The growing needs of genetic counselling—Feasibility in utilization of tele-genetic counselling in Asia and Hong Kong

The need for the expansion of genomic services has been at a record time high in the past decade. As technological advancement continues to strengthen the entire genetic and genomic pipeline and clinical operational workflow, the major challenge remains to be the speed of workforce development to meet service growth. In particular, the international expansion of genetic counselling (GC) services has been a topic of interest for the past few years. GC is an emerging profession in most of Asia, and in many countries the profession of GC often refers to physicians or front-line health workers with expertise in genetics to provide GC services rather than being a specific independent profession. As genetic and genomic services, especially pre-test and post-test GC, expand globally, the need to tackle the longstanding obstacles of GC personnel shortage and funding issues must not be overlooked. There is an urgent need internationally, and especially in Asia, where GC profession is comparatively less well-established, to seek alternative approaches to meet service demand. The present review examines the global development and feasibility of tele-genetics and tele-genetic counselling (TGC), and serves as the foundation to explore a possible roadmap in Hong Kong via the Hong Kong Genome Project

Morton Lecture Morton Lecture Form and flexibility in phosphoinositide 3-kinases

Abstract PI3Ks (phosphoinositide 3-kinases) have important roles in a variety of cellular activities, including survival, proliferation, growth, shape, migration and intracellular sorting. Consistent with their function in cell survival and growth, the gene for the class Iα PI3K catalytic subunit is a common site of gain-of-function mutations in cancers. Ongoing structural studies of these enzymes and the complexes they make with their regulatory subunits have helped to clarify the mechanistic basis of this role in tumour development. The broad spectrum of biological activities associated with various isotypes of class I PI3Ks has led to an intense search for isotype-specific inhibitors as tools in mammalian cell biology and for therapeutic application. Structural studies of the class I PI3Ks suggest that flexibility may be a component of the catalytic cycle of the enzymes

The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors.

Deregulation of the phosphoinositide-3-OH kinase (PI(3)K) pathway has been implicated in numerous pathologies including cancer, diabetes, thrombosis, rheumatoid arthritis and asthma. Recently, small-molecule and ATP-competitive PI(3)K inhibitors with a wide range of selectivities have entered clinical development. In order to understand the mechanisms underlying the isoform selectivity of these inhibitors, we developed a new expression strategy that enabled us to determine to our knowledge the first crystal structure of the catalytic subunit of the class IA PI(3)K p110 delta. Structures of this enzyme in complex with a broad panel of isoform- and pan-selective class I PI(3)K inhibitors reveal that selectivity toward p110 delta can be achieved by exploiting its conformational flexibility and the sequence diversity of active site residues that do not contact ATP. We have used these observations to rationalize and synthesize highly selective inhibitors for p110 delta with greatly improved potencies

「回首．動情．傳承」長者生命故事計劃

嶺南大學亞太老年學研究中心獲華人永遠墳場管理委員會（「華永會」）資助為期一年的「回首．動情．傳承」長者生命故事計劃(「計劃」)。此計劃旨在讓青年人認識長者生命經驗，學習克服困難與挫折以提升抗逆力，建立正向人生觀。 近年，主流媒體經常批評年輕人的負面人生觀，例如：「躺平主義」、「享樂主義」、「犬儒心態」等，亦不時看到青年人輕生的新聞。我們曾在大學內處理過不少受情緒困擾及企圖自殺的個案，與學生深入交流後，發現他們面對着沉重的學業壓力、財政困難或複雜的家庭關係，內心充滿掙扎不安。 此計劃讓嶺大學生與長者導師進行深度的對談，透過了解長者走過的路、他們經歷過的挫折和教訓，給予年輕人生命的啟示。如果我們以旅遊比喻人生，長者就像環遊世界的資深背包客，即使大家遊覽不同的地點、觀賞過不同的風景，他們總能夠分享一些旅遊的心得，讓新手遊客走少一點冤枉路，或領悟到旅遊的樂趣和意義。長者亦可以藉由敍述人生片段回顧他們生命中的故事，學習接納過去，增加自我認同感。青年人創作生命教育書冊，將長者積極的人生觀傳給年輕一代，並藉此鼓勵其他長者豁達地度過餘年。 我們於2022年初招募嶺南大學學生接受「生命故事敍述」培訓，內容包括：本港的人口老化現象、敍述治療理論、與長者溝通的技巧及模擬實踐練習等，以裝備同學的知識和技巧。本中心再向屯門、元朗區的長者機構發邀請信，誠邀長者擔任生命導師接受訪問。 嶺大安排同學以兩人一組的小隊形式，於2022年6至7月期間前往長者中心、日間護理中心、嶺南大學或長者家中，與十二位長者進行深入訪談。訪談結束後，同學根據訪談的內容，為長者書寫他們獨特的生命故事。例如在人離鄉賤的異國環境下，努力打拼事業的Alfred；堅持不懈持續進修的淑芹和馮春林；即使沒機會求學，仍憑一雙巧手闖出一片天的譚惠；在文化大革命的漩渦中，憑着熱忱而改變命運的蘭英；還有為家人無私奉獻的鳳群、歐婆婆、雅芳及細女；離鄉別井勇闖異地的阿美和阿水；即使被家人賣去做「妹仔」，仍能以「阿Q精神」面對的諒餘。 為保障長者的私隱權益，本書內所有刊登之故事皆經過受訪者或社工審閱，部份受訪者選擇以化名的形式來分享自己的故事，我們亦移除了部份敏感的個人資料。https://commons.ln.edu.hk/apias_guide/1008/thumbnail.jp

Towards a global partnership model in interprofessional education for cross-sector problem-solving

Objectives A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. Methods This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students’ data. Results We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest–posttest differences in students’ readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students’ social interaction anxiety after the IPE simulation. Conclusions The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education

Evolutionary and Transmission Dynamics of Reassortant H5N1 Influenza Virus in Indonesia

H5N1 highly pathogenic avian influenza (HPAI) viruses have seriously affected the Asian poultry industry since their recurrence in 2003. The viruses pose a threat of emergence of a global pandemic influenza through point mutation or reassortment leading to a strain that can effectively transmit among humans. In this study, we present phylogenetic evidences for the interlineage reassortment among H5N1 HPAI viruses isolated from humans, cats, and birds in Indonesia, and identify the potential genetic parents of the reassorted genome segments. Parsimony analyses of viral phylogeography suggest that the reassortant viruses may have originated from greater Jakarta and surroundings, and subsequently spread to other regions in the West Java province. In addition, Bayesian methods were used to elucidate the genetic diversity dynamics of the reassortant strain and one of its genetic parents, which revealed a more rapid initial growth of genetic diversity in the reassortant viruses relative to their genetic parent. These results demonstrate that interlineage exchange of genetic information may play a pivotal role in determining viral genetic diversity in a focal population. Moreover, our study also revealed significantly stronger diversifying selection on the M1 and PB2 genes in the lineages preceding and subsequent to the emergence of the reassortant viruses, respectively. We discuss how the corresponding mutations might drive the adaptation and onward transmission of the newly formed reassortant viruses

Functional annotation of human long noncoding RNAs via molecular phenotyping

Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-todate lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.Peer reviewe

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Identification of Diverse Stress-Responsive Xylem Sap Peptides in Soybean

Increasing evidence has revealed that plant secretory peptides are involved in the long-distance signaling pathways that help to regulate plant development and signal stress responses. In this study, we purified small peptides from soybean (Glycine max) xylem sap via o-chlorophenol extraction and conducted an in-depth peptidomic analysis using a mass spectrometry (MS) and bioinformatics approach. We successfully identified 14 post-translationally modified peptide groups belonging to the peptide families CEP (C-terminally encoded peptides), CLE (CLAVATA3/embryo surrounding region-related), PSY (plant peptides containing tyrosine sulfation), and XAP (xylem sap-associated peptides). Quantitative PCR (qPCR) analysis showed unique tissue expression patterns among the peptide-encoding genes. Further qPCR analysis of some of the peptide-encoding genes showed differential stress-response profiles toward various abiotic stress factors. Targeted MS-based quantification of the nitrogen deficiency-responsive peptides, GmXAP6a and GmCEP-XSP1, demonstrated upregulation of peptide translocation in xylem sap under nitrogen-deficiency stress. Quantitative proteomic analysis of GmCEP-XSP1 overexpression in hairy soybean roots revealed that GmCEP-XSP1 significantly impacts stress response-related proteins. This study provides new insights that root-to-shoot peptide signaling plays important roles in regulating plant stress-response mechanisms