Functional characterization of tissue inhibitor of metalloproteinase-1 (TIMP-1) N- and C-terminal domains during xenopus laevis development

Extracellular matrix (ECM) remodeling is essential for facilitating developmental processes. ECM remodeling, accomplished by matrix metalloproteinases (MMPs), is regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs). While the TIMP N-terminal domain is involved in inhibition of MMP activity, the C-terminal domain exhibits cell-signaling activity, which is TIMP and cell type dependent. We have previously examined the distinct roles of the Xenopus laevis TIMP-2 and -3 C-terminal domains during development and here examined the unique roles of TIMP-1 N- and C-terminal domains in early X. laevis embryos. mRNA microinjection was used to overexpress full-length TIMP-1 or its individual N- or C-terminal domains in embryos. Full-length and C-terminal TIMP-1 resulted in increased lethality compared to N-terminal TIMP-1. Overexpression of C-terminal TIMP-1 resulted in significant decreases in mRNA levels of proteolytic genes including TIMP-2, RECK, MMP-2, and MMP-9, corresponding to decreases in MMP-2 and -9 protein levels, as well as decreased MMP-2 and MMP-9 activities. These trends were not observed with the N-terminus. Our research suggests that the individual domains of TIMP-1 are capable of playing distinct roles in regulating the ECM proteolytic network during development and that the unique functions of these domains are moderated in the endogenous full-length TIMP-1 molecule. © 2014 M. A. Nieuwesteeg et al

Colitis linfoplasmocitaria canina : un hallazgo frecuente en la exploración colonoscópica

En este trabajo se describen los hallazgos clínicos, laboratoriales y colonoscópicos de la colitis linfoplasmocitaria canina, aparte de tratar los aspectos más relevantes sobre su etiopatogenia y diagnóstico, para describir finalmente las pautas de tratamiento del proceso

Stable expression of α1-antitrypsin Portland in MDA-MB-231 cells increased MT1-MMP and MMP-9 levels, but reduced tumour progression.

The membrane bound matrix metalloproteinase MT1-MMP plays roles in modulating cell movement, independent of its abilities to remodel the extracellular matrix. Unlike many MMPs, MT1-MMP is activated in the Golgi prior to secretion by a pro-protein convertase, primarily furin. Regulation of the activation of pro-MT1-MMP has been methodically investigated, as altering the level of the active protein has broad implications in both activating other proMMPs, including pro-MMP-2, and many subsequent remodelling events. Our previous work in MCF-7 cells has demonstrated that modest, and not extremely high, levels of active MT1-MMP manifests into altered cell morphology and movement. At this low but optimal amount of MT1-MMP protein, changes to MT1-MMP levels are always mirrored by MMP-9 and pERK levels, and always opposite to MMP-2 levels. In this study, stable expression of the furin inhibitor α1- antitrypsin Portland (α1-PDX) in MDA-MB-231 cells increased overall MT1-MMP levels, but cells maintained a 21% proportion of pro-MT1-MMP. The increase in MT1- MMP was mirrored by increases in MMP-9 and pERK, but a decrease in MMP-2. These changes were associated with increased NF-κB transcription. In vitro analysis showed that α1-PDX decreased cell protrusions and migration, and this manifested as decreased tumourigenesis when examined in vivo using a chick CAM assay

Cabin-fuselage-wing structural design concept with engine installation

The purpose of this project is to provide a fuselage structural assembly and wing structural design that will be able to withstand the given operational parameters and loads provided by Federal Aviation Regulation Part 23 (FAR 23) and the Statement of Work (SOW). The goal is to provide a durable lightweight structure that will transfer the applied loads through the most efficient load path. Areas of producibility and maintainability of the structure will also be addressed. All of the structural members will also meet or exceed the desired loading criteria, along with providing adequate stiffness, reliability, and fatigue life as stated in the SOW. Considerations need to be made for control system routing and cabin heating/ventilation. The goal of the wing structure and carry through structure is also to provide a simple, lightweight structure that will transfer the aerodynamic forces produced by the wing, tailboom, and landing gear. These forces will be channeled through various internal structures sized for the pre-determined loading criteria. Other considerations were to include space for flaps, ailerons, fuel tanks, and electrical and control system routing. The difficulties encountered in the fuselage design include expanding the fuselage cabin to accept a third occupant in a staggered configuration and providing ample volume for their safety. By adding a third person the CG of aircraft will move forward so the engine needs to be moved aft to compensate for the difference in the moment. This required the provisions of a ring frame structure for the new position of the engine mount. The difficulties encountered in the wing structural design include resizing the wing for the increased capacity and weight, and compensating for a large torsion produced by the tail boom by placing a great number of stiffeners inside the boom, which will result in the relocation of the fuel tank. Finally, an adequate carry through structure for the wing and fuselage interface will be designed to effectively transmit loads through the fuselage

Project Reach: Implementation of Evidence-Based Psychotherapy Within Integrated Healthcare for Hurricane Harvey Affected Individuals

Project Reach was established to deliver evidence-based mental healthcare services to children and adults affected by Hurricane Harvey and its aftermath. Through Project Reach, an innovative multi-component assessment and treatment service is utilized to identify and treat in integrated healthcare settings both children and adults exhibiting significant behavioral health concerns in Houston. The aim is to provide sustainable, integrated mental health services through primary care and school-based settings to post-Harvey affected individuals whose emotional needs remain unmet. This paper describes the design and implementation of Project Reach as well as special considerations for implementation. The overall goal of Project Reach is to form a platform for expanding integrated services for those affected by Harvey that will maximize behavioral health outcomes while reducing cost and improving access

Spontaneous intratumoral bleeding and rupture of giant gastric stromal tumor (> 30 cm) in a young patient

<p>Abstract</p> <p>Background</p> <p>Few cases of GIST bigger than 15 cm have been reported in medical literature, all primarily in elderly patients. We report an unusual case, in which a giant gastric GIST – in a young patient – presented as spontaneous intratumoral bleeding followed by intraluminal rupture.</p> <p>Case presentation</p> <p>A 37-year-old man was admitted with an acute onset of abdominal pain. CT showed a 32 × 25 cm mass with some cystic lesions and areas of calcification. Twelve hours after admission the patient presented with an episode of upper GI bleeding, and a significant decrease of tumor size and hemoglobin level. An upper endoscopy showed a large bulge in the posterior aspect of the gastric wall, and a small ulcer with continuous bleeding coming from a central orifice. A subtotal gastrectomy was carried out. Pathological examination showed a giant gastric GIST measuring 32 × 25 × 21 cm and weighing 3.750 g. Immunohistochemical staining demonstrated positive reactivity to C-kit protein, CD34, and α-smooth muscle actin; but negative reactivity to S-100 protein.</p> <p>Conclusion</p> <p>Intratumoral bleeding is a very rare presentation of GIST; preoperative diagnosis is always made difficult by the absence of pathognomonic signs or symptoms. Emergency local excision with negative margins associated with adjuvant therapy with imatinib mesylate remains the main modality of treatment for high risk GISTs.</p

Levels of insulin and HOMA-IR in adolescents in Saltillo, Coahuila, Mexico

An alarming rise of obesity in adolescents has been observed, placing them at risk of developing resistance to insulin (IR) and its adverse metabolic consequences such as diabetes mellitus type 2 (DM2), metabolic syndrome and cardiovascular disease. Objective: To know the prevalence of obesity, and the levels of glucose, insulin and HOMA-IR and its association with the BMIz, waist circumference and the pubertal stage in a random sample of adolescents. Materials and methods: 292 adolescents between 12 and 15 years (152 female and 140 male), whose anthropometric measurements (weight, height and waist circumference) were taken, body mass index calculated and Z-score determined. Blood glucose and insulin levels were evaluated from a sample of blood and their HOMA-IR was determined. Results: The results showed that 32.5% were obese, 22.3% were overweight and 23.6% showed adolescent central obesity. Glucose levels (p = 0.016), insulin (p = 0.0001) and HOMA-IR (p = 0.0001) showed significant differences in the group with obesity. Values of the three parameters were increased with the stage of puberty. We found significant differences in the levels of glucose (p = 0.0388), insulin (p = 0.0005) and HOMA-IR (p = 0.0001) between the prepubertal and postpubertal stages

Going Beyond Promoting: Preparing Students to Creatively Solve Future Problems

While we cannot know what problems the future will bring, we can be almost certain that solving them will require creativity. In this article we describe how our course, a first-year undergraduate mathematics course, supports creative problem solving. Creative problem solving cannot be learned through a single experience, so we provide our students with a blend of experiences. We discuss how the course structure enables creative problem solving through class instruction, during class activities, during out of class assessments, and during in class assessments. We believe this course structure increases student comfort with solving open-ended and ill-defined problems similar to what they will encounter in the real world

2D-Coordination polymers based on 1H-indazole4-carboxylic acid and transition metal ions: magnetic, luminescence and biological properties

We report the formation of five novel multifunctional coordination polymers based on 1H-indazole-4- carboxylic acid (HL). To the best of our knowledge, these complexes are the first examples of coordination compounds constructed with this interesting ligand. These materials were synthesized by solvothermal routes, possess different 2D-structures and show interesting magnetic properties due to the copper compound showing an unusual spin-canted effect while the anisotropic cobalt material behaves as a fieldinduced single molecule magnet. MTT assays performed on human embryonic kidney (HEK293) and mouse skin melanoma (B16-F10) cell lines indicated that the Cd-based compound was the only one exhibiting dose-dependent toxicity on B16-F10 cells, most likely due to the release of toxic Cd(II). Cadmium and zinc polymers exhibit interesting luminescence properties. The fact that zinc polymers did not exhibit inherent toxicity against both cancer and non-cancerous cells make this new family an excellent candidate for further investigation in the field of luminescent materials with biomedical applications.Junta de Andalucia FQM-394 FQM-1484Red Guipuzcoana de Ciencia, Tecnologia e Innovacion OF218/2018University of Basque Country GIU 17/13Basque Government IT1005-16Spanish Ministry of Science, Innovation and Universities (MCIU/AEI/FEDER, UE) PGC2018-102052-A-C22 PGC2018-102052-B-C21Junta de Andalucia FQM-394 FQM-1484European Union (EU)ESFGovernment of the Basque CountryFEDER/MCIU/AEI RYC-2016-21042 JdC-201