Rac signaling in breast cancer: a tale of GEFs and GAPs

Rac GTPases, small G-proteins widely implicated in tumorigenesis and metastasis, transduce signals from tyrosine-kinase, G-protein-coupled receptors (GPCRs), and integrins, and control a number of essential cellular functions including motility, adhesion, and proliferation. Deregulation of Rac signaling in cancer is generally a consequence of enhanced upstream inputs from tyrosine-kinase receptors, PI3K or Guanine nucleotide Exchange Factors (GEFs), or reduced Rac inactivation by GTPase Activating Proteins (GAPs). In breast cancer cells Rac1 is a downstream effector of ErbB receptors and mediates migratory responses by ErbB1/EGFR ligands such as EGF or TGFα and ErbB3 ligands such as heregulins. Recent advances in the field led to the identification of the Rac-GEF P-Rex1 as an essential mediator of Rac1 responses in breast cancer cells. P-Rex1 is activated by the PI3K product PIP3 and Gβγ subunits, and integrates signals from ErbB receptors and GPCRs. Most notably, P-Rex1 is highly overexpressed in human luminal breast tumors, particularly those expressing ErbB2 and estrogen receptor (ER). The P-Rex1/Rac signaling pathway may represent an attractive target for breast cancer therapy.     

Trypanosoma cruzi: in vivo evaluation of iron in skin employing X-ray fluorescence (XRF) in mouse strains that differ in their susceptibility to infection

Trypanosoma cruzi, the causative agent of Chagas' disease (CD), is a substantial public health concern in Latin America. Laboratory mice inoculated with T. cruzi have served as important animal models of acute CD. Host hypoferremic responses occur during T. cruzi infection; therefore, it has been hypothesized that T. cruzi requires iron for optimal growth in host cells and, unlike extracellular pathogens, may benefit from host hypoferremic responses. Recent technological improvements of X-ray fluorescence are useful for diagnostics or monitoring in biomedical applications. The goal of our study was to determine whether the iron availabilities in Swiss and C57BL/6 mice differ during the acute phase of T. cruzi infection and whether the availability correlates with oxidative stress in the susceptible and resistant phenotypes identified in these mice. Our results showed that the decrease in iron levels in the skin of resistant infected mice correlated with the increase in oxidative stress associated with anemia and the reduction in parasite burden.     

Sea urchin Arbacia dufresnei (Blainville 1825) larvae response to ocean acidification

Increased atmospheric CO₂ emissions are inducing changes in seawater carbon chemistry, lowering its pH, decreasing carbonate ion availability and reducing calcium carbonate saturation state. This phenomenon, known as ocean acidification, is happening at a faster rate in cold regions, i.e., polar and sub-polar waters. The larval development of Arbacia dufresnei from a sub-Antarctic population was studied at high (8.0), medium (7.7) and low (7.4) pH waters. The results show that the offspring from sub-Antarctic populations of A. dufresnei are susceptible to a development delay at low pH, with no significant increase in abnormal forms. Larvae were isometric between pH treatments. Even at calcium carbonate (CaCO₃) saturation states (of both calcite and aragonite, used as proxies of the magnesium calcite) <1, skeleton deposition occurred. Polar and sub-polar sea urchin larvae can show a certain degree of resilience to acidification, also emphasizing A. dufresnei potential to poleward migrate and further colonize southern regions.     

Hyperbaric oxygen therapy treatment for the fixation of implant prosthesis in oncology patients irradiated

doi: 10.1111/j.1741‐2358.2012.00636.x Hyperbaric oxygen therapy treatment for the fixation of implant prosthesis in oncology patients irradiated Objectives: This study aimed to present a clinical report of an irradiated oncologic patient who underwent hyperbaric oxygen therapy to be rehabilitated with implant‐supported prosthesis. Materials and Methods: A 67‐year‐old man was admitted at Oral Oncology Center (FOA‐UNESP) presenting a lesion on the mouth floor. After clinical evaluation, incisional biopsy and histopathological exam, a grade II squamous cell carcinoma was diagnosed. The patient was subjected to surgery to remove the lesion and partial glossectomy. Afterwards, the radiotherapy, in the left/right cervicofacial area of the supraclavicular fossa, was conducted. After 3 years of the surgery, the patient was submitted to hyperbaric oxygen therapy. Then, four implants were installed in patient’s mandible. Five months later, an upper conventional complete denture and lower full‐arch implant‐supported prosthesis were fabricated. Conclusion: The treatment resulted in several benefits such as improving his chewing efficiency, swallowing and speech, less denture trauma on the mucosa and improving his self‐esteem.     

Evaluation of Vickers hardness of different types of acrylic denture base resins with and without glass fibre reinforcement

doi: 10.1111/j.1741‐2358.2010.00435.x
Evaluation of Vickers hardness of different types of acrylic denture base resins with and without glass fibre reinforcement Objective: To evaluate the Vickers hardness of different acrylic resins for denture bases with and without the addition of glass fibres. Background: It has been suggested that different polymerisation methods, as well as the addition of glass fibre (FV) might improve the hardness of acrylic. Materials and methods: Five types of acrylic resin were tested: Vipi Wave (VW), microwave polymerisation; Vipi Flash (VF), auto‐polymerisation; Lucitone (LT), QC20 (QC) and Vipi Cril (VC), conventional heat‐polymerisation, all with or without glass fibre reinforcement (GFR) and distributed into 10 groups (n = 12). Specimens were then submitted to Vickers hardness testing with a 25‐g load for 30 s. All data were submitted to anova and Tukey’s HSD test. Results: A significant statistical difference was observed with regard to the polymerisation method and the GFR (p < 0.05). Without the GFR, the acrylic resin VC presented the highest hardness values, and VF and LT presented the lowest. In the presence of GFR, VC resin still presented the highest Vickers hardness values, and VF and QC presented the lowest. Conclusions: The acrylic resin VC and VW presented higher hardness values than VF and QC resins. Moreover, GFR increased the Vickers hardness of resins VW, VC and LT.     

Effect of repeated microwave disinfections on bonding of different commercial teeth to resin denture base

doi: 10.1111/j.1741‐2358.2011.00516.x Effect of repeated microwave disinfections on bonding of different commercial teeth to resin denture base Objective: To verify the influence of repeated microwave disinfections on the shear bond strength of two commercial types of teeth to acrylic resin, when the ridge lap surfaces were unmodified, bur abraded, bur grooved or etched by monomer. Material and methods: Eighty specimens (n = 10) were adhered to the tooth ridge lap surface, polymerised in a water bath at 74°C for 9 h. Microwaved specimens were individually immersed in 150 ml of water and submitted to five simulated disinfections in a microwave oven calibrated at 650 W for 3 min. Control specimens were not microwave treated. Shear bond strength tests were performed in an Instron machine with a cross‐speed of 1 mm/min. The fracture load values were transformed into shear bond strength as a function of the bonding area (0.28 cm²). Data were submitted to anova and Tukey’s test (α = 0.05). Fractured areas were classified as adhesive, cohesive (resin or tooth) or mixed failures. Results: Repeated microwave disinfections increased the shear strength of the tooth/resin bond. Mechanical retention in microwaved and non‐microwaved procedures improved the shear bond strength. Conclusions: The different commercial types of teeth influenced shear bond strength values, with Biotone teeth showing the lower values.     

Rehabilitation with ear prosthesis linked to osseointegrated implants

doi: 10.1111/j.1741‐2358.2011.00612.x Rehabilitation with ear prosthesis linked to osseointegrated implants Background: The absence of an ear, which can be the result of a congenital malformation, surgical tumour resection or traumatic injury, is a significant aesthetic problem. Attachment of ear prostheses with adhesives can cause local irritation for the wearer and affect the colour of the prostheses. Use of implants in craniofacial reconstruction can improve the retention and stability of prostheses giving to patient greater comfort and security relative to adhesive attachment. Objective: The aim of this report was to present a clinical case of a mutilated patient who was rehabilitated by means of installing an ear prosthesis fixed through osseointegrated implants. Materials and methods: The patient had two implants installed in the mastoid region that were linked by a bar, and a clip‐type system was used. The ear prosthesis was constructed from medical‐use silicone, pigmented to match the patient’s skin colour and linked to the retention system. Conclusion: The patient’s rehabilitation was satisfactory from both a functional and an aesthetic point of view, making it possible for the patient to return to a normal social life and regain lost self‐esteem.     

Effect of accelerated ageing and surface sealing on the permanent deformation of auto‐polymerising soft linings

doi: 10.1111/j.1741‐2358.2010.00419.x
Effect of accelerated ageing and surface sealing on the permanent deformation of auto‐polymerising soft linings Purpose: To compare the effects of different ageing methods on the permanent deformation of two permanent soft liners. Materials and methods: The materials selected were auto‐polymerising acrylic resin and silicone‐based reliners. Sealer coating was also evaluated. Sixty specimens of each reliner were manufactured (12.7 mm diameter and 19 mm length). Specimens were randomly distributed into 12 groups (n = 10) and submitted to one of the accelerated ageing processes. Permanent deformation tests were conducted with a mechanical device described within the American Dental Association specification number 18 with a compressive load of 750 gf applied for 30 s. All data were submitted for statistical analysis. Mann–Whitney test compared the effect of the surface sealer on each material and the permanent deformation of the materials in the same ageing group (p = 0.05). Kruskal–Wallis and Dunn tests compared all ageing groups of each material (p = 0.05). Results: The silicone‐based reliner presented a lower permanent deformation than the acrylic resin‐based reliner, regardless of the ageing procedure. The surface sealer coating was effective only for the thermocycled silicone group and the accelerated ageing processes affected only the permanent deformation of the acrylic resin‐based material. Conclusion: The silicone‐based reliner presented superior elastic properties and the thermocycling was more effective in ageing the materials.     

Seasonal variation of temporal niche in wild owl monkeys (Aotus azarai azarai) of the Argentinean Chaco: a matter of masking?

Among the more than 40 genera of anthropoid primates (monkeys, apes, and humans), only the South American owl monkeys, genus Aotus, are nocturnal. However, the southernmostly distributed species, Aotus azarai azarai, of the Gran Chaco may show considerable amounts of its 24-h activity during bright daylight. Due to seasonal changes in the duration of photophase and climatic parameters in their subtropical habitat, the timing and pattern of their daily activity are expected to show significant seasonal variation. By quantitative long-term activity recordings with Actiwatch AW4 accelerometer data logger devices of 10 wild owl monkeys inhabiting a gallery forest in Formosa, Argentina, the authors analyzed the seasonal variation in the temporal niche and activity pattern resulting from entrainment and masking of the circadian activity rhythm by seasonally and diurnally varying environmental factors. The owl monkeys always displayed a distinct bimodal activity pattern, with prominent activity bouts and peaks during dusk and dawn. Their activity rhythm showed distinct lunar and seasonal variations in the timing and daily pattern. During the summer, the monkeys showed predominantly crepuscular/nocturnal behavior, and a crepuscular/cathemeral activity pattern with similar diurnal and nocturnal activity levels during the cold winter months. The peak times of the evening and morning activity bouts were more closely related to the times of sunset and sunrise, respectively, than activity-onset and -offset. Obviously, they were better circadian markers for the phase position of the entrained activity rhythm than activity-onset and -offset, which were subject to more masking effects of environmental and/or internal factors. Total daily activity was lowest during the two coldest lunar months, and almost twice as high during the warmest months. Nighttime (21:00-06:00 h) and daytime (09:00-18:00 h) activity varied significantly across the year, but in an opposite manner. Highest nighttime activity occurred in summer and maximal daytime activity during the cold winter months. Dusk and dawn activity, which together accounted for 43% of the total daily activity, barely changed. The monkeys tended to terminate their nightly activity period earlier on warm and rainy days, whereas the daily amount of activity showed no significant correlation either with temperature or precipitation. These data are consistent with the dual-oscillator hypothesis of circadian regulation. They suggest the seasonal variations of the timing and pattern of daily activity in wild owl monkeys of the Argentinean Chaco result from a specific interplay of light entrainment of circadian rhythmicity and strong masking effects of various endogenous and environmental factors. Since the phase position of the monkeys' evening and morning activity peaks did not vary considerably over the year, the seasonal change from a crepuscular/nocturnal activity pattern in summer to a more crepuscular/cathemeral one in winter does not depend on a corresponding phase shift of the entrained circadian rhythm, but mainly on masking effects. Thermoregulatory and energetic demands and constraints seem to play a crucial role.     

Sex ratios among Canadian liveborn infants of mothers from different countries

Background:

There has been much discussion about whether female feticide occurs in certain immigrant groups in Canada. We examined data on live births in Ontario and compared sex ratios in different groups according to the mother’s country or region of birth and parity.

Methods:

We completed a population-based study of 766 688 singleton live births between 2002 and 2007. We used birth records provided by Ontario Vital Statistics for live births in the province between 23 and 41 weeks’ gestation. We categorized each newborn according to the mother’s country or region of birth, namely Canada (n = 486 599), Europe (n = 58 505), South Korea (n = 3663), China (n = 23 818), Philippines (n = 15 367), rest of East Asia (n = 18 971), Pakistan (n = 18 018), India (n = 31 978), rest of South Asia (n = 20 695) and other countries (n = 89 074). We calculated male:female ratios and 95% confidence intervals (CIs) for all live births by these regions and stratified them by maternal parity at the time of delivery (0, 1, 2 or ≥ 3).

Results:

Among infants of nulliparous women, the male:female ratio was about 1.05 overall. As parity increased, the ratio remained unchanged among infants of Canadian-born women. In contrast, the male:female ratio was significantly higher among infants of primiparous women born in South Korea (1.20, 95% CI 1.09–1.34) and India (1.11, 95% CI 1.07–1.15) than among infants of Canadian-born primiparous women. Among multiparous women, those born in India were significantly more likely than Canadian-born women to have a male infant (parity 2, ratio 1.36, 95% CI 1.27–1.46; parity ≥ 3, ratio 1.25, 95% CI 1.09–1.43).

Interpretation:

Our study of male:female ratios in Ontario showed that multiparous women born in India were significantly more likely than multiparous women born in Canada to have a male infant.Although there are some myths about correctly guessing the sex of a fetus,¹ modern-day prenatal ultrasound enables the identification of whether a fetus is a boy or girl with 99% accuracy.² There has been much discussion about whether female fetuses are at higher risk of pregnancy termination than male fetuses in certain ethnic groups. In India, a study of data from the National Family Health Survey for 265 516 births showed a sharp increase in the male:female ratio among second-order births when the firstborn was a girl, and no significant increase when the firstborn was a boy.³ The authors attributed this trend to the practice of selective abortion of female fetuses. A recent editorial⁴ and news item⁵ in CMAJ suggested that female feticide may also be occurring in Canada.⁶ Rather than using live-birth statistics, the Canadian study cited in CMAJ used data from the 2001 and 2006 Canada Census long-form questionnaires, which were completed by 20% of the population and relied on self-reporting of additional information, including the number of family members in a given household.We used contemporary data on live births in Ontario, Canada’s most populous and ethnically diverse province, and compared sex ratios among infants of Canadian-born women with sex ratios in different immigrant groups. We focused on immigrant groups from countries purported to have the highest rates of preference for a son following the birth of one or more daughters.^3–6 We determined whether the male:female ratio increased with increasing parity in certain immigrant groups, as has been previously suggested.^3,6