Anti-Tumor Effects of Ganoderma lucidum (Reishi) in Inflammatory Breast Cancer in In Vivo and In Vitro Models

The medicinal mushroom Ganoderma lucidum (Reishi) was tested as a potential therapeutic for Inflammatory Breast Cancer (IBC) using in vivo and in vitro IBC models. IBC is a lethal and aggressive form of breast cancer that manifests itself without a typical tumor mass. Studies show that IBC tissue biopsies overexpress E-cadherin and the eukaryotic initiation factor 4GI (eIF4GI), two proteins that are partially responsible for the unique pathological properties of this disease. IBC is treated with a multimodal approach that includes non-targeted systemic chemotherapy, surgery, and radiation. Because of its non-toxic and selective anti-cancer activity, medicinal mushroom extracts have received attention for their use in cancer therapy. Our previous studies demonstrate these selective anti-cancer effects of Reishi, where IBC cell viability and invasion, as well as the expression of key IBC molecules, including eIF4G is compromised. Thus, herein we define the mechanistic effects of Reishi focusing on the phosphoinositide-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, a regulator of cell survival and growth. The present study demonstrates that Reishi treated IBC SUM-149 cells have reduced expression of mTOR downstream effectors at early treatment times, as we observe reduced eIF4G levels coupled with increased levels of eIF4E bound to 4E-BP, with consequential protein synthesis reduction. Severe combined immunodeficient mice injected with IBC cells treated with Reishi for 13 weeks show reduced tumor growth and weight by ∼50%, and Reishi treated tumors showed reduced expression of E-cadherin, mTOR, eIF4G, and p70S6K, and activity of extracellular regulated kinase (ERK1/2). Our results provide evidence that Reishi suppresses protein synthesis and tumor growth by affecting survival and proliferative signaling pathways that act on translation, suggesting that Reishi is a potential natural therapeutic for breast and other cancers.     

Bax Inhibitor-1-mediated Ca leak is decreased by cytosolic acidosis

Bax Inhibitor-1 (BI-1) is an evolutionarily conserved six-transmembrane domain endoplasmic reticulum (ER)-localized protein that protects against ER stress-induced apoptotic cell death. This function is closely connected to its ability to lower steady-state ER Ca²⁺ levels. Recently, we elucidated BI-1's Ca²⁺-channel pore in the C-terminal part of the protein and identified the critical amino acids of its pore. Based on these insights, a Ca²⁺-channel pore-dead mutant BI-1 (BI-1^D213R) was developed. We determined whether BI-1 behaves as a bona fide H⁺/Ca²⁺ antiporter or as an ER Ca²⁺-leak channel by investigating the effect of pH on unidirectional Ca²⁺-efflux rates. At pH 6.8, wild-type BI-1 expression in BI-1^−/− cells increased the ER Ca²⁺-leak rate, correlating with its localization in the ER compartment. In contrast, BI-1^D231R expression in BI-1^−/−, despite its ER localization, did not increase the ER Ca²⁺-leak rate. However, at pH < 6.8, the BI-1-mediated ER Ca²⁺ leak was blocked. Finally, a peptide representing the Ca²⁺-channel pore of BI-1 promoting Ca²⁺ flux from the ER was used. Lowering the pH from 6.8 to 6.0 completely abolished the ability of the BI-1 peptide to mediate Ca²⁺ flux from the ER. We propose that this pH dependence is due to two aspartic acid residues critical for the function of the Ca²⁺-channel pore and located in the ER membrane-dipping domain, which facilitates the protonation of these residues.     

Environmental Exchange Box

In this activity, teachers in one state create and share an “exchange box” of environmental and cultural items with students of another state. The Environmental Exchange Box activity enables teachers to improve students' skills in scientific inquiry and develop attitudes and values conducive to science learning such as wonder, curiosity, and respect for different social perceptions. Teachers will be able to work beyond the limits of the classroom and introduce outside resources to help increase students' global awareness and promote respect for the culture and environment of diverse populations. Specifically, this activity can help teachers fulfill national Teaching Standards B, D, and E.     

Dasycladales from the Upper Maastrichtian of Salento Peninsula (Puglia, southern Italy)

Summary A rich dasycladalean assemblage, mainly consisting of new taxa, has been discovered in upper Maastrichtian coarse bioclastic limestones of shelf margin facies cropping out along the southeastern coast of Salento peninsula (Puglia, Southern Italy). It consists of 8 species grouped into 6 genera:Cymopolia decastroi Parente 1994;C. barattoloi Parente, 1994;Zittelina fluegeli n.sp;Jodotella koradae (Dieni, Massari & Radoicic, 1983) nov. comb.;Barattoloporella salentina n. gen. n. sp.;Morelletpora dienii n. sp.;Neomeris spp. (two different species). Zittelina fluegeli n. sp. is characterized by an ovoid thallus with calcification made by a calcareous wall enveloping only the proximal part of the branches (except in basal whorls) and by closely packed, and partly coalescent, calcified ampullae arranged all around the median and distal portion of branches. The transferral ofNeomeris (Larvaria) koradae Dieni, Massari & Radoicic, 1983 into the genusJodotella, with the new combinationJodotella koradae, is proposed on the basis of new observations on the number and arrangement of fertile ampullae. The new genusBarattoloporella, type-speciesBarattoloporella salentina n. gen. n. sp., is erected for dasycladalean algae characterized by a segmented thallus. Each segment consists of: a) basal and apical sterile whorls made by primary branches only, b) central fertile whorls made by primary branches bearing in terminal position one fertile ampulla and one or two secondary branches. morelletpora dienii n. sp. is characterized by a segmented thallus with barrel shaped to pear shaped repetitive elements, consisting of simple whorls of first order branches only. Shape of the branches varies from regularly phloiophorous to more or less differentiated in a stalk and a swollen portion, with or without a subterminal constriction. This is by far the most diverse dasycladalean assemblage ever found in the Maastrichtian. Its diversity supports the conclusion that, within the Late Cretaceous, the Maastrichtian represents a maximum in dasycladalean diversity. Its taxonomic composition strenghtens the hypothesis that dasycladaleans were hardly affected by K/T mass extinction.     

Zur Kenntnis vonChlamydomonas suboogama

Zusammenfassung Die Variatonsbreite der Merkmale von vegetativen Zellen und von Gametangien ist beiChl. suboogama größer als es nach früheren Untersuchungen schien.Vegetative Zellen können ellipsoidische, eiförmige oder zylindrische Gestalt haben.—Die Oberfläche des Chromatophors herangewachsener vegetativer Zellen ist durch kurze, längs verlaufende Rippen gegliedert.Außer in Gruppen von drei Makrogametangien und einem Spermatogon (was die Regel bildet) bzw. einem Makrogametangien und einem Spermatogon, können die Gametangien auch isoliert vorkommen; sie sind dann relativ groß und entstehen höchstwahrscheinlich durch direkte Umwandlung aus einer Gametangienmutterzelle. In den großen Spermatogonen entsthen 16 oder 32 Spermein (sonst 4 oder 8).Die frisch entleerten Spermein besitzen eine Wand. Diese wird—früher oder später—vor der Befruchtung abgestreift.An den Makrogameten, jungen Zygoten sowie an den mitunger stellenweise abgehobenen Protoplasten vegetativer Zellen ist ein hyaliner Saum ausgebildet, dessen Natur sich nicht klären ließ.Der Entwicklungsgang der Gametangien und Gameten ist tagezeitlich gebunden. Unter den Beleuchtungs-und Temperaturverhältnissen, wie sie in der ersten Hälfte Mai herrschen, zerlegen sich die Gametangienmutterzellen in den Nachmittags-und Nachtstungen in vier Tochterzellen; diese reifen am folgenden Vormittag zu drei Makrogametangien und einem spermatogon heran und entlassen die Hauptmasse der Gameten in den Mittagsstunden.Mit 5 Textabbildungen     

The lateral photoreceptor of the barnacle,Balanus eburneus

Summary The lateral eye of the barnacle, Balanus eburneus, fixed in highly concentrated osmium is a lens-shaped body of approximately 250 m in diameter and about 75 m thick. It contains three photoreceptor cells which occupy about 42% of its volume. The photoreceptor cells are irregularly shaped and extend countless dendritic processes which bear rhabdomeres at their ends. Individual rhabdomeres come into contact with rhabdomeres originating from dendrites of the same or of one of the other visual cells. Thirteen per cent of the volume of the photoreceptor cells is taken up by the rhabdomeres. The membranes of the rhabdomeric microvilli contain globular subunits which suggest a 70 Å spacing of rhodopsin molecules. There are two kinds of glial cells. One kind, type A glial cells, makes contact with the fibrous capsule of the photoreceptor. The other kind, type B glial cells, is associated with the photoreceptor cells and extends countless tiny cytoplasmic extensions which interdigitate with similar extensions of the receptor cells. There are approximately 95 type B glial cells and 130 type A glial cells in the receptor. The cytoplasm of the photoreceptor cells contains countless small Golgi fields, mitochondria, microtubules, multivesicular and multilamellar bodies. The extracellular space of the photoreceptor is less than 0.1% of its total volume.The authors wish to thank Mrs. G. Theisen and Miss D. Hupp for expert technical assistance and Drs. M. Behrens, C. Helrich, and C.C. Krischer for many inspiring discussions. This study was partly supported by the SFB 160 of the Deutsche Forschungsgemeinschaft     

Adrenal glomerulosa mitotic stimulation by posterior pituitary hormones

Summary Injection of posterior pituitary powder induces an intense mitotic stimulation in the zona glomerulosa of the adrenal gland of young rats. This effect is much more pronounced in females than in males. It is maximal at two days treatment. Longer periods result in a hypertrophied zona glomerulosa and lower mitotic activity. A search for the hormone responsible for the stimulation shows that vasopressin, and to a lesser extent oxytocin, are mitogenic. ACTH, -MSH, -MSH and the pineal hormones have no effect. Renin (but not angiotensin) induces a significant stimulation. It is concluded that vasopressin exerts a potent influence on the glomerulosa. This is in contrast with the prevalent view that the glomerulosa is little affected by the hypophysis.     

New observations on lecanoid spermatogenesis in the mealy bug,Planococcus citri

Summary A reexamination of the second spermatogenic division of the mealy bug, Planococcus citri (Risso), a lecanoid coccid, has revealed hitherto unknown spindle activity of the euchromatic set of chromosomes during anaphase II. An initial large half spindle elaborated by the heterochromatic chromosomes in early metaphase, gives way to a less pronounced, but clearly visible bipolar spindle involving both sets of chromosomes at early anaphase. There is no lengthening of the spindle or cell, but the separation of the chromosomes occurs around the periphery of the cell with the aid of interzonal activity. The active participation of the euchromatic chromosome during the separation is furthermore inferred by the formation of bridges resulting from euchromatic-heterochromatic translocations.     

Über physikalisch-chemische Erklärungen der Veränderungen der Kernsubstanz

Ohne Zusammenfassung mit besonderer Berücksichtigung der Arbeit von Paolo Della Valle: La morfologia della cromatina dal punto di vista fisico)