65 research outputs found
The Genomic Signature of Crop-Wild Introgression in Maize
The evolutionary significance of hybridization and subsequent introgression
has long been appreciated, but evaluation of the genome-wide effects of these
phenomena has only recently become possible. Crop-wild study systems represent
ideal opportunities to examine evolution through hybridization. For example,
maize and the conspecific wild teosinte Zea mays ssp. mexicana, (hereafter,
mexicana) are known to hybridize in the fields of highland Mexico. Despite
widespread evidence of gene flow, maize and mexicana maintain distinct
morphologies and have done so in sympatry for thousands of years. Neither the
genomic extent nor the evolutionary importance of introgression between these
taxa is understood. In this study we assessed patterns of genome-wide
introgression based on 39,029 single nucleotide polymorphisms genotyped in 189
individuals from nine sympatric maize-mexicana populations and reference
allopatric populations. While portions of the maize and mexicana genomes were
particularly resistant to introgression (notably near known
cross-incompatibility and domestication loci), we detected widespread evidence
for introgression in both directions of gene flow. Through further
characterization of these regions and preliminary growth chamber experiments,
we found evidence suggestive of the incorporation of adaptive mexicana alleles
into maize during its expansion to the highlands of central Mexico. In
contrast, very little evidence was found for adaptive introgression from maize
to mexicana. The methods we have applied here can be replicated widely, and
such analyses have the potential to greatly informing our understanding of
evolution through introgressive hybridization. Crop species, due to their
exceptional genomic resources and frequent histories of spread into sympatry
with relatives, should be particularly influential in these studies
Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication
Background & Aims: The risk of hepatocellular carcinoma (HCC)
is reduced but not eradicated among patients with hepatitis C
virus (HCV)-induced advanced hepatic fibrosis who attained sustained viral response (SVR). We aimed to assess the risk of
cirrhosis-related complications in this specific group of patients.
Methods: Data from previously reported Western cohort studies
including patients with chronic HCV infection and bridging fibrosis or cirrhosis who attained SVR were pooled for survival analyses on the individual patient level. The primary endpoint was
HCC and the secondary endpoint was clinical disease progression,
defined as liver failure, HCC or death.
Results: Included were 1000 patients with SVR. Median age was
52.7 (IQR 45.1–59.7) years, 676 (68%) were male and 842 (85%)
had cirrhosis. Median follow-up was 5.7 (IQR 2.9–8.0) years.
Fifty-one patients developed HCC and 101 had clinical disease
progression. The cumulative 8-year HCC incidence was 1.8 (95%
CI 0.0–4.3) among patients with bridging fibrosis and 8.7% (95%
CI 6.0–11.4) among those with cirrhosis (p = 0.058). Within the
cirrhosis group, the 8-year HCC incidence was 2.6% (95% CI
0.0–5.5) among patients <45 years, 9.7% (95% CI 5.8–13.6) among
patients from 45–60 years, and 12.2% (95% CI 5.3–19.1) among
patients >60 years of age at start of therapy (p = 0.006).
Multivariable Cox analyses indicated that higher age, lower platelet
count and diabetes mellitus were independently associated with
development of HCC. After 8 years 4.2% (95% CI 0.1–8.3) of patients
with bridging fibrosis and 15.8% (95% CI 12.3–19.3) of patients with
cirrhosis experienced clinical disease progression (p = 0.007).
Conclusions: Patients with HCV-induced cirrhosis and SVR
showed an annual risk of approximately 1% for HCC and 2% for
clinical disease progression. Therefore, to prevent HCC surveillance, chronic HCV infection should preferably be treated before
cirrhosis has developed.
Lay summary: Patients with cirrhosis who were able to eradicate
their chronic HCV infection remain at substantial risk of primary
liver cancer. The risk of liver cancer increases with higher age,
laboratory makers suggesting more severe liver disease, and
presence of diabetes mellitus. Also after successful antiviral therapy patients with HCV-induced cirrhosis should thus remain
included in follow-up for early detection of liver cancer.
2016 European Association for the Study of the Liver. Published
by Elsevier B.V. All rights reserve
Basal ganglia dysfunction in OCD: subthalamic neuronal activity correlates with symptoms severity and predicts high-frequency stimulation efficacy
Functional and connectivity changes in corticostriatal systems have been reported in the brains of patients with obsessive–compulsive disorder (OCD); however, the relationship between basal ganglia activity and OCD severity has never been adequately established. We recently showed that deep brain stimulation of the subthalamic nucleus (STN), a central basal ganglia nucleus, improves OCD. Here, single-unit subthalamic neuronal activity was analysed in 12 OCD patients, in relation to the severity of obsessions and compulsions and response to STN stimulation, and compared with that obtained in 12 patients with Parkinson's disease (PD). STN neurons in OCD patients had lower discharge frequency than those in PD patients, with a similar proportion of burst-type activity (69 vs 67%). Oscillatory activity was present in 46 and 68% of neurons in OCD and PD patients, respectively, predominantly in the low-frequency band (1–8 Hz). In OCD patients, the bursty and oscillatory subthalamic neuronal activity was mainly located in the associative–limbic part. Both OCD severity and clinical improvement following STN stimulation were related to the STN neuronal activity. In patients with the most severe OCD, STN neurons exhibited bursts with shorter duration and interburst interval, but higher intraburst frequency, and more oscillations in the low-frequency bands. In patients with best clinical outcome with STN stimulation, STN neurons displayed higher mean discharge, burst and intraburst frequencies, and lower interburst interval. These findings are consistent with the hypothesis of a dysfunction in the associative–limbic subdivision of the basal ganglia circuitry in OCD's pathophysiology
FGFR3IIIS: a novel soluble FGFR3 spliced variant that modulates growth is frequently expressed in tumour cells
Fibroblast growth factor receptor 3 (FGFR3) is one of four high-affinity tyrosine kinase receptors for the FGF family of ligands, frequently associated with growth arrest and induction of differentiation. The extracellular immunoglobulin (IgG)-like domains II and III are responsible for ligand binding; alternative usage of exons IIIb and IIIc of the Ig-like domain III determining the ligand-binding specificity of the receptor. By reverse transcriptase polymerase chain reaction (RT–PCR) a novel FGFR3IIIc variant FGFR3IIIS, expressed in a high proportion of tumours and tumour cell lines but rarely in normal tissues, has been identified. Unlike recently described nonsense transcripts of FGFR3, the coding region of FGFR3IIIS remains in-frame producing a novel protein. The protein product is coexpressed with FGFR3IIIc in the membrane and soluble cell fractions; expression in the soluble fraction is decreased after exposure to bFGF but not aFGF. Knockout of FGFR3IIIS using antisense has a growth-inhibitory effect in vitro, suggesting a dominant-negative function for FGFR3IIIS inhibiting FGFR3-induced growth arrest. In summary, alternative splicing of the FGFR3 Ig-domain III represents a mechanism for the generation of receptor diversity. FGFR3IIIS may regulate FGF and FGFR trafficking and function, possibly contributing to the development of a malignant phenotype
Development of Immune-Specific Interaction Potentials and Their Application in the Multi-Agent-System VaccImm
Peptide vaccination in cancer therapy is a promising alternative to conventional methods. However, the parameters for this personalized treatment are difficult to access experimentally. In this respect, in silico models can help to narrow down the parameter space or to explain certain phenomena at a systems level. Herein, we develop two empirical interaction potentials specific to B-cell and T-cell receptor complexes and validate their applicability in comparison to a more general potential. The interaction potentials are applied to the model VaccImm which simulates the immune response against solid tumors under peptide vaccination therapy. This multi-agent system is derived from another immune system simulator (C-ImmSim) and now includes a module that enables the amino acid sequence of immune receptors and their ligands to be taken into account. The multi-agent approach is combined with approved methods for prediction of major histocompatibility complex (MHC)-binding peptides and the newly developed interaction potentials. In the analysis, we critically assess the impact of the different modules on the simulation with VaccImm and how they influence each other. In addition, we explore the reasons for failures in inducing an immune response by examining the activation states of the immune cell populations in detail
Gene Flow and Hybridization between Numerically Imbalanced Populations of Two Duck Species in the Falkland Islands
Interspecific hybridization is common in plants and animals, particularly in waterfowl (Anatidae). One factor shown to contribute to hybridization is restricted mate choice, which can occur when two species occur in sympatry but one is rare. The Hubbs principle, or “desperation hypothesis,” states that under such circumstances the rarer species is more likely to mate with heterospecifics. Here we report interspecific hybridization between two waterfowl species that coexist in broad sympatry and mixed flocks throughout southern South America. Speckled teal (Anas flavirostris) and yellow-billed pintails (Anas georgica) are abundant in continental South America, but in the Falkland Islands speckled teal outnumber yellow-billed pintails approximately ten to one. Using eight genetic loci (mtDNA and 7 nuclear introns) coupled with Bayesian assignment tests and relatedness analysis, we identified a speckled teal x yellow-billed pintail F1 hybrid female and her duckling sired by a male speckled teal. Although our sample in the Falkland Islands was small, we failed to identify unequivocal evidence of hybridization or introgression in a much larger sample from Argentina using a three-population “isolation with migration” coalescent analysis. While additional data are needed to determine if this event in the Falkland Islands was a rare singular occurrence, our results provide further support for the “desperation hypothesis,” which states that scarcity in one population and abundance of another will often lead to hybridization
Allergic diseases in the elderly
Demographic distribution of the population is progressively changing with the proportion of elderly persons increasing in most societies. This entails that there is a need to evaluate the impact of common diseases, such as asthma and other allergic conditions, in this age segment. Frailty, comorbidities and polymedication are some of the factors that condition management in geriatric patients. The objective of this review is to highlight the characteristics of allergic diseases in older age groups, from the influence of immunosenescence, to particular clinical implications and management issues, such as drug interactions or age-related side effects
Dengue in an elderly patient
Although elderly populations are more exposed to the risk of getting dengue, the clinical peculiarities of this disease in this age range are not well known. This report is about an 80-year-old woman with dengue complications, self-medicated with salicylate. Literature indicates a more severe clinical condition, high hospitalization rate and significant mortality. This is caused by previous infections by other serotypes of this arbovirus, presence of chronic diseases, immunosenescence and high drug consumption, especially salicylates and the like. Analyses are required in a public health perspective in order to help health professionals that care for patients with dengue in this age range.Embora cada vez mais populações idosas estejam expostas ao risco de contrair dengue, pouco se sabe sobre peculiaridades clĂnicas desta doença nesta faixa etária, fato este que motivou este relato sobre octogenária com dengue agravada por automedicação de salicilato. A literatura consultada aponta para quadro clĂnico mais grave, elevado Ăndice de hospitalizações e mortalidade significativa. Deve-se isto a infecções prĂ©vias com outros sorotipos desta arbovirose, presença de doenças crĂ´nico degenerativas, imunosenescĂŞncia e alto consumo de medicamentos, particularmente salicilatos e similares. Análises, sob a Ăłtica da saĂşde pĂşblica, sĂŁo necessárias para auxiliar aos profissionais de saĂşde que assistem pacientes com dengue nesta faixa etári
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