Oxidation States, Thouless' Pumps, and Nontrivial Ionic Transport in Nonstoichiometric Electrolytes

Thouless' quantization of adiabatic particle transport permits one to associate an integer topological charge with each atom of an electronically gapped material. If these charges are additive and independent of atomic positions, they provide a rigorous definition of atomic oxidation states and atoms can be identified as integer-charge carriers in ionic conductors. Whenever these conditions are met, charge transport is necessarily convective; i.e., it cannot occur without substantial ionic flow, a transport regime that we dub trivial. We show that the topological requirements that allow these conditions to be broken are the same that would determine a Thouless' pump mechanism if the system were subject to a suitably defined time-periodic Hamiltonian. The occurrence of these requirements determines a nontrivial transport regime whereby charge can flow without any ionic convection, even in electronic insulators. These results are first demonstrated with a couple of simple molecular models that display a quantum-pump mechanism upon introduction of a fictitious time dependence of the atomic positions along a closed loop in configuration space. We finally examine the impact of our findings on the transport properties of nonstoichiometric alkali-halide melts, where the same topological conditions that would induce a quantum-pump mechanism along certain closed loops in configuration space also determine a nontrivial transport regime such that most of the total charge current results to be uncorrelated from the ionic ones

Factors affecting variations in the detailed fatty acid profile of Mediterranean buffalo milk determined by 2-dimensional gas chromatography

Buffalo milk is the world\u2019s second most widely pro- duced milk, and increasing attention is being paid to its composition, particularly the fatty acid profile. The ob- jectives of the present study were (1) to characterize the fatty acid composition of Mediterranean buffalo milk, and (2) to investigate potential sources of variation in the buffalo milk fatty acid profile. We determined the profile of 69 fatty acid traits in 272 individual samples of Mediterranean buffalo milk using gas chromatogra- phy. In total, 51 individual fatty acids were identified: 24 saturated fatty acids, 13 monounsaturated fatty acids, and 14 polyunsaturated fatty acids. The ma- jor individual fatty acids in buffalo milk were in the order 16:0, 18:1 cis-9, 14:0, and 18:0. Saturated fatty acids were the predominant fraction in buffalo milk fat (70.49%); monounsaturated and polyunsaturated fatty acids were at 25.95 and 3.54%, respectively. Adopt- ing a classification based on carbon-chain length, we found that medium-chain fatty acids (11\u201316 carbons) represented the greater part (53.7%) of the fatty acid fraction of buffalo milk, whereas long-chain fatty acids (17\u201324 carbons) and short-chain fatty acids (4\u201310 car- bons) accounted for 32.73 and 9.72%, respectively. The n-3 and n-6 fatty acids were 0.46 and 1.77%, respec- tively. The main conjugated linoleic acid, rumenic acid, represented 0.45% of total milk fatty acids. Herd/test date and stage of lactation were confirmed as important sources of variation in the fatty acid profile of buffalo milk. The percentages of short-chain and medium-chain fatty acids in buffalo milk increased in early lactation (+0.6 and +3.5%, respectively), whereas long-chain fatty acids decreased ( 124.2%). The only exception to this pattern was butyric acid, which linearly decreased from the beginning of lactation, confirmation that its synthesis is independent of malonyl-CoA. These results seem to suggest that in early lactation the mobilization of energy reserves may have less influence on the fatty acid profile of buffalo milk than that of cow milk, prob- ably due to a shorter and less severe period of negative energy balance. Parity affected the profiles of a few traits and had the most significant effects on branched- chain fatty acids. This work provided a detailed over- view of the fatty acid profile in buffalo milk including also those fatty acids present in small concentrations, which may have beneficial effects for human health. Our results contributed also to increase the knowledge about the effects of some of the major factors affecting buffalo production traits and fatty acid concentrations in milk, and consequently its technological and nutritional properties

Genetic and genomic analyses of latent variables related to the milk fatty acid profile, milk composition, and udder health in dairy cattle

The aim of this study was to perform genetic, genome-wide association (GWAS), and gene-set enrichment analyses with latent variables related to milk fatty acid profile (i.e., fatty acids factor scores; FAF), milk composition, and udder health in a cohort of 1,158 Italian Brown Swiss cows. The phenotypes under study were 12 FAF previously identified through factor analysis and classified as follows: de novo FA (F1), branched-chain FA-milk yield (F2), biohydrogenation (F3), long-chain fatty acids (F4), desaturation (F5), short-chain fatty acids (F6), milk protein and fat contents (F7), odd fatty acids (F8), conjugated linoleic acids (F9), linoleic acid (F10), udder health (F11) and vaccelenic acid (F12). (Co)variance components were estimated for factor scores using a Bayesian linear animal model via Gibbs sampling. The animals were genotyped with the Illumina BovineSNP50 BeadChip v.2 (Illumina Inc., San Diego, CA). A single marker regression model was fitted for GWAS analysis. The gene-set enrichment analysis was run on the GWAS results using the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway databases to identify the ontologies and pathways associated with the FAF. Marginal posterior means of the heritabilities of the aforementioned FAF ranged from 0.048 for F12 to 0.310 for F5. Factors F1 and F6 had the highest number of relevant genetic correlations with the other traits. The genomic analysis detected a total of 39 significant SNP located on 17 Bos taurus autosomes. All latent variables produced signals except for F2 and F10. The traits with the highest number of significant associations were F11 (17) and F12 (7). Gene-set enrichment analyses identified significant pathways (false discovery rate 5%) for F3 and F7. In particular, systemic lupus erythematosus was enriched for F3, whereas the MAPK (mitogen-activated protein kinase) signaling pathway was overrepresented for F7. The results support the existence of important and exploitable genetic and genomic variation in these latent explanatory phenotypes. Information acquired might be exploited in selection programs and when designing further studies on the role of the putative candidate genes identified in the regulation of milk composition and udder health

Longitudinal transcriptomic and genetic landscape of radiotherapy response in canine melanoma

Canine malignant melanoma (MM) is a highly aggressive tumour with a low survival rate and represents an ideal spontaneous model for the human counterpart. Considerable progress has been recently obtained, but the therapeutic success for canine melanoma is still challenging. Little is known about the mechanisms beyond pathogenesis and melanoma development, and the molecular response to radiotherapy has never been explored before. A faster and deeper understanding of cancer mutational processes and developing mechanisms are now possible through next generation sequencing technologies. In this study, we matched whole exome and transcriptome sequencing in four dogs affected by MM at diagnosis and at disease progression to identify possible genetic mechanisms associated with therapy failure. According to previous studies, a genetic similarity between canine MM and its human counterpart was observed. Several somatic mutations were functionally related to MAPK, PI3K/AKT and p53 signalling pathways, but located in genes other than BRAF, RAS and KIT. At disease progression, several mutations were related to therapy effects. Natural killer cell-mediated cytotoxicity and several immune-system-related pathways resulted activated opening a new scenario on the microenvironment in this tumour. In conclusion, this study suggests a potential role of the immune system associated to radiotherapy in canine melanoma, but a larger sample size associated with functional studies are needed

Application of an artificial intelligence algorithm to prognostically stratify grade II gliomas

(1) Background: Recently, it has been shown that the extent of resection (EOR) and molecular classification of low-grade gliomas (LGGs) are endowed with prognostic significance. However, a prognostic stratification of patients able to give specific weight to the single parameters able to predict prognosis is still missing. Here, we adopt classic statistics and an artificial intelligence algorithm to define a multiparametric prognostic stratification of grade II glioma patients. (2) Methods: 241 adults who underwent surgery for a supratentorial LGG were included. Clinical, neuroradiological, surgical, histopathological and molecular data were assessed for their ability to predict overall survival (OS), progression-free survival (PFS), and malignant progression-free survival (MPFS). Finally, a decision-tree algorithm was employed to stratify patients. (3) Results: Classic statistics confirmed EOR, pre-operative-and post-operative tumor volumes, Ki67, and the molecular classification as independent predictors of OS, PFS, and MPFS. The decision tree approach provided an algorithm capable of identifying prognostic factors and defining both the cut-off levels and the hierarchy to be used in order to delineate specific prognostic classes with high positive predictive value. Key results were the superior role of EOR on that of molecular class, the importance of second surgery, and the role of different prognostic factors within the three molecular classes. (4) Conclusions: This study proposes a stratification of LGG patients based on the different combinations of clinical, molecular, and imaging data, adopting a supervised non-parametric learning method. If validated in independent case studies, the clinical utility of this innovative stratification approach might be proved

A novel comprehensive clinical stratification model to refine prognosis of glioblastoma patients undergoing surgical resection

Despite recent discoveries in genetics and molecular fields, glioblastoma (GBM) prognosis still remains unfavorable with less than 10% of patients alive 5 years after diagnosis. Numerous studies have focused on the research of biological biomarkers to stratify GBM patients. We addressed this issue in our study by using clinical/molecular and image data, which is generally available to Neurosurgical Departments in order to create a prognostic score that can be useful to stratify GBM patients undergoing surgical resection. By using the random forest approach [CART analysis (classification and regression tree)] on Survival time data of 465 cases, we developed a new prediction score resulting in 10 groups based on extent of resection (EOR), age, tumor volumetric features, intraoperative protocols and tumor molecular classes. The resulting tree was trimmed according to similarities in the relative hazard ratios amongst groups, giving rise to a 5-group classification tree. These 5 groups were different in terms of overall survival (OS) (p < 0.000). The score performance in predicting death was defined by a Harrell\u2019s c-index of 0.79 (95% confidence interval [0.76\u20130.81]). The proposed score could be useful in a clinical setting to refine the prognosis of GBM patients after surgery and prior to postoperative treatment

Predicting lymphoma in Sjogren's syndrome and the pathogenetic role of parotid microenvironment through precise parotid swelling recording

Objective Parotid swelling (PSW) is a major predictor of non-Hodgkin's lymphoma (NHL) in primary SS (pSS). However, since detailed information on the time of onset and duration of PSW is scarce, this was investigated to verify whether it may lead to further improved prediction. NHL localization was concomitantly studied to evaluate the role of the parotid gland microenvironment in pSS-related lymphomagenesis. Methods A multicentre study was conducted among patients with pSS who developed B cell NHL during follow-up and matched controls that did not develop NHL. The study focused on the history of salivary gland and lachrymal gland swelling, evaluated in detail at different times and for different durations, and on the localization of NHL at onset. Results PSW was significantly more frequent among the cases: at the time of first referred pSS symptoms before diagnosis, at diagnosis and from pSS diagnosis to NHL. The duration of PSW was evaluated starting from pSS diagnosis, and the NHL risk increased from PSW of 2-12 months to >12 months. NHL was prevalently localized in the parotid glands of the cases. Conclusion A more precise clinical recording of PSW can improve lymphoma prediction in pSS. PSW as a very early symptom is a predictor, and a longer duration of PSW is associated with a higher risk of NHL. Since lymphoma usually localizes in the parotid glands, and not in the other salivary or lachrymal glands, the parotid microenvironment appears to be involved in the whole history of pSS and related lymphomagenesis

Phenotypic and genetic variation of ultraviolet\u2013visible-infrared spectral wavelengths of bovine meat

Spectroscopic predictions can be used for the genetic improvement of meat quality traits in cattle. No information is however available on the genetics of meat absorbance spectra. This research investigated the phenotypic variation and the heritability of meat absorbance spectra at individual wavelengths in the ultraviolet\u2013visible and near-infrared region (UV\u2013Vis-NIR) obtained with portable spectrometers. Five spectra per instrument were taken on the ribeye surface of 1185 Piemontese young bulls from 93 farms (13,182 Herd-Book pedigree relatives). Linear animal model analyses of 1481 single-wavelengths from UV\u2013Vis-NIRS and 125 from Micro-NIRS were carried out separately. In the overlapping regions, the proportions of phenotypic variance explained by batch/date of slaughter (14 \ub1 6% and 17 \ub1 7%,), rearing farm (6 \ub1 2% and 5 \ub1 3%), and the residual variances (72 \ub1 10% and 72 \ub1 5%) were similar for the UV\u2013Vis-NIRS and Micro-NIRS, but additive genetics (7 \ub1 2% and 4 \ub1 2%) and heritability (8.3 \ub1 2.3% vs 5.1 \ub1 0.6%) were greater with the Micro-NIRS. Heritability was much greater for the visible fraction (25.2 \ub1 11.4%), especially the violet, blue and green colors, than for the NIR fraction (5.0 \ub1 8.0%). These results allow a better understanding of the possibility of using the absorbance of visible and infrared wavelengths correlated with meat quality traits for the genetic improvement in beef cattle

Milk protein composition in purebred Holsteins and in first/second-generation crossbred cows from Swedish Red, Montbeliarde and Brown Swiss bulls

The aim of this study was to analyze milk protein composition in purebred and crossbred dairy cattle and estimate the effects of individual sources of variation on the investigated traits. Milk samples were collected from 505 cows from three commercial farms located in Northern Italy, some of which had originated from crossbreeding programs, although most were purebred Holsteins (HO). The basic crossbreeding scheme was a three-breed rotational system using Swedish Red (SR) semen on HO cows (SR×HO), Montbeliarde (MO) semen on SR×HO cows (MO×(SR×HO)) and HO semen again on MO×(SR×HO) cows. A smaller number of purebred HO from each of the herds were mated inverting the breed order (MO×HO and SR×(MO×HO)) or using Brown Swiss (BS) bulls (BS×HO) then MO bulls (MO×(BS×HO)). Milk samples were analyzed by reverse-phase HPLC to obtain protein fraction amounts (g/l) and proportions (% of total true protein). Traits were analyzed using a linear model, which included the fixed effects of herd-test-day (HTD), parity, days in milk and breed combination. Results showed that milk protein fractions were influenced by HTD, stage of lactation, parity and breed combination. The increase in protein concentration during lactation was due in particular to β-casein (β-CN), α S1-CN and β-lactoglobulin (β-LG). The higher protein content of primiparous milk was mainly due to higher concentrations of all casein fractions. The milk from crossbred cows had higher contents and proportions of κ-CN and α-lactalbumin (α-LA), lower proportions of β-LG and greater proportion of caseins/smaller in whey proteins on milk true protein than purebred HO. The three-way crossbreds differed from two-way crossbreds only in having greater proportions of α-LA in their milk. Of the three-way crossbreds, the SR sired cows yielded milk with a smaller content and proportion of β-LG than the MO sired cows, and, consequently, a higher proportion of caseins than whey proteins. Results from this study support the feasibility of using crossbreeding programs to alter milk protein profiles with the aim of improving milk quality and cheese-making properties