Akt1 Is Essential for Postnatal Mammary Gland Development, Function, and the Expression of Btn1a1

Akt1, a serine-threonine protein kinase member of the PKB/Akt gene family, plays critical roles in the regulation of multiple cellular processes, and has previously been implicated in lactation and breast cancer development. In this study, we utilized Akt1+/+ and Akt1−/− C57/Bl6 female mice to assess the role that Akt1 plays in normal mammary gland postnatal development and function. We examined postnatal morphology at multiple time points, and analyzed gene and protein expression changes that persist into adulthood. Akt1 deficiency resulted in several mammary gland developmental defects, including ductal outgrowth and defective terminal end bud formation. Adult Akt1−/− mammary gland composition remained altered, exhibiting fewer alveolar buds coupled with increased epithelial cell apoptosis. Microarray analysis revealed that Akt1 deficiency altered expression of genes involved in numerous biological processes in the mammary gland, including organismal development, cell death, and tissue morphology. Of particular importance, a significant decrease in expression of Btn1a1, a gene involved in milk lipid secretion, was observed in Akt1−/− mammary glands. Additionally, pseudopregnant Akt1−/− females failed to induce Btn1a1 expression in response to hormonal stimulation compared to their wild-type counterparts. Retroviral-mediated shRNA knockdown of Akt1 and Btn1a1 in MCF-7 human breast epithelial further illustrated the importance of Akt1 in mammary epithelial cell proliferation, as well as in the regulation of Btn1a1 and subsequent expression of ß-casein, a gene that encodes for milk protein. Overall these findings provide mechanistic insight into the role of Akt1 in mammary morphogenesis and function

Facilitated Monocyte-Macrophage Uptake and Tissue Distribution of Superparmagnetic Iron-Oxide Nanoparticles

BACKGROUND: We posit that the same mononuclear phagocytes (MP) that serve as target cells and vehicles for a host of microbial infections can be used to improve diagnostics and drug delivery. We also theorize that physical and biological processes such as particle shape, size, coating and opsonization that affect MP clearance of debris and microbes can be harnessed to facilitate uptake of nanoparticles (NP) and tissue delivery. METHODS: Monocytes and monocyte-derived macrophages (MDM) were used as vehicles of superparamagnetic iron oxide (SPIO) NP and immunoglobulin (IgG) or albumin coated SPIO for studies of uptake and distribution. IgG coated SPIO was synthesized by covalent linkage and uptake into monocytes and MDM investigated related to size, time, temperature, concentration, and coatings. SPIO and IgG SPIO were infused intravenously into naïve mice. T(2) measures using magnetic resonance imaging (MRI) were used to monitor tissue distribution in animals. RESULTS: Oxidation of dextran on the SPIO surface generated reactive aldehyde groups and permitted covalent linkage to amino groups of murine and human IgG and F(ab')(2) fragments and for Alexa Fluor(R) 488 hydroxylamine to form a Schiff base. This labile intermediate was immediately reduced with sodium cyanoborohydride in order to stabilize the NP conjugate. Optical density measurements of the oxidized IgG, F(ab')(2), and/or Alexa Fluor(R) 488 SPIO demonstrated approximately 50% coupling yield. IgG-SPIO was found stable at 4 degrees C for a period of 1 month during which size and polydispersity index varied little from 175 nm and 200 nm, respectively. In vitro, NP accumulated readily within monocyte and MDM cytoplasm after IgG-SPIO exposure; whereas, the uptake of native SPIO in monocytes and MDM was 10-fold less. No changes in cell viability were noted for the SPIO-containing monocytes and MDM. Cell morphology was not changed as observed by transmission electron microscopy. Compared to unconjugated SPIO, intravenous injection of IgG-SPIO afforded enhanced and sustained lymphoid tissue distribution over 24 hours as demonstrated by MRI. CONCLUSIONS: Facilitated uptake of coated SPIO in monocytes and MDM was achieved. Uptake was linked to particle size and was time and concentration dependent. The ability of SPIO to be rapidly taken up and distributed into lymphoid tissues also demonstrates feasibility of macrophage-targeted nanoformulations for diagnostic and drug therapy

Climate and colonialism

Recent years have seen a growth in scholarship on the intertwined histories of climate, science and European imperialism. Scholarship has focused both on how the material realities of climate shaped colonial enterprises, and on how ideas about climate informed imperial ideologies. Historians have shown how European expansion was justified by its protagonists with theories of racial superiority, which were often closely tied to ideas of climatic determinism. Meanwhile, the colonial spaces established by European powers offered novel ‘laboratories’ where ideas about acclimatisation and climatic improvement could be tested on the ground. While historical scholarship has focused on how powerful ideas of climate informed imperial projects, emerging scholarship in environmental history, history of science and historical geography focuses instead on the material and cognitive practices by which the climates of colonial spaces were made known and dealt with in fields such as forestry, agriculture and human health. These heretofore rather disparate areas of historical research carry great contemporary relevance of studies of how climates and their changes have been understood, debated and adapted to in the past

Retention force assessment in conical crowns in different material combinations

The puprose of this study was to evaluate retention force of conical double crowns in two material connections: gold casting alloy/gold casting alloy and gold casting alloy/gold electroforming alloy. 12 crown pairs of both material connections with the cone angles of 2°, 4° and 6° were made. Experiment of 10.000 in-and-out cycles was performed using a new device which allows the retentive force to be measured in continuous way without necessity of moving the samples to another device. It has been found that the higher the retentive force values, the lower the cone angle. Dispersion of the retention value was similar in both groups, but when cone angle was 2° or 4°, stability of retention force with the passage of time was higher in combinations with electroformed copings. The optimum solution was the cast alloy/cast alloy connection but only with cone angle 6°. However, retentive values seem to be too low to achieve proper retention of dentures

Denticles. A literature review

Denticles are pulp degenerations in the form of calcified deposits of mineral salts, usually found in molars and lower incisors, as well as in impacted teeth and deciduous molars. Denticles may come in various sizes, from microscopic particles to larger mass that almost obliterate the pulp chamber and are visible only on X-ray images. Denticles form as a result of chronic inflammatory lesions, but may also be caused by injuries and conservative treatment. They are most frequently found in necrotic foci. Denticles may cause problems for root canal treatment, as their presence might make it difficult to obtain proper access to the pulp chamber bottom and the canal orifices. There is also the increased risk of bending or breaking the endodontic instruments. Sometimes, denticles fill the entire space of the tooth chamber and pushing the pulp to the edges of the chamber. Denticles can cause pain due to the pressure on the nerves and blood vessels supplying the internal tissue of the tooth. The presence of large denticles might eventually lead to necrosis of the pulp. Denticles accompany certain diseases, such as dentin dysplasia, odontodysplasia or Albright hereditary dystrophy

Four-year results of a prospective-controlled clinical study evaluating healing of intra-bony defects following treatment with an enamel matrix protein derivative alone or combined with a bioactive glass.

Contains fulltext : 53550.pdf (publisher's version ) (Closed access)AIM: To evaluate the 4-year results following regenerative periodontal surgery at intra-bony defects with either a combination of an enamel matrix protein derivative (EMD) and a bioactive glass (BG) or with EMD alone. METHODS: Twenty-five patients with one deep intra-bony defect each were randomly treated with either an EMD+BG (test) or with EMD alone (control). Measurements were recorded at baseline, at 1 and at 4 years following therapy. The primary outcome variable was the clinical attachment level (CAL). RESULTS: The test group demonstrated a mean CAL change from 10.3+/-1.6 to 6.7+/-1.2 mm (p/=3 mm was found at 4 years in 10 defects in both groups. Between the treatment groups, no statistically significant differences in any of the investigated parameters were observed at 1 and at 4 years. CONCLUSIONS: Within their limits, the present results indicate that the clinical improvements obtained with both regenerative modalities can be maintained over a period of 4 years

Healing of human intrabony defects following regenerative periodontal therapy with an enamel matrix protein derivative alone or combined with a bioactive glass. A controlled clinical study.

Item does not contain fulltextAIM: The purpose of the present study was to compare clinically the treatment of deep intrabony defects with a combination of an enamel matrix protein derivative (EMD) and a bioactive glass (BG) to EMD alone. METHODS: Thirty patients (16 females and 14 males) suffering from advanced marginal periodontitis were included in this prospective, controlled parallel design multicenter study. In each of the patients, one intrabony defect was randomly treated with either EMD+BG (test) or with EMD alone (control). Clinical measurements were recorded at baseline and at 1 year following therapy. RESULTS: No differences in any of the investigated parameters were observed at baseline between the two groups. Healing was uneventful in all patients. At 1 year after therapy, the test group showed a reduction in mean probing depth (PD) from 8.5+/-1.1 to 4.4+/-1.2 mm (p<0.001) and a change in mean clinical attachment level (CAL) from 10.4+/-1.5 to 7.1+/-1.5 mm (p<0.0001). In the control group, the mean PD was reduced from 8.5+/-1.5 to 4.0+/-1.6 mm (p<0.001) and the mean CAL changed from 10.2+/-2.1 to 6.3+/-2.2 mm (p<0.01). In the test group, 12 sites (80%) gained at least 3 mm or more of CAL, whereas in the control group a CAL gain of 3 mm or more was measured at 13 sites (87%). No statistically significant differences in terms of PD reduction and CAL gain were found between the test and the control treatment. CONCLUSIONS: Within the limits of the present study it can be concluded that: (i) at 1 year after surgery, both therapies resulted in significant PD reductions and CAL gains, and (ii) the combination of EMD+BG does not seem to additionally improve the clinical results