52 research outputs found
Recommended from our members
Ubiquitin sets the timer: impacts on aging and longevity
Protein homeostasis is essential for cellular function, organismal growth and viability. Damaged and aggregated proteins are turned over by two major proteolytic routes of the cellular quality-control pathways: the ubiquitin-proteasome system and autophagy. For both these pathways, ubiquitination provides the recognition signal for substrate selection. This Commentary discusses how ubiquitin-dependent proteolytic pathways are coordinated with stress- and aging-induced signals
High transcript levels of vitamin D receptor are correlated with higher mRNA expression of human beta defensins and IL-10 in mucosa of HIV-1-exposed seronegative individuals
RESUMEN: La vitamina D (VitD) es un inmunomodulador endógena que podrÃa proteger de la infección por VIH-1 la reducción de la activación inmune y la inducción de la expresión de VIH-1 anti-péptidos. Para establecer una correlación entre VitD y resistencia natural a la infección VIH-1, un estudio de casos y controles utilizando sangre y mucosa muestras de 58 VIH-1 expuesto, pero seronegativos (HESN) individuos , 43 VIH-1 seropositivos (SP) y 59 no controles sanos -exposed (HCS) se llevó a cabo. La concentración VitD en el plasma se determinó por ELISA, y de ARNm de unidades relativas (RU) de VDR, IL-10 , TGF-β, TNF-α e IL-1β en las células mononucleares de sangre periférica (PBMCs), oral y genital mucosa se cuantificó por QRT-PCR. mRNA niveles de humana beta -defensin (HBD) -2 y -3 se informó anteriormente y utilizados para correlaciones. Significativamente más altos niveles de VitD se encontraron en plasma, asà como mayor mRNA RU de VDR en PBMCs, y en genital mucosa de HESN en comparación con HC. Además, superior mRNA RU de TNF-α, IL-1β y IL-10 , e inferior mRNA RU de TGF-β se encontraron en PBMC de HESNs en comparación con HC. También se observó mayor IL-10 mRNA RU en genital mucosa de HESNs en comparación con HC, y los ARNm de los niveles de TNF-α en oral y genital mucosa de SPs estábamos más alta en comparación con HESNs. Por otra parte, las correlaciones positivas entre VDR y la IL-10 mRNA RU en PBMCs y genital mucosa encontrados de HESNs. Por último, HBD-2 y HBD-3 ARNm RU fueron positivamente correlacionadas con VDR mRNA expresión en forma oral mucosa de HESNs. Estos resultados sugieren que los altos niveles de VitD y su receptor están asociadas con resistencia natural a la infección por VIH-1. Sobre regulación de los anti-inflamatoria IL-10 , y la inducción de anti-VIH-1 defensinas en la mucosa podrÃa ser parte de los mecanismos implicados en esta asociación. Sin embargo, se necesitan más estudios para definir las asociaciones causales.ABSTRACT: Vitamin D (VitD) is an endogenous immunomodulator that could protect from HIV-1 infection reducing immune activation and inducing the expression of anti-HIV-1 peptides. To establish a correlation between VitD and natural resistance to HIV-1 infection, a case-control study using blood and mucosa samples of 58 HIV-1-exposed but seronegative (HESN) individuals, 43 HIV-1 seropositives (SPs) and 59 non-exposed healthy controls (HCs) was carried out. The VitD concentration in plasma was determined by ELISA, and mRNA relative units (RU) of VDR, IL-10, TGF-β, TNF-α and IL-1β in peripheral blood mononuclear cells (PBMCs), oral and genital mucosa was quantified by qRT-PCR. mRNA levels of human beta-defensin (HBD) -2 and -3 were previously reported and used for correlations. Significantly higher levels of VitD were found in plasma as well as higher mRNA RU of VDR in PBMCs, and in genital mucosa from HESN compared to HCs. In addition, higher mRNA RU of TNF-α, IL-1β and IL-10, and lower mRNA RU of TGF-β were found in PBMC from HESNs compared to HCs. We also observed higher IL-10 mRNA RU in genital mucosa of HESNs compared to HCs, and the mRNA levels of TNF-α in oral and genital mucosa of SPs were higher compared to HESNs. Furthermore, positive correlations between VDR and IL-10 mRNA RU in PBMCs and genital mucosa of HESNs were found. Finally, HBD-2 and HBD-3 mRNA RU were positively correlated with VDR mRNA expression in oral mucosa from HESNs. These results suggest that high levels of VitD and its receptor are associated with natural resistance to HIV-1 infection. Up-regulation of the anti-inflammatory IL-10, and the induction of anti-HIV-1 defensins in mucosa might be part of the mechanisms involved in this association. However, further studies are required to define causal associations
Auditory Feedback Control of Vocal Pitch during Sustained Vocalization: A Cross-Sectional Study of Adult Aging
Background: Auditory feedback has been demonstrated to play an important role in the control of voice fundamental frequency (F0), but the mechanisms underlying the processing of auditory feedback remain poorly understood. It has been well documented that young adults can use auditory feedback to stabilize their voice F0 by making compensatory responses to perturbations they hear in their vocal pitch feedback. However, little is known about the effects of aging on the processing of audio-vocal feedback during vocalization. Methodology/Principal Findings: In the present study, we recruited adults who were between 19 and 75 years of age and divided them into five age groups. Using a pitch-shift paradigm, the pitch of their vocal feedback was unexpectedly shifted 650 or 6100 cents during sustained vocalization of the vowel sound/u/. Compensatory vocal F0 response magnitudes and latencies to pitch feedback perturbations were examined. A significant effect of age was found such that response magnitudes increased with increasing age until maximal values were reached for adults 51–60 years of age and then decreased for adults 61–75 years of age. Adults 51–60 years of age were also more sensitive to the direction and magnitude of the pitch feedback perturbations compared to younger adults. Conclusion: These findings demonstrate that the pitch-shift reflex systematically changes across the adult lifespan. Understanding aging-related changes to the role of auditory feedback is critically important for our theoretica
Evaluating alternate models to estimate genetic parameters of calving traits in United Kingdom Holstein-Friesian dairy cattle
<p>Abstract</p> <p>Background</p> <p>The focus in dairy cattle breeding is gradually shifting from production to functional traits and genetic parameters of calving traits are estimated more frequently. However, across countries, various statistical models are used to estimate these parameters. This study evaluates different models for calving ease and stillbirth in United Kingdom Holstein-Friesian cattle.</p> <p>Methods</p> <p>Data from first and later parity records were used. Genetic parameters for calving ease, stillbirth and gestation length were estimated using the restricted maximum likelihood method, considering different models i.e. sire (−maternal grandsire), animal, univariate and bivariate models. Gestation length was fitted as a correlated indicator trait and, for all three traits, genetic correlations between first and later parities were estimated. Potential bias in estimates was avoided by acknowledging a possible environmental direct-maternal covariance. The total heritable variance was estimated for each trait to discuss its theoretical importance and practical value. Prediction error variances and accuracies were calculated to compare the models.</p> <p>Results and discussion</p> <p>On average, direct and maternal heritabilities for calving traits were low, except for direct gestation length. Calving ease in first parity had a significant and negative direct-maternal genetic correlation. Gestation length was maternally correlated to stillbirth in first parity and directly correlated to calving ease in later parities. Multi-trait models had a slightly greater predictive ability than univariate models, especially for the lowly heritable traits. The computation time needed for sire (−maternal grandsire) models was much smaller than for animal models with only small differences in accuracy. The sire (−maternal grandsire) model was robust when additional genetic components were estimated, while the equivalent animal model had difficulties reaching convergence.</p> <p>Conclusions</p> <p>For the evaluation of calving traits, multi-trait models show a slight advantage over univariate models. Extended sire models (−maternal grandsire) are more practical and robust than animal models. Estimated genetic parameters for calving traits of UK Holstein cattle are consistent with literature. Calculating an aggregate estimated breeding value including direct and maternal values should encourage breeders to consider both direct and maternal effects in selection decisions.</p
Low vitamin D status is associated with systemic and gastrointestinal inflammation in dogs with a chronic enteropathy
Vitamin D is traditionally known for its role in calcium homeostasis and bone metabolism.
However, it has been demonstrated that numerous types of cells express the vitamin D
receptor and it is now clear that the physiological roles of vitamin D extend beyond the
maintenance of skeletal health. Vitamin D insufficiency, which is typically assessed by
measuring the major circulating form of vitamin D, 25 hydroxyvitamin D (25(OH)D), has
been associated with a number of disorders in people including hypertension, diabetes,
cardiovascular diseases, cancer, autoimmune conditions and infectious diseases. Meta-analyses
have demonstrated that serum 25(OH)D concentrations are an important predictor
of survival in people with a wide variety of illnesses and have been linked to all-cause
mortality in the general human population.
The role of vitamin D in non-skeletal disorders in cats and dogs is poorly understood. This is
surprising since cats and dogs could act as excellent models for probing the biology of
vitamin D. Vitamin D status in people is largely dependent on cutaneous production of
vitamin D. This is influenced by many factors such as season, latitude and exposure to
ultraviolet (UV) radiation. The interpretation of human studies investigating the effects
vitamin D status on disease outcomes are therefore influenced by a number of confounding
variables. Unlike humans, domesticated cats and dogs do not produce vitamin D cutaneously
and obtain vitamin D only from their diet. The physiological functions and regulation of
vitamin D are otherwise similar to humans. Most pets are fed commercial diets containing a
relatively standard amount of vitamin D. Consequently, companion animals are attractive
model systems in which to examine the relationship vitamin D status and health outcomes.
Furthermore, spontaneously occurring model systems which did not require disease to be
induced in healthy animals would allow the numbers of animals used in scientist research to
be reduced.
This thesis aimed to define vitamin D homeostasis in companion animals in three disease
settings; in cats with feline immunodeficiency virus (FIV) infection, dogs with chronic
enteropathies (CE) and in hospitalised ill cats. Additional aims were to assess the prognostic
significance of serum 25(OH)D concentrations in companion animals and the relationship
between serum 25(OH)D concentrations and markers of inflammation. The hypothesis of
this thesis was that vitamin status D would negatively correlate with presence of disease,
markers of inflammation and disease outcomes. As similar findings have been demonstrated
in human medicine, the hypothesis was that cats and dogs would be suitable models to
investigate the role of vitamin D in human disease.
This thesis demonstrates that in dogs with a CE serum 25(OH)D concentrations are
negatively correlated with inflammation and are predictive of clinical outcomes. Vitamin D
status was also lower in cats with FIV and importantly vitamin D status was predictive of
short term mortality in hospitalised ill cats. This research will be of interest to veterinary
surgeons and opens the possibility for clinical trials which examine if low vitamin D status is
causally associated with ill health and whether vitamin D supplementation results in superior
treatment outcomes in companion animals. This thesis also demonstrates the potential of cats
and dogs as model systems in which to examine the role of vitamin D in human health
- …