Title: Chicago's Short-Lived 'Soda Tax' Cut Consumption, Boosted Health Care Funds
Category: Health News
Created: 2/24/2020 12:00:00 AM
Last Editorial Review: 2/25/2020 12:00:00 AM

Title: Breast Self-Exam Rates Go Up With Counseling
Category: Health News
Created: 5/1/2009 2:00:00 AM
Last Editorial Review: 5/1/2009 12:00:00 AM

Title: Higher Vitamin D, Better Golden Years?
Category: Health News
Created: 4/26/2010 11:08:00 AM
Last Editorial Review: 4/26/2010 11:08:04 AM

Title: Health Tip: Understanding Impetigo
Category: Health News
Created: 4/30/2010 8:10:00 AM
Last Editorial Review: 4/30/2010 12:00:00 AM

Title: Record Number of Americans Got Flu Shots, CDC Says
Category: Health News
Created: 4/29/2010 4:10:00 PM
Last Editorial Review: 4/30/2010 12:00:00 AM

Title: Secondhand Smoke Tied to Lower 'Good' Cholesterol in Teen Girls
Category: Health News
Created: 4/30/2013 2:35:00 PM
Last Editorial Review: 5/1/2013 12:00:00 AM

Title: Health Tip: Got Power?
Category: Health News
Created: 5/3/2013 8:35:00 AM
Last Editorial Review: 5/3/2013 12:00:00 AM

Title: Statin Users Eating More Bad Food Than a Decade Ago, Study Shows
Category: Health News
Created: 4/25/2014 12:35:00 PM
Last Editorial Review: 4/28/2014 12:00:00 AM

Title: Alzheimer's Variation May Often Go Unrecognized: Study
Category: Health News
Created: 5/2/2014 9:35:00 AM
Last Editorial Review: 5/2/2014 12:00:00 AM

Title: Got Unwanted Pills? Drug Take-Back Day Is April 30
Category: Health News
Created: 4/28/2016 12:00:00 AM
Last Editorial Review: 4/28/2016 12:00:00 AM

Title: Health Tip: Got Eczema?
Category: Health News
Created: 4/28/2016 12:00:00 AM
Last Editorial Review: 4/28/2016 12:00:00 AM

Title: Gotta Minute? Get a Good Workout
Category: Health News
Created: 4/27/2016 12:00:00 AM
Last Editorial Review: 4/28/2016 12:00:00 AM

Title: Spanking: More Harm Than Good?
Category: Health News
Created: 4/27/2016 12:00:00 AM
Last Editorial Review: 4/28/2016 12:00:00 AM

Title: Coffee, Wine Good for Healthy Gut, Sodas May Be Bad
Category: Health News
Created: 4/28/2016 12:00:00 AM
Last Editorial Review: 4/29/2016 12:00:00 AM

Title: 'You've Got Cancer' Can Take Devastating Mental Toll
Category: Health News
Created: 4/28/2016 12:00:00 AM
Last Editorial Review: 4/29/2016 12:00:00 AM

Title: Life Expectancy Goes Up for Black Americans
Category: Health News
Created: 5/2/2017 12:00:00 AM
Last Editorial Review: 5/3/2017 12:00:00 AM

Title: 'Dr. Google' May Undermine Parents' Trust in Their Pediatrician
Category: Health News
Created: 5/5/2017 12:00:00 AM
Last Editorial Review: 5/5/2017 12:00:00 AM

Title: With 'Super Gonorrhea' a Threat, Many Still Getting Wrong Antibiotics
Category: Health News
Created: 4/27/2018 12:00:00 AM
Last Editorial Review: 4/30/2018 12:00:00 AM

Title: Rock Climbing Goes Mainstream for Exercise Buffs
Category: Health News
Created: 5/1/2018 12:00:00 AM
Last Editorial Review: 5/1/2018 12:00:00 AM

Title: Skin's 'Good' Bacteria May Be Promising Weapon Against Eczema
Category: Health News
Created: 5/3/2018 12:00:00 AM
Last Editorial Review: 5/3/2018 12:00:00 AM

Title: Care at VA Hospitals as Good or Better Than Elsewhere in U.S.: Report
Category: Health News
Created: 5/4/2018 12:00:00 AM
Last Editorial Review: 5/4/2018 12:00:00 AM

Title: Scientists Probe Mystery of How Hair Prematurely Goes Gray
Category: Health News
Created: 5/3/2018 12:00:00 AM
Last Editorial Review: 5/4/2018 12:00:00 AM

Title: For Kids, Obesity and Mental Health Woes Often Go Hand-in-Hand
Category: Health News
Created: 4/27/2019 12:00:00 AM
Last Editorial Review: 4/29/2019 12:00:00 AM

Title: MS Patients Now Pay 20 Times More for Drugs Than a Decade Ago
Category: Health News
Created: 5/1/2019 12:00:00 AM
Last Editorial Review: 5/2/2019 12:00:00 AM

Title: AHA News: Firefighter In Need of a New Heart Got By With a Little Help From His Friends
Category: Health News
Created: 4/24/2020 12:00:00 AM
Last Editorial Review: 4/27/2020 12:00:00 AM

Title: Bats and Coronaviruses Go Back Centuries
Category: Health News
Created: 4/28/2020 12:00:00 AM
Last Editorial Review: 4/28/2020 12:00:00 AM

Title: In COVID Crisis, Nearly Half of People in Some U.S. States Are Going Hungry
Category: Health News
Created: 4/28/2020 12:00:00 AM
Last Editorial Review: 4/28/2020 12:00:00 AM

Title: Pangolins Hold Clues to How COVID-19 Began -- and Might End
Category: Health News
Created: 5/8/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 12:00:00 AM

Title: Trump Says Obamacare Must Go as U.S. Coronavirus Cases Climb Past 1.2 Million
Category: Health News
Created: 5/7/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 12:00:00 AM

Bill Hanage describes the many uncertainties surrounding current data examining the prevalence of SARS-CoV-2.

Many doctors are considering retiring, but fear they'll miss the patient interaction, mental stimulation, and income. There are ways to have it all.

In a sign of the times and things to come, in-person cardiovascular society meetings pivot to virtual events.

COVID-19 has led the ESC to transition its annual congress to a virtual format; ESC 2020 Congress 'Challenging Times, Infinite Possibilities' will run online from August 29 to September 1.

Learning more about this evolutionary advantage in pangolins may suggest possible treatments for coronavirus in humans, the team said.

Title: HDL vs. LDL Cholesterol (Good and Bad)
Category: Diseases and Conditions
Created: 7/14/2017 12:00:00 AM
Last Editorial Review: 12/11/2019 12:00:00 AM

For any journal issue that has at least one open access or early access article, PMC is now displaying the table of contents (TOC) in advance of the whole issue becoming available. Not to worry, though—only those articles specified for early release are immediately viewable in PMC. As consistent with the terms of access in the journal agreement, the other articles will only become available on their specified release date, as shown in the TOC below.

The journal's accessiblity, as indicated on the PMC Journal list also has not changed; for example, Plant Physiology's embargo period is still 12 months. What has changed is that the issues with “preview” TOCs now additionally appear on the journal's archive page. Publishers and others can rest assured, however, that no access terms for any journal have been changed with the unveiling of this new format.

The PMC Canada manuscript submission system was released on April 28, 2010. The system will enable researchers funded by the Canadian Institutes of Health Research to deposit their peer-reviewed research publications, in compliance with CIHR's Policy on Access to Research Outputs.

Title: Pilates May Be Good Medicine for High Blood Pressure
Category: Health News
Created: 4/6/2020 12:00:00 AM
Last Editorial Review: 4/7/2020 12:00:00 AM

Title: Baqsimi (glucagon)
Category: Medications
Created: 4/22/2020 12:00:00 AM
Last Editorial Review: 4/22/2020 12:00:00 AM

Title: Money Not a Good Measure of Your Self-Worth
Category: Health News
Created: 4/14/2020 12:00:00 AM
Last Editorial Review: 4/15/2020 12:00:00 AM

Title: Want Fewer UTIs? Go Vegetarian, Study Suggests
Category: Health News
Created: 1/30/2020 12:00:00 AM
Last Editorial Review: 1/31/2020 12:00:00 AM

Title: Got Flu? Deal Quickly With Complications
Category: Health News
Created: 2/2/2020 12:00:00 AM
Last Editorial Review: 2/3/2020 12:00:00 AM

Title: Have a Hangover? Try This Herbal Remedy
Category: Health News
Created: 5/1/2020 12:00:00 AM
Last Editorial Review: 5/4/2020 12:00:00 AM

Title: A Consistent Bedtime Is Good for Your Heart
Category: Health News
Created: 4/3/2020 12:00:00 AM
Last Editorial Review: 4/6/2020 12:00:00 AM

Title: First Good Evidence That Brain Hits 'Replay' While You Sleep
Category: Health News
Created: 5/5/2020 12:00:00 AM
Last Editorial Review: 5/6/2020 12:00:00 AM

TNF-related apoptosis-inducing ligand (TRAIL) and an agonistic antibody against the death-inducing TRAIL receptor 5, DR5, are thought to selectively induce tumor cell death and therefore, have gained attention as potential therapeutics currently under investigation in several clinical trials. However, some tumor cells are resistant to TRAIL/DR5–induced cell death, even though they express DR5. Previously, we reported that DR5 is transported into the nucleus by importin β1, and knockdown of importin β1 upregulates cell surface expression of DR5 resulting in increased TRAIL sensitivity in vitro. Here, we examined the impact of importin β1 knockdown on agonistic anti-human DR5 (hDR5) antibody therapy. Drug-inducible importin β1 knockdown sensitizes HeLa cells to TRAIL-induced cell death in vitro, and exerts an antitumor effect when combined with agonistic anti-hDR5 antibody administration in vivo. Therapeutic importin β1 knockdown, administered via the atelocollagen delivery system, as well as treatment with the importin β inhibitor, importazole, induced regression and/or eradication of two human TRAIL-resistant tumor cells when combined with agonistic anti-hDR5 antibody treatment. Thus, these findings suggest that the inhibition of importin β1 would be useful to improve the therapeutic effects of agonistic anti-hDR5 antibody against TRAIL-resistant cancers.

Many clinical studies and epidemiological investigations have clearly demonstrated that women are twice as likely to develop cholesterol gallstones as men, and oral contraceptives and other estrogen therapies dramatically increase that risk. Further, animal studies have revealed that estrogen promotes cholesterol gallstone formation through the estrogen receptor (ER) α, but not ERβ, pathway. More importantly, some genetic and pathophysiological studies have found that G protein-coupled estrogen receptor (GPER) 1 is a new gallstone gene, Lith18, on chromosome 5 in mice and produces additional lithogenic actions, working independently of ERα, to markedly increase cholelithogenesis in female mice. Based on computational modeling of GPER, a novel series of GPER-selective antagonists were designed, synthesized, and subsequently assessed for their therapeutic effects via calcium mobilization, cAMP, and ERα and ERβ fluorescence polarization binding assays. From this series of compounds, one new compound, 2-cyclohexyl-4-isopropyl-N-(4-methoxybenzyl)aniline (CIMBA), exhibits superior antagonism and selectivity exclusively for GPER. Furthermore, CIMBA reduces the formation of 17β-estradiol-induced gallstones in a dose-dependent manner in ovariectomized mice fed a lithogenic diet for 8 weeks. At 32 μg/day/kg CIMBA, no gallstones are found, even in ovariectomized ERα (^–/–) mice treated with 6 μg/day 17β-estradiol and fed the lithogenic diet for 8 weeks. In conclusion, CIMBA treatment protects against the formation of estrogen-induced cholesterol gallstones by inhibiting the GPER signaling pathway in female mice. CIMBA may thus be a new agent for effectively treating cholesterol gallstone disease in women.­

ABSTRACT

In the absence of a vaccine, multidrug-resistant Neisseria gonorrhoeae has emerged as a major human health threat, and new approaches to treat gonorrhea are urgently needed. N. gonorrhoeae pili are posttranslationally modified by a glycan that terminates in a galactose. The terminal galactose is critical for initial contact with the human cervical mucosa via an interaction with the I-domain of complement receptor 3 (CR3). We have now identified the I-domain galactose-binding epitope and characterized its galactose-specific lectin activity. Using surface plasmon resonance and cellular infection assays, we found that a peptide mimic of this galactose-binding region competitively inhibited the N. gonorrhoeae-CR3 interaction. A compound library was screened for potential drugs that could similarly prohibit the N. gonorrhoeae-CR3 interaction and be repurposed as novel host-targeted therapeutics for multidrug-resistant gonococcal infections in women. Two drugs, methyldopa and carbamazepine, prevented and cured cervical cell infection by multidrug-resistant gonococci by blocking the gonococcal-CR3 I-domain interaction.

IMPORTANCE Novel therapies that avert the problem of Neisseria gonorrhoeae with acquired antibiotic resistance are urgently needed. Gonococcal infection of the human cervix is initiated by an interaction between a galactose modification made to its surface appendages, pili, and the I-domain region of (host) complement receptor 3 (CR3). By targeting this crucial gonococcal–I-domain interaction, it may be possible to prevent cervical infection in females. To this end, we identified the I-domain galactose-binding epitope of CR3 and characterized its galactose lectin activity. Moreover, we identified two drugs, carbamazepine and methyldopa, as effective host-targeted therapies for gonorrhea treatment. At doses below those currently used for their respective existing indications, both carbamazepine and methyldopa were more effective than ceftriaxone in curing cervical infection ex vivo. This host-targeted approach would not be subject to N. gonorrhoeae drug resistance mechanisms. Thus, our data suggest a long-term solution to the growing problem of multidrug-resistant N. gonorrhoeae infections.

ABSTRACT

The ubiquitous parasite Toxoplasma gondii exhibits an impressive ability to maintain chronic infection of its host for prolonged periods. Despite this, little is known regarding whether and how T. gondii bradyzoites, a quasi-dormant life stage residing within intracellular cysts, manipulate the host cell to maintain persistent infection. A previous proteomic study of the cyst wall, an amorphous layer of proteins that forms underneath the cyst membrane, identified MYR1 as a putative cyst wall protein in vitro. Because MYR1 is known to be involved in the translocation of parasite-derived effector proteins into the host cell, we sought to determine whether parasites transitioning toward the bradyzoite life stage retain the capacity to translocate proteins via this pathway. By epitope tagging the endogenous loci of four known effectors that translocate from the parasitophorous vacuole into the host cell nucleus, we show, by immunofluorescence assays, that most effectors accumulate in the host nucleus at early but not late time points after infection, during the tachyzoite-to-bradyzoite transition and when parasites further along the bradyzoite differentiation continuum invade a new host cell. We demonstrate that the suppression of interferon gamma signaling, which was previously shown to be mediated by the effector TgIST, also occurs in the context of prolonged infection with bradyzoites and that TgIST export is a process that occurs beyond the early stages of host cell infection. These findings have important implications regarding how this highly successful parasite maintains persistent infection of its host.

IMPORTANCE Toxoplasma bradyzoites persist within tissue cysts and are refractory to current treatments, serving as a reservoir for acute complications in settings of compromised immunity. Much remains to be understood regarding how this life stage successfully establishes and maintains persistent infection. In this study, we investigated whether the export of parasite effector proteins into the host cell occurs during the development of in vitro tissue cysts. We quantified the presence of four previously described effectors in host cell nuclei at different time points after bradyzoite differentiation and found that they accumulated largely during the early stages of infection. Despite a decline in nuclear accumulation, we found that one of these effectors still mediated its function after prolonged infection with bradyzoites, and we provide evidence that this effector is exported beyond early infection stages. These findings suggest that effector export from within developing tissue cysts provides one potential mechanism by which this parasite achieves chronic infection.

ABSTRACT

Bacillus subtilis contains two known cyclic di-GMP (c-di-GMP)-dependent receptors, YdaK and DgrA, as well as three diguanylate cyclases (DGCs): soluble DgcP and membrane-integral DgcK and DgcW. DgrA regulates motility, while YdaK is responsible for the formation of a putative exopolysaccharide, dependent on the activity of DgcK. Using single-molecule tracking, we show that a majority of DgcK molecules are statically positioned in the cell membrane but significantly less so in the absence of YdaK but more so upon overproduction of YdaK. The soluble domains of DgcK and of YdaK show a direct interaction in vitro, which depends on an intact I-site within the degenerated GGDEF domain of YdaK. These experiments suggest a direct handover of a second messenger at a single subcellular site. Interestingly, all three DGC proteins contribute toward downregulation of motility via the PilZ protein DgrA. Deletion of dgrA also affects the mobility of DgcK within the membrane and also that of DgcP, which arrests less often at the membrane in the absence of DgrA. Both, DgcK and DgcP interact with DgrA in vitro, showing that divergent as well as convergent direct connections exist between cyclases and their effector proteins. Automated determination of molecule numbers in live cells revealed that DgcK and DgcP are present at very low copy numbers of 6 or 25 per cell, respectively, such that for DgcK, a part of the cell population does not contain any DgcK molecule, rendering signaling via c-di-GMP extremely efficient.

IMPORTANCE Second messengers are free to diffuse through the cells and to activate all responsive elements. Cyclic di-GMP (c-di-GMP) signaling plays an important role in the determination of the life style transition between motility and sessility/biofilm formation but involves numerous distinct synthetases (diguanylate cyclases [DGCs]) or receptor pathways that appear to act in an independent manner. Using Bacillus subtilis as a model organism, we show that for two c-di-GMP pathways, DGCs and receptor molecules operate via direct interactions, where a synthesized dinucleotide appears to be directly used for the protein-protein interaction. We show that very few DGC molecules exist within cells; in the case of exopolysaccharide (EPS) formation via membrane protein DgcK, the DGC molecules act at a single site, setting up a single signaling pool within the cell membrane. Using single-molecule tracking, we show that the soluble DGC DgcP arrests at the cell membrane, interacting with its receptor, DgrA, which slows down motility. DgrA also directly binds to DgcK, showing that divergent as well as convergent modules exist in B. subtilis. Thus, local-pool signal transduction operates extremely efficiently and specifically.