A prognostic model was proposed using seric levels of ANGPT2, STC1 and CD138 in 97 mCRC patients. Our results provide evidence that ANGPT2 is a prognostic factor in localized CRC and defined a specific CRC subset with potential clinical implementation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.A single albino specimen of the lanternshark, Lucifer’s shark (Etmopterus lucifer), is reported here. The specimen was found amongst museum collections, having been captured near Cape Palliser, off the North Island of New Zealand in 1984. Morphometrics are reported, and with no retainment of pigmentation, the specimen is considered a complete albino. This is the first record of albinism for the family Etmopteridae and one of a handful of records for any deep-sea chondrichthyans. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Diatoms have relatively high biomass in mid- to high-latitude oceans, which is also the most sensitive region to climate change. Photoautotrophs are thus predicted to become exposed to both higher temperatures and increased solar irradiance. In this study we examined the consequences of such changes for the growth and photo-physiology of two diatoms by mimicking the scenarios that correspond to present day and that predicted for the end of this century. Elevated light induced higher rates of damage to photosystem II (PSII) that significantly reduced photochemical yields of both diatoms. Treatments including UV radiation induced ~50% inhibition of PSII under present PAR levels. Generally, warming alleviated UVR inhibition, resulting in higher photochemical yields, and faster recovery during dim light exposure. Therefore, concurrent increase of irradiance and temperature mitigated UV inhibition of PSII by 8-15%. The growth was stimulated by warming under PAR treatment, while less stimulation, or even decreased growth rates, were found under the PAR+UVR treatment. Results suggest that ocean warming could fully offset the inhibition of high light on PSII. However, under the latter higher UVR stress scenario, the energetic expenditure required by the diatoms to repair damage could lead to their lower overall growth in future oceans. This article is protected by copyright. All rights reserved.Deficiency of activity-induced expression of brain-derived neurotrophic factor BDNF) disturbs neurotransmitter gene expression. Enriched environment treatment (EET) ameliorates the defects. However, how BDNF deficiency and EET affect neurotransmitter gene expression differently across ages remains unclear. We addressed this question by determining neurotransmitter gene expression across three life stages in wild-type and activity-dependent BDNF deficient (KIV) mice. Mice received 2-months of standard control treatment (SCT) or EET at early-life development (ED 0-2 months), young adulthood (2-4 months), and old adulthood (12-14 months)(N=16/group). Half of these mice received additional one-month SCT to examine persisting EET effects. High-throughput qRT-PCR measured expression of 81 genes for dopamine, adrenaline, serotonin, GABA, glutamate, acetylcholine, and BDNF systems in the frontal cortex (FC) and hippocampus. Results revealed that BDNF deficiency mostly reduced neurotransmitter gene expression, greatest at ED in the FC. EET increased expression of a larger number of genes at ED than adulthood, particularly in the KIV FC. Many genes downregulated in KIV mice were upregulated by EET, which persisted when EET was provided at ED (e.g., 5HTT, ADRA1D, GRIA3, GABRA5, GABBR2). In both regions, BDNF deficiency decreased the density of gene co-expression network specifically at ED, while EET increased the density and hub genes (e.g., GAT1, GABRG3, GRIN1, CHRNA7). These results suggest that BDNF deficiency, which occurs under chronic stress, causes neurotransmitter dysregulations prominently at ED, particularly in the FC. EET at ED may be most effective to normalize the dysregulations, providing persisting effects later in life. This article is protected by copyright. All rights reserved.Long-chain polyunsaturated fatty acid biosynthesis, a process to convert C18 polyunsaturated fatty acids to eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or arachidonic acid (ARA) requires the concerted activities of two enzymes, the fatty acyl desaturase (Fads) and elongase (Elovl). This study highlights the cloning, functional characterisation and tissue expression pattern of a Fads and an Elovl from the Boddart’s goggle-eyed goby (Boleophthalmus boddarti), a mudskipper species widely distributed in the Indo-Pacific region. Phylogenetic analysis revealed that the cloned Fads and Elovl are clustered with other teleost Fads2 and Elovl5 orthologs, respectively. Interrogation of the genome of several mudskipper species, namely B. pectinirostris, Periophthalmus schlosseri and P. magnuspinnatus revealed a single Fads2 for each respective species while two elongases, Elovl5 and Elovl4 were detected. Using a heterologous yeast assay, the B. boddarti Fads2 was shown to possess low desaturation activity on C18 PUFA. In addition, there was no desaturation of C20 and C22 substrates. In comparison, the Elovl5 showed a wide range of substrate specificity, with capacity to elongate C18, C20 and C22 PUFA substrates. We identified an amino acid residue in the B. boddarti Elovl5 that affect the capacity to elongate C225n-3. Both genes are highly expressed in brain tissue. Among all tissues, DHA is highly concentrated in neuron-rich tissues while EPA is highly deposited in gills. Taken together, the results showed that due to disability of desaturation steps, B. boddarti is unable to biosynthesis LC-PUFA, relying on dietary intake to acquire these nutrients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.TIM-3 has been considered as a target in cancer immunotherapy. In T cells, inhibitory as well as activating functions 0have been ascribed to this molecule. Its role may therefore depend on the state of T cells and on the presence of interaction partners capable to perform functional pairing. CEACAM1 has been proposed to bind TIM-3 and to regulate its function. Using a T cell reporter platform we confirmed CEACAM1 mediated inhibition, but CEACAM1 did not functionally engage TIM-3. TIM-3 and CEACAM1 co-expression was limited to a small subset of activated T cells. Moreover, results obtained in extensive binding studies, were not in support for an interaction between TIM-3 and CEACAM1. Cytoplasmic sequences derived from TIM-3 induced inhibitory signaling in our human T cell reporter system. Our results indicate that TIM-3 functions independently of CEACAM1 and that this receptor has the capability to promote inhibitory signaling pathways in human T cells. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Targeted photodynamic therapy (PDT) in head/neck cancer patients with a conjugate of the anti-epidermal growth factor receptor (EGFR) antibody, Cetuximab and a phthalocyanine photosensitizer IR700DX is under way, but the exact mechanisms of action are still not fully understood. In this study the EGFR over-expressing human head/neck OSC-19-luc2-cGFP tumour with transfected GFP gene was used in a skin-fold window-chamber model in BALB/c nude mice. The uptake and localization of the conjugate in the tumour and its surrounding normal tissues were studied by an intravital confocal laser scanning microscopy with image analyses. The tumour was also irradiated with 690 nm laser light 24 hours after conjugate administration. The vascular and tumour responses were examined by morphological evaluation and immunohistochemistry (IHC). The amount of conjugate in the tumour peaked at 24-48 hours after injection. Image analyses of colocalization correlation parameters demonstrated a high fraction of the conjugate IR700DX colocalised in the GFP-expressing tumour cells. PDT-treated tumours showed extensive necrotic/apoptotic destruction with little vascular damage; while IHC showed no HIF-1α expression and decreased EGFR and Ki67 expression with activated caspase-3 overexpression, indicating a direct killing of tumour cells through both necrotic and apoptotic cell death. This article is protected by copyright. All rights reserved.A laboratory flume was constructed to examine substrate effects on aquatic development. The flume was designed as a once through system with a submerged cobble filled corebox. Lake whitefish (Coregonus clupeaformis) embryos and temperature probes were deployed at multiple sites within the cobble and in the open water channel. Embryos were incubated in the flume for two different experimental periods; one to examine substrate impacts during natural lake cooling (37 d December 5, 2016 – January 10, 2017) and the second to investigate substrate effects while administering a twice weekly 1 h heat shock (51 d January 11 – March 2, 2017). During incubation, no significant difference was found in the average temperature between locations; however, temperatures were more stable within the cobble. Following both incubation periods, embryos retrieved from the cobble were significantly smaller in both dry mass and body length by up to 20%. These results demonstrate differences between embryos submerged in a cobble substrate and in the open water column, highlighting the need to consider the physical influences from the incubation environment when assessing development effects as part of any scientific study or environmental assessment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Hereditary nemaline myopathy (NM) is one of the most common congenital myopathies with the histopathological findings of nemaline bodies. We used targeted next-generation sequencing to identify causative mutations in 48 NM patients with confirmed myopathological diagnosis, analyze the mutational spectrum and phenotypic features. Furthermore, reverse transcription polymerase chain reaction (RT-PCR) was used to confirm the pathogenic effect of one nebulin (NEB) splicing variant. The results showed that variants were found in five NM-associated genes, including NEB, actin alpha 1 (ACTA1), troponin T1, Kelch repeat and BTB domain-containing 13, and cofilin-2, in 34 (73.9%), 7 (15.2%), 3 (6.5%), 1 (2.2%), and 1 (2.2%) patients, respectively, in a total of 46/48 (95.8%) NM patients. Of the total 64 variants identified, 51 were novel variants including 26 pathogenic, 1 probably pathogenic, and 24 variant of uncertain significance (VUS). Notably, one NEB splicing mutation, c.21417+3A>G causing exon 144 splicing (NM_001164508.1), as confirmed by RT-PCR, was found in 52.9% (18 patients) of NEB variant-carrying patients. Typical congenital NM, the most common clinical subtype (60.4%), was associated with five NM genes. We concluded that hereditary NM showed a highly variable genetic spectrum. NEB was the most frequent causative gene in this Chinese cohort, followed by ACTA1. We found a hotspot splicing mutation in NEB among Chinese cohort. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.