Nursing home report card and performance gap.
With the aging of our society, concerns about the quality of nursing homes have been increasing. The Nursing Home Compare (NHC) report card is believed to reduce information asymmetry between the facility and potential residents and, consequently, improve nursing home quality. However, there is limited evidence about how nursing homes use this publicly disseminated performance information. The aim of this study was to analyze the performance gap between nursing home administrators' self-assessment and the NHC report card performance ratings and explore the factors contributing to the gap. All 515 Medicare- and Medicaid-certified nursing homes in Indiana were surveyed between August and December 2013. The response rate was approximately 45%. The survey data were compared with the NHC data to identify the gap. Ordered logistic regression analysis was conducted. Despite voluntary participation, a reasonably high response rate, and anonymity, this study found that 62% of respondents either under- or overrated their facilities' performance, with the majority overrating their performance. The following factors were associated with a smaller performance gap: nonprofit or government-owned status, higher staffing levels, a higher percentage of hours worked by registered nurses, and a higher market concentration. Longer work experience and greater county occupancy rates were associated with a larger performance gap. The significant gap implies that administrators either do not regularly review the NHC report card or do not concur with the NHC ratings. To reduce the gap and thereby improve performance, it is necessary to stabilize the administrators' position so that administrators know how they stand in the market and are consequently better equipped to successfully respond to the market. Facilities may also need to provide regular training on current technologies and facilitate use of the NHC report card, targeting administrators who are old and have many years of work experience.


Ischaemia-induced changes in canine cardiac sarcoplasmic reticulum.
Effects of myocardial ischaemia on sarcoplasmic reticulum (SR) of dog hearts were investigated. Regional ischaemia was produced by occlusion of the left circumflex artery, and a microsomal fraction enriched in vesicles of SR was isolated from subendocardium (Endo) and subepicardium (Epi) of control and ischaemic areas of the heart. No significant changes occurred in ischaemic Epi. A loss of in vitro activities (ie calcium transport and ATPase) was found for SR from ischaemic Endo which paralleled the changes in the histology of the tissue. At 5 min of coronary occlusion, Ca2+ binding and Ca2+-ATPase activities of SR from ischaemic Endo were normal. A decrease in the activities of SR was first evident at 15 min after the occlusion, decreased further at about 30 min and remained at that level at 60 min of ischaemia. The maximal rate of Ca2+ uptake did not parallel the Ca2+-binding and Ca2+-ATPase activities. The degree of cAMP-dependent phosphorylation by endogenous and exogenous protein kinase was not different between SR from control and ischaemic areas. A participatory role of SR in the ischaemic impairment of left ventricular systolic and diastolic performance is discussed.


Analysis of the negative complementation of abruptex alleles in gynandromorphs of Drosophila melanogaster.
Certain Abruptex alleles in the Notch pseudoallelic series of Drosophila melanogaster show strong negative complementation. Heterozygous combinations of some viable alleles are lethal. As a lethal system this is unique. Analysis of this type of allelic interaction in gynandromorphs suggests that the lethal focus has a fate-map site in the anterior part of the fly, probably close to the central part of the thorax. In addition to the lethal effect, negative interaction of the alleles can also be seen in the morphological level, the negative interaction of the alleles can also be seen in the morphogenesis of wings and chaetae of thorax and head. At this morphological level, the negative interaction of the alleles appears to be autonomous.


Caspase-2-mediated cleavage of Mdm2 creates a p53-induced positive feedback loop.
Caspase-2 is an evolutionarily conserved caspase, yet its biological function and cleavage targets are poorly understood. Caspase-2 is activated by the p53 target gene product PIDD (also known as LRDD) in a complex called the Caspase-2-PIDDosome. We show that PIDD expression promotes growth arrest and chemotherapy resistance by a mechanism that depends on Caspase-2 and wild-type p53. PIDD-induced Caspase-2 directly cleaves the E3 ubiquitin ligase Mdm2 at Asp 367, leading to loss of the C-terminal RING domain responsible for p53 ubiquitination. As a consequence, N-terminally truncated Mdm2 binds p53 and promotes its stability. Upon DNA damage, p53 induction of the Caspase-2-PIDDosome creates a positive feedback loop that inhibits Mdm2 and reinforces p53 stability and activity, contributing to cell survival and drug resistance. These data establish Mdm2 as a cleavage target of Caspase-2 and provide insight into a mechanism of Mdm2 inhibition that impacts p53 dynamics upon genotoxic stress.


Investigating error-related processing in incarcerated adolescents with self-report psychopathy measures.
Disparate results have been found in previous reports when incorporating both interview-based and self-report measures of psychopathic traits within the same sample, suggesting such assessments should not be used interchangeably. We previously found Total and Facet 4 scores from Hare's Psychopathy Checklist: Youth Version (PCL:YV) were negatively related to amplitude of the error-related positivity (Pe) event-related potential (ERP) component. Here, we investigated using the same previously published sample whether scores on four different self-report measures of adolescent psychopathic traits (the Antisocial Process Screening Device [APSD], Child Psychopathy Scale [CPS], Inventory of Callous-Unemotional Traits [ICU], and Youth Psychopathic Traits Inventory [YPI]) were similarly associated with reduced Pe amplitude. Unlike our previous results, adolescent self-report psychopathy scores were not associated with reduced Pe amplitude in multiple regression analyses. Results obtained in the current report support previous research observing incongruent findings when incorporating different assessment types within the same sample.


The actions of amphetamine on neurotransmitters: a brief review.
The central stimulant actions of d-amphetamine are not altered in animals in which brain stores of catecholamines have been depleted with reserpine, but they are blocked by alpha-methyltyrosine, which inhibits catecholamine synthesis. The results of a variety of experiments suggest that the central actions of amphetamine result primarily from the ability of the drug to facilitate the release of newly synthesized dopamine from nerve terminals in the forebrain. The results of experiments in animals in which dopaminergic nerve terminals in various brain regions have been selectively destroyed by intracranial microinjection of 6-hydroxydopamine reveal that the locomotor stimulant actions of relatively low doses of amphetamine are dependent upon mesolimbic dopaminergic neurons, whereas the stereotyped behaviors induced by relatively larger doses of amphetamine are dependent upon nigrostriatal dopaminergic neurons. The central actions of amphetamine appear to be the primary result of interactions with dopamine neurons, but secondarily the drug also alters the dynamics of other putative neurotransmitters (e.g. acetylcholine, 5-hydroxytryptamine) in the brain.


Breast Implant-Associated Anaplastic Large Cell Lymphoma.
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently recognised malignancy of T lymphocytes exclusively associated with textured breast implants. This review aims to evaluate existing theories regarding the epidemiology, pathogenesis, clinical evaluation and management of the disease. The true incidence of BIA-ALCL is difficult to define. Prevailing pathogenic theories recognise the interplay between textured implants, Gram-negative bacteria, host genetics (e.g. JAK/STAT, p53) and time. Patients typically present with a delayed seroma and less commonly with a capsular mass or systemic disease at an average of 8-10 years after implantation. BIA-ALCL staging has evolved from a "liquid tumour" model to a "solid tumour" classification. For localised disease, surgery involving complete capsulectomy and implant removal is the cornerstone of treatment. For more advanced disease, treatment includes surgery followed by chemotherapy (combination anthracycline-based), radiotherapy and the antibody drug conjugate (brentuximab vedotin). The interplay between the Gram-negative biofilm, implant texturing, genetic mutations and time has been implicated in pathogenesis of BIA-ALCL. The identification of a putative infectious cause is not unique to lymphomagenesis. Future research, investigating BIA-ALCL genetic mutations and immunological modulation with Gram-negative biofilm in BIA-ALCL models is warranted.


Self-docking and cross-docking simulations of G protein-coupled receptor-ligand complexes: Impact of ligand type and receptor activation state.
G protein-coupled receptors (GPCR) are the largest family of cell surface receptors in vertebrates. Their abundance and role in nearly all physiological systems make GPCR the largest protein family targeted for development of pharmaceuticals. Ligand discovery aimed at identification of chemical tools and drug leads is aided by molecular docking simulations that allow critical analysis of the potential interactions between small molecules and proteins in resulting complexes. However, blind assessments of ligand pose quality and affinity prediction have thus far not provided broadly generalizable performance expectations for docking into experimentally-characterized GPCR targets. Likewise, the relative importance of receptor activation state and ligand function differences have also not been systematically assessed. This study compares performance when docking ligands of varied function into varied GPCR activation states in the absence of extensive resampling of the input GPCR structure, and only limited sidechain flexibility after ligand placement. Simulations were performed using 37 experimental structures of 11 Class A GPCR crystallized in multiple activation states (giving rise to 37 self-docking and 68 cross docking simulations). Our results show that one specific subset of cross-docking simulations gave results of similar quality to self-docking. Median ligand RMSD values for top-scored poses were 1.2 Å and 2.0 Å for self-docking and StateMatch/FunctionMatch cross-docking, respectively. The distributions of ligand RMSD values were not statistically different for these two conditions, according to a Kolmogorov-Smirnov test. Therefore, docking performance against GPCR targets can be estimated in advance based on docking target structure activation states, with higher accuracy expected when docking agonists into active state structures and inverse agonists or antagonists into inactive state structures. Receptor conformational sampling in advance of docking or receptor conformational adjustment after docking are more likely to produce substantial improvements for other pairings of receptor activation state and ligand function.


Population with an increased risk of severe COVID-19 in Germany. Analyses from GEDA 2019/2020-EHIS.
Only a minority of people who test positive for COVID-19 develop a severe or critical form of the disease. Many of these have risk factors such as old age or pre-existing conditions and, therefore, are at the focus of protective measures. This article determines the number of people at risk in Germany and differentiates them according to age, sex, education, household type and federal state. The analyses presented here are based on data from the German Health Update (GEDA) 2019/2020-EHIS, which was carried out as a nationwide cross-sectional telephone-based survey between April 2019 and October 2020. The definition of being at increased risk of severe COVID-19 is primarily based on a respondent's age and the presence of pre-existing conditions. Around 36.5 million people in Germany are at an increased risk of developing severe COVID-19. Of these, 21.6 million belong to the high-risk group. An above-average number of people at risk live alone. The prevalence of an increased risk is higher among middle-aged men than among women of the same age, and significantly higher among people with a low level of education than among people with a high level of education. The highest proportion of people with an increased risk live in Saarland and in the eastern German federal states. When fighting the pandemic, it is important to account for the fact that more than half of the population aged 15 or over is at increased risk of severe illness. Moreover, the regional differences in risk burden should be taken into account when planning interventions.


Redescription of the type species of the genus Cypretta (Ostracoda, Crustacea), with notes on the taxonomy of the genus.
With 53 formally described species, the genus Cypretta is one of the most common freshwater ostracod genera in the world. It has a mainly circumtropical distribution. The type species, Cypretta tenuicauda (Vávra, 1895), was described from Zanzibar (Africa) in a superficial way. Therefore, the morphology and identity of this species and of the genus remained problematic until today. Here, we redescribe Cypretta tenuicauda from the original type material and discuss the morphology of the species and the diagnosis of the genus. The species is characterized by the presence of anterior marginal septa in both valves, the sub-triangular carapace shape in lateral view, the right valve overlapping the left valve, the generally wide carapace and the presence of a serrated posteroventral inner list in the right valve. In addition, both α and β setae on the mandibular palp are long and thin, claws Ga and Gp on the caudal ramus are elongated and seta-like, while the caudal ramus itself is equally slender. The caudal ramus attachment is reduced to a simple branch. The present redescription of the type species will assist in creating order in what is now a taxonomically confused genus.


Integrating flood depth and plant resistance with chlorantraniliprole seed treatments for management of rice water weevil, Lissorhoptrus oryzophilus (Coleoptera: Curculionidae).
Chlorantraniliprole seed treatments in rice provide effective suppression of rice water weevil populations in the United States; however, heavy reliance on prophylactic insecticide treatments as a sole strategy could destabilize management programs for this insect. The present research evaluated the compatibility of seed treatments with two other potential management tactics-plant resistance and shallow flooding-by conducting two split-plot experiments in 2009 and 2011. In both experiments, no substantial antagonism was found among the 3 different tactics. Statistical interactions in these experiments arose from the strong and persistent effects of chlorantraniliprole on larval densities rather than incompatibility of tactics. In 2009, weevil densities differed among varieties and were significantly lower on the cultivar "Jefferson." In 2011, weevil densities were reduced significantly in shallow-flooded plots compared to deep-flooded plots. Significant reductions in weevil numbers by chlorantraniliprole seed treatments, even at application rates 5 fold lower than commercially recommended rates, demonstrated the potential to reduce application rates of this highly potent larvicide. These latter results suggest that future studies on the relationship between chlorantraniliprole seed treatment rate and weevil fitness are warranted.


Operative versus nonoperative care of displaced midshaft clavicular fractures: a meta-analysis of randomized clinical trials.
Recent studies have suggested benefits following primary operative fixation of substantially displaced midshaft fractures of the clavicle. We reviewed randomized clinical trials of operative versus nonoperative treatment of these fractures, and pooled the functional outcome and complication rates to arrive at summary estimates of these outcomes. A systematic review of the literature was performed to identify studies of randomized clinical trials comparing operative versus nonoperative care for displaced midshaft clavicular fractures. Six studies (n = 412 patients, mean Detsky score = 15.3) were included. The nonunion rate was higher in the nonoperatively treated patients (twenty-nine of 200) than it was in patients treated operatively (three of 212) (p = 0.001). The rate of symptomatic malunion was higher in the nonoperative group (seventeen of 200) than it was in the operative group (0 of 212) (p < 0.001). Operative treatment provided a significantly lower rate of nonunion and symptomatic malunion and an earlier functional return compared with nonoperative treatment. However, there is little evidence at present to show that the long-term functional outcome of operative intervention is significantly superior to nonoperative care.


Effect of rate or rhythm control on quality of life in persistent atrial fibrillation. Results from the Rate Control Versus Electrical Cardioversion (RACE) Study.
We studied the influence of rate control or rhythm control in patients with persistent atrial fibrillation (AF) on quality of life (QoL). Atrial fibrillation may cause symptoms like fatigue and dyspnea. This can impair QoL. Treatment of AF with either rate or rhythm control may influence QoL. Quality of life was assessed in patients included in the Rate Control Versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) study (rate vs. rhythm control in persistent AF). Rate control patients (n = 175) were given negative chronotropic drugs and oral anticoagulation. Rhythm control patients (n = 177) received serial electrocardioversion, antiarrhythmic drugs, and oral anticoagulation, as needed. Quality of life was studied using the Short Form (SF)-36 health survey questionnaire at baseline, one year, and the end of the study (after 2 to 3 years of follow-up). At baseline, QoL was compared with that of healthy control subjects. Patient characteristics related to QoL changes were determined. Mean follow-up was 2.3 years. At baseline, QoL was lower in patients than in age-matched healthy controls. At study end, under rate control, three subscales of the SF-36 improved. Under rhythm control, no significant changes occurred compared with baseline. At study end, QoL was comparable between both groups. The presence of complaints of AF at baseline, a short duration of AF, and the presence of sinus rhythm (SR) at the end of follow-up, rather than the assigned strategy, were associated with QoL improvement. Quality of life is impaired in patients with AF compared with healthy controls. Treatment strategy does not affect QoL. Patients with complaints related to AF, however, may benefit from rhythm control if SR can be maintained.


Does 5HTTLPR Genotype Moderate the Association of Family Environment With Child Attention-Deficit Hyperactivity Disorder Symptomatology?
Problematic family dynamics are common among youth with attention-deficit hyperactivity disorder (ADHD). Multiple mechanisms, including diathesis-stress (vulnerability) and differential susceptibility Gene × Environment interaction effects (G × E), have been proposed to account for this association. G × E effects for ADHD were examined via interactions between a genetic marker hypothesized to influence sensitivity to the environment (the promoter polymorphism of the serotonin transporter gene -5HTTLPR) and family conflict and cohesion in predicting ADHD symptoms. There were 498 youth ages 6-17 years (251 ADHD, 213 non-ADHD) and their parents who completed a multistage, multi-informant assessment (including parent and youth reports on the Family Environment Scale), and saliva sample collection for genotyping. Linear regression analyses examined interactions between 5HTTLPR genotype and the Family Environment Scale scales of conflict and cohesion reported by parent and child. Criteria laid out by Roisman et al. ( 2012 ) were applied to evaluate diathesis stress versus differential susceptibility G × E mechanisms. Results demonstrated interactions between 5HTTLPR genotype and both conflict and cohesion in predicting inattention but not hyperactivity-impulsivity. Both interactions were highly consistent with differential susceptibility models of G × E effects. 5HTTLPR genotype appeared to moderate the relationship between family conflict/cohesion and inattentive symptoms. Interactions highlight the role of 5HTTLPR genotype as a potential marker of environmental sensitivity and provide support for differential susceptibility models of G × E effects for ADHD.


The evolution of division of labour in structured and unstructured groups.
Recent theory has overturned the assumption that accelerating returns from individual specialisation are required to favour the evolution of division of labour. Yanni et al., 2020, showed that topologically constrained groups, where cells cooperate with only direct neighbours such as for filaments or branching growths, can evolve a reproductive division of labour even with diminishing returns from individual specialisation. We develop a conceptual framework and specific models to investigate the factors that can favour the initial evolution of reproductive division of labour. We find that selection for division of labour in topologically constrained groups: (1) is not a single mechanism to favour division of labour-depending upon details of the group structure, division of labour can be favoured for different reasons; (2) always involves an efficiency benefit at the level of group fitness; and (3) requires a mechanism of coordination to determine which individuals perform which tasks. Given that such coordination must evolve prior to or concurrently with division of labour, this could limit the extent to which topological constraints favoured the initial evolution of division of labour. We conclude by suggesting experimental designs that could determine why division of labour is favoured in the natural world.


NRG/RTOG 0837: Randomized, phase II, double-blind, placebo-controlled trial of chemoradiation with or without cediranib in newly diagnosed glioblastoma.
A randomized, phase II, placebo-controlled, and blinded clinical trial (NCT01062425) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, versus placebo in combination with radiation and temozolomide in newly diagnosed glioblastoma. Patients with newly diagnosed glioblastoma were randomly assigned 2:1 to receive (1) cediranib (20 mg) in combination with radiation and temozolomide; (2) placebo in combination with radiation and temozolomide. The primary endpoint was 6-month progression-free survival (PFS) based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted MRI brain scans and was tested using a 1-sided Z test for 2 proportions. Adverse events (AEs) were evaluated per CTCAE version 4. One hundred and fifty-eight patients were randomized, out of which 9 were ineligible and 12 were not evaluable for the primary endpoint, leaving 137 eligible and evaluable. 6-month PFS was 46.6% in the cediranib arm versus 24.5% in the placebo arm (P = .005). There was no significant difference in overall survival between the 2 arms. There was more grade ≥ 3 AEs in the cediranib arm than in the placebo arm (P = .02). This study met its primary endpoint of prolongation of 6-month PFS with cediranib in combination with radiation and temozolomide versus placebo in combination with radiation and temozolomide. There was no difference in overall survival between the 2 arms.


Detection of disseminated tumor cells: strategies and diagnostic implications.
Disseminated cells from primary solid tumors are considered to be the cause of metastases formation and relapse of disease. Consequently, their detection is of high importance for staging, prognosis and decisions about adjuvant therapy. Residual disease is conventionally detected by histological evaluation of biopsy specimens. Continuing efforts to increase the sensitivity to identify occult tumor cells in lymph node, bone marrow and blood have led to the development of various strategies. This review will discuss histological, immunological and molecular approaches to detect micrometastases from solid tumors.


Experimental microsurgery of salivary ducts in dogs.
The results achieved by experimental microsurgical suturing of salivary ducts in dogs are presented. Nine partial lesions and one complete transection of the ducts were made on parotid and submandibular ducts. Four to seven interrupted microsutures were used for each lesion. The operations were successful in seven out of 10 cases, as observed by sialography. Histologically, granulation tissue compressing the ducts was observed after suturing the lesions. Four venous graft transplantations were performed and none were successful. After venous graft transplantation, the transplant was not apparent histologically, raising doubt as to the potential success of this technique. The use of stenting is discussed based on a summary of the published literature. Those reports indicate that long-term stenting can benefit the outcome of salivary duct repair. The use of dogs as a model for experimental salivary duct operations has been shown to be valuable in assessing various surgical techniques.


[Absorption routes of stearic acid and leucine in the small intestine of the rat after gamma irradiation].
The aim of the investigation was to study transport of 3H-stearic acid in ultrastructural compartments of epitheliocytes during absorbtion, resynthesis and translocation of lipids having the form of chylomicrons after a local large fractionated gamma-irradiation of the rat small intestine with a total dose of 35 Gr. In the anesthesized animals the ligated fragments of the jejunum, which kept their blood supply and innervation, were separated, fatty emulsion with 3H-stearic acid (a label) was administered into their lumen. Intensity of the label incorporation was quantitatively estimated in the electron microscopic autographs every 2, 5, 10 and 20 min after the isotope administration. Time distribution of the label concentration after irradiation characterized the sequence of the transport stages of 3H-stearic acid across microvilli and the terminal reticulum (MV + TR) triglycerides resynthesis in the agranular and granular endoplasmic reticulum (AER, GER), chylomicrons formation in Golgi complex (GC), as well as their exudation into the lacunar intercellular space (LIS), basal membrane and capillaries. Transport deceleration of the label at the level MV + TR and decreasing synthesis of triglycerides in GER was accompanied with a delay in the chylomicrons formation in the GC and their excretion into the LIS. Conglomerates of the aggregated chylomicrons were formed in the LIS. The radioautographic data on 3H-leucine incorporation characterized a decreased activity of the protein-synthesizing system of epitheliocytes.


Synovial sarcoma. An immunohistochemical study of the epithelial component.
Twenty-five synovial sarcomas were studied with a battery of antibodies directed against keratin and epithelial membrane antigen (EMA). The keratin antibody MNF 116 showed reactivity in 24 tumors. In addition, 22 tumors showed reactivity with the antibody Keratin Wide Spectrum, 20 with the antibody Keratin 56, 64, and 19 with CAM 5.2. Seventeen tumors showed reactivity with EMA. The keratin and EMA reactivity was present in cells lining obvious cleft-like structures in biphasic tumors. In the spindle cell areas of both biphasic and monophasic fibrous tumors, we found clusters of a few reacting cells apparently located around small clefts. In the synovioblastic tumors, clusters of plump tumor cells reactive for both the keratins and EMA were present. In conclusion, we found that proper identification of epithelial differentiation in synovial sarcomas is facilitated by an immunohistochemical application of anti-epithelial antibodies. In most tumors, there was immunoreactivity for the same type of keratins as are normally identified in simple epithelia (the antibody CAM 5.2), but also for those found in stratified squamous epithelia (the antibody Keratin 56, 64). The results indicate that screening for epithelial features on paraffin sections in the various types of synovial sarcoma, even the poorly differentiated synovioblastic tumors, is improved if epithelial antibodies with a broad spectrum of reactivity are chosen.


[Determination of the fibrinolytic activity of renal tissue in children].
A method for the determination of the fibrinolytic activity of renal tissue obtained by puncture biopsy is suggested. Three cryostate sections are placed on slides, covered by a film of a mixture of bovine fibrinogen and thrombine in saline (in the control section plasminogen activator is pre-destroyed), placed in a thermostate at 37 degrees C for 24 hours, stained with Ehrlich hematoxylin and embedded in glycerol-gelatine. The fibrinolytic activity is evaluated by calculating the ratio expressing the ratio between the lysis surface and the surface of the kidney cortex section. The advantage of the method lies in the technical simplicity combined with the objective evaluation of the results.


Psychosocial predictors of body image dissatisfaction in patients referred for NHS aesthetic surgery.
A limited number of studies have researched psychosocial predictors of body image dissatisfaction exclusively within the National Health Service (NHS) aesthetic surgery patient populations, despite aesthetic surgery being offered on an exceptional basis. The Adult Exceptional Aesthetic Referral Protocol (AEARP) defines criteria for aesthetic surgery under the NHS in Scotland. The protocol requires psychological assessment prior to surgery for the majority of aesthetic surgery procedures offered. It is therefore important to establish psychological predictors of body image dissatisfaction to aid with assessment and provision of psychological therapy for this patient group. 334 consecutive potential aesthetic surgery patients referred for psychological assessment under the AEARP completed psychosocial self-report assessment measures as part of routine practice. Multiple regression analysis using the forced entry method was used to investigate psychosocial predictors of body image dissatisfaction. Multiple regression analysis indicated that younger age, greater symptoms of depression, lower levels of self-esteem and greater interpersonal sensitivity significantly predicted higher levels of self-reported body image dissatisfaction. Symptoms of anxiety did not significantly predict body image dissatisfaction. This study indicates that both self perception and perception of self in relation to others, especially fear of being judged by others, significantly relates to body image dissatisfaction in this patient group. Psychological assessment of patients' suitability for aesthetic surgery should consider factors such as the patients' interpersonal functioning. Psychological intervention targeted at symptoms of depression, difficulties with self-esteem and interpersonal functioning may be of significant benefit to patients either prior to undergoing surgery or as an alternative to aesthetic surgery.


Transposition in Shigella dysenteriae: isolation and analysis of IS911, a new member of the IS3 group of insertion sequences.
Twenty-nine clear-plaque mutants of bacteriophage lambda were isolated from a Shigella dysenteriae lysogen. Three were associated with insertions in the cI gene: two were due to insertion of IS600, and the third resulted from insertion of a new element, IS911. IS911 is 1,250 base pairs (bp) long, carries 27-bp imperfect terminal inverted repeats, and generates 3-bp duplications of the target DNA on insertion. It was found in various copy numbers in all four species of Shigella tested and in Escherichia coli K-12 but not in E. coli W. Analysis of IS911-mediated cointegrate molecules indicated that the majority were generated without duplication of IS911. They appeared to result from direct insertion via one end of the element and the neighboring region of DNA, which resembles a terminal inverted repeat of IS911. Nucleotide sequence analysis revealed that IS911 carries two consecutive open reading frames which code for potential proteins showing similarities to those of the IS3 group of elements.


Topical application of a Chinese medicine, Qingpeng ointment, ameliorates 2, 4-dinitrofluorobenzene-induced allergic contact dermatitis in BALB/c mice.
Qingpeng ointment (QP) is a traditional Chinese medicine which has been used for treatment of eczema in China. However, the mechanisms of its anti-inflammatory activities are not known. To assess the anti-inflammatory effects of QP using a mouse model of allergic contact dermatitis, compare the effects with mometasone furoate cream (MF), and to relate the effects to modulation of inflammatory cytokines. Persistent dermatitis was induced in BALB/c mice using dinitrofluorobenzene. Topical treatment, including the vehicle of QP, 50%, 75%, 100% QP in vehicle, and MF was applied for 14 days. Dermatitis was evaluated macroscopically and microscopically at day 8 and day 15 after treatment. The levels of IL1B, IL2, TNFA, IFNG in both sera and skin tissue were detected with Enzyme-Linked Immunosorbent Assay (ELISA). Significant reductions of skin inflammation in mice skin were observed after treatment with QP and MF, but not with the vehicle of QP. Similar to MF, QP also suppressed the expression of IL1B, IL2, TNFA and IFNG. This study demonstrates that QP inhibits allergic contact dermatitis in mice, similar to MF. QP suppresses the expression of Th1 cytokines in both sera and skin tissue, by which it may exert its anti-inflammatory effects.


Removal of estrogenic activity and formation of oxidation products during ozonation of 17alpha-ethinylestradiol.
This study investigated the oxidation of the oral contraceptive 17alpha-ethinylestradiol (EE2) during ozonation. First, the effect of ozone (O3) on the estrogenic activity of aqueous solutions of EE2 was studied using a yeast estrogen screen (YES). It could be shown that O3 doses typically applied for the disinfection of drinking waters were sufficient to reduce estrogenicity by a factor of more than 200. However, it proved impossible to completely remove estrogenic activity due to the slow reappearance of 0.1-0.2% of the initial EE2 concentration after ozonation. Second, oxidation products formed during ozonation of EE2 were identified with LC-MS/MS and GC/MS and the help of the model compounds 5,6,7,8-tetrahydro-2-naphthol (THN) and 1-ethinyl-1-cyclohexanol (ECH), which represent the reactive phenolic moiety and the ethinyl group of EE2. Additionally, oxidation products of the natural steroid hormones 17beta-estradiol (E2) and estrone (E1) were identified. The chemical structures of the oxidation products were significantly altered as compared to the parent compounds, explaining the diminished estrogenic activity after ozonation. Overall,the results demonstrate that ozonation is a promising tool for the control of EE2, E2, and E1 in drinking water and wastewater.


Aberrant E-cadherin, β-catenin, and glial fibrillary acidic protein (GFAP) expression in canine choroid plexus tumors.
Expression of E-cadherin and β-catenin has been widely studied in various human and canine epithelial tumors and has been correlated with dedifferentiation, invasiveness, and metastasis. Choroid plexus tumors (CPTs) are of epithelial origin, and the most important prognostic factor in human medicine is the tumor grade. Limited information is available regarding E-cadherin and β-catenin expression in human CPTs, and no information is found in the veterinary literature. In the current study, 42 canine CPTs (19 choroid plexus papillomas and 23 choroid plexus carcinomas) were retrospectively reviewed, and the intensity and cellular staining pattern of E-cadherin and β-catenin were correlated with histological features, paying special attention to grade, invasion, and metastasis. In addition, cytokeratin and glial fibrillary acidic protein (GFAP) antibodies were evaluated as markers for canine CPTs. It was found that loss of E-cadherin and β-catenin expression was uncommon in canine CPTs. Rather, membranous expression of both molecules was increased in CPTs compared to normal choroid plexus (NCP), regardless of tumor grade. Additionally, aberrant cytoplasmic or nuclear expression of both E-cadherin and β-catenin was often observed in CPTs. GFAP was frequently expressed in CPTs in contrast to NCP. None of these parameters were correlated with malignancy, and therefore, do not appear to be useful for prognostic information. Nevertheless, a panel of antibodies including E-cadherin and GFAP might be useful to support the diagnosis of CPTs and help to differentiate them from other tumors, such as ependymomas and metastatic epithelial tumors.


Shoot circumnutation and winding movements require gravisensing cells.
Circumnutation and winding in plants are universal growth movements that allow plants to survive despite their sessile nature. However, the detailed molecular mechanisms controlling these phenomena remain unclear. We previously found that a gravitropic mutant of Japanese morning glory (Pharbitis nil or Ipomoea nil), Shidare-asagao (weeping), is defective not only in circumnutation but also in the winding response. This phenotype is similar to that of the Arabidopsis SCARECROW (SCR) mutant. We therefore investigated whether morning glory SCR (PnSCR) is involved in the weeping phenotype. We found that one amino acid was inserted into the highly conserved VHIID motif in weeping-type PnSCR; this mutation caused abnormal endodermal differentiation. We introduced either the mutant or WT PnSCR into Arabidopsis scr mutants for complementation tests. PnSCR of the WT, but not of weeping, rescued the shoot gravitropism and circumnutation of scr. These results show that both the abnormal gravitropism and the circumnutation defect in weeping are attributable to a loss of PnSCR function. Thus, our data show that gravisensing endodermal cells are indispensable for shoot circumnutation and the winding response and that PnSCR is responsible for the abnormal phenotypes of weeping.


Sildenafil citrate for erectile dysfunction in patients with multiple sclerosis.
Erectile dysfunction (ED) is a common sexual disease in male patients with multiple sclerosis (MS). Sildenafil citrate is considered as an effective drug in the treatment of male ED in the general population, but it has not been systematically reviewed in patients with MS. To assess the efficacy and safety of sildenafil citrate for ED in patients with MS. We searched the Cochrane (November 2011), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4 of 4, 2011), MEDLINE (PubMed) (January 1966 to November 2011), EMBASE (January 1974 to November 2011) and the China Biological Medicine Database (CBM) (1979 to November 2011). We searched trials registers and conference proceedings and contacted pharmaceutical company and authors of included studies for additional data. There were no language restrictions. Randomised controlled trials comparing sildenafil citrate with placebo or no treatment for ED in patients with MS. Two review authors independently selected articles for inclusion, extracted data and assessed trial quality. Disagreements were resolved by discussion between review authors. Authors of included studies were contacted for additional information. Results were presented as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI). Two randomised controlled trials involving a total of 420 patients were identified. Both trials investigated the short-term efficacy and safety of sildenafil citrate for ED in patients with MS. Patients taking sildenafil citrate were more likely to improve their ability to achieve and maintain an erection measured by International Index of Erectile Function and achieve vaginal penetration ( (RR 1.28, 95%CI 0.92 to 1.78) and complete intercourse measured by Sexual Encounter Profile diary (RR RR 1.38, 95%CI 1.00 to 1.90). and receive A global well respond measured by Global Assessment Question (RR 2.72, 95%CI 1.40 to 5.28) was reported. One trial showed sildenafil citrate is effective in quality of life improvement, while the other trial did not find any significant difference between both groups. Both included trials were judged as high risk of attrition bias. Adverse events were also reported: the most common were headache, flushing, rhinitis, visual disturbances and dyspepsia. Two patients suffered serious adverse events: one with coronary artery disease requiring triple bypass surgery and one with a cerebrovascular accident. There is limited evidence to support sildenafil citrate as an effective treatment for ED in patients with MS. Future well designed randomised, double blinded, placebo-controlled trials with long-term duration are needed.


[Mechanism of the anabolic action of phytoecdisteroids in mammals].
In experiments with white mice it has been established that phytoecdisteroides turkesteron, ecdisteron and 2-desoxy-alpha-ecdison in the dose of 5 mg on 1 kg of body mass stimulate the protein synthesis. Using the model of protein synthesis from mice liver it has been shown that the action of phytoecdisteroides is connected with the rise of poliribosome functional activity and rate increase of protein macromolecules formation. Preliminary administration of actinomycin D does not prevent the effect of protein synthesis stimulation. It has been concluded that the anabolic effect of phytoecdisteroides in mammals organism is connected not with induction of RNA synthesis but with the acceleration of translocation processes.


Effect of biosolids-derived triclosan and triclocarban on the colonization of plant roots by arbuscular mycorrhizal fungi.
Arbuscular mycorrhizal fungi (AMF) form a symbiotic relationship with the majority of crop plants. AMF provide plants with nutrients (e.g., P), modulate the effect of metal and pathogen exposure, and increase tolerance to moisture stress. The benefits of AMF to plant growth make them important to the development of sustainable agriculture. The land application of biosolids is becoming an increasingly common practice in sustainable agriculture, as a source of nutrients. However, biosolids have been found to contain numerous pharmaceutical and personal care products including antimicrobial chemicals such as triclosan and triclocarban. The potential risks that these two compounds may pose to plant-AMF interactions are poorly understood. The current study investigated whether biosolids-derived triclosan and triclocarban affect the colonization of the roots of lettuce and corn plants by AMF. Plants were grown in soil amended with biosolids that contained increasing concentrations of triclosan (0 to 307 μg/g dw) or triclocarban (0 to 304 μg/g dw). A relationship between the concentration of triclosan or triclocarban and colonization of plants roots by AMF was not observed. The presence of biosolids did not have a significant (p>0.05) effect on percent colonization of corn roots but had a significant, positive effect (p<0.05) on lettuce roots. Biosolids-derived triclosan and triclocarban did not inhibit the colonization of crop plant roots by AMF.


Burnout and Turnover Intention Among Peer Providers and Other Providers of Mental Health Services in a Rural Two-County Area.
Peer providers in the mental health field, having their own lived experience with mental illness, use their personal experience to assist the consumers of their services. Given high burnout rates in the mental health field, there have been two prior investigations of burnout among peer providers. The present study extends those prior investigations to a sample of peer providers working in community mental health programs in a rural area of the United States. Consistent with the prior studies, there were no differences in burnout between peer providers and other providers employed by those programs, with particularly strong support for the null hypothesis regarding the emotional exhaustion component of burnout. There were also no differences in strength of turnover intentions. However, among the non-consumer providers emotional exhaustion was correlated with both types of turnover intention assessed in this study (intent to change job setting within the mental health field and intent to leave the mental health workforce), whereas among the peer providers emotional exhaustion was correlated only with intent to leave the mental health field. Workload dissatisfaction was the workplace variable most strongly associated with emotional exhaustion among both types of providers. Other moderately strong inverse predictors of emotional exhaustion among peer providers were workplace community and workplace control, and the correlation between emotional exhaustion and workplace control was significantly stronger among the peer providers than among the other providers.


Dental trauma and mouthguard awareness and use among contact and noncontact athletes in central India.
We investigated the associations of mouthguard awareness and use with the rate and type of orofacial trauma during sports activities among professional athletes. In this cross-sectional study of athletes aged 12 to 22 years who trained for participation in national and international competitions, data were collected by using a questionnaire and a clinical examination that included an index of dental injury. There were significant differences in mouthguard awareness and use and injury rates, i.e., athletes who did not wear mouthguards had more injuries. Traumatic injuries to teeth were significantly more frequent among contact athletes (15; 9%) than among noncontact athletes (4; 2.5%). Limited mouthguard awareness could be due to lack of information and education on dental injuries and their prevention.


The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds.
The purpose of this project report is to introduce the European "GOLIATH" project, a new research project which addresses one of the most urgent regulatory needs in the testing of endocrine-disrupting chemicals (EDCs), namely the lack of methods for testing EDCs that disrupt metabolism and metabolic functions. These chemicals collectively referred to as "metabolism disrupting compounds" (MDCs) are natural and anthropogenic chemicals that can promote metabolic changes that can ultimately result in obesity, diabetes, and/or fatty liver in humans. This project report introduces the main approaches of the project and provides a focused review of the evidence of metabolic disruption for selected EDCs. GOLIATH will generate the world's first integrated approach to testing and assessment (IATA) specifically tailored to MDCs. GOLIATH will focus on the main cellular targets of metabolic disruption-hepatocytes, pancreatic endocrine cells, myocytes and adipocytes-and using an adverse outcome pathway (AOP) framework will provide key information on MDC-related mode of action by incorporating multi-omic analyses and translating results from in silico, in vitro, and in vivo models and assays to adverse metabolic health outcomes in humans at real-life exposures. Given the importance of international acceptance of the developed test methods for regulatory use, GOLIATH will link with ongoing initiatives of the Organisation for Economic Development (OECD) for test method (pre-)validation, IATA, and AOP development.


Upscaled Synthesis Protocol for Phase-Pure, Colloidally Stable MXenes with Long Shelf Lives.
MXenes are electrically conductive 2D transition metal carbides/nitrides obtained by the etching of nanolaminated MAX phase compounds, followed by exfoliation to single- or few-layered nanosheets. The mainstream chemical etching processes have evolved from pure hydrofluoric acid (HF) etching into the innovative "minimally intensive layer delamination" (MILD) route. Despite their current popularity and remarkable application potential, the scalability of MILD-produced MXenes remains unproven, excluding MXenes from industrial applications. This work proposes a "next-generation MILD" (NGMILD) synthesis protocol for phase-pure, colloidally stable MXenes that withstand long periods of dry storage. NGMILD incorporates the synergistic effects of a secondary salt, a richer lithium (Li) environment, and iterative alcohol-based washing to achieve high-purity MXenes, while improving etching efficiency, intercalation, and shelf life. Moreover, NGMILD comprises a sulfuric acid (H2 SO4 ) post-treatment for the selective removal of the Li3 AlF6 impurity that commonly persists in MILD-produced MXenes. This work demonstrates the upscaled NGMILD synthesis of (50 g) phase-pure Ti3 C2 Tz MXene clays with high extraction yields (>22%) of supernatant dispersions. Finally, NGMILD-produced MXene clays dry-stored for six months under ambient conditions experience minimal degradation, while retaining excellent redispersibility. Overall, the NGMILD protocol is a leap forward toward the industrial production of MXenes and their subsequent market deployment.


Treatment of fractures of the condylar head with resorbable pins or titanium screws: an experimental study.
We aimed to compare in vivo the stability of fixation of condylar fractures in sheep using sonic bone welding and standard titanium screws. We assessed stability of the osteosynthesis and maintenance of the height of the mandibular ramus. Height decreased slightly in both groups compared with the opposite side. The volume of the condyle increased considerably in both groups mainly because callus had formed. The results showed no significant disadvantages for pin fixation compared with osteosynthesis using titanium screws.


Aortic isthmus Doppler velocimetry: role in assessment of preterm fetal growth restriction.
Intrauterine fetal growth restriction (IUGR) is an important pregnancy complication associated with significant adverse clinical outcome, stillbirth, perinatal morbidity and cerebral palsy. To date, no uniformly accepted management protocol of Doppler surveillance that reduces mortality and cognitive morbidity has emerged. Aortic isthmus (AoI) evaluation has been proposed as a potential monitoring tool for IUGR fetuses. In this review, the current knowledge of the relationship between AoI Doppler velocimetry and preterm fetal growth restriction is reviewed. Relevant technical aspects and reproducibility data are reviewed as we discuss AoI Doppler and its place within the existing repertoire of Doppler assessments in placental insufficiency. The AoI is a link between the right and left ventricles which perfuse the lower and upper body, respectively. The clinical use of AoI waveforms for monitoring fetal deterioration in IUGR has been limited, but preliminary work suggests that abnormal AoI impedance indices are an intermediate step between placental insufficiency-hypoxemia and cardiac decompensation. Further prospective studies correlating AoI indices with arterial and venous Doppler indices and perinatal outcome are required before encorporating this index into clinical practice.


Cardiogenic shock in pregnancy.
Cardiac disease complicates 1%-4% of pregnancies globally, with a predominance in low and middle-income countries (LMICs). Increasing maternal age, rates of obesity, cardiovascular comorbidities, pre-eclampsia and gestational diabetes all contribute to acquired cardiovascular disease in pregnancy. Additionally, improved survival in congenital heart disease (CHD) has led to increasing numbers of women with CHD undergoing pregnancy. Implementation of individualised care plans formulated through pre-conception counselling and based on national and international guidance have contributed to improved clinical outcomes. However, there remains a significant proportion of women of reproductive age with no apparent comorbidities or risk factors that develop heart disease during pregnancy, with no indication for pre-conception counselling. The most extreme manifestation of cardiac disease is cardiogenic shock (CS), where the primary cardiac pathology results in inadequate cardiac output and hypoperfusion, and is associated with significant mortality and morbidity. Key to management is early recognition, intervention to treat any potentially reversible underlying pathology and supportive measures, up to and including mechanical circulatory support (MCS). In this narrative review we discuss recent developments in the classification of CS, and how these may be adapted to improve outcomes of pregnant women with, or at risk of developing, this potentially lethal condition.


Associations Between Drinking and Cortical Thickness in Younger Adult Drinkers: Findings From the Human Connectome Project.
Previous neuroimaging studies examining relations between alcohol misuse and cortical thickness have revealed that increased drinking quantity and alcohol-related problems are associated with thinner cortex. Although conflicting regional effects are often observed, associations are generally localized to frontal regions (e.g., dorsolateral prefrontal cortex [DLPFC], inferior frontal gyrus [IFG], and anterior cingulate cortex). Inconsistent findings may be attributed to methodological differences, modest sample sizes, and limited consideration of sex differences. This study examined neuroanatomical correlates of drinking quantity and heavy episodic drinking in a large sample of younger adults (N = 706; Mage = 28.8; 51% female) using magnetic resonance imaging data from the Human Connectome Project. Exploratory analyses examined neuroanatomical correlates of executive function (flanker task) and working memory (list sorting). Hierarchical linear regression models (controlling for age, sex, education, income, smoking, drug use, twin status, and intracranial volume) revealed significant inverse associations between drinks in past week and frequency of heavy drinking and cortical thickness in a majority of regions examined. The largest effect sizes were found for frontal regions (DLPFC, IFG, and the precentral gyrus). Follow-up regression models revealed that the left DLPFC was uniquely associated with both drinking variables. Sex differences were also observed, with significant effects largely specific to men. This study adds to the understanding of brain correlates of alcohol use in a large, gender-balanced sample of younger adults. Although the cross-sectional methodology precludes causal inferences, these findings provide a foundation for rigorous hypothesis testing in future longitudinal investigations.


The role of compassion, suffering, and intrusive thoughts in dementia caregiver depression.
Exposure to suffering of a relative or friend increases the risk for psychological and physical morbidity. However, little is known about the mechanisms that account for this effect. We test a theoretical model that identifies intrusive thoughts as a mediator of the relation between perceived physical and psychological suffering of the care recipient and caregiver depression. We also assess the role of compassion as a moderator of the relation between perceived suffering and intrusive thoughts. Hispanic and African American caregivers (N = 108) of persons with dementia were assessed three times within a one-year period. Using multilevel modeling, we assessed the mediating role of intrusive thoughts in the relation between perceived physical and psychological suffering and CG depression, and we tested moderated mediation to assess the role of caregiver compassion in the relation between perceived suffering and intrusive thoughts. The effects of perceived physical suffering on depression were completely mediated through intrusive thoughts, and compassion moderated the relation between physical suffering and intrusive thoughts. Caregivers who had greater compassion reported more intrusive thoughts even when perceived physical suffering of the CR was low. For perceived psychological suffering, the effects of suffering on depression were partially mediated through intrusive thoughts. Understanding the role of intrusive thoughts and compassion in familial relationships provides new insights into mechanisms driving caregiver well-being and presents new opportunities for intervention.


NIPA1 polyalanine repeat expansions are associated with amyotrophic lateral sclerosis.
Mutations in NIPA1 cause Hereditary Spastic Paraplegia type 6, a neurodegenerative disease characterized by an (upper) motor neuron phenotype. Deletions of NIPA1 have been associated with a higher susceptibility to amyotrophic lateral sclerosis (ALS). The exact role of genetic variation in NIPA1 in ALS susceptibility and disease course is, however, not known. We sequenced the entire coding sequence of NIPA1 and genotyped a polyalanine repeat located in the first exon of NIPA1. A total of 2292 ALS patients and 2777 controls from three independent European populations were included. We identified two sequence variants that have a potentially damaging effect on NIPA1 protein function. Both variants were identified in ALS patients; no damaging variants were found in controls. Secondly, we found a significant effect of 'long' polyalanine repeat alleles on disease susceptibility: odds ratio = 1.71, P = 1.6 × 10(-4). Our analyses also revealed a significant effect of 'long' alleles on patient survival [hazard ratio (HR) = 1.60, P = 4.2 × 10(-4)] and on the age at onset of symptoms (HR = 1.37, P = 4.6 × 10(-3)). In patients carrying 'long' alleles, median survival was 3 months shorter than patients with 'normal' genotypes and onset of symptoms occurred 3.6 years earlier. Our data show that NIPA1 polyalanine repeat expansions are a common risk factor for ALS and modulate disease course.


Dialectical behavior therapy for Binge-Eating Disorder.
Binge-eating episodes have alternately been described as stemming from strict dieting behaviors driven by overvalued ideas of weight and shape, or as arising from problematic interpersonal experiences. A third way of conceptualizing an eating binge is as a maladaptive emotion-regulation strategy, suggesting that facilitating more adaptive and effective affect regulation capacities may be a useful treatment. Dialectical Behavior Therapy (DBT), a treatment aimed at increasing emotion regulation skill, is currently being adapted for use with a binge-eating disorder population. Assumptions underlying the treatment, methods in treatment delivery, and goals of the treatment package are discussed. A pilot study currently underway of group DBT therapy for individuals with Binge-Eating Disorder is described.


Predictive power of peer behavioral assessment for subsequent maladjustment in community samples of disruptive and nondisruptive children.
In a prospective, longitudinal study with community samples of disruptive and nondisruptive children, the predictive relations between peer-assessed dimensions of behavioral reputation in elementary school and teacher-rated behavioral adjustment and test scores of academic achievement were examined over a 4-year period. The Revised Class Play (RCP), a social role matching instrument completed by students about their classmates, was used to assess behavioral dimensions of children's peer reputation at baseline. Regression analyses showed that the RCP dimensions of aggressive-disruptive, sensitive-isolated, and social etiquette were the best predictors of later teacher-rated externalizing problems, internalizing problems, and subsequent adaptive skills respectively. Only IQ predicted later academic achievement. When IQ and disruptive/nondisruptive group status were added to each regression equation they further contributed as significant predictors. When parent and teacher ratings of behavior problems at baseline were entered jointly with RCP dimensions into regression equations, the peer dimensions further explained outcome variance. Additive effects of the RCP dimensions were found only for the externalizing problems outcome. Disruptive children with mild levels of aggressive behavior and high levels of sensitive-isolated behavior had less externalizing problems at outcome. A comparison of the difference between disruptive and nondisruptive groups in the relationship of baseline RCP scores to teacher outcomes showed no difference between groups, suggesting that the groups did not depart appreciably from their initial differences relative to each other over time.


AUCpreD: proteome-level protein disorder prediction by AUC-maximized deep convolutional neural fields.
Protein intrinsically disordered regions (IDRs) play an important role in many biological processes. Two key properties of IDRs are (i) the occurrence is proteome-wide and (ii) the ratio of disordered residues is about 6%, which makes it challenging to accurately predict IDRs. Most IDR prediction methods use sequence profile to improve accuracy, which prevents its application to proteome-wide prediction since it is time-consuming to generate sequence profiles. On the other hand, the methods without using sequence profile fare much worse than using sequence profile. This article formulates IDR prediction as a sequence labeling problem and employs a new machine learning method called Deep Convolutional Neural Fields (DeepCNF) to solve it. DeepCNF is an integration of deep convolutional neural networks (DCNN) and conditional random fields (CRF); it can model not only complex sequence-structure relationship in a hierarchical manner, but also correlation among adjacent residues. To deal with highly imbalanced order/disorder ratio, instead of training DeepCNF by widely used maximum-likelihood, we develop a novel approach to train it by maximizing area under the ROC curve (AUC), which is an unbiased measure for class-imbalanced data. Our experimental results show that our IDR prediction method AUCpreD outperforms existing popular disorder predictors. More importantly, AUCpreD works very well even without sequence profile, comparing favorably to or even outperforming many methods using sequence profile. Therefore, our method works for proteome-wide disorder prediction while yielding similar or better accuracy than the others. http://raptorx2.uchicago.edu/StructurePropertyPred/predict/ firstname.lastname@example.com, firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


Effect of electric fields on the director field and shape of nematic tactoids.
Tactoids are spindle-shaped droplets of a uniaxial nematic phase suspended in the coexisting isotropic phase. They are found in dispersions of a wide variety of elongated colloidal particles, including actin, fd virus, carbon nanotubes, vanadium peroxide, and chitin nanocrystals. Recent experiments on tactoids of chitin nanocrystals in water show that electric fields can very strongly elongate tactoids even though the dielectric properties of the coexisting isotropic and nematic phases differ only subtly. We develop a model for partially bipolar tactoids, where the degree of bipolarness of the director field is free to adjust to optimize the sum of the elastic, surface, and Coulomb energies of the system. By means of a combination of a scaling analysis and a numerical study, we investigate the elongation and director field's behavior of the tactoids as a function of their size, the strength of the electric field, the surface tension, anchoring strength, the elastic constants, and the electric susceptibility anisotropy. We find that tactoids cannot elongate significantly due to an external electric field, unless the director field is bipolar or quasibipolar and somehow frozen in the field-free configuration. Presuming that this is the case, we find reasonable agreement with experimental data.


How many nights are enough? The short-term stability of sleep parameters in elderly insomniacs and normal sleepers.
Temporal stability is an important fundamental quality when measuring sleep parameters, yet it has been infrequently assessed. Generalizability theory was used to estimate the short-term temporal stability of five variables commonly used to characterize insomnia: sleep onset latency, total sleep time, wake after sleep onset, time in bed, and sleep efficiency. Estimates were calculated for 32 elderly primary insomniacs and 32 elderly normal sleepers, both in the lab and at home, using both sleep logs and polysomnography (PSG). A week of recording using either PSG or sleep logs was typically sufficient to achieve adequate stability (defined as G coefficient of at least 0.80) with some notable exceptions: (a) when using log-derived measures with insomniacs, a 3-week average was necessary for wake after sleep onset and (b) more than a 2-week average was necessary for sleep onset latency. Because of the substantial commitment involved in the physiological recording of sleep, alternative forms of aggregation are considered with the intent of improving temporal stability.


The Design and Delivery of an Astrobiology Massive Open Online Class.
MOOCs, or massive open online classes have reached hundreds of millions of people around the world in the past decade with a model of free open access learning. They are an excellent vehicle for delivering science to lifelong learners. Building on experience in designing astronomy MOOCs for Udemy and Coursera, we have created an astrobiology MOOC for Coursera called "Astrobiology: Exploring Other Worlds" that launched in April 2019. As of early 2022, about 9000 people have started the course, and nearly 10% of those have completed it. The average user rating is 4.9 out of 5. The core content is 10 h of video lectures, divided into six modules, which cover the possibilities of life in the Solar System, the search for exoplanets, the concept of habitability, the definition of life and basics of biology, evolution of life on Earth, and the search for extraterrestrial intelligence. Pedagogy was designed around clear learning objectives and includes quizzes, writing assignments, and a final project that draws on all the concepts presented in the course where students design their own mission to characterize exoplanets. In this study, we describe the design, implementation, and subsequent success of our 2019 astrobiology MOOC.


Implications of built and social environments on the academic success among African American youth: testing Strong African American Families intervention effects on parental academic racial socialization.
Studies exploring widening academic disparities have highlighted the role of racialized school settings, which have given way to incidents of discrimination and unfair treatment for students of color, disproportionately affecting African American youth. Research also shows that family-based preventive interventions may avert negative outcomes for this population through the promotion of protective socialization practices. Consequently, the current study tests the efficacy of a culturally tailored preventive family-based program to foster induced changes in academic promotive parenting practices that prepare youth to advance academically by navigating negative race-related experiences in school settings. Data collected over four time periods from the Strong African American Families (SAAF) efficacy trial (Murry and Brody, 2004) with 667 African American families in rural Georgia were used for this study. Structural equation modeling analyses demonstrated that the SAAF program was associated with positive intervention induced changes in parental academic race-related socialization, which in turn, was indirectly associated with reduced school compromising behaviors through the enhancement of racial pride. While discrimination compromised academic success, our findings highlight the protective nature of racial pride in dissuading academic failure and school dropout through the promotion of academic success. This study confirms that a family-based prevention program holds promise to address academic disparities through the enhancement of parenting and youth protective processes that buffer youth from succumbing to racialized social environments such as schools. Implications for research, educational policy, and preventive interventions are discussed.


Chromosome-scale genomes provide new insights into subspecies divergence and evolutionary characteristics of the giant panda.
Extant giant pandas are divided into Sichuan and Qinling subspecies. The giant panda has many species-specific characteristics, including comparatively small organs for body size, small genitalia of male individuals, and low reproduction. Here, we report the most contiguous, high-quality chromosome-level genomes of two extant giant panda subspecies to date, with the first genome assembly of the Qinling subspecies. Compared with the previously assembled giant panda genomes based on short reads, our two assembled genomes increased contiguity over 200-fold at the contig level. Additional sequencing of 25 individuals dated the divergence of the Sichuan and Qinling subspecies into two distinct clusters from 10,000 to 12,000 years ago. Comparative genomic analyses identified the loss of regulatory elements in the dachshund family transcription factor 2 (DACH2) gene and specific changes in the synaptotagmin 6 (SYT6) gene, which may be responsible for the reduced fertility of the giant panda. Positive selection analysis between the two subspecies indicated that the reproduction-associated IQ motif containing D (IQCD) gene may at least partly explain the different reproduction rates of the two subspecies. Furthermore, several genes in the Hippo pathway exhibited signs of rapid evolution with giant panda-specific variants and divergent regulatory elements, which may contribute to the reduced inner organ sizes of the giant panda.


Characterization of the total and viable bacterial and fungal communities associated with the International Space Station surfaces.
The International Space Station (ISS) is a closed system inhabited by microorganisms originating from life support systems, cargo, and crew that are exposed to unique selective pressures such as microgravity. To date, mandatory microbial monitoring and observational studies of spacecraft and space stations have been conducted by traditional culture methods, although it is known that many microbes cannot be cultured with standard techniques. To fully appreciate the true number and diversity of microbes that survive in the ISS, molecular and culture-based methods were used to assess microbial communities on ISS surfaces. Samples were taken at eight pre-defined locations during three flight missions spanning 14 months and analyzed upon return to Earth. The cultivable bacterial and fungal population ranged from 104 to 109 CFU/m2 depending on location and consisted of various bacterial (Actinobacteria, Firmicutes, and Proteobacteria) and fungal (Ascomycota and Basidiomycota) phyla. Amplicon sequencing detected more bacterial phyla when compared to the culture-based analyses, but both methods identified similar numbers of fungal phyla. Changes in bacterial and fungal load (by culture and qPCR) were observed over time but not across locations. Bacterial community composition changed over time, but not across locations, while fungal community remained the same between samplings and locations. There were no significant differences in community composition and richness after propidium monoazide sample treatment, suggesting that the analyzed DNA was extracted from intact/viable organisms. Moreover, approximately 46% of intact/viable bacteria and 40% of intact/viable fungi could be cultured. The results reveal a diverse population of bacteria and fungi on ISS environmental surfaces that changed over time but remained similar between locations. The dominant organisms are associated with the human microbiome and may include opportunistic pathogens. This study provides the first comprehensive catalog of both total and intact/viable bacteria and fungi found on surfaces in closed space systems and can be used to help develop safety measures that meet NASA requirements for deep space human habitation. The results of this study can have significant impact on our understanding of other confined built environments on the Earth such as clean rooms used in the pharmaceutical and medical industries.


The effect of BMP9 on inflammation in the early stage of pulpitis.
Bone morphogenetic protein 9 (BMP9) tends to be associated with various inflammatory responses of diseases, but its relationship with pulpitis remains unknown. This study aimed to evaluate the effects and mechanisms of BMP9 in pulpitis. A rat model of pulpitis was used to evaluate the expression of BMP9, which was also analysed in Porphyromonas gingivalis lipopolysaccharide (Pg-LPS)-stimulated human dental pulp cells (hDPCs). The effects and mechanism of BMP9 on the regulation of inflammatory factors and matrix metalloproteinase-2 (MMP2) were evaluated using real-time quantitative PCR, western blotting, and immunocytofluorescence. Moreover, the migration ability of THP-1 monocyte-macrophages, treated with inflammatory supernate inhibited by BMP9, was previously tested by a transwell migration assay. Finally, a direct rat pulp capping model was used to evaluate in vivo the influence of the overexpression of BMP9 in pulpitis. The expression of BMP9 decreased after 24 h and increased after 3 and 7 d in rat pulpitis and inflammatory hDPCs. The overexpression of BMP9 inhibited the gene expression of inflammatory factors (IL-6, IL-8, and CCL2) and the secretion of IL-6 and MMP2 in Pg-LPS-stimulated hDPCs. The level of phosphorylated Smad1/5 was upregulated and the levels of phosphorylated ERK and JNK were downregulated. The inflammatory supernate of hDPCs inhibited by BMP9 reduced the migration of THP-1 cells. In rat pulp capping models, overexpressed BMP9 could partially restrain the development of dental pulp inflammation. This is the first study to confirm that BMP9 is involved in the occurrence and development of pulpitis and can partially inhibit its severity in the early stage. These findings provided a theoretical reference for future studies on the mechanism of pulpitis and application of bioactive molecules in vital pulp therapy.


Diversity-disturbance relationships: frequency and intensity interact.
An influential ecological theory, the intermediate disturbance hypothesis (IDH), predicts that intermediate levels of disturbance will maximize species diversity. Empirical studies, however, have described a wide variety of diversity-disturbance relationships (DDRs). Using experimental populations of microbes, we show that the form of the DDR depends on an interaction between disturbance frequency and intensity. We find that diversity shows a monotonically increasing, unimodal or flat relationship with disturbance, depending on the values of the disturbance aspects considered. These results confirm recent theoretical predictions, and potentially reconcile the conflicting body of empirical evidence on DDRs.


[Elaboration of instant corn flour by hydrothermal process I].
The objective of this research was to investigate a simplified hydrothermal process for the production of instant corn flour and evaluate some variables that affected the degree of gelatinization of corn flour, and evaluate some technological characteristics of the flour. The use of grits of lesser particle diameter and increasing temperature of the soaking water resulted in an increase in the rate of absorption of water of grits, permitting a reduction of soaking time necessary for the process. The instant corn flour prepared by the hydrothermal process using corn grits soaked in water at room temperature (28-30 degrees C) for 5 hours and steaming for 1 minute at 118 degrees C presented characteristics of viscosity, water absorption index and water solubility index similar to that of flours prepared with grits soaked in water at a temperature higher tan room temperature and different steaming time (5 and 15 minutes). The characteristics of color and shelf life of corn flour were improved with the hydrothermal process.


Diffuse reflectance technique for infrared analysis of urinary calculi.
We investigated the application of diffuse reflectance infrared Fourier transform spectroscopy to analysis of urinary calculi and compared its operation with that of older sampling techniques (pellet, mull, and attenuated total reflectance). The new method requires shorter sample preparation time and less sample (30 micrograms). Quantitative measurements are easier. Because of the additivity of the Kubelka-Munk functions, a quasi-exhaustive collection of infrared spectra of mixtures of possible components of stones can be compiled, facilitating a computerized intrepretation of infrared spectra of urinary calculi.


Downregulation of microRNA-630 inhibits cell proliferation and invasion and enhances chemosensitivity in human ovarian carcinoma.
MicroRNAs (miRNAs) are a family of small non-coding RNAs (approximately 21-23 nt long) that can target genes for either degradation of mRNA or inhibition of translation. miRNAs have not been comprehensively studied in human epithelial ovarian carcinoma (EOC). MicroRNA-630 (miR-630) has been frequently observed to be aberrantly expressed in various types of tumors. The present study explored the functions of miR-630 in the proliferation, apoptosis, chemosensitivity, and invasion of EOC. Using real-time polymerase chain reaction, we detected the miR-630 expression in cancerous, benign, and normal human ovarian tissues. Then, we evaluated the role of miR-630 in cell proliferation, chemosensitivity, apoptosis, and invasion by using the Cell Counting Kit-8, Annexin-V/FITC, and transwell assay on A2780 and SKOV3 cells. Western blotting was performed for analyzing the phosphatase and tensin homolog gene (PTEN) protein expression. The miR-630 expression level was higher in ovarian cancerous tissues than in benign and normal ovarian tissues. Decreased expression of miR-630 suppressed EOC cells' proliferation, migration, and invasion as well as significantly enhanced cell apoptosis and chemosensitivity to cisplatin. Furthermore, PTEN expression was increased in A2780 cells transfected by miR-630 inhibitor in comparison with inhibitor-negative control-transfected cells. In conclusion, downregulation of miR-630 dramatically increased apoptotic cell death chemosensitivity to cisplatin and decreased the proliferation, invasion, and migration of EOC cells. MiR-630 may thus play an important role in the biological behaviors of EOC cells through negative control of the PTEN expression.


A qualitative study of family carers views on how end-of-life communication contributes to palliative-oriented care in nursing home.
Although family-centered communication about end-of-life care has been recognized to promote palliative-oriented care in nursing home (NH), how this communication may work is still unknown. Therefore, we explored the mechanisms by which end-of-life communication may contribute to palliative-oriented care in NH from the perspective of bereaved family carers. A descriptive qualitative design was performed. Interviews were conducted with 32 bereaved family carers whose relative had died between 45 days to 9 months prior from 13 different NHs. A two-steps analysis process firstly with deductive and then with inductive content analysis was adopted. Four mechanisms by which end-of-life communication contributed to palliative-oriented care were identified: a) promoting family carers understanding about their relative's health conditions, prognosis, and treatments available; b) fostering shared decision-making between healthcare professionals and residents/family carers; c) improving knowledge of residents' preferences; and d) improving knowledge of family carers' preferences. Clear and in-depth communication provides insight into residents' and family carers' preferences for care and treatment at the end-of-life, and increases understanding and shared decision-making.


Proton to hydride umpolung at a phosphonium center via electron relay: a new strategy for main-group based water reduction.
Generation of dihydrogen from water splitting, also known as water reduction, is a key process to access a sustainable hydrogen economy for energy production and usage. The key step is the selective reduction of a protic hydrogen to an accessible and reactive hydride, which has proven difficult at a p-block element. Although frustrated Lewis pair (FLP) chemistry is well known for water activation by heterolytic H-OH bond cleavage, to the best of our knowledge, there has been only one case showing water reduction by metal-free FLP systems to date, in which silylene (SiII) was used as the Lewis base. This work reports the molecular design and synthesis of an ortho-phenylene linked bisborane-functionalized phosphine, which reacts with water stoichiometrically to generate H2 and phosphine oxide quantitatively under ambient conditions. Computational investigations revealed an unprecedented multi-centered electron relay mechanism offered by the molecular framework, shuttling a pair of electrons from hydroxide (OH-) in water to the separated proton through a borane-phosphonium-borane path. This simple molecular design and its water reduction mechanism opens new avenues for this main-group chemistry in their growing roles in chemical transformations.


Robustness analysis of a constraint-based metabolic model links cell growth and proteomics of Thermoanaerobacter tengcongensis under temperature perturbation.
The integration of omic data with metabolic networks has been demonstrated to be an effective approach to elucidate the underlying metabolic mechanisms in life. Because the metabolic pathways of Thermoanaerobacter tengcongensis (T. tengcongensis) are incomplete, we used a 1-(13)C-glucose culture to monitor intracellular isotope-labeled metabolites by GC/MS and identified the gap gene in glucose catabolism, Re-citrate synthase. Based on genome annotation and biochemical information, we reconstructed the metabolic network of glucose metabolism and amino acid synthesis in T. tengcongensis, including 253 reactions, 227 metabolites, and 236 genes. Furthermore, we performed constraint based modeling (CBM)-derived robustness analysis on the model to study the dynamic changes of the metabolic network. By perturbing the culture temperature from 75 to 55 °C, we collected the bacterial growth rates and differential proteomes. Assuming that protein abundance changes represent metabolic flux variations, we proposed that the robustness analysis of the CBM model could decipher the effect of proteome change on the bacterial growth under perturbation. For approximately 73% of the reactions, the predicted cell growth changes due to such reaction flux variations matched the observed cell growth data. Our study, therefore, indicates that differential proteome data can be integrated with metabolic network modeling and that robustness analysis is a strong method for representing the dynamic change in cell phenotypes under perturbation.


Self-reported bovine milk intake is associated with oral microbiota composition.
Bovine milk intake has been associated with various disease outcomes, with modulation of the gastro-intestinal microbiome being suggested as one potential mechanism. The aim of the present study was to explore the oral microbiota in relation to variation in self-reported milk intake. Saliva and tooth biofilm microbiota was characterized by 16S rDNA sequencing, PCR and cultivation in 154 Swedish adolescents, and information on diet and other lifestyle markers were obtained from a questionnaire, and dental caries from clinical examination. A replication cohort of 31,571 adults with similar information on diet intake, other lifestyle markers and caries was also studied. Multivariate partial least squares (PLS) modelling separated adolescents with low milk intake (lowest tertile with <0.4 servings/day) apart from those with high intake of milk (≥3.7 servings/day) based on saliva and tooth biofilm, respectively. Taxa in several genera contributed to this separation, and milk intake was inversely associated with the caries causing Streptococcus mutans in saliva and tooth biofilm samples by sequencing, PCR and cultivation. Despite the difference in S. mutans colonization, caries prevalence did not differ between milk consumption groups in the adolescents or the adults in the replication cohort, which may reflect that a significant positive association between intake of milk and sweet products was present in both the study and replication group. It was concluded that high milk intake correlates with different oral microbiota and it is hypothesized that milk may confer similar effects in the gut. The study also illustrated that reduction of one single disease associated bacterial species, such as S. mutans by milk intake, may modulate but not prevent development of complex diseases, such as caries, due to adverse effects from other causal factors, such as sugar intake in the present study.


[Automutilation of the palate in a psychiatric patient].
A 46-year-old man with a history of alcohol abuse was referred to an oral and maxillofacial surgeon with a large necrotic wound with raised edges on the palate. After history taking, radiography and clinical assessment, together with a psychiatrist, the lesion was diagnosed as an automutilation resulting from a period of alcohol abstinence. After a period of care in a medical centre, the lesion improved quickly. Following this treatment, the patient was admitted to a psychiatric treatment centre for supplemental treatment of his addiction problems.


Comparison of susceptibilities of M. tuberculosis H37Ra and M. chelonei subsp. abscessus to disinfectants.
To determine the susceptibilities of M. tuberculosis H37Ra and M. chelonei subsp. absecessus to several frequently-used disinfectants and to evaluate the practicability of surrogating M. tuberculosis by the latter. A suspension quantitative bactericidal test was set up in accordance with Chinese Technique Standard for Disinfection to evaluate the susceptibility of each mycobacteria strain to each selected disinfectant. Killing log value was used as criterion in comparing the susceptibility to disinfectants between the two strains. M. chelonei subsp. abscessus was more resistant to chlorine disinfectant than M. tuberculosis while the two strains were similarly resistant to iodophor disinfectant, peracetic acid, alcohol and glutaraldehyde disinfectant. M. chelonei subsp. abscessus has the potential to surrogate M. tuberculosis in evaluating mycobactericidal efficacies of disinfectants.


Placenta extrachorialis in the stumptailed macaque (Macaca arctoides).
Placenta extrachorialis was diagnosed in two of 56 placentas obtained from stumtailed macaques (Macaca arctoides) after elective cesarean section. The condition was characterized by the presence of an annular ring of necrotic tissue and fibrin at the margin of the villous chorion. Because these cases occurred in two of six known primiparous females, it was suggested that thte condition may account, at least in part, for the high incidence of pregnancy-related problems observed in primiparous stumptailed macaques.


Modeling collagen fibril self-assembly from extracellular medium in embryonic tendon.
Collagen is a key structural component of multicellular organisms and is arranged in a highly organized manner. In structural tissues such as tendons, collagen forms bundles of parallel fibers between cells, which appear within a 24-h window between embryonic day 13.5 (E13.5) and E14.5 during mouse embryonic development. Current models assume that the organized structure of collagen requires direct cellular control, whereby cells actively lay down collagen fibrils from cell surfaces. However, such models appear incompatible with the time and length scales of fibril formation. We propose a phase-transition model to account for the rapid development of ordered fibrils in embryonic tendon, reducing reliance on active cellular processes. We develop phase-field crystal simulations of collagen fibrillogenesis in domains derived from electron micrographs of inter-cellular spaces in embryonic tendon and compare results qualitatively and quantitatively to observed patterns of fibril formation. To test the prediction of this phase-transition model that free protomeric collagen should exist in the inter-cellular spaces before the formation of observable fibrils, we use laser-capture microdissection, coupled with mass spectrometry, which demonstrates steadily increasing free collagen in inter-cellular spaces up to E13.5, followed by a rapid reduction of free collagen that coincides with the appearance of less-soluble collagen fibrils. The model and measurements together provide evidence for extracellular self-assembly of collagen fibrils in embryonic mouse tendon, supporting an additional mechanism for rapid collagen fibril formation during embryonic development.


Cardiac dysfunction in pauci symptomatic human immunodeficiency virus patients: a meta-analysis in the highly active antiretroviral therapy era.
Human immunodeficiency virus infection (HIV) has been associated with cardiac dysfunction that, if present, can negatively affect morbidity and mortality of HIV-infected patients. Unfortunately, many of the studies on this topic were performed before the highly active antiretroviral therapy (HAART) was established. Thus, we performed a comprehensive meta-analysis to critically appraise the incidence of cardiac dysfunction in HIV-infected pauci symptomatic patients. Medline, Cochrane Library, and Biomed Central were systematically screened for studies reporting on systolic and/or diastolic dysfunctions in HIV pauci-symptomatic patients. Baseline treatment and cardiac imaging data were appraised and pooled with random effect methods computing summary. At pooled analysis, including a total of 2242 patients from 11 studies, an overall average incidence of traditional cardiovascular risk factors was observed, while a low rate of previous coronary artery disease was reported. Incidence of systolic and diastolic left ventricular dysfunction was 8.33% (95% CI: 2.20-14.25) and 43.38% (95% CI: 31.73-55.03), respectively. Diastolic dysfunction was graded as first [31.85% (95% CI: 24.85-43.73)], second [8.53% (95% CI: 2.12-14.93)], and third degree [3.02% (95% CI: 1.78-4.27)]. At multivariate analysis, a high sensitivity C-reactive protein level >5 mg/L, active tobacco smoking and previous history of myocardial infarction were predictors of left ventricular systolic dysfunction [odd ratio 1.70 (95% CI: 1.03-2.77); 1.57 (95% CI: 1.03-2.34); and 15.90 (95% CI: 1.94-329.00), respectively]. Hypertension (OR = 2.30; 95% CI: 1.20-4.50) and older age (OR = 2.50 per 10 years increase; 95% CI: 1.70-3.60) were predictors of left ventricular diastolic dysfunction (Figure 3). Systolic and diastolic dysfunction represent a common finding in pauci symptomatic HIV-infected patients, regardless to HAART.


In Vivo Clearance of Apoptotic Debris From Tumor Xenografts Exposed to Chemically Modified Tetrac: Is There a Role for Thyroid Hormone Analogues in Efferocytosis?
Apoptosis is induced in cancer cells and tumor xenografts by the thyroid hormone analogue tetraiodothyroacetic acid (tetrac) or chemically modified forms of tetrac. The effect is initiated at a hormone receptor on the extracellular domain of plasma membrane integrin αvβ3. The tumor response to tetrac includes 80% reduction in size of glioblastoma xenograft in two weeks of treatment, with absence of residual apoptotic cancer cell debris; this is consistent with efferocytosis. The molecular basis for efferocytosis linked to tetrac is incompletely understood, but several factors are proposed to play roles. Tetrac-based anticancer agents are pro-apoptotic by multiple intrinsic and extrinsic pathways and differential effects on specific gene expression, e.g., downregulation of the X-linked inhibitor of apoptosis (XIAP) gene and upregulation of pro-apoptotic chemokine gene, CXCL10. Tetrac also enhances transcription of chemokine CXCR4, which is relevant to macrophage function. Tetrac may locally control the conformation of phagocyte plasma membrane integrin αvβ3; this is a cell surface recognition system for apoptotic debris that contains phagocytosis signals. How tetrac may facilitate the catabolism of the engulfed apoptotic cell debris requires additional investigation.


Membrane-induced allosteric control of phospholipase C-β isozymes.
All peripheral membrane proteins must negotiate unique constraints intrinsic to the biological interface of lipid bilayers and the cytosol. Phospholipase C-β (PLC-β) isozymes hydrolyze the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) to propagate diverse intracellular responses that underlie the physiological action of many hormones, neurotransmitters, and growth factors. PLC-β isozymes are autoinhibited, and several proteins, including Gαq, Gβγ, and Rac1, directly engage distinct regions of these phospholipases to release autoinhibition. To understand this process, we used a novel, soluble analog of PIP2 that increases in fluorescence upon cleavage to monitor phospholipase activity in real time in the absence of membranes or detergents. High concentrations of Gαq or Gβ1γ2 did not activate purified PLC-β3 under these conditions despite their robust capacity to activate PLC-β3 at membranes. In addition, mutants of PLC-β3 with crippled autoinhibition dramatically accelerated the hydrolysis of PIP2 in membranes without an equivalent acceleration in the hydrolysis of the soluble analog. Our results illustrate that membranes are integral for the activation of PLC-β isozymes by diverse modulators, and we propose a model describing membrane-mediated allosterism within PLC-β isozymes.


Inheritance of resistance to pyriproxyfen in Bemisia tabaci (Hemiptera: Aleyrodidae) males and females (B biotype).
We evaluated effects of the insect growth regulator pyriproxyfen on Bemisia tabaci (Gennadius) (B biotype) (Hemiptera: Aleyrodidae) males and females in laboratory bioassays. Insects were treated with pyriproxyfen as either eggs or nymphs. In all tests, the LC50 for a laboratory-selected resistant strain was at least 620 times greater than for an unselected susceptible strain. When insects were treated as eggs, survival did not differ between males and females of either strain. When insects were treated as nymphs, survival did not differ between susceptible males and susceptible females, but resistant males had higher mortality than resistant females. The dominance of resistance decreased as pyriproxyfen concentration increased. Resistance was partially or completely dominant at the lowest concentration tested and completely recessive at the highest concentration tested. Hybrid female progeny from reciprocal crosses between the susceptible and resistant strains responded alike in bioassays; thus, maternal effects were not evident. Rapid evolution of resistance to pyriproxyfen could occur if individuals in field populations had resistance with traits similar to those of the laboratory-selected strain examined here.


IL-22 deficiency increases CD4 T cell responses to mucosal immunization.
Mucosal vaccines are a promising platform for combatting infectious diseases for which we still lack effective preventative measures. Optimizing these vaccines to generate the best protective immune responses with the least complicated immunization regimen is imperative. Mucosal barriers are the first line of defense against many pathogens and, as such, we looked to their biology for strategies to improve vaccine delivery. Interleukin-22 (IL-22) is a key cytokine in both healthy and inflamed mucosal tissues. IL-22 promotes epithelial cell proliferation and inhibits apoptosis, upregulates mucin and antimicrobial peptides, all of which promote mucosal barrier integrity. In this study, we find that IL-22 impairs the development of a T cell response during mucosal immunization. Compared to wild-type control mice, IL-22 deficient mice had increased antigen-specific CD4 T cell responses to intrarectal immunization using a protein and cholera toxin adjuvant vaccine. When immunized systemically with the same protein antigen adsorbed to alum, no differences in the CD4 T cell response between wild-type and IL-22 deficient mice were detected. This suggests that transiently inhibiting IL-22 during mucosal vaccination could enhance T cell responses. The broad-applicability of this proposed approach would allow for improvement of many existing mucosal vaccine regimens and have positive implications in the development of more efficacious mucosal vaccines.


Possible significance of cells within intraluminal collagen masses in equine oviducts.
In addition to the unique feature of retention of unfertilized ova, the oviducts of mares frequently contain large intraluminal masses with a fibrillar component and some cells. The aim of this study was to identify the cells and examine their relationship to the extracellular components of these masses. Intraluminal masses were examined both in situ and flushed from the oviducts. The nature of the contained cells and their relationship to the fibrils were examined by light microscopy and by transmission and scanning electron microscopy. In some mares the large masses distended the oviduct, but neither loss of the oviductal epithelium nor damage to this epithelium was seen. Electron microscopy verified that the principal cellular component was fibroblasts, and that the fibrils were type I collagen. Collagen masses collected shortly after ovulation frequently contained viable fibroblasts with collagen fibrils associated with their cell surfaces and with surface clefts. Although such collagen masses were present in pregnant and nonpregnant mares, masses with viable fibroblasts were chronologically associated with recent ovulation. It was concluded that connective tissue drawn into the oviduct at ovulation is retained, and collagen synthesis continues at least for a few days. Although the fibroblasts eventually disintegrate, the collagen remains and may in some cases aggregate within the oviductal lumen to the extent that oviductal transport and embryonic viability could be affected.