353 research outputs found
A close connection: Alzheimer’s disease and type 2 diabetes
In the recent years a growing body of evidence
links insulin resistance and insulin action to
neurodegenerative diseases, especially Alzheimer’s
disease (AD). The importance of insulin in ageing
as well as its role in cognition and other aspects of
normal brain functions are well established. The
hippocampus and cerebral cortex-distributed insulin
and insulin receptor (IR) have been shown to be
involved in brain cognitive functions. Conversely,
deterioration of IR signaling is involved in agingrelated
brain degeneration such as in AD and
cognitive impairment in type 2 diabetes patients.
Insulin administration, while maintaining
euglycemia, improves memory in both healthy
adults and Alzheimer’s disease patients. In the
present review, some common links between AD
and type 2 diabetes are presented. Furthermore,
several biochemical aspects existing in both
pathologies are highlighted
Cure of mammary carcinomas in Her-2 transgenic mice through sequential stimulation of innate (neoadjuvant interleukin-12) and adaptive (DNA vaccine electroporation) immunity.
Purpose: Whereas neoadjuvant therapy is emerging as
a treatment option in early primary breast cancer, no data
are available on the use of antiangiogenic and immunomodulatory
agents in a neoadjuvant setting. In a model of
Her-2 spontaneous mammary cancer, we investigated the
efficacy of neoadjuvant interleukin 12 (IL-12) followed by
‘‘immune-surgery’’ of the residual tumor.
Experimental Design: Female BALB/c mice transgenic
for the rat Her-2 oncogene inexorably develop invasive
carcinomas in all their mammary glands by the 23rd week of
age. Mice with multifocal in situ carcinomas received four
weekly i.p. injections of 100 ng IL-12 followed by a 3-week
rest. This course was given four times. A few mice
additionally received DNA plasmids encoding portions of
the Her-2 receptor electroporated through transcutaneous
electric pulses.
Results: The protection elicited by IL-12 in combination
with two DNA vaccine electroporations kept 63% of
mice tumor-free. Complete protection of all 1-year-old mice
was achieved when IL-12-treated mice received four
vaccine electroporations. Pathologic findings, in vitro tests,
and the results from immunization of both IFN-; andimmunoglobulin gene knockout transgenic mice and of
adoptive transfer experiments all show that IL-12 augments
the B- and T-cell response elicited by vaccination and
slightly decreases the number of regulatory T cells. In
addition, IL-12 strongly inhibits tumor angiogenesis.
Conclusions: In Her-2 transgenic mice, IL-12 impairs
tumor progression and triggers innate immunity so markedly
that DNA vaccination becomes effective at late points in time
when it is ineffective on its own
Interplay between telecommunications and face-to-face interactions - a study using mobile phone data
In this study we analyze one year of anonymized telecommunications data for
over one million customers from a large European cellphone operator, and we
investigate the relationship between people's calls and their physical
location. We discover that more than 90% of users who have called each other
have also shared the same space (cell tower), even if they live far apart.
Moreover, we find that close to 70% of users who call each other frequently (at
least once per month on average) have shared the same space at the same time -
an instance that we call co-location. Co-locations appear indicative of
coordination calls, which occur just before face-to-face meetings. Their number
is highly predictable based on the amount of calls between two users and the
distance between their home locations - suggesting a new way to quantify the
interplay between telecommunications and face-to-face interactions
The Water Bugs (Heteroptera: Nepomorpha) of the Guyana Region
NEPOMORPHA OF THE GUYANA REGION
The Nepomorpha of the Guyana Region are keyed out and described. In addition distributional, faunistical and comparative notes on the species are given.
New species and subspecies: Ochterus aeneifrons surinamensis, O. tenebrosus; Limnocoris fittkaui surinamensis; Ranatra adelomorpha; Neoplea globoidea; Buenoa amnigenopsis; Tenagobia pseudoromani from Suriname and Ranatra ornitheia from Guyana.
New synonyms (junior ones between parenthesis): Gelaslocorus flavus flavus Guér. (G. nebulosus nebulosus Guér.); Pelocoris impicticollis Stål (P. horváthi Mont.), P. poeyi (Guér.) not identical with P. femoratus (P.-B.) (P. convexus Nieser), P. procurrens White (P. minutus Mont.); Belostoma bicavum Lauck ( B. parvoculum Lauck); Ranatra doesburgi De Carlo (R. usingeri De C.), R. macrophthalma H.-S. (R. surinamensis De C.), R. mediana Mont. (R. williamsi Kuitert), R. obscura Mont. (R. annulipes White 1879 not Stål), R. sarmentoi De C. (R. ameghinoi De C.); Buenoa amnigenopsis n. sp. ( B. amnigenus Nieser 1968, 1970 not White), B. amnigenus (White) (B. amnigenoidea Nieser 1970), B. nitida Truxal (B. doesburgi Nieser); Heterocorixa surinamensis Nieser ( H. boliviensis Nieser 1970 not Hungerford); Tenagobia incerta Lundbl. ( T. signata and T. serrata in part, Nieser 1970 not White and Deay respectively), T. socialis (White) (T. serrata in part, Nieser 1970 not Deay)
FCR (Fludarabine, Cyclophosphamide, Rituximab) regimen followed by 90yttrium ibritumomab tiuxetan consolidation for the treatment of relapsed grades 1 and 2 follicular lymphoma: a report of 9 cases
<p>Abstract</p> <p>Background</p> <p>This retrospective analysis is focused on the efficacy and safety of radioimmunotherapy (RIT) with Zevalin<sup>® </sup>in nine patients with recurrent follicular lymphoma (FL) who were treated in a consolidation setting after having achieved complete remission or partial remission with FCR.</p> <p>Methods</p> <p>The median age was 63 yrs (range 46-77), all patients were relapsed with histologically confirmed CD20-positive (grade 1 or 2) FL, at relapse they received FCR every 28 days: F (25 mg/m<sup>2</sup>x 3 days), C (1 gr/m<sup>2 </sup>day 1) and R (375 mg/m<sup>2 </sup>day 4) for 4 cycles. Who achieved at least a partial remission, with < 25% bone marrow involvement, was treated with <sup>90</sup>Yttrium Ibritumomab Tiuxetan 11.1 or 14.8 MBq/Kg up to a maximum dose 1184 MBq, at 3 months after the completion of FCR. The patients underwent a further restaging at 12 weeks after <sup>90</sup>Y-RIT with total body CT scan, FDG-PET/CT and bilateral bone marrow biopsy.</p> <p>Results</p> <p>Nine patients have completed the treatment: FCR followed by <sup>90</sup>Y-RIT (6 patients at 14.8 MBq/Kg, 3 patients at 11.1 MBq/Kg). After FCR 7 patients obtained CR and 2 PR; after <sup>90</sup>Y-RIT two patients in PR converted to CR 12 weeks later. With median follow up of 34 months (range 13-50) the current analysis has shown that overall survival (OS) is 89% at 2 years, 76% at 3 years and 61% at 4 years. The most common grade 3 or 4 adverse events were hematologic, one patient developed herpes zoster infection after 8 months following valacyclovir discontinuation; another patient developed fungal infection.</p> <p>Conclusions</p> <p>Our experience indicate feasibility, tolerability and efficacy of FCR regimen followed by <sup>90</sup>Y-RIT in patients relapsed with grades 1 and 2 FL with no unexpected toxicities. A longer follow up and a larger number of patients with relapsed grades 1 and 2 FL are required to determine the impact of this regimen on long-term duration of response and PFS.</p
Narcissism and prosocial behavior
There are many motivations for prosocial behavior, some more altruistic and some more egoistic. We posit that more narcissistic people may perform prosocial acts strategically, for example, to improve their reputations or to receive something in return
Oxidized LDL Receptor 1 (OLR1) as a Possible Link between Obesity, Dyslipidemia and Cancer
Recent studies have linked expression of lectin-like ox-LDL receptor 1
(OLR1) to tumorigenesis. We analyzed microarray data from
Olr1 knockout (KO) and wild type (WT) mice for genes
involved in cellular transformation and evaluated effects of
OLR1 over-expression in normal mammary epithelial cells
(MCF10A) and breast cancer cells (HCC1143) in terms of gene expression,
migration, adhesion and transendothelial migration. Twenty-six out of 238 genes
were inhibited in tissues of OLR1 KO mice; the vast majority of OLR1 sensitive
genes contained NF-κB binding sites in their promoters. Further studies
revealed broad inhibition of NF-kB target genes outside of the
transformation-associated gene pool, with enrichment themes of defense response,
immune response, apoptosis, proliferation, and wound healing. Transcriptome of
Olr1 KO mice also revealed inhibition of de
novo lipogenesis, rate-limiting enzymes fatty acid synthase
(Fasn), stearoyl-CoA desaturase (Scd1) and
ELOVL family member 6 (Elovl6), as well as lipolytic
phospholipase A2 group IVB (Pla2g4b). In studies comparing
MCF10A and HCC1143, the latter displayed 60% higher OLR1
expression. Forced over-expression of OLR1 resulted in
upregulation of NF-κB (p65) and its target pro-oncogenes involved in
inhibition of apoptosis (BCL2, BCL2A1,
TNFAIP3) and regulation of cell cycle
(CCND2) in both cell lines. Basal expression of
FASN, SCD1 and PLA2G4B,
as well as lipogenesis transcription factors PPARA,
SREBF2 and CREM, was higher in HCC1143
cells. Over-expression of OLR1 in HCC1143 cells also enhanced
cell migration, without affecting their adherence to TNFα-activated
endothelium or transendothelial migration. On the other hand,
OLR1 neutralizing antibody inhibited both adhesion and
transmigration of untreated HCC1143 cells. We conclude that
OLR1 may act as an oncogene by activation of NF-kB target
genes responsible for proliferation, migration and inhibition of apoptosis and
de novo lipogenesis genes
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