Decades after the discovery that ionic zinc is present at high levels in glutamatergic synaptic vesicles, where, when, and how much zinc is released during synaptic activity remains highly ...controversial. Here we provide a quantitative assessment of zinc dynamics in the synaptic cleft and clarify its role in the regulation of excitatory neurotransmission by combining synaptic recordings from mice deficient for zinc signaling with Monte Carlo simulations. Ambient extracellular zinc levels are too low for tonic occupation of the GluN2A-specific nanomolar zinc sites on NMDA receptors (NMDARs). However, following short trains of physiologically relevant synaptic stimuli, zinc transiently rises in the cleft and selectively inhibits postsynaptic GluN2A-NMDARs, causing changes in synaptic integration and plasticity. Our work establishes the rules of zinc action and reveals that zinc modulation extends beyond hippocampal mossy fibers to excitatory SC-CA1 synapses. By specifically moderating GluN2A-NMDAR signaling, zinc acts as a widespread activity-dependent regulator of neuronal circuits.
•Ambient zinc levels are low (<10 nM), insufficient to occupy GluN2A-NMDA receptors•Repetitive synaptic stimuli are required for zinc modulation of NMDA-EPSCs•By targeting GluN2A-NMDARs, zinc controls synaptic integration and plasticity•Zinc action is prominent at both hippocampal mossy fibers and SC-CA1 synapses
Zinc has long been known to concentrate in synaptic vesicles of a subset of glutamatergic synapses. Vergnano et al. reveal the dynamics and function of synaptic zinc in regulating synaptic transmission, integration, and plasticity at hippocampal synapses.
Cancer Statistics for Hispanics/Latinos, 2018 Miller, Kimberly D.; Goding Sauer, Ann; Ortiz, Ana P. ...
CA: a cancer journal for clinicians,
November/December 2018, Letnik:
68, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Cancer is the leading cause of death among Hispanics/Latinos, who represent the largest racial/ethnic minority group in the United States, accounting for 17.8% (57.5 million) of the total population ...in the continental United States and Hawaii in 2016. In addition, more than 3 million Hispanic Americans live in the US territory of Puerto Rico. Every 3 years, the American Cancer Society reports on cancer occurrence, risk factors, and screening for Hispanics in the United States based on data from the National Cancer Institute, the North American Association of Central Cancer Registries, and the Centers for Disease Control and Prevention. For the first time, contemporary incidence and mortality rates for Puerto Rico, which has a 99% Hispanic population, are also presented. An estimated 149,100 new cancer cases and 42,700 cancer deaths will occur among Hispanics in the continental United States and Hawaii in 2018. For all cancers combined, Hispanics have 25% lower incidence and 30% lower mortality compared with non‐Hispanic whites, although rates of infection‐related cancers, such as liver, are up to twice as high in Hispanics. However, these aggregated data mask substantial heterogeneity within the Hispanic population because of variable cancer risk, as exemplified by the substantial differences in the cancer burden between island Puerto Ricans and other US Hispanics. For example, during 2011 to 2015, prostate cancer incidence rates in Puerto Rico (146.6 per 100,000) were 60% higher than those in other US Hispanics combined (91.6 per 100,000) and 44% higher than those in non‐Hispanic whites (101.7 per 100,000). Prostate cancer is also the leading cause of cancer death among men in Puerto Rico, accounting for nearly 1 in 6 cancer deaths during 2011‐2015, whereas lung cancer is the leading cause of cancer death among other US Hispanic men combined. Variations in cancer risk are driven by differences in exposure to cancer‐causing infectious agents and behavioral risk factors as well as the prevalence of screening. Strategies for reducing cancer risk in Hispanic populations include targeted, culturally appropriate interventions for increasing the uptake of preventive services and reducing cancer risk factor prevalence, as well as additional funding for Puerto Rico‐specific and subgroup‐specific cancer research and surveillance.
Cancer statistics for Hispanics/Latinos, 2015 Siegel, Rebecca L.; Fedewa, Stacey A.; Miller, Kimberly D. ...
CA: a cancer journal for clinicians,
November/December 2015, Letnik:
65, Številka:
6
Journal Article
Glutamate acts on postsynaptic glutamate receptors to mediate excitatory communication between neurons. The discovery that additional presynaptic glutamate receptors can modulate neurotransmitter ...release has added complexity to the way we view glutamatergic synaptic transmission. Here we review evidence of a physiological role for presynaptic glutamate receptors in neurotransmitter release. We compare the physiological roles of ionotropic and metabotropic glutamate receptors in short- and long-term regulation of synaptic transmission. Furthermore, we discuss the physiological conditions that are necessary for their activation, the source of the glutamate that activates them, their mechanisms of action and their involvement in higher brain function.
BACKGROUND
Stomach cancer was a leading cause of cancer‐related deaths early in the 20th century and has steadily declined over the last century in the United States. Although incidence and death ...rates are now low, stomach cancer remains an important cause of morbidity and mortality in black, Asian and Pacific Islander, and American Indian/Alaska Native populations.
METHODS
Data from the CONCORD‐2 study were used to analyze stomach cancer survival among males and females aged 15 to 99 years who were diagnosed in 37 states covering 80% of the US population. Survival analyses were corrected for background mortality using state‐specific and race‐specific (white and black) life tables and age‐standardized using the International Cancer Survival Standard weights. Net survival is presented up to 5 years after diagnosis by race (all, black, and white) for 2001 through 2003 and 2004 through 2009 to account for changes in collecting Surveillance, Epidemiology, and End Results Summary Stage 2000 data from 2004.
RESULTS
Almost one‐third of stomach cancers were diagnosed at a distant stage among both whites and blacks. Age‐standardized 5‐year net survival increased between 2001 to 2003 and 2004 to 2009 (26.1% and 29%, respectively), and no differences were observed by race. The 1‐year, 3‐year, and 5‐year survival estimates were 53.1%, 33.8%, and 29%, respectively. Survival improved in most states. Survival by stage was 64% (local), 28.2% (regional), and 5.3% (distant).
CONCLUSIONS
The current results indicate high fatality for stomach cancer, especially soon after diagnosis. Although improvements in stomach cancer survival were observed, survival remained relatively low for both blacks and whites. Primary prevention through the control of well‐established risk factors would be expected to have the greatest impact on further reducing deaths from stomach cancer. Cancer 2017;123:4994‐5013. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.
In this analysis of stomach cancer survival for 80% of the US population, age‐standardized 5‐year net survival remains low, but it improved slightly between 2001‐2003 and 2004‐2009. The differences between blacks and whites in pooled 5‐year survival for 37 states combined are not large. Primary prevention through control of well‐established risk factors will be an important public health action for the longer term.
Background Endometrial cancer (EC) mortality is particularly high among non-Hispanic Blacks and is twice that of non-Hispanic Whites. However, comparisons of EC survival outcomes by race/ethnicity ...are often confounded by histology and grade. Here, we analyze EC survival disparities in multiracial Florida with a focus on EC types (1 and 2) and subtypes, defined according to histology and grade. Methods All 27,809 cases of EC diagnosed during 2005–2016 were obtained from the Florida Cancer Registry. Age-standardized, 5-year cause-specific survival by race/ethnicity and histological type were calculated. Fine and Gray competing risk regression was used to estimate sub-distribution hazard ratios (sHRs) for associations between risk of death due to EC and potential predictive factors such as histology/grade, age, stage at diagnosis, and insurance. Results Type 2 EC accounted for only 38.7% of all incident EC-cases but 74.6% of all EC-deaths. Blacks were disproportionately affected by type 2 EC (57.6%) compared to Whites, Hispanics, and Asians (35.6%, 37.7%, and 43.0%, respectively). Age-adjusted 5-year survival for types 1 and 2 were 85.3% and 51.6%, respectively; however, there was wide variation within type 2 subtypes, ranging from 60.2% for mixed cell EC to as low as 30.1% for carcinosarcoma. In the multivariable model, Blacks with type 2 EC had a 23% higher risk of death due to EC (sHR: 1.23, 95%CI: 1.12–1.36) compared to Whites. Conclusions Population-based analyses should consider the histological heterogeneity of EC because the less common type 2 EC drives racial/ethnic survival disparities in EC. Black women have a higher proportion of more aggressive histological types and an overall higher risk of death due to EC than Whites. To the extent that some of these histological types may be considered different diseases and require specific treatment approaches, further research on etiology and prognosis for detailed type 2 EC subtypes is warranted.
Cancer incidence disparities exist among specific Asian American populations. However, the existing reports exclude data from large metropoles like Chicago, Houston and New York. Moreover, incidence ...rates by subgroup have been underestimated due to the exclusion of Asians with unknown subgroup. Cancer incidence data for 2009 to 2011 for eight states accounting for 68% of the Asian American population were analyzed. Race for cases with unknown subgroup was imputed using stratified proportion models by sex, age, cancer site and geographic regions. Age‐standardized incidence rates were calculated for 17 cancer sites for the six largest Asian subgroups. Our analysis comprised 90,709 Asian and 1,327,727 non‐Hispanic white cancer cases. Asian Americans had significantly lower overall cancer incidence rates than non‐Hispanic whites (336.5 per 100,000 and 541.9 for men, 299.6 and 449.3 for women, respectively). Among specific Asian subgroups, Filipino men (377.4) and Japanese women (342.7) had the highest overall incidence rates while South Asian men (297.7) and Korean women (275.9) had the lowest. In comparison to non‐Hispanic whites and other Asian subgroups, significantly higher risks were observed for colorectal cancer among Japanese, stomach cancer among Koreans, nasopharyngeal cancer among Chinese, thyroid cancer among Filipinos, and liver cancer among Vietnamese. South Asians had remarkably low lung cancer risk. Overall, Asian Americans have a lower cancer risk than non‐Hispanic whites, except for nasopharyngeal, liver and stomach cancers. The unique portrayal of cancer incidence patterns among specific Asian subgroups in this study provides a new baseline for future cancer surveillance research and health policy.
What's new?
The U.S. Asian American population is remarkably diverse, with subgroups differing culturally as well as in lifestyle and genetics. The extreme heterogeneity, however, presents significant challenges for cancer incidence assessments. Here, data from the Surveillance, Epidemiology, and End Results program and the National Program of Cancer Registries were combined, ensuring a broad representation of U.S. Asian Americans, and Asians of unknown subgroup were stratified according to multiple factors. The analyses show that overall cancer incidence is lower in Asian Americans than non‐Hispanic whites. Asian Americans, however, are at increased risk of liver, stomach, and nasopharyngeal cancers.
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