A balanced formula of essential amino acids promotes brain mitochondrial biogenesis and protects neurons from ischemic insult

Mitochondrial dysfunction plays a key role in the aging process, and aging is a strong risk factor for neurodegenerative diseases or brain injury characterized by impairment of mitochondrial function. Among these, ischemic stroke is one of the leading causes of death and permanent disability worldwide. Pharmacological approaches for its prevention and therapy are limited. Although non-pharmacological interventions such as physical exercise, which promotes brain mitochondrial biogenesis, have been shown to exert preventive effects against ischemic stroke, regular feasibility is complex in older people, and nutraceutical strategies could be valuable alternatives. We show here that dietary supplementation with a balanced essential amino acid mixture (BCAAem) increased mitochondrial biogenesis and the endogenous antioxidant response in the hippocampus of middle-aged mice to an extent comparable to those elicited by treadmill exercise training, suggesting BCAAem as an effective exercise mimetic on brain mitochondrial health and disease prevention. In vitro BCAAem treatment directly exerted mitochondrial biogenic effects and induced antioxidant enzyme expression in primary mouse cortical neurons. Further, exposure to BCAAem protected cortical neurons from the ischemic damage induced by an in vitro model of cerebral ischemia (oxygen-glucose deprivation, OGD). BCAAem-mediated protection against OGD was abolished in the presence of rapamycin, Torin-1, or L-NAME, indicating the requirement of both mTOR and eNOS signaling pathways in the BCAAem effects. We propose BCAAem supplementation as an alternative to physical exercise to prevent brain mitochondrial derangements leading to neurodegeneration and as a nutraceutical intervention aiding recovery after cerebral ischemia in conjunction with conventional drugs

Real-time imaging of polymersome nanoparticles in zebrafish embryos engrafted with melanoma cancer cells: Localization, toxicity and treatment analysis

BACKGROUND: The developing zebrafish is an emerging tool in nanomedicine, allowing non-invasive live imaging of the whole animal at higher resolution than is possible in the more commonly used mouse models. In addition, several transgenic fish lines are available endowed with selected cell types expressing fluorescent proteins; this allows nanoparticles to be visualized together with host cells. METHODS: Here, we introduce the zebrafish neural tube as a robust injection site for cancer cells, excellently suited for high resolution imaging. We use light and electron microscopy to evaluate cancer growth and to follow the fate of intravenously injected nanoparticles. FINDINGS: Fluorescently labelled mouse melanoma B16 cells, when injected into this structure proliferated rapidly and stimulated angiogenesis of new vessels. In addition, macrophages, but not neutrophils, selectively accumulated in the tumour region. When injected intravenously, nanoparticles made of Cy5-labelled poly(ethylene glycol)-block-poly(2-(diisopropyl amino) ethyl methacrylate) (PEG-PDPA) selectively accumulated in the neural tube cancer region and were seen in individual cancer cells and tumour associated macrophages. Moreover, when doxorubicin was released from PEG-PDPA, in a pH dependant manner, these nanoparticles could strongly reduce toxicity and improve the treatment outcome compared to the free drug in zebrafish xenotransplanted with mouse melanoma B16 or human derived melanoma cells. INTERPRETATION: The zebrafish has the potential of becoming an important intermediate step, before the mouse model, for testing nanomedicines against patient-derived cancer cells. FUNDING: We received funding from the Norwegian research council and the Norwegian cancer society

Conservative surgery with and without radiotherapy in elderly patients with early-stage breast cancer: a prospective randomised multicentre trial.

ABSTRACT Breast conserving therapy (BCT) including postoperative irradiation of the remaining breast tissue is generally accepted as the best treatment for the majority of patients with early-stage breast cancer. The question is whether there is a necessity for irradiating all patients. Between 2001 and 2005, 749 women aged 55–75 years with infiltrating breast carcinoma were randomly assigned to breast conservative surgery, with or without radiotherapy (RT), to evaluate the incidence of in-breast recurrence (IBR). After 5 years of median follow-up, the cumulative incidence of IBR was 2.5% in the surgery-only arm and 0.7% in the surgery plus RT arm. There are no differences in terms of overall survival and distant disease-free survival. The preliminary evaluation suggests that breast irradiation after conservative surgery can be avoided without exposing these patients to an increased risk of distant-disease recurrence. Prolonged follow-up will further clarify the possible risks and late sequelae potentially induced by breast RT

Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis

In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes

On the relations between historical epistemology and students’ conceptual developments in mathematics

There is an ongoing discussion within the research field of mathematics education regarding the utilization of the history of mathematics within mathematics education. In this paper we consider problems that may emerge when the historical epistemology of mathematics is paralleled to students’ conceptual developments in mathematics. We problematize this attempt to link the two fields on the basis of Grattan-Guinness’ distinction between “history” and “heritage”. We argue that when parallelism claims are made, history and heritage are often mixed up, which is problematic since historical mathematical definitions must be interpreted in its proper historical context and conceptual framework. Furthermore, we argue that cultural and local ideas vary at different time periods, influencing conceptual developments in different directions regardless of whether historical or individual developments are considered, and thus it may be problematic to uncritically assume a platonic perspective. Also, we have to take into consideration that an average student of today and great mathematicians of the past are at different cognitive levels

Modular synthesis of semiconducting graft co-polymers to achieve ‘clickable’ fluorescent nanoparticles with long circulation and specific cancer targeting

Semiconducting polymer nanoparticles (SPNs) are explored for applications in cancer theranostics because of their high absorption coefficients, photostability, and biocompatibility. However, SPNs are susceptible to aggregation and protein fouling in physiological conditions, which can be detrimental for in vivo applications. Here, a method for achieving colloidally stable and low-fouling SPNs is described by grafting poly(ethylene glycol) (PEG) onto the backbone of the fluorescent semiconducting polymer, poly(9,9′-dioctylfluorene-5-fluoro-2,1,3-benzothiadiazole), in a simple one-step substitution reaction, postpolymerization. Further, by utilizing azide-functionalized PEG, anti-human epidermal growth factor receptor 2 (HER2) antibodies, antibody fragments, or affibodies are site-specifically “clicked” onto the SPN surface, which allows the functionalized SPNs to specifically target HER2-positive cancer cells. In vivo, the PEGylated SPNs are found to have excellent circulation efficiencies in zebrafish embryos for up to seven days postinjection. SPNs functionalized with affibodies are then shown to be able to target HER2 expressing cancer cells in a zebrafish xenograft model. The covalent PEGylated SPN system described herein shows great potential for cancer theranostics

Conservative surgery with and without radiotherapy in elderly patients with early-stage breast cancer: a prospective randomised multicentre trial. Breast 2009

a b s t r a c t Breast conserving therapy (BCT) including postoperative irradiation of the remaining breast tissue is generally accepted as the best treatment for the majority of patients with early-stage breast cancer. The question is whether there is a necessity for irradiating all patients. Between 2001 and 2005, 749 women aged 55-75 years with infiltrating breast carcinoma were randomly assigned to breast conservative surgery, with or without radiotherapy (RT), to evaluate the incidence of in-breast recurrence (IBR). After 5 years of median follow-up, the cumulative incidence of IBR was 2.5% in the surgery-only arm and 0.7% in the surgery plus RT arm. There are no differences in terms of overall survival and distant disease-free survival. The preliminary evaluation suggests that breast irradiation after conservative surgery can be avoided without exposing these patients to an increased risk of distant-disease recurrence. Prolonged follow-up will further clarify the possible risks and late sequelae potentially induced by breast RT

Food, flavouring and feed plant traditions in the Tyrrhenian sector of Basilicata, Italy

BACKGROUND: Research was carried out in the years 2002–2003 into food, flavouring and feed folk traditions of plants in the Tyrrhenian part of the Basilicata region (southern Italy). This area was colonized in ancient times by Greeks. Data was collected through field interviews, especially of farmers. METHODS: Field data were collected through structured interviews. The informants, numbered 49, belonged to families which had strong links with the traditional activities of the area. RESULTS: 61 taxa are cited, belonging to 26 botanical families, amongst which 44 used as food or flavouring and 22 for animal alimentation. Besides 7 taxa are involved in rituals especially connected with agriculture and plant growth. CONCLUSION: The preservation of some rituals especially concerning agricultural plants is noteworthy in the area, together with a certain degree of continuity in food uses. Knowledge and rediscovery of recipes in human and animal diet could represent an economic potential for the area

Ethnobotanical remarks on Central and Southern Italy

<p>Abstract</p> <p>Background</p> <p>The present paper is a brief survey on the ethnobotanical works published by the Authors since 1981, concerning the research carried out in some southern and central Italian regions. Before Roman domination these territories were first inhabited by local people, while the southern areas were colonized by the Greeks. These different cultural contributions left certain traces, both in the toponyms and in the vernacular names of the plants and, more generally, in the culture as a whole.</p> <p>Methods</p> <p>Field data were collected through open interviews, mainly of farmers, shepherds and elderly people, born or living in these areas for a long time. Voucher specimens of collected plants are preserved in the respective herbaria of the Authors and in the herbarium of "Roma Tre" University. Important contributions have been made by several students native to the areas under consideration. A comparative analysis with local specific ethnobotanical literature was carried out.</p> <p>Results</p> <p>The paper reports several examples concerning human and veterinary popular medicine and in addition some anti-parasitic, nutraceutic, dye and miscellaneous uses are also described. Moreover vernacular names and toponyms are cited. Eight regions of central and southern Italy (particularly Latium, Abruzzo, Marche and Basilicata) were investigated and the data obtained are presented in 32 papers. Most of the species of ethnobotanical interest have been listed in Latium (368 species), Marche (274) and Abruzzo (203). The paper also highlights particularly interesting aspects or uses not previously described in the specific ethnobotanical literature.</p> <p>Conclusion</p> <p>Phyto-therapy in central and southern Italy is nowadays practised by a few elderly people who resort to medicinal plants only for mild complaints (on the contrary food uses are still commonly practised). Nowadays therapeutic uses, unlike in the past, are less closely or not at all linked to ritual aspects. Several plants deserve to be taken into consideration not only from the anthropological or cultural point of view, but also for further phyto-chemical investigation. Our studies, as well as those of other authors, try to provide an original picture of the local ethno-biodiversity.</p