffin embedded normal and malignant human colonic tissues from ten different patients. Our method is based on microscopic infrared study (FT-IR-microscopy) of thin tissue specimens in parallel with normal histopathological analysis, which serves as a reference. Our results indicate that the normal colonic tissue has a stronger absorption than the cancerous type over a wide region in all ten cases. The detailed analysis showed that there is a significant decrease in carbohydrate levels, total phosphate and also possibly creatine contents for cancerous tissue in comparison to the controls. Also, RNA/DNA ratio increased in cancerous tissues relative to the normals in all the patients. The results of Linear Discriminant Analysis (LDA) showed that the normal and malignant cells could be identified with about 89% accuracy.


[Extracorporeal lithotripsy in the treatment of biliary calculi].
The authors present their experience from February 1988 with biliary lithotripsy in 125 patients. They review the protocol inclusion criteria and the various forms of complementary medical treatment. From this group, 30% of the patients underwent cholecystectomy, 45% received medical treatment and only 25% did not eventually require complementary medical therapy.


Metabolism of adenine nucleotides by ectoenzymes of vascular endothelial and smooth-muscle cells in culture.
1. Pig aortic endothelial and smooth-muscle cells in culture rapidly catabolize exogenous ATP, ADP or AMP. 2. In both cell types catabolism is due to Mg2+-stimulated ectoenzymes. 3. Inhibition and substrate-specificity studies suggest that both cell types possess three distinct ectonucleotidases, namely nucleoside triphosphatase (EC 18.104.22.168), nucleoside diphosphatase (EC 184.108.40.206) and 5'-nucleotidase (EC 126.96.36.199), as well as nucleoside diphosphate kinase (EC 126.96.36.199). 4. These ectonucleotidase systems could be of importance in the regulation of neurotransmission, blood platelet function and vasodilation.


Efficacy and tolerability of natalizumab in relapsing-remitting multiple sclerosis patients: a post-marketing observational study.
To evaluate the efficacy and safety of natalizumab in patients with active relapsing-remitting multiple sclerosis (MS). We included 285 MS patients receiving natalizumab. Clinical, neuroradiological and safety data were registered every 6 months. Neutralizing antibodies (NABs) were tested after 6 months of treatment. After 1 year, the annualized relapse rate decreased to 0.26, with a significant reduction compared to the previous year (2.13). At 24 months the proportion of "relapse free" patients was 78% while that of "MRI free" patients was 69%. Considering clinical and MRI cumulative activity, "disease free" patients were 63% at 24 months. A total of 18 patients showed NABs positivity. We reported 34 cases of treatment interruptions. In conclusion, our data confirm the remarkable efficacy of natalizumab in a group of patients with higher disease activity than that of pivotal studies.


T-shaped GaAs quantum-wire lasers and the exciton Mott transition.
T-shaped GaAs quantum-wire (T-wire) lasers fabricated by the cleaved-edge overgrowth method with molecular beam epitaxy on the interface improved by a growth-interrupt high-temperature anneal are measured to study the laser device physics and fundamental many-body physics in clean one-dimensional (1D) systems. A current-injection T-wire laser that has 20 periods of T-wires in the active region and a 0.5 mm long cavity with high-reflection coatings shows a low threshold current of 0.27 mA at 30 K. The origin of the laser gain above the lasing threshold is studied with the high-quality T-wire lasers by means of optical pumping. The lasing energy is about 5 meV below the photoluminescence (PL) peak of free excitons, and is on the electron-hole (e-h) plasma PL band at a high e-h carrier density. The observed energy shift excludes the laser gain due to free excitons, and it suggests a contribution from the e-h plasma instead. A systematic micro-PL study reveals that the PL evolves with the e-h density from a sharp exciton peak, via a biexciton peak, to an e-h-plasma PL band. The data demonstrate an important role of biexcitons in the exciton Mott transition. Comparison with microscopic theories points out some problems in the picture of the exciton Mott transition.


Albumin/Mitotane Interaction Affects Drug Activity in Adrenocortical Carcinoma Cells: Smoke and Mirrors on Mitotane Effect with Possible Implications for Patients' Management.
Mitotane is the only drug approved for the treatment of adrenocortical carcinoma (ACC). Although it has been used for many years, its mechanism of action remains elusive. H295R cells are, in ACC, an essential tool to evaluate drug mechanisms, although they often lead to conflicting results. Using different in vitro biomolecular technologies and biochemical/biophysical experiments, we evaluated how the presence of "confounding factors" in culture media and patient sera could reduce the pharmacological effect of mitotane and its metabolites. We discovered that albumin, the most abundant protein in the blood, was able to bind mitotane. This interaction altered the effect of the drug by blocking its biological activity. This blocking effect was independent of the albumin source or methodology used and altered the assessment of drug sensitivity of the cell lines. In conclusion, we have for the first time demonstrated that albumin does not only act as an inert drug carrier when mitotane or its metabolites are present. Indeed, our experiments clearly indicated that both albumin and human serum were able to suppress the pharmacological effect of mitotane in vitro. These experiments could represent a first step towards the individualization of mitotane treatment in this rare tumor.


The Involvement of Type 2 Innate Lymphoid Cells in Airway Inflammation of Asthma.
The airway inflammatory response is closely associated with asthma. The purpose of this article was to study the roles of innate lymphoid cells (ILCs) in the process of airway inflammatory response in asthma. We established the asthmatic mice model with intraperitoneal injected ovalbumin medium, then with the flow cytometry analysis, we detected the ILCs and their surface proteins in the mice blood samples, besides, we analyzed the amounts of inflammatory cytokines and secreted proteins in the mice bronchoalveolar lavage fluid and blood serum. Moreover, Western blot analyzed the proteins in the mice bronchial epithelial tissues. The ILC2 amounts were obviously increased in young asthmatic mice model. And, the proteins CD25 and CCR10 were highly expressed in the sorted ILC2s. Besides, the cytokines interleukin (IL)-5, IL-13, IL-33, CCL22, and CCL27 were abundant in the bronchoalveolar lavage fluid of asthmatic mice model. And, the secretion of IL-5, IL-13, IL-33, TSLP, and CCL22 in blood serum was much more in asthmatic mice model than in the normal control mice, whereas the secretion of PGD2 was suppressed in asthmatic mice bronchoalveolar lavage fluid and blood serum. Additionally, the guanine nucleotide-binding proteins Gα12 and Gα13 were upregulated in asthmatic mice bronchial tissues, and the protein SERCA2 was downregulated; moreover, the proteins NFAT, IRF4, and its downstream signal STAT6 were all upregulated in the asthmatic mice bronchial tissues. ILC2s were involved in the response of airway inflammation through secretion of proinflammatory cytokines and chemokines to dysregulate the Ca2+ homeostasis in airway in the process of asthma. [Figure: see text].


Virulence factors identified by Cryptococcus neoformans mutant screen differentially modulate lung immune responses and brain dissemination.
Deletions of cryptococcal PIK1, RUB1, and ENA1 genes independently rendered defects in yeast survival in human CSF and within macrophages. We evaluated virulence potential of these genes by comparing wild-type Cryptococcus neoformans strain H99 with deletant and complement strains in a BALB/c mouse model of pulmonary infection. Survival of infected mice; pulmonary cryptococcal growth and pathology; immunological parameters; dissemination kinetics; and CNS pathology were examined. Deletion of each PIK1, RUB1, and ENA1 differentially reduced pulmonary growth and dissemination rates of C. neoformans and extended mice survival. Furthermore, pik1Δ induced similar pathologies to H99, however, with significantly delayed onset; rub1Δ was more efficiently contained within pulmonary macrophages and was further delayed in causing CNS dissemination/pathology; whereas ena1Δ was progressively eliminated from the lungs and did not induce pathological lesions or disseminate into the CNS. The diminished virulence of mutant strains was associated with differential modulation of pulmonary immune responses, including changes in leukocyte subsets, cytokine responses, and macrophage activation status. Compared to H99 infection, mutants induced more hallmarks of a protective Th1 immune response, rather than Th2, and more classical, rather than alternative, macrophage activation. The magnitude of immunological effects precisely corresponded to the level of virulence displayed by each strain. Thus, cryptococcal PIK1, RUB1, and ENA1 differentially contribute to cryptococcal virulence, in correlation with their differential capacity to modulate immune responses.


Relevancy and reproducibility of magnetic resonance imaging (MRI) interpretation in multiple-ligament injuries and dislocations of the knee.
After multiple-ligament injuries and dislocations of the knee, clinical assessment of the soft tissues is difficult and MRI is generally performed. MRI is a reliable examination, providing a precise and reproducible assessment of soft-tissue lesions after multiple-ligament injuries or dislocations of the knee. Forty patients presenting multiple-ligament lesions of the knee were included in this multicenter prospective study. All had an MRI of the knee in the 48 h following their accident. Thirty-four patients were treated surgically. A 17-item standardized interpretation guide was created. Intraobserver reproducibility was assessed by comparing the interpretations of five surgeons at two different times 3 weeks apart. Interobserver reproducibility was evaluated by comparing the results of the interpretations of 40 MRIs performed by three pairs of surgeons. The relevance of the MRI interpretations was determined by comparing the results of the surgeons to those of a radiologist and with the data from the surgical reports. The overall intraobserver and interobserver agreement was low. Comparing the surgeon's results with the radiologist's results and the surgical data, the agreement was low. After multiple-ligament injuries and dislocations of the knee, a precise diagnosis is necessary. This study provides an isolated demonstration of the lack of precision and reproducibility of MRI interpretations for the diagnosis of the lesion's topography. MRI should be integrated into a complete assessment with a precise clinical exam and stress X-rays. Level IV, prospective case-control study.