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Plastic, as a form of marine litter, is found in varying quantities and sizes around the globe from surface waters to deep-sea sediments. Identifying patterns of microplastic distribution will benefit an understanding of the scale of their potential effect on the environment and organisms. As sea ice extent is reducing in the Arctic, heightened shipping and fishing activity may increase marine pollution in the area. Microplastics may enter the region following ocean transport and local input, although baseline contamination measurements are still required. Here we present the first study of microplastics in Arctic waters, south and southwest of Svalbard, Norway. Microplastics were found in surface (top 16 cm) and sub-surface (6 m depth) samples using two independent techniques. Origins and pathways bringing microplastic to the Arctic remain unclear. Particle composition (95% fibres) suggests they may either result from the breakdown of larger items (transported over large distances by prevailing currents, or derived from local vessel activity), or input in sewage and wastewater from coastal areas. Concurrent observations of high zooplankton abundance suggest a high probability for marine biota to encounter microplastics and a potential for trophic interactions. Further research is required to understand the effects of microplastic-biota interaction within this productive environment. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to evaluate the in vitro activity of tedizolid against several clinically significant species of Nocardia by comparing with that of linezolid. A total of 286 isolates of Nocardia species, including 236 clinical isolates recovered from patients in Japan and 50 strains (43 species) purchased from NITE Biological Resource Center, were studied. Antimicrobial susceptibility testing was performed using the broth microdilution method. For the 286 Nocardia isolates, the minimal inhibitory concentration (MIC)50 and MIC90 values of tedizolid were 0.25 and 0.5 μg/ml, and those of linezolid were 2 and 2 μg/ml, respectively. The distribution of the linezolid/tedizolid ratios (MICs of linezolid/MICs of tedizolid) showed that tedizolid had four- to eight-fold higher activity than linezolid in 96.1% (275/286) of Nocardia isolates. Both the tedizolid and linezolid MIC90 values for Nocardia brasiliensis were two-fold higher than those for the other Nocardia species. Both tedizolid and linezolid had low MIC values, 0.25–1 μg/ml and 0.5–4 μg/ml, respectively, even against nine isolates (five species) that were resistant to trimethoprim/sulfamethoxazole. One Nocardia sputorum isolate showed reduced susceptibility to tedizolid (4 μg/ml). Bioinformatics analysis suggests different resistance mechanisms than the oxazolidinone resistance seen in enterococci and staphylococci. [ABSTRACT FROM AUTHOR]

Abundance of data on the role of inflammatory immune responses in the progression or inhibition of hepatocellular carcinoma (HCC) has failed to offer a curative immunotherapy for HCC. This is largely because of focusing on detailed specific cell types and missing the collective function of the hepatic immune system. To discover the collective immune function, we take systems immunology approach by performing high-throughput analysis of snRNAseq data collected from the liver of DIAMOND mice during the progression of nonalcoholic fatty liver disease (NAFLD) to HCC. We report that mutual signaling interactions of the hepatic immune cells in a dominant-subdominant manner, as well as their interaction with structural cells shape the immunological pattern manifesting a collective function beyond the function of the cellular constituents. Such pattern discovery approach recognized direct role of the innate immune cells in the progression of NASH and HCC. These data suggest that discovery of the immune pattern not only detects the immunological mechanism of HCC in spite of dynamic changes in immune cells during the course of disease but also offers immune modulatory interventions for the treatment of NAFLD and HCC. [ABSTRACT FROM AUTHOR]

Changes in the three-dimensional (3D) structure of the genome are an emerging hallmark of cancer. Cancer-associated copy number variants and single nucleotide polymorphisms promote rewiring of chromatin loops, disruption of topologically associating domains (TADs), active/inactive chromatin state switching, leading to oncogene expression and silencing of tumor suppressors. However, little is known about 3D changes during cancer progression to a chemotherapy-resistant state. We integrated chromatin conformation capture (Hi-C), RNA-seq, and whole-genome sequencing obtained from triple-negative breast cancer patient-derived xenograft primary tumors (UCD52) and carboplatin-resistant samples and found increased short-range (< 2 Mb) interactions, chromatin looping, formation of TAD, chromatin state switching into a more active state, and amplification of ATP-binding cassette transporters. Transcriptome changes suggested the role of long-noncoding RNAs in carboplatin resistance. Rewiring of the 3D genome was associated with TP53, TP63, BATF, FOS-JUN family of transcription factors and led to activation of aggressiveness-, metastasis- and other cancer-related pathways. Integrative analysis highlighted increased ribosome biogenesis and oxidative phosphorylation, suggesting the role of mitochondrial energy metabolism. Our results suggest that 3D genome remodeling may be a key mechanism underlying carboplatin resistance. [ABSTRACT FROM AUTHOR]

Tarsometatarsal joint arthrodesis is used to treat a variety of injuries and deformities in the midfoot. However, the surgical technique has not been optimized, in part due to limited knowledge of morphologic features and variation in the related joints. Previous research has relied primarily on dissection-based anatomical analysis, but quantitative imaging may allow for a more sophisticated description of this complex. Here, we used quantitative micro-CT imaging to examine dimensions, distance maps, and curvature of the four articular surfaces in the first and second tarsometatarsal joints. Image segmentation, articular surface identification, and anatomic coordinate systems were all done with semi or fully automatic methods, and distance and size measurements were all taken utilizing these anatomic planes. Surface curvature was studied using Gaussian curvature and a newly defined measure of curvature similarity on the whole joint and on four subregions of each surface. These data show larger articular surfaces on the cuneiforms, rather than metatarsals, and define the generally tall and narrow articular surfaces seen in these joints. Curvature analysis shows minimally curved opposing convex surfaces. Our results are valuable for furthering knowledge of surgical anatomy in this poorly understood region of the foot. [ABSTRACT FROM AUTHOR]

Central poststroke pain (CPSP) develops after a stroke around the somatosensory pathway. CPSP is hypothesized to be caused by maladaptive reorganization between various brain regions. The treatment for CPSP has not been established; however, repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex has a clinical effect. To verify the functional reorganization hypothesis for CPSP development and rTMS therapeutic mechanism, we longitudinally pursued the structural and functional changes of the brain by using two male CPSP model monkeys (Macaca fuscata) developed by unilateral hemorrhage in the ventral posterolateral nucleus of the thalamus. Application of rTMS to the ipsilesional primary motor cortex relieved the induced pain of the model monkeys. A tractography analysis revealed a decrease in the structural connectivity in the ipsilesional thalamocortical tract, and rTMS had no effect on the structural connectivity. A region of interest analysis using resting-state functional magnetic resonance imaging revealed inappropriately strengthened functional connectivity between the ipsilesional mediodorsal nucleus of the thalamus and the amygdala, which are regions associated with emotion and memory, suggesting that this may be the cause of CPSP development. Moreover, rTMS normalizes this strengthened connectivity, which may be a possible therapeutic mechanism of rTMS for CPSP. [ABSTRACT FROM AUTHOR]

To better understand the molecular control of leaf senescence, we examined transcriptome changes during seasonal leaf senescence in Populus trichocarpa Nisqually-1, the Populus reference genome, growing in its natural habitat. Using monthly (from May to October) transcriptomes for three years (2009, 2015, and 2016), we identified 17,974 differentially expressed genes (DEGs; false discovery rate <0.05; log-fold change cutoff = 0) from 36,007 expressed Populus gene models. A total of 14,415 DEGs were directly related to transitions between four major developmental phases – growth, senescence initiation, reorganization, and senescence termination. These DEGs were significantly (p < 0.05) enriched in 279 gene ontology (GO) terms, including those related to photosynthesis, metabolic process, catalytic activity, protein phosphorylation, kinase activity, pollination, and transport. Also, there were 881 differentially expressed transcription factor (TF) genes from 54 TF families, notably bHLH, MYB, ERF, MYB-related, NAC, and WRKY. We also examined 28 DEGs known as alternative splicing (AS) factors that regulate AS process, and found evidence for a reduced level of AS activity during leaf senescence. Furthermore, we were able to identify a number of promoter sequence motifs associated with leaf senescence. This work provides a comprehensive resource for identification of genes involved in seasonal leaf senescence in trees, and informs efforts to explore the conservation and divergence of molecular mechanisms underlying leaf senescence between annual and perennial species. [ABSTRACT FROM AUTHOR]

Although the advent of several new breeding techniques (NBTs) is revolutionizing agricultural production processes, technical information necessary for their regulation is yet to be provided. Here, we show that high-throughput DNA sequencing is effective for the detection of unintended remaining foreign DNA segments in genome-edited rice. A simple k-mer detection method is presented and validated through a series of computer simulations and real data analyses. The data show that a short foreign DNA segment of 20 nucleotides can be detected and the probability that the segment is overlooked is 10−3 or less if the average sequencing depth is 30 or more, while the number of false hits is less than 1 on average. This method was applied to real sequencing data, and the presence and absence of an external DNA segment were successfully proven. Additionally, our in-depth analyses also identified some weaknesses in current DNA sequencing technologies. Hence, for a rigorous safety assessment, the combination of k-mer detection and another method, such as Southern blot assay, is recommended. The results presented in this study will lay the foundation for the regulation of NBT products, where foreign DNA is utilized during their generation. [ABSTRACT FROM AUTHOR]

Consanguineous populations of the Arabian Peninsula, which has seen an uncontrolled rise in type 2 diabetes incidence, are underrepresented in global studies on diabetes genetics. We performed a genome-wide association study on the quantitative trait of fasting plasma glucose (FPG) in unrelated Arab individuals from Kuwait (discovery-cohort:n = 1,353; replication-cohort:n = 1,196). Genome-wide genotyping in discovery phase was performed for 632,375 markers from Illumina HumanOmniExpress Beadchip; and top-associating markers were replicated using candidate genotyping. Genetic models based on additive and recessive transmission modes were used in statistical tests for associations in discovery phase, replication phase, and meta-analysis that combines data from both the phases. A genome-wide significant association with high FPG was found at rs1002487 (RPS6KA1) (p-discovery = 1.64E-08, p-replication = 3.71E-04, p-combined = 5.72E-11; β-discovery = 8.315; β-replication = 3.442; β-combined = 6.551). Further, three suggestive associations (p-values < 8.2E-06) with high FPG were observed at rs487321 (CADPS), rs707927 (VARS and 2Kb upstream of VWA7), and rs12600570 (DHX58); the first two markers reached genome-wide significance in the combined analysis (p-combined = 1.83E-12 and 3.07E-09, respectively). Significant interactions of diabetes traits (serum triglycerides, FPG, and glycated hemoglobin) with homeostatic model assessment of insulin resistance were identified for genotypes heterozygous or homozygous for the risk allele. Literature reports support the involvement of these gene loci in type 2 diabetes etiology. [ABSTRACT FROM AUTHOR]

The whole genome sequencing data generated in this study have been submitted to the NCBI SRA database (https://www.ncbi.nlm.nih.gov/bioproject/) under accession number PRJNA832117, reviewer's accession link: https://dataview.ncbi.nlm.nih.gov/object/PRJNA832117. All original code has been deposited at Github (https://github.com/dozmorovlab/PDXHiC supplemental)." now reads: "All raw and processed sequencing data generated in this study have been submitted to the NCBI Gene Expression Omnibus (GEO; https://www.ncbi.nlm.nih.gov/geo/), under accession number GSE201435. The whole genome sequencing data generated in this study have been submitted to the NCBI SRA database (https://www.ncbi.nlm.nih.gov/bioproject/), under accession number PRJNA832117: https://dataview.ncbi.nlm.nih.gov/object/PRJNA832117. [Extracted from the article]

External cephalic version (ECV) is associated with a moderate degree of pain. Virtual reality (VR) is a technology that has shown promise in offering procedural analgesia. We undertook a clinical pilot to assess the viability of VR to reduce pain during ECV. In an open randomised controlled trial (RCT), we randomised 50 women to either VR or standard care each (25 per group). Women receiving VR were administered VR content (Skylights) via a headset. Pre- and post-procedural measures of pain, anxiety, device experience and vital signs were measured. There were no significant differences between groups (VR/no VR) in pain scores (60.68 vs 49.76; p = 0.2), ECV success rates (80% vs 76%; p = 0.7) or anxiety levels. The women receiving VR had a significantly higher anticipation of pain pre-procedurally (70.0 vs 50.0; p = 0.03). 20 (80%) of the VR women indicated that they would use VR again and 22 (88%) indicated they would recommend it to a friend having ECV. There were no significant differences between groups for side effects encountered or changes in vital signs. We have shown that using VR during ECV is feasible and appears safe. Our results inform the design of future RCTs.

GRP94 is an ATP-dependent chaperone able to regulate pro-oncogenic signaling pathways. Previous studies have shown a critical role of GRP94 in brain metastasis (BrM) pathogenesis and progression. In this work, an untargeted lipidomic analysis revealed that some lipid species were altered in GRP94-deficient cells, specially GM2 and GM3 gangliosides. The catalytic pathway of GM2 is affected by the low enzymatic activity of β-Hexosaminidase (HexA), responsible for the hydrolysis of GM2 to GM3. Moreover, a deficiency of the GM2-activator protein (GM2-AP), the cofactor of HexA, is observed without alteration of gene expression, indicating a post-transcriptional alteration of GM2-AP in the GRP94-ablated cells. One plausible explanation of these observations is that GM2-AP is a client of GRP94, resulting in defective GM2 catabolic processing and lysosomal accumulation of GM2 in GRP94-ablated cells. Overall, given the role of gangliosides in cell surface dynamics and signaling, their imbalance might be linked to modifications of cell behaviour acquired in BrM progression. This work indicates that GM2-AP could be an important factor in ganglioside balance maintenance. These findings highlight the relevance of GM3 and GM2 gangliosides in BrM and reveal GM2-AP as a promising diagnosis and therapeutic target in BrM research. [ABSTRACT FROM AUTHOR]

Accidental introduction through ballast water and biofouling are currently the main factors responsible for spreading non-indigenous species in the marine realm. In the Southwestern Atlantic, two scleractinian corals, Tubastraea coccinea and T. tagusensis, have been introduced by opportunistic colonization in 1980 and are now widespread along more than 3,500 km of coastline. To better understand the invasion process and the role of vectors in spreading these species, we sampled 306 and 173 colonies of T. coccinea and T. tagusensis from invaded sites, possible vectors and one native population. Analyses revealed a higher diversity of multi-locus genotypes (MLGs) on vectors, suggesting that they were contaminated prior to their arrival in the Southwestern Atlantic, and a high proportion of clones at invaded sites, with few genotypes spread over ~2,000 km. This broad distribution is most likely a result of secondary introductions through the transport of contaminated vectors. Results also suggest the occurrence of multiple invasions, mainly in the northernmost sites. In summary, clonality, secondary introductions, and multiple invasions are the main reasons for the broad spread and invasive success of Tubastraea spp. in the Southwestern Atlantic. Consequently, the correct control of vectors is the most effective approach for management and prevention of new invasions. [ABSTRACT FROM AUTHOR]

Pesticide use is one of the main causes of pollinator declines in agricultural ecosystems. Traditionally, most laboratory studies on bee ecotoxicology test acute exposure to single compounds. However, under field conditions, bees are often chronically exposed to a variety of chemicals, with potential synergistic effects. We studied the effects of field-realistic concentrations of three pesticides measured in pollen and nectar of commercial melon fields on the solitary bee Osmia bicornis L. We orally exposed females of this species throughout their life span to 8 treatments combining two neonicotinoid insecticides (acetamiprid, imidacloprid) and a triazole fungicide (myclobutanil) via pollen and sugar syrup. We measured pollen and syrup consumption, longevity, ovary maturation and thermogenesis. Pesticide intake was three orders of magnitude higher via syrup than pollen. At the tested concentrations, no synergistic effects emerged, and we found no effects on longevity and ovary maturation. However, all treatments containing imidacloprid resulted in suppressed syrup consumption and drastic decreases in thoracic temperature and bee activity. Our results have important implications for pesticide regulation. If we had measured only lethal effects we would have wrongly concluded that the pesticide combinations containing imidacloprid were safe to O. bicornis. The incorporation of tests specifically intended to detect sublethal effects in bee risk assessment schemes should be an urgent priority. In this way, the effects of pesticide exposure on the dynamics of bee populations in agroecosystems will be better assessed. [ABSTRACT FROM AUTHOR]

Cognitive biases, often used as indices of affective and emotional states, are associated with individual differences in personality in humans and have been observed in nonhuman animals, including dogs. Although dogs have complementary advantages over traditional animal models of human cognition, little is known about the relationship between dogs' cognitive bias and personality. Here, we examined in 29 family dogs (representing 14 breeds and 12 mutts; Mage = 4.59 years, SD = 2.90), the association between naturally occurring – as opposed to experimentally induced – cognitive bias, indexed via active choice behavior in a Go/No-Go (GNG) paradigm reflecting positive/negative expectations about ambiguous stimuli, and owner-rated personality. In a subsample we additionally assessed whether prior inhibition, personality, and inattention (IA)/hyperactivity/impulsivity (H/I) results could be replicated in a modified paradigm. We also explored whether expanding the response time-window would increase GNG errors and whether dogs exhibited differences in their behavioral approach to uncertainty. Findings indicated dogs with higher conscientiousness and extraversion scores were more likely to exhibit a "go" response to ambiguous stimuli. Replicability across prior and current results was generally established, e.g., as previously, IA did not predict GNG performance but extraversion did, whereas H/I predicted different indices of GNG performance. Increased response time-window did not result in differential performance, except for less commission errors. No differences in behavioral response strategy to trained "no-go" and to ambiguous stimuli were apparent. Results evince the dog is a promising animal model of the association between an optimistic cognitive bias and personality. [ABSTRACT FROM AUTHOR]

Appetitive memories play a crucial role in learning and behavior, but under certain circumstances, such memories become maladaptive and play a vital role in addiction and other psychopathologies. Recent scientific research has demonstrated that memories can be modified following their reactivation through memory retrieval in a process termed memory reconsolidation. Several nonpharmacological behavioral manipulations yielded mixed results in their capacity to alter maladaptive memories in humans. Here, we aimed to translate the promising findings observed in rodents to humans. We constructed a novel three-day procedure using aversive counterconditioning to alter appetitive memories after short memory retrieval. On the first day, we used appetitive conditioning to form appetitive memories. On the second day, we retrieved these appetitive memories in one group (Retrieval group) but not in a second group. Subsequently, all participants underwent counterconditioning. On the third day, we attempted to reinstate the appetitive memories from day one. We observed a significant reduction in the reinstatement of the original appetitive memory when counterconditioning was induced following memory retrieval. Here, we provide a novel human paradigm that models several memory processes and demonstrate memory attenuation when counterconditioned after its retrieval. This paradigm can be used to study complex appetitive memory dynamics, e.g., memory reconsolidation and its underlying brain mechanisms. [ABSTRACT FROM AUTHOR]

While the phrase ‘foraging bumblebee’ brings to mind a bumbling bee flying flower to flower in a sunny meadow, foraging is a complicated series of behaviors such as: locating a floral patch; selecting a flower-type; learning handling skills for pollen and nectar extraction; determining when to move-on from a patch; learning within-patch paths (traplining); and learning efficient hive-to-patch routes (spatial navigation). Thus the term ‘forager’ encompasses multiple distinct behaviors that rely on different sensory modalities. Despite a robust literature on bumblebee foraging behavior, few studies are directly relevant to sensory-guided search; i.e. how workers locate novel patches. The first step in answering this question is to determine what sensory information is available to searching bumblebees. This manuscript presents a computational model that elucidates the relative frequency of visual and olfactory cues that are available to workers searching for floral resources under a range of ecologically relevant scenarios. Model results indicate that odor is the most common sensory cue encountered during search flights. When the likelihood of odor-plume contact is higher, odor-encounter is ubiquitous. While integrative (visual + olfactory) cues are common when foragers are searching for larger flowers (e.g. Echinacea), they become rare when foragers are searching for small flowers (e.g. Penstemon). Visual cues are only encountered in isolation when foragers are seeking large flowers with a low odor-plume contact probability. These results indicate that despite the multisensory nature of floral signals, different modalities may be encountered in isolation during search-behavior, as opposed to the reliably multimodal signals encountered during patch-exploitation or nectar/ pollen acquisition. [ABSTRACT FROM AUTHOR]