Measles virus glycoprotein-based lentiviral targeting vectors that avoid neutralizing antibodies

Lentiviral vectors (LVs) are potent gene transfer vehicles frequently applied in research and recently also in clinical trials. Retargeting LV entry to cell types of interest is a key issue to improve gene transfer safety and efficacy. Recently, we have developed a targeting method for LVs by incorporating engineered measles virus (MV) glycoproteins, the hemagglutinin (H), responsible for receptor recognition, and the fusion protein into their envelope. The H protein displays a single-chain antibody (scFv) specific for the target receptor and is ablated for recognition of the MV receptors CD46 and SLAM by point mutations in its ectodomain. A potential hindrance to systemic administration in humans is pre-existing MV-specific immunity due to vaccination or natural infection. We compared transduction of targeting vectors and non-targeting vectors pseudotyped with MV glycoproteins unmodified in their ectodomains (MV-LV) in presence of α-MV antibody-positive human plasma. At plasma dilution 1:160 MV-LV was almost completely neutralized, whereas targeting vectors showed relative transduction efficiencies from 60% to 90%. Furthermore, at plasma dilution 1:80 an at least 4-times higher multiplicity of infection (MOI) of MV-LV had to be applied to obtain similar transduction efficiencies as with targeting vectors. Also when the vectors were normalized to their p24 values, targeting vectors showed partial protection against α-MV antibodies in human plasma. Furthermore, the monoclonal neutralizing antibody K71 with a putative epitope close to the receptor binding sites of H, did not neutralize the targeting vectors, but did neutralize MV-LV. The observed escape from neutralization may be due to the point mutations in the H ectodomain that might have destroyed antibody binding sites. Furthermore, scFv mediated cell entry via the target receptor may proceed in presence of α-MV antibodies interfering with entry via the natural MV receptors. These results are promising for in vivo applications of targeting vectors in humans

Fast responsive, optical trace level ammonia sensor for environmental monitoring

BACKGROUND: Ammonia is a ubiquitous chemical substance which is created in technical and biological processes and harmful to many different organisms. One specific problem is the toxicity of ammonia in fish at levels of 25 μg/l - a very common issue in today’s aqua culture. In this study we report a development of a fast responsive, optical ammonia sensor for trace concentrations. RESULTS: Different hydrogels have been investigated as host polymers for a pH based sensing mechanism based on fluorescent dyes. A porous hydrophobic fluoropolymer membrane was used as an ion barrier cover layer to achieve a good ammonia permeability. The sensor’s sensitivity towards ammonia as well as crosssensitivity towards pH-value and salinity, and the temperature dependency have been determined. Two different methods to reference fluorescence signals have been employed to eliminate intensity-based measurement drawbacks. CONCLUSION: The presented sensor features high sensitivity and a fast response even at concentrations near 1 ppb. No cross sensitivity towards pH and salinity could be observed and temperature dependency was determined as compensateable. Both referencing approaches prove themselves to be able to provide a simple use of the sensor for in-field applications

Phase-Sensitive Amplification of 28 GBaud DP-QPSK Signal

We demonstrate, for the first time, amplification of a DP-QPSK signal using a vector phase-sensitive amplifier (PSA). The PSA-based receiver shows an about 0.7 dB sensitivity improvement compared to an EDFA-based receiver

Frequency-Comb Regeneration for Self-Homodyne Superchannels

We demonstrate frequency-comb regeneration from two received unmodulated carriers using a parametric mixer. For 10 dB optical signal-to-noise ratio of the unmodulated carriers, up to 60 carriers are generated without linewidth degradation

A role for eisosomes in maintenance of plasma membrane phosphoinositide levels

The plasma membrane delineates the cell and mediates its communication and material exchange with the environment. Many processes of the plasma membrane occur through interactions of proteins with phosphatidylinositol(4,5)-bisphosphate (PI(4,5)P2), which is highly enriched in this membrane and is a key determinant of its identity. Eisosomes function in lateral organization of the plasma membrane, but the molecular function of their major protein subunits, the BAR domain–containing proteins Pil1 and Lsp1, is poorly understood. Here we show that eisosomes interact with the PI(4,5)P2 phosphatase Inp51/Sjl1, thereby recruiting it to the plasma membrane. Pil1 is essential for plasma membrane localization and function of Inp51 but not for the homologous phosphatidylinositol bisphosphate phosphatases Inp52/Sjl2 and Inp53/Sjl3. Consistent with this, absence of Pil1 increases total and available PI(4,5)P2 levels at the plasma membrane. On the basis of these findings, we propose a model in which the eisosomes function in maintaining PI(4,5)P2 levels by Inp51/Sjl1 recruitment

The Ursinus Weekly, November 1, 1907

Phantom party at Olevian • Football • Historical Political meeting • The Schubert string quartette • Editorial: Smiles • Society • Personals • Seminary notes • College world • Alumni notes • Literary Supplement: The lack of appreciation of the beautiful; A defense of American poetry; The danger of hero worship in a democracy; Hallowe\u27en; The price of an experience; Hannibalhttps://digitalcommons.ursinus.edu/weekly/2882/thumbnail.jp

How Mechanization Shapes Coups

Civil-military relations are characterized by a fundamental dilemma. To lower coup risk, leaders frequently empower the military, which satisfies the armed forces with the status quo and enables them to fight against threats challenging the civilian leadership. Simultaneously, a too powerful military itself constitutes a potential threat that is capable of overthrowing the government. Our research adds to this debate by examining the impact of mechanization, that is, the degree to which militaries rely on armored vehicles relative to manpower, on coup risk. We discuss several (opposing) mechanisms before developing the theoretical expectation that higher levels of mechanization should lower the likelihood of a coup due to the increased costs of coup execution. Empirical evidence strongly supports this claim and, thus, contributes to our understanding of the emergence of coups as an essential breakdown of civil-military relations, while adding to the debate surrounding the many trade-offs leaders face when coup-proofing their regimes

Purchasing Behavior, Setting, Pricing, Family: Determinants of School Lunch Participation

Despite growing school lunch availability in Germany, its utilization is still low, and students resort to unhealthy alternatives. We investigated predictors of school lunch participation and reasons for nonparticipation in 1215 schoolchildren. Children reported meal habits, parents provided family-related information (like socioeconomic status), and anthropometry was conducted on-site in schools. Associations between school lunch participation and family-related predictors were estimated using logistic regression controlling for age and gender if necessary. School was added as a random effect. School lunch participation was primarily associated with family factors. While having breakfast on schooldays was positively associated with school lunch participation (ORadj = 2.20, p = 0.002), lower secondary schools (ORadj = 0.52, p < 0.001) and low SES (ORadj = 0.25, p < 0.001) were negatively associated. The main reasons for nonparticipation were school- and lunch-related factors (taste, time constraints, pricing). Parents reported pricing as crucial a reason as an unpleasant taste for nonparticipation. Nonparticipants bought sandwiches and energy drinks significantly more often on school days, whereas participants were less often affected by overweight (OR = 0.66, p = 0.043). Our data stress school- and lunch-related factors as an important opportunity to foster school lunch utilization

Will We Do If We Can? Habitual Qualitative and Quantitative Physical Activity in Multi-Morbid, Older Persons with Cognitive Impairment

This study aimed to identify determinants of quantitative dimensions of physical activity (PA; duration, frequency, and intensity) in community-dwelling, multi-morbid, older persons with cognitive impairment (CI). In addition, qualitative and quantitative aspects of habitual PA have been described. Quantitative PA and qualitative gait characteristics while walking straight and while walking turns were documented by a validated, sensor-based activity monitor. Univariate and multiple linear regression analyses were performed to delineate associations of quantitative PA dimensions with qualitative characteristics of gait performance and further potential influencing factors (motor capacity measures, demographic, and health-related parameters). In 94 multi-morbid, older adults (82.3 ± 5.9 years) with CI (Mini-Mental State Examination score: 23.3 ± 2.4), analyses of quantitative and qualitative PA documented highly inactive behavior (89.6% inactivity) and a high incidence of gait deficits, respectively. The multiple regression models (adjusted R$^{2}$ = 0.395–0.679, all p < 0.001) identified specific qualitative gait characteristics as independent determinants for all quantitative PA dimensions, whereas motor capacity was an independent determinant only for the PA dimension duration. Demographic and health-related parameters were not identified as independent determinants. High associations between innovative, qualitative, and established, quantitative PA performances may suggest gait quality as a potential target to increase quantity of PA in multi-morbid, older persons

And yet Again: Having Breakfast Is Positively Associated with Lower BMI and Healthier General Eating Behavior in Schoolchildren

Given the high prevalence of childhood overweight, school-based programs aiming at nutritional behavior may be a good starting point for community-based interventions. Therefore, we investigated associations between school-related meal patterns and weight status in 1215 schoolchildren. Anthropometry was performed on-site in schools. Children reported their meal habits, and parents provided family-related information via questionnaires. Associations between nutritional behavior and weight status were estimated using hierarchical linear and logistic regression. Analyses were adjusted for age, socio–economic status, school type, migration background, and parental weight status. Having breakfast was associated with a lower BMI-SDS (βadj = −0.51, p = 0.004) and a lower risk of being overweight (ORadj = 0.30, p = 0.009), while having two breakfasts resulting in stronger associations (BMI-SDS: βadj = −0.66, p < 0.001; risk of overweight: ORadj = 0.22, p = 0.001). Likewise, children who regularly skipped breakfast on school days showed stronger associations (BMI-SDS: β = 0.49, p < 0.001; risk of overweight: OR = 3.29, p < 0.001) than children who skipped breakfast only occasionally (BMI-SDS: β = 0.43, p < 0.001; risk of overweight: OR = 2.72, p = 0.032). The associations persisted after controlling for parental SES and weight status. Therefore, our data confirm the school setting as a suitable starting point for community-based interventions and may underline the necessity of national programs providing free breakfast and lunch to children