Gravitational lensing model degeneracies: Is steepness all-important?

In gravitational lensing, steeper mass profiles generically produce longer time delays but smaller magnifications, without necessarily changing the image positions or magnification ratios between different images. This is well known. We find in this paper, however, that even if steepness is fixed, time delays can still have significant model dependence, which we attribute to shape modeling degeneracies. This conclusion follows from numerical experiments with models of 35 galaxy lenses. We suggest that varying and twisting ellipticities, features that are explored by pixelated lens models but not so far by parametric models, have an important effect on time delays.Comment: To appear in Ap

Evaluación del desempeño reproductivo en vacas y vaquillonas cruza índica con protocolo convencional y J-Synch

The objective of this study was evaluate the reproductive performance of índics cross cows and heifers with a conventional protocol and prolonged proestrus in a breeding system at Chaco. Were used 264 cows without calf and 236 heifers with body condition 4 to 6 (scale 1-9). On day 0 a device with 0.5 g of progesterone (DIB) and 2 mg of estradiol benzoate was applied. Animals were randomly distributed into 2 groups: a) conventional: day 8: DIB was withdrawn, D-Cloprostenol (PG) (150μg) and estradiol cypionate (0.5 mg) were administered. Artificial insemination (AI) was performed 48 to 54 hours after withdrawal DIB. b) J-Synch: day 6 DIB was withdrawn, PG (150 μg) and equine chorionic gonadotropin (eCG) (300 or 400 IU) were applied in heifers and cows respectively. The sacro-coccygeal region was painted to determine estrus manifestation, performing AI on the unpainted ones at 60 h and 72 hand in those that were still painted at 72 h in addition to AI buserelin acetate (10 μg) was applied. Ultrasonography diagnosis was made 40 days post-AI. Using Chi 2 test were compared the effect of treatment (conventional vs. J-Synch without eCG) and category (heifer and cow) on the rates of pregnancy and in J-Synch (without vs. with eCG) in addition to estrus manifestation. No association was found between treatments evaluated with reproductive performance with pregnancies of 43% vs 54% in cows and 59% vs 51% in heifers with conventional and J-Synch respectively. In J-Synch of 52 and 56% in cows (54 vs 62%) and heifers (51 vs 50%) without and with eCG respectively. The general pregnancy was 55% in animals that showed estrus and 44% in those that did not. In conclusion, the cows had a tendency to perform better with J-Synch where the use of eCG had no influence on pregnancy.El objetivo de este estudio fue evaluar el desempeño reproductivo en vacas y vaquillonas cruza índica con protocolo convencional y de proestro alargado, en un sistema de cría de Chaco. Se utilizaron 264 vacas secas y 236 vaquillonas, con condición corporal 4 a 6 (escala 1-9). El día 0 se aplicó dispositivo con 0,5 g de progesterona (DIB) y 2 mg de benzoato de estradiol. Los animales se distribuyeron aleatoriamente en 2 grupos: a) convencional (día 8) se retiró DIB, administrándose D-Cloprostenol (PG) (150 μg) y cipionato de estradiol (0,5 mg). La inseminación artificial (IA) se realizó de 48 a 54 h del retiro, b) J-Synch: día 6 se retiró DIB, aplicándose PG (150 μg) y gonadotrofina coriónica equina (eCG: 300 y 400 UI) en vaquillonas y vacas, respectivamente. Se pintó la región sacrocoxígea para determinar manifestación de celo, inseminando a las 60 h y 72 h a las despintadas y en las que seguían pintadas a las 72 h además de IA se aplicó acetato de buserelina (10μg). El diagnóstico por ultrasonografía se efectuó 40 días post-IA. Mediante prueba Chi 2, 3 se comparó el efecto tratamiento (convencional vs J-Synch sin eCG) y categoría (vaquillona y vaca) sobre el porcentaje de preñez y en J-Synch (sin vs con eCG), además de manifestación de celo. No se encontró asociación de los tratamientos evaluados con el desempeño reproductivo, con preñeces del 43% vs 54% en vacas y en vaquillonas del 59% vs 51% con convencional y J-Synch, respectivamente. En J-Synch de 52 y 56%, en vacas (54 vs 62%) y vaquillonas (51 vs 50%) sin y con eCG, respectivamente. La preñez general fue de 55% en animales que manifestaron celo y 44% en aquellos que no lo hicieron. Como conclusión las vacas tuvieron una tendencia a desempeñarse mejor con J-Synch, donde la utilización de eCG no tuvo influencias sobre la preñez

Antemortem CSF Aβ42/Aβ40 ratio predicts Alzheimer's disease pathology better than Aβ42 in rapidly progressive dementias

Objective: Despite the critical importance of pathologically confirmed samples for biomarker validation, only a few studies have correlated CSF Aβ42 values in vivo with postmortem Alzheimer's disease (AD) pathology, while none evaluated the CSF Aβ42/Aβ40 ratio. We compared CSF Aβ42 and Aβ42/Aβ40 ratio as biomarkers predicting AD neuropathological changes in patients with a short interval between lumbar puncture and death. Methods: We measured CSF Aβ40 and Aβ42 and assessed AD pathology in 211 subjects with rapidly progressive dementia (RPD) and a definite postmortem diagnosis of Creutzfeldt-Jakob disease (n = 159), AD (n = 12), dementia with Lewy bodies (DLB, n = 4), AD/DLB mixed pathologies (n = 5), and various other pathologies (n = 31). Results: The score reflecting the severity of Aβ pathology showed a better correlation with ln(Aβ42/Aβ40) (R 2  = 0.506, β = −0.713, P < 0.001) than with ln(Aβ42) (R 2  = 0.206, β = −0.458, P < 0.001), which was confirmed after adjusting for covariates. Aβ42/Aβ40 ratio showed significantly higher accuracy than Aβ42 in the distinction between cases with or without AD pathology (AUC 0.818 ± 0.028 vs. 0.643 ± 0.039), especially in patients with Aβ42 levels ≤495 pg/mL (AUC 0.888 ± 0.032 vs. 0.518 ± 0.064). Using a cut-off value of 0.810, the analysis of Aβ42/Aβ40 ratio yielded 87.0% sensitivity, 88.2% specificity in the distinction between cases with an intermediate-high level of AD pathology and those with low level or no AD pathology. Interpretation: The present data support the use of CSF Aβ42/Aβ40 ratio as a biomarker of AD pathophysiology and noninvasive screener for Aβ pathology burden, and its introduction in the research diagnostic criteria for AD

The characterization of AD/PART co-pathology in CJD suggests independent pathogenic mechanisms and no cross-seeding between misfolded Aβ and prion proteins

Current evidence indicating a role of the human prion protein (PrP) in amyloid-beta (Aβ) formation or a synergistic effect between Aβ and prion pathology remains controversial. Conflicting results also concern the frequency of the association between the two protein misfolding disorders and the issue of whether the apolipoprotein E gene (APOE) and the prion protein gene (PRNP), the major modifiers of Aβ- and PrP-related pathologies, also have a pathogenic role in other proteinopathies, including tau neurofibrillary degeneration. Here, we thoroughly characterized the Alzheimer's disease/primary age-related tauopathy (AD/PART) spectrum in a series of 450 cases with definite sporadic or genetic Creutzfeldt-Jakob disease (CJD). Moreover, we analyzed: (i) the effect of variables known to affect CJD pathogenesis and the co-occurring Aβ- and tau-related pathologies; (II) the influence of APOE genotype on CJD pathology, and (III) the effect of AD/PART co-pathology on the clinical CJD phenotype. AD/PART characterized 74% of CJD brains, with 53.3% and 8.2% showing low or intermediate-high levels of AD pathology, and 12.4 and 11.8% definite or possible PART. There was no significant correlation between variables affecting CJD (i.e., disease subtype, prion strain, PRNP genotype) and those defining the AD/PART spectrum (i.e., ABC score, Thal phase, prevalence of CAA and Braak stage), and no difference in the distribution of APOE ε4 and ε2 genotypes among CJD subtypes. Moreover, AD/PART co-pathology did not significantly affect the clinical presentation of typical CJD, except for a tendency to increase the frequency of cognitive symptoms. Altogether, the present results seem to exclude an increased prevalence AD/PART co-pathology in sporadic and genetic CJD, and indicate that largely independent pathogenic mechanisms drive AD/PART and CJD pathology even when they coexist in the same brain

CSF SerpinA1 in Creutzfeldt\u2013Jakob disease and frontotemporal lobar degeneration

Objective: SerpinA1 (alpha-1 antitrypsin) is an acute inflammatory protein, which seems to play a role in neurodegeneration and neuroinflammation. In Alzheimer\u2019s disease and synucleinopathies, SerpinA1 is overexpressed in the brain and the cerebrospinal fluid (CSF) showing abnormal patterns of its charge isoforms. To date, no comprehensive studies explored SerpinA1 CSF isoforms in Creutzfeldt\u2013Jakob disease (CJD) and frontotemporal lobar degeneration (FTLD). Methods: Using a capillary isoelectric focusing immunoassay, we analyzed CSF SerpinA1 isoforms in control cases (n = 31) and patients with a definite or probable diagnosis of CJD (n=77) or FTLD (n = 30), belonging to several disease subtypes. Results: The overall SerpinA1 signal was significantly higher than in controls in CJD subtypes linked to abnormal prion protein (PrPSc) type 1, such as sporadic CJD (sCJD) MM(V)1, and in FTLD-TDP. Moreover, CJD linked to PrPSc type 1 and FTLD-TAU groups showed a significant relative increase of acidic and basic isoforms in comparison with controls, thereby forming two distinct SerpinA1 isoform profiles. Interpretation: CJD linked to PrPSc type 1 and FTLD show a differential upregulation and post-translational modifications of CSF SerpinA1. Further studies are needed to clarify whether these findings may reflect a common, albeit disease-specific, pathogenetic mechanism related to neurodegeneration

Effects of different experimental conditions on the PrPSc core generated by protease digestion: implications for strain typing and molecular classification of CJD.

The discovery of molecular subtypes of the pathological prion protein PrPSc has provided the basis for a novel classification of human transmissible spongiform encephalopathies (TSEs) and a potentially powerful method for strain typing. However, there is still a significant disparity regarding the understanding and nomenclature of PrPSc types. In addition, it is still unknown whether a specific PrPSc type is associated with each TSE phenotypic variant. In sporadic Creutzfeldt-Jakob disease (sCJD), five disease phenotypes are known, but only two major types of PrPSc, types 1 and 2, have been consistently reproduced. We further analyzed PrPSc properties in sCJD and variant CJD using a high resolution gel electrophoresis system and varying experimental conditions. We found that pH varies among CJD brain homogenates in standard buffers, thereby influencing the characteristics of protease-treated PrPSc. We also show that PrPSc type 1 and type 2 are heterogeneous species which can be further distinguished into five molecular subtypes that fit the current histopathological classification of sCJD variants. Our results shed light on previous disparities in PrPSc typing, provide a refined classification of human PrPSc types, and support the notion that the pathological TSE phenotype is related to PrPSc structure

Diferencias de pesos entre terneros Braford enteros y castrados a diferentes edades

We compared entire versus castrated male Braford calves, at different ages of castration, with the objective to evaluate this effect on growth by means of the total and daily weight gain. Twenty-eight Braford male suckling calves, were used. Animals were randomly divided into groups of 7 individuals: C45: castrated at 45 days of age; E45: entire, with 45 days of age; C90: castrated at 90 days of age and E90: entire, with 90 days of age. Individual weights were recorded on day 0 (castration’s day) and then on days 15, 30 and 45. Castration was performed by means of surgery. The studied variables were total gain (GT, kg of live weight) and average daily gain (GMD, kg/day). Descriptive statistics, analysis of variance (ANOVA) and Duncan’s test (p<0.05) were performed, considering as the main effect the age of castration (45 and 90 days), with the intact males as controls. The means for GT were: C45: 34.86 kg; E45: 37.29 kg; C90: 51.14 kg and E90: 44.29 kg. For GMD, they were: C45: 0.58 kg; E45: 0.62 kg; C90: 0.85 kg and E90: 0.74 kg. The ANOVA test showed significant differences for both variables, GT (p=0.0156) and GMD (p=0.0157), with C90 being the higher, considering the other groups. In particular, E90 group obtained intermediate values between C90 and calves of 45 days. Between C45 and E45, no significant differences were found for both variables. We conclude that a recommended castration time should be close to three months of age, since at 45 days of age live weight was more affected by the surgical technique.Se compararon terneros braford machos enteros y castrados, con diferentes edades de esterilización, con el objetivo de evaluar este efecto en el crecimiento mediante la ganancia total y diaria de peso. Se utilizaron 28 terneros al pie de madre en campo natural. Se dividieron aleatoriamente en grupos de 7 individuos: C45: castrados a los 45 días de edad; E45: enteros con 45 días de edad; C90: castrados a los 90 días de edad y E90: enteros con 90 días de edad. Los pesos se registraron individualmente el día 0 (día de la castración) y posteriormente los días 15, 30 y 45. La técnica de castración se realizó por cirugía cruenta. Las variables estudiadas para el peso vivo fueron: ganancia total (GT, kg) y ganancia media diaria (GMD, kg/día). Se obtuvieron estadísticas descriptivas, análisis de varianza (ANOVA) y test de Duncan (p<0,05), tomándose como efecto principal la edad de castración (45 y 90 días), obrando los enteros como testigos. Las medias para GT fueron: C45: 34,86 kg; E45: 37,29 kg; C90: 51,14 kg y E90: 44,29 kg. Para GMD fueron: C45: 0,58 kg; E45: 0,62 kg; C90: 0,85 kg y E90: 0,74 kg. El ANOVA arrojó diferencias significativas para ambas variables: GT (p=0,0156) y GMD (p=0,0157), siendo C90 superior al resto de los grupos. Por su parte, E90 obtuvo valoresintermedios entre C90 y los terneros de 45 días. Entre C45 y E45 no se hallaron diferenciassignificativas en ambas variables. Se concluye que el momento elegido para la castracióndebe ser cercano a los tres meses, ya que a los 45 días el peso vivo resultó más afectado porla cirugía