Transport properties of bovine and reindeer beta-lactoglobulin in the Caco-2 cell model

Beta-lactoglobulin (betaLG) is a protein that binds ligands like fatty acids and retinol into the hydrophobic pocket. Our purpose was to study bovine and reindeer betaLG as transporter molecules and compare their transport properties across Caco-2 cell membrane. The reindeer betaLG has more valuable binder characteristics than bovine betaLG because it has only one genetic phenotype and it seems to exhibit better immunological properties. The permeation of betaLG in Caco-2 cells was evaluated by immunoblotting, and the permeation of the model substances retinol, palmitic acid and cholesterol with and without betaLG was determined using [(3)H]-labelled ligands. Both bovine and reindeer betaLG were able to pass across a Caco-2 cell monolayer similarly. Unbound and betaLG-bound [(3)H]retinol and [(3)H]palmitic acid were equally transported across the Caco-2 cell layer, whereas [(3)H]cholesterol could not pass across Caco-2 cells with or without betaLG at any of the studied circumstances. Thus, the bovine and reindeer milk betaLG is not a suitable protein to enhance transport of ligands across the Caco-2 cell membrane, used for predicting intestinal absorption.     

The CD40-induced protection against CD95-mediated apoptosis is associated with a rapid upregulation of anti-apoptotic c-FLIP

CD95/Fas and CD40 receptors are important regulators of cell survival during germinal center reaction. In this study we used a human follicular lymphoma cell line, HF1A3, to study molecular mechanisms of CD95-mediated apoptosis and CD40-induced rescue from apoptosis. CD95 stimulation induced activation of caspase-8 and -3, collapse of mitochondrial membrane potential (DeltaPsim), release of cytochrome c and fragmentation of nuclear DNA. All these apoptotic events were abrogated, when cells were pretreated with CD40 antibodies before CD95 stimulation. CD40 induced a rapid up regulation of both short and long isoforms of c-FLIP, as these proteins were detectable 4h after receptor stimulation. The induction of c-FLIP as well as the anti-apoptotic function of CD40 was completely abolished when NF-kappaB activity was inhibited by a selective inhibitor PDTC. We conclude that the anti-apoptotic signaling of CD40 involves NF-kappaB-mediated induction of c-FLIP proteins which can interfere with caspase-8 activation. However, it remains to be seen whether c-FLIP proteins are the only one ones involved in CD40-mediated protection.     

Live fast,die young? A review on the developmental trajectories of ADHD across the lifespan

Attention-deficit/hyperactivity disorder (ADHD) is highly heritable and the most common neurodevelopmental disorder in childhood. In recent decades, it has been appreciated that in a substantial number of cases the disorder does not remit in puberty, but persists into adulthood. Both in childhood and adulthood, ADHD is characterised by substantial comorbidity including substance use, depression, anxiety, and accidents. However, course and symptoms of the disorder and the comorbidities may fluctuate and change over time, and even age of onset in childhood has recently been questioned. Available evidence to date is poor and largely inconsistent with regard to the predictors of persistence versus remittance. Likewise, the development of comorbid disorders cannot be foreseen early on, hampering preventive measures. These facts call for a lifespan perspective on ADHD from childhood to old age. In this selective review, we summarise current knowledge of the long-term course of ADHD, with an emphasis on clinical symptom and cognitive trajectories, treatment effects over the lifespan, and the development of comorbidities. Also, we summarise current knowledge and important unresolved issues on biological factors underlying different ADHD trajectories. We conclude that a severe lack of knowledge on lifespan aspects in ADHD still exists for nearly every aspect reviewed. We encourage large-scale research efforts to overcome those knowledge gaps through appropriately granular longitudinal studies.     

Efficacy of accelerated dose titration of olanzapine with adjunctive lorazepam to treat acute agitation in schizophrenia

We conducted a prospective double-blind study of accelerated dose titration of olanzapine in the treatment of newly admitted acutely agitated patients with schizophrenia. Patients were randomized to either oral olanzapine (10 mg per day) or oral haloperidol (10 mg per day), plus lorazepam as needed (up to 12 mg per day). Antipsychotic dosage was increased to 20 mg per day as early as day 3. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) Agitation subscale during the first 24 hours of treatment, daily for the first week, then weekly until study completion. Significant within-group improvement was demonstrated in PANSS Agitation scores for both groups as early as 1 hour after initiating therapy (-5.79 +/- 6.30 for olanzapine and -4.89 +/- 6.05 for haloperidol, P <.001). This study demonstrated that accelerated dose titration of oral olanzapine is as efficacious as oral haloperidol in reducing acute agitation in patients with schizophrenia.     

Intrarater and interrater reliability of a manual technique to assess anterior humeral head translation of the glenohumeral joint

The purpose of this study was to determine the intrarater and interrater reliability of a manual anterior humeral head translation test. Fifteen subjects were positioned lying in a supine position with their identity shielded from examiners. A standard manual anterior humeral head translation test was performed and repeated with the glenohumeral joint in 90 degrees of elevation in the scapular plane, with use of the grading method proposed by Altchek and Dines in 1993. Reliability was assessed with the coefficient of agreement and kappa statistic. Intrarater reliability was 81.4% comparing grade I and II translation. This decreased to 54% when examiners distinguished between grades I, I+, II, and II+. Interrater reliability for the same comparisons was 70.4%, decreasing to 37.3%.On the basis of these data, the technique of manually assessing anterior humeral head translation studied has poor overall interrater reliability and only fair intrarater reliability. The test-retest accuracy of humeral head translation is enhanced when examiners only determine the relationship of the humeral head relative to the glenoid rim.     

Historical Prevalence and Distribution of Avian Influenza Virus A(H7N9) among Wild Birds

We examined 48 published studies for which sample sizes could be ascertained to determine the historic prevalence of influenza A(H7N9) virus in wild bird populations and reviewed GenBank data to further establish its distribution. Low prevalence (0.0093%) in Asia suggests > 30,000 samples would be required to detect the H7N9 subtype in wild birds.     

California Very Preterm Birth Study: design and characteristics of the population- and biospecimen bank-based nested case-control study

Very preterm birth (VPTB) is a leading cause of infant mortality, morbidity and racial disparity in the US. The underlying causes of VPTB are multiple and poorly understood. The California Very Preterm Birth Study was conducted to discover maternal and infant genetic and environmental factors associated with VPTB. This paper describes the study design, population, data and specimen collection, laboratory methods and characteristics of the study population. Using a large, population-based cohort created through record linkage of livebirths delivered from 2000 to 2007 in five counties of southern California, and existing data and banked specimens from statewide prenatal and newborn screening, 1100 VPTB cases and 796 control mother-infant pairs were selected for study (385/200 White, 385/253 Hispanic and 330/343 Black cases/controls, respectively). Medical record abstraction of cases was conducted at over 50 hospitals to identify spontaneous VPTB, improve accuracy of gestational age, obtain relevant clinical data and exclude cases that did not meet eligibility criteria. VPTB was defined as birth at <32 weeks in Whites and Hispanics and <34 weeks in Blacks. Approximately 55% of all VPTBs were spontaneous and 45% had medical indications or other exclusions. Of the spontaneous VPTBs, approximately 41% were reported to have chorioamnionitis. While the current focus of the California Very Preterm Birth Study is to assess the role of candidate genetic markers on spontaneous VPTB, its design enables the pursuit of other research opportunities to identify social, clinical and biological determinants of different types of VPTB with the ultimate aim of reducing infant mortality, morbidity and racial disparities in these health outcomes in the US and elsewhere.     

JAG1-Mediated Notch Signaling Regulates Secretory Cell Differentiation of the Human Airway Epithelium

Basal cells (BC) are the stem/progenitor cells of the human airway epithelium capable of differentiating into secretory and ciliated cells. Notch signaling activation increases BC differentiation into secretory cells, but the role of individual Notch ligands in regulating this process in the human airway epithelium is largely unknown. The objective of this study was to define the role of the Notch ligand JAG1 in regulating human BC differentiation. JAG1 over-expression in BC increased secretory cell differentiation, with no effect on ciliated cell differentiation. Conversely, knockdown of JAG1 decreased expression of secretory cell genes. These data demonstrate JAG1-mediated Notch signaling regulates differentiation of BC into secretory cells.