New record of the Japanese seahorse Hippocampus mohnikei Bleeker, 1853 (Syngnathiformes: Syngnathidae) in Hong Kong waters

Funding: This study was supported by the Consultancy Project (AFCD/SQ/13/17) of the Agriculture, Fisheries and Conservation Department of the Government of the Hong Kong SAR and the Collaborative Research Fund (C7013-19G) of the Hong Kong Research Grants Council.A new record of Hippocampus mohnikei Bleeker, 1853 was confirmed in Hong Kong through morphological and molecular identification. It is highly possible that there is an established population of H. mohnikei in Hong Kong due to continuous sightings by citizen scientists in the past nine years. The record is significant from a biogeographical perspective as it connects the distributions of known populations in northern China and Japan to those spanning Thailand to India. This further affirms the status of Hong Kong as a hotspot for seahorse biodiversity and conservation in China.Publisher PDFPeer reviewe

The apobec mutational activity in multiple myeloma: from diagnosis to cell lines

Next generation sequencing (NGS) studies have highlighted the role of aberrant activity of APOBEC DNA deaminases in generating the mu- tational repertoire of multiple myeloma (MM). However, the contribu- tion of this mutational process across the landscape of plasma cell dyscrasias, or its prognostic role, has never been investigated in detail. To answer these unexplored aspects of MM biology, we used published NGS data from our own work as well as others, including the large CoMMpass trial for a total of 1153 whole-exomes of MM. Furthermore, we investigated 5 MGUS, 6 primary plasma cell leukemias (pPCL) and 18 MM cell lines (MMCL). Overall, we identified signatures of two mu- tational processes, one related to spontaneous deamination of methy- lated cytosines (30% of variants, range 0-100%) and one attributed to aberrant APOBEC activity (70% of variants, range 0-100%). APOBEC contribution was extremely heterogeneous among MM patients, but was correlated with a higher mutational burden (r=0.71, p=<0.0001) and with MAF gene translocations t(14;16) and t(14;20). The activity of APOBEC increased from MGUS to MM to pPCL, both in terms of ab- solute number of mutations and as percentage contribution. In MMCL we instead observed a bi-modal distribution whereby 8 cell lines showed the highest numbers of mutations caused by APOBEC (5/8 car- ried MAF translocations), while 10 where virtually devoid of APOBEC mutations (0/10 carried MAF translocations). The contribution of APOBEC to the total mutational repertoire in MM had a clear prognos- tic impact. MM patients with APOBEC mutations in the lowest quartile had a survival advantage over patients with APOBEC mutations in the highest quartile both in terms of progression-free survival (3-y PFS 46% vs 67% months, p=<0.0001) and overall survival (3-y OS 52% vs 83%, p=0.0084). This association was retained in a multivariate model that included age, gender, cytogenetic class, ISS, and quartiles of mutational load both in PFS [p=0.02, HR 2.06 (95IC 1.11-3.81] and OS [p=0.02, HR 2.88 (95IC 1.17-7.09)]. Interestingly we found that APOBEC mutations in the 4th quartile retained its independent prognostic respect to high mutational load and presence of MAF translocations. Overall, our data suggest that APOBEC-mediated mutagenesis is strongly involved in MM pathogenesis and its activity persists during different phases of evolution, playing a critical role in MM genomic complexity, and im- pacting prognosis of the patients

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

APRIL and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment

Here we show that overexpression or activation of B-cell maturation antigen (BCMA) by its ligand, a proliferation-inducing ligand (APRIL), promotes human multiple myeloma (MM) progression in vivo. BCMA downregulation strongly decreases viability and MM colony formation; conversely, BCMA overexpression augments MM cell growth and survival via induction of protein kinase B (AKT), MAPK, and nuclear factor (NF)-\u3baB signaling cascades. Importantly, BCMA promotes in vivo growth of xenografted MM cells harboring p53 mutation in mice. BCMA-overexpressing tumors exhibit significantly increased CD31/microvessel density and vascular endothelial growth factor compared with paired control tumors. These tumors also express increased transcripts crucial for osteoclast activation, adhesion, and angiogenesis/metastasis, as well as genes mediating immune inhibition including programmed death ligand 1, transforming growth factor \u3b2, and interleukin 10. These target genes are consistently induced by paracrine APRIL binding to BCMA on MM cells, which is blocked by an antagonistic anti-APRIL monoclonal antibody hAPRIL01A (01A). 01A is cytotoxic against MM cells even in the presence of protective bone marrow (BM) myeloid cells including osteoclasts, macrophages, and plasmacytoid dendritic cells. 01A further decreases APRIL-induced adhesion and migration of MM cells via blockade of canonical and noncanonical NF-\u3baB pathways. Moreover, 01A prevents in vivo MM cell growth within implanted human bone chips in SCID mice. Finally, the effect of 01A on MM cell viability is enhanced by lenalidomide and bortezomib. Taken together, these data delineate new molecular mechanisms of in vivo MM growth and immunosuppression critically dependent on BCMA and APRIL in the BM microenvironment, further supporting targeting this prominent pathway in MM