immunocytochemical localization of urokinase-type plasminogen activator in lewis lung carcinoma

The invasively growing and metasizing Lewis lung carcinoma consistently contained urokinase-type plasminogen activator (u-PA) enzyme activity. When investigated immunocytochemically with antibodies against u-PA, different parts of individual tumors showed a pronounced heterogeneity in staining intensity. Strong staining was found in areas with invasive growth and degradation of surrounding normal tissue, while other areas were completely devoid of staining. Immunoreactivity occurred both with a perinuclear cytoplasmic localization in tumor cells and associated with apparently extracellular material. SDS PAGE of tumor extracts, under both reducing and nonreducing conditions, followed by immunoblotting, showed only one immunocytochemically stainable band with an electrophoretic mobility corresponding to that of purified proenzyme to u-PA, while no two-chain u-PA was detected. This indicates that the major part of the activator in Lewis lung carcinoma is present as one-chain pro-u-PA.     

LEDPatNet19: Automated Emotion Recognition Model based on Nonlinear LED Pattern Feature Extraction Function using EEG Signals

Electroencephalography (EEG) signals collected from human brains have generally been used to diagnose diseases. Moreover, EEG signals can be used in several areas such as emotion recognition, driving fatigue detection. This work presents a new emotion recognition model by using EEG signals. The primary aim of this model is to present a highly accurate emotion recognition framework by using both a hand-crafted feature generation and a deep classifier. The presented framework uses a multilevel fused feature generation network. This network has three primary phases, which are tunable Q-factor wavelet transform (TQWT), statistical feature generation, and nonlinear textural feature generation phases. TQWT is applied to the EEG data for decomposing signals into different sub-bands and create a multilevel feature generation network. In the nonlinear feature generation, an S-box of the LED block cipher is utilized to create a pattern, which is named as Led-Pattern. Moreover, statistical feature extraction is processed using the widely used statistical moments. The proposed LED pattern and statistical feature extraction functions are applied to 18 TQWT sub-bands and an original EEG signal. Therefore, the proposed hand-crafted learning model is named LEDPatNet19. To select the most informative features, ReliefF and iterative Chi2 (RFIChi2) feature selector is deployed. The proposed model has been developed on the two EEG emotion datasets, which are GAMEEMO and DREAMER datasets. Our proposed hand-crafted learning network achieved 94.58%, 92.86%, and 94.44% classification accuracies for arousal, dominance, and valance cases of the DREAMER dataset. Furthermore, the best classification accuracy of the proposed model for the GAMEEMO dataset is equal to 99.29%. These results clearly illustrate the success of the proposed LEDPatNet19.     

Evolutionary history of the SARS-CoV-2 Gamma variant of concern (P.1): a perfect storm

Our goal was to describe in more detail the evolutionary history of Gamma and two derived lineages (P.1.1 and P.1.2), which are part of the arms race that SARS-CoV-2 wages with its host. A total of 4,977 sequences of the Gamma strain of SARS-CoV-2 from Brazil were analyzed. We detected 194 sites under positive selection in 12 genes/ORFs: Spike, N, M, E, ORF1a, ORF1b, ORF3, ORF6, ORF7a, ORF7b, ORF8, and ORF10. Some diagnostic sites for Gamma lacked a signature of positive selection in our study, but these were not fixed, apparently escaping the action of purifying selection. Our network analyses revealed branches leading to expanding haplotypes with sites under selection only detected when P.1.1 and P.1.2 were considered. The P.1.2 exclusive haplotype H_5 originated from a non-synonymous mutational step (H3509Y) in H_1 of ORF1a. The selected allele, 3509Y, represents an adaptive novelty involving ORF1a of P.1. Finally, we discuss how phenomena such as epistasis and antagonistic pleiotropy could limit the emergence of new alleles (and combinations thereof) in SARS-COV-2 lineages, maintaining infectivity in humans, while providing rapid response capabilities to face the arms race triggered by host immuneresponses.     

Leptin activation of mTOR pathway in intestinal epithelial cell triggers lipid droplet formation,cytokine production and increased cell proliferation

Accumulating evidence suggests that obesity and enhanced inflammatory reactions are predisposing conditions for developing colon cancer. Obesity is associated with high levels of circulating leptin. Leptin is an adipocytokine that is secreted by adipose tissue and modulates immune response and inflammation. Lipid droplets (LD) are organelles involved in lipid metabolism and production of inflammatory mediators, and increased numbers of LD were observed in human colon cancer. Leptin induces the formation of LD in macrophages in a PI3K/mTOR pathway-dependent manner. Moreover, the mTOR is a serine/threonine kinase that plays a key role in cellular growth and is frequently altered in tumors. We therefore investigated the role of leptin in the modulation of mTOR pathway and regulation of lipid metabolism and inflammatory phenotype in intestinal epithelial cells (IEC-6 cells). We show that leptin promotes a dose- and time-dependent enhancement of LD formation. The biogenesis of LD was accompanied by enhanced CXCL1/CINC-1, CCL2/MCP-1 and TGF-β production and increased COX-2 expression in these cells. We demonstrated that leptin-induced increased phosphorylation of STAT3 and AKT and a dose and time-dependent mTORC activation with enhanced phosphorilation of the downstream protein P70S6K protein. Pre-treatment with rapamycin significantly inhibited leptin effects in LD formation, COX-2 and TGF-β production in IEC-6 cells. Moreover, leptin was able to stimulate the proliferation of epithelial cells on a mTOR-dependent manner. We conclude that leptin regulates lipid metabolism, cytokine production and proliferation of intestinal cells through a mechanism largely dependent on activation of the mTOR pathway, thus suggesting that leptin-induced mTOR activation may contribute to the obesity-related enhanced susceptibility to colon carcinoma.     

Effect of exposure to 50 Hz magnetic field with or without insulin on blood–brain barrier permeability in streptozotocin‐induced diabetic rats

We investigated the effect of long‐term exposure to modulation magnetic field (MF), insulin, and their combination on blood–brain barrier (BBB) permeability in a diabetic rat model. Fifty‐three rats were randomly assigned to one of six groups: sham, exposed to no MF; MF, exposed to MF; diabetes mellitus (DM), DM induced with streptozotocin (STZ); DM plus MF (DMMF); DM plus insulin therapy (DMI); and DM plus insulin therapy plus MF (DMIMF). All the rats underwent Evans blue (EB) measurement to evaluate the BBB 30 days after the beginning of experiments. The rats in MF, DMMF, and DMIMF groups were exposed to MF (B = 5 mT) for 165 min every day for 30 days. Mean arterial blood pressure (MABP), body mass, and serum glucose level of the study rats were recorded. The extravasation of brain EB of the MF, DM, DMMF, DMI, and DMIMF groups was higher than that of the sham group and the extravasation of right hemisphere of the DMIMF group was highest (P < 0.05). The post‐procedure body mass of the sham and MF groups were significantly higher than those of the DM and DMMF groups (P < 0.05). In the DM, DMMF, DMI, and DMIMF groups, the baseline glucose was significantly lower than the post‐procedure glucose (P < 0.05). DM and MF increase BBB permeability; in combination, they cause more increase in BBB permeability, and insulin decreases their effect on BBB. Improved glucose metabolism may prevent body mass loss and the hypoglycemic effect of MF. DM increases MABP but MF causes no additional effect. Bioelectromagnetics 31:262–269, 2010. © 2009 Wiley‐Liss, Inc.     

Reconstruction of orbital floor fracture using solvent-preserved bone graft

The orbital floor is one of the most frequently damaged parts of the maxillofacial skeleton during facial trauma. Unfavorable aesthetic and functional outcomes are frequent when it is treated inadequately. The treatment consists of spanning the floor defect with a material that can provide structural support and restore the orbital volume. This material should also be biocompatible with the surrounding tissues and easily reshaped to fit the orbital floor. Although various autografts or synthetic materials have been used, there is still no consensus on the ideal reconstruction method of orbital floor defects. This study evaluated the applicability of solvent-preserved cadaveric cranial bone graft and its preliminary results in the reconstruction of the orbital floor fractures. Twenty-five orbital floor fractures of 21 patients who underwent surgical repair with cadaveric bone graft during a 2-year period were included in this study. Pure blowout fractures were determined in nine patients, whereas 12 patients had other accompanying maxillofacial fractures. Of the 21 patients, 14 had clinically evident diplopia (66.7 percent), 12 of them had enophthalmos (57.1 percent), and two of them had gaze restriction preoperatively. Reconstruction of the floor of the orbit was performed following either the subciliary or the transconjunctival approach. A cranial allograft was placed over the defect after sufficient exposure. The mean follow-up period was 9 months. Postoperative diplopia, enophthalmos, eye motility, cosmetic appearance, and complications were documented. None of the patients had any evidence of diplopia, limited eye movement, inflammatory reactions in soft tissues, infection, or graft extrusion in the postoperative period. Providing sufficient orbital volume, no graft resorption was detected in computed tomography scan controls. None of the implants required removal for any reason. Enophthalmos was seen in one patient, and temporary scleral show lasting up to 3 to 6 weeks was detected in another three patients. Satisfactory cosmetic results were obtained in all patients. This study showed that solvent-preserved bone, which is a nonsynthetic, human-originated, processed bioimplant, can be safely used in orbital floor repair and can be considered as another reliable treatment alternative.     

A review of 35 cases of asymmetric crying facies

A review of 35 cases of asymmetric crying facies: Congenital asymmetric crying facies (ACF) is caused by congenital hypoplasia or agenesis of the depressor anguli oris muscle (DAOM) on one side of the mouth. It is well known that this anomaly is frequently associated with cardiovascular, head and neck, musculoskeletal, respiratory, gastrointestinal, central nervous system, and genitourinary anomalies. In this article we report 35 ACF patients (28 children and 7 adults) and found additional abnormalities in 16 of them (i.e. 45%). The abnormalities were cerebral and cerebellar atrophy, mega-cisterna magna, mental motor retardation, convulsions, corpus callosum dysgenesis, cranial bone defect, dermoid cyst, spina bifida occulta, hypertelorism, micrognatia, retrognatia, hemangioma on the lower lip, short frenulum, cleft palate, low-set ears, preauricular tag, mild facial hypoplasia, sternal cleft, congenital heart defect, renal hypoplasia, vesicoureteral reflux, hypertrophic osteoarthropathy, congenital joint contractures, congenital hip dislocation, polydactyly, and umbilical and inguinal hernia. Besides these, one infant was born to a diabetic mother, and had atrial septal defect and the four other children had 4p deletion, Klinefelter syndrome, isolated CD4 deficiency and Treacher-Collins like facial appearance, respectively Although many of these abnormalities were reported in association with ACF, cerebellar atrophy, sternal cleft, cranial bone defect, infant of diabetic mother, 4p deletion, Klinefelter syndrome, isolated CD4 deficiency and Treacher-Collins like facial appearance were not previously published.     

Influence of various antioxidants added to TCM-199 on post-thaw bovine sperm parameters,DNA integrity and fertilizing ability

Supplementation of the semen extender with antioxidants did not produce any significant effect on CASA and progressive motilities and sperm motility characteristics, in comparison to the control group (P > 0.05).