METHANOGENESIS IN RABBIT CAECUM AS AFFECTED BY THE FERMENTATION PATTERN: IN VITRO AND IN VIVO MEASUREMENTS

[EN] Methane formation and caecal fermentation patterns were studied in vivo and in vitro in 16 white New Zealand rabbits (70-80 d and 2.27 ± 0.064 kg) allocated to four diets formulated to have a similar neutral detergent fibre (33.8±0.53%) and protein (17.7±0.33%) content, with two different fibre sources (alfalfa hay, AH or sugar beet pulp, SP) and starch (wheat or maize). Animals received the diet for 16 to 20 days before methane production was measured in vivo in a respiratory chamber. Animals were subsequently slaughtered at approximately 9:00 and caecal contents were sampled and used as inoculum for in vitro incubations to determine gas and methane production. Volatile fatty acid (VFA) and purine base (PB) concentrations were determined from both caecal content and incubation medium after 6 h. Total VFA concentration in caecal content decreased (P<0.05) in rabbits fed AH-maize diet compared with rabbits fed AH-wheat and SP-maize diets (37.7 vs. 59.6 mM), with those fed SP-wheat showing an intermediate value (53.0 mM). Fermentation pattern was affected when maize was the source of starch compared to wheat, with lower acetate (0.72 vs. 0.79; P<0.01) and higher butyrate (0.19 vs. 0.14; P<0.001) molar proportions. Fermentation in vivo vs. in vitro showed some differences (molar proportions of acetate, 0.76 vs. 0.73, P<0.001, and propionate, 0.069 vs. 0.091, P<0.001, in vivo and in vitro, respectively), probably due to differences in pH (6.0 vs. 6.7 in vivo and in vitro; P<0.001). Only 2 out of 16 rabbits produced a substantial volume of methane in vivo (on average, 12.6 ml/BW0.75/d or 0.56 mmol/BW0.75/d), showing a high inter-individual variability that hindered comparison of treatment differences. In contrast, methane was detected in vitro in all cases and volumes were more homogenous, a higher formation (P<0.05) being observed with maize compared to wheat. A similar effect was shown in total gas production. The low methane production and H2 recovery suggest the importance of H2 disposal mechanisms other than methanogenesis, such as reductive acetogenesis. PB concentration in caecal content and the incubation medium, as an index of microbial concentration, was highest when SP was added with maize (P<0.05).For the realisation of this work, A. Belenguer and L. Abecia received grants from the Spanish Ministry of Education and Science and the Basque Government, respectively. This work was financed by the Diputación General de Aragón through project DGA PM095/2006.Belenguer, A.; Fondevila, M.; Balcells, J.; Abecia, L.; Lachica, M.; Carro, M. (2011). METHANOGENESIS IN RABBIT CAECUM AS AFFECTED BY THE FERMENTATION PATTERN: IN VITRO AND IN VIVO MEASUREMENTS. World Rabbit Science. 19(2):75-83. doi:10.4995/wrs.2011.826SWORD758319

Chronic renal disease in Spain: Prevalence and related factors in persons with diabetes mellitus older than 64 years

Introducción La diabetes mellitus tipo 2 y la enfermedad renal crónica (ERC) son afecciones de elevada prevalencia en personas = 65 años y constituyen un importante problema de salud pública. Objetivos Conocer la prevalencia de la ERC, sus categorías y su relación con diversos factores demográficos y clínicos, en pacientes ancianos con diabetes mellitus tipo 2 en España. Métodos Estudio epidemiológico, observacional, transversal, multicéntrico, ámbito nacional. Se incluyeron pacientes con diabetes mellitus tipo 2 conocida, edad = 65 años atendidos en Atención Primaria. Se recogieron variables demográficas, antropométricas y analíticas de los últimos 12 meses, incluyendo el cociente albúmina-creatinina y el filtrado glomerular estimado para evaluar la función renal. Resultados La prevalencia de ERC fue del 37, 2% (IC95%, 34, 1-40, 3%), de insuficiencia renal del 29, 7% (IC95%, 26, 8-32, 6%) y de elevación de la albuminuria del 20, 6% (IC95%, 17, 3-23, 9%), moderadamente elevada 17, 8% (IC95%, 14, 7-20, 9%), severamente elevada 2, 8% (IC95%, 1, 4-4, 2%). La prevalencia de las categorías de ERC fueron: G1 1, 3% (IC95%, 0, 6-2%), G2 6, 2% (IC95%, 4, 6-7, 8%), G3a 17, 2% (IC95%, 14, 8-19, 6%), G3b 9, 8% (IC95%, 7, 9-11, 7%), G4 2% (IC95%, 1, 1-2, 9%) y G5 0, 7% (IC95%, 0, 2-1, 2%). En el análisis multivariante, después de ajustar por el resto de variables, la ERC se asoció a mayor edad OR 5, 13, (IC95%, 3, 15-8, 35), alta comorbilidad OR 3, 36 (IC95%, 2, 2-5, 12) y la presencia de tratamiento antihipertensivo OR 2, 43 (IC95%, 1, 48-4, 02). Conclusiones La ERC es frecuente en la población diabética = 65 años y se asocia con mayor edad, alta comorbilidad e hipertensión tratada. No se ha encontrado asociación con el género y años de evolución de la diabetes. Introduction: Type 2 diabetes mellitus and chronic kidney disease (CKD) are conditions which have a high prevalence in individuals =65 years of age and represent a major public health problem. Objectives: To determine the prevalence of CKD, its categories and its relationship with various demographic and clinical factors in elderly patients with type 2 diabetes mellitus in Spain. Methods: Observational, cross-sectional, multicenter, Spanish epidemiological study. Patients with known type 2 diabetes mellitus, age =65 years of age treated in Primary Care were included. We collected demographic, anthropometric and analytical variables from the previous 12 months, including the albumin-to-creatinine ratio and estimated glomerular filtration rate to evaluate renal function. Results: The prevalence of CKD was 37.2% (95% CI, 34.1–40.3%), renal failure was 29.7% (95% CI, 26.8–32.6%) and increased albuminuria was 20.6% (95% CI, 17.3–23.9%), moderately increased albuminuria was 17.8% (95% CI, 14.7–20.9%) and severely increased albuminuria was 2.8% (95% CI, 1.4–4.2%). In turn, the prevalence of CKD categories were: G1 1.3% (95% CI, 0.6–2%), G2 6.2% (95% CI, 4.6–7.8%), G3a 17.2% (95% CI, 14.8–19.6%), G3b 9.8% (95% CI, 7.9–11.7%), G4 2% (95% CI, 1.1–2.9%) and G5 0.7% (95% CI, 0.2–1.2%). In the multivariate analysis, after adjusting for the remaining variables, CKD was associated with elderly age (OR 5.13, 95% CI, 3.15–8.35), high comorbidity (OR 3.36, 95% CI, 2.2–5.12) and presence of antihypertensive treatment (OR 2.43, 95% CI, 1.48–4.02). Conclusions: CKD is frequent in the diabetic population =65 years of age and is associated with elderly age, high comorbidity and with treated hypertension. No relationship has been found with gender and time in years since onset of diabetes

Formula for the nnth kk-Generalized Fibonacci-like Number

In this paper we provided a formula for the $n$th term of the $k$-generalized Fibonacci-like sequence, a generalization of the well-known Fibonacci sequence, having $k$ arbitrary initial terms, where the succeeding terms are obtained by adding its previous $k$ terms. The formula for the $n$th term of the $k$-generalized Fibonacci-like sequence was obtained by observing patterns in the derived formula for the nth term of the Fibonacci-like, Tribonacci-like, and Tetrabonacci-like sequence. The formula for the $k$-generalized Fibonacci sequence was also derived and was used in the process of proving the main result of this paper

Enfermedad renal crónica en España: prevalencia y factores relacionados en personas con diabetes mellitus mayores de 64 años

Introducción: La diabetes mellitus tipo 2 y la enfermedad renal crónica (ERC) son afecciones de elevada prevalencia en personas = 65 años y constituyen un importante problema de salud pública. Objetivos: Conocer la prevalencia de la ERC, sus categorías y su relación con diversos factores demográficos y clínicos, en pacientes ancianos con diabetes mellitus tipo 2 en España. Métodos: Estudio epidemiológico, observacional, transversal, multicéntrico, ámbito nacional. Se incluyeron pacientes con diabetes mellitus tipo 2 conocida, edad = 65 años atendidos en Atención Primaria. Se recogieron variables demográficas, antropométricas y analíticas de los últimos 12 meses, incluyendo el cociente albúmina-creatinina y el filtrado glomerular estimado para evaluar la función renal. Resultados: La prevalencia de ERC fue del 37, 2% (IC95%, 34, 1-40, 3%), de insuficiencia renal del 29, 7% (IC95%, 26, 8-32, 6%) y de elevación de la albuminuria del 20, 6% (IC95%, 17, 3-23, 9%), moderadamente elevada 17, 8% (IC95%, 14, 7-20, 9%), severamente elevada 2, 8% (IC95%, 1, 4-4, 2%). La prevalencia de las categorías de ERC fueron: G1 1, 3% (IC95%, 0, 6-2%), G2 6, 2% (IC95%, 4, 6-7, 8%), G3a 17, 2% (IC95%, 14, 8-19, 6%), G3b 9, 8% (IC95%, 7, 9-11, 7%), G4 2% (IC95%, 1, 1-2, 9%) y G5 0, 7% (IC95%, 0, 2-1, 2%). En el análisis multivariante, después de ajustar por el resto de variables, la ERC se asoció a mayor edad OR 5, 13, (IC95%, 3, 15-8, 35), alta comorbilidad OR 3, 36 (IC95%, 2, 2-5, 12) y la presencia de tratamiento antihipertensivo OR 2, 43 (IC95%, 1, 48-4, 02). Conclusiones: La ERC es frecuente en la población diabética = 65 años y se asocia con mayor edad, alta comorbilidad e hipertensión tratada. No se ha encontrado asociación con el género y años de evolución de la diabetes. Introduction: Type 2 diabetes mellitus and chronic kidney disease (CKD) are conditions which have a high prevalence in individuals >= 65 years of age and represent a major public health problem. Objectives: To determine the prevalence of CKD, its categories and its relationship with various demographic and clinical factors in elderly patients with type 2 diabetes mellitus in Spain. Methods: Observational, cross-sectional, multicenter, Spanish epidemiological study. Patients with known type 2 diabetes mellitus, age >= 65 years of age treated in Primary Care were included. We collected demographic, anthropometric and analytical variables from the previous 12 months, including the albumin-to-creatinine ratio and estimated glomerular filtration rate to evaluate renal function. Results: The prevalence of CKD was 37.2% (95% CI, 34.1-40.3%), renal failure was 29.7% (95% CI, 26.8-32.6%) and increased albuminuria was 20.6% (95% CI, 17.3-23.9%), moderately increased albuminuria was 17.8% (95% CI, 14.7-20.9%) and severely increased albuminuria was 2.8% (95% CI, 1.4-4.2%). In turn, the prevalence of CKD categories were: G1 1.3% (95% CI, 0.6-2%), G2 6.2% (95% CI, 4.6-7.8%), G3a 17.2% (95% CI, 14.8-19.6%), G3b 9.8% (95% CI, 7.9-11.7%), G4 2% (95% CI, 1.1-2.9%) and G5 0.7% (95% CI, 0.2-1.2%). In the multivariate analysis, after adjusting for the remaining variables, CKD was associated with elderly age (OR 5.13, 95% CI, 3.15-8.35), high comorbidity (OR 3.36. 95% CI, 2.2-5.12) and presence of antihypertensive treatment (OR 2.43. 95% CI, 1.48-4.02). Conclusions: CKD is frequent in the diabetic population >= 65 years of age and is associated with elderly age, high comorbidity and with treated hypertension. No relationship has been found with gender and time in years since onset of diabetes

Microglia-synapse engulfment via PtdSer-TREM2 ameliorates neuronal hyperactivity in Alzheimer's disease models

Neuronal hyperactivity is a key feature of early stages of Alzheimer's disease (AD). Genetic studies in AD support that microglia act as potential cellular drivers of disease risk, but the molecular determinants of microglia-synapse engulfment associated with neuronal hyperactivity in AD are unclear. Here, using super-resolution microscopy, 3D-live imaging of co-cultures, and in vivo imaging of lipids in genetic models, we found that spines become hyperactive upon Aβ oligomer stimulation and externalize phosphatidylserine (ePtdSer), a canonical "eat-me" signal. These apoptotic-like spines are targeted by microglia for engulfment via TREM2 leading to amelioration of Aβ oligomer-induced synaptic hyperactivity. We also show the in vivo relevance of ePtdSer-TREM2 signaling in microglia-synapse engulfment in the hAPP NL-F knock-in mouse model of AD. Higher levels of apoptotic-like synapses in mice as well as humans that carry TREM2 loss-of-function variants were also observed. Our work supports that microglia remove hyperactive ePtdSer+ synapses in Aβ-relevant context and suggest a potential beneficial role for microglia in the earliest stages of AD

Reduction of the frequency of herbaceous roots as an effect of soil compaction induced by heavy grazing in rangelands of SW Spain

Rangelands in SW Spain constitute the most extensive ranching system on the Iberian Peninsula. During the last few decades, a significant increase in livestock numbers, along with a progressive substitution of cattle for sheep, have led to land degradation processes such as the reduction of grass cover and increased soil compaction in heavily grazed areas. Nevertheless, a better understanding of how soil compaction affects grass production is still needed. In this study, some of the effects of soil compaction due to heavy grazing are analysed, mainly the reduction of the frequency of herbaceous roots and its relationships with bulk density and soil penetration resistance. The study was carried out in 22 fenced areas grazed under different intensities (animal stocking rates: 0.19-15.76 AU ha−1). Undisturbed soil core and bulk samples were collected at 3 depth intervals in order to determine select soil properties (texture, organic matter content, and bulk density). Additionally, soil penetration resistance was quantified at 890 random points at different depths and soil moisture contents. Frequency of herbaceous roots was estimated for each soil horizon in 47 soil profiles and categorized into 4 classes: none, few, common and many. Results showed negative relationships between bulk density (> 10 cm depth) and the content of soil organic matter from 0 to 5 cm (r =−0.061, p < 0.05) and 5-10 m depth (r = −0.824, p < 0.005). Furthermore, a tendency for decreasing mean values of soil penetration resistance as the frequency of herbaceous roots increased was also observed. The values observed confirm that soil compaction provoked by an excessive number of animals reduced the quantity of herbaceous roots. The value of 2 MPa traditionally accepted as restrictive for root growth is discussed. Findings presented here could be of interest for policy makers and farm owners to guide decisions about optimum animal stocking rates

Lethal Antibody Enhancement of Dengue Disease in Mice Is Prevented by Fc Modification

Immunity to one of the four dengue virus (DV) serotypes can increase disease severity in humans upon subsequent infection with another DV serotype. Serotype cross-reactive antibodies facilitate DV infection of myeloid cells in vitro by promoting virus entry via Fcγ receptors (FcγR), a process known as antibody-dependent enhancement (ADE). However, despite decades of investigation, no in vivo model for antibody enhancement of dengue disease severity has been described. Analogous to human infants who receive anti-DV antibodies by transplacental transfer and develop severe dengue disease during primary infection, we show here that passive administration of anti-DV antibodies is sufficient to enhance DV infection and disease in mice using both mouse-adapted and clinical DV isolates. Antibody-enhanced lethal disease featured many of the hallmarks of severe dengue disease in humans, including thrombocytopenia, vascular leakage, elevated serum cytokine levels, and increased systemic viral burden in serum and tissue phagocytes. Passive transfer of a high dose of serotype-specific antibodies eliminated viremia, but lower doses of these antibodies or cross-reactive polyclonal or monoclonal antibodies all enhanced disease in vivo even when antibody levels were neutralizing in vitro. In contrast, a genetically engineered antibody variant (E60-N297Q) that cannot bind FcγR exhibited prophylactic and therapeutic efficacy against ADE-induced lethal challenge. These observations provide insight into the pathogenesis of antibody-enhanced dengue disease and identify a novel strategy for the design of therapeutic antibodies against dengue

Mitochondrial dysfunction is a key pathological driver of early stage Parkinson’s

Background:The molecular drivers of early sporadic Parkinson’s disease (PD) remain unclear, and the presence of widespread end stage pathology in late disease masks the distinction between primary or causal disease-specific events and late secondary consequences in stressed or dying cells. However, early and mid-stage Parkinson’s brains (Braak stages 3 and 4) exhibit alpha-synuclein inclusions and neuronal loss along a regional gradient of severity, from unaffected-mild-moderate-severe. Here, we exploited this spatial pathological gradient to investigate the molecular drivers of sporadic PD. Methods: We combined high precision tissue sampling with unbiased large-scale profiling of protein expression across 9 brain regions in Braak stage 3 and 4 PD brains, and controls, and verified these results using targeted proteomic and functional analyses. Results: We demonstrate that the spatio-temporal pathology gradient in early-mid PD brains is mirrored by a biochemical gradient of a changing proteome. Importantly, we identify two key events that occur early in the disease, prior to the occurrence of alpha-synuclein inclusions and neuronal loss: (i) a metabolic switch in the utilisation of energy substrates and energy production in the brain, and (ii) perturbation of the mitochondrial redox state. These changes may contribute to the regional vulnerability of developing alpha-synuclein pathology. Later in the disease, mitochondrial function is affected more severely, whilst mitochondrial metabolism, fatty acid oxidation, and mitochondrial respiration are affected across all brain regions. Conclusions: Our study provides an in-depth regional profile of the proteome at different stages of PD, and highlights that mitochondrial dysfunction is detectable prior to neuronal loss, and alpha-synuclein fibril deposition, suggesting that mitochondrial dysfunction is one of the key drivers of early disease

Rearrangement of Retinogeniculate Projection Patterns after Eye-Specific Segregation in Mice

It has been of interest whether and when the rearrangement of neuronal circuits can be induced after projection patterns are formed during development. Earlier studies using cats reported that the rearrangement of retinogeniculate projections could be induced even after eye-specific segregation has occurred, but detailed and quantitative characterization of this rearrangement has been lacking. Here we delineate the structural changes of retinogeniculate projections in the C57BL/6 mouse in response to monocular enucleation (ME) after eye-specific segregation. When ME was performed after eye-specific segregation, rearrangement of retinogeniculate axons in the dorsal lateral geniculate nucleus (dLGN) was observed within 5 days. Although this rearrangement was observed both along the dorsomedial-ventrolateral and outer-inner axes in the dLGN, it occurred more rapidly along the outer-inner axis. We also examined the critical period for this rearrangement and found that the rearrangement became almost absent by the beginning of the critical period for ocular dominance plasticity in the primary visual cortex. Taken together, our findings serve as a framework for the assessment of phenotypes of genetically altered mouse strains as well as provide insights into the mechanisms underlying the rearrangement of retinogeniculate projections

Identification of a Carboxyl group at the Active Site of Barley MaIt Phosphatase

The dependence of the maximal velocity, Vm with pH for barley malt phosphatase has been studied from pH 4.0 to 5.4. The data show that an ionizable group in the enzyme-substrate complex with a pK2 of 4-4.6 is important for enzymic activity. These results suggest strongly the involvement of a carboxyl group of a glutamic or aspartic acid residue at the active site of this enzyme