1,497 research outputs found
Chromosomal and environmental contributions to sex differences in the vulnerability to neurological and neuropsychiatric disorders: Implications for therapeutic interventions
Neurological and neuropsychiatric disorders affect men and women differently. Multiple sclerosis, Alzheimer's disease, anxiety disorders, depression, meningiomas and late-onset schizophrenia affect women more frequently than men. By contrast, Parkinson's disease, autism spectrum condition, attention-deficit hyperactivity disorder, Tourette's syndrome, amyotrophic lateral sclerosis and early-onset schizophrenia are more prevalent in men. Women have been historically under-recruited or excluded from clinical trials, and most basic research uses male rodent cells or animals as disease models, rarely studying both sexes and factoring sex as a potential source of variation, resulting in a poor understanding of the underlying biological reasons for sex and gender differences in the development of such diseases. Putative pathophysiological contributors include hormones and epigenetics regulators but additional biological and non-biological influences may be at play. We review here the evidence for the underpinning role of the sex chromosome complement, X chromosome inactivation, and environmental and epigenetic regulators in sex differences in the vulnerability to brain disease. We conclude that there is a pressing need for a better understanding of the genetic, epigenetic and environmental mechanisms sustaining sex differences in such diseases, which is critical for developing a precision medicine approach based on sex-tailored prevention and treatment
Cytoplasmic Prep1 Interacts with 4EHP Inhibiting Hoxb4 Translation
embryo development. Interestingly, Prep1 contains a putative binding motif for 4EHP, which may reflect a novel unknown function. development effect. mRNA to the 5′ cap structure. This is the first demonstration that a mammalian homeodomain transcription factor regulates translation, and that this function can be possibly essential for the development of female germ cells and involved in mammalian zygote development
Molecular analysis of representative Streptococcus gordonii Spp phase variants reveals no differences in the glucosyltransferase structural gene, gtfG
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73398/1/j.1399-302X.1997.tb00622.x.pd
Deficiency of immunoregulatory indoleamine 2,3-dioxygenase 1 in juvenile diabetes
A defect in indoleamine 2,3-dioxygenase 1 (IDO1), which is responsible for immunoregulatory tryptophan catabolism, impairs development of immune tolerance to autoantigens in NOD mice, a model for human autoimmune type 1 diabetes (T1D). Whether IDO1 function is also defective in T1D is still unknown. We investigated IDO1 function in sera and peripheral blood mononuclear cells (PBMCs) from children with T1D and matched controls. These children were further included in a discovery study to identify SNPs in IDO1 that might modify the risk of T1D. T1D in children was characterized by a remarkable defect in IDO1 function. A common haplotype, associated with dysfunctional IDO1, increased the risk of developing T1D in the discovery and also confirmation studies. In T1D patients sharing such a common IDO1 haplotype, incubation of PBMCs in vitro with tocilizumab (TCZ) - an IL-6 receptor blocker - would, however, rescue IDO1 activity. In an experimental setting with diabetic NOD mice, TCZ was found to restore normoglycemia via IDO1-dependent mechanisms. Thus, functional SNPs of IDO1 are associated with defective tryptophan catabolism in human T1D, and maneuvers aimed at restoring IDO1 function would be therapeutically effective in at least a subgroup of T1D pediatric patients.The authors wish to thank patients and subjects who participated in this study, as well as nurses and staff of the Pediatric Clinic of S. Maria della Misericordia Hospital (Perugia), Juvenile Diabetes Center-Anna Meyer Children's Hospital (Florence), Unit of Endocrinology and Diabetes-'Bambino Gesu' Children's Hospital (Rome), Hopital Necker-Enfants Malades (Paris), and Diabetes and Metabolism Service-University Hospital Centre of Coimbra (Coimbra). The authors wish also to thank Roberto Gerli for the gift of TCZ, Giovanni Ricci for histologies, and Francisco Carrilho and Eduarda Coutinho for providing and processing, respectively, DNA samples from the Portuguese cohorts. This work was supported by the European Research Council (338954-DIDO to UG) and, in part, by Associazione per l'Aiuto ai Giovani con Diabete Italia e dell'Umbria (to UG) and the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013 to AC) and the Fundacao para a Ciencia e Tecnologia (contracts IF/00735/2014 to AC, and SFRH/BPD/96176/2013 to CC).info:eu-repo/semantics/publishedVersio
Germline EPHB2 Receptor Variants in Familial Colorectal Cancer
Familial clustering of colorectal cancer occurs in 15–20% of cases, however recognized cancer syndromes explain only a small fraction of this disease. Thus, the genetic basis for the majority of hereditary colorectal cancer remains unknown. EPHB2 has recently been implicated as a candidate tumor suppressor gene in colorectal cancer. The aim of this study was to evaluate the contribution of EPHB2 to hereditary colorectal cancer. We screened for germline EPHB2 sequence variants in 116 population-based familial colorectal cancer cases by DNA sequencing. We then estimated the population frequencies and characterized the biological activities of the EPHB2 variants identified. Three novel nonsynonymous missense alterations were detected. Two of these variants (A438T and G787R) result in significant residue changes, while the third leads to a conservative substitution in the carboxy-terminal SAM domain (V945I). The former two variants were found once in the 116 cases, while the V945I variant was present in 2 cases. Genotyping of additional patients with colorectal cancer and control subjects revealed that A438T and G787R represent rare EPHB2 alleles. In vitro functional studies show that the G787R substitution, located in the kinase domain, causes impaired receptor kinase activity and is therefore pathogenic, whereas the A438T variant retains its receptor function and likely represents a neutral polymorphism. Tumor tissue from the G787R variant case manifested loss of heterozygosity, with loss of the wild-type allele, supporting a tumor suppressor role for EPHB2 in rare colorectal cancer cases. Rare germline EPHB2 variants may contribute to a small fraction of hereditary colorectal cancer
Search for a Technicolor omega_T Particle in Events with a Photon and a b-quark Jet at CDF
If the Technicolor omega_T particle exists, a likely decay mode is omega_T ->
gamma pi_T, followed by pi_T -> bb-bar, yielding the signature gamma bb-bar. We
have searched 85 pb^-1 of data collected by the CDF experiment at the Fermilab
Tevatron for events with a photon and two jets, where one of the jets must
contain a secondary vertex implying the presence of a b quark. We find no
excess of events above standard model expectations. We express the result of an
exclusion region in the M_omega_T - M_pi_T mass plane.Comment: 14 pages, 2 figures. Available from the CDF server (PS with figs):
http://www-cdf.fnal.gov/physics/pub98/cdf4674_omega_t_prl_4.ps
FERMILAB-PUB-98/321-
emm gene diversity, superantigen gene profiles and presence of SlaA among clinical isolates of group A, C and G streptococci from western Norway
In order to investigate molecular characteristics of beta-hemolytic streptococcal isolates from western Norway, we analysed the entire emm gene sequences, obtained superantigen gene profiles and determined the prevalence of the gene encoding streptococcal phospholipase A2 (SlaA) of 165 non-invasive and 34 contemporary invasive group A, C and G streptococci (GAS, GCS and GGS). Among the 25 GAS and 26 GCS/GGS emm subtypes identified, only emm3.1 was significantly associated with invasive disease. M protein size variation within GAS and GCS/GGS emm types was frequently identified. Two non-invasive and one invasive GGS possessed emm genes that translated to truncated M proteins as a result of frameshift mutations. Results suggestive of recombinations between emm or emm-like gene segments were found in isolates of emm4 and stG485 types. One non-invasive GGS possessed speC, speG, speH, speI and smeZ, and another non-invasive GGS harboured SlaA. speA and SlaA were over-represented among invasive GAS, probably because they were associated with emm3. speGdys was identified in 83% of invasive and 63% of non-invasive GCS/GGS and correlated with certain emm subtypes. Our results indicate the invasive potential of isolates belonging to emm3, and show substantial emm gene diversity and possible lateral gene transfers in our streptococcal population
Measurement of the B0 anti-B0 oscillation frequency using l- D*+ pairs and lepton flavor tags
The oscillation frequency Delta-md of B0 anti-B0 mixing is measured using the
partially reconstructed semileptonic decay anti-B0 -> l- nubar D*+ X. The data
sample was collected with the CDF detector at the Fermilab Tevatron collider
during 1992 - 1995 by triggering on the existence of two lepton candidates in
an event, and corresponds to about 110 pb-1 of pbar p collisions at sqrt(s) =
1.8 TeV. We estimate the proper decay time of the anti-B0 meson from the
measured decay length and reconstructed momentum of the l- D*+ system. The
charge of the lepton in the final state identifies the flavor of the anti-B0
meson at its decay. The second lepton in the event is used to infer the flavor
of the anti-B0 meson at production. We measure the oscillation frequency to be
Delta-md = 0.516 +/- 0.099 +0.029 -0.035 ps-1, where the first uncertainty is
statistical and the second is systematic.Comment: 30 pages, 7 figures. Submitted to Physical Review
Search for New Particles Decaying to top-antitop in proton-antiproton collisions at squareroot(s)=1.8 TeV
We use 106 \ipb of data collected with the Collider Detector at Fermilab to
search for narrow-width, vector particles decaying to a top and an anti-top
quark. Model independent upper limits on the cross section for narrow, vector
resonances decaying to \ttbar are presented. At the 95% confidence level, we
exclude the existence of a leptophobic \zpr boson in a model of
topcolor-assisted technicolor with mass M_{\zpr} 480 \gev for natural
width = 0.012 M_{\zpr}, and M_{\zpr} 780 \gev for =
0.04 M_{\zpr}.Comment: The CDF Collaboration, submitted to PRL 25-Feb-200
A Measurement of the Differential Dijet Mass Cross Section in p-pbar Collisions at sqrt{s}=1.8 TeV
We present a measurement of the cross section for production of two or more
jets as a function of dijet mass, based on an integrated luminosity of 86 pb^-1
collected with the Collider Detector at Fermilab. Our dijet mass spectrum is
described within errors by next-to-leading order QCD predictions using CTEQ4HJ
parton distributions, and is in good agreement with a similar measurement from
the D0 experiment.Comment: 18 pages including 2 figures and 3 tables. Submitted to Phys. Rev. D
Rapid Communication
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