A microbial expression system for high-level production of scFv HIV-neutralizing antibody fragments in Escherichia coli

Microbial Biotechnolog

Determinant Representations for Correlation Functions of Spin-1/2 XXX and XXZ Heisenberg Magnets

We consider correlation functions of the spin-\half XXX and XXZ Heisenberg chains in a magnetic field. Starting from the algebraic Bethe Ansatz we derive representations for various correlation functions in terms of determinants of Fredholm integral operators.Comment: 23 pages, TeX, BONN-TH-94-14, revised version: typos correcte

Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19

BACKGROUND REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019 (Covid-19). Whether subcutaneous REGEN-COV prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent Covid-19 in persons at high risk for infection because of household exposure to a person with SARS-CoV-2 infection is unknown. METHODS We randomly assigned, in a 1:1 ratio, participants (=12 years of age) who were enrolled within 96 hours after a household contact received a diagnosis of SARSCoV- 2 infection to receive a total dose of 1200 mg of REGEN-COV or matching placebo administered by means of subcutaneous injection. At the time of randomization, participants were stratified according to the results of the local diagnostic assay for SARS-CoV-2 and according to age. The primary efficacy end point was the development of symptomatic SARS-CoV-2 infection through day 28 in participants who did not have SARS-CoV-2 infection (as measured by reverse-transcriptase- quantitative polymerase-chain-reaction assay) or previous immunity (seronegativity). RESULTS Symptomatic SARS-CoV-2 infection developed in 11 of 753 participants in the REGEN-COV group (1.5%) and in 59 of 752 participants in the placebo group (7.8%) (relative risk reduction [1 minus the relative risk], 81.4%; P104 copies per milliliter) was shorter (0.4 weeks and 1.3 weeks, respectively). No dose-limiting toxic effects of REGEN-COV were noted. CONCLUSIONS Subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons. Among the participants who became infected, REGEN-COV reduced the duration of symptomatic disease and the duration of a high viral load

Critical role for the alpha-1B adrenergic receptor at the sympathetic neuroeffector junction.

The alpha-1 adrenergic receptors (alpha(1)ARs) are critical in sympathetically mediated vasoconstriction. The specific role of each alpha(1)AR subtype in regulating vasoconstriction remains highly controversial. Limited pharmacological studies suggest that differential alpha(1)AR responses may be the result of differential activation of junctional versus extrajunctional receptors. We tested the hypothesis that the alpha(1B)AR subtype is critical in mediating sympathetic junctional neurotransmission. We measured in vivo integrated cardiovascular responses to a hypotensive stimulus (induced via transient bilateral carotid occlusion [TBCO]) in alpha(1B)AR knockout (KO) mice and their wild-type (WT) littermates. In WT mice, after dissection of the carotid arteries and denervation of aortic baroreceptor buffering nerves, TBCO produced significant pressor and positive inotropic effects. Both responses were markedly attenuated in alpha(1B)AR KO mice (change systolic blood pressure 46+/-8 versus 11+/-2 mm Hg; percentage change in the end-systolic pressure-volume relationship [ESPVR] 36+/-7% versus 12+/-2%; WT versus KO; P<0.003). In vitro alpha(1)AR mesenteric microvascular contractile responses to endogenous norepinephrine (NE; elicited by electrical field stimulation 10 Hz) was markedly depressed in alpha(1B)AR KO mice compared with WT (12.4+/-1.7% versus 21.5+/-1.2%; P<0.001). In contrast, responses to exogenous NE were similar in alpha(1B)AR KO and WT mice (22.4+/-7.3% versus 33.4+/-4.3%; NS). Collectively, these results demonstrate a critical role for the alpha(1B)AR in baroreceptor-mediated adrenergic signaling at the vascular neuroeffector junction. Moreover, alpha(1B)ARs modulate inotropic responses to baroreceptor activation. The critical role for alpha(1B)AR in neuroeffector regulation of vascular tone and myocardial contractility has profound clinical implications for designing therapies for orthostatic intolerance

Relevance of nitric oxide for myocardial remodeling.

Endogenous myocardial nitric oxide (NO) may modulate the transition from adaptive to maladaptive remodeling leading to heart failure. In rodent models of pressure overload or myocardial infarction, the three NO synthase (NOS) isoforms were shown to play a neutral, protective, or even adverse role in myocardial remodeling, depending on the quantity of NO produced, the location of each NOS and their regulators, the prevailing oxidant stress and resultant NO/oxidant balance, as well as NOS coupling/dimerization. Beside neuronal NOS and--in specific conditions--inducible NOS isoforms, endothelial NOS (eNOS) exerts cardioprotective effects on pressure-overload, ischemia/reperfusion, and myocardial infarction-induced myocardial remodeling, provided the enzyme remains in a coupled state. Besides its effects on excitation-contraction coupling in response to stretch, eNOS acts as an "endogenous beta-blocker" by restoring the sympathovagal balance, opposing excessive hypertrophy as well as promoting vasodilatation and neoangiogenesis, thereby contributing to tissue repair. As eNOS was also shown to mediate the beneficial effects of cardiovascular drugs commonly used in patients with heart failure, strategies to increase its expression and/or coupled catalytic activity in the myocardium offer new therapeutic avenues for the treatment of this disease