Resolving content moderation dilemmas between free speech and harmful misinformation.

In online content moderation, two key values may come into conflict: protecting freedom of expression and preventing harm. Robust rules based in part on how citizens think about these moral dilemmas are necessary to deal with this conflict in a principled way, yet little is known about people's judgments and preferences around content moderation. We examined such moral dilemmas in a conjoint survey experiment where US respondents ( = 2, 564) indicated whether they would remove problematic social media posts on election denial, antivaccination, Holocaust denial, and climate change denial and whether they would take punitive action against the accounts.

Pancreatic beta-cell overexpression of the glucagon receptor gene results in enhanced beta-cell function and mass.

In addition to its primary role in regulating glucose production from the liver, glucagon has many other actions, reflected by the wide tissue distribution of the glucagon receptor (Gcgr). To investigate the role of glucagon in the regulation of insulin secretion and whole body glucose homeostasis in vivo, we generated mice overexpressing the Gcgr specifically on pancreatic beta-cells (RIP-Gcgr). In vivo and in vitro insulin secretion in response to glucagon and glucose was increased 1.

Lentivectors encoding immunosuppressive proteins genetically engineer pancreatic beta-cells to correct diabetes in allogeneic mice.

The effectiveness of genetic engineering with lentivectors to protect transplanted cells from allogeneic rejection was examined using, as a model, type 1 diabetes treatment with beta-cell transplantation, whose widespread use has been limited by the requirement for sustained immunosuppressive treatment to prevent graft rejection. We examined whether lentivectors expressing select immunosuppressive proteins encoded by the adenoviral genome early region 3 (AdE3) would protect transplanted beta-cells from an alloimmune attack. The insulin-producing beta-cell line beta TC-tet (C3HeB/FeJ-derived) was transduced with lentiviruses encoding the AdE3 proteins gp19K and RID alpha/beta.

Anatomical but not functional recovery from a sciatic nerve crush is enhanced by treatment with testosterone.

PURPOSE: Until recently, there has been a limited amount of research comparing functional and anatomical recovery following nerve injury. Previous studies emphasizing anatomical recovery (such as axonal number) have shown that testosterone promotes regeneration in crushed and transected nerves. The purpose of this study was to assess the effect of testosterone on the functional recovery of the sciatic nerve follow-ing a unilateral crush injury.

A new approach for point mutation detection based on a ligase chain reaction.

A new method for the identification of point mutations is proposed. The method is based on ligase chain reaction (LCR) and it includes a procedure for correction of ligation by Cleavase. Reaction products are detected by a colorimetric method after adsorption of the resulting DNA duplexes to the solid phase.

Discordant effects of glucosamine on insulin-stimulated glucose metabolism and phosphatidylinositol 3-kinase activity.

The impact of increased GlcN availability on insulin-stimulated p85/p110 phosphatidylinositol 3-kinase (PI3K) activity in skeletal muscle was examined in relation to GlcN-induced defects in peripheral insulin action. Primed continuous GlcN infusion (750 micromol/kg bolus; 30 micromol/kg.min) in conscious rats limited both maximal stimulation of muscle PI3K by acute insulin (I) (1 unit/kg) bolus (I + GlcN = 1.

Functional analysis of a conditionally transformed pancreatic beta-cell line.

Development of beta-cell lines for cell therapy of diabetes is hindered by functional deviations of the replicating cells from the normal beta-cell phenotype. In a recently developed cell line, denoted betaTC-tet, derived from transgenic mice expressing the SV40 T antigen (Tag) under control of the tetracycline (Tc) gene regulatory system, growth arrest can be induced by shutting off Tag expression in the presence of Tc. Here, we compared differentiated cell functions in dividing and growth-arrested betaTC-tet cells, both in culture and in vivo.

cAMP-dependent phosphorylation of the cardiac-type alpha 1 subunit of the voltage-dependent Ca2+ channel in a murine pancreatic beta-cell line.

Two voltage-dependent calcium channels (VDCCs) have been reported in pancreatic islets: the beta-cell/endocrine-brain and cardiac subtypes. The cardiac-type alpha 1 subunit was isolated from cultured beta TC3 cells, a murine pancreatic beta-cell line, by immunoprecipitation with a specific polyclonal antibody. We have examined the effects of 1-isobutyl-3-methylxanthine (IBMX) and forskolin, agonists that elevate cAMP in these cells, on the phosphorylation of this subunit in intact beta TC3 cells using a sensitive back-phosphorylation technique.

Animal model for maturity-onset diabetes of the young generated by disruption of the mouse glucokinase gene.

Glucokinase catalyzes a rate-limiting step in glucose metabolism in hepatocytes and pancreatic beta cells and is considered the "glucose sensor" for regulation of insulin secretion. Patients with maturity-onset diabetes of the young (MODY) have heterozygous point mutations in the glucokinase gene that result in reduced enzymatic activity and decreased insulin secretion. However, it remains unclear whether abnormal liver glucose metabolism contributes to the MODY disease.

Evidence that Rap1 carboxylmethylation is involved in regulated insulin secretion.

Protein carboxylmethylation is a reversible posttranslational modification that regulates protein function. We examined the carboxylmethylation of small GTP-binding proteins in a pancreatic beta-cell line (beta TC cells). In vitro assays showed that carboxylmethylation of a membrane 23-kDa protein was induced by guanine nucleotides, best demonstrated by the nonhydrolyzable GTP analog, guanosine 5'-(3-O-thio)triphosphate (GTP gamma S).

Clonal insulinoma cell line that stably maintains correct glucose responsiveness.

A number of pancreatic beta-tumor cell (beta TC) lines have been derived from insulinomas arising in transgenic mice expressing the SV40 T antigen gene under control of the insulin promoter. Some of these lines secrete insulin in response to physiological glucose concentrations. However, this phenotype is unstable.

Ribozyme-mediated attenuation of pancreatic beta-cell glucokinase expression in transgenic mice results in impaired glucose-induced insulin secretion.

Phosphorylation of glucose to glucose 6-phosphate by glucokinase (GK; EC 2.7.1.

Murine insulinoma cell line with normal glucose-regulated insulin secretion.

Pancreatic beta TC lines derived from insulinomas arising in transgenic mice expressing SV40 Tag under control of the insulin promoter manifest a differentiated beta-cell phenotype and secrete insulin in response to glucose. Previously reported beta TC lines respond to subphysiological extracellular glucose levels compared with normal beta-cells. Recently, several beta TC lines were developed with normal glucose-regulated insulin secretion from insulinomas obtained by breeding of the RIP-Tag transgene from the original C57BI/6 mouse strain into the C3HeB/FeJ strain.

[Val12] HRAS downregulates GLUT2 in beta cells of transgenic mice without affecting glucose homeostasis.

Glucose-induced insulin release from pancreatic beta cells depends on the beta-cell metabolism of glucose, which generates intracellular signals for secretion. The beta-cell glucose transporter isotype GLUT2 and the glucose phosphorylating enzyme glucokinase have both been implicated in coupling insulin secretion to extracellular glucose levels. Here we present evidence that a pronounced decrease in beta-cell GLUT2 has no immediate effect on glucose homeostasis.

Calcium-binding proteins in the parathyroid gland. Detailed studies of parathyroid secretory protein.

In order to identify calcium (Ca2+)-binding proteins in the parathyroid gland, we used electrophoretic blots of proteins separated by a two-dimensional nondenaturing/denaturing gel system and incubated them with 45Ca2+. Parathyroid secretory protein (PSP) and proteins with approximate molecular weights of 98,000, 88,000, 58,000, and 30,000 were noted to bind Ca2+ in cytosolic fractions from bovine parathyroid, adrenal, and pituitary glands. However, differences in the binding affinity and capacity of the various proteins were observed.

Nucleotide sequence of beet western yellows virus RNA.

The nucleotide sequence of the genomic RNA (5641 nt) of beet western yellow virus (BWYV) isolated from lettuce has been determined and its genetic organization deduced. The sequence of the 3'terminal 2208 nt of RNA of a second BWYV isolate, obtained from sugarbeet, was also determined and was found to be very similar but not identical to that of the lettuce isolate. The complete sequence of BWYV RNA contains six long open reading frames (ORFs).

Interaction of the regulatory subunit of a type II cAMP-dependent protein kinase with mammalian sperm flagellum.

We have reported previously (Horowitz, J. A., Toeg, H.

Enhanced activation of cAMP-dependent protein kinase by rapid synthesis and degradation of cAMP.

Activation of cAMP-dependent protein kinase II by static and dynamic steady-state cAMP levels was studied by reconstituting an in vitro model system composed of hormone-sensitive adenylate cyclase, cyclic nucleotide phosphodiesterase, and cAMP-dependent protein kinase II. The rates of cAMP synthesis were regulated by incubating isolated membranes from AtT20 cells with various concentrations of forskolin. In the presence of 3-methylisobutylxanthine, the rate of protein kinase activation was proportional to the rate at which cAMP was synthesized, and there was a direct relationship between the degree of activation and the level of cAMP produced.

Somatostatin inhibits corticotropin-releasing factor-stimulated adrenocorticotropin release, adenylate cyclase, and activation of adenosine 3',5'-monophosphate-dependent protein kinase isoenzymes in AtT20 cells.

The mechanisms by which somatostatin (SRIF) inhibits CRF-induced ACTH secretion from AtT20 cells were characterized by comparing the effects of SRIF on cAMP production, adenylate cyclase activity, and activation of cAMP-dependent protein kinase isoenzymes with its effects on ACTH release. In isolated membranes, CRF (100 nM) stimulated adenylate cyclase activity 4- to 5-fold. SRIF inhibited CRF-stimulated adenylate cyclase in a concentration-dependent manner.

Differential binding of the regulatory subunits (RII) of cAMP-dependent protein kinase II from bovine brain and muscle to RII-binding proteins.

The association of regulatory subunits (RII) of Type II cAMP-dependent protein kinase from bovine cerebral cortex (RII-B) and bovine cardiac and skeletal muscle (RII-H) with specific binding proteins in bovine brain cytosol and purified brain microtubules was demonstrated using a solid phase binding assay. RII-binding proteins present in bovine cerebral cortex were immobilized on nitrocellulose filters after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Incubation of the filters with 32P-labeled regulatory subunits showed that both RII-B and RII-H interact with the 75,000-dalton calmodulin-binding protein (P75) and microtubule-associated protein 2 (MAP-2).

Postillumination adenosine triphosphate synthesis in Rhodospirillum rubrum chromatophores. I. Conditions for maximal yields.

The very low level of postillumination ATP synthesis in chromatophores was markedly stimulated when permeant anions (thiocyanate or perchlorate) or permeant cations (potassium in the presence of valinomycin) were added to the light stage. Although these compounds stimulated also light-induced proton uptake in chromatophores the pH dependence of both photoreactions was different. Proton uptake peaked at pH 6.

Postillumination adenosine triphosphate synthesis in Rhodospirillum rubrum chromatophores. II. Stimulation by a K+ diffusion potential.

Addition of valinomycin, nonactin, or monactin plus KCl in the dark to preilluminated chromatophores induced the synthesis of a large amount of ATP. This stimulation of postillumination ATP synthesis by a dark-imposed K+ diffusion potential was different from the stimulation caused by addition of permeant anions or cations in the light, since it increases when the pH of the light stage decreased from 8.0 to 6.