p32 is a novel mammalian Lgl binding protein that enhances the activity of protein kinase Cζ and regulates cell polarity

Lgl (lethal giant larvae) plays an important role in cell polarity. Atypical protein kinase C (aPKC) binds to and phosphorylates Lgl, and the phosphorylation negatively regulates Lgl activity. In this study, we identify p32 as a novel Lgl binding protein that directly binds to a domain on mammalian Lgl2 (mLgl2), which contains the aPKC phosphorylation site. p32 also binds to PKCζ, and the three proteins form a transient ternary complex. When p32 is bound, PKCζ is stimulated to phosphorylate mLgl2 more efficiently. p32 overexpression in Madin–Darby canine kidney cells cultured in a 3D matrix induces an expansion of the actin-enriched apical membrane domain and disrupts cell polarity. Addition of PKCζ inhibitor blocks apical actin accumulation, which is rescued by p32 overexpression. p32 knockdown by short hairpin RNA also induces cell polarity defects. Collectively, our data indicate that p32 is a novel regulator of cell polarity that forms a complex with mLgl2 and aPKC and enhances aPKC activity

Pten loss promotes MAPK pathway dependency in HER2/neu breast carcinomas

Loss of the tumor suppressor gene PTEN is implicated in breast cancer progression and resistance to targeted therapies, and is thought to promote tumorigenesis by activating PI3K signaling. In a transgenic model of breast cancer, Pten suppression using a tetracycline-regulatable short hairpin (sh)RNA cooperates with human epidermal growth factor receptor 2 (HER2/neu), leading to aggressive and metastatic disease with elevated signaling through PI3K and, surprisingly, the mitogen-activated protein kinase (MAPK) pathway. Restoring Pten function is sufficient to down-regulate both PI3K and MAPK signaling and triggers dramatic tumor regression. Pharmacologic inhibition of MAPK signaling produces similar effects to Pten restoration, suggesting that the MAPK pathway contributes to the maintenance of advanced breast cancers harboring Pten loss

Involvement of Lgl and Mahjong/VprBP in Cell Competition

Mahjong is a novel Lethal giant larvae-binding protein that plays a vital role in cell competition in both flies and mammals

Functional Identification of Tumor Suppressor Genes Through an in vivo RNA Interference Screen in a Mouse Lymphoma Model

2010 April 6Short hairpin RNAs (shRNAs) capable of stably suppressing gene function by RNA interference (RNAi) can mimic tumor-suppressor-gene loss in mice. By selecting for shRNAs capable of accelerating lymphomagenesis in a well-characterized mouse lymphoma model, we identified over ten candidate tumor suppressors, including Sfrp1, Numb, Mek1, and Angiopoietin 2. Several components of the DNA damage response machinery were also identified, including Rad17, which acts as a haploinsufficient tumor suppressor that responds to oncogenic stress and whose loss is associated with poor prognosis in human patients. Our results emphasize the utility of in vivo RNAi screens, identify and validate a diverse set of tumor suppressors, and have therapeutic implications

The Musical Sources of the Former Miners’ Orchestra of Wałbrzych (Waldenburger Bergkapelle) from the Collection of Warsaw University Library

In the article, the author investigates 24 musical manuscripts belonging to former Miners’ Orchestra of Wałbrzych (Waldenburger Bergkapelle), which used the sources for concerts of the orchestra. The analysed manuscripts have not yet been researched or catalogued in RISM (Répertoire International des Sources Musicales) database before. The ensemble’s repertoire was analysed and the collection’s characteristics, including copyists, watermarks and stamps, were examined. It allowed to assess the provenience of the manuscripts and make certain remarks about the type of repertoire played by Waldenburger Bergkapelle. The results of the analysis were presented in the context that can be found in secondary sources, widely describing the activity of the orchestra. The author also carried on cataloguing in Warsaw University Library, creating the catalogue in the Muscat RISM system. Considering the numbers on shelfmarks, it can be assumed that the original collection contained circa one hundred of musical sources. However, only a small part of them is known and catalogued. Therefore, the knowledge of the collection remains incomplete and is worth further investigation

Sequential extraction of chromium, molybdenum, and vanadium in basic oxygen furnace slags

Basic oxygen furnace slags (BOS) are by-products of basic oxygen steel production. Whereas the solubility of some elements from these slags has been well investigated, information about the mineralogy and related leaching, i.e., availability of the environmentally relevant elements chromium (Cr), molybdenum (Mo), and vanadium (V), is still lacking. The aim of this study was to investigate these issues with a modified, four-fraction-based, sequential extraction procedure (F1-F4), combined with X-ray diffraction, of two BOS. Extractants with increasing strength were used (F1 demineralized water, F2 CH3COOH + HCl, F3 Na(2)EDTA + NH2OH center dot HCl, and F4 HF + HNO3 + H2O2), and after each fraction, X-ray diffraction was performed. The recovery of Cr was moderate (66.5%) for one BOS, but significantly better (100.2%) for the other one. High recoveries were achieved for the other elements (Mo, 100.8-107.9% and V, 112.6-87.0%), indicating that the sequential extraction procedure was reliable when adapted to BOS. The results showed that Cr and Mo primarily occurred in F4, representing rather immobile elements under natural conditions, which were strongly bound into/onto Fe minerals (srebrodolskite, magnetite, hematite, or wustite). In contrast, V was more mobile with proportional higher findings in F2 and F3, and the X-ray diffraction results reveal that V was not solely bound into Ca minerals (larnite, hatrurite, kirschsteinite, and calcite), but also bound to Fe minerals. The results indicated that the total amount of recovery was a poor indicator of the availability of elements and did not correspond to the leaching of elements from BOS

Chromium, molybdenum, vanadium, and fluoride sorption from steelwork slag eluates by different mineral additives

Today, the environmental behavior of steelwork slags is very important for their application. When slags are used as building materials, they can interact with water and soil, with the possibility of leaching of harmful components, e.g., metals such as vanadium or anions such as fluoride. The leachable concentrations of various environmentally relevant parameters have to be below defined limit values, which are given by environmental authorities. In this study, different mineral additives have been investigated for their suitability to reduce chromium, molybdenum, vanadium, and fluoride concentrations in slag eluates, as a basis for planned investigations of the long-term leaching behavior of slag/additive mixtures. Seven mineral additives including iron oxide hydroxide, sludge from aluminum production, triple superphosphate, two water work sludges I and II, zeolite powder, and zeolite granules were tested for their efficiency to sorb trace elements and fluoride from four slag eluates comprising two basic oxygen furnace slags and two electric arc furnace slags. The limit values according to the German Alternative Construction Material Ordinance were used to verify which additives were able to minimize concentrations of trace elements and fluoride in slags eluates. Due to high eluate concentrations, the sludge from aluminum production and the triple superphosphate could be excluded from further investigations. The efficiency of the other additives follows the trend iron oxide hydroxide > water work sludges > zeolites. Particularly, the iron oxide hydroxide and the water work sludge I seem to be appropriate to enhance possible applications of slags with respect to the German regulation

Influence of Natural and Accelerated Carbonation of Steel Slags on Their Leaching Behavior

The influence of natural and accelerated carbonation on the leaching behavior of a basic oxygen furnace slag (BOS), electric arc furnace slag from carbon steel production (EAF C), and electric arc furnace slag from high-alloy/stainless steel production (EAF S) has been investigated in this study. The carbonation reaction is examined using two experimental series: (i) outdoor-exposure tests; and (ii) accelerated carbonation treatments in the laboratory. The achieved leaching results for the exposed steel slags show a distinct increase in Si and V concentrations and a decrease of Ca, with lower pH, due to carbonation. The other elements (Al, Cr, F, and Mo) react differently to carbonation depending on the mineral binding. However, the achieved results show that the German LAGA emplacement category can be improved from Z 2, for restricted applications with defined safeguarding measures, to Z 1 restricted open applications, due to carbonation. With regard to the storage of carbon dioxide (CO2) in slags and CO2 reduction of the atmosphere, the EAF S appears to be best suited for carbonation, because this slag reveals the highest CO2 uptake. Moreover, for this slag type significant decreases of the leached amount of Al, Ca, Cr, and Mo could be achieved