Quantifying epistatic interactions among the components constituting the protein translation system

In principle, the accumulation of knowledge regarding the molecular basis of biological systems should allow the development of large-scale kinetic models of their functions. However, the development of such models requires vast numbers of parameters, which are difficult to obtain in practice. Here, we used an in vitro translation system, consisting of 69 defined components, to quantify the epistatic interactions among changes in component concentrations through Bahadur expansion, thereby obtaining a coarse-grained model of protein synthesis activity. Analyses of the data measured using various combinations of component concentrations indicated that the contributions of larger than 2-body inter-component epistatic interactions are negligible, despite the presence of larger than 2-body physical interactions. These findings allowed the prediction of protein synthesis activity at various combinations of component concentrations from a small number of samples, the principle of which is applicable to analysis and optimization of other biological systems. Moreover, the average ratio of 2- to 1-body terms was estimated to be as small as 0.1, implying high adaptability and evolvability of the protein translation system

Stereotactic Radiosurgery for Postoperative Spine Malignancy: A Systematic Review and International Stereotactic Radiosurgery Society Practice Guidelines.

To determine safety and efficacy of postoperative spine stereotactic body radiation therapy (SBRT) in the published literature, and to present practice recommendations on behalf of the International Stereotactic Radiosurgery Society. A systematic review of the literature was performed, specific to postoperative spine SBRT, using PubMed and Embase databases. A meta-analysis for 1-year local control (LC), overall survival (OS), and vertebral compression fracture probability was conducted. The literature search revealed 251 potentially relevant articles after duplicates were removed. Of these 56 were reviewed in-depth for eligibility and 12 met all the inclusion criteria for analysis. 7 studies were retrospective, 2 prospective observational and 3 were prospective phase 1 and 2 clinical trials. Outcomes for a total of 461 patients and 499 spinal segments were reported. Ten studies used a magnetic resonance imaging (MRI) scan fused to computed tomography (CT) simulation for treatment planning, and 2 investigations reported on all patients receiving a CT-myelogram at the time of planning. Meta-analysis for 1 year LC and OS was 88.9% and 57%, respectively. The crude reported vertebral compression fracture rate was 5.6%. One case of myelopathy was described in a patient with a previously irradiated spinal segment. One patient developed an esophageal fistula requiring surgical repair. Postoperative spine SBRT delivers a high 1-year LC with acceptably low toxicity. Patients who may benefit from this include those with oligometastatic disease, radioresistant histology, paraspinal masses, or those with a history of prior irradiation to the affected spinal segment. The International Stereotactic Radiosurgery Society recommends a minimum interval of 8 to 14 days after invasive surgery before simulation for SBRT, with initiation of radiation therapy within 4 weeks of surgery. An MRI fused to the planning CT, or the use of a CT-myelogram, are necessary for target and organ-at-risk delineation. A planning organ-at-risk volume (PRV) of 1.5 to 2 mm for the spinal cord is advised

Coexistence of Superconductivity and Charge Density Wave in SrPt2As2

SrPt2As2 is a novel arsenide superconductor, which crystallizes in the CaBe2Ge2-type structure as a different polymorphic form of the ThCr2Si2-type structure. SrPt2As2 exhibits a charge-density-wave (CDW) ordering at about 470 K and enters into a superconducting state at Tc = 5.2 K. The coexistence of superconductivity and CDW refers to Peierls instability with a moderately strong electron-phonon interaction. Thus SrPt2As2 can be viewed as a nonmagnetic analog of iron-based superconductors, such as doped BaFe2As2, in which superconductivity emerges in close proximity to spin-density-wave ordering.Comment: 4 pages, 5 figure

Pneumococcal carriage in sub-Saharan Africa--a systematic review.

BACKGROUND: Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era. METHODS: A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region. RESULTS: Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6-70.8) in children less than 5 years, 42.6% (95% CI: 29.9-55.4) in children 5-15 years and 28.0% (95% CI: 19.0-37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9-24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes. CONCLUSION: Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination

A Case of Corticotroph Carcinoma that Caused Multiple Cranial Nerve Palsies, Destructive Petrosal Bone Invasion, and Liver Metastasis

A 52-year-old woman experienced sudden onset of double vision due to a right abducens nerve palsy and was diagnosed as having a pituitary macroadenoma that invaded into the right cavernous sinus. Otherwise, she was asymptomatic despite marked elevation of ACTH (293 pg/ml) and cortisol (24.6 μg/dl) levels. The patient underwent transsphenoidal surgery followed by γ-knife radiosurgery (GKR), which healed the diplopia and ameliorated the hypercortisolemia. The excised tumor was diffusely stained for ACTH with a high (15%) Ki-67 labeling index. Early tumor recurrence occurred twice thereafter, producing right lower cranial nerve palsies with petrosal bone destruction at 8 months and an ipsilateral oculomotor nerve palsy at 12 months after GKR; all palsies resolved completely with the second and third GKRs. Hypercortisolemia worsened rapidly soon after the third GKR, and the patient developed marked weight gain, hypokalemia, and hypertension. Multiple liver lesions were incidentally detected with computer tomography and identified as metastatic pituitary tumor on immunohistochemistry. An ACTH-producing adenoma should be followed carefully for early recurrence and/or metastatic spread when the tumor is an invasive macroadenoma with a high proliferation marker level. The unique aggressive behavior and high potential for malignant transformation of this case are discussed

Ongoing Phenotypic and Genomic Changes in Experimental Coevolution of RNA Bacteriophage Qβ and Escherichia coli

According to the Red Queen hypothesis or arms race dynamics, coevolution drives continuous adaptation and counter-adaptation. Experimental models under simplified environments consisting of bacteria and bacteriophages have been used to analyze the ongoing process of coevolution, but the analysis of both parasites and their hosts in ongoing adaptation and counter-adaptation remained to be performed at the levels of population dynamics and molecular evolution to understand how the phenotypes and genotypes of coevolving parasite–host pairs change through the arms race. Copropagation experiments with Escherichia coli and the lytic RNA bacteriophage Qβ in a spatially unstructured environment revealed coexistence for 54 days (equivalent to 163–165 replication generations of Qβ) and fitness analysis indicated that they were in an arms race. E. coli first adapted by developing partial resistance to infection and later increasing specific growth rate. The phage counter-adapted by improving release efficiency with a change in host specificity and decrease in virulence. Whole-genome analysis indicated that the phage accumulated 7.5 mutations, mainly in the A2 gene, 3.4-fold faster than in Qβ propagated alone. E. coli showed fixation of two mutations (in traQ and csdA) faster than in sole E. coli experimental evolution. These observations suggest that the virus and its host can coexist in an evolutionary arms race, despite a difference in genome mutability (i.e., mutations per genome per replication) of approximately one to three orders of magnitude