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The multidomain ribosomal protein bS1 is the biggest and the most flexible and dynamic protein in the 30S small subunit. Despite being essential for mRNA recruitment and its primary role in the accommodation of the start codon within the decoding centre, there has not yet been a high-resolution description of its structure. Here, we present a 3D atomic model of OB1 and OB2, bS1’s first two N-terminal domains, bound to an elongation-competent 70S ribosome. Our structure reveals that, as previously reported, bS1 is anchored both by a π-stacking to the 30S subunit and via a salt bridge with the Zn2+ pocket of bS1. These contacts are further stabilized by other interactions with additional residues on OB1. Our model also shows a new conformation of OB2, interacting with the Shine–Dalgarno portion of the mRNA. This study confirms that OB1 plays an anchoring role, but also highlights a novel function for OB2, which is directly involved in the modulation and support of mRNA binding and accommodation on the ribosome.

International audience; The arrest of protein synthesis caused when ribosomes stall on an mRNA lacking a stop codon is a deadly risk for all cells. In bacteria, this situation is remedied by the trans-translation quality control system. Trans-translation occurs because of the synergistic action of two main partners, transfer-messenger RNA (tmRNA) and small protein B (SmpB). These act in complex to monitor protein synthesis, intervening when necessary to rescue stalled ribosomes. During this process, incomplete nascent peptides are tagged for destruction, problematic mRNAs are degraded and the previously stalled ribosomes are recycled. In this 'Structural Snapshot' article, we describe the mechanism at the molecular level, a view updated after the most recent structural studies using cryo-electron microscopy.

Gliomas are the second-most-common primary brain tumors in dogs. Surgery and radiotherapy are established treatment approaches with similar median survival time, whereas conventional chemotherapy is burdened by severe adverse effects. Spinal and leptomeningeal spread of gliomas have been described following radiotherapy treatment alone. The purpose of this study was to evaluate the outcome for four dogs with primary high-grade gliomas in the forebrain without evidence, at diagnosis, of neoplastic invasion along the spinal cord, that were treated with concomitant chemotherapy (temozolomide) and hypofractionated volumetric-modulated arc radiotherapy (VMAT-RT). Temozolomide was selected for its radiosensitive properties, and radiotherapy dose protocols of 37 Gy in 7 fractions or 42 Gy in 10 fractions were used. After an initial complete or partial response, tumors recurred across the cranial–spinal pathway. Post-mortem macroscopic examinations confirmed swollen spinal cord and hyperemic meningeal sleeve, with nodular lesions on the meningeal surface. Microscopically, infiltration of the spinal cord and meninges by neoplastic cells (with features of oligodendrogliomas) were observed. This work seems to suggest that the entire central nervous system should be investigated in diagnostic examinations of canine gliomas. Dose-escalation trials and/or spinal cord prophylaxis treatment could also be evaluated to prevent tumor progression.

The aims of this pilot study were to evaluate the feasibility and efficacy of high-dose hypofractionated volumetric modulated arc radiotherapy (VMAT) applied to whole pelvic region radiotherapy (WPRT) with multilevel simultaneous integrated boost (MLSIB) combined with piroxicam and chemotherapy for the treatment of canine transitional cell carcinoma (TCC) of the lower urinary tract with muscle invasion TCC. Twelve dogs were enrolled, according to stage, in two groups: group 1, TCC confined to the urinary tract; group 2, TCC with metastasis. The planning target volume dose was tailored from 36 to 42 Gy in 6 fractions. All dogs were prescribed piroxicam and radiosensitizing carboplatin, and six received chemotherapy after radiotherapy. Serial follow-ups with computed tomography and magnetic resonance imaging were performed. Disease control and toxicity effects were evaluated according to the Response Evaluation Criteria in Solid Tumors and Veterinary Radiation Therapy Oncology Group criteria. The treatment was well tolerated, and no high-grade side effects were reported. The median overall survival times for groups 1 and 2 were 1,230 and 150 days, respectively. A considerable percentage of patients in group1 (50%) were still alive at the time of writing this paper, and a longer follow-up could enable a more accurate survival analysis. This preliminary analysis shows that VMAT applied to the WPRT with MLSIB is an effective and safe option for dogs with lower urinary TCC, although the presence of metastases worsens the prognosis.

Radiation therapy has become the standard of care in the treatment of canine intranasal neoplasia, but because of the poor prognosis associated with stage IV nasal tumours and the proximity of the brain to the irradiation target, few data regarding the treatment of very advanced neoplasms are available. The aim of this pilot study was to evaluate the feasibility, safety and effectiveness of a combined treatment composed of definitive high-dose hypofractionated volumetric modulated arc radiotherapy on tumours with concurrent treatment of regional lymph nodes if positive or as prophylaxis, carboplatin radio-sensitising, and adjuvant metronomic chemotherapy for stage IV canine nasal tumours with intracranial extension. A pilot observational study was conducted in 7 dogs. Magnetic resonance imaging follow-up examinations revealed complete responses in 5 dogs and partial responses in 2. The median overall survival time, evaluated via Kaplan-Meier survival analysis, was 310 days with a 95% confidence interval of 210-400 days, whereas the median progression-free survival was 240 days with a 95% confidence interval of 190-290 days. Despite the proximity of highly sensitive organs at risk, no grade III or IV toxicities were observed, and volumetric modulated arc radiotherapy seemed to be a feasible treatment option for stage IV canine nasal tumours where conformal 3D radiotherapy has proven to give higher doses with severe damage to the surrounding unaffected tissues. Further studies are needed on the role of the sphenoid bone microscopic infiltration and regional lymph node involvement. The absence of severe toxicity could also lead to a dose escalation study and chemotherapy scheme.

Thymoma is a relatively common tumor in rabbits. Treatment with surgery, radiation therapy, and chemotherapy alone or in combination has been reported with varying outcomes. Stereotactic volumetric modulated arc radiotherapy delivered in a hypofractionated manner allows high doses of radiation to be delivered to the target volume while allowing sparing of adjacent critical structures. This therapy is ideally suited for thymomas in rabbits given their size, the difficulty of multiple anesthesia episodes and the complexity of the radiotherapy plans required due to the tumor's proximity to the heart, lungs, and mediastinal structures. Fifteen rabbits with thymoma were prospectively recruited for this observational, single institution, single arm clinical study. All rabbits were imaged with both computed tomography (CT) and magnetic resonance imaging (MRI). A total dose of 40 Gy in six fractions was delivered using a single arc over an 11-day period with repeat CT simulation done every other fraction for adaptive planning. Follow-up evaluation was done through repeat CT and MRI imaging and revealed complete responses using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Two rabbits had died at 618 and 718 days, 10 were alive and three were lost to follow-up. Observed acute and late effects were graded according to the Veterinary Radiation Therapy Oncology Group (VRTOG) criteria and were found to be minimal.

A prospective study to assess high-dose hypofractionated volume modulated arc radiotherapy feasibility and efficacy in canine meningiomas was conducted. Thirty-nine patients with encephalic and spinal meningiomas assumed from MRI findings were recruited and received high-dose hypofractionated volumetric modulated arc radiotherapy by a linear accelerator equipped with an external beam modulator micro-multileaf collimator and an XVI cone beam computed tomography system. The prescribed mean dose was 33 Gy in five fractions. The treatment feasibility was tested through planned and delivered dose agreement checks. Regular clinical examinations were performed during and after irradiation time, with regard to mentation, deambulation, cranial nerve dysfunction, and seizures. Serial MRI exams were done 60 days after irradiation and after 4, 6, 12, 18, and 24 mo. Volumetric disease reduction criteria implemented with clinical neurological systematic evaluation were adopted to assess the course and to categorize patients’ responses. Complete and partial responses were observed on the whole in 65.5% of alive patients 24 mo after irradiation. Two-yr overall and disease-specific survival rates were 74.3% and 97.4%, respectively, and the putative radiotoxic effects were found to be few and slight.

Volumetric Modulated Arc Therapy (VMAT) is a modern technique, widely used in human radiotherapy, which allows a high dose to be delivered to tumor volumes and low doses to the surrounding organs at risk (OAR). Veterinary clinics takes advantage of this feature due to the small target volumes and distances between the target and the OAR. Sparing the OAR permits dose escalation, and hypofractionation regimens reduce the number of treatment sessions with a simpler manageability in the veterinary field. Multimodal volumes definition is mandatory for the small volumes involved and a positioning device precisely reproducible with a setup confirmation is needed before each session for avoiding missing the target. Additionally, the elaborate treatment plan must pursue hard constraints and objectives, and its feasibility must be evaluated with a per patient quality control. The aim of this work is to report results with regard to brain meningiomas and gliomas, trigeminal nerve tumors, brachial plexus tumors, adrenal tumors with vascular invasion and rabbit thymomas, in comparison with literature to determine if VMAT is a safe and viable alternative to surgery or chemotherapy alone, or as an adjuvant therapy in pets.

The aim of this prospective pilot study was to evaluate the feasibility and effectiveness of curative intent high dose hypofractionated frameless volumetric modulated arc radiotherapy for treatment of canine trigeminal peripheral nerve sheath tumors. Client-owned dogs with a presumptive imaging-based diagnosis of trigeminal peripheral nerve sheath tumor were recruited for the study during the period of February 2010 to December 2013. Seven dogs were enrolled and treated with high dose hypofractionated volumetric modulated arc radiotherapy delivered by a 6 MV linear accelerator equipped with a micro-multileaf beam collimator. The plans were computed using a Monte Carlo algorithm with a prescription dose of 37 Gy delivered in five fractions on alternate days. Overall survival was estimated using a Kaplan-Meier curve analysis. Magnetic resonance imaging (MRI) follow-up examinations revealed complete response in one dog, partial response in four dogs, and stable disease in two dogs. Median overall survival was 952 days with a 95% confidence interval of 543-1361 days. Volumetric modulated arc radiotherapy was demonstrated to be feasible and effective for trigeminal peripheral nerve sheath tumor treatment in this sample of dogs. The technique required few sedations and spared organs at risk. Even though larger studies are required, these preliminary results supported the use of high dose hypofractionated volumetric modulated arc radiotherapy as an alternative to other treatment modalities.

Objective: To compare magnetic resonance imaging (MRI) and spectroscopy (MRS) findings in dogs affected by persistent hepatic encephalopathy (HE) before and after treatment and assess any correlation between plasma ammonia levels and metabolite concentrations.Methods: In dogs with persistent HE, plasma ammonia measurement, brain MRI and single voxel MRS were performed before and 4 months after treatment. The concentrations of N-acetyl aspartate, (NAA) glutamate-glutamine complex (Glx), creatine (Cr), choline (Cho) and myo-inositol (mI) as well as the MRI findings werecompared and the correlation with plasma ammonia concentration was evaluated. Statistical analysis included Shapiro Wilk test, Student t-test and linear-fit regression.Results: Twenty dogs were enrolled. Initial MRI and MRS showed alterations in 18/20 and 20/20 dogs respectively. The MRI findings were normalized in dogs aged less than 3 years. Comparing post-treatment metabolite concentrations with the control group, no statistically significant differences were evident for dogs aged less than 3 years, whereas dogs aged more than 5 years showed a persistent but not significant reduction in NAA and mI, with a statistically significant increase in Glx. In dogs younger than 3 years, but not in dogs older than 5 years, a positive correlation was detected between plasma ammonia levels and Glx (r=0.80, p=0.041) and a negative correlation between ammonia level and NAA (r=-0.96, p=0.03) and between NAA and Glx (r=-0.87, p=0.037). No correlation was observed for Cr, Cho and mI.Conclusion: In young dogs MRI and MRS findings of persistent HE can normalize after effective treatment whereas abnormalities are still detected in older dogs. MRI and MRS could therefore be useful in the short-term treatment response evaluation of persistent canine HE.

Treatment of canine peripheral nerve sheath tumours (PNSTs) is challenging and prognosis after surgical resection is considered poor. The aim of this study was to evaluate the feasibility and effectiveness of stereotactic radiotherapy (RT) of these tumours.10 dogs with clinical symptoms and MRI findings consistent with PNSTs of the brachial plexus, branches and nerve roots were treated with linear accelerator-based volumetric-modulated arc radiotherapy (VMAT) with a dose of 35 Gy/5 fractions. Clinical and MRI follow-up examinations were planned and radiotoxicity and survival times were investigated.Tumours involved the plexus and proximal nerves in three dogs, the plexus, proximal nerves and nerve roots in five dogs and the nerve roots and proximal nerves in two dogs. Partial response and partial or complete reductions of neurological deficits were observed in all the treated dogs. Local recurrence was observed in 9/10 of treated dogs. No symptom directly referable to radiotoxicity was observed. Mean overall survival of 371 ± 30 days [95% confidence interval (CI) of (315-427)] and mean progression-free survival of 240 ± 30 days (95% CI of 188-291) from this work are comparable with surgical literature data regarding the plexus and proximal nerve localization, but are superior in comparison with nerve root localization.VMAT can be a safe and viable alternative to surgery in cases of canine brachial plexus PNSTs involving the proximal nerves and nerve roots. Advances in knowledge: To our knowledge, this is the first prospective observational clinical study regarding VMAT stereotactic RT treatment for canine brachial plexus PNSTs and suggests that VMAT may achieve at least similar clinical outcome than surgery in a safer way.

Thymoma is a relatively common tumor in rabbits. Treatment with surgery, radiation therapy, and chemotherapy alone or in combination has been reported with varying outcomes. Stereotactic volumetric modulated arc radiotherapy delivered in a hypofractionated manner allows high doses of radiation to be delivered to the target volume while allowing sparing of adjacent critical structures. This therapy is ideally suited for thymomas in rabbits given their size, the difficulty of multiple anesthesia episodes and the complexity of the radiotherapy plans required due to the tumor's proximity to the heart, lungs, and mediastinal structures. Fifteen rabbits with thymoma were prospectively recruited for this observational, single institution, single arm clinical study. All rabbits were imaged with both computed tomography (CT) and magnetic resonance imaging (MRI). A total dose of 40 Gy in six fractions was delivered using a single arc over an 11-day period with repeat CT simulation done every other fraction for adaptive planning. Follow-up evaluation was done through repeat CT and MRI imaging and revealed complete responses using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Two rabbits had died at 618 and 718 days, 10 were alive and three were lost to follow-up. Observed acute and late effects were graded according to the Veterinary Radiation Therapy Oncology Group (VRTOG) criteria and were found to be minimal.

To evaluate the efficacy of different radiotherapy treatment modalities in radioresistant brain metastasis.A retrospective analysis was conducted on 78 patients with brain metastases from melanoma, sarcoma, or renal cell carcinoma primary tumours who underwent radiosurgery (20 Gy) and/or hypofractionated stereotactic radiotherapy (6x4 Gy or 7x4 Gy) with or without whole-brain radiotherapy at our Center.The actuarial median survival times for melanoma, renal cell carcinoma and sarcoma were 23, 22 and 7 months respectively, with a significant correlation to recursive partitioning analysis class.Our results show that these treatments were effective both in symptom palliation and in improving survival, suggesting that although outcomes generally remained poor in this study population, it is possible and important to control intracranial brain metastases.

A multichannel time-resolved system for medical optical tomography has been developed. Its main components are an eight channel single-photon counting detector and an ultrafast picosecond solid state laser. Several instrumental aspects concerning the optical coupling between the MCP-PMT and the optical fiber bundles, the electronic components and the roto-translation stages control have been examined. Moreover the accuracy limits in the determination of optical properties of phantom objects have been largely investigated taking into account the role played by the theoretical description of light propagation, the instrumental response function (by means of a convolution procedure) and the fitting algorithm. Information on image quality parameters (spatial resolution, contrast and SNR) have been also obtained by measuring Edge Response Function in different experimental conditions. In such a work, aqueous Intralipid solutions have been used as phantom objects. Furthermore, experimental investigations on well controlled inhomogeneous with different optical properties embedded in Intralipid solutions have been carried on. As last step of the work, preliminary imaging of cylindrical objects has been performed and a Linux version of TOAST code has been used in the imaging reconstruction.

Time-Correlated Single-Photon-Counting (TCSPC) systems have been often adopted to prepare more compact and less expensive instruments for medical imaging. Then it is important to investigate in detail the performances of each imaging system in measuring the optical properties of turbid media. Our experimental apparatus is composed by an Hamamatsu PLP02 pulsed diode laser at 824 nm with 1 Mhz repetition rate and a pulse duration of 40 ps. The signal has been collected from the investigated sample by means of fiber bundles and has been analyzed by an Edinburgh Instrument TCSPCS equipped with an 8 channels Hamamatsu multichannel plate R411OU-F008 and an SPC300 acquisition module. Solutions of distilled water and commercial Intralipid 10% at different concentrations have been investigated. To obtain optical parameters, the experimental data have been fitted with an analytic solution to the diffusion equation. Also the convolution effect of the measured Temporal Point Spread Functions (TPSF) by the Impulse Response Function (IRF) of the system has been investigated. A linear trend has been obtained for the reduced scattering coefficient (mu) 's with concentration in solution of the scattering agent (Intralipid 10%) and an agreement within few percent has been reported with Mie theory predictions. The results here obtained confirm that all the details in fitting and convolution procedures become particularly important when slight difference in absorption and scattering coefficients have to be examined.© (2000) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The optical characterization of scattering media and biological samples is a very important topic due to the interest in using optical techniques as medical diagnostic tool. In this paper we reported experimental results concerning absorption and reduced scattering coefficients obtained in different scattering thick samples like latex and intralipid solutions, bovine muscle, chicken and turkey breast using a tunable time-resolved laser transmittance set-up. Our experimental data have been compared with the result of other different techniques and with the predictions of Mie theory indicating advantages and limits of time-resolved transmittance spectroscopy.