PIN domain of Nob1p is required for D-site cleavage in 20S pre-rRNA

Nob1p (Yor056c) is essential for processing of the 20S pre-rRNA to the mature 18S rRNA. It is part of a pre-40S ribosomal particle that is transported to the cytoplasm and subsequently cleaved at the 3' end of mature 18S rRNA (D-site). Nob1p is also reported to participate in proteasome biogenesis, and it was therefore unclear whether its primary activity is in ribosome synthesis. In this work, we describe a homology model of the PIN domain of Nob1p, which structurally mimics Mg(2+)-dependent exonucleases despite negligible similarity in primary sequence. Insights gained from this model were used to design a point mutation that was predicted to abolish the postulated enzymatic activity. Cells expressing Nob1p with this mutation failed to cleave the 20S pre-rRNA. This supports both the significance of the structural model and the idea that Nob1p is the long-sought D-site endonuclease

Dynamic Smagorinsky model on anisotropic grids

Large Eddy Simulation (LES) of complex-geometry flows often involves highly anisotropic meshes. To examine the performance of the dynamic Smagorinsky model in a controlled fashion on such grids, simulations of forced isotropic turbulence are performed using highly anisotropic discretizations. The resulting model coefficients are compared with a theoretical prediction (Scotti et al., 1993). Two extreme cases are considered: pancake-like grids, for which two directions are poorly resolved compared to the third, and pencil-like grids, where one direction is poorly resolved when compared to the other two. For pancake-like grids the dynamic model yields the results expected from the theory (increasing coefficient with increasing aspect ratio), whereas for pencil-like grids the dynamic model does not agree with the theoretical prediction (with detrimental effects only on smallest resolved scales). A possible explanation of the departure is attempted, and it is shown that the problem may be circumvented by using an isotropic test-filter at larger scales. Overall, all models considered give good large-scale results, confirming the general robustness of the dynamic and eddy-viscosity models. But in all cases, the predictions were poor for scales smaller than that of the worst resolved direction

C/EBPα-p30 protein induces expression of the oncogenic long non-coding RNA UCA1 in acute myeloid leukemia

Accumulating evidences indicate that different long non-coding RNAs (lncRNAs) might play a relevant role in tumorigenesis, with their expression and function already associated to cancer development and progression. CCAAT/enhancer-binding protein-α (CEBPA) is a critical regulator of myeloid differentiation whose inactivation contributes to the development of acute myeloid leukemia (AML). Mutations in C/EBPα occur in around 10% of AML cases, leading to the expression of a 30-kDa dominant negative isoform (C/EBPα-p30). In this study, we identified the oncogenic urothelial carcinoma associated 1 (UCA1) lncRNA as a novel target of the C/EBPα-p30. We show that wild-type C/EBPα and C/EBPα-p30 isoform can bind the UCA1 promoter but have opposite effects on UCA1 expression. While wild-type C/EBPα represses, C/EBPα-p30 can induce UCA1 transcription. Notably, we also show that UCA1 expression increases in cytogenetically normal AML cases carrying biallelic CEBPA mutations. Furthermore, we demonstrate that UCA1 sustains proliferation of AML cells by repressing the expression of the cell cycle regulator p27kip1. Thus, we identified, for the first time, an oncogenic lncRNA functioning in concert with the dominant negative isoform of C/EBPα in AML

The effect of body mass index on chest trauma severity and prognosis

AIM: Patients with thoracic trauma constitute one third of all the trauma cases, in west Sicily were recorded 941 thoracic trauma during the period between 2006 and 2009. Sicily is one of the Italian regions with the highest rate of obesity: some studies have demonstrated that obesity is an independent risk factor for mortality in high energy blunt traumas. MATERIAL OF STUDY: This study was conducted with trauma patients older than 20 years old who presented to our Department during the last five years. We only included thoracic injuries and politrauma with a thoracic involvement and a BMI > 25- Patients were divided into two groups: HET and LET patients. RESULTS: Thoracic trauma was more common in patients with a BMI > 25 than in normo-weight and clinic admission rate, length of hospital stay and ISS score increased in proportion with the increase of BMI. Both HET (high energy trauma) and LET (low energy trauma) revealed that overweight, obese and morbidly obese patients had greater admissions and length of hospital stay. DISCUSSION: The overweight and obese population has increased substantially over the last two decades and 61,5% of the Sicilian population is above normal weight. A large body mass with excess adiposity may contribute to HET injuries in several ways. Obesity has a number of comorbidities that reduce chances of recovery in overweight and obese patients experienced thoracic trauma both HET and LET. CONCLUSION: Obesity increases morbidity independently of injury severity in thoracic trauma patients. As BMI increased, length of hospital stay increased and prognosis deteriorates

Direct numerical simulations of turbulent pipe flow at high Reynolds number

This paper is associated with a video winner of a 2021 American Physical Society’s Division of Fluid Dynamics (DFD) Gallery of Fluid Motion Award for work presented at the DFD Gallery of Fluid Motion. The original video is available online at the Gallery of Fluid Motion, https://doi.org/10.1103/APS.DFD.2021.GFM.V005

Dynamic Smagorinsky model on anisotropic grids

To examine the performance of the dynamic Smagorinsky model in a controlled fashion on anisotropic grids, simulations of forced isotropic turbulence are performed using highly anisotropic discretizations. The resulting model coefficients are compared with an earlier prediction. Two extreme cases are considered: pancake-like grids, for which two directions are poorly resolved compared to the third, and pencil-like grids, where one direction is poorly resolved when compared to the other two

Macro Minerals and Trace Elements in Milk of Dairy Buffaloes and Cows Reared in Mediterranean Areas

Aim of this study was to evaluate the differences in Ca, P, K, Na, Mg, Zn, Fe, Cu, Mn, Se, Mo, Co, Li, B, Ti, Rb, and Sr concentrations in milk from buffaloes and cows reared in the same farm in Mediterranean areas and fed diets including the same ingredients. Individual milk samples were obtained from 32 Mediterranean buffaloes and 29 Italian Friesian cows and samples of milk, dietary ingredients and drinking water were analyzed for the investigated chemical elements by inductively coupled plasma-mass spectrometry. Data about milk element concentrations were processed by one-way analysis of variance. Buffalo milk contains higher concentrations of Ca, P, Mg, Zn, Fe, Cu, B, Ti, and Sr, and lower concentrations of K, Na, Mo, Li, and Rb compared to cow milk, whereas milk from both species contains similar concentrations of Mn, Se, and Co. The concentrations of the investigated elements in the diet were similar for both species and the differences observed between buffalo and cow milk were not dependent on environmental factors

Isolation and characterization of CD146+ multipotent mesenchymal stromal cells

Mesenchymal stromal cells (MSCs) represent a bone marrow (BM) population, classically defined by five functional properties: extensive proliferation, ability to differentiate into osteoblasts, chondrocytes, adipocytes, and stromal cells−supporting hematopoiesis. However, research progress in this area has been hampered by lack of suitable markers and standardized procedures for MSC isolation. We have isolated a CD146+ multipotent MSC population from 20 human BM donors displaying the phenotype of self-renewing osteoprogenitors; an extensive 12-week proliferation; and the ability to differentiate in osteoblasts, chondrocytes, adipocytes, and stromal cells supporting hematopoiesis. Furthermore, the CD146+ MSCs secrete a complex combination of growth factors (GFs) controlling hematopoietic stem cells (HSCs) function, while providing a >2-log increase in the long-term culture (LTC) colony output in 8-week LTC over conventional assays. The hematopoietic stromal function exhibited by the MSCs was further characterized by manipulating LTCs with the chemical inhibitors Imatinib or SU-5416, targeting two GF receptors (GFRs), KIT or VEGFR2/1, respectively. Both treatments similarly impaired LTC colony output, indicating key roles for these two GF/GFR interactions to support LTC-initiating cell activity. CD146+ MSCs may thus represent a tool to explore the MSC-HSC cross-talk in an in vitro surrogate model for HSC “niches,” and for regenerative therapy studies. In addition, the MSC microRNA (miRNA) expression profile was analyzed by microarrays in both basic conditions and chondrogenic differentiation. Our analysis revealed that several miRNAs are modulated during chondrogenesis, and many of their putative targets are genes involved in chondrogenic differentiation

3D CT scan for perioperative identification of anatomical variations of lungs

Aim: The aim of this study is to investigate anatomical lung variations and vascular patterns using volumetric 3D computed tomography (CT) representations. Methods & results: We considered 24 major thoracic surgery performed in our ward. In these, we discovered some interesting anatomical variations of the main pulmonary fissures. These findings were not visible on the plain x-ray or during routine examination of a preoperative CT scan. After re-examination of 3D CT scan reconstruction the anatomical variations were detected. Discussion: General thoracic surgeons must familiarize themselves with anatomical variations in lungs. 3D images may aid the general thoracic surgeon in performing safer surgeries. Conclusion: 3D CT scan should be performed before surgery if possible

Case report of polymyalgia rheumatica in a male patient with three different neoplasms treated with pembrolizumab.

In this manuscript we aim to describe a particular case of a 63 years-old man who developed three different malignancies (one was a rare case of breast cancer) among nearly five years. In particular, for the diagnosis of melanoma, he was treated with pembrolizumab, a PD-1 inhibitor. After few months of treatment with pembrolizumab, the patient reported the onset of musculoskeletal symptoms such as inflammatory pain at the shoulders and morning stiffness, with raised CRP and ESR and imaging evidence of bursitis and tenosynovitis. A polymyalgia-like syndrome was diagnosed. Understanding if these manifestations are linked to the use of pembrolizumab or to a paraneoplastic syndrome, and how to manage the patient, was the real challenge