Postpartalni nastavak ciklične funkcije jajnika, prvi estrus i ponovno oplođenje i njihov odnos prema metabolizmu energije kod visoko-mlečnih krava

In the last few decades a continuous increase was observed in average milk production of dairy cows all over the world. Simultaneously, however, a dramatic decrease was seen in reproductive performance. This tendency is attributed to the increased incidence of bacterial complications in uterine involution, as well as to the high occurrence of ovarian malfunctions in the postpartum period. The aim of this paper is to review the physiology and pathology of the latter, really complex phenomenon. The nutritional basis of this process, that the requirements of high-producing dairy cows shift abruptly after parturition as the daily milk yield rapidly increases and the ensuing negative energy balance (NEB) will extend 10-12 weeks. In the context of the high genetic merit dairy cow, the pp NEB is the difference between the dietary intake of utilizable energy and the expenditure of energy for body mass maintenance and milk synthesis. In principle, it is a physiological phenomenon, which may, however, result in more or less severe disorders in both the metabolism and reproduction and so it may lead to great economic losses in modern dairy practice [112]. In the first 3-4 weeks after calving the NEB is highly correlated with both milk yield and the interval to first ovulation. Because the number of ovulatory estrous cycles preceding the insemination (AI) has been shown to influence the conception rate, the length of the pp interval to first ovulation provides an important parameter for assessing the effect of NEB on reproductive performance [19, 20].U proteklih nekoliko decenija uočeno je stalno povećanje prosečne proizvodnje mleka kod mlečnih krava širom sveta. U isto vreme, međutim, zapaženo je dramatično smanjenje reproduktivnih rezultata. Ova tendencija je pripisana povećanom pojavljivanju bakterijskih komplikacija tokom involucije uterusa, kao i velikom broju disfunkcija jajnika u postpartalnom periodu. Cilj ovoga rada je da se razmotri fiziologija i patologija ove druge pojave, tog zaista kompleksnog fenomena. Nutriciona osnova ovog procesa je da se potrebe visoko mlečnih krava naglo promene posle partusa kada se dnevni prinos mleka naglo povećava, a posledični negativni energetski bilans se produžava na 10 do 12 sedmica. U kontekstu visoke genetske vrednosti mlečnih krava, postpartalni negativni energetski bilans je razlika između dijetetskog unosa iskoristive energije i potrošnje energije za održavanje telesne mase i sinteze mleka. U principu, to je fiziološki fenomen koji, međutim, može da rezultira u manje ili više teškim poremećajima kako u metabolizmu, tako i u reprodukciji, i tako može da dovede i do velikih finansijskih gubitaka u savremenoj proizvodnji mleka [112]. U prvih tri do četiri sedmice posle teljenja, negativni energetski bilans je u visokoj korelaciji i sa prinosom mleka i intervalom do prve ovulacije. Zbog toga što je ukazano da broj ovulatornih estrusnih ciklusa, koji prethode inseminaciji, utiče na stepen koncepcije, dužina postpartalnog intervala do prve ovulacije obezbeđuje važan parametar za procenu efekta negativnog energetskog bilansa na reproduktivne rezultate [19, 20]

A meta-analysis and critical review of prospective memory in autism spectrum disorder

Prospective memory (PM) is the ability to remember to carry out a planned intention at an appropriate moment in the future. Research on PM in ASD has produced mixed results. We aimed to establish the extent to which two types of PM (event-based/time-based) are impaired in ASD. In part 1, a meta-analysis of all existing studies indicates a large impairment of time-based, but only a small impairment of event-based, PM in ASD. In Part 2, a critical review concludes that time-based PM appears diminished in ASD, in line with the meta-analysis, but that caution should be taken when interpreting event-based PM findings, given potential methodological limitations of several studies. Clinical implications and directions for future research are discussed

Genetic Ablation of Pannexin1 Protects Retinal Neurons from Ischemic Injury

Pannexin1 (Panx1) forms large nonselective membrane channel that is implicated in paracrine and inflammatory signaling. In vitro experiments suggested that Panx1 could play a key role in ischemic death of hippocampal neurons. Since retinal ganglion cells (RGCs) express high levels of Panx1 and are susceptible to ischemic induced injury, we hypothesized that Panx1 contributes to rapid and selective loss of these neurons in ischemia. To test this hypothesis, we induced experimental retinal ischemia followed by reperfusion in live animals with the Panx1 channel genetically ablated either in the entire mouse (Panx1 KO), or only in neurons using the conditional knockout (Panx1 CKO) technology. Here we report that two distinct neurotoxic processes are induced in RGCs by ischemia in the wild type mice but are inactivated in Panx1KO and Panx1 CKO animals. First, the post-ischemic permeation of RGC plasma membranes is suppressed, as assessed by dye transfer and calcium imaging assays ex vivo and in vitro. Second, the inflammasome-mediated activation of caspase-1 and the production of interleukin-1β in the Panx1 KO retinas are inhibited. Our findings indicate that post-ischemic neurotoxicity in the retina is mediated by previously uncharacterized pathways, which involve neuronal Panx1 and are intrinsic to RGCs. Thus, our work presents the in vivo evidence for neurotoxicity elicited by neuronal Panx1, and identifies this channel as a new therapeutic target in ischemic pathologies

The assessment and rehabilitation of prospective memory problems in people with neurological disorders: A review

People with neurological disorders often report difficulty with prospective memory (PM), that is, remembering to do things they had intended to do. This paper briefly reviews the literature regarding the neuropsychology of PM function, concluding that from the clinical perspective, PM is best considered in terms of its separable but interacting mnemonic and executive components. Next, the strengths and limitations in the current clinical assessment of PM, including the assessment of component processes, desktop analogues of PM tasks, and naturalistic PM tasks, are outlined. The evidence base for the rehabilitation of PM is then considered, focusing on retraining PM, using retrospective memory strategies, problem-solving training, and finally, electronic memory aids. It is proposed that further research should focus on establishing the predictive validity of PM assessment, and refining promising rehabilitation techniques

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Effects of clinical mastitis on ovarian function in postpartum dairy cows

Mastitis-induced ovarian abnormalities were studied in a field trial. At 1-3 day after calving, ≥2 parity cows not affected with chronic recurrent mastitis and yielding <400 000/ml somatic cell count (SCC) individual milk in the previous lactation, were enrolled in the study. Thereafter milk samples were collected three times weekly for 95-100 day for progesterone (P 4) assay. Individual P4 profiles were used to monitor ovarian cyclicity. When mastitis was diagnosed in the first 80 day post-partum (pp), clinical signs were recorded and scored, and aseptic milk samples were taken to identify the mastitis pathogens. Depending on the isolated pathogens the cows were blocked into one of the three sub-groups affected by either Gram-positive (GP), or Gram-negative (GN) bacteria, or of those with no detected pathogens (NDP). Cows suffering from any type of mastitis between days 15 and 28 (n = 27) showed a delay in the onset of ovarian cyclicity, and estrus was postponed compared to cows affected during the first 14 day pp (n = 59) and controls (n = 175) (38.6 ± 2.3 vs 33.4 ± 2.1 and 32.0 ± 1.0 day, respectively, for onset of ovarian cyclicity and 90.7 ± 2.5 vs 80.2 ± 2.8 and 83.9 ± 2.1 day, respectively, for estrus; both p < 0.05). The percentage of cows ovulating by day 28 was lower in those affected by mastitis between days 14 and 28 compared to cows between days 1 and 14 and controls (22.2% vs 47.5 and 50.3%, respectively; p < 0.05). A significantly higher rate of premature luteolysis was observed in GN + NDP compared to GP mastitis and healthy cows (46.7% vs 8.3 and 2.0%, respectively; p < 0.001). If the mastitis outbreak occurred during the follicular phase, the duration of this cycle segment was lengthened in GN + NDP mastitis compared to GP mastitis and healthy cows (10.8 ± 0.9 vs 7.9 ± 0.1 and 7.2 ± 0.1, respectively; p < 0.001). The results indicate that mastitis can affect the resumption of ovarian activity in pp dairy cows. Mastitis may also impair reproduction also in cyclic cows: this effect can be the consequence of premature luteolysis or a prolonged follicular phas