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The folate biosynthesis pathway is an essential pathway for cell growth and survival. Folate derivatives serve as a source of the one-carbon units in several intracellular metabolic reactions. Rapidly dividing cells rely heavily on the availability of folate derivatives for their proliferation. As a result, drugs targeting this pathway have shown to be effective against tumor cells and pathogens, but drug resistance against the available antifolate drugs emerged quickly. Therefore, there is a need to develop new treatment strategies and identify alternative metabolic targets. The two de novo folate biosynthesis pathway enzymes, GTP cyclohydrolase I (GCH1) and 6-pyruvoyl tetrahydropterin synthase (PTPS), can provide an alternative strategy to overcome the drug resistance that emerged in the two primary targeted enzymes dihydrofolate reductase and dihydropteroate synthase. Both GCH1 and PTPS enzymes contain Zn 2+ ions in their active sites, and to accurately study their dynamic behaviors using all-atom molecular dynamics (MD) simulations, appropriate parameters that can describe their metal sites should be developed and validated. In this study, force field parameters of the GCH1 and PTPS metal centers were generated using quantum mechanics (QM) calculations and then validated through MD simulations to ensure their accuracy in describing and maintaining the Zn 2+ ion coordination environment. The derived force field parameters will provide accurate and reliable MD simulations involving these two enzymes for future in-silico identification of drug candidates against the GCH1 and PTPS enzymes. Communicated by Ramaswamy H. Sarma.

Objectives: To identify factors predicting renal recovery in patients presenting with renal failure secondary to bilateral obstructing urolithiasis., Patients and Methods: Data from electronic records of consecutive adult patients presenting with bilateral obstructing urolithiasis between January 2007 and April 2011 were retrieved. Ultrasonography of the abdomen, and kidney, ureter, bladder (KUB study) X-ray or abdominal non-contrast computed tomography confirmed the diagnosis. Interventional radiologists placed bilateral nephrostomies. Definitive intervention was planned after reaching nadir creatinine. Renal recovery was defined as nadir creatinine of ⩽2 mg/dL., Results: In all, 53 patients were assessed, 50 (94.3%) were male, and 18 (33.9%) were aged ⩽40 years. Renal recovery was achieved in 20 patients (37.7%). A symptom duration of ⩽25 days ( P  < 0.01), absence of hypertension ( P  = 0.018), maximum renal parenchymal thickness of >16.5 mm ( P  = 0.001), and haemoglobin >9.85 g/dL ( P  < 0.01) were significant on unadjusted analysis. Symptom duration of ⩽25 days alone remained significant after adjusted analysis. Symptom duration of ⩽25 days (hazard ratio (HR) 13.83, 95% confidence interval (CI) 4.52-42.26; P  < 0.01), parenchymal thickness of ⩾16.5 mm (HR 5.91, 95% CI 1.94-17.99; P  = 0.002), and absence of hypertension (HR 9.99, CI 95% 1.32-75.37; P  = 0.026) were significantly related to time to nadir creatinine. Symptom duration of ⩽25 days (HR 17.44, 95% CI 2.48-122.79; P  = 0.004) alone remained significant after adjusted analysis. A symptom duration of ⩽25 days ( P  = 0.007) was 22-times more likely to indicate renal recovery., Conclusions: Shorter symptom duration (⩽25 days) is predictive of renal recovery in renal failure secondary to bilateral obstructive urolithiasis.

In this age of rapidly developing online learning, the advent of a series of talks and supplementary material devoted to genetics in agriculture from Henry Stewart Talks ( http://hstalks.com/main/browse&#95;talks.php?r=776&c=252 ) is welcome indeed. The series is designed for researchers and graduate students in the fields of genetics, plant science, animal science, agricultural science, food science, human nutrition and environmental science, advanced undergraduate students, policy makers and managers in public and private sectors, and continuing professional education/development.

The rapid global development of agricultural production systems using seeds derived from genetic modification (GM) has been paralleled by the growth of attempts to keep at least a part of the world's agriculture and food as free from GM-crops and their products as possible. The ideal for some proponents of such "GM-free" activity would be a total absence, usually styled "zero content"; others, perhaps more realistically, opt for a definition usually not precisely defined that allows for minimal trace levels of GM material. The reasons for wanting "GM-free" agriculture and its products are varied; they include philosophical and religious beliefs, concern for human (and animal) health--and for "the environment"-as well as commercial and political interests. With such a variety of motivations, and in the absence of legal rulings, the definitions of "GM-free" vary according to inclination and circumstances. Whatever the precise meaning, the maintenance of a "GM-free" product stream in a world where GM crop production is widespread requires the establishment of identity preservation and segregation systems in which traceability and testing are cornerstones. Inevitably these have cost implications for the supply chain and/or the ultimate consumer. In a number of countries different forms of "GM-free" labels exist for some products; the style of such labels is variable with schemes and labels typically voluntary or privately organized. In more recent years, some governments have begun to regularize the definition and meaning of "GM-free." We conclude our analysis by exploring consumer reactions both to "GM-free" and to "GM-free" labels, and ask who ultimately benefits from preserving a product stream substantially or entirely devoid of GM-content.

Intraoperative ultrasound (IOUS) has been described to be useful during central corpectomy for compressive cervical myelopathy. This study aimed at documenting the utility of IOUS in oblique cervical corpectomy (OCC). Prospective data from 24 patients undergoing OCC for cervical spondylotic myelopathy and ossified posterior longitudinal ligament (OPLL) were collected. Patients had a preoperative cervical spine magnetic resonance (MR) image, IOUS and a postoperative cervical CT scan. Retrospective data from 16 historical controls that underwent OCC without IOUS were analysed to compare the incidence of residual compression between the two groups. IOUS identified the vertebral artery in all cases, detected residual cord compression in six (27%) and missed compression in two cases (9%). In another two cases with OPLL, IOUS was sub-optimal due to shadowing. IOUS measurement of the corpectomy width correlated well with these measurements on the postoperative CT. The extent of cord expansion noted on IOUS after decompression showed no correlation with immediate or 6-month postoperative neurological recovery. No significant difference in residual compression was noted in the retrospective and prospective groups of the study. Craniocaudal spinal cord motion was noted after the completion of the corpectomy. IOUS is an inexpensive and simple real-time imaging modality that may be used during OCC for cervical spondylotic myelopathy. It is helpful in identifying the vertebral artery and determining the trajectory of approach, however, it has limited utility in patients with OPLL due to artifacts from residual ossification.