Rapid input-restricted change in gene expression is an important aspect of synaptic plasticity requiring complex mechanisms of post-transcriptional mRNA trafficking and regulation. Small non-coding miRNA are uniquely poised to support these functions by providing a nucleic-acid-based specificity component for universal-sequence-dependent RNA binding complexes. We investigated the subcellular distribution of these molecules in resting and potassium chloride depolarized human neuroblasts, and found both selective enrichment and depletion in neurites. Depolarization was associated with a neurite-restricted decrease in miRNA expression; a subset of these molecules was recovered from the depolarization medium in nuclease resistant extracellular exosomes. These vesicles were enriched with primate specific miRNA and the synaptic-plasticity-associated protein MAP1b. These findings further support a role for miRNA as neural plasticity regulators, as they are compartmentalized in neurons and undergo activity-associated redistribution or release into the extracellular matrix.

Abstract. Nearly all general circulation models significantly fail to reproduce the observed behaviour of the southern wintertime polar vortex. It has been suggested that these biases result from an underestimation of gravity wave drag on the atmosphere at latitudes near 60 • S, especially around the "hot spot" of intense gravity wave fluxes above the mountainous Southern Andes and Antarctic peninsula. Here, we use Global Positioning System radio occultation (GPS-RO) data from the COSMIC satellite constellation to determine the properties of gravity waves in the hot spot and beyond. We show considerable southward propagation to latitudes near 60 • S of waves apparently generated over the southern Andes. We propose that this propagation may account for much of the wave drag missing from the models. Furthermore, there is a long leeward region of increased gravity wave energy that sweeps eastwards from the mountains over the Southern Ocean. Despite its striking nature, the source of this region has historically proved difficult to determine. Our observations suggest that this region includes both waves generated locally and orographic waves advected downwind from the hot spot. We describe and use a new wavelet-based analysis technique for the quantitative identification of individual waves from COSMIC temperature profiles. This analysis reveals different geographical regimes of wave amplitude and short-timescale variability in the wave field over the Southern Ocean. Finally, we use the increased numbers of closely spaced pairs of profiles from the deployment phase of the COSMIC constellation in 2006 to make estimates of gravity wave horizontal wavelengths. We show that, given sufficient observations, GPS-RO can produce physically reasonable estimates of stratospheric gravity wave momentum flux in the hot spot that are consistent with measurements made by other techniques. We discuss our results in the context of previous satellite and modelling studies and explain how they advance our understanding of the nature and origins of waves in the southern stratosphere.

Implication By understanding Matrix Metalloprotease (MMP) dysregulation from a pan-cancer perspective, this study sheds light on the diagnostic potentials of MMPs across multiple neoplasms. Background MMPs are intriguing genes related to cancer disease progression, functional promotion of angiogenesis, invasion, metastasis, and avoidance of immune surveillance. Many studies have noted these genes are frequently upregulated in cancer. However, expression patterns of all MMPs and their diagnostic and prognostic potential have not been investigated in a pan-cancer perspective. Methods The Cancer Genome Atlas (TCGA) data were used to evaluate diagnostic and prognostic potential of 24 MMPs in fifteen different cancer types. Gene expression measured by RNA-seq was analyzed by differential expression, hierarchical clustering, and ROC analysis for individual genes and in combination. Results MMP1, MMP9 , MMP10 , MMP11 , and MMP13 were almost universally upregulated across all cancers, with significant ( p < 0.05) fold change (FC > 2) in ten of fifteen cancers. MMP3 , MMP7 , MMP12 and MMP14 ) are significantly up-regulated in at least 10 cancer types. Interestingly, MMP2 , MMP7 , MMP23B , MMP27 and MMP28 ) are significantly down-regulated in seven to nine cancer types. Multiple MMPs possess AUC’s > 0.9 in more than one cancer. However, survival analyses suggest that the prognostic value of MMPs is limited to clear cell renal carcinoma. Conclusions Most MMPs have consistently increased gene expression across cancers, while several MMPs have consistently decreased expression in several cancer types. Many MMPs have diagnostic value individually or in combination, while the prognostic value of MMPs is restricted to one subtype of kidney cancer. Electronic supplementary material The online version of this article (10.1186/s12885-019-5768-0) contains supplementary material, which is available to authorized users.

Summary DNA repair has long been considered impossible in human spermatozoa due to the high level of DNA compaction observed in these cells. However, detailed examination of the base excision repair pathway in human spermatozoa has revealed the presence of an enzyme critical to this pathway, 8-oxoguanine DNA glycosylase 1 (OGG1). This glycosylase was associated with the sperm nucleus and mitochondria and could actively excise 8-hydroxy-29-deoxyguanosine (8OHdG), releasing this adduct into the extracellular space. This activity was significantly reduced in the presence of cadmium (II), a recognized inhibitor of OGG1, in a time-and dose-dependent manner (P,0.001). Remarkably, spermatozoa do not possess the downstream components of the base excision repair pathway, apurinic endonuclease 1 (APE1) and X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1). The absence of these proteins was particularly significant, as APE1 is required to create a 39-hydroxyl (39-OH) terminus at the apurinic site created by OGG1, which would be recognized by the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. As a result, TUNEL was unable to detect oxidatively induced DNA damage in spermatozoa following exposure to hydrogen peroxide. In the same cells, intracellular and extracellular 8OHdG could be clearly detected in a manner that was highly correlated with the outcome of the sperm chromatin structure assay (SCSA). However, incubation of these cells for 48 hours revealed a time-dependent increase in TUNEL positivity, suggesting the perimortem activation of a nuclease. These results emphasize the limited capacity of mature spermatozoa to mount a DNA repair response to oxidative stress, and highlight the importance of such mechanisms in the oocyte in order to protect the embryo from paternally mediated genetic damage.

Shigella flexneri causes a severe form of bacillary dysentery also known as shigellosis. Onset of shigellosis requires bacterial invasion of colonic epithelial cells which is initiated by the delivery of translocator and effector proteins to the host cell membrane and cytoplasm, respectively, by the Shigella type III secretion system (TTSS). The Shigella translocator proteins, IpaB and IpaC, form a pore complex in the host cell membrane to facilitate effector delivery; however, prior to their secretion IpaB and IpaC are partitioned in the bacterial cytoplasm by association with the cytoplasmic chaperone IpgC. To determine their structural and biophysical properties, recombinant IpaB/IpgC and IpaC/IpgC complexes were prepared for their first detailed in vitro analysis. Both IpaB/IpgC and IpaC/IpgC complexes are highly stable and soluble heterodimers whose formation prevents IpaB-IpaC interaction as well as Ipa-dependent disruption of phospholipid membranes. Circular dichroism spectroscopy shows that IpgC binding has a detectable influence on IpaC secondary/tertiary structure and stability. In contrast, IpaB structure is not as dramatically affected by chaperone binding. To more precisely ascertain the influence of chaperone binding on IpaC structure and stability, single tryptophan mutants were generated for detailed fluorescence spectroscopy analysis. These mutants provide a low-resolution picture of how IpaC exists in the Shigella cytoplasm with chaperone binding possibly involving distinct regions within the N- and C-terminal halves of IpaC. This preliminary assessment of the IpaC-IpgC interaction is supported by initial deletion mutagenesis studies. The data provide the first structural analysis of IpgC association with IpaB and IpaC.

Abstract. Atmospheric gravity waves play a key role in the transfer of energy and momentum between layers of the Earth's atmosphere. However, nearly all general circulation models (GCMs) seriously under-represent the momentum fluxes of gravity waves at latitudes near 60∘ S, which can lead to significant biases. A prominent example of this is the “cold pole problem”, where modelled winter stratospheres are unrealistically cold. There is thus a need for large-scale measurements of gravity wave fluxes near 60∘ S, and indeed globally, to test and constrain GCMs. Such measurements are notoriously difficult, because they require 3-D observations of wave properties if the fluxes are to be estimated without using significant limiting assumptions. Here we use 3-D satellite measurements of stratospheric gravity waves from NASA's Atmospheric Infrared Sounder (AIRS) Aqua instrument. We present the first extended application of a 3-D Stockwell transform (3DST) method to determine localised gravity wave amplitudes, wavelengths and directions of propagation around the entire region of the Southern Ocean near 60∘ S during austral winter 2010. We first validate our method using a synthetic wavefield and two case studies of real gravity waves over the southern Andes and the island of South Georgia. A new technique to overcome wave amplitude attenuation problems in previous methods is also presented. We then characterise large-scale gravity wave occurrence frequencies, directional momentum fluxes and short-timescale intermittency over the entire Southern Ocean. Our results show that highest wave occurrence frequencies, amplitudes and momentum fluxes are observed in the stratosphere over the mountains of the southern Andes and Antarctic Peninsula. However, we find that around 60 %–80 % of total zonal-mean momentum flux is located over the open Southern Ocean during June–August, where a large “belt” of increased wave occurrence frequencies, amplitudes and fluxes is observed. Our results also suggest significant short-timescale variability of fluxes from both orographic and non-orographic sources in the region. A particularly striking result is a widespread convergence of gravity wave momentum fluxes towards latitudes around 60∘ S from the north and south. We propose that this convergence, which is observed at nearly all longitudes during winter, could account for a significant part of the under-represented flux in GCMs at these latitudes.

Background: Mammalian fertilization is initiated by sperm-zona pellucida (ZP) interactions. Results: The chaperonin-containing TCP1 complex (CCT/TRiC) was identified on the surface of mouse spermatozoa and shown to have an indirect role in ZP adhesion.

Abstract. Gravity waves (GWs) play a crucial role in the dynamics of the earth's atmosphere. These waves couple lower, middle and upper atmospheric layers by transporting and depositing energy and momentum from their sources to great heights. The accurate parameterisation of GW momentum flux is of key importance to general circulation models but requires accurate measurement of GW properties, which has proved challenging. For more than a decade, the nadir-viewing Atmospheric Infrared Sounder (AIRS) aboard NASA's Aqua satellite has made global, two-dimensional (2-D) measurements of stratospheric radiances in which GWs can be detected. However, one problem with current one-dimensional methods for GW analysis of these data is that they can introduce significant unwanted biases. Here, we present a new analysis method that resolves this problem. Our method uses a 2-D Stockwell transform (2DST) to measure GW amplitudes, horizontal wavelengths and directions of propagation using both the along-track and cross-track dimensions simultaneously. We first test our new method and demonstrate that it can accurately measure GW properties in a specified wave field. We then show that by using a new elliptical spectral window in the 2DST, in place of the traditional Gaussian, we can dramatically improve the recovery of wave amplitude over the standard approach. We then use our improved method to measure GW properties and momentum fluxes in AIRS measurements over two regions known to be intense hotspots of GW activity: (i) the Drake Passage/Antarctic Peninsula and (ii) the isolated mountainous island of South Georgia. The significance of our new 2DST method is that it provides more accurate, unbiased and better localised measurements of key GW properties compared to most current methods. The added flexibility offered by the scaling parameter and our new spectral window presented here extend the usefulness of our 2DST method to other areas of geophysical data analysis and beyond.