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Ribosome and protein synthesis lie at the core of cell growth and are major consumers of the cellular budget. Here we review recent progress in the coupling of ribosome synthesis and translational capacity with cell growth in bacteria. We elaborate on the different strategies of bacteria to modulate the protein synthesis rate at fast and slow growth rates. In particular, bacterial cells maintain translational potential at very slow growth as a strategy to keep fitness in fluctuating environments. We further discuss the important role of ribosome synthesis in rapidly proliferating eukaryotic cells such as yeast cells and cancer cells. The tight relation between ribosome and cell growth provides a broad research avenue for researchers from various disciplines. At fast growth rates, cellular ribosome synthesis is tightly coupled with cell growth by guanosine tetra- or pentaphosphate [(p)ppGpp] to attain optimal proteome resource allocation in bacterial cells. Under slow growth conditions, bacterial cells adopt an ingenious strategy to keep translational potential through maintaining both a basal inactive ribosome pool and a moderate translational elongation rate; such a design reflects an adaptive mechanism to fluctuating environments. Ribosome synthesis is also tightly coupled with growth rate in yeast cells, being similar to that in bacterial cells. Excessive ribosome synthesis is crucial for cancer cells to support rapid proliferation and a high protein synthesis rate, and upregulation of ribosome synthesis promotes cancer progression. [ABSTRACT FROM AUTHOR]

In nature, bacteria are constantly adapting to various stressful conditions. Timely activation of stress response programs is crucial for bacteria to smoothly survive under stressful conditions. Stress response, demanding the de novo synthesis of many defense proteins, is generally activated at the transcriptional level by specific regulators. However, the effect of the global protein translational status on stress response has been largely overlooked. The translational capacity is limited by the number of translating ribosomes and the translational elongation rate. Recent work has shown that certain environmental stressors (e.g. oxidative stress) could severely compromise the stress response progress of bacteria by causing either slow-down or even complete stalling of the translational elongation process. The maintenance of ribosome elongation rate, being crucial for timely synthesis of stress defense proteins, becomes the physiological bottleneck that limits the survival of bacteria in some stressful conditions. Here, we briefly summarize some recent progress on the translational status of bacteria under two distinct stress conditions, nutrient deprivation and oxidative stress. We further discuss several important open questions on the translational regulation of bacteria during stress. The ribosome translation should be investigated in parallel with traditional transcriptional regulation in order to gain a better understanding on bacterial stress defense. [ABSTRACT FROM AUTHOR]

A fundamental question in microbiology is how bacterial cells manage to coordinate gene expression with cell growth during adapting to various environmental conditions. Although the cellular responses to changing environments have been extensively studied using transcriptomic and proteomic approaches, it remains poorly understood regarding the molecular strategy enabling bacteria to manipulate the global gene expression patterns. The alarmone (p)ppGpp is a key secondary messenger involved in regulating various biochemical and physiological processes of bacterial cells. However, despite of the extensive studies of (p)ppGpp signaling in stringent response during the past 50 years, the connection between (p)ppGpp and exponential growth remains poorly understood. Our recent work demonstrates that (p)ppGpp is strongly involved in regulating cell growth of Escherichia coli through balancing the cellular investment on metabolic proteins and ribosomes, highlighting itself as a magic governor of bacterial global resource allocation. In this mini-review, we briefly summarize some historical perspectives and current progress of the relation between (p)ppGpp and bacterial exponential growth. Two important future directions are also highlighted: the first direction is to elucidate the cellular signal that triggers (p)ppGpp accumulation during poor growth conditions; the second direction is to investigate the relation between (p)ppGpp and exponential growth for bacterial species other than E. coli. [ABSTRACT FROM AUTHOR]

In nature, the maximal growth rates vary widely among different bacteria species. Fast-growing bacteria species such as Escherichia coli can have a shortest generation time of 20 min. Slow-growing bacteria species are perhaps best known for Mycobacterium tuberculosis, a human pathogen with a generation time being no less than 16 h. Despite of the significant progress made on understanding the pathogenesis of M. tuberculosis, we know little on the origin of its intriguingly slow growth. From a global view, the intrinsic constraint of the maximal growth rate of bacteria remains to be a fundamental question in microbiology. In this review, we analyze and discuss this issue from the angle of protein translation capacity, which is the major demand for cell growth. Based on quantitative analysis, we propose four parameters: rRNA chain elongation rate, abundance of RNA polymerase engaged in rRNA synthesis, polypeptide chain elongation rate, and active ribosome fraction, which potentially limit the maximal growth rate of bacteria. We further discuss the relation of these parameters with the growth rate for M. tuberculosis as well as other bacterial species. We highlight future comprehensive investigation of these parameters for different bacteria species to understand how bacteria set their own specific growth rates. [ABSTRACT FROM AUTHOR]

Understanding how the homeostasis of cellular size and composition is accomplished by different organisms is an outstanding challenge in biology. For exponentially growing Escherichia coli cells, it is long known that the size of cells exhibits a strong positive relation with their growth rates in different nutrient conditions. Here, we characterized cell sizes in a set of orthogonal growth limitations. We report that cell size and mass exhibit positive or negative dependences with growth rate depending on the growth limitation applied. In particular, synthesizing large amounts of “useless” proteins led to an inversion of the canonical, positive relation, with slow growing cells enlarged 7- to 8-fold compared to cells growing at similar rates under nutrient limitation. Strikingly, this increase in cell size was accompanied by a 3- to 4-fold increase in cellular DNA content at slow growth, reaching up to an amount equivalent to ~8 chromosomes per cell. Despite drastic changes in cell mass and macromolecular composition, cellular dry mass density remained constant. Our findings reveal an important role of protein synthesis in cell division control. [ABSTRACT FROM AUTHOR]

We performed the first circular permutation analysis for E. coli 5-enolpyruvylshikimate-3-phosphate synthase, and identified one circular permutant with notably increased resistance to its specific inhibitor and several others with moderately improved catalytic activity. Valid circular permutation sites can be used as effective split sites of protein fragment complementation. [ABSTRACT FROM AUTHOR]

Background/Aims: To investigate whether the invasively obtained central aortic systolic blood pressure (CSBP) predicts chronic kidney disease (CKD) better than brachial systolic blood pressure (SBP), brachial diastolic blood pressure (DBP) and brachial pulse pressure (PP) in the middle-aged Chinese population. Methods: A cross-sectional study was carried out across China in 2009-2010 among the subjects aged 35-64 years. CSBP was measured non-invasively by radial artery applanation tonometry B-pro (A-PULSE CASP and corresponding software). CSBP, SBP, DBP and PP were standardized with Z-score and the odds ratios were calculated with multivariable logistic regression model. Results: Data of 10197 participants were analyzed. The multivariable logistic regression after adjusting for possible confounders showed that a 1-standard deviation increment in each blood pressure measurement was associated with greater risk of CKD in both men and women (P < 0.05). The association of CSBP with CKD was stronger than SBP, DBP and PP in women, while in men the association of CSBP with CKD was stronger only than PP. With CSBP and SBP entering into the multivariable logistic regression models jointly, the odds ratio (95% confidence interval) for CSBP and SBP was 1.57 (1.39-1.79) and 1.22 (1.07-1.38) in women and 1.20 (1.03-1.39) and 1.48 (1.28-1.72) in men, respectively. With CSBP and DBP entering into the multivariable logistic regression models jointly, the odds ratio (95% confidence interval) for CSBP and DBP was 1.68 (1.52-1.84) and 1.15 (1.04-1.27) in women and 1.30 (1.15-1.46) and 1.45 (1.29-1.63) in men, respectively. With CSBP and PP entering into the multivariable logistic regression models jointly, the odds ratio (95% confidence interval) for CSBP and PP was 1.75 (1.58-1.94) and 1.06 (0.96-1.17) in women and 1.58 (1.41-1.77) and 1.04 (0.93-1.17) in men, respectively. Conclusion: CSBP and brachial blood pressure measurements are all predictors of CKD, however the non-invasively obtained CSBP may offer advantages over brachial blood pressure measurements in CKD risk prediction in women. [ABSTRACT FROM AUTHOR]

Background Living at high altitude may have undesirable effects on the kidney. We explored the chronic kidney disease (CKD) prevalence and risk factors among the residents living at different altitude in Tibetan Plateau. Methods A cross-sectional study was carried out in 2014 to 2016 in Linzhi (2900 m altitude), Lhasa (3650 m) and Anduo (4700 m). Information on the cardiovascular risk factors was collected and blood and urine samples were measured. Results The data of 1707 subjects aged ≥35 y were analyzed. The age-standardized prevalence of CKD in Linzhi, Lhasa and Anduo was 27.7% (95% CI: 22.1–33.3%), 18.3% (12.7–24.0%) and 30.4% (23.5–37.3%) in men and 37.7% (31.8–43.6%), 29.5% (24.6–34.4%) and 36.7% (29.0–44.4%) in women, respectively. Multivariable logistic regression showed that age, female gender, systolic blood pressure, fasting serum glucose, with primary school education or lower were associated with higher risk of CKD and living in Lhasa was associated with lower risk of CKD. Conclusion A higher prevalence of CKD was found in the residents living in the Tibetan Plateau. However, for the highlanders living at higher altitude does not mean higher risk. The CKD risk factors found in this study are similar to those in other studies. [ABSTRACT FROM AUTHOR]

Background: Although the prevalence of hypertension (HTN) continues to increase in developing countries, including China, recent data are lacking. A nationwide survey was conducted from October 2012 to December 2015 to assess the prevalence of HTN in China.Methods: A stratified multistage random sampling method was used to obtain a nationally representative sample of 451 755 residents ≥18 years of age from 31 provinces in mainland China from October 2012 to December 2015. Blood pressure (BP) was measured after resting for 5 minutes by trained staff using a validated oscillometric BP monitor. HTN was defined as systolic BP (SBP) ≥140 mm Hg/or diastolic BP (DBP) ≥90 mm Hg or use of antihypertensive medication within 2 weeks. Pre-HTN was defined as SBP 120 to 139 mm Hg and DBP 80 to 89 mm Hg without antihypertensive medication. HTN control was defined as SBP <140 mm Hg and DBP<90 mm Hg. In addition, the prevalence of HTN (SBP ≥130 or DBP ≥80 mm Hg) and control rate (SBP <130 and DBP <80 mm Hg) of HTN were also estimated according to the 2017 American College of Cardiology/American Heart Association High Blood Pressure Guideline.Results: Overall, 23.2% (≈244.5 million) of the Chinese adult population ≥18 years of age had HTN, and another 41.3% (≈435.3 million) had pre-HTN according to the Chinese guideline. There were no significant differences of HTN prevalence between urban and rural residents (23.4% versus 23.1%, P=0.819). Among individuals with HTN, 46.9% were aware of their condition, 40.7% were taking prescribed antihypertensive medications, and 15.3% had controlled HTN. Calcium channel blockers were the most commonly used antihypertensive medication (46.5%) as monotherapy, and 31.7% of treated hypertensive patients used ≥2 medications. The prevalence of HTN based on the 2017 American College of Cardiology/American Heart Association guideline was twice as high as that based on 2010 Chinese guideline (46.4%), whereas the control rate fell to 3.0%.Conclusions: In China, there is a high prevalence of HTN and pre-HTN, and awareness, treatment, and control of HTN were low. Management of medical therapy for HTN needs to improve. [ABSTRACT FROM AUTHOR]

An increasing body of evidence has emerged showing that the central systolic blood pressure (CSBP) is more relevant to the risk of cardiovascular (CV) diseases than brachial blood pressure. However, there are no agreed CSBP threshold values above which the risk of CV disease is increased. The aim of our study was to define the threshold values of the CSBP in a normotensive Chinese population; 10 012 adults 35 to 65 years of age were eligible for analysis. We excluded 3765 participants with hypertension, and the final normotensive reference sample consisted of 6247 participants. We defined abnormally high CSBP as exceeding the 90th percentile age- and sex-specific values in the normotensive population. The 90th percentile cutoff value for CSBP in the reference sample was 125 mm Hg in men and 126 mm Hg in women. The CSBP was significantly higher in participants with diabetes, history of CV disease, and hyperlipidemia (P < .001). The CSBP values increased with age (P < .001). We established that the 90th percentile of the CSBP threshold value in normotensive Chinese middle-aged population is 125 mm Hg for men and 126 mm Hg for women. [ABSTRACT FROM AUTHOR]

We assessed the relationship between alcohol consumption and serum lipids in a middle-aged Chinese population. The overall prevalence of drinking among 10 154 participants was 34.07% in males and 3.61% in females. Heavy alcohol drinkers (≥ 30 g/d) tended to be older, smokers, hypertensive, do heavy physical activity, and have a lower body mass index. Levels of high-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo) A1, low-density lipoprotein cholesterol–HDL-C ratio, and apo B–apo A1 ratio rose with increase in alcohol intake in males. An increase of 0.27 mmol/L in triglycerides and a decrease of 2.10 mg/dL in lipoprotein(a), Lp(a), were observed in male alcohol drinkers who consumed ≥30 g alcohol/d compared with abstainers after controlling for all confounders. Levels of total cholesterol, HDL-C, and apo A1 increased with increase in alcohol intake in both genders and Lp(a) decreased with the increase in alcohol intake in males. [ABSTRACT FROM AUTHOR]

We assessed the prevalence of microalbuminuria (MAU) and the relationships with other cardiovascular (CV) risk factors among a middle-aged Chinese population. Data from 10 313 participants were included in our cross-sectional survey. Microalbuminuria was defined as the urine albumin to creatinine ratio of 30:300 mg/g from a single-spot morning urine sample. Microalbuminuria was found to be common in males and females (15.04% vs 10.09%) aged 35 to 64 years in this Chinese general population, especially in those with obesity, hypertension, and diabetes. Multivariate analysis found that body mass index, triglyceride, high-sensitivity C-reactive protein, alcohol consumption, hypertension, and diabetes were independently associated with MAU. Microalbuminuria may be a useful indicator for risk of CV disease in general populations. [ABSTRACT FROM AUTHOR]

Body mass index (BMI) and hypertension have been found to be associated in most studies of diverse populations; however, little information is available on whether the positive relationship is consistent among individuals at work sites. A work site-based screening was performed in 30 682 employees with a mean age of 40.3 years. In crude models, higher BMI quartiles above the lowest quartiles (BMI <20.6 kg/m2) were associated with progressively higher odds ratio (OR) of hypertension with an OR of 2.80 (95% confidence interval [CI]: 2.67-2.93) for the top quartile (BMI ≥24.6 kg/m2). Similar trends were found in fully adjusted models. Moreover, a 1-standard deviation (SD) increase in BMI was associated with a 42% significantly higher (95% CI 38-46) risk of hypertension after adjusting for other factors. Concordant relationships were revealed in all evaluated subgroups, even among those without traditional cardiovascular risk factors. [ABSTRACT FROM PUBLISHER]

Background: Smoking is a risk factor for many diseases and has been increasingly prevalent in economically developing regions of the world. We aimed to estimate the number of deaths attributable to smoking in China. Methods: We conducted a large, prospective cohort study in a nationally representative sample of 169,871 Chinese adults who were 40 years of age or older. Investigators for the China National Hypertension Survey collected data on smoking and other risk factors at a baseline examination in 1991 using a standard protocol. Follow-up evaluation was conducted in 1999 and 2000, with a response rate of 93.4%. We used multivariable-adjusted relative risk, prevalence of smoking, mortality, and population size in each age group, stratified according to sex, to calculate the number of deaths attributable to smoking in 2005. Results: There was a significant, dose–response association between pack-years smoked and death from any cause in both men and women after adjustment for multiple risk factors (P<0.001 for trend). We estimated that in 2005, a total of 673,000 deaths (95% confidence interval [CI], 564,700 to 781,400) were attributable to smoking in China: 538,200 (95% CI, 455,800 to 620,600) among men and 134,800 (95% CI, 108,900 to 160,800) among women. The leading causes of smoking-related deaths were as follows: cancer, 268,200 (95% CI, 214,500 to 321,900); cardiovascular disease, 146,200 (95% CI, 79,200 to 213,100); and respiratory disease, 66,800 (95% CI, 20,300 to 113,300). Conclusions: Our study documents that smoking is a major risk factor for mortality in China. Continued strengthening of national programs and initiatives for smoking prevention and cessation is needed to reduce smoking-related deaths in China. N Engl J Med 2009;360:150-9. [ABSTRACT FROM AUTHOR]