494 research outputs found
DNMT Inhibitors Increase Methylation in the Cancer Genome
DNA methyltransferase inhibitors (DNMTi) decitabine and azacytidine are approved therapies for myelodysplastic syndrome and acute myeloid leukemia, and their combinations with other anticancer agents are being tested as therapeutic options for multiple solid cancers such as colon, ovarian, and lung cancer. However, the current therapeutic challenges of DNMTis include development of resistance, severe side effects and no or partial treatment responses, as observed in more than half of the patients. Therefore, there is a critical need to better understand the mechanisms of action of these drugs. In order to discover molecular targets of DNMTi therapy, we identified 638 novel CpGs with an increased methylation in response to decitabine treatment in HCT116 cell lines and validated the findings in multiple cancer types (e.g., bladder, ovarian, breast, and lymphoma) cell lines, bone marrow mononuclear cells from primary leukemia patients, as well as peripheral blood mononuclear cells and ascites from platinum resistance epithelial ovarian cancer patients. Azacytidine treatment also increased methylation of these CpGs in colon, ovarian, breast, and lymphoma cancer cell lines. Methylation at 166 identified CpGs strongly correlated (vertical bar r vertical bar >= 0.80) with corresponding gene expression in HCT116 cell line. Differences in methylation at some of the identified CpGs and expression changes of the corresponding genes was observed in TCGA colon cancer tissue as compared to adjacent healthy tissue. Our analysis revealed that hypermethylated CpGs are involved in cancer cell proliferation and apoptosis by P53 and olfactory receptor pathways, hence influencing DNMTi responses. In conclusion, we showed hypermethylation of CpGs as a novel mechanism of action for DNMTi agents and identified 638 hypermethylated molecular targets (CpGs) common to decitabine and azacytidine therapy. These novel results suggest that hypermethylation of CpGs should be considered when predicting the DNMTi responses and side effects in cancer patients
SynToxProfiler: An interactive analysis of drug combination synergy, toxicity and efficacy
Drug combinations are becoming a standard treatment of many complex diseases due to their capability to overcome resistance to monotherapy. In the current preclinical drug combination screening, the top combinations for further study are often selected based on synergy alone, without considering the combination efficacy and toxicity effects, even though these are critical determinants for the clinical success of a therapy. To promote the prioritization of drug combinations based on integrated analysis of synergy, efficacy and toxicity profiles, we implemented a web-based open-source tool, SynToxProfiler (Synergy-Toxicity-Profiler). When applied to 20 anti-cancer drug combinations tested both in healthy control and T-cell prolymphocytic leukemia (T-PLL) patient cells, as well as to 77 anti-viral drug pairs tested in Huh7 liver cell line with and without Ebola virus infection, SynToxProfiler prioritized as top hits those synergistic drug pairs that showed higher selective efficacy (difference between efficacy and toxicity), which offers an improved likelihood for clinical success
Spectroscopic investigation of quantum confinement effects in ion implanted silicon-on-sapphire films
Crystalline Silicon-on-Sapphire (SOS) films were implanted with boron (B)
and phosphorous (P) ions. Different samples, prepared by varying the ion
dose in the range to 5 x and ion energy in the range
150-350 keV, were investigated by the Raman spectroscopy, photoluminescence
(PL) spectroscopy and glancing angle x-ray diffraction (GAXRD). The Raman
results from dose dependent B implanted samples show red-shifted and
asymmetrically broadened Raman line-shape for B dose greater than
ions cm. The asymmetry and red shift in the Raman line-shape is
explained in terms of quantum confinement of phonons in silicon nanostructures
formed as a result of ion implantation. PL spectra shows size dependent visible
luminescence at 1.9 eV at room temperature, which confirms the presence
of silicon nanostructures. Raman studies on P implanted samples were also
done as a function of ion energy. The Raman results show an amorphous top SOS
surface for sample implanted with 150 keV P ions of dose 5 x ions
cm. The nanostructures are formed when the P energy is increased to
350 keV by keeping the ion dose fixed. The GAXRD results show consistency with
the Raman results.Comment: 9 Pages, 6 Figures and 1 Table, \LaTex format To appear in
SILICON(SPRINGER
Influence of calcination temperature on structural and magnetic properties of nanocomposites formed by Co-ferrite dispersed in sol-gel silica matrix using tetrakis(2-hydroxyethyl) orthosilicate as precursor
Effects of calcination temperatures varying from 400 to 1000°C on structural and magnetic properties of nanocomposites formed by Co-ferrite dispersed in the sol-gel silica matrix using tetrakis(2-hydroxyethyl) orthosilicate (THEOS) as water-soluble silica precursor have been investigated. Studies carried out using XRD, FT-IR, TEM, STA (TG-DTG-DTA) and VSM techniques. Results indicated that magnetic properties of samples such as superparamagnetism and ferromagnetism showed great dependence on the variation of the crystallinity and particle size caused by the calcination temperature. The crystallization, saturation magnetization Ms and remenant magnetization Mr increased as the calcination temperature increased. But the variation of coercivity Hc was not in accordance with that of Ms and Mr, indicating that Hc is not determined only by the crystallinity and size of CoFe2O4 nanoparticles. TEM images showed spherical nanoparticles dispersed in the silica network with sizes of 10-30 nm. Results showed that the well-established silica network provided nucleation locations for CoFe2O4 nanoparticles to confinement the coarsening and aggregation of nanoparticles. THEOS as silica matrix network provides an ideal nucleation environment to disperse CoFe2O4 nanoparticles and thus to confine them to aggregate and coarsen. By using THEOS as water-soluble silica precursor over the currently used TEOS and TMOS, the organic solvents are not needed owing to the complete solubility of THEOS in water. Synthesized nanocomposites with adjustable particle sizes and controllable magnetic properties make the applicability of Co-ferrite even more versatile
Cucurbita plants: From farm to industry
The Cucurbita genus, a member of Cucurbitaceae family, also known as cucurbits, is native to the Americas. Genus members, like Cucurbita pepo and Cucurbita maxima, have been used for centuries in folk medicine for treating gastrointestinal diseases and intestinal parasites. These pharmacological effects are mainly attributed to their phytochemical composition. Indeed, Cucurbita species are a natural source of carotenoids, tocopherols, phenols, terpenoids, saponins, sterols, fatty acids, functional carbohydrates, and polysaccharides, that beyond exerting remarkable biological effects, have also been increasingly exploited for biotechnological applications. In this article, we specifically cover the habitat, cultivation, phytochemical composition, and food preservative abilities of Cucurbita plants.This work was supported by CONICYT PIA/APOYO CCTE AFB170007. N. Martins would like to thank the Portuguese Foundation for Science and Technology (FCT-Portugal) for the Strategic project ref. UID/BIM/04293/2013 and “NORTE2020-Northern Regional Operational Program” (NORTE-01-0145-FEDER-000012)
Testing the role of predicted gene knockouts in human anthropometric trait variation
National Heart, Lung, and Blood Institute (NHLBI)
S.L. is funded by a Canadian Institutes of Health Research
Banting doctoral scholarship. G.L. is funded by Genome Canada
and Génome Québec; the Canada Research Chairs program; and
the Montreal Heart Institute Foundation. C.M.L. is supported by
Wellcome Trust (grant numbers 086596/Z/08/Z, 086596/Z/08/A);
and the Li Ka Shing Foundation. N.S. is funded by National Institutes
of Health (grant numbers HL088456, HL111089, HL116747).
The Mount Sinai BioMe Biobank Program is supported by the Andrea
and Charles Bronfman Philanthropies. GO ESP is supported
by NHLBI (RC2 HL-103010 to HeartGO, RC2 HL-102923 to LungGO,
RC2 HL-102924 to WHISP). The ESP exome sequencing was
performed through NHLBI (RC2 HL-102925 to BroadGO, RC2 HL-
102926 to SeattleGO). EGCUT work was supported through the
Estonian Genome Center of University of Tartu by the Targeted
Financing from the Estonian Ministry of Science and Education
(grant number SF0180142s08); the Development Fund of the University
of Tartu (grant number SP1GVARENG); the European Regional
Development Fund to the Centre of Excellence in
Genomics (EXCEGEN) [grant number 3.2.0304.11-0312]; and
through FP7 (grant number 313010). EGCUT were further supported
by the US National Institute of Health (grant number
R01DK075787). A.K.M. was supported by an American Diabetes
Association Mentor-Based Postdoctoral Fellowship (#7-12-MN-
02). The BioVU dataset used in the analyses described were obtained
from Vanderbilt University Medical Centers BioVU which
is supported by institutional funding and by the Vanderbilt CTSA
grant ULTR000445 from NCATS/NIH. Genome-wide genotyping
was funded by NIH grants RC2GM092618 from NIGMS/OD and
U01HG004603 from NHGRI/NIGMS. Funding to pay the Open Access
publication charges for this article was provided by a block
grant from Research Councils UK to the University of Cambridge
Testing the role of predicted gene knockouts in human anthropometric trait variation
National Heart, Lung, and Blood Institute (NHLBI)
S.L. is funded by a Canadian Institutes of Health Research
Banting doctoral scholarship. G.L. is funded by Genome Canada
and Génome Québec; the Canada Research Chairs program; and
the Montreal Heart Institute Foundation. C.M.L. is supported by
Wellcome Trust (grant numbers 086596/Z/08/Z, 086596/Z/08/A);
and the Li Ka Shing Foundation. N.S. is funded by National Institutes
of Health (grant numbers HL088456, HL111089, HL116747).
The Mount Sinai BioMe Biobank Program is supported by the Andrea
and Charles Bronfman Philanthropies. GO ESP is supported
by NHLBI (RC2 HL-103010 to HeartGO, RC2 HL-102923 to LungGO,
RC2 HL-102924 to WHISP). The ESP exome sequencing was
performed through NHLBI (RC2 HL-102925 to BroadGO, RC2 HL-
102926 to SeattleGO). EGCUT work was supported through the
Estonian Genome Center of University of Tartu by the Targeted
Financing from the Estonian Ministry of Science and Education
(grant number SF0180142s08); the Development Fund of the University
of Tartu (grant number SP1GVARENG); the European Regional
Development Fund to the Centre of Excellence in
Genomics (EXCEGEN) [grant number 3.2.0304.11-0312]; and
through FP7 (grant number 313010). EGCUT were further supported
by the US National Institute of Health (grant number
R01DK075787). A.K.M. was supported by an American Diabetes
Association Mentor-Based Postdoctoral Fellowship (#7-12-MN-
02). The BioVU dataset used in the analyses described were obtained
from Vanderbilt University Medical Centers BioVU which
is supported by institutional funding and by the Vanderbilt CTSA
grant ULTR000445 from NCATS/NIH. Genome-wide genotyping
was funded by NIH grants RC2GM092618 from NIGMS/OD and
U01HG004603 from NHGRI/NIGMS. Funding to pay the Open Access
publication charges for this article was provided by a block
grant from Research Councils UK to the University of Cambridge
Testing the role of predicted gene knockouts in human anthropometric trait variation
National Heart, Lung, and Blood Institute (NHLBI)
S.L. is funded by a Canadian Institutes of Health Research
Banting doctoral scholarship. G.L. is funded by Genome Canada
and Génome Québec; the Canada Research Chairs program; and
the Montreal Heart Institute Foundation. C.M.L. is supported by
Wellcome Trust (grant numbers 086596/Z/08/Z, 086596/Z/08/A);
and the Li Ka Shing Foundation. N.S. is funded by National Institutes
of Health (grant numbers HL088456, HL111089, HL116747).
The Mount Sinai BioMe Biobank Program is supported by the Andrea
and Charles Bronfman Philanthropies. GO ESP is supported
by NHLBI (RC2 HL-103010 to HeartGO, RC2 HL-102923 to LungGO,
RC2 HL-102924 to WHISP). The ESP exome sequencing was
performed through NHLBI (RC2 HL-102925 to BroadGO, RC2 HL-
102926 to SeattleGO). EGCUT work was supported through the
Estonian Genome Center of University of Tartu by the Targeted
Financing from the Estonian Ministry of Science and Education
(grant number SF0180142s08); the Development Fund of the University
of Tartu (grant number SP1GVARENG); the European Regional
Development Fund to the Centre of Excellence in
Genomics (EXCEGEN) [grant number 3.2.0304.11-0312]; and
through FP7 (grant number 313010). EGCUT were further supported
by the US National Institute of Health (grant number
R01DK075787). A.K.M. was supported by an American Diabetes
Association Mentor-Based Postdoctoral Fellowship (#7-12-MN-
02). The BioVU dataset used in the analyses described were obtained
from Vanderbilt University Medical Centers BioVU which
is supported by institutional funding and by the Vanderbilt CTSA
grant ULTR000445 from NCATS/NIH. Genome-wide genotyping
was funded by NIH grants RC2GM092618 from NIGMS/OD and
U01HG004603 from NHGRI/NIGMS. Funding to pay the Open Access
publication charges for this article was provided by a block
grant from Research Councils UK to the University of Cambridge
Erratum to: Synthesis and Magnetic Properties of Nearly Monodisperse CoFe2O4 Nanoparticles Through a Simple Hydrothermal Condition
<p>Abstract</p> <p>Nearly monodisperse cobalt ferrite (CoFe<sub>2</sub>O<sub>4</sub>) nanoparticles without any size-selection process have been prepared through an alluring method in an oleylamine/ethanol/water system. Well-defined nanospheres with an average size of 5.5 nm have been synthesized using metal chloride as the law materials and oleic amine as the capping agent, through a general liquid–solid-solution (LSS) process. Magnetic measurement indicates that the particles exhibit a very high coercivity at 10 K and perform superparamagnetism at room temperature which is further illuminated by ZFC/FC curves. These superparamagnetic cobalt ferrite nanomaterials are considered to have potential application in the fields of biomedicine. The synthesis method is possible to be a general approach for the preparation of other pure binary and ternary compounds.</p
Sustainable food security in India—Domestic production and macronutrient availability
<div><p>India has been perceived as a development enigma: Recent rates of economic growth have not been matched by similar rates in health and nutritional improvements. To meet the second Sustainable Development Goal (SDG2) of achieving zero hunger by 2030, India faces a substantial challenge in meeting basic nutritional needs in addition to addressing population, environmental and dietary pressures. Here we have mapped—for the first time—the Indian food system from crop production to household-level availability across three key macronutrients categories of ‘calories’, ‘digestible protein’ and ‘fat’. To better understand the potential of reduced food chain losses and improved crop yields to close future food deficits, scenario analysis was conducted to 2030 and 2050. Under India’s current self-sufficiency model, our analysis indicates severe shortfalls in availability of all macronutrients across a large proportion (>60%) of the Indian population. The extent of projected shortfalls continues to grow such that, even in ambitious waste reduction and yield scenarios, enhanced domestic production alone will be inadequate in closing the nutrition supply gap. We suggest that to meet SDG2 India will need to take a combined approach of optimising domestic production and increasing its participation in global trade.</p></div
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