The extinct ray-finned fish taxon Robustichthys luopingensis from Luoping, eastern Yunnan, China represents the largest holostean known in the Middle Triassic. Despite its potential significance for investigating the holostean phylogeny and reconstructing the Triassic marine ecosystems, Robustichthys has so far not been described in detail and its phylogenetic position within the Holostei was controversy. This study provides a redescription and revision of Robustichthys based upon a comparative study of eight type specimens and nine new specimens. Newly recognized information includes a toothed parasphenoid, a pair of premaxillae not pierced by the olfactory nerve, a splint-like quadratojugal, a hatchet-shaped hyomandibula, an hourglass-shaped symplectic, anterior and posterior ceratohyals, a complete series of branchiostegal rays, and sclerotic bones. A revised reconstruction of Robustichthys is presented. Results of a cladistic analysis confirmed Robustichthys as an ionoscopiform within the Halecomorphi; the previous placements of Robustichthys as a basal ginglymodian and Ionoscopidae as a basal amiiform clade are not supported. The sister group relationship between Sinamiinae (Sinamia and Ikechaoamia) and Amiinae (Amia and Cyclurus) within the Amiidae is newly recognized. This revised topology provides new insights into the evolution and historical paleoecology of halecomorph fishes.

It is vital to understand the conservation and evolution of gene promoter sequences in order to understand environmental adaptation. The level of promoter conservation varies greatly between housekeeping (HK) and tissue-specific (TS) genes, denoting differences in the strength of the evolutionary constraints. Here, we analyzed promoter conservation and evolution to exploit differential regulation between HK and TS genes. The analysis of conserved elements showed CpG islands, short tandem repeats and G-quadruplex sequences are highly enriched in HK promoters relative to TS promoters. In addition, the type and density of regulatory motifs in TS promoters are much higher than HK promoters, indicating that TS genes show more complex regulatory patterns than HK genes. Moreover, the evolutionary dynamics of promoters showed similar evolutionary trend to coding sequences. HK promoters suffer more stringent selective pressure in the long-term evolutionary process. HK genes tend to show increased upstream sequence conservation due to stringent selection pressures acting on the promoter regions. The specificity of TS gene expression may be due to complex regulatory motifs acting in different tissues or conditions. The results from this study can be used to deepen our understanding of adaptive evolution.

DNA replication is precisely regulated in cells and its dysregulation can trigger tumorigenesis. Here we identified that the TOPBP1 interacting checkpoint and replication regulator (TICRR) mRNA level was universally and highly expressed in 15 solid cancer types. Depletion of TICRR significantly inhibited tumor cell growth, colony formation and migration in vitro, and strikingly inhibited tumor growth in the xenograft model. We reveal that knockdown of TICRR inhibited not only the initiation but also the fork progression of DNA replication. Suppression of DNA synthesis by TICRR silencing caused DNA damage accumulation, subsequently activated the ATM/CHK2 dependent p53 signaling, and finally induced cell cycle arrest and apoptosis at least in p53-wild cancer cells. Further, we show that a higher TICRR level was associated with poorer overall survival (OS) and disease free survival (DFS) in multiple cancer types. In conclusion, our study shows that TICRR is involved in tumorigenesis by regulating DNA replication, acting as a common biomarker for cancer prognosis and could be a promising target for drug-development and cancer treatment.

WWOX (WW domain containing oxidoreductase) expression loss is common in various cancers and characteristic of poor prognosis. Deletions, translocations, and loss of expression affecting the WWOX gene are a common feature of various B cell neoplasms such as certain B cell lymphomas and multiple myeloma. However, the role of this common abnormality in B cell tumor initiation and/or progression has not been defined. In this study, we conditionally deleted Wwox early in B cell development by means of breeding Cd19-Cre transgenic mice crossed to Wwox floxed mice (Cd19 Wwox KO). We observed a significant reduced survival in Cd19 Wwox KO mice and the development of B cell neoplasms including B cell lymphomas, plasma cell neoplasias characterized by increased numbers of CD138+ populations as well as monoclonal gammopathies detected by serum protein electrophoresis. To investigate whether Wwox loss could play a role in genomic instability, we analyzed DNA repair functions during immunoglobulin class switch joining between DNA segments in antibody genes. While class switch recombination (CSR) was only slightly impaired, Wwox deficiency resulted in a dramatic shift of double strand break (DSB) repair from normal classical-NHEJ toward the microhomology-mediated alternative-NHEJ pathway, a pathway associated with chromosome translocations and genome instability. Consistent with this, Wwox deficiency resulted in a marked increase of spontaneous translocations during CSR. This work defines for the first time a role for Wwox for maintaining B cell genome stability during a process that can promote neoplastic transformation and monoclonal gammopathies.

Infectious diseases remain a serious public health concern globally, while the need for reliable and representative surveillance systems remains as acute as ever. The public health surveillance of infectious diseases uses reported positive results from sentinel clinical laboratories or laboratory networks, to survey the presence of specific microbial agents known to constitute a threat to public health in a given population. This monitoring activity is commonly based on a representative fraction of the microbiology laboratories nationally reporting to a single central reference point. However, in recent years a number of clinical microbiology laboratories (CML) have undergone a process of consolidation involving a shift toward laboratory amalgamation and closer real-time informational linkage. This report aims to investigate whether such merging activities might have a potential impact on infectious diseases surveillance. Influenza data was used from Belgian public health surveillance 2014-2017, to evaluate whether national infection trends could be estimated equally as effectively from only just one centralized CML serving the wider Brussels area (LHUB-ULB). The overall comparison reveals that there is a close correlation and representativeness of the LHUB-ULB data to the national and international data for the same time periods, both on epidemiological and molecular grounds. Notably, the effectiveness of the LHUB-ULB surveillance remains partially subject to local regional variations. A subset of the Influenza samples had their whole genome sequenced so that the observed epidemiological trends could be correlated to molecular observations from the same period, as an added-value proposition. These results illustrate that the real-time integration of high-throughput whole genome sequencing platforms available in consolidated CMLs into the public health surveillance system is not only credible but also advantageous to use for future surveillance and prediction purposes. This can be most effective when implemented for automatic detection systems that might include multiple layers of information and timely implementation of control strategies.

With more than a million seizures of illegal drugs reported annually across Europe, the variety of psychoactive compounds available is vast and ever-growing. The multitude of risks associated with these compounds are well-known and can be life threatening. Hence the need for the development of new analytical techniques and approaches that allow for the rapid, sensitive, and specific quantitative detection and discrimination of such illicit materials, ultimately with portability for field testing, is of paramount importance. The aim of this study was to demonstrate the application of Raman spectroscopy and surface-enhanced Raman scattering (SERS) combined with chemometrics approaches, as rapid and portable techniques for the quantitative detection and discrimination of a wide range of novel psychoactive substances (methcathinone and aminoindane derivatives), both in powder form and in solution. The Raman spectra of the psychoactive compounds provided clear separation and classification of the compounds based on their core chemical structures; viz. methcathinones, aminoindanes, diphenidines, and synthetic cannabinoids. The SERS results also displayed similar clustering patterns, with improved limits of detections down to ~2 mM (0.41 g L-1). As mephedrone is currently very popular for recreational use we performed multiplexed quantitative detection of mephedrone (4-methylmethcathinone), and its two major metabolites (nor-mephedrone and 4-methylephedrine), as tertiary mixtures in water and healthy human urine. These findings readily illustrate the potential application of SERS for simultaneous detection of multiple NPS as mixtures without the need for lengthy prior chromatographic separation or enrichment methods.

Ischemia-reperfusion (IR) injury is unavoidable during organ transplantation and impacts graft quality. New paradigms are emerging including preservation at higher temperature than "hypothermia" or "cold": although 4°C remains largely used for kidney preservation, recent studies challenged this choice. We and others hypothesized that a higher preservation temperature, closer to physiological regimen, could improve organ quality. For this purpose, we used an in vitro model of endothelial cells exposed to hypoxia-reoxygenation sequence (mimicking IR) and an ex vivo ischemic pig kidneys static storage model. In vitro, 19°C, 27°C, and 32°C provided protection against injuries versus 4°C, by reducing cell death, mitochondrial dysfunction, leukocyte adhesion, and inflammation. However, ex vivo, the benefits of 19°C or 32°C were limited, showing similar levels of tissue preservation damage. Ex vivo 4°C-preserved kidneys displayed a trend towards reduced damage, including apoptosis. Macrophage infiltration, tubulitis, and necrosis were increased in the 19°C and 32°C versus 4°C preserved kidneys. Thus, despite a trend for an advantage of subnormothermia as preservation temperature, our in vitro and ex vivo models bring different insights in terms of preservation temperature effect. This study suggests that temperature optimization for kidney preservation will require thorough investigation, combining the use of complementary relevant models and the design of elaborated preservation solution and new technologies.

The association of age at menopause with endometrial cancer remains controversial. Therefore, we quantitatively summarized the evidence from observational studies with a meta-analysis.

This prospective study aimed to investigate the use of real-time three-dimensional hysterosalpingo-contrast sonography (4D-HyCoSy), using contrast agent SonoVue, with B mode hysterosalpingo-contrast sonography (B mode-HyCoSy), to evaluate tubal patency and the wall of the Fallopian tubes in infertility patients.

Depression is an important risk factor for Alzheimer's disease (AD) but little is known about the mechanisms of this association. Given sex differences in both AD and depression, we sought to conduct a systematic review and meta-analysis to examine whether there are sex differences in their association, as this may improve understanding of underlying mechanisms.

Tiletamine-xylazine-tramadol (XFM) has few side effects and can provide good sedation and analgesia. Adenosine 5'-monophosphate-activated protein kinase (AMPK) can attenuate trigeminal neuralgia. The study aimed to investigate the effects of XFM and its specific antagonist on AMPK in different regions of the brain.

Field-grown plants have variable exposure to sunlight as a result of shifting cloud-cover, seasonal changes, canopy shading, and other environmental factors. As a result, they need to have developed a method for dissipating excess energy obtained from periodic excessive sunlight exposure. Non-photochemical quenching (NPQ) dissipates excess energy as heat, however, the physical and molecular genetic mechanics of NPQ variation are not understood. In this study, we investigated the genetic loci involved in NPQ by first growing different Arabidopsis thaliana accessions in local and seasonal climate conditions, then measured their NPQ kinetics through development by chlorophyll fluorescence. We used genome-wide association studies (GWAS) to identify 15 significant quantitative trait loci (QTL) for a range of photosynthetic traits, including a QTL co-located with known NPQ gene PSBS (AT1G44575). We found there were large alternative regulatory segments between the PSBS promoter regions of the functional haplotypes and a significant difference in PsbS protein concentration. These findings parallel studies in rice showing recurrent regulatory evolution of this gene. The variation in the PSBS promoter and the changes underlying other QTLs could give insight to allow manipulations of NPQ in crops to improve their photosynthetic efficiency and yield.

To provide a comprehensive review of radiological clinical practice guidelines (CPGs) and to establish their characteristics and impact in the field of radiology.

Evidence suggests that high-level physical activity may potentially reduce cancer mortality through its immune enhancement effect. We therefore hypothesized that survival benefits associated with physical activity might be stronger in colorectal carcinomas with lower immune reaction at diagnosis.

BACKGROUND Osteosarcoma (OS) is a common primary malignant bone tumor for which the molecular mechanisms remain unclear. Studies on coding and non-coding RNAs are needed to determine the molecular mechanism. MATERIAL AND METHODS To explore the potential roles of miRNAs and mRNA in OS, we determined the miRNA and mRNA expression profile of 3 pairs of OS and paracancerous tissues from patients with OS by sequencing and bioinformatics analysis. The expression levels of critical miRNAs and mRNAs were verified in 10 pairs of OS and paracancerous tissues. An miRNA inhibitor and mimics were used to investigate the interactions between miRNAs and target genes. The cell counting kit-8 assay was performed to evaluate OS cell proliferation after miRNA interference. RESULTS A total of 184 miRNAs and 2501 mRNAs were identified (fold-change >2.0 or <2.0, P<0.05), with up-regulation of 82 miRNAs and 1320 mRNAs and down-regulation of 102 miRNAs and 1181 mRNAs in OS tissue. The protein protein interaction network revealed that UQCRC1 (ubiquinol-cytochrome c reductase core protein 1) is a critical gene and a potential target gene of miR-214-3p. Both UQCRC1 and miR-214-3p were significantly differentially expressed in OS tissue and cell lines (down and up-regulated, respectively). Down-regulated miR-214-3p expression increased UQCRC1 expression and suppressed OS cell proliferation. In contrast, overexpression of miR-214-3p decreased UQCRC1 expression and promoted OS cell proliferation. CONCLUSIONS High miR-214-3p expression may promote OS cell proliferation by targeting UQCRC1, providing insight into a potential therapeutic target for preventing and treating OS.

Sleep disorders and vitamin D deficiency are among the most common health problems. Few studies investigated the effect of vitamin D on objectively recorded sleep with sound methodological quality and reasonable temporal proximity.

Living creatures must accurately infer the nature of their environments. They do this despite being confronted by stochastic and context sensitive contingencies-and so must constantly update their beliefs regarding their uncertainty about what might come next. In this work, we examine how we deal with uncertainty that evolves over time. This prospective uncertainty (or imprecision) is referred to as volatility and has previously been linked to noradrenergic signals that originate in the locus coeruleus. Using pupillary dilatation as a measure of central noradrenergic signalling, we tested the hypothesis that changes in pupil diameter reflect inferences humans make about environmental volatility. To do so, we collected pupillometry data from participants presented with a stream of numbers. We generated these numbers from a process with varying degrees of volatility. By measuring pupillary dilatation in response to these stimuli-and simulating the inferences made by an ideal Bayesian observer of the same stimuli-we demonstrate that humans update their beliefs about environmental contingencies in a Bayes optimal way. We show this by comparing general linear (convolution) models that formalised competing hypotheses about the causes of pupillary changes. We found greater evidence for models that included Bayes optimal estimates of volatility than those without. We additionally explore the interaction between different causes of pupil dilation and suggest a quantitative approach to characterising a person's prior beliefs about volatility.

The Madagascar National Strategic Plan for Malaria Control 2018 (NSP) outlines malaria control pre-elimination strategies that include detailed goals for mosquito control. Primary surveillance protocols and mosquito control interventions focus on indoor vectors of malaria, while many potential vectors feed and rest outdoors. Here we describe the application of tools that advance our understanding of diversity, host choice, and Plasmodium infection in the Anopheline mosquitoes of the Western Highland Fringe of Madagascar.

The mouse organ of Corti, housed inside the cochlea, contains hair cells and supporting cells that transduce sound into electrical signals. These cells develop in two main steps: progenitor specification followed by differentiation. Fibroblast Growth Factor (FGF) signaling is important in this developmental pathway, as deletion of FGF receptor 1 (Fgfr1) or its ligand, Fgf20, leads to the loss of hair cells and supporting cells from the organ of Corti. However, whether FGF20-FGFR1 signaling is required during specification or differentiation, and how it interacts with the transcription factor Sox2, also important for hair cell and supporting cell development, has been a topic of debate. Here, we show that while FGF20-FGFR1 signaling functions during progenitor differentiation, FGFR1 has an FGF20-independent, Sox2-dependent role in specification. We also show that a combination of reduction in Sox2 expression and Fgf20 deletion recapitulates the Fgfr1-deletion phenotype. Furthermore, we uncovered a strong genetic interaction between Sox2 and Fgf20, especially in regulating the development of hair cells and supporting cells towards the basal end and the outer compartment of the cochlea. To explain this genetic interaction and its effects on the basal end of the cochlea, we provide evidence that decreased Sox2 expression delays specification, which begins at the apex of the cochlea and progresses towards the base, while Fgf20-deletion results in premature onset of differentiation, which begins near the base of the cochlea and progresses towards the apex. Thereby, Sox2 and Fgf20 interact to ensure that specification occurs before differentiation towards the cochlear base. These findings reveal an intricate developmental program regulating organ of Corti development along the basal-apical axis of the cochlea.

Despite reducing the prevalent foodborne pathogen Campylobacter jejuni in chickens decreases campylobacteriosis, few effective approaches are available. The aim of this study was to use microbial metabolic product bile acids to reduce C. jejuni chicken colonization. Broiler chicks were fed with deoxycholic acid (DCA), lithocholic acid (LCA), or ursodeoxycholic acid (UDCA). The birds were also transplanted with DCA modulated anaerobes (DCA-Anaero) or aerobes (DCA-Aero). The birds were infected with human clinical isolate C. jejuni 81-176 or chicken isolate C. jejuni AR101. Notably, C. jejuni 81-176 was readily colonized intestinal tract at d16 and reached an almost plateau at d21. Remarkably, DCA excluded C. jejuni cecal colonization below the limit of detection at 16 and 28 days of age. Neither chicken ages of infection nor LCA or UDCA altered C. jejuni AR101 chicken colonization level, while DCA reduced 91% of the bacterium in chickens at d28. Notably, DCA diet reduced phylum Firmicutes but increased Bacteroidetes compared to infected control birds. Importantly, DCA-Anaero attenuated 93% of C. jejuni colonization at d28 compared to control infected birds. In conclusion, DCA shapes microbiota composition against C. jejuni colonization in chickens, suggesting a bidirectional interaction between microbiota and microbial metabolites.