LGBTQ Utilization of a Statewide Tobacco Quitline: Engagement and Quitting Behavior, 2010-2022.

INTRODUCTION: Lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) individuals use tobacco at disproportionately high rates but are as likely as straight tobacco users to want to quit and to use quitlines. Little is known about the demographics and geographic distribution of LGBTQ quitline participants, their engagement with services, or their long-term outcomes. AIMS AND METHODS: Californians (N = 333 429) who enrolled in a statewide quitline 2010-2022 were asked about their sexual and gender minority (SGM) status and other baseline characteristics. All were offered telephone counseling. A subset (n = 19 431) was followed up at seven months. Data were analyzed in 2023 by SGM status (LGBTQ vs. straight) and county type (rural vs. urban). RESULTS: Overall, 7.0% of participants were LGBTQ, including 7.4% and 5.4% of urban and rural participants, respectively. LGBTQ participants were younger than straight participants but had similar cigarette consumption. Fewer LGBTQ participants reported a physical health condition (42.1% vs. 48.4%) but more reported a behavioral health condition (71.1% vs. 54.5%; both p's < .001). Among both LGBTQ and straight participants, nearly 9 in 10 chose counseling and both groups completed nearly three sessions on average. The groups had equivalent 30-day abstinence rates (24.5% vs. 23.2%; p = .263). Similar patterns were seen in urban and rural subgroups. CONCLUSIONS: LGBTQ tobacco users engaged with and appeared to benefit from a statewide quitline even though it was not LGBTQ community-based. A quitline with staff trained in LGBTQ cultural competence can help address the high prevalence of tobacco use in the LGBTQ community and reach members wherever they live. IMPLICATIONS: This study describes how participants of a statewide tobacco quitline broke down by sexual orientation and gender. It compares participants both by SGM status and by type of county to provide a more complete picture of quitline participation both in urban areas where LGBTQ community-based cessation programs may exist and in rural areas where they generally do not. To our knowledge, it is the first study to compare LGBTQ and straight participants on their use of quitline services and quitting aids, satisfaction with services received, and rates of attempting quitting and achieving prolonged abstinence from smoking.

Ultrastructural analysis of throat dermal tissue and chromatophore components in the threespine stickleback (Gasterosteus aculeatus).

The threespine stickleback (Gasterosteus aculeatus) is an important model for studying the evolution of nuptial coloration, but histological analyses of color are largely lacking. Previous analyses of one nuptial coloration trait, orange-red coloration along the body, have indicated carotenoids are the main pigment producing this color. In addition, recent gene expression studies found variation in the correlates of throat coloration between the sexes and between populations, raising the possibility of variation in the mechanisms underlying superficially similar coloration. We used transmission electron microscopy (TEM) to investigate the histological correlates of color in the throat dermal tissue of threespine stickleback from Western North America, within and between sexes, populations, and ecotypes. Ultrastructural analysis revealed carotenoid-containing erythrophores to be the main chromatophore component associated with orange-red coloration in both males and females across populations. In individuals where some darkening of the throat tissue was present, with no obvious orange-red coloration, erythrophores were not detected. Melanophore presence was more population-specific in expression, including being the only chromatophore component detected in a population of darker fish. We found no dermal chromatophore units within colorless throat tissue. This work confirms the importance of carotenoids and the erythrophore in producing orange-red coloration across sexes, as well as melanin within the melanophore in producing darkened coloration, but does not reveal broad histological differences among populations with similar coloration.

Fishing for subsistence constitutes a livelihood safety net for populations dependent on aquatic foods around the world.

Fishing for subsistence constitutes a livelihood safety net for poverty, malnutrition and gender inequality for populations dependent upon aquatic foods around the world. Here we provide global estimates showing that almost the same amount of small-scale fishers engage in subsistence fishing at some point during the year as in commercial employment and use subsistence estimates to measure small-scale fisheries' livelihood safety net function. In 2016, we estimate that 52.8 million people were engaged in subsistence fishing at some point during the year, while another 60.2 million people were commercially employed (90% of global fisheries employment). From 14 country case studies, it was possible to estimate that the subsistence catch provided an average apparent intake of six nutrients critical for positive health outcomes, equivalent to 26% of the recommended daily nutrient intake for 112.5 million people, higher than the national average contribution of beef or poultry.

Compensatory cross-talk between autophagy and glycolysis regulates senescence and stemness in heterogeneous glioblastoma tumor subpopulations.

Despite tremendous research efforts, successful targeting of aberrant tumor metabolism in clinical practice has remained elusive. Tumor heterogeneity and plasticity may play a role in the clinical failure of metabolism-targeting interventions for treating cancer patients. Moreover, compensatory growth-related processes and adaptive responses exhibited by heterogeneous tumor subpopulations to metabolic inhibitors are poorly understood. Here, by using clinically-relevant patient-derived glioblastoma (GBM) cell models, we explore the cross-talk between glycolysis, autophagy, and senescence in maintaining tumor stemness. We found that stem cell-like GBM tumor subpopulations possessed higher basal levels of glycolytic activity and increased expression of several glycolysis-related enzymes including, GLUT1/SLC2A1, PFKP, ALDOA, GAPDH, ENO1, PKM2, and LDH, compared to their non-stem-like counterparts. Importantly, bioinformatics analysis also revealed that the mRNA expression of glycolytic enzymes positively correlates with stemness markers (CD133/PROM1 and SOX2) in patient GBM tumors. While treatment with glycolysis inhibitors induced senescence in stem cell-like GBM tumor subpopulations, as evidenced by increased ß-galactosidase staining and upregulation of the cell cycle regulators p21Waf1/Cip1/CDKN1A and p16INK4A/CDKN2A, these cells maintained their aggressive stemness features and failed to undergo apoptotic cell death. Using various techniques including autophagy flux and EGFP-MAP1LC3B+ puncta formation analysis, we determined that inhibition of glycolysis led to the induction of autophagy in stem cell-like GBM tumor subpopulations, but not in their non-stem-like counterparts. Similarly, blocking autophagy in stem cell-like GBM tumor subpopulations induced senescence-associated growth arrest without hampering stemness capacity or inducing apoptosis while reciprocally upregulating glycolytic activity. Combinatorial treatment of stem cell-like GBM tumor subpopulations with autophagy and glycolysis inhibitors blocked the induction of senescence while drastically impairing their stemness capacity which drove cells towards apoptotic cell death. These findings identify a novel and complex compensatory interplay between glycolysis, autophagy, and senescence that helps maintain stemness in heterogeneous GBM tumor subpopulations and provides a survival advantage during metabolic stress.

Deleting specific residues from the HNH linkers creates a CRISPR-SpCas9 variant with high fidelity and efficiency.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) systems are immunological defenses used in archaea and bacteria to recognize and destroy DNA from external invaders. The CRISPR-SpCas9 system harnessed from Streptococcus pyogenes (SpCas9) has become the most widely utilized genome editing tool and shows promise for clinical application. However, the off-target effect is still the major challenge for the genome editing of CRISPR-SpCas9. Based on analysis of the structure and cleavage procedures, we proposed two strategies to modify the SpCas9 structure and reduce off-target effects. Shortening the HNH or REC3 linkers (Strategy #1) aimed to move the primary position of HNH or REC3 far away from the single-guide RNA (sgRNA)/DNA hybrid (hybrid), while elongating the helix around the sgRNA (Strategy #2) aimed to strengthen the contacts between SpCas9 and the sgRNA/DNA. We designed 11 SpCas9 variants (variant No.1- variant No.11) and verified their efficiencies on the classic genome site EMX1-1, EMX1-1-OT1, and EMX1-1-OT2. The top three effective SpCas9 variants, variant No.1, variant No.2, and variant No.5, were additionally validated on other genome sites. The further selected variant No.1 was compared with two previous SpCas9 variants, HypaCas9 (a hyper-accurate Cas9 variant released in 2017) and eSpCas9 (1.1) (an "enhanced specificity" SpCas9 variant released in 2016), on two genome sites, EMX1-1 and FANCF-1. The results revealed that the deletion of Thr769 and Gly906 could substantially decrease off-target effects, while maintaining robust on-target efficiency in most of the selected genome sites.

Laparoscopic Graham Patch for Anterior Duodenal Perforation in a 6-Year-Old.

Peptic ulcer disease causing perforation is extremely rare in children and primarily affects teenagers. We present a case of a perforated peptic ulcer in a 6-year-old with abdominal pain and emesis with CT findings of moderate pneumoperitoneum and pelvic free fluid without a distinct cause. He was emergently transferred, found to be peritonitic, and taken to the operating room for diagnostic laparoscopy revealing an anterior duodenal ulcer, and underwent laparoscopic Graham patch repair. Postoperatively, the child had positive fecal antigen for H. pylori. He was treated with triple therapy and underwent subsequent testing to confirm eradication. Perforated peptic ulcer is an uncommon pediatric surgical problem, and imaging may not be diagnostic as in the case presented here. Thus, clinicians need to maintain a high index of suspicion when evaluating children with free air and a surgical abdomen in the setting of long-standing abdominal pain.

Implementation, Maintenance, and Outcomes of an Electronic Referral to a Tobacco Quitline Across Five Health Systems.

INTRODUCTION: Electronic referral (e-referral) to quitlines helps connect tobacco-using patients to free, evidence-based cessation counseling. Little has been published about the real-world implementation of e-referrals across U.S. health systems, their maintenance over time, and the outcomes of e-referred patients. AIMS AND METHODS: Beginning in 2014, the University of California (UC)-wide project called UC Quits scaled up quitline e-referrals and related modifications to clinical workflows from one to five UC health systems. Implementation strategies were used to increase site readiness. Maintenance was supported through ongoing monitoring and quality improvement programs. Data on e-referred patients (n = 20 709) and quitline callers (n = 197 377) were collected from April 2014 to March 2021. Analyses of referral trends and cessation outcomes were conducted in 2021-2022. RESULTS: Of 20 709 patients referred, the quitline contacted 47.1%, 20.6% completed intake, 15.2% requested counseling, and 10.9% received it. In the 1.5-year implementation phase, 1813 patients were referred. In the 5.5-year maintenance phase, volume was sustained, with 3436 referrals annually on average. Among referred patients completing intake (n = 4264), 46.2% were nonwhite, 58.8% had Medicaid, 58.7% had a chronic disease, and 48.8% had a behavioral health condition. In a sample randomly selected for follow-up, e-referred patients were as likely as general quitline callers to attempt quitting (68.5% vs. 71.4%; p = .23), quit for 30 days (28.3% vs. 26.9%; p = .52), and quit for 6 months (13.6% vs. 13.9%; p = .88). CONCLUSIONS: With a whole-systems approach, quitline e-referrals can be established and sustained across inpatient and outpatient settings with diverse patient populations. Cessation outcomes were similar to those of general quitline callers. IMPLICATIONS: This study supports the broad implementation of tobacco quitline e-referrals in health care. To the best of our knowledge, no other paper has described the implementation of e-referrals across multiple U.S. health systems or how they were sustained over time. Modifying electronic health records systems and clinical workflows to enable and encourage e-referrals, if implemented and maintained appropriately, can be expected to improve patient care, make it easier for clinicians to support patients in quitting, increase the proportion of patients using evidence-based treatment, provide data to assess progress on quality goals, and help meet reporting requirements for tobacco screening and prevention.

Re-engagement of Low-Income Smokers in Quitline Services: Effects of Incentives and Method of Contact.

INTRODUCTION: Financial incentives have been shown to improve recruitment of low-income smokers into tobacco quitline services and to improve cessation outcomes. The present study evaluated their use to re-engage low-income smokers who had already used a quitline. AIMS AND METHODS: Randomly selected Medicaid smokers (N = 5200) who had previously enrolled in a quitline were stratified by time since enrollment (3, 6, 9, or 12 months) and randomly assigned in a 2 × 4 factorial design to receive, by mail or telephone, an invitation to reengage, with an offer of no financial incentive or $10, $20, or $40. The primary outcome measure was re-engagement, defined as use of an additional evidence-based quitline service within 90 days. Data were collected from May 2014 to October 2015 and analyzed in 2022. RESULTS: Of 5200 participants invited to reengage in quitline services, 9.3% did so within 90 days, compared to 6.3% of a randomly selected comparison group (n = 22 614, p < .0001). Letters resulted in greater re-engagement than calls (10.9% vs. 7.8%, respectively, p = .0001). Among letters, there was a dose-response relationship between incentive level and re-engagement rates (p = .003). Re-engagement decreased as time since enrollment increased, from 13.7% at 3 months to 5.7% at 12 months (all p's < 0.0001). CONCLUSIONS: Low-income smokers who previously used quitline services can be motivated to reengage in treatment. Mailed letters and automated calls are effective re-engagement strategies. Financial incentives can increase the effectiveness of re-engagement letters. Inviting Medicaid smokers to re-engage with quitline treatment may help to address socioeconomic health disparities and should be standard practice. IMPLICATIONS: Nicotine addiction is a chronic relapsing disorder, yet most cessation services are designed to help smokers through only one quit attempt. Smoking is increasingly concentrated in populations with physical and psychological co-morbidities, which can make quitting more difficult and impact whether smokers reach out for additional help following relapse. This study examined whether the timing, method, and content of an offer for further assistance influenced re-engagement rates for a vulnerable population of smokers-Medicaid beneficiaries. Relapsing smokers are responsive to re-engagement offers as early as three months, but there is a closing window of opportunity to reach them.

Quitline Promotion to Medicaid Members Who Smoke: Effects of COVID-19-Specific Messaging and a Free Patch Offer.

INTRODUCTION: People who smoke are at increased risk of serious COVID-19-related disease but have had reduced access to cessation treatment during the pandemic. This study tested 2 approaches to promoting quitline services to Medicaid members who smoke at high rates: using COVID-19-specific messaging and offering free nicotine patches. The hypotheses were that both would increase enrollment. METHODS: A California Medicaid mailing from October 2020 to January 2021 (N=7,489,093) included 4 versions of a flyer following a 2 × 2 design comparing generic with COVID-19-specific messaging and a no-patch with free-patch offer. The main outcome measure was quitline enrollments. Quit outcomes (attempted quitting, quit ≥7 days, quit ≥30 days) were assessed at 2 months. A subsequent free-patch offer was sent to all members (N=7,577,198) from April 2021 to June 2021. Data were collected in 2020-2021 and analyzed in 2022. RESULTS: The first mailing generated 1,753 enrollments. Response rates were 0.023% and 0.024% for generic and COVID-19-specific messaging, respectively (p=0.538), and 0.006% and 0.041% for no-patch and free-patch offers, respectively, the latter being 6.7 times more effective than the former (p<0.0001). Quit outcomes were comparable across conditions. The subsequent free-patch offer generated 3,546 enrollments at $40.28 per enrollee. CONCLUSIONS: In a Medicaid mailing during COVID-19, offering free patches generated more than 6 times as many quitline enrollments as offering generic help. COVID-19-specific messaging was no more effective than generic messaging. Offering free patches was highly cost-effective. Medicaid programs partnering with quitlines should consider using similar strategies, especially during a pandemic when regular health care is disrupted.

Effects of blueberry polyphenolic extract on vascular remodeling in spontaneously hypertensive rats.

Blueberry is considered a functional food due to various beneficial health effects associated with its consumption. Therefore, we examined the cardiovascular benefits of a blueberry polyphenolic extract in spontaneously hypertensive rats (SHR). Male SHR and Wistar-Kyoto (WKY) rats were administered with blueberry polyphenolic extract for 15 weeks. SHR showed significant augmented media-to-lumen ratio compared to WKY rats and blueberry polyphenolic extract significantly improved media-to-lumen ratio. SHR also had high blood pressure (BP), cardiac remodeling, and diastolic dysfunction and treatment did not affect BP or cardiac structure and function. SHR showed significantly increased the levels of malondialdehyde (MDA) and blueberry polyphenolic extract did not lower MDA. The levels of interleukin 6 and nitrate/nitrite ratio were unaltered in SHR. SHR showed a significant increase in the pro-apoptotic marker, Bax. Blueberry polyphenolic extract significantly lowered Bax. Our study shows that blueberry polyphenolic extract is beneficial in preventing vascular remodeling and cardiac apoptosis. PRACTICAL APPLICATIONS: Similar to many other berries, blueberries are repertoire of many phytochemicals including polyphenols. Along with its considerably well-established role as a sought after berry, blueberries have been at the forefront of approaches to hharnessing health benefits from plant food sources. Several studies have attempted to unravel the role of blueberry and their major phytochemicals in reducing the risk of cardiovascular diseases and reported their beneficial effects. Our pre-clinical study found that blueberry polyphenolic extract can reduce vascular remodeling in the setting of hypertension. This new finding further suggests the potential of blueberry-based phytochemicals. Further exploration of blueberries and their phytochemicals and positive outcomes from such studies can lead to substantial benefits for consumers and economy as a whole.

Evaluation of the Asian Smokers' Quitline: A Centralized Service for a Dispersed Population.

INTRODUCTION: Asian immigrants to the U.S. smoke at higher rates than U.S.-born Asians. However, few programs exist to help these immigrants quit and little is known about their real-world effectiveness. The Centers for Disease Control and Prevention funded the Asian Smokers' Quitline to serve Chinese, Korean, and Vietnamese immigrants nationwide. This study examines service utilization and outcomes from the first 7 years of the program. METHODS: From August 2012 to July 2019, the Asian Smokers' Quitline enrolled 14,073 Chinese-, Korean-, and Vietnamese-speaking smokers. Service utilization rates and cessation outcomes were compared with those of an earlier trial (conducted 2004-2008) that demonstrated the efficacy of an Asian-language telephone counseling protocol. Data were analyzed in 2019. RESULTS: Asian Smokers' Quitline participants came from all 50 states and the District of Columbia. The main referral sources were Asian-language newspapers (37.2%), family and friends (16.4%), healthcare providers (11.9%), and radio (11.9%). Overall, 37.6% were uninsured, 38.8% had chronic health conditions, and 15.4% had mental health conditions. Compared with participants in the earlier trial, Quitline participants received 1 fewer counseling session (3.8 vs 4.9, p<0.001) but were more likely to use pharmacotherapy (73.6% vs 20.9%, p<0.001). More than 90% were satisfied with the services they received. Six-month prolonged abstinence rates were higher in the Quitline than in the trial (complete case analysis: 28.6% vs 20.0%, p<0.001; intention-to-treat analysis: 20.5% vs 16.4%, p=0.005). CONCLUSIONS: The Asian Smokers' Quitline was utilized by >14,000 Asian-language-speaking smokers across the U.S. in its first 7 years. This quitline could serve as a model for delivering other behavioral services to geographically dispersed linguistic minority populations.

Correction: Shifting focus: The impacts of sustainable seafood certification.

[This corrects the article DOI: 10.1371/journal.pone.0233237.].

Shifting focus: The impacts of sustainable seafood certification.

Alongside government driven management initiatives to achieve sustainable fisheries management, there remains a role for market-based mechanisms to improve fisheries outcomes. Market-based mechanisms are intended to create positive economic incentives that improve the status and management of fisheries. Research to understand consumer demand for certified fish is central but needs to be mirrored by supply side understanding including why fisheries decide to gain or retain certification and the impact of certification on them and other stakeholders involved. We apply semi-structured interviews in seven different Marine Stewardship Council (MSC) certified fisheries that operate in (or from) Western Australia with the aim of better understanding fisheries sector participation in certification schemes (the supply side) and the impacts and unintended benefits and costs of certification. We find that any positive economic impacts of certification were only realised in a limited number of MSC fisheries in Western Australia, which may be explained by the fact that only a small proportion of Western Australian state-managed fisheries are sold with the MSC label and ex-vessel or consumer market price premiums are therefore mostly not obtained. Positive impacts of certification in these Western Australian fisheries are more of a social and institutional nature, for example, greater social acceptability and increased efficiency in the governance process respectively. However, opinion is divided on whether the combined non-monetary and monetary benefits outweigh the costs.

Effective fisheries management instrumental in improving fish stock status.

Marine fish stocks are an important part of the world food system and are particularly important for many of the poorest people of the world. Most existing analyses suggest overfishing is increasing, and there is widespread concern that fish stocks are decreasing throughout most of the world. We assembled trends in abundance and harvest rate of stocks that are scientifically assessed, constituting half of the reported global marine fish catch. For these stocks, on average, abundance is increasing and is at proposed target levels. Compared with regions that are intensively managed, regions with less-developed fisheries management have, on average, 3-fold greater harvest rates and half the abundance as assessed stocks. Available evidence suggests that the regions without assessments of abundance have little fisheries management, and stocks are in poor shape. Increased application of area-appropriate fisheries science recommendations and management tools are still needed for sustaining fisheries in places where they are lacking.

Making seafood accessible to low-income and nutritionally vulnerable populations on the U.S. West Coast.

Along the U.S. West Coast, sustainable management has rebuilt fish stocks, providing an opportunity to supply nutrient-rich food to adjacent coastal communities where food insecurity and diet-based diseases are common. However, the market has not successfully supplied locally sourced seafood to nutritionally vulnerable people. Rather, a few organizations make this connection on a limited scale. We used a "positive deviant" approach to learn how these organizations' efforts developed, how they overcame challenges, and what conditions enabled their interventions. We found that organizations in these positive deviant cases provided fish from a wide variety of species and sources, and distributed them through different channels to a diversity of end consumers. A key factor facilitating success was the ability to negotiate a price point that was both profitable and reasonable for organizations supplying nutritionally vulnerable or low-income consumers. Further-more, securing access to grants overcame initial costs of establishing new supply channels. All cases highlighted the importance of individual champions who encouraged development and cultural connections between the initiative and the nearby community. Organizations overcame key challenges by establishing regulations governing these new channels and either using partnerships or vertically integrating to reduce costs associated with processing and transport. Oftentimes training and education were also critical to instruct workers on how to process unfamiliar fish and to increase consumer awareness of local fish and how to prepare them. These lessons illuminate pathways to improve the contribution of local seafood to the healthy food system.

Activation of Cannabinoid Receptors Attenuates Endothelin-1-Induced Mitochondrial Dysfunction in Rat Ventricular Myocytes.

Evidence suggests that the activation of the endocannabinoid system offers cardioprotection. Aberrant energy production by impaired mitochondria purportedly contributes to various aspects of cardiovascular disease. We investigated whether cannabinoid (CB) receptor activation would attenuate mitochondrial dysfunction induced by endothelin-1 (ET1). Acute exposure to ET1 (4 hours) in the presence of palmitate as primary energy substrate induced mitochondrial membrane depolarization and decreased mitochondrial bioenergetics and expression of genes related to fatty acid oxidation (ie, peroxisome proliferator-activated receptor-gamma coactivator-1α, a driver of mitochondrial biogenesis, and carnitine palmitoyltransferase-1ß, facilitator of fatty acid uptake). A CB1/CB2 dual agonist with limited brain penetration, CB-13, corrected these parameters. AMP-activated protein kinase (AMPK), an important regulator of energy homeostasis, mediated the ability of CB-13 to rescue mitochondrial function. In fact, the ability of CB-13 to rescue fatty acid oxidation-related bioenergetics, as well as expression of proliferator-activated receptor-gamma coactivator-1α and carnitine palmitoyltransferase-1ß, was abolished by pharmacological inhibition of AMPK using compound C and shRNA knockdown of AMPKα1/α2, respectively. Interventions that target CB/AMPK signaling might represent a novel therapeutic approach to address the multifactorial problem of cardiovascular disease.

Poly(ADP-ribose) polymerase-1 inhibits mitochondrial respiration by suppressing PGC-1α activity in neurons.

Poly(ADP-ribose) polymerase-1 (PARP1) is a ubiquitous nuclear enzyme that regulates DNA repair and genomic stability. In oxidative genotoxic conditions, PARP1 activity is enhanced significantly, leading to excessive depletion of nicotinamide adenine dinucleotide (NAD+) and mitochondrial dysfunction. We hypothesized that PARP1-induced NAD+ depletion inhibits NAD+-dependent sirtuin deacetylase activity, thereby interfering with the mitochondrial regulator, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). The DNA alkylator, N'-Nitro-N-nitroso-N-methylguanidine (MNNG), induced NAD+ depletion, inhibited sirtuin deacetylase activity and enhanced acetylation of PGC-1α. This was associated with reduced interaction between PGC-1α and nuclear respiratory factor 1 (NRF-1), which is a nuclear transcription factor that drives mitochondrial replication by regulating mitochondrial transcription factor A (TFAM). MNNG also reduced binding of NRF-1 to the tfam upstream promoter region and reduced TFAM mRNA, mitochondrial DNA copy number and respiratory function. MNNG effects were mitigated by PARP1 inhibition and genetic loss of function, by enhancing intracellular NAD+ levels, and with sirtuin (SIRT1) gain of function, supporting a mechanism dependent on PARP1 activity, NAD+-depletion and SIRT1 inhibition. This and other work from our group supports a destructive sequelae of events related to PARP1-induced sirtuin inhibition and sirtuin-mediated regulation of transcription.

Endothelial NMDA receptors mediate activity-dependent brain hemodynamic responses in mice.

Dynamic coupling of blood supply with energy demand is a natural brain property that requires signaling between synapses and endothelial cells. Our previous work showed that cortical arteriole lumen diameter is regulated by N-methyl-d-aspartate receptors (NMDARs) expressed by brain endothelial cells. The purpose of this study was to determine whether endothelial NMDARs (eNMDARs) regulate functional hyperemia in vivo. In response to whisker stimulation, regional cerebral blood flow (rCBF) and hemodynamic responses were assessed in barrel cortex of awake wild-type or eNMDAR loss-of-function mice using two-photon microscopy. Hyperemic enhancement of rCBF and vasodilation throughout the vascular network was observed in wild-type mice. eNMDAR loss of function reduced hyperemic responses in rCBF and plasma flux in individual vessels. Discovery of an endothelial receptor that regulates brain hyperemia provides insight into how neuronal activity couples with endothelial cells.

The fishery performance indicators for global tuna fisheries.

We characterize the ecological, economic, and community performance of 21 major tuna fisheries, accounting for at least 77% of global tuna production, using the Fishery Performance Indicators. Our analysis reveals that the biggest variations in performance among tuna fisheries are driven by the final markets that they target: international sashimi market tuna fisheries considerably outperform a comparison set of 62 non-tuna fisheries in the Fishery Performance Indicator database, international canned tuna market fisheries perform similarly to the comparison set, and tuna fisheries supplying local markets in coastal states considerably underperform the comparison set. Differences among regional fishery management organizations primarily reflect regional species composition and market access, despite stark variation in governance, management, and other enabling conditions. With a legacy of open access, tuna's harvest sector performance is similar across all fisheries, reflecting only a normal return on the capital and skill invested: industrial vessels slightly outperform semi-industrial and artisanal vessels. Differences emerge in the post-harvest sector however, as value chains able to preserve quality and transport fish to high value markets outperform others.