C. Tintarev
St. Petersburg Math. J. 31 (2020), 421-434.
Abstract, references and article information

In view of the severe economic repercussions caused by the COVID-19 pandemic globally and locally, the Government announced another package of measures to support the affected individuals and businesses last Wednesday. Two of which are particularly relevant to the legal and dispute resolution sector - the LawTech Fund and the COVID-19 Online Dispute Resolution (ODR) Scheme. The LawTech Fund was briefly introduced in this blog a few days ago. Today, I would like to give an online explanation of the COVID-19 ODR.

In anticipation of an upsurge of disputes arising from or relating to COVID-19, the scheme aims to provide speedy and cost-effective means to resolve such disputes, especially for those involving micro, small and medium-sized enterprises (MSMEs) that may be adversely affected or hard hit by the pandemic. The scheme will engage eBRAM (electronic Business Related Arbitration & Mediation system) to provide ODR services to the general public and businesses, in particular MSMEs, involved in low value disputes.

The scheme plans to cover COVID-19 related disputes with the claim amount for each case to be capped at $500,000. Either one of the parties (claimant or respondent) must be a Hong Kong resident or company and they will only be required to each pay $200 registration fees. Under the scheme, the parties are required to enter into a dispute resolution agreement to record their consent.

The process to be adopted is a multi-tiered dispute resolution mechanism where the parties will first attempt to negotiate their disputes, followed by mediation and if that does not result in settlement, then subsequently to arbitration for a final and binding award. This is in line with the "Mediate First" policy that we have been advocating under our "Mediate First" Pledge Programmes.

The scheme aims to offer a fast and effective means to resolve disputes among parties. Each tier of dispute resolution will be conducted within a limited time. The tiers are devised with a view to avoiding disputes and differences from being entrenched. If the disputes can be resolved successfully and amicably through negotiation or mediation, we hope it will help build and reinforce a harmonious society and enable the parties to preserve their long term business relationship.

We also hope the scheme will have the benefit of job creation and job advancement for mediators and arbitrators (including their pupils). Parties are at liberty to appoint the third party neutral of their choice and if no agreement is reached, there will be a mechanism for appointment. The third party neutrals and the parties or their representatives can still handle cases under the social distancing measures online and indeed to practice on the handling of cases online. We would like the scheme to be launched in June if funding is provided in April.

It is a global trend to develop and use ODR to provide reliable and efficient platform to facilitate alternative dispute resolution. The scheme is in line with the development under Asia-Pacific Economic Cooperation's Collaborative Framework on ODR (APEC Framework), with MSMEs as the major beneficiary. The mechanism of adopting negotiation and mediation in the first stage under the APEC Framework is also to prevent entrenched views on the conflicts, thereby helping to create harmony in society.

Some forms of alternative dispute resolution, such as mediation, are a more cost-effective way to resolve disputes. The costs of mediation are almost always lower than the disputed amounts, making it an economical way to resolve disputes. Mediation can save time too. Some cases may be resolved following just one day of mediation.

LawTech has greatly helped the development of dispute resolution services. The establishment of a safe, reliable and credible platform to provide enterprises with convenient and cost-effective online dispute resolution will become a new trend.

It is one of the major long-term policy objectives of the Department of Justice (DoJ) in recent years to enhance and promote Hong Kong's status as an international legal hub for deal-making and dispute resolution. A further promotion of the use of ODR will help consolidate Hong Kong's position as an international business and financial centre.

The social media accounts of the DoJ's IDAR Office have been introducing the procedure, characteristics and benefits of mediation and arbitration. You may wish to visit the dedicated pages of the IDAR Office to keep abreast of the dispute resolution services.

In addition to the relief measures announced by the Government, the DoJ has also taken the initiative to speed up payment of fees to counsel. Counsel engaged by the DoJ could submit their interim fee notes together with the interim case reports after certain work has been completed. Each case will be considered individually on a case-by-case basis and interim payments could be made. I have enquired and am also glad to learn from the Legal Aid Department and the Duty Lawyer Service that they made similar arrangements.

We are confident that Hong Kong can weather the storm with our fundamental strengths and resilience. We also trust that we would overcome this unprecedented challenge by standing in solidarity.

Secretary for Justice Teresa Cheng wrote this article and posted it on her blog on April 13.

Priscilla Hollander
Jul 1, 2007; 20:159-165
Articles

Cas12a (Cpf1) is an RNA-guided endonuclease in the bacterial type V-A CRISPR-Cas anti-phage immune system that can be repurposed for genome editing. Cas12a can bind and cut dsDNA targets with high specificity in vivo, making it an ideal candidate for expanding the arsenal of enzymes used in precise genome editing. However, this reported high specificity contradicts Cas12a's natural role as an immune effector against rapidly evolving phages. Here, we employed high-throughput in vitro cleavage assays to determine and compare the native cleavage specificities and activities of three different natural Cas12a orthologs (FnCas12a, LbCas12a, and AsCas12a). Surprisingly, we observed pervasive sequence-specific nicking of randomized target libraries, with strong nicking of DNA sequences containing up to four mismatches in the Cas12a-targeted DNA-RNA hybrid sequences. We also found that these nicking and cleavage activities depend on mismatch type and position and vary with Cas12a ortholog and CRISPR RNA sequence. Our analysis further revealed robust nonspecific nicking of dsDNA when Cas12a is activated by binding to a target DNA. Together, our findings reveal that Cas12a has multiple nicking activities against dsDNA substrates and that these activities vary among different Cas12a orthologs.

The transfer of a phosphate from ATP to a protein substrate, a modification known as protein phosphorylation, is catalyzed by protein kinases. Protein kinases play a crucial role in virtually every cellular activity. Recent studies of atypical protein kinases have highlighted the structural similarity of the kinase superfamily despite notable differences in primary amino acid sequence. Here, using a bioinformatics screen, we searched for putative protein kinases in the intracellular bacterial pathogen Legionella pneumophila and identified the type 4 secretion system effector Lpg2603 as a remote member of the protein kinase superfamily. Employing an array of biochemical and structural biology approaches, including in vitro kinase assays and isothermal titration calorimetry, we show that Lpg2603 is an active protein kinase with several atypical structural features. Importantly, we found that the eukaryote-specific host signaling molecule inositol hexakisphosphate (IP6) is required for Lpg2603 kinase activity. Crystal structures of Lpg2603 in the apo-form and when bound to IP6 revealed an active-site rearrangement that allows for ATP binding and catalysis. Our results on the structure and activity of Lpg2603 reveal a unique mode of regulation of a protein kinase, provide the first example of a bacterial kinase that requires IP6 for its activation, and may aid future work on the function of this effector during Legionella pathogenesis.

Nucleoside analogues are a valuable experimental tool. Incorporation of these molecules into newly synthesized DNA (i.e. pulse-labeling) is used to monitor cell proliferation or to isolate nascent DNA. Some of the most common nucleoside analogues used for pulse-labeling of DNA in cells are the deoxypyrimidine analogues 5-ethynyl-2'-deoxyuridine (EdU) and 5-ethynyl-2'-deoxycytidine (EdC). Click chemistry enables conjugation of an azide molecule tagged with a fluorescent dye or biotin to the alkyne of the analog, which can then be used to detect incorporation of EdU and EdC into DNA. The use of EdC is often recommended because of the potential cytotoxicity associated with EdU during longer incubations. Here, by comparing the relative incorporation efficiencies of EdU and EdC during short 30-min pulses, we demonstrate significantly lower incorporation of EdC than of EdU in noninfected human fibroblast cells or in cells infected with either human cytomegalovirus or Kaposi's sarcoma-associated herpesvirus. Interestingly, cells infected with herpes simplex virus type-1 (HSV-1) incorporated EdC and EdU at similar levels during short pulses. Of note, exogenous expression of HSV-1 thymidine kinase increased the incorporation efficiency of EdC. These results highlight the limitations when using substituted pyrimidine analogues in pulse-labeling and suggest that EdU is the preferable nucleoside analogue for short pulse-labeling experiments, resulting in increased recovery and sensitivity for downstream applications. This is an important discovery that may help to better characterize the biochemical properties of different nucleoside analogues with a given kinase, ultimately leading to significant differences in labeling efficiency of nascent DNA.

(University of Barcelona) The yellow-legged gull has a high ability to adapt to human activities and benefit from these as a food resource during all year. This is stated in a scientific article published in the journal Ecology and Evolution whose first author is the researcher Francisco Ramírez, from the Faculty of Biology and the Biodiversity Research Institute (IRBio) of the University of Barcelona.

(American Marketing Association) The positive outcomes of customer reacquisition more than offset the costs. Successful reacquisition management, though, requires a failure-tolerant company culture and guidelines.

(University of Iowa Health Care) A $3.7 million grant from the Centers for Disease Control and Prevention (CDC) has been awarded to the University of Iowa Carver College of Medicine and the David Geffen School of Medicine at UCLA to study ways to reduce the risk of COVID-19 infection among frontline health care workers in hospital emergency departments.

(Carnegie Mellon University) A new study sought to determine how the impact of recommender systems (also called recommenders) is affected by factors such as product type, attributes, and other sources of information about products on retailers' websites. The study found that recommenders increased the number of consumer views of product pages as well as the number of products consumers consider, but that the increase was moderated by product attributes and review ratings.

(King's College London) A study of female astronauts has assessed the risk of blood clots associated with spaceflight.The study, published in Aerospace Medicine and Human Performance, in collaboration with King's College London, the Centre for Space Medicine Baylor College of Medicine, NASA Johnson Space Centre and the International Space University, examines the potential risk factors for developing a blood clot (venous thromboembolism) in space.

(JAMA Network) This randomized clinical trial looked at the effect of a face-aging mobile app on daily sunscreen use and other skin protection among teens in Brazil. Selfies of students were altered to show UV effects on their future faces and shown to their class, accompanied by information about sun protection. Reducing UV exposure in children and adolescents is important because of the increased risk of skin cancer with cumulative UV exposure and sunburns early in life.

(University of Maryland) Many historians have claimed the Justinianic Plague (c. 541-750 CE) killed half of the population of Byzantine (Eastern Roman) Empire. New historical research and mathematical modeling challenge the death rate and severity of this first plague pandemic, named for Emperor Justinian I.

(Institute of Atmospheric Physics, Chinese Academy of Sciences) Scientists investigate how nitrogen dynamics affects carbon and water budgets in China by incorporating the terrestrial nitrogen cycle into the Noah Land Surface Model.

Jan Pearson
Apr 1, 2001; 14:
Articles

Lawrence Fisher
Oct 1, 2004; 17:215-219
Articles

Carolé R. Mensing
Apr 1, 2003; 16:
Articles

Invitation Only Research Event

Event participants

Joyce Hakmeh, Cyber Research Fellow, International Security Department, Chatham House

6 April 2020

Background: Accurate definition of the extent and severity of left-ventricular assist device (LVAD) infection may facilitate therapeutic decision making and targeted surgical intervention. Here, we explore the value of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for guidance of patient management. Methods: Fifty-seven LVAD-carrying patients received 85 whole-body ¹⁸F-FDG PET/CT scans for the work-up of device infection. Clinical follow-up was obtained over a period of up to two years. Results: PET/CT showed various patterns of infectious involvement of the 4 LVAD components: driveline entry point (77% of cases), subcutaneous driveline path (87%), pump pocket (49%) and outflow tract (58%). Driveline smears revealed staphylococcus or pseudomonas strains as the underlying pathogen in a majority of cases (48 and 34%, respectively). At receiver-operating characteristics analysis, an ¹⁸F-FDG standardized uptake value (SUV) >2.5 was most accurate to identify smear-positive driveline infection. Infection of 3 or all 4 LVAD components showed a trend towards lower survival vs infection of 2 or less components (P = 0.089), while involvement of thoracic lymph nodes was significantly associated with adverse outcome (P = 0.001 for nodal SUV above vs below median). Finally, patients that underwent early surgical revision within 3 months after PET/CT (n = 21) required significantly less inpatient hospital care during follow-up when compared to those receiving delayed surgical revision (n = 11; p<0.05). Conclusion: Whole-body ¹⁸F-FDG PET/CT identifies the extent of LVAD infection and predicts adverse outcome. Initial experience suggests that early image-guided surgical intervention may facilitate a less complicated subsequent course.

Purpose: To determine the effect of smooth filter and partial volume correction (PVC) method on measured prostate-specific membrane antigen (PSMA) activity in small metastatic lesions and to determine the impact of these changes on the molecular imaging (mi) PSMA scoring. Materials & Methods: Men with biochemical recurrence of prostate cancer with negative CT and bone scintigraphy were referred for ¹⁸F-DCFPyL PET/CT. Examinations were performed on one of 2 PET/CT scanners (GE Discovery 610 or Siemens mCT40). All suspected tumor sites were manually contoured on co-registered CT and PET images, and each was assigned a miPSMA score as per the PROMISE criteria. The PVC factors were calculated for every lesion using the anatomical CT and then applied to the unsmoothed PET images. The miPSMA scores, with and without the corrections, were compared, and a simplified "rule of thumb" (RoT) correction factor (CF) was derived for lesions at various sizes (<4mm, 4-7mm, 7-9mm, 9-12mm). This was then applied to the original dataset and miPSMA scores obtained using the RoT CF were compared to those found using the actual corrections. Results: There were 75 men (median age, 69 years; median serum PSA of 3.69 ug/L) with 232 metastatic nodes < 12 mm in diameter (mean lesion volume of 313.5 ± 309.6 mm³). Mean SUV_max before and after correction was 11.0 ± 9.3 and 28.5 ± 22.8, respectively (p<0.00001). The mean CF for lesions <4mm (n = 22), 4-7mm (n = 140), 7-9mm (n = 50), 9-12 mm (n = 20) was 4 (range: 2.5-6.4), 2.8 (range: 1.6-4.9), 2.3 (range: 1.6-3.3) and 1.8 (range 1.4-2.4), respectively. Overall miPSMA scores were concordant between the corrected dataset and RoT in 205/232 lesions (88.4%). Conclusion: There is a significant effect of smooth filter and partial volume correction on measured PSMA activity in small nodal metastases, impacting the miPSMA score.

McCune-Albright syndrome (MAS) is a mosaic disorder arising from gain-of-function mutations in the GNAS gene, which encodes the 3', 5'-cyclic adenosine monophosphate (cAMP) pathway-associated G-protein, Gsα. Clinical manifestations of MAS in a given individual, including fibrous dysplasia, are determined by the timing and location of the GNAS mutation during embryogenesis, the tissues involved, and the role of Gsα in the affected tissues. The Gsα mutation results in dysregulation of the cAMP signaling cascade, leading to upregulation of phosphodiesterase type 4 (PDE4), which catalyzes the hydrolysis of cAMP. Increased cAMP levels have been found in vitro in both animal models of fibrous dysplasia and in cultured cells from individuals with MAS, but not in humans with fibrous dysplasia. Positron emission tomography (PET) imaging of PDE4 with ¹¹C-(R)-rolipram has been used successfully to study the in vivo activity of the cAMP cascade. To date, it remains unknown whether fibrous dysplasia and other symptoms of MAS, including neuropsychiatric impairments, are associated with increased PDE4 activity in humans. Methods: ¹¹C-(R)-rolipram whole-body and brain PET scans were performed in six individuals with MAS (three for brain scans and six for whole-body scans) and nine healthy controls (seven for brain scans and six for whole-body scans). Results: ¹¹C-(R)-rolipram binding correlated with known locations of fibrous dysplasia in the periphery of individuals with MAS; no uptake was observed in the bones of healthy controls. In peripheral organs and the brain, no difference in ¹¹C-(R)-rolipram uptake was noted between participants with MAS and healthy controls. Conclusion: This study is the first to find evidence for increased cAMP activity in areas of fibrous dysplasia in vivo. No differences in brain uptake between MAS participants and controls were detected, which could be due to several reasons, including the limited anatomic resolution of PET. Nevertheless, the results confirm the usefulness of PET scans with ¹¹C-(R)-rolipram to indirectly measure increased cAMP pathway activation in human disease.

It was hypothesized that the brain β-amyloid buildup curve plateaus at an early symptomatic Alzheimer's disease (AD) stage. Atrophy-related partial volume effects (PVEs) degrade signal in hot-spot imaging techniques, such as amyloid positron emission tomography (PET). This longitudinal analysis of amyloid-sensitive PET data investigated the shape of the β-amyloid curve in AD applying PVE correction (PVEC). We analyzed baseline and 2-year follow-up data of 216 symptomatic individuals on the AD continuum (positive amyloid status) enrolled in Alzheimer's Disease Neuroimaging Initiative (17 AD dementia, 199 mild cognitive impairment), including 18F-florbetapir PET, magnetic resonance imaging and mini mental state examination (MMSE) scores. For PVEC, the modified Müller-Gärtner method was performed. Compared to non-PVE-corrected data, PVE-corrected data yielded significantly higher regional and composite standardized uptake value ratio (SUVR) changes over time (P=0.0002 for composite SUVRs). Longitudinal SUVR changes in relation to MMSE decreases showed a significantly higher slope of the regression line in the PVE-corrected as compared to the non-PVE-corrected PET data (F=7.1, P=0.008). These PVEC results indicate that the β-amyloid buildup curve does not plateau at an early symptomatic disease stage. A further evaluation of the impact of PVEC on the in-vivo characterization of time-dependent AD pathology, including the reliable assessment and comparison of other amyloid tracers, is warranted.

The prostate-specific membrane antigen (PSMA) is an excellent target for theranostic applications in prostate cancer (PCa). However, PSMA-targeted radioligand therapy can cause undesirable effects due to high accumulation of PSMA radiotracers in salivary glands and kidneys. This study assessed orally administered monosodium glutamate (MSG) as a potential means of reducing kidney and salivary gland radiation exposure using a PSMA targeting radiotracer. Methods: This prospective, double-blind, placebo-controlled study enrolled 10 biochemically recurrent PCa patients. Each subject served as his own control. [¹⁸F]DCFPyl PET/CT imaging sessions were performed 3 – 7 days apart, following oral administration of either 12.7 g of MSG or placebo. Data from the two sets of images were analyzed by placing regions of interest on lacrimal, parotid and submandibular glands, left ventricle, liver, spleen, kidneys, bowel, urinary bladder, gluteus muscle and malignant lesions. The results from MSG and placebo scans were compared by paired analysis of the ROI data. Results: A total of 142 pathological lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in maximal standardized uptake values corrected for lean body mass (SULmax) on images obtained following MSG administration in the parotids (24 ± 14%, P = 0.001), submandibular glands (35 ± 11%, P<0.001) and kidneys (23 ± 26%, P = 0.014). Significant decreases were also observed in lacrimal glands (49 ± 13%, P<0.001), liver (15 ± 6%, P<0.001), spleen (28 ± 13%, P = 0.001) and bowel (44 ± 13%, P<0.001). Mildly lower blood pool SULmean was observed after MSG administration (decrease of 11 ± 13%, P = 0.021). However, significantly lower radiotracer uptake in terms of SULmean, SULpeak, and SULmax was observed in malignant lesions on scans performed after MSG administration compared to the placebo studies (SULmax median decrease 33%, range -1 to 75%, P<0.001). No significant adverse events occurred and vital signs were stable following placebo or MSG administration. Conclusion: Orally administered MSG significantly decreased salivary gland, kidney and other normal organ PSMA radiotracer uptake in human subjects, using [¹⁸F]DCFPyL as an exemplar. However, MSG caused a corresponding reduction in tumor uptake, which may limit the benefits of this approach for diagnostic and therapeutic applications.

Human antibody response studies are largely restricted to periods of high immune activity (e.g. vaccination). To comprehensively understand the healthy B cell immune repertoire and how this changes over time and through natural infection, we conducted immune repertoire RNA sequencing on flow cytometry-sorted B cell subsets to profile a single individual's antibodies over 11 months through two periods of natural viral infection. We found that 1) a baseline of healthy variable (V) gene usage in antibodies exists and is stable over time, but antibodies in memory cells consistently have a different usage profile relative to earlier B cell stages; 2) a single complementarity-determining region 3 (CDR3) is potentially generated from more than one VJ gene combination; and 3) IgG and IgA antibody transcripts are found at low levels in early human B cell development, suggesting that class switching may occur earlier than previously realized. These findings provide insight into immune repertoire stability, response to natural infections, and human B cell development.

Recurrent urinary tract infections (UTIs) pose a significant burden on the health care system. Underlying mechanisms predisposing children to UTIs and associated changes in the urinary proteome are not well understood. We aimed to investigate the urinary proteome of a subset of children who have vesicoureteral reflux (VUR) and recurrent UTIs because of their risk of developing infection-related renal damage. Improving diagnostic modalities to identify UTI risk factors would significantly alter the clinical management of children with VUR. We profiled the urinary proteomes of 22 VUR patients with low grade VUR (1–3 out of 5), a history of recurrent UTIs, and renal scarring, comparing them to those obtained from 22 age-matched controls. Urinary proteins were analyzed by mass spectrometry followed by protein quantitation based on spectral counting. Of the 2,551 proteins identified across both cohorts, 964 were robustly quantified, as defined by meeting criteria with spectral count (SC) ≥2 in at least 7 patients in either VUR or control cohort. Eighty proteins had differential expression between the two cohorts, with 44 proteins significantly up-regulated and 36 downregulated (q <0.075, FC ≥1.2). Urinary proteins involved in inflammation, acute phase response (APR), modulation of extracellular matrix (ECM), and carbohydrate metabolism were altered among the study cohort.

Male infertility is widespread and estimated to affect 1 in 20 men. Although in some cases the etiology of the condition is well understood, for at least 50% of men, the underlying cause is yet to be classified. Male infertility, or subfertility, is often diagnosed by looking at total sperm produced, motility of the cells and overall morphology. Although counting spermatozoa and their associated motility is routine, morphology assessment is highly subjective, mainly because of the procedure being based on microscopic examination. A failure to diagnose male-infertility or sub-fertility has led to a situation where assisted conception is often used unnecessarily. As such, biomarkers of male infertility are needed to help establish a more consistent diagnosis. In the present study, we compared nuclear extracts from both high- and low-quality spermatozoa by LC-MS/MS based proteomic analysis. Our data shows that nuclear retention of specific proteins is a common facet among low-quality sperm cells. We demonstrate that the presence of Topoisomerase 2A in the sperm head is highly correlated to poor head morphology. Topoisomerase 2A is therefore a potential new biomarker for confirming male infertility in clinical practice.

The respiratory epithelium comprises polarized cells at the interface between the environment and airway tissues. Polarized apical and basolateral protein secretions are a feature of airway epithelium homeostasis. Human respiratory syncytial virus (hRSV) is a major human pathogen that primarily targets the respiratory epithelium. However, the consequences of hRSV infection on epithelium secretome polarity and content remain poorly understood. To investigate the hRSV-associated apical and basolateral secretomes, a proteomics approach was combined with an ex vivo pediatric human airway epithelial (HAE) model of hRSV infection (data are available via ProteomeXchange and can be accessed at https://www.ebi.ac.uk/pride/ with identifier PXD013661). Following infection, a skewing of apical/basolateral abundance ratios was identified for several individual proteins. Novel modulators of neutrophil and lymphocyte activation (CXCL6, CSF3, SECTM1 or CXCL16), and antiviral proteins (BST2 or CEACAM1) were detected in infected, but not in uninfected cultures. Importantly, CXCL6, CXCL16, CSF3 were also detected in nasopharyngeal aspirates (NPA) from hRSV-infected infants but not healthy controls. Furthermore, the antiviral activity of CEACAM1 against RSV was confirmed in vitro using BEAS-2B cells. hRSV infection disrupted the polarity of the pediatric respiratory epithelial secretome and was associated with immune modulating proteins (CXCL6, CXCL16, CSF3) never linked with this virus before. In addition, the antiviral activity of CEACAM1 against hRSV had also never been previously characterized. This study, therefore, provides novel insights into RSV pathogenesis and endogenous antiviral responses in pediatric airway epithelium.

Phosphoglycerate kinase 1 (PGK1) plays important roles in glycolysis, yet its forward reaction kinetics are unknown, and its role especially in regulating cancer cell glycolysis is unclear. Here, we developed an enzyme assay to measure the kinetic parameters of the PGK1-catalyzed forward reaction. The Km values for 1,3-bisphosphoglyceric acid (1,3-BPG, the forward reaction substrate) were 4.36 μm (yeast PGK1) and 6.86 μm (human PKG1). The Km values for 3-phosphoglycerate (3-PG, the reverse reaction substrate and a serine precursor) were 146 μm (yeast PGK1) and 186 μm (human PGK1). The Vmax of the forward reaction was about 3.5- and 5.8-fold higher than that of the reverse reaction for the human and yeast enzymes, respectively. Consistently, the intracellular steady-state concentrations of 3-PG were between 180 and 550 μm in cancer cells, providing a basis for glycolysis to shuttle 3-PG to the serine synthesis pathway. Using siRNA-mediated PGK1-specific knockdown in five cancer cell lines derived from different tissues, along with titration of PGK1 in a cell-free glycolysis system, we found that the perturbation of PGK1 had no effect or only marginal effects on the glucose consumption and lactate generation. The PGK1 knockdown increased the concentrations of fructose 1,6-bisphosphate, dihydroxyacetone phosphate, glyceraldehyde 3-phosphate, and 1,3-BPG in nearly equal proportions, controlled by the kinetic and thermodynamic states of glycolysis. We conclude that perturbation of PGK1 in cancer cells insignificantly affects the conversion of glucose to lactate in glycolysis.

Dong-Jae Jun
May 1, 2020; 61:746-757
Research Articles

M John Chapman
Apr 15, 2020; 0:jlr.P119000543v1-jlr.P119000543
Patient-Oriented and Epidemiological Research

Sookyoung Jeon
Apr 1, 2020; 61:470-479
Reviews