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A novel bacterium was isolated from the subgingival plaque of a patient with periodontal disease. Bacterial strain BA112T is a facultative Gram-positive coccus. It metabolizes alanine, arginine, glycine, histidine, leucine, proline, serine and tyrosine, but does not appear to use carbohydrates. Urease, esculin, indole, catalase and nitrate reduction tests were all negative. Major cellular fatty acids were C18:0 , C12:0 , C16:0 , C18:1 w9c and C20:0 . The genome was sequenced and is 2.4 Mbp in length and has 64% GC content. Based on phylogenetics of the 16S rRNA sequence and concatenated alignments of 37 conserved proteins, BA112T belongs to the family Actinomycetaceae but is located on a branch of the tree without currently named members. Based on our phenotypic and phylogenetic studies, we propose that BA112T is the first known representative of a new genus, for which the name Peptidiphaga gingivicola gen. nov., sp. nov. is proposed. The type strain is BA112T . [ABSTRACT FROM AUTHOR]

Aim: Recently we have observed differences in the ability of metformin and AICAR to repress glucose production from hepatocytes using 8CPT-cAMP. Previous results indicate that, in addition to activating protein kinase A, 8CPT-modified cAMP analogues suppress the nitrobenzylthioinosine (NBMPR)-sensitive equilibrative nucleoside transporter ENT1. We aimed to exploit 8CPT-cAMP, 8CPT-2-Methyl-O-cAMP and NBMPR, which is highly selective for a high-affinity binding-site on ENT1, to investigate the role of ENT1 in the liver-specific glucose-lowering properties of AICAR and metformin., Methods: Primary mouse hepatocytes were incubated with AICAR and metformin in combination with cAMP analogues, glucagon, forskolin and NBMPR. Hepatocyte glucose production (HGP) and AMPK signalling were measured, and a uridine uptake assay with supporting LC-MS was used to investigate nucleoside depletion from medium by cells., Results: AICAR and metformin increased AMPK pathway phosphorylation and decreased HGP induced by dibutyryl cAMP and glucagon. HGP was also induced by 8CPT-cAMP, 8CPT-2-Methyl-O-cAMP and NBMPR; however, in each case this was resistant to suppression by AICAR but not by metformin. Cross-validation of tracer and mass spectrometry studies indicates that 8CPT-cAMP, 8CPT-2-Methyl-O-cAMP and NBMPR inhibited the effects of AICAR, at least in part, by impeding its uptake into hepatocytes., Conclusions: We report for the first time that suppression of ENT1 induces HGP. ENT1 inhibition also impedes uptake and the effects of AICAR, but not metformin, on HGP. Further investigation of nucleoside transport may illuminate a better understanding of how metformin and AICAR each regulate HGP., (© 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To test the hypothesis that, given the role of AMP-activated protein kinase (AMPK) in regulating intracellular ATP levels, AMPK may alter ATP release from astrocytes, the main sources of extracellular ATP (eATP) within the brain., Materials and Methods: Measurements of ATP release were made from human U373 astrocytoma cells, primary mouse hypothalamic (HTAS) and cortical astrocytes (CRTAS) and wild-type and AMPK α1/α2 null mouse embryonic fibroblasts (MEFs). Cells were treated with drugs known to modulate AMPK activity: A-769662, AICAR and metformin, for up to 3 hours. Intracellular calcium was measured using Fluo4 and Fura-2 calcium-sensitive fluorescent dyes., Results: In U373 cells, A-769662 (100 μM) increased AMPK phosphorylation, whereas AICAR and metformin (1 mM) induced a modest increase or had no effect, respectively. Only A-769662 increased eATP levels, and this was partially blocked by AMPK inhibitor Compound C. A-769662-induced increases in eATP were preserved in AMPK α1/α2 null MEF cells. A-769662 increased intracellular calcium in U373, HTAS and CRTAS cells and chelation of intracellular calcium using BAPTA-AM reduced A-769662-induced eATP levels. A-769662 also increased ATP release from a number of other central and peripheral endocrine cell types., Conclusions: AMPK is required to maintain basal eATP levels but is not required for A-769662-induced increases in eATP. A-769662 (>50 μM) enhanced intracellular calcium levels leading to ATP release in an AMPK and purinergic receptor independent pathway., (© 2017 John Wiley & Sons Ltd.)

Background: This retrospective follow-up study evaluated mortality during 1970-1996 among 6,956 employees at a petrochemical research facility in Illinois., Methods: Standardized mortality ratios (SMRs) compared employees' mortality rates with those of the Illinois general population. Poisson regression procedures estimated rate ratios for various subject subgroups compared to other facility employees., Results: Subjects had 267 observed/524 expected deaths (SMR = 51) from all causes combined and a large deficit of deaths from all cancers (76/136, SMR = 56) and from most other major diseases. Other results included fewer than expected brain cancers (1/4.0, SMR = 25) and a slight increase in colorectal cancer (20/14, SMR = 139) that was concentrated in white male scientists employed for one of the three main companies at the facility (SMR = 295, RR = 2.6)., Conclusions: The deficit of brain cancer deaths contrasts with an excess incidence seen in a companion study. Subjects' generally favorable mortality experience probably reflects socioeconomic advantages of employees relative to the Illinois general population., (Copyright 2001 Wiley-Liss, Inc.)

Background: From 1970 through 1997, 17 intracranial neoplasms were identified among 6,800 employees of a petrochemical research facility. This investigation describes the case-series., Methods: The intracranial neoplasms were identified by self reports and record linkages, and were confirmed by medical records and a pathology review. Standardized incidence ratios (SIRs) compare observed and expected numbers of cases according to certain work characteristics., Results: Overall, there were 17 observed and 10.5 expected intracranial neoplasms, including 11/4.7 benign intracranial tumors and 6/5.9 brain cancers. All brain cancers occurred among male research scientists or technicians. Four had worked at some time on the same floor of one building (SIR=12.6, 95% CI=3.4-32.1), and several had worked on a research project with at least one other brain cancer case. The benign intracranial neoplasm cases did not have common building assignments or work activities., Conclusions: The occurrence pattern of brain cancers, but not that of benign tumors, suggests a possible occupational etiology., (Copyright 1999 Wiley-Liss, Inc.)

A range of variation in percent of oxygen saturation of arterial hemoglobin (SaO2) among healthy individuals at a given high altitude indicates differences in physiological hypoxemia despite uniform ambient hypoxic stress. In populations native to the Tibetan plateau, a significant portion of the variance is attributable to additive genetic factors, and there is a major gene influencing SaO2. To determine whether there is genetic variance in other high-altitude populations, we designed a study to test the hypothesis that additive genetic factors contribute to phenotypic variation in SaO2 among Aymara natives of the Andean plateau, a population geographically distant from the Tibetan plateau and with a long, separate history of high-altitude residence. The average SaO2 of 381 Aymara at 3,900-4,000 m was 92+/-0.15% (SEM) with a range of 84-99%. The average was 2.6% higher than the average SaO2 of a sample of Tibetans at 3,800-4,065 m measured with the same techniques. Quantitative genetic analyses of the Aymara sample detected no significant variance attributable to genetic factors. The presence of genetic variance in SaO2 in the Tibetan sample and its absence in the Aymara sample indicate there is potential for natural selection on this trait in the Tibetan but not the Aymara population.

Elevated hemoglobin concentrations have been reported for high-altitude sojourners and Andean high-altitude natives since early in the 20th century. Thus, reports that have appeared since the 1970s describing relatively low hemoglobin concentration among Tibetan high-altitude natives were unexpected. These suggested a hypothesis of population differences in hematological response to high-altitude hypoxia. A case of quantitatively different responses to one environmental stress would offer an opportunity to study the broad evolutionary question of the origin of adaptations. However, many factors may confound population comparisons. The present study was designed to test the null hypothesis of no difference in mean hemoglobin concentration of Tibetan and Aymara native residents at 3,800-4,065 meters by using healthy samples that were screened for iron deficiency, abnormal hemoglobins, and thalassemias, recruited and assessed using the same techniques. The hypothesis was rejected, because Tibetan males had a significantly lower mean hemoglobin concentration of 15.6 gm/dl compared with 19.2 gm/dl for Aymara males, and Tibetan females had a mean hemoglobin concentration of 14.2 gm/dl compared with 17.8 gm/dl for Aymara females. The Tibetan hemoglobin distribution closely resembled that from a comparable, sea-level sample from the United States, whereas the Aymara distribution was shifted toward 3-4 gm/dl higher values. Genetic factors accounted for a very high proportion of the phenotypic variance in hemoglobin concentration in both samples (0.86 in the Tibetan sample and 0.87 in the Aymara sample). The presence of significant genetic variance means that there is the potential for natural selection and genetic adaptation of hemoglobin concentration in Tibetan and Aymara high-altitude populations.

Newcomers acclimatizing to high altitude and adult male Tibetan high altitude natives have increased ventilation relative to sea level natives at sea level. However, Andean and Rocky Mountain high altitude natives have an intermediate level of ventilation lower than that of newcomers and Tibetan high altitude natives although generally higher than that of sea level natives at sea level. Because the reason for the relative hypoventilation of some high altitude native populations was unknown, a study was designed to describe ventilation from adolescence through old age in samples of Tibetan and Andean high altitude natives and to estimate the relative genetic and environmental influences. This paper compares resting ventilation and hypoxic ventilatory response (HVR) of 320 Tibetans 9-82 years of age and 542 Bolivian Aymara 13-94 years of age, native residents at 3,800-4,065 m. Tibetan resting ventilation was roughly 1.5 times higher and Tibetan HVR was roughly double that of Aymara. Greater duration of hypoxia (older age) was not an important source of variation in resting ventilation or HVR in either sample. That is, contrary to previous studies, neither sample acquired hypoventilation in the age ranges under study. Within populations, greater severity of hypoxia (lower percent of oxygen saturation of arterial hemoglobin) was associated with slightly higher resting ventilation among Tibetans and lower resting ventilation and HVR among Aymara women, although the associations accounted for just 2-7% of the variation. Between populations, the Tibetan sample was more hypoxic and had higher resting ventilation and HVR. Other systematic environmental contrasts did not appear to elevate Tibetan or depress Aymara ventilation. There was more intrapopulation genetic variation in these traits in the Tibetan than the Aymara sample. Thirty-five percent of the Tibetan, but none of the Aymara, resting ventilation variance was due to genetic differences among individuals. Thirty-one percent of the Tibetan HVR, but just 21% of the Aymara, HVR variance was due to genetic differences among individuals. Thus there is greater potential for evolutionary change in these traits in the Tibetans. Presently, there are two different ventilation phenotypes among high altitude natives as compared with sea level populations at sea level: lifelong sustained high resting ventilation and a moderate HVR among Tibetans in contrast with a slightly elevated resting ventilation and a low HVR among Aymara.

This retrospective follow-up study evaluated the mortality experience of 11,271 women employed in a large motor vehicle manufacturing company in 1973. Company computerized personnel records were used to identify subjects and to obtain their employment histories. Follow-up through December 31, 1985, was conducted using company, state, and national data sources. The mortality rates of the cohort were compared with the rates of the U.S. general population of white or black women, adjusting for age and calendar time and using the standardized mortality ratio (SMR) as the measure of association. The overall mortality rate of the cohort was lower than the U.S. rate by 15% among whites (SMR = 85, 95% confidence interval (CI) = 78-93) and by 40% among blacks (SMR = 59, CI = 49-70). Among whites, the low mortality rate was due primarily to deficits of noncancer deaths, although a 32% deficit also was observed for breast cancer (SMR = 68, CI = 48-92). Black female workers had 40% fewer deaths than expected overall, and their all cancer SMR also was below expectation (SMR = 82, CI = 60-109). Despite evidence of a strong healthy worker effect among women in the motor vehicle manufacturing industry, the study found excesses of lung cancer among white women in assembly jobs (SMR = 158, CI = 107-226) and of pancreatic cancer among white assembly workers in upholstery and trim operations (SMR = 302, CI = 97-704).

This report employs a statistical genetic approach to analyze quantitative oxygen transport variables in a high-altitude (4,850-5,450 m) native Tibetan population and demonstrates the presence of a major gene influencing % O2 saturation of arterial hemoglobin. This result suggests the hypothesis that individuals with the dominant allele for higher % O2 saturation have a selective advantage at high altitude. Studies of the biologically distinctive Himalayan and Andean populations have greatly influenced thinking about ongoing human evolution and adaptation; this is the first statistical evidence for a major gene enhancing oxygen transport in a high-altitude native population.

This study tests the hypothesis that optimum birthweight for survival is lower among hospital-born infants in Puno, Peru (altitude 3860 m) than that among their counterparts at low altitude in Tacna, Peru (altitude 600 m). The data are derived from hospital birth records for 1971 and 1972 and municipal death records for 1971 through 1973. Linking these records permits analysis of the patterns of mortality in relation to birthweight. Stabilizing selection upon birthweight is operating in both populations. The high altitude population has a lower mean birthweight and a lower optimal birthweight. The Puno population is closer to its optimal birthweight distribution and, as a result of mortality during infancy, is approaching its optimum birthweight distribution for survival more rapidly than the Tacna population. It appears that the high altitude Puno population may well be adapted to its environment in the sense that there is less selective mortality on birthweight phenotypes.

This paper presents data on the hemoglobin concentration of a sample of 103 pastoral nomads who are lifelong residents of Phala, at 4,850-5,450 m, on the northern plateau of the Tibet Autonomous Region of the Peoples' Republic of China. This native population resides at the highest altitude of which we are aware and is thus exposed to the most extreme chronic hypoxic stress. However, they do not exhibit the most pronounced physiological adaptations, i.e., hemoglobin concentrations exceeding those found in all other high-altitude populations. Adult male and female mean hemoglobin concentrations of 18.2 and 16.7 gm/dl, respectively, were found. These data, in conjunction with earlier studies of ethnic Tibetans living at 3,400 m, demonstrate a pattern of increasing hemoglobin concentration (erythrocytosis) at increasing altitude of residence in the Himalayas and Tibet. At the same time, however, the hemoglobin concentration is lower than that found among Andean highlanders. These new data raise the possibility of quantitative population differences in hematological adaptation to high altitude hypoxia.