Structures and dynamics of hibernating ribosomes from Staphylococcus aureus mediated by intermolecular interactions of HPF

In bacteria, ribosomal hibernation shuts down translation as a response to stress, through reversible binding of stress‐induced proteins to ribosomes. This process typically involves the formation of 100S ribosome dimers. Here, we present the structures of hibernating ribosomes from human pathogen Staphylococcus aureus containing a long variant of the hibernation‐promoting factor (SaHPF) that we solved using cryo‐electron microscopy. Our reconstructions reveal that the N‐terminal domain (NTD) of SaHPF binds to the 30S subunit as observed for shorter variants of HPF in other species. The C‐terminal domain (CTD) of SaHPF protrudes out of each ribosome in order to mediate dimerization. Using NMR, we characterized the interactions at the CTD‐dimer interface. Secondary interactions are provided by helix 26 of the 16S ribosomal RNA. We also show that ribosomes in the 100S particle adopt both rotated and unrotated conformations. Overall, our work illustrates a specific mode of ribosome dimerization by long HPF, a finding that may help improve the selectivity of antimicrobials.     

Kinetics of nutrient utilization and photosynthetic enzyme activities during floral versus vegetative differentiation of Spathiphyllum in air-lift bioreactor cultures

The present study reports on the kinetics of nutrient utilization during in vitro flowering of Spathiphyllum in air-lift bioreactor cultures. Levels of electrical conductivity (EC), anions and cations, pH, ethylene, sugar content and photosynthetic enzymes were determined in bioreactor cultures of both flowering (FPs) and non-flowering (NFPs) plantlets over a growth period of 12 weeks. A decrease in ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) activity with a corresponding increase in phosphoenolpyruvate carboxylase (PEPcase) activity occurred during floral induction of Spathiphyllum in vitro. Sucrose concentration decreased significantly in FPs, while no changes in glucose, fructose and total sugars were observed in both FPs and NFPs up to 8 weeks of culture. There were significant variations in mineral nutrient utilization between FP and NFP cultures. These results provide an insight to the physiological processes involved in inflorescence formation in Spathiphyllum.     

The association between air travel and deep vein thrombosis: Systematic review & meta-analysis

Background

The management of acute myocardial infarction (AMI) has improved over the last 50 years with the more frequent use of effective medicines and procedures. The clinical benefit of the speciality of the attending physician is less clear. The United Kingdom National Service Framework for coronary heart disease (CHD) suggested that patients with CHD are likely to benefit from cardiological supervision. We set out to assess the effect of access to cardiologists on survival among AMI patients admitted in two UK hospitals.

Methods

The study was conducted in a university hospital and a district general hospital in England. Information was obtained on age, sex, ethnicity, Carstairs socioeconomic deprivation category derived from postcode of residence, comorbidity, distance from hospital and medication from all patients admitted with acute myocardial infarction in two acute trusts between July 1999 and June 2000. Record linkage to subsequent Hospital Episode Statistics and Registrar General's death records provided follow up information on procedures and mortality up to eighteen months after admission. Cox proportional hazard models were used to investigate the main hypothesis controlling for confounding. The main outcome measure was 18-month survival after myocardial infarction.

Results

Access to a cardiologist was univariately associated with improved survival (hazard ratio 0.16, 95% CI 0.10 to 0.25). This effect remained after controlling for the effect of patient characteristics (hazard ratio 0.22, 95% CI 0.14 to 0.25). The effect disappeared after controlling for access to effective medication (hazard ratio 0.70, 95% CI 0.33 to 1.46).

Conclusions

Access to a cardiologist is associated with better survival compared to no access to a cardiologist among a cohort of patients already admitted with AMI. This effect is mainly due to the more frequent use of effective medicines by the group referred to cardiologists. Hospitals may improve survival by improving access to effective medicines and by coordinating care between cardiologists and general physicians.     

Critical limb ischemia: Current and novel therapeutic strategies

Critical limb ischemia (CLI) is the advanced stage of peripheral artery disease spectrum and is defined by limb pain or impending limb loss because of compromised blood flow to the affected extremity. Current conventional therapies for CLI include amputation, bypass surgery, endovascular therapy, and pharmacological approaches. Although these conventional therapeutic strategies still remain as the mainstay of treatments for CLI, novel and promising therapeutic approaches such as proangiogenic gene/protein therapies and stem cell-based therapies have emerged to overcome, at least partially, the limitations and disadvantages of current conventional therapeutic approaches. Such novel CLI treatment options may become even more effective when other complementary approaches such as utilizing proper bioscaffolds are used to increase the survival and engraftment of delivered genes and stem cells. Therefore, herein, we address the benefits and disadvantages of current therapeutic strategies for CLI treatment and summarize the novel and promising therapeutic approaches for CLI treatment. Our analyses also suggest that these novel CLI therapeutic strategies show considerable advantages to be used when current conventional methods have failed for CLI treatment.     

Breast cancer-linked lncRNA u-Eleanor is upregulated in breast of healthy women with lack or short duration of breastfeeding

Recently, it has been revealed that estrogen-related reproductive factors are linked with some early gene expression lesions associated with malignancy in clinically healthy breasts. Accordingly, the aim of the current study was to evaluate the association of expression levels of estrogen-related long noncoding RNAs (lncRNAs) upstream Eleanor (u-Eleanor) and HOX antisense intergenic RNA (HOTAIR) with the different patterns of reproductive factors in breast tissue of healthy women. The subjects of this study were 98 cancer-free women who had undergone cosmetic mammoplasty. The expression levels of u-Eleanor and HOTAIR were measured using quantitative real-time polymerase chain reaction. The results of the current study showed that the women without a history of breastfeeding had a high-level expression of u-Eleanor compared with the women with a breastfeeding duration greater than 6 to 24 months (P = 0.03) as well as the women with a breastfeeding duration of more than 24 months (P = 0.005). Furthermore, a higher expression of u-Eleanor was found in the women with a short breastfeeding duration for 1 to 6 months than that in the women with a breastfeeding duration of greater than 24 months (P = 0.02). In the same way, the results of correlation test (r = −0.258; P = 0.036) and multivariate regression model (β = −0.321; P = 0.023) are indicative of a significant relationship of elevated expression of u-Eleanor with decreasing breastfeeding duration in the women. These findings could be important to identify the molecular mechanisms behind the relationship between a lack or short duration of the breastfeeding and the risk of breast cancer, which has previously been reported by epidemiological studies.     

Protective role of soluble adenylyl cyclase against reperfusion-induced injury of cardiac cells

Aims

Disturbance of mitochondrial function significantly contributes to the myocardial injury that occurs during reperfusion. Increasing evidence suggests a role of intra-mitochondrial cyclic AMP (cAMP) signaling in promoting respiration and ATP synthesis. Mitochondrial levels of cAMP are controlled by type 10 soluble adenylyl cyclase (sAC) and phosphodiesterase 2 (PDE2), however their role in the reperfusion-induced injury remains unknown. Here we aimed to examine whether sAC may support cardiomyocyte survival during reperfusion.

Sustainable Sourcing of Global Agricultural Raw Materials: Assessing Gaps in Key Impact and Vulnerability Issues and Indicators

Understanding how to source agricultural raw materials sustainably is challenging in today’s globalized food system given the variety of issues to be considered and the multitude of suggested indicators for representing these issues. Furthermore, stakeholders in the global food system both impact these issues and are themselves vulnerable to these issues, an important duality that is often implied but not explicitly described. The attention given to these issues and conceptual frameworks varies greatly—depending largely on the stakeholder perspective—as does the set of indicators developed to measure them. To better structure these complex relationships and assess any gaps, we collate a comprehensive list of sustainability issues and a database of sustainability indicators to represent them. To assure a breadth of inclusion, the issues are pulled from the following three perspectives: major global sustainability assessments, sustainability communications from global food companies, and conceptual frameworks of sustainable livelihoods from academic publications. These terms are integrated across perspectives using a common vocabulary, classified by their relevance to impacts and vulnerabilities, and categorized into groups by economic, environmental, physical, human, social, and political characteristics. These issues are then associated with over 2,000 sustainability indicators gathered from existing sources. A gap analysis is then performed to determine if particular issues and issue groups are over or underrepresented. This process results in 44 “integrated” issues—24 impact issues and 36 vulnerability issues —that are composed of 318 “component” issues. The gap analysis shows that although every integrated issue is mentioned at least 40% of the time across perspectives, no issue is mentioned more than 70% of the time. A few issues infrequently mentioned across perspectives also have relatively few indicators available to fully represent them. Issues in the impact framework generally have fewer gaps than those in the vulnerability framework.     

Prediction of S-Sulfenylation Sites Using Statistical Moments Based Features via CHOU’S 5-Step Rule

Post-translation modification (PTM) of cysteine S-sulfenylation sites in protein is important in cellular biology. S-sulfenylation plays a significant role     

Methylation of progesterone receptor isoform A promoter in normal breast tissue: An epigenetic link between early age at menarche and risk of breast cancer?

Emerging evidence indicates that some altered patterns of methylation that occur in breast tumors may also be found in breast tissue of healthy women in relation to the breast cancer (BC) risk factors. Progesterone receptor (PR) isoform α is a crucial regulator of breast hormone responsiveness and its hypermethylation plays an important role in the initiation and development of breast tumors. However, such a methylation change in healthy women and its link with the different risk factors has not yet been investigated. In the present study, we aimed to examine the relationship of possible methylation changes within a critical region in the promoter CpG island of PGR-α (progesterone receptor α) gene in the healthy women with a set of reproductive and nonreproductive BC risk factors. The breast tissues were collected from 120 cancer-free women who had undergone cosmetic mammoplasty. The genomic DNA was extracted from the breast tissues and the methylation level of PGR-α promoter CpG island was determined by using MeDIP-qPCR assay. Using regression analysis, we found that increasing menarche age is inversely associated with the high methylation of PGR-α promoter ( β = −0.790, SE = 0.362; P = 0.031). Although lactating women had more methylation than nonlactating women (P = 0.026, the t test), this result was not confirmed by regression models. Such an observation may be helpful in better understanding of the underlying mechanisms by which early age at menarche increases the risk of BC. However, this perspective requires further validations in larger studies of more subjects as well as the inclusion of other related genes.     

Visualizing the transfer-messenger RNA as the ribosome resumes translation

Bacterial ribosomes stalled by truncated mRNAs are rescued by transfer-messenger RNA (tmRNA), a dual-function molecule that contains a tRNA-like domain (TLD) and an internal open reading frame (ORF). Occupying the empty A site with its TLD, the tmRNA enters the ribosome with the help of elongation factor Tu and a protein factor called small protein B (SmpB), and switches the translation to its own ORF. In this study, using cryo-electron microscopy, we obtained the first structure of an in vivo-formed complex containing ribosome and the tmRNA at the point where the TLD is accommodated into the ribosomal P site. We show that tmRNA maintains a stable 'arc and fork' structure on the ribosome when its TLD moves to the ribosomal P site and translation resumes on its ORF. Based on the density map, we built an atomic model, which suggests that SmpB interacts with the five nucleotides immediately upstream of the resume codon, thereby determining the correct selection of the reading frame on the ORF of tmRNA.