Structure of the processive rubber oxygenase RoxA from Xanthomonas sp

Rubber oxygenase A (RoxA) is one of only two known enzymes able to catalyze the oxidative cleavage of latex for biodegradation. RoxA acts as a processive dioxygenase to yield the predominant product 12-oxo-4,8-dimethyl-trideca-4,8-diene-1-al (ODTD), a tri-isoprene unit. Here we present a structural analysis of RoxA from Xanthomonas sp. strain 35Y at a resolution of 1.8 Å. The enzyme is a 75-kDa diheme c-type cytochrome with an unusually low degree of secondary structure. Analysis of the heme group arrangement and peptide chain topology of RoxA confirmed a distant kinship with diheme peroxidases of the CcpA family, but the proteins are functionally distinct, and the extracellular RoxA has evolved to have twice the molecular mass by successively accumulating extensions of peripheral loops. RoxA incorporates both oxygen atoms of its cosubstrate dioxygen into the rubber cleavage product ODTD, and we show that RoxA is isolated with O₂ stably bound to the active site heme iron. Activation and cleavage of O₂ require binding of polyisoprene, and thus the substrate needs to use hydrophobic access channels to reach the deeply buried active site of RoxA. The location and nature of these channels support a processive mechanism of latex cleavage.     

Surfer's ear: external auditory exostoses are more prevalent in cold water surfers.

OBJECTIVE: The study goal was to demonstrate the prevalence and severity of external auditory exostoses (EAEs) in a population of surfers and to examine the relationship between these lesions and the length of time surfed as well as water temperature in which the swimmers surfed. It was hypothesized that subjects who predominantly surfed in colder waters had more frequent and more severe exostoses. METHODS: Two hundred two avid surfers (91% male and 9% female, median age 17 years) were included in the study. EAEs were graded based on the extent of external auditory canal patency; grades of normal (100% patency), mild (66% to 99% patency), and moderate-severe (<66% patency) were assigned. Otoscopic findings were correlated with data collected via questionnaires that detailed surfing habits. RESULTS: There was a 38% overall prevalence of EAEs, with 69% of lesions graded as mild and 31% graded as moderate-severe. Professional surfers (odds ratio 3.8) and those subjects who surfed predominantly in colder waters (odds ratio 5.8) were found to be at a significantly increased risk for the development of EAEs. The number of years surfed was also found to be significant, increasing one's risk for developing an exostosis by 12% per year and for developing more severe lesions by 10% per year. Individuals who had moderate-severe EAEs were significantly more likely to be willing to surf in colder waters than were those who had mild EAEs (odds ratio 4.3). CONCLUSIONS: EAEs are more prevalent in cold water surfers, and additional years surfing increase one's risk not only for developing an EAE but also for developing more severe lesions.     

Contralateral recurrence of a malignant solitary fibrous tumor of the pleura

We present an unusual case of a contralateral recurrence of malignant solitary fibrous tumor of the pleura (SFTP) nine years after a complete resection. Recurrence of malignant SFTP has already been described, but is usually localized. In our case the patient underwent surgical resection for a malignant SFTP of the left upper lobe in 2000. Nine years later computed tomography (CT)-scans showed lesions that were suspicious of tumor recurrence in the right lung. Thoracoscopy, wedge-resections and pathological findings revealed four nodules of a malignant SFTP of the right middle and lower lobe, histopathologically identical to the tumor, which had been resected nine years ago. A coincidental mucinous bronchioloalveolar carcinoma of the left lower lobe was resected by thoracotomy. To our knowledge this is the first report of contralateral recurrence of a malignant SFTP years after complete resection in the literature. The possibility of a new primary tumor on the right with local metastasis could not be excluded in the clinical and histopathological examinations. Therefore, contralateral recurrence of malignant SFTP should be considered in the postoperative follow-up even years after complete resection.     

A New Zero-profile Implant for Stand-alone Anterior Cervical Interbody Fusion

Background  

Several studies suggest fusion rates are higher with anterior cervical discectomy and fusion procedures if supplemented with a plate. However, plates may be associated with higher postoperative morbidity and higher rates of dysphagia. This led to the development of a cervical stand-alone cage with integrated fixation for zero-profile segmental stabilization.     

Downregulation of the antioxidant protein peroxiredoxin 2 contributes to angiotensin II-mediated podocyte apoptosis

Podocytes have a significant role in establishing selective permeability of the glomerular filtration barrier. Sustained renin-angiotensin-aldosterone system activation is crucial to the pathogenesis of podocyte injury, but the mechanisms by which angiotensin II modulates podocyte survival due to physiological or injurious stimuli remain unclear. Here, we used proteomic analysis to find new mediators of angiotensin II-induced podocyte injury. Antioxidant protein peroxiredoxin 2 expression was decreased in cultured podocytes stimulated with angiotensin II. Peroxiredoxin 2 was found to be expressed in podocytes in vivo, and its expression was decreased in the glomeruli of rats transgenic for angiotensin II type 1 receptors in a podocyte-specific manner, or in rats infused with angiotensin II. Downregulation of peroxiredoxin 2 in podocytes resulted in increased reactive oxygen species release, protein overoxidation, and inhibition of the Akt pathway. Both treatment with angiotensin II and downregulation of peroxiredoxin 2 expression led to apoptosis of podocytes. Thus, peroxiredoxin 2 is an important modulator of angiotensin II-induced podocyte injury.     

The most altruistic living organ donor: a best friend

Living organ donors are growing in number and account for a substantial proportion of organs transplanted. Types of living organ donors include family members, anonymous donors, and friends. Although familial donation is the most common form of living organ donation, anonymous donation and donation among friends are gaining popularity. Society has placed living organ donors at the top of the altruistic ladder. However, one's altruistic motives for living organ donation may be affected by the type of relationship he or she has with the organ recipient. Although family relationships are close, pressure and coercion from family members may make informed consent difficult. Anonymous donors do not have the pressure associated with a familial donation, but psychological and self-worth issues may influence their choice to donate. Friendship incorporates the close relationships associated with familial donation and the freedom associated with anonymous donation. Using Aristotle's definition of true friendship, the author argues that best friends are the only true altruistic living organ donors and therefore may be preferable to family donors or anonymous donors.     

Pulmonary magnetic resonance angiography

In the past few years magnetic resonance angiography (MRA) of the pulmonary vasculature has advanced from a research tool to a clinically relevant imaging modality. Early 2D phase-contrast and time-of-flight (TOF) sequences without the use of contrast agents were time-consuming and limited by considerable imaging and motion artifacts. Since the introduction of MR scanners with stronger gradients (> 20 mT/m) and contrast-enhanced techniques, imaging of the pulmonary vasculature with adequate spatial resolution within a single breathhold is now possible. In the detection of pulmonary embolism in the lobar or segmental arteries, contrast-enhanced MRA is now on the verge of being considered an established modality, possibly competing with conventional pulmonary angiography and contrast-enhanced helical CT. In the future, utilization of phased-array torso coils, the application of navigator pulse sequences, and 3D time-resolved ultrafast MRA will overcome the final limitations of current techniques. Blood-pool MR contrast agents may provide a “one-stop-shopping” approach to the investigation of lower extremity veins and pulmonary arteries in venous thromboembolism.     

Comparison of quality of life in patients undergoing abdominoperineal extirpation or anterior resection for rectal cancer

OBJECTIVE: To evaluate the quality of life (QoL) in patients undergoing anterior resection (AR) or abdominoperineal extirpation (APE) for rectal cancer in a sample of patients recruited from a field trial. SUMMARY BACKGROUND DATA: Abdominoperineal resection has been reported to put patients at higher risk of disruption to QoL than sphincter-preserving surgery. METHODS: Fifty patients treated with AR and 23 patients treated with APE were prospectively followed up. All patients were treated in curative attempt and were disease-free throughout the study. QoL was assessed before surgery and 6 to 9 and 12 to 15 months after surgery. RESULTS: Multivariate analysis of variance and subsequent post hoc comparisons revealed a main effect for time (role function, emotional function, body image, future perspective, and micturition-related problems) and group in favor of APE (sleeping problems, constipation, diarrhea), and a time-by-group interaction (role function). No significant results were obtained for the remaining scores, but patients undergoing APE consistently had more favorable QoL scores than those undergoing AR. Multivariate analysis and post hoc comparisons revealed a particularly poor QoL for patients undergoing low AR. They had a significantly lower total QoL, role function, social function, body image, and future perspective, and more gastrointestinal and defecation-related symptoms than patients undergoing high AR. CONCLUSION: Patients undergoing APE do not have a poorer QoL than patients undergoing AR. Patients undergoing low AR have a lower QoL than those undergoing APE. Attention should be paid to QoL concerns expressed by patients undergoing low AR.