Stromal Liver Kinase B1 [STK11] Signaling Loss Induces Oviductal Adenomas and Endometrial Cancer by Activating Mammalian Target of Rapamycin Complex 1

Germline mutations of the Liver Kinase b1 (LKB1/STK11) tumor suppressor gene have been linked to Peutz-Jeghers Syndrome (PJS), an autosomal-dominant, cancer-prone disorder in which patients develop neoplasms in several organs, including the oviduct, ovary, and cervix. We have conditionally deleted Lkb1 in Müllerian duct mesenchyme-derived cells of the female reproductive tract and observed expansion of the stromal compartment and hyperplasia and/or neoplasia of adjacent epithelial cells throughout the reproductive tract with paratubal cysts and adenomyomas in oviducts and, eventually, endometrial cancer. Examination of the proliferation marker phospho-histone H3 and mammalian Target Of Rapamycin Complex 1 (mTORC1) pathway members revealed increased proliferation and mTORC1 activation in stromal cells of both the oviduct and uterus. Treatment with rapamycin, an inhibitor of mTORC1 activity, decreased tumor burden in adult Lkb1 mutant mice. Deletion of the genes for Tuberous Sclerosis 1 (Tsc1) or Tsc2, regulators of mTORC1 that are downstream of LKB1 signaling, in the oviductal and uterine stroma phenocopies some of the defects observed in Lkb1 mutant mice, confirming that dysregulated mTORC1 activation in the Lkb1-deleted stroma contributes to the phenotype. Loss of PTEN, an upstream regulator of mTORC1 signaling, along with Lkb1 deletion significantly increased tumor burden in uteri and induced tumorigenesis in the cervix and vagina. These studies show that LKB1/TSC1/TSC2/mTORC1 signaling in mesenchymal cells is important for the maintenance of epithelial integrity and suppression of carcinogenesis in adjacent epithelial cells. Because similar changes in the stromal population are also observed in human oviductal/ovarian adenoma and endometrial adenocarcinoma patients, we predict that dysregulated mTORC1 activity by upstream mechanisms similar to those described in these model systems contributes to the pathogenesis of these human diseases

Ni-Co Alloy and Multisegmented Ni/Co Nanowire Arrays Modulated in Composition: Structural Characterization and Magnetic Properties

Design of novel multisegmented magnetic nanowires can pave the way for the next generation of data storage media and logical devices, magnonic crystals, or in magneto-plasmonics, among other energy conversion, recovery, and storage technological applications. In this work, we present a detailed study on the synthesis, morphology, structural, and magnetic properties of Ni, Co, and Ni-Co alloy and multisegmented Ni/Co nanowire

Evaluation of physiological effects induced by manuka honey upon staphylococcus aureus and escherichia coli

Several studies have explored the antimicrobial properties of manuka honey (MkH). However, the data available regarding antibacterial action mechanisms are scarcer. The aim of this study was to scrutinize and characterize primary e ects of manuka honey (MkH) upon the physiological status of Staphylococcus aureus and Escherichia coli (as Gram-positive and Gram-negative bacteria models, respectively), using flow cytometry (FC) to reveal its antibacterial action mechanisms. E ects of MkH on membrane potential, membrane integrity and metabolic activity were assessed using di erent fluorochromes in a 180 min time course assay. Time-kill experiments were carried out under the same conditions. Additionally, MkH e ect on e ux pumps was also studied in an E. coli strain with an over-expression of several e ux pumps. Exposure of bacteria to MkH resulted in physiological changes related to membrane potential and membrane integrity; these e ects displayed slight di erences among bacteria. MkH induced a remarkable metabolic disruption as primary physiological effect upon S. aureus and was able to block effux pump activity in a dose-dependent fashion in the E. coli strain.This work was supported by the Consejería de Sanidad of Junta de Castilla y León; under grant GRS 551/A/10. Patricia Combarros-Fuertes was funded by Consejería de Educación of Junta de Castilla y León and European Social Fund.info:eu-repo/semantics/publishedVersio

Effect of nacl replacement by other salts on the quality of bísaro pork sausages (Pgi chouriça de vinhais)

Concerned about the trend to reduce salt consumption, the meat industry has been increasing the strategies to produce and commercialize products where the reduction or even the replacement of NaCl is an important goal. The aim of this study was to test the effect of partial NaCl replacement by KCl and Sub4Salt® on the quality of pork sausages. Three different formulations (NaCl + KCl, NaCl + Sub4Salt®, and KCl + Sub4Salt®) were considered and compared to the control (2% NaCl). Physicochemical properties, chemical composition, and microbiological and sensory characteristics were evaluated. The replacement of NaCl did not affect pH, water activity (aw) or its chemical composition after eight or 16 days ripening time, while a significant sodium reduction was achieved. The oxidation index expressed in TBARS was also not affected by the NaCl substitution and varied between 0.01 to 0.04 of malonaldehyde (MDA) per kg of sample. Similarly, the NaCl replacement did not change the microbiological quality of the sausages, and the production of healthier meat sausages had also no significant effect on their sensory characteristics. Therefore, according to the results obtained, it is viable and a good strategy for the meat industry to produce “reduced sodium content” sausages without affecting their traditional quality.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support by national funds FCT/MCTES to CIMO (UIDB/00690/2020); to Bísaro-Salsicharia Tradicional industry and to Laboratory of Carcass and Meat Quality of Agriculture School of Polytechnic Institute of Bragança ‘Cantinho do Alfredo’. Thanks are extended to GAIN (Axencia Galega de Innovación) for supporting this work (grant number IN607A2019/01). The authors are members of the Healthy Meat network, funded by CYTED (ref. 119RT0568).info:eu-repo/semantics/publishedVersio

Antibacterial action mechanisms of honey: physiological effects of avocado, chestnut, and polyfloral honey upon Staphylococcus aureus and Escherichia coli

Numerous studies have explored the antibacterial properties of di erent types of honey from all around the world. However, the data available describing how honey acts against bacteria are few. The aim of this study was to apply a flow cytometry (FC) protocol to examine and characterize the primary e ects of three varieties of honey (avocado, chestnut and polyfloral) upon physiological status of Staphylococcus aureus and Escherichia coli cells to reveal their antibacterial action mechanisms. The e ects of honey samples on membrane potential, membrane integrity, and metabolic activity were assessed using di erent fluorochromes, in a 180 min time course assay. Time-kill experiments were also carried out under similar conditions. Exposure of S. aureus and E. coli to the distinct honey samples resulted in physiological changes related to membrane polarization and membrane integrity. Moreover, honey induced a remarkable metabolic disruption as primary physiological e ect upon S. aureus. The di erent honey samples induced quite similar e ects on both bacteria. However, the depth of bacteria response throughout the treatment varied depending on the concentration tested and among honey varieties, probably due to compositional di erences in the honey.This work was supported by the Consejería de Sanidad of Junta de Castilla y León; under Grant GRS 551/A/10. Patricia Combarros-Fuertes was funded by Consejería de Educación of Junta de Castilla y León and European Social Fund.info:eu-repo/semantics/publishedVersio

Influence of a physical education plan on psychomotor development profiles of preschool children

This study aimed to investigate the influence of structured physical education on the psychomotor development of 3 to 5 year-old preschool children. The sample consisted of 324 students of both sexes (3 to 5 year-old) from 9 public kindergarten classes in Porto, Portugal. A battery of psychomotor tests (pre-test) was used to assess the students’ psychomotor development profiles. The sample was divided in 2 groups: an experimental group (162 students) and a control group (162 students). Physical Education (PE) teachers used a structured 24-week PE plan in the experimental group. After the plan completion, the same battery of tests (post-test) was run on both groups. The outcome was that both groups grew their psychomotor profiles; however this growth was always statistically higher in the experimental group (at all ages and in all variables analysed p 0.05). Structured physical education is important for preschool children’s psychomotor development. Physical activity impact on children’s interaction with the outside world was proved, through their overall development motivated by the structured physical education lessons

A C2HC zinc finger is essential for the RING-E2 interaction of the ubiquitin ligase RNF125

The activity of RING ubiquitin ligases (E3s) depends on an interaction between the RING domain and ubiquitin conjugating enzymes (E2), but posttranslational events or additional structural elements, yet largely undefined, are frequently required to enhance or regulate activity. Here, we show for the ubiquitin ligase RNF125 that, in addition to the RING domain, a C2HC Zn finger (ZnF) is crucial for activity, and a short linker sequence (Li2(120-128)) enhances activity. The contribution of these regions was first shown with truncated proteins, and the essential role of the ZnF was confirmed with mutations at the Zn chelating Cys residues. Using NMR, we established that the C2HC ZnF/Li2(120-128) region is crucial for binding of the RING domain to the E2 UbcH5a. The partial X-ray structure of RNF125 revealed the presence of extensive intramolecular interactions between the RING and C2HC ZnF. A mutation at one of the contact residues in the C2HC ZnF, a highly conserved M112, resulted in the loss of ubiquitin ligase activity. Thus, we identified the structural basis for an essential role of the C2HC ZnF and conclude that this domain stabilizes the RING domain, and is therefore required for binding of RNF125 to an E2

The role of physical frailty independent components on increased disabilities in institutionalized older women

The purpose of this study was to identify the independent components of physical frailty that most influence disability indicators in institutionalized older women. A cross-sectional study with 319 participants (81.96+/-7.89 years old) was performed. Disability was assessed through dynamic and static balance tests, activities of daily life and falls risk screen. Fried physical frailty protocol was used to access physical frailty. The frail subgroup displayed the weakest results for all disability indicators (p < 0.05). Regression analysis showed that in the two models tested, low physical activity levels and slowness were the physical frailty independent components that better associated with the disability indicators. More studies with larger samples will help to better understand the independent relationship of each physical frailty component with disability outcomes and assist to design a co-adjuvant treatment to reverse physical frailty

Immobilization and application of the recombinant xylanase GH10 of Malbranchea pulchella in the production of xylooligosaccharides from hydrothermal liquor of the eucalyptus (Eucalyptus grandis) wood chips

Xylooligosaccharides (XOS) are widely used in the food industry as prebiotic components. XOS with high purity are required for practical prebiotic function and other biological benefits, such as antioxidant and inflammatory properties. In this work, we immobilized the recombinant endo-1,4-β-xylanase of Malbranchea pulchella (MpXyn10) in various chemical supports and evaluated its potential to produce xylooligosaccharides (XOS) from hydrothermal liquor of eucalyptus wood chips. Values >90% of immobilization yields were achieved from amino-activated supports for 120 min. The highest recovery values were found on Purolite (142%) and MANAE-MpXyn10 (137%) derivatives, which maintained more than 90% residual activity for 24 h at 70 °C, while the free-MpXyn10 maintained only 11%. In addition, active MpXyn10 derivatives were stable in the range of pH 4.0–6.0 and the presence of the furfural and HMF compounds. MpXyn10 derivatives were tested to produce XOS from xylan of various sources. Maximum values were observed for birchwood xylan at 8.6 mg mL−1 and wheat arabinoxylan at 8.9 mg mL−1, using Purolite-MpXyn10. Its derivative was also successfully applied in the hydrolysis of soluble xylan present in hydrothermal liquor, with 0.9 mg mL−1 of XOS after 3 h at 50 °C. This derivative maintained more than 80% XOS yield after six cycles of the assay. The results obtained provide a basis for the application of immobilized MpXyn10 to produce XOS with high purity and other high-value-added products in the lignocellulosic biorefinery field.The authors gratefully acknowledge FAPESP (São Paulo Research Foundation, grants No: 2018/07522-6) and FCT (POCI-01-0145-FEDER-032206)—transnational cooperation project EcoTech, and National Institute of Science and Technology of Bioethanol, INCT, CNPq 465319/2014-9/FAPESP n ◦ 2014/50884- 5) for financial support. Research scholarships were granted to RCA, DA, and JCSS by FAPESP (Grant No: 2020/00081-4, 2020/15510-8, and 2019/21989-7, respectively), to CCVD and VEP by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Finance Code 001).info:eu-repo/semantics/publishedVersio

Post-thaw viability of in vivo-produced canine blastocysts cryopreserved by slow freezing

The objectives were to evaluate the reexpansion blastocoele rate, post-thaw viability, and in vitro development of canine blastocysts cryopreserved by slow freezing in 1.0 m glycerol (GLY) or 1.5 m ethylene glycol (EG). Fifty-one in vivo-produced canine blastocysts were randomly allocated in two groups: GLY (n = 26) and EG (n = 25). After thawing, embryos from MO were immediately stained with the fluorescent probes propidium iodide and Hoechst 33 342 to evaluate cellular viability. Frozen-thawed embryos from M3 and M6 were cultured in SOFaa medium + 10% FCS at 38.5 degrees C under an atmosphere of 5% CO2 with maximum humidity, for 3 and 6 days, respectively, and similarly stained. The blastocoele reexpansion rate (24 h after in vitro culture) did not differ between GLY (76.5%) and EG (68.8%). Post-thaw viable cells rate were not significantly different between GLY and EG (66.5 +/- 4.8 and 57.3 +/- 4.8, respectively, mean +/- SEM), or among MO (62.3 +/- 5.7%), M3 (56.9 +/- 6.0%), and M6 (66.5 +/- 6.0%). In conclusion, canine blastocysts cryopreserved by slow freezing in 1.0 m glycerol or 1.5 m ethylene glycol, had satisfactory blastocoele reexpansion rates, similar post-thawing viability, and remained viable for up to 6 days of in vitro culture. (C) 2012 Elsevier Inc. All rights reserved.Fundacao de Amparo a Pesquisa do Espirito Santo (FAPES/MCT/CNPq/CTINFRA)CAPES/REUNIDuMilho Raçõe