BACKGROUND Whereas studies have revealed that the cryopreservation of human semen increases sperm DNA fragmentation, the mechanisms involved in this type of cryo-injury are largely unknown. ...Elucidation of these mechanisms may provide insight into preventing such injury. METHODS We obtained 60 semen samples from 60 men and conducted experiments to determine the cause of cryopreservation-induced DNA fragmentation using 8-oxo-7,8-dihydro-2′deoxyguanosine (8OHdG) as a biomarker of oxidative stress, percentage caspase positive cells as an indicator of apoptosis, the potential antioxidant genistein and the caspase inhibitor Z-VAD(OMe)-FMK. RESULTS Cryopreservation led to a significant increase in percentage DNA fragmentation, percentage 8OHdG and percentage caspase positive cells (P < 0.001). Percentage DNA fragmentation was positively correlated with percentage 8OHdG before (r = 0.756, P < 0.001) and after cryopreservation (r = 0.528, P = 0.017). The addition of 50 and 100 µM genistein to the cryoprotectant had a significant protective effect on sperm DNA (P < 0.001) although the caspase inhibitor demonstrated no difference to the control. CONCLUSIONS Human sperm DNA fragmentation is associated with an increase in oxidative stress during cryopreservation, rather than the activation of caspases and apoptosis. The estrogenic compound genistein may be useful in reducing this effect but larger trials are needed to confirm this.
APOGEE-2 is a high-resolution, near-infrared spectroscopic survey observing ∼3 × 105 stars across the entire sky. It is the successor to APOGEE and is part of the Sloan Digital Sky Survey IV ...(SDSS-IV). APOGEE-2 is expanding on APOGEE's goals of addressing critical questions of stellar astrophysics, stellar populations, and Galactic chemodynamical evolution using (1) an enhanced set of target types and (2) a second spectrograph at Las Campanas Observatory in Chile. APOGEE-2 is targeting red giant branch and red clump stars, RR Lyrae, low-mass dwarf stars, young stellar objects, and numerous other Milky Way and Local Group sources across the entire sky from both hemispheres. In this paper, we describe the APOGEE-2 observational design, target selection catalogs and algorithms, and the targeting-related documentation included in the SDSS data releases.
Identification of the coding elements in the genome is a fundamental step to understanding the building blocks of living systems. Short peptides (< 100 aa) have emerged as important regulators of ...development and physiology, but their identification has been limited by their size. We have leveraged the periodicity of ribosome movement on the mRNA to define actively translated ORFs by ribosome footprinting. This approach identifies several hundred translated small ORFs in zebrafish and human. Computational prediction of small ORFs from codon conservation patterns corroborates and extends these findings and identifies conserved sequences in zebrafish and human, suggesting functional peptide products (micropeptides). These results identify micropeptide‐encoding genes in vertebrates, providing an entry point to define their function in vivo.
Synopsis
The combination of ORFscore and micPDP enable high confidence prediction of many, small translated ORFs that were functionally not appreciated or previously annotated as lincRNAs.
“ORFScore” explores high‐resolution footprinting with ribosome phasing to identify novel, translated micropeptides in genes previously thought to lack coding potential.
“micPDP” is a new computational pipeline that identifies micropeptides under negative selection across species.
The combination of these techniques enabled high confidence prediction of numerous small translated ORFs suitable for functional characterization.
The combination of ORFscore and micPDP enable high confidence prediction of many, small translated ORFs that were functionally not appreciated or previously annotated as lincRNAs.
We report a time-calibrated stratigraphic section in Colorado that contains unusually complete fossils of mammals, reptiles, and plants and elucidates the drivers and tempo of biotic recovery during ...the poorly known first million years after the Cretaceous-Paleogene mass extinction (KPgE). Within ~100 thousand years (ka) post-KPgE, mammalian taxonomic richness doubled, and maximum mammalian body mass increased to near pre-KPgE levels. A threefold increase in maximum mammalian body mass and dietary niche specialization occurred at ~300 ka post-KPgE, concomitant with increased megafloral standing species richness. The appearance of additional large mammals occurred by ~700 ka post-KPgE, coincident with the first appearance of Leguminosae (the bean family). These concurrent plant and mammal originations and body-mass shifts coincide with warming intervals, suggesting that climate influenced post-KPgE biotic recovery.
Is metacognition a general resource shared across domains? Previous research has documented consistent biases in judgments across tasks. In contrast, there is debate regarding the domain generality ...or the domain specificity of the ability to discriminate between correct and incorrect answers (metacognitive sensitivity) because most previous work has documented nonsignificant correlations across domains. However, such null findings may be due to low statistical power and differences in task structure or performance, thereby masking a latent domain generality in metacognition. We examined across-domain correlations in confidence level and sensitivity in a large sample (N = 181). Participants performed 4 2-alternative forced-choice tasks (episodic memory, semantic memory, executive function, and visual perception) with trial-by-trial confidence judgments. We found significant correlations in average confidence level across tasks. By applying a hierarchical Bayesian model to estimate cross-task covariance, we found five out 6 cross-task correlations in metacognitive efficiency (meta-d′/d′) were significant, even for pairs of tasks in which first-order performance was not correlated. This suggests that at least some components of metacognitive efficiency in retrospective confidence are domain general.
An understanding of the factors that drive inter‐population variability in home‐range size is essential for managing the impacts of invasive species with broad global distributions, such as the feral ...domestic cat (Felis catus). The assumption that home‐range sizes scale negatively with landscape productivity is fundamental to many spatial behaviour models, and inter‐site variation in landscape productivity has often been invoked to explain the vast differences in feral cat home‐range sizes among different regions. However, the validity of this explanation has not been tested or described. We used regression models to examine the ability of remotely sensed landscape productivity data, average body weight and population density to explain differences in the size of feral cat home ranges estimated across a diverse collection of sites across the globe. As expected for a solitary polygynous carnivore, female cats occupied smaller home ranges in highly productive sites, and range sizes of male cats scaled positively with those of females. However, the relationship between range size and productivity broke down at highly seasonal sites. Home‐range size also scaled negatively with population density, but there was no clear relationship with average body weight. The relationships we describe should be useful for predicting home‐range sizes and for designing effective feral cat control and monitoring programmes in many situations. More generally, these results confirm the importance of landscape productivity in shaping the spatial distribution of solitary carnivores, but the nature of the relationship is more complicated than is often appreciated.
Skeletal muscle (SkM) regenerates following injury, replacing damaged tissue with high fidelity. However, in serious injuries, non-regenerative defects leave patients with loss of function, increased ...re-injury risk and often chronic pain. Progress in treating these non-regenerative defects has been slow, with advances only occurring where a comprehensive understanding of regeneration has been gained. Tissue engineering has allowed the development of bioengineered models of SkM which regenerate following injury to support research in regenerative physiology. To date, however, no studies have utilised human myogenic precursor cells (hMPCs) to closely mimic functional human regenerative physiology.
Here we address some of the difficulties associated with cell number and hMPC mitogenicity using magnetic association cell sorting (MACS), for the marker CD56, and media supplementation with fibroblast growth factor 2 (FGF-2) and B-27 supplement. Cell sorting allowed extended expansion of myogenic cells and supplementation was shown to improve myogenesis within engineered tissues and force generation at maturity. In addition, these engineered human SkM regenerated following barium chloride (BaCl
) injury. Following injury, reductions in function (87.5%) and myotube number (33.3%) were observed, followed by a proliferative phase with increased MyoD+ cells and a subsequent recovery of function and myotube number. An expansion of the Pax7+ cell population was observed across recovery suggesting an ability to generate Pax7+ cells within the tissue, similar to the self-renewal of satellite cells seen in vivo.
This work outlines an engineered human SkM capable of functional regeneration following injury, built upon an open source system adding to the pre-clinical testing toolbox to improve the understanding of basic regenerative physiology.
Background
Axillary lymph node status remains a significant prognostic indicator in breast cancer. Here, the diagnostic accuracy of ultrasound‐guided fine‐needle aspiration (US‐FNA) and ...ultrasound‐guided core needle biopsy (US‐CNB) in axillary staging was compared.
Methods
A comprehensive search was undertaken of all published studies comparing the diagnostic accuracy of US‐CNB and US‐FNA of axillary lymph nodes in breast cancer. Studies were included if raw data were available on the diagnostic performance of both US‐FNA and US‐CNB, and compared with final histology results. Relevant data were extracted from each study for systematic review. Meta‐analysis was performed using a random‐effects model. The pooled sensitivity and specificity of US‐FNA and US‐CNB were obtained using a bivariable model. Summary receiver operating characteristic (ROC) graphs were created to confirm diagnostic accuracy.
Results
Data on a total of 1353 patients from six studies met the inclusion criteria and were included in the final analysis. US‐CNB was superior to US‐FNA in diagnosing axillary nodal metastases: sensitivity 88 (95 per cent c.i. 84 to 91) versus 74 (70 to 78) per cent respectively. Both US‐CNB and US‐FNA had a high specificity of 100 per cent. Reported complication rates were significantly higher for US‐CNB compared with US‐FNA (7·1 versus 1·3 per cent; P < 0·001). Conversely, the requirement for repeat diagnostic procedures was significantly greater for US‐FNA (4·0 versus 0·5 per cent; P < 0·001).
Conclusion
US‐CNB is a superior diagnostic technique to US‐FNA for axillary staging in breast cancer.
Core needle biopsy better
At least 20% of all arthropods and some nematode species are infected with intracellular bacteria of the genus WOLBACHIA: This highly diverse genus has been subdivided into eight "supergroups" (A to ...H) on the basis of nucleotide sequence data. Here, we report the discovery of a new Wolbachia supergroup recovered from the spider mite species Bryobia species V (Acari: Tetranychidae), based on the sequences of three protein-coding genes (ftsZ, gltA, and groEL) and the 16S rRNA gene. Other tetranychid mites possess supergroup B Wolbachia strains. The discovery of another Wolbachia supergroup expands the known diversity of Wolbachia and emphasizes the high variability of the genus. Our data also clarify the existing supergroup structure and highlight the use of multiple gene sequences for robust phylogenetic analysis. In addition to previous reports of recombination between the arthropod-infecting supergroups A and B, we provide evidence for recombination between the nematode-infecting supergroups C and D. Robust delineation of supergroups is essential for understanding the origin and spread of this common reproductive parasite and for unraveling mechanisms of host adaptation and manipulation across a wide range of hosts.
The endogenous opioid system is thought to play an important role in mother-infant attachment. In infant rhesus macaques, variation in the μ-opioid receptor gene (OPRM1) is related to differences in ...attachment behavior that emerges following repeated separation from the mother; specifically, infants carrying at least one copy of the minor G allele of the OPRM1 C77G polymorphism show heightened and more persistent separation distress, as well as a pattern of increased contact-seeking behavior directed towards the mother during reunions (at the expense of affiliation with other group members). Research in adult humans has also linked the minor G allele of the analogous OPRM1 A118G polymorphism with greater interpersonal sensitivity. Adopting an interactionist approach, we examined whether OPRM1 A118G genotype and maternal (in)sensitivity are associated with child attachment style, predicting that children carrying the G allele may be more likely to develop an ambivalent attachment pattern in response to less sensitive maternal care. The sample consisted of 191 mothers participating with their children (n = 223) in the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) project, a community-based, birth cohort study of Canadian mothers and their children assessed longitudinally across the child's development. Maternal sensitivity was coded from at-home mother-child interactions videotaped when the child was 18 months of age. Child attachment was assessed at 36 months using the Strange Situation paradigm. As predicted, G allele carriers, but not AA homozygotes, showed increasing odds of being classified as ambivalently attached with decreasing levels of maternal sensitivity. Paralleling earlier non-human animal research, this work provides support for the theory that endogenous opioids contribute to the expression of attachment behaviors in humans.
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