Publications by authors named "Y Amy Siu"

95 Publications

Total Synthesis of Leiodermatolide A via Transfer Hydrogenative Allylation, Crotylation, and Propargylation: Polyketide Construction beyond Discrete Allyl- or Allenylmetal Reagents.

J Am Chem Soc 2021 Jul 8;143(28):10590-10595. Epub 2021 Jul 8.

Department of Chemistry, University of Texas at Austin, 105 East 24th Street, Austin, Texas 78712, United States.

The total synthesis of leiodermatolide A was accomplished in 13 steps (LLS). Transfer hydrogenative variants of three carbonyl additions that traditionally rely on premetalated reagents (allylation, crotylation, and propargylation) are deployed together in one total synthesis.
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http://dx.doi.org/10.1021/jacs.1c06062DOI Listing
July 2021

The study of 2-dimensional computed tomography scans of the glenoid anatomy in relation to reverse shoulder arthroplasty in the Southern Chinese population.

JSES Int 2021 Jul 3;5(4):714-721. Epub 2021 Apr 3.

Chief of Service, Department of Orthopaedics and Traumatology, North District Hospital, Sheung Shui, Hong Kong S.A.R.

Background: Reverse shoulder arthroplasty is becoming an increasingly common surgical procedure in Hong Kong, as well as in many other countries worldwide. The aim of this study is to describe the glenoid anatomy in the Southern Chinese population. We are interested to know whether commercially available glenoid implants are suitable for this population and whether there are any steps or precautions we can take during surgery to optimize the clinical outcome for these patients.

Method: A total of 244 shoulders of Southern Chinese patients were analyzed using 2-dimensional computed tomography, formatted to align along the scapular axis. The anatomic parameters analyzed included the shape, axial configuration, maximum width, maximum height, version, and presence of bone defect.

Results: In our study, 76.6% of glenoids were pear-shaped, 23.0% were elliptical, and only 0.4% were inverted pear in shape. Of all glenoids, 95.1% of glenoids had posterior-prominent axial configuration, whereas 4.9% had neutral axial configuration. The mean maximum glenoid height for both genders was 33.8 mm, whereas the mean maximum glenoid height was 32.2 mm for women and 36.6 mm for men. The mean maximum glenoid width for both genders was 25.8 mm, whereas the mean maximum glenoid width was 24.8 mm for women and 27.3 mm for men. The differences in measurements between genders were statistically significant. Of all glenoids, 46.3% of the glenoids were retroverted, whereas 53.7% of the glenoids were anteverted. The mean version for both genders was 0.77 degrees anteversion. The mean version was 1.16 degrees anteversion for women and 0.10 degrees anteversion for men. Of the 244 glenoids, 4 had bone defects. In our study, 39.8% of patients had mean maximum glenoid widths that were less than 25 mm, which is the smallest size available for most conventional glenoid baseplates.

Conclusion: A significant portion of the Southern Chinese population has glenoid widths that are smaller than the smallest commercially available glenoid baseplates. Understanding the glenoid anatomy is crucial in the case of reverse shoulder arthroplasty, as it has significant implications in implant design, operative planning, and surgical outcomes.
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http://dx.doi.org/10.1016/j.jseint.2021.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246002PMC
July 2021

Metabolomic Expression of Laryngeal and Hindlimb Muscles in Adult versus Senescent Rats.

Ann Otol Rhinol Laryngol 2021 May 27:34894211014692. Epub 2021 May 27.

Department of Otolaryngology-Head and Neck Surgery, New York University Grossman School of Medicine, New York, NY, USA.

Objectives: (1) Determine the feasibility of obtaining a global, unbiased metabolomic profile on laryngeal muscle in a rat model; (2) evaluate the impact of biological aging on the laryngeal metabolome; and (3) characterize biochemical expression differences between aged and non-aged laryngeal and hindlimb muscle.

Methods: Thyroarytenoid laryngeal muscle and plantaris hindlimb muscle were harvested from 5 young adult (9 months old) and 5 older adult (32 months old) F344BN rats. Tissue was processed and analyzed using LC-MS methods. Detected metabolites were compared to widely used metabolite databases and KEGG pathway enrichment was performed on significant metabolites.

Results: The greatest differences in metabolite expression were between laryngeal and limb muscle with 126 different metabolites found between laryngeal and limb within the young group and 149 different metabolites within the old group. Significant hits between muscle groups highlighted amino acid differences between these tissues. There were more robust differences with age in limb muscle compared to laryngeal muscle.

Conclusions: Amino acid metabolism is a key difference between muscles of the limbs and larynx. Due to the number of differentially expressed metabolites between the 2 muscle groups, caution should be exercised when applying skeletal limb muscle physiology and biology concepts to the vocal muscles in both aged and non-aged musculoskeletal systems. Mechanisms underlying less robust effects of age on laryngeal muscle compared to limb muscle require elucidation.
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http://dx.doi.org/10.1177/00034894211014692DOI Listing
May 2021

CRL4 is a master regulator of D-type cyclins.

Nature 2021 Apr 14;592(7856):789-793. Epub 2021 Apr 14.

Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY, USA.

D-type cyclins are central regulators of the cell division cycle and are among the most frequently deregulated therapeutic targets in human cancer, but the mechanisms that regulate their turnover are still being debated. Here, by combining biochemical and genetics studies in somatic cells, we identify CRL4 (also known as CRL4) as the ubiquitin ligase that targets all three D-type cyclins for degradation. During development, loss of Ambra1 induces the accumulation of D-type cyclins and retinoblastoma (RB) hyperphosphorylation and hyperproliferation, and results in defects of the nervous system that are reduced by treating pregnant mice with the FDA-approved CDK4 and CDK6 (CDK4/6) inhibitor abemaciclib. Moreover, AMBRA1 acts as a tumour suppressor in mouse models and low AMBRA1 mRNA levels are predictive of poor survival in cancer patients. Cancer hotspot mutations in D-type cyclins abrogate their binding to AMBRA1 and induce their stabilization. Finally, a whole-genome, CRISPR-Cas9 screen identified AMBRA1 as a regulator of the response to CDK4/6 inhibition. Loss of AMBRA1 reduces sensitivity to CDK4/6 inhibitors by promoting the formation of complexes of D-type cyclins with CDK2. Collectively, our results reveal the molecular mechanism that controls the stability of D-type cyclins during cell-cycle progression, in development and in human cancer, and implicate AMBRA1 as a critical regulator of the RB pathway.
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http://dx.doi.org/10.1038/s41586-021-03445-yDOI Listing
April 2021

Intracranial artery calcification to screen patients at high risk of recurrent stroke: abridged secondary publication.

Hong Kong Med J 2020 Dec;26 Suppl 7(6):42-44

Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong.

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December 2020
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