Jonathan P. Sorenson and Jonathan Webster
Math. Comp. 89 (2020), 1953-1968.
Abstract, references and article information

Ning Zhang, Jia Wu and Liwei Zhang
Math. Comp. 89 (2020), 1867-1894.
Abstract, references and article information

Changfeng Gui, Kelei Wang and Jucheng Wei
Trans. Amer. Math. Soc. 373 (2020), 3649-3668.
Abstract, references and article information

Feng Xu
Trans. Amer. Math. Soc. 373 (2020), 3515-3539.
Abstract, references and article information

Joseph Reid
Proc. Amer. Math. Soc. 148 (2020), 2331-2343.
Abstract, references and article information

In recent times, criminal damage has been repeatedly inflicted on our court buildings through graffiti. Some went as far as making derogatory remarks against specific judges which may amount to contempt of court. It is bewildering as to what such acts could achieve except a futile attempt to undermine the very core value that we cherish and respect.

Judicial independence is the key building block to our society. These rampant acts and statements, and for that matter, any views expressed in society or media, would not in any way usurp the decision-making process in court proceedings, nor will they affect our judicial independence as our judges will continue to decide cases based only on evidence and law, setting out how they have arrived at such decisions in their judgments, which are available to the general public. They have taken a judicial oath to administer justice without fear or favour and it is their duty to so do.

Judges in Hong Kong are appointed upon the recommendation by a statutory committee comprising nine members including the Chief Justice of the Court of Final Appeal, the Secretary for Justice, two judges from the Judiciary, one barrister and one solicitor, as well as three eminent and respected members of the society not connected with the practice of law. Our judges would not be subjected to any political vetting. The only criteria upon which they are considered before appointment is the judicial and professional quality that contributes to our renowned judicial independence.

Judges enjoy security of tenure and immunity. Upon the appointment, district court judges and above are precluded from returning to practice in Hong Kong as a barrister or a solicitor. This “non-revolving door” system has worked well in preventing perceived potential conflicts of interest and enhances the independence of our judiciary.

Our judges manifest the highest professional and judicial quality as well as impartiality through the reasoned judgments that they deliver. Hong Kong cases are often cited in overseas jurisprudence evidencing the confidence and respect of the global legal community in Hong Kong’s judicial and legal systems.

The institutional framework described above, the guarantee of judicial independence explicitly set out in the Basic Law and the quality of our judgments contribute to the much respected judiciary and rule of law in Hong Kong. To top it all is that eminent and highly respected judges from apex court of other common law jurisdictions sit on our Court of Final Appeal as non-permanent judges. They sit on all types of cases, from commercial, criminal to constitutional and have witnessed Hong Kong’s system in administering justice.

One of our non-permanent judges of the Court of Final Appeal, the Right Honourable the Lord Neuberger of Abbotsbury (former President of the Supreme Court of England and Wales who presided over the Brexit case), pointed out in a seminar in 2017 that his own direct experience as a non-permanent judge since 2010 proved that the Permanent Judges of the Court of Final Appeal are as institutionally independent and impartial. He also said that he has every reason to believe that this is equally true of the judges in the other courts of Hong Kong. He even said he would not be sitting in the Court of Final Appeal if he had any serious concerns about judicial independence or judicial impartiality in Hong Kong.

More recently, the Right Honourable Beverley McLachlin, PC, another non-permanent judge of the Court of Final Appeal and also a retired chief justice of Canada, described in an interview that Hong Kong’s law is very rigorously applied, the judges are of high calibre, it is a very high level of judging, and the court is independent.

These remarks from eminent and respected judges from around the world speak volume about Hong Kong. One cannot help but be perplexed as to why some chose to try to undermine these core values baselessly and insidiously. It behoves each of us, in particular the legal sector including the two branches of the legal profession, to protect our judicial independence that underpins Hong Kong’s success and encourage others to join hands through our own sphere of influence. It is high time we bring back the Hong Kong we are familiar with.

Secretary for Justice Teresa Cheng wrote this article and posted it on her blog on January 5.

The 52nd edition of the Index of Streets, House Numbers & Lots in Hong Kong, Kowloon & New Kowloon, and the 21st edition of the New Territories Lot/Address Cross Reference Table on compact disc are now on sale.

Licences for using the street index and the cross reference table on computer networks are also available for sale.

An online version of the new street index and cross reference table is available on the Land Registry's website or the Integrated Registration Information System Online Services website.

They are designed to facilitate land record searches by correlating property addresses, building names or lot numbers.

The latest edition of the index features 444 amendments, 11 new streets, and the addition of 30 new lots, sections or subsections.

The latest edition of the table features 1,522 amendments, 10 new streets, and 1,146 new lots, sections or subsections.

Click here for order forms.

Joseph B. Nelson
Aug 1, 2017; 30:171-174
From Research to Practice

Mays H. Vue
Aug 1, 2011; 24:171-177
Pharmacy and Therapeutics

Abdur Rehman
Nov 1, 2011; 24:234-238
Pharmacy and Therapeutics

DeepMind's cofounder and head of applied artificial intelligence, Mustafa Suleyman, has abruptly left the company for an indefinite period

General Stations: 1 to 2 (Health Risk: Low)

Roadside Stations: 2 (Health Risk: Low)

(Fundação de Amparo à Pesquisa do Estado de São Paulo) Thanks to its magnetic properties, the material -- zinc-doped manganese chromite -- can be used in a range of products, from gas sensors to data storage devices.

The peroxisome is a subcellular organelle that functions in essential metabolic pathways, including biosynthesis of plasmalogens, fatty acid β-oxidation of very-long-chain fatty acids, and degradation of hydrogen peroxide. Peroxisome biogenesis disorders (PBDs) manifest as severe dysfunction in multiple organs, including the central nervous system (CNS), but the pathogenic mechanisms in PBDs are largely unknown. Because CNS integrity is coordinately established and maintained by neural cell interactions, we here investigated whether cell-cell communication is impaired and responsible for the neurological defects associated with PBDs. Results from a noncontact co-culture system consisting of primary hippocampal neurons with glial cells revealed that a peroxisome-deficient astrocytic cell line secretes increased levels of brain-derived neurotrophic factor (BDNF), resulting in axonal branching of the neurons. Of note, the BDNF expression in astrocytes was not affected by defects in plasmalogen biosynthesis and peroxisomal fatty acid β-oxidation in the astrocytes. Instead, we found that cytosolic reductive states caused by a mislocalized catalase in the peroxisome-deficient cells induce the elevation in BDNF secretion. Our results suggest that peroxisome deficiency dysregulates neuronal axogenesis by causing a cytosolic reductive state in astrocytes. We conclude that astrocytic peroxisomes regulate BDNF expression and thereby support neuronal integrity and function.

The dextransucrase DSR-OK from the Gram-positive bacterium Oenococcus kitaharae DSM17330 produces a dextran of the highest molar mass reported to date (∼109 g/mol). In this study, we selected a recombinant form, DSR-OKΔ1, to identify molecular determinants involved in the sugar polymerization mechanism and that confer its ability to produce a very-high-molar-mass polymer. In domain V of DSR-OK, we identified seven putative sugar-binding pockets characteristic of glycoside hydrolase 70 (GH70) glucansucrases that are known to be involved in glucan binding. We investigated their role in polymer synthesis through several approaches, including monitoring of dextran synthesis, affinity assays, sugar binding pocket deletions, site-directed mutagenesis, and construction of chimeric enzymes. Substitution of only two stacking aromatic residues in two consecutive sugar-binding pockets (variant DSR-OKΔ1-Y1162A-F1228A) induced quasi-complete loss of very-high-molar-mass dextran synthesis, resulting in production of only 10–13 kg/mol polymers. Moreover, the double mutation completely switched the semiprocessive mode of DSR-OKΔ1 toward a distributive one, highlighting the strong influence of these pockets on enzyme processivity. Finally, the position of each pocket relative to the active site also appeared to be important for polymer elongation. We propose that sugar-binding pockets spatially closer to the catalytic domain play a major role in the control of processivity. A deep structural characterization, if possible with large-molar-mass sugar ligands, would allow confirming this hypothesis.

Knowledge of the molecular events in mitochondrial DNA (mtDNA) replication is crucial to understanding the origins of human disorders arising from mitochondrial dysfunction. Twinkle helicase is an essential component of mtDNA replication. Here, we employed atomic force microscopy imaging in air and liquids to visualize ring assembly, DNA binding, and unwinding activity of individual Twinkle hexamers at the single-molecule level. We observed that the Twinkle subunits self-assemble into hexamers and higher-order complexes that can switch between open and closed-ring configurations in the absence of DNA. Our analyses helped visualize Twinkle loading onto and unloading from DNA in an open-ringed configuration. They also revealed that closed-ring conformers bind and unwind several hundred base pairs of duplex DNA at an average rate of ∼240 bp/min. We found that the addition of mitochondrial single-stranded (ss) DNA–binding protein both influences the ways Twinkle loads onto defined DNA substrates and stabilizes the unwound ssDNA product, resulting in a ∼5-fold stimulation of the apparent DNA-unwinding rate. Mitochondrial ssDNA-binding protein also increased the estimated translocation processivity from 1750 to >9000 bp before helicase disassociation, suggesting that more than half of the mitochondrial genome could be unwound by Twinkle during a single DNA-binding event. The strategies used in this work provide a new platform to examine Twinkle disease variants and the core mtDNA replication machinery. They also offer an enhanced framework to investigate molecular mechanisms underlying deletion and depletion of the mitochondrial genome as observed in mitochondrial diseases.

VOLUME 289 (2014) PAGES 30635–30644This article has been withdrawn by Guangnan Chen, Dongkyoo Park, Francis A. Cucinotta, David S. Yu, Xingming Deng, William S. Dynan, Paul W. Doetsch, and Ya Wang. Hongyan Wang, Xiang Wang, Xiangming Zhang, and Xiaobing Tang could not be reached. The last two lanes of the actin immunoblot in Fig. 1A were reused in the last two lanes of the actin immunoblot in Fig. 1C. In Fig. 2A, the γ-H2AX and the merge with DAPI images for no IR treatment do not match. In Fig. 3A, lanes 3 and 4 of the γ-H2AX immunoblot were reused in lanes 7 and 8, and lanes 5 and 6 of the H2A immunoblot were reused in lanes 7 and 8. In Fig. 3B, lanes 5 and 6 of the H2A immunoblot were reused in lanes 7 and 8. In Fig. 3C, lanes 5 and 6 of the γ-H2AX immunoblot were reused in lanes 7 and 8. Additionally, lanes 1 and 2 of the H2A immunoblot were reused in lanes 3 and 4. In Fig. 3D, lanes 1 and 2 of the Mre11 immunoblot from lysates were reused in lanes 4 and 5. In the γ-H2AX immunoblot, lane 3 was reused in lane 7, and lane 4 was reused in lanes 6 and 8. Also in the H2A immunoblot, lanes 1 and 2 were reused in lanes 3 and 4. In Fig. 4B, lanes 2 and 6 of the Mre11 immunoblot from Ogg1−/− cells are the same. In the Ape1...

Although a robust inflammatory response is needed to combat infection, this response must ultimately be terminated to prevent chronic inflammation. One mechanism that terminates inflammatory signaling is the production of alternative mRNA splice forms in the Toll-like receptor (TLR) signaling pathway. Whereas most genes in the TLR pathway encode positive mediators of inflammatory signaling, several, including that encoding the MyD88 signaling adaptor, also produce alternative spliced mRNA isoforms that encode dominant-negative inhibitors of the response. Production of these negatively acting alternatively spliced isoforms is induced by stimulation with the TLR4 agonist lipopolysaccharide (LPS); thus, this alternative pre-mRNA splicing represents a negative feedback loop that terminates TLR signaling and prevents chronic inflammation. In the current study, we investigated the mechanisms regulating the LPS-induced alternative pre-mRNA splicing of the MyD88 transcript in murine macrophages. We found that 1) the induction of the alternatively spliced MyD88 form is due to alternative pre-mRNA splicing and not caused by another RNA regulatory mechanism, 2) MyD88 splicing is regulated by both the MyD88- and TRIF-dependent arms of the TLR signaling pathway, 3) MyD88 splicing is regulated by the NF-κB transcription factor, and 4) NF-κB likely regulates MyD88 alternative pre-mRNA splicing per se rather than regulating splicing indirectly by altering MyD88 transcription. We conclude that alternative splicing of MyD88 may provide a sensitive mechanism that ensures robust termination of inflammation for tissue repair and restoration of normal tissue homeostasis once an infection is controlled.

Kindlins are focal adhesion proteins that regulate integrin activation and outside-in signaling. The kindlin family consists of three members, kindlin-1, -2, and -3. Kindlin-2 is widely expressed in multiple cell types, except those from the hematopoietic lineage. A previous study has reported that the Drosophila Fit1 protein (an ortholog of kindlin-2) prevents abnormal spindle assembly; however, the mechanism remains unknown. Here, we show that kindlin-2 maintains spindle integrity in mitotic human cells. The human neuroblastoma SH-SY5Y cell line expresses only kindlin-2, and we found that when SH-SY5Y cells are depleted of kindlin-2, they exhibit pronounced spindle abnormalities and delayed mitosis. Of note, acetylation of α-tubulin, which maintains microtubule flexibility and stability, was diminished in the kindlin-2–depleted cells. Mechanistically, we found that kindlin-2 maintains α-tubulin acetylation by inhibiting the microtubule-associated deacetylase histone deacetylase 6 (HDAC6) via a signaling pathway involving AKT Ser/Thr kinase (AKT)/glycogen synthase kinase 3β (GSK3β) or paxillin. We also provide evidence that prolonged hypoxia down-regulates kindlin-2 expression, leading to spindle abnormalities not only in the SH-SY5Y cell line, but also cell lines derived from colon and breast tissues. The findings of our study highlight that kindlin-2 regulates mitotic spindle assembly and that this process is perturbed in cancer cells in a hypoxic environment.

We previously reported that overexpression of cytochrome P450 family 24 subfamily A member 1 (CYP24A1) increases lung cancer cell proliferation by activating RAS signaling and that CYP24A1 knockdown inhibits tumor growth. However, the mechanism of CYP24A1-mediated cancer cell proliferation remains unclear. Here, we conducted cell synchronization and biochemical experiments in lung adenocarcinoma cells, revealing a link between CYP24A1 and anaphase-promoting complex (APC), a key cell cycle regulator. We demonstrate that CYP24A1 expression is cell cycle–dependent; it was higher in the G2-M phase and diminished upon G1 entry. CYP24A1 has a functional destruction box (D-box) motif that allows binding with two APC adaptors, CDC20-homologue 1 (CDH1) and cell division cycle 20 (CDC20). Unlike other APC substrates, however, CYP24A1 acted as a pseudo-substrate, inhibiting CDH1 activity and promoting mitotic progression. Conversely, overexpression of a CYP24A1 D-box mutant compromised CDH1 binding, allowing CDH1 hyperactivation, thereby hastening degradation of its substrates cyclin B1 and CDC20, and accumulation of the CDC20 substrate p21, prolonging mitotic exit. These activities also occurred with a CYP24A1 isoform 2 lacking the catalytic cysteine (Cys-462), suggesting that CYP24A1's oncogenic potential is independent of its catalytic activity. CYP24A1 degradation reduced clonogenic survival of mutant KRAS-driven lung cancer cells, and calcitriol treatment increased CYP24A1 levels and tumor burden in Lsl-KRASG12D mice. These results disclose a catalytic activity-independent growth-promoting role of CYP24A1 in mutant KRAS-driven lung cancer. This suggests that CYP24A1 could be therapeutically targeted in lung cancers in which its expression is high.