PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer.

The promyelocytic leukemia (PML) protein organizes nuclear aggregates known as PML nuclear bodies (PML-NBs), where many transcription factors localize to be regulated. In addition, associations of PML and PML-NBs with chromatin are described in various cell types, further implicating PML in transcriptional regulation. However, a complete understanding of the functional consequences of PML association to DNA in cellular contexts where it promotes relevant phenotypes is still lacking. We examined PML chromatin association in triple-negative breast cancer (TNBC) cell lines, where it exerts important oncogenic functions. We find that PML associates discontinuously with large heterochromatic PML-associated domains (PADs) that contain discrete gene-rich euchromatic sub-domains locally depleted of PML. PML promotes heterochromatic organization in PADs and expression of pro-metastatic genes embedded in these sub-domains. Importantly, this occurs outside PML-NBs, suggesting that nucleoplasmic PML exerts a relevant gene regulatory function. We also find that PML plays indirect regulatory roles in TNBC cells by promoting the expression of pro-metastatic genes outside PADs. Our findings suggest that PML is an important transcriptional regulator of pro-oncogenic metagenes in TNBC cells, via transcriptional regulation and epigenetic organization of heterochromatin domains that embed regions of local transcriptional activity.

Multicenter trans-Atlantic experience with fenestrated-branched endovascular aortic repair of chronic post-dissection thoracoabdominal aortic aneurysms.

OBJECTIVE: This multicenter international study aimed to describe outcomes of fenestrated-branched endovascular aortic repairs (FB-EVAR) in a cohort of patients treated for chronic post-dissection thoracoabdominal aortic aneurysms (PD-TAAAs). METHODS: We reviewed the clinical data of all consecutive patients treated by FB-EVAR for repair of extent I to III PD-TAAAs in 16 centers from the United States and Europe (2008-2021). Data were extracted from institutional prospectively maintained databases and electronic patient records. All patients received off-the-shelf or patient-specific manufactured fenestrated-branched stent grafts. Endpoints were any cause mortality and major adverse events at 30 days, technical success, target artery (TA) patency, freedom from TA instability, minor (endovascular with <12 Fr sheath) and major (open or ≥12 Fr sheath) secondary interventions, patient survival, and freedom from aortic-related mortality (ARM). RESULTS: A total of 246 patients (76% male; median age, 67 years [interquartile range, 61-73 years]) were treated for extent I (7%), extent II (55%), and extent III (35%) PD-TAAAs by FB-EVAR. The median aneurysm diameter was 65 mm (interquartile range, 59-73 mm). Eighteen patients (7%) were octogenarians, 212 (86%) were American Society of Anesthesiologists class ≥3, and 21 (9%) presented with contained ruptured or symptomatic aneurysms. There were 917 renal-mesenteric vessels targeted by 581 fenestrations (63%) and 336 directional branches (37%), with a mean of 3.7 vessels per patient. Technical success was 96%. Mortality and rate of major adverse events at 30 days was 3% and 28%, including disabling complications such as new onset dialysis in 1%, major stroke in 1%, and permanent paraplegia in 2%. Mean follow-up was 24 months. Kaplan-Meier (KM) estimated patient survival at 3 and 5 years was 79% ± 6% and 65% ± 10%. KM estimated freedom from ARM was 95% ± 3% and 93% ± 5% at the same intervals. Unplanned secondary interventions were needed in 94 patients (38%), including minor procedures in 64 (25%) and major procedures in 30 (12%). There was one conversion to open surgical repair (<1%). KM estimated freedom from any secondary intervention was 44% ± 9% at 5 years. KM estimated primary and secondary TA patency were 93% ± 2% and 96% ± 1% at 5 years, respectively. CONCLUSIONS: FB-EVAR for chronic PD-TAAAs was associated with high technical success and a low rate of mortality (3%) and disabling complications at 30 days. Although the procedure is effective in the prevention of ARM, patient survival was low at 5 years (65%), likely due to the significant comorbidities in this cohort of patients. Freedom from secondary interventions at 5 years was 44%, although most procedures were minor. The significant rate of reinterventions highlights the need for continued patient surveillance.

Editor's Choice - Estimated Radiation Dose to the Operator During Endovascular Aneurysm Repair.

OBJECTIVE: To estimate operator organ doses from fluoroscopically guided infrarenal endovascular aneurysm repair (EVAR) procedures, using the detailed exposure information contained in radiation dose structured reports. METHODS: Conversion factors relating kerma area product (PKA) to primary operator organ doses were calculated using Monte Carlo methods for 91 beam angles and seven x-ray spectra typical of clinical practice. A computer program was written, which selects the appropriate conversion factor for each exposure listed in a structured report and multiplies it by the respective PKA. This system was used to estimate operator doses for 81 EVAR procedures for which structured reports were available. The impact of different shielding scenarios and variations in operator position was also investigated. RESULTS: Without any shielding, the median estimated effective dose was 113 µSv (interquartile range [IQR] 71, 252 µSv). The highest median organ doses were for the colon (154 µSv, IQR 81, 343) and stomach (133 µSv, IQR 76, 307). These dose estimates represent all exposures, including fluoroscopy and non-fluoroscopic digital acquisitions. With minimal shielding provided by 0.25 mm of Pb covering the torso and upper legs, the effective dose was reduced by a factor of around 6. With additional shielding from ceiling and table shields, a 25 to 50 fold reduction in dose is achievable. Estimated doses were highest where the primary beam was pointed directly away from the operator. CONCLUSION: The models suggest that with optimal use of shielding, operator doses can be reduced to levels equivalent to one to two days of natural background exposure and well below statutory dose limits.

Fabrication of hierarchical flower-like WO3 nanoparticles for effective metal ions sensing and catalytic degradation of organic dyes.

In this work, we report on the synthesis of flower-like tungsten oxide nanoparticles (WO3 NPs) using a simple precipitation method. This paper reports a simple method for synthesizing flower-like WO3 NPs, which can be used for environmentally treating hazardous organic pollutants. The photocatalytic degradation of model artificial Orange II and Congo red was assessed under natural sunlight irradiation. The surface morphologies, crystallinity, and binding energy of the synthesized WO3 NPs were determined. The synthesized WO3 NPs exhibited good photodegradation percentages of approximately Orange II (97.6%) and Congo red dye (98.2%) after 120 min of irradiation. Furthermore, the WO3 NPs maintained their degradation ability for up to three cycles. In addition, WO3 NPs were examined in different metal ions sensing (Hg2+, Fe2+, Cu2+, Ni2+, and Cd2+) in an aqueous solution. The results showed that the WO3 NPs exhibited excellent Cd2+ ion sensing. Based on the investigations, WO3 NPs proved to be an efficient photocatalyst and hold promise as the best material for future applications in preventing water pollution.

Development of luminescence carbon quantum dots for metal ions detection and photocatalytic degradation of organic dyes from aqueous media.

In the present study, fish scale waste was used for the organic synthesis of luminescence CQDs by the hydrothermal method. The impact of CQDs on improved photocatalytic degradation of organic dyes and metal ions detection is examined in this study. The synthesized CQDs had a variety of characteristics that were detected, such as crystallinity, morphology, functional groups, and binding energies. The luminescence CQDs showed outstanding photocatalytic effectiveness for the destruction of methylene blue (96.5%) and reactive red 120 dye (97.8%), respectively after 120 min exposure to visible light (420 nm). The high electron transport properties of the CQDs edges, which make it possible to efficiently separate electron-hole pairs, are attributed to the enhanced photocatalytic activity of the CQDs. These degradation results prove that the CQDs are the outcome of a synergistic interaction between visible light (adsorption); a potential mechanism is also suggested, and the kinetics is analyzed to use a pseudo-first-order model. Additionally, the metal ions detection of CQDs was studied by various metal ions (Hg2+, Fe2+, Cu2+, Ni2+, and Cd2+) in an aqueous solution and results revealed that the PL intensity of CQDs in presence of cadmium ions decreased. Studies show that the organic fabrication of CQDs are effective photocatalyst and may one day serve as the ideal material to reduce water pollution.

Effects of Antioxidant Combinations on the Renal Toxicity Induced Rats by Gold Nanoparticles.

This study investigated some possible mechanisms underlying the nephrotoxic effect of gold nanoparticles (AuNPs) in rats and compared the protective effects of selected known antioxidants-namely, melanin, quercetin (QUR), and α-lipoic acid (α-LA). Rats were divided into five treatment groups (eight rats per group): control, AuNPs (50 nm), AuNPs + melanin (100 mg/kg), AuNPs + QUR (200 mg/kg), and AuNPs + α-LA (200 mg/kg). All treatments were administered i.p., daily, for 30 days. AuNPs promoted renal glomerular and tubular damage and impaired kidney function, as indicated by the higher serum levels of creatinine (Cr), urinary flow, and urea and albumin/Cr ratio. They also induced oxidative stress by promoting mitochondrial permeability transition pore (mtPTP) opening, the expression of NOX4, increasing levels of malondialdehyde (MDA), and suppressing glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). In addition, AuNPs induced renal inflammation and apoptosis, as evidenced by the increase in the total mRNA and the cytoplasmic and nuclear levels of NF-κB, mRNA levels of Bax and caspase-3, and levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Treatment with melanin, QUR, and α-lipoic acid (α-LA) prevented the majority of these renal damage effects of AuNPs and improved kidney structure and function, with QUR being the most powerful. In conclusion, in rats, AuNPs impair kidney function by provoking oxidative stress, inflammation, and apoptosis by suppressing antioxidants, promoting mitochondrial uncoupling, activating NF-κB, and upregulating NOX4. However, QUR remains the most powerful drug to alleviate this toxicity by reversing all of these mechanisms.

Concomitant Sub-Chronic Administration of Small-Size Gold Nanoparticles Aggravates Doxorubicin-Induced Liver Oxidative and Inflammatory Damage, Hyperlipidemia, and Hepatic Steatosis.

This study examined the effect of gold nanoparticles (AuNPs) on doxorubicin (DOX)-induced liver damage and steatosis in rats and tested its effect mechanism. Wistar male rats were divided into four groups (each of eight rats) as control, AuNPs (50 µL of 10 nm), DOX (15 mg/kg; 3 mg/kg/week), and DOX + AuNPs-treated rats. DOX is known to induce fasting hyperglycemia and hyperinsulinemia in treated rats. Individual treatment of both DOX and AuNPs also promoted liver damage, increased circulatory levels of ALT and AST, and stimulated serum and liver levels of TGs, CHOL, LDL-c, and FFAs. They also stimulated MDA, TNF-α, and IL-6, reduced GSH, SOD, HO-1, and CAT, upregulated mRNA levels of Bax and caspases-3 and -8 and downregulated mRNA levels of Bcl2 in the livers of rats. However, while DOX alone reduced hepatic levels of PPARα, both AuNPs and DOX stimulated mRNA levels of SREBP1, reduced the mRNA, cytoplasmic and nuclear levels of Nrf2, and increased mRNA, cytoplasmic, and nuclear levels of NF-κB. The liver damage and the alterations in all these parameters were significantly more profound when both AuNPs and DOX were administered together. In conclusion, AuNPs exaggerate liver damage, hyperlipidemia, and hepatic steatosis in DOX-treated rats by activating SREBP1 and NF-κB and suppressing the Nrf2/antioxidant axis.

Prediabetes and older age increase the risk of post-transplantation diabetes mellitus: Qatar experience.

Post-transplantation diabetes mellitus (PTDM) is a major complication in kidney transplant recipients leading to reduced allograft and patient survival. Given the high prevalence of diabetes in Qatar, which is twice the global average, we were interested in determining the incidence of PTDM, identifying risk factors, and comparing clinical outcomes in kidney transplant recipients with and without diabetes. We retrospectively followed up 191 adult kidney allograft recipients transplanted between January 1, 2012, and December 31, 2016, for a median of 41 months. A total of 76 patients (40%) had pre-existing diabetes. A total of 39 patients developed PTDM during follow-up; they represent 34% of patients who did not have diabetes prior to transplantation. Two thirds of PTDM occurred within 3-6 months post-transplantation. Prediabetes before transplant [OR = 6.07 (1.24-29.74), P = .026] older recipient's age at the time of transplantation [OR = 1.10 (1.00-1.20), P = .039] and average fasting blood sugar during 3-6 months post-transplant [OR = 1.06 (1.01-1.11), P = .010] were independently associated with PTDM. Patient and kidney allograft survival rates exceeded 97% in all groups. The incidence of PTDM in kidney transplant recipients living in Qatar is high. Older age and prediabetes are independent risk factors for developing PTDM.

Patient radiation dose from x-ray guided endovascular aneurysm repair: a Monte Carlo approach using voxel phantoms and detailed exposure information.

Endovascular aneurysm repair (EVAR) is a well-established minimally invasive technique that relies on x-ray guidance to introduce a stent through the femoral artery and manipulate it into place. The aim of this study was to estimate patient organ and effective doses from EVAR procedures using anatomically realistic computational phantoms and detailed exposure information from radiation dose structured reports (RDSR). Methods: Lookup tables of conversion factors relating kerma area product (PKA) to organ doses for 49 different beam angles were produced using Monte Carlo simulations (MCNPX2.7) with International Commission on Radiological Protection (ICRP) adult male and female voxel phantoms for EVAR procedures of varying complexity (infra-renal, fenestrated/branched and thoracic EVAR). Beam angle specific correction factors were calculated to adjust doses according to x-ray energy. A MATLAB function was written to find the appropriate conversion factor in the lookup table for each exposure described in the RDSR, perform energy corrections and multiply by the respective exposure PKA. Using this approach, organ doses were estimated for 183 EVAR procedures in which RDSRs were available. A number of simplified dose estimation methodologies were also investigated for situations in which RDSR data are not available. Results: Mean estimated bone marrow doses were 57 (range: 2-247), 86 (2-328) and 54 (8-250) mGy for infra-renal, fenestrated/branched and thoracic EVAR, respectively. Respective effective doses were 27 (1-208), 54 (1-180) and 37 (5-167) mSv. Dose estimates using non-individualised, average conversion factors, along with those produced using the alternative Monte Carlo code PCXMC, yielded reasonably similar results overall, though variation for individual procedures could exceed 100% for some organs. In conclusion, radiation doses from x-ray guided endovascular aneurysm repairs are potentially high, though this must be placed in the context of the life sparing nature and high success rate for this procedure.

Management of super-super obese patients: comparison between one anastomosis (mini) gastric bypass and Roux-en-Y gastric bypass.

BACKGROUND: Gastric bypass can be technically challenging in super-super obese patients. Both Roux-en-Y gastric bypass (RYGB) and one anastomosis (mini) gastric bypass (OAGB/MGB) have been described in these patients, but direct comparisons are lacking. The purpose of this study was to compare the early outcomes with these two procedures in patients with body mass index (BMI) of ≥60 kg/m2 in our unit. METHODS: We identified all super-super obese patients who underwent either OAGB/MGB or RYGB from our prospectively maintained database. Information was also obtained from the case notes and from hospital computerized records. We obtained data regarding patient demographics, operative details, complications, and weight loss, in both groups, and compared them using standard statistical methods. RESULTS: This study compares our results with 19 OAGB/MGB and 47 RYGB super-super obese patients performed in our unit between October 2012 and June 2015. OAGB/MGB group patients had a significantly higher weight and body mass index. There was no mortality or major complication in either group. There were two late complications in the OAGB/MGB group compared to six in the RYGB group. One patient in the OAGB/MGB group needed conversion to RYGB for persistent reflux symptoms. OAGB/MGB patients achieved a significantly higher EWL of 70.4% at 2 years compared to 57.1% in the RYGB group. The difference between TWL of 44.4 and 33.4%, respectively, was also significant at 2 years. TWL of 43.0 and 29.3%, respectively, in OAGB/MGB and RYGB groups at 18 months was also significantly different, but the difference in EWL at 18 months did not reach significance. CONCLUSION: One anastomosis (mini) gastric bypass yields superior weight loss at 18 and 24 months in comparison with Roux-en-Y gastric bypass in patients with BMI of ≥60 kg/m2. Findings need confirmation in larger randomized studies.

The dosimetric properties of phosphate glass systems prepared by different chemical nanomaterials.

The synthesis and characterization of glass systems were carried out using prepared nanocrystals injected into a glass matrix as a thermoluminescence (TL) activator using the melt-quenching method. Sample 1 was prepared as [40P2 O5 50BaO:2.5MgO, 2.5Na2 O, 5TiO2 ], sample 2 as [37.5P2 O5 37.5CaO:25TiO2 ] and sample 3 as [50P2 O5 -50Li2 O]. Formation of the synthesized compound was confirmed by studying the X-ray diffraction (XRD) patterns and scanning electron microscopy (SEM) images. An annealing procedure was carried out for 1 h at 400 °C. The glow curve position and shape shifted dramatically and linearly to the higher temperature values on increasing the heating rate. A heating rate of 30 °C/s was the most suitable for obtaining a high TL response. Samples 2 and 3 have the highest TL response, which approached the effective atomic number (Zeff ) of natural bone. The observed TL sensitivity of the prepared samples 2 and 3 is less than that of commercially available 'TLD-200 chips' and LiF:Mg,Ti (TLD-100) phosphor. Sample [37.5P2 O5 37.5CaO:25TiO2 ] would be useful in personal and environmental dosimetry for measuring high doses of gamma radiation. Sample [50P2 O5 -50Li2 O] is a good dosimeter, although it requires the addition of an appropriate transitional metal (activator) to overcome the problem of high fading. Copyright © 2016 John Wiley & Sons, Ltd.

The influence of zinc on the blood serum of cadmium-treated rats through the rheological properties.

The blood rheological properties serve as an important indicator for the early detection of many diseases. This study aimed to investigate the influence of zinc (Zn) on blood serum of cadmium (Cd) intoxication-treated male rats through the rheological properties. The rheological parameters were measured in serum of control, Cd, and Cd+Zn groups at wide range of shear rates (225-1875 s(-1)). The rat blood serum showed a non-significant change in cadmium-treated rats' %torque and shear stress at the lower shear rates (200-600 s(-1)) while a significant increase was observed at the higher shear rates (650-1875 s(-1)) compared with the control. The rat blood serum viscosity increased significantly in the Cd-treated group at each shear rate compared with the control. The viscosity and shear rate exhibited a non-Newtonian behavior for all groups. The increase in blood serum viscosity in Cd-treated male rats might be attributed to destruction or changes in the non-clotting proteins, and other blood serum components. In Cd+Zn-treated rats, the rat blood serum viscosity values returned nearer to the control values at each shear rate. Our results confirmed that Zn displaced Cd or compete with the binding sites for Cd uptake.

Short Communication: Rheological properties of blood serum of rats after irradiation with different gamma radiation doses in vivo.

The blood serum rheological properties open the door to find suitable radio-protectors and convenient therapy for many cases of radiation exposure. The present study aimed to investigate the rheological properties of rat blood serum at wide range of shear rates after whole body irradiation with different gamma radiation doses in vivo. Healthy male rats were divided into five groups; one control group and 4 irradiated groups. The irradiation process was carried out using Co60 source with dose rate of 0.883cG/sec. Several rheological parameters were measured using Brookfield LVDV-III Programmable rheometer. A significant increase in viscosity and shear stress was observed with 25 and 50Gy corresponding to each shear rate compared with the control; while a significant decrease observed with 75 and 100Gy. The viscosity exhibited a Non-Newtonian behaviour with the shear rate while shear stress values were linearly related with shear rate. The decrease in blood viscosity might be attributed to changes in molecular weight, pH sensitivity and protein structure. The changes in rheological properties of irradiated rats' blood serum might be attributed to destruction changes in the haematological and dimensional properties of rats' blood products.

The changes in serum and whole blood rheological properties of rabbits during the progression of atherosclerosis.

This study aimed to evaluate the role of zinc (Zn)-supplemented with high cholesterol diet (HCD) on the serum and whole blood rheological properties of rabbits fed a HCD. Twenty-four New Zealand white rabbits were divided into three groups. The HCD group was fed a diet with 1.0% cholesterol and 1.0% olive oil. The HCD + Zn group was fed a diet with 1.0% cholesterol, 1.0% olive oil, and Zn. Blood viscosity, shear stress, and torque (%) were measured at shear rates ranging from 225 to 1875 s-1 for serum and 75-900 s-1 for whole blood. Serum viscosity and shear stress in HCD rabbits were significantly higher at all shear rates compared to controls; while whole blood viscosity and shear stress in HCD rabbits were significantly lower at all shear rates compared to controls. Viscosity and shear stress in both serum and whole blood from rabbits in the HCD + Zn group returned to normal values at all shear rates. The Zn supplemented to HCD rabbits, delays the progression of atherosclerosis. Changes in blood serum viscosity could reflect changes in non-clotting proteins, glucose, nutrients and trace elements; while changes in whole blood viscosity could result from changes in hematocrit, hemoglobin, and erythrocyte count. One of the factors responsible for increasing the serum viscosity values of HCD rabbits might be attributed to increase in Fe and decrease in Zn levels in the blood serum.

Ultraviolet-visible and fluorescence spectroscopy can be used as a diagnostic tool for gamma irradiation detection in vivo.

The spectroscopic properties can indicate important features about the nature and severity of the disease. However, no earlier studies have been used the spectroscopic properties as a diagnostic tool for radiation detection. This study was aimed to use ultraviolet-visible and fluorescence spectroscopy as a diagnostic tool for gamma irradiation detection in rats in vivo. Adult male rats were exposed to 25, 50, 75 and 100 Gray as single dose, using Cobalt-60 (Co-60) source with a dose rate of 0.883 centi Gray/sec (cGy/s). Ultraviolet and fluorescence spectroscopy of rat's blood serum were measured. After gamma irradiation of rats in vivo, the blood serum absorbance peaks for 25, 50, 75 and 100 Gray (Gy) decreased and shifted towards the ultra violet wavelength. A maximal change in fluorescence intensity of blood serum at 350 nm was obtained when exciting light at 194 nm after irradiation. The fluorescence intensity also decreased with the dose. The highest radiation gamma dose might be accompanied with the highest oxidative stress. This study suggests that at the above mentioned gamma radiation doses, the blood is highly fragmented; with low aggregation at 25 Gy and with high aggregation at 50-100 Gy.

The effects of intraperitoneal administration of gold nanoparticles size and exposure duration on oxidative and antioxidants levels in various rat organs.

As one of the toxic mechanism of nanoparticles (NPs), the reactive oxygen species (ROS) generation which has been widely studied. Nevertheless, the link between GNPs and antioxidant and oxidative stress markers has not been well established. The effects of gold nanoparticles (GNPs) size and exposure duration on antioxidant and oxidative stress markers including reduced glutathione (GSH), super oxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), total antioxidant capacity and malondialdehyde (MDA) were evaluated in different rat organs. Adult male Wistar-Kyoto rats were randomly divided into 6 groups of 5 animals each. One group served as control and received vehicle only. The 10 nm GNPs were used in this study. The GNPs electron density and homogeneity in shape and size was evaluated. Dose of 50 µl of 10 nm GNPs in aqueous solution were administered to animals via intraperitoneal administration daily for exposure duration of 3 or 7 days. The rats were sacrificed 24 h after the last injection of GNPs. The specimens of liver, lung, kidney and heart were collected for biochemical analyses. The GPx, total antioxidant capacity, GSH and MDA levels significantly increased after administration of 10 nm GNPs for exposure duration of 3 and 7 days in the organs of rats compared with the control while the GR and SOD levels significantly decreased. The GNPs have the potential to interact with the biological system and cause undesirable effects. One of these damaging effects could be the disturbance in the natural balance between oxidative stress and antioxidant defense indices, which in turn can lead to various pathological effects. The changes in antioxidant and oxidative stress markers might be attributed to the production of ROS.

The effects of gamma-radiation on red blood cell corpuscles and dimensional properties in rats.

In an attempt to understand the toxicity and the potential role of gamma-radiation as a therapeutic tool, the effects of different Gamma-radiation doses on haematological and dimensional properties of rats' blood were investigated in vivo. 60 healthy male Wistar-Kyoto rats were used, which were randomly divided into five groups, 4 Gamma-radiated rat groups (1st group was radiated with five Gamma-radiation dose, 2nd group 25 Gy; 3rd group with 50 Gy, 4th group with 100 Gy, and 5th group was control). Different haematological and dimensional parameters were measured using the standard haematological technique. A significant decrease in red blood cells (RBCs) count, haemoglobin (HGB), and haematocrit (HCT) was observed compared with the control. While a significant increase in mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC), red distribution width (RDW) were observed compared with the control. This study suggested that low RBCs, HGB, and HCT might produce anemia and cessation of erythrocytes production in the bone marrow. Moreover, the RBCs size increase might be attributed to changes in the morphology and deformability of RBCs, which was confirmed by a slightly increase in RDW.

Effect of incubating egg exposure to magnetic field on the biophysical blood properties of newly-hatched chicks.

Due to widespread of human exposure to electromagnetic fields, there has been increasing public concern about the potential health risks from low-frequency electromagnetic fields; ELF-EMF. The magnetic fields (MFs) affects functions of the living organisms, such as DNA synthesis and ion transportation through the cell membranes. In the present work, the effects of short-term exposure to magnetic fields (MFs) prior to incubation were investigated on the biophysical blood properties of chicks hatched from layer-type breeder eggs. The eggs were exposed to a MF of 0.75 mT at 50 Hz for 20, 40 and 60 min before incubation. This study was performed by measuring the dielectric relaxation of hemoglobin (Hb) molecules and the membrane solubility of red blood cells (RBCs) using the non-ionic detergent octylglucoside. Exposure of the eggs to a MF increased the conductivity of the Hb molecules. The pronounced increase in the conductivity of the exposed eggs might be attributed to an increase in the surface charge of the Hb macromolecules, resulted from the formation of highly active molecular species. This speculation can be supported by the increase in the relaxation time of the exposed groups. The solubilization process of the RBC membrane indicates a loss in the mobility of RBCs in the blood of hatching chicks.

Alternative isoform expression of key thermogenic genes in human beige adipocytes.

Background: The beneficial effect of thermogenic adipocytes in maintaining body weight and protecting against metabolic disorders has raised interest in understanding the regulatory mechanisms defining white and beige adipocyte identity. Although alternative splicing has been shown to propagate adipose browning signals in mice, this has yet to be thoroughly investigated in human adipocytes. Methods: We performed parallel white and beige adipogenic differentiation using primary adipose stem cells from 6 unrelated healthy subjects and assessed differential gene and isoform expression in mature adipocytes by RNA sequencing. Results: We find 777 exon junctions with robust differential usage between white and beige adipocytes in all 6 subjects, mapping to 562 genes. Importantly, only 10% of these differentially spliced genes are also differentially expressed, indicating that alternative splicing constitutes an additional layer of gene expression regulation during beige adipocyte differentiation. Functional classification of alternative isoforms points to a gain of function for key thermogenic transcription factors such as PPARG and CITED1, and enzymes such as PEMT, or LPIN1. We find that a large majority of the splice variants arise from differential TSS usage, with beige-specific TSSs being enriched for PPARγ and MED1 binding compared to white-specific TSSs. Finally, we validate beige specific isoform expression at the protein level for two thermogenic regulators, PPARγ and PEMT. Discussion: These results suggest that differential isoform expression through alternative TSS usage is an important regulatory mechanism for human adipocyte thermogenic specification.