The South African Artificial Intelligence Association wants LinkedIn to be investigated, as it claims the social networking platforms new data use practice violates local personal information protection law.

Mathias Uhlén
Dec 1, 2005; 4:1920-1932
Research

Linn Fagerberg
Feb 1, 2014; 13:397-406
Research

The dimeric ectonucleotidase CD73 catalyzes the hydrolysis of AMP at the cell surface to form adenosine, a potent suppressor of the immune response. Blocking CD73 activity in the tumor microenvironment can have a beneficial effect on tumor eradication and is a promising approach for cancer therapy. Biparatopic antibodies binding different regions of CD73 may be a means to antagonize its enzymatic activity. A panel of biparatopic antibodies representing the pairwise combination of 11 parental monoclonal antibodies against CD73 was generated by Fab-arm exchange. Nine variants vastly exceeded the potency of their parental antibodies with ≥90% inhibition of activity and subnanomolar EC50 values. Pairing the Fabs of parents with nonoverlapping epitopes was both sufficient and necessary whereas monovalent antibodies were poor inhibitors. Some parental antibodies yielded potent biparatopics with multiple partners, one of which (TB19) producing the most potent. The structure of the TB19 Fab with CD73 reveals that it blocks alignment of the N- and C-terminal CD73 domains necessary for catalysis. A separate structure of CD73 with a Fab (TB38) which complements TB19 in a particularly potent biparatopic shows its binding to a nonoverlapping site on the CD73 N-terminal domain. Structural modeling demonstrates a TB19/TB38 biparatopic antibody would be unable to bind the CD73 dimer in a bivalent manner, implicating crosslinking of separate CD73 dimers in its mechanism of action. This ability of a biparatopic antibody to both crosslink CD73 dimers and fix them in an inactive conformation thus represents a highly effective mechanism for the inhibition of CD73 activity.

Yi Liu
Dec 1, 2020; 19:1968-1985
Research

Lipoprotein (a) [Lp(a)] is a risk factor for CVD and a target of therapy, but Lp(a) measurements are not globally standardized. Commercially available assays generally use polyclonal antibodies that detect multiple sites within the kringle (K)IV₂ repeat region of Lp(a) and may lead to inaccurate assessments of plasma levels. With increasing awareness of Lp(a) as a cardiovascular risk factor and the active clinical development of new potential therapeutic approaches, the broad availability of reagents capable of providing isoform independence of Lp(a) measurements is paramount. To address this issue, we generated a murine monoclonal antibody that binds to only one site on apo(a). A BALB/C mouse was immunized with a truncated version of apo(a) that contained eight total KIV repeats, including only one copy of KIV₂. We generated hybridomas, screened them, and successfully produced a KIV₂-independent monoclonal antibody, named LPA-KIV9. Using a variety of truncated apo(a) constructs to map its binding site, we found that LPA-KIV9 binds to KIV₉ without binding to plasminogen. Fine peptide mapping revealed that LPA-KIV9 bound to the sequence ⁴⁰⁷⁶LETPTVV⁴⁰⁸² on KIV₉. In conclusion, the generation of monoclonal antibody LPA-KIV9 may be a useful reagent in basic research studies and in the clinical application of Lp(a) measurements.

For three decades, the LPL–specific monoclonal antibody 5D2 has been used to investigate LPL structure/function and intravascular lipolysis. 5D2 has been used to measure LPL levels, block the triglyceride hydrolase activity of LPL, and prevent the propensity of concentrated LPL preparations to form homodimers. Two early studies on the location of the 5D2 epitope reached conflicting conclusions, but the more convincing report suggested that 5D2 binds to a tryptophan (Trp)-rich loop in the carboxyl terminus of LPL. The same loop had been implicated in lipoprotein binding. Using surface plasmon resonance, we showed that 5D2 binds with high affinity to a synthetic LPL peptide containing the Trp-rich loop of human (but not mouse) LPL. We also showed, by both fluorescence and UV resonance Raman spectroscopy, that the Trp-rich loop binds lipids. Finally, we used X-ray crystallography to solve the structure of the Trp-rich peptide bound to a 5D2 Fab fragment. The Trp-rich peptide contains a short α-helix, with two Trps projecting into the antigen recognition site. A proline substitution in the α-helix, found in mouse LPL, is expected to interfere with several hydrogen bonds, explaining why 5D2 cannot bind to mouse LPL.

Mallory-Denk-bodies (MDBs) are hepatic protein aggregates associated with inflammation both clinically and in MDB-inducing models. Similar protein aggregation in neurodegenerative diseases also triggers inflammation and NF-B activation. However, the precise mechanism that links protein aggregation to NF-B-activation and inflammatory response remains unclear. Herein we find that treating primary hepatocytes with MDB-inducing agents (N-methylprotoporphyrin (NMPP), protoporphyrin IX (PPIX), or Zinc-protoporphyrin IX (ZnPP)) elicited an IBα-loss with consequent NF-B activation. Four known mechanisms of IBα-loss i.e. the canonical ubiquitin-dependent proteasomal degradation (UPD), autophagic-lysosomal degradation, calpain degradation and translational inhibition, were all probed and excluded. Immunofluorescence analyses of ZnPP-treated cells coupled with 8 M urea/CHAPS-extraction revealed that this IBα-loss was due to its sequestration along with IBβ into insoluble aggregates, thereby releasing NF-B. Through affinity pulldown, proximity biotinylation by antibody recognition, and other proteomic analyses, we verified that NF-B subunit p65, which stably interacts with IBα under normal conditions, no longer binds to it upon ZnPP-treatment. Additionally, we identified 10 proteins that interact with IBα under baseline conditions, aggregate upon ZnPP-treatment, and maintain the interaction with IBα after ZnPP-treatment, either by cosequestering into insoluble aggregates or through a different mechanism. Of these 10 proteins, the nucleoporins Nup153 and Nup358/RanBP2 were identified through RNA-interference, as mediators of IBα-nuclear import. The concurrent aggregation of IBα, NUP153, and RanBP2 upon ZnPP-treatment, synergistically precluded the nuclear entry of IBα and its consequent binding and termination of NF-B activation. This novel mechanism may account for the protein aggregate-induced inflammation observed in liver diseases, thus identifying novel targets for therapeutic intervention. Because of inherent commonalities this MDB cell model is a bona fide protoporphyric model, making these findings equally relevant to the liver inflammation associated with clinical protoporphyria.

Antibodies play essential roles in both diagnostics and therapeutics. Epitope mapping is essential to understand how an antibody works and to protect intellectual property. Given the millions of antibodies for which epitope information is lacking, there is a need for high-throughput epitope mapping. To address this, we developed a strategy, Antibody binding epitope Mapping (AbMap), by combining a phage displayed peptide library with next generation sequencing. Using AbMap, profiles of the peptides bound by 202 antibodies were determined in a single test, and linear epitopes were identified for >50% of the antibodies. Using spike protein (S1 and S2)-enriched antibodies from the convalescent serum of one COVID-19 patient as the input, both linear and conformational epitopes of spike protein specific antibodies were identified. We defined peptide-binding profile of an antibody as the Binding Capacity (BiC). Conceptually, the BiC could serve as a systematic and functional descriptor of any antibody. Requiring at least one order of magnitude less time and money to map linear epitopes than traditional technologies, AbMap allows for high-throughput epitope mapping and creates many possibilities.

Russia's war on everybody 6 December 2022 — 5:00PM TO 6:00PM Anonymous (not verified) 14 October 2022 Chatham House and Online

Experts discuss the methods Moscow has employed to exert influence around the world over recent decades.

Russia’s assault on Ukraine has reminded the world about the threat it faces from Moscow. But that’s not the only war that Russia has been fighting and Ukraine is not the only target.

Long before February 2022, Russia was already engaged in semi-covert campaigns across Europe and around the world, using any means possible to expand its power and influence and leaving a trail of destruction along the way.

In his new book Russia’s War on Everybody, Chatham House associate fellow Keir Giles examines what this longer war means for us all. Instead of talking only to diplomats, politicians and generals, Giles has looked instead at the effect of Russia’s ambition on ordinary people.

Interviewing 40 eyewitnesses from four continents, he has tried to tell the stories the world doesn’t hear about the impact of Russia’s hostility on individuals and societies that may not even realize they are a target.

At this event, Giles introduces the book at Chatham House. He is joined by experts to talk about the human impact of Russia’s campaigns waged through leveraging corruption and cyber offensives respectively.

As with all members events, questions from the audience drive the conversation.

Read the transcript. 

Methods to shorten [¹⁸F]FDG Patlak PET imaging procedures ranging from 65–90 to 20–30 min after injection, using a population-averaged input function (PIF) scaled to patient-specific image-derived input function (IDIF) values, were recently evaluated. The aim of the present study was to explore the feasibility of ultrashort 10-min [¹⁸F]FDG Patlak imaging at 55–65 min after injection using a PIF combined with direct Patlak reconstructions to provide reliable quantitative accuracy of lung tumor uptake, compared with a full-duration 65-min acquisition using an IDIF. Methods: Patients underwent a 65-min dynamic PET acquisition on a long-axial-field-of-view (LAFOV) Biograph Vision Quadra PET/CT scanner. Subsequently, direct Patlak reconstructions and image-based (with reconstructed dynamic images) Patlak analyses were performed using both the IDIF (time to relative kinetic equilibrium between blood and tissue concentration (t*) = 30 min) and a scaled PIF at 30–60 min after injection. Next, direct Patlak reconstructions were performed on the system console using only the last 10 min of the acquisition, that is, from 55 to 65 min after injection, and a scaled PIF using maximum crystal ring difference settings of both 85 and 322. Tumor lesion and healthy-tissue uptake was quantified and compared between the differently obtained parametric images to assess quantitative accuracy. Results: Good agreement was obtained between direct- and image-based Patlak analyses using the IDIF (t* = 30 min) and scaled PIF at 30–60 min after injection, performed using the different approaches, with no more than 8.8% deviation in tumor influx rate value (K_i) (mean difference ranging from –0.0022 to 0.0018 mL/[min x g]). When direct Patlak reconstruction was performed on the system console, excellent agreement was found between the use of a scaled PIF at 30–60 min after injection versus 55–65 min after injection, with 2.4% deviation in tumor K_i (median difference, –0.0018 mL/[min x g]; range, –0.0047 to 0.0036 mL/[min x g]). For different maximum crystal ring difference settings using the scan time interval of 55–65 min after injection, only a 0.5% difference (median difference, 0.0000 mL/[min x g]; range, –0.0004 to 0.0013 mL/[min x g]) in tumor K_i was found. Conclusion: Ultrashort whole-body [¹⁸F]FDG Patlak imaging is feasible on an LAFOV Biograph Vision Quadra PET/CT system without loss of quantitative accuracy to assess lung tumor uptake compared with a full-duration 65-min acquisition. The ultrashort 10-min direct Patlak reconstruction with PIF allows for its implementation in clinical practice.

Mutations of p53 protein occur in over half of all cancers, with profound effects on tumor biology. We present the first—to our knowledge—method for noninvasive visualization of p53 in tumor tissue in vivo, using SPECT, in 3 different models of cancer. Methods: Anti-p53 monoclonal antibodies were conjugated to the cell-penetrating transactivator of transcription (TAT) peptide and a metal ion chelator and then radiolabeled with ¹¹¹In to allow SPECT imaging. ¹¹¹In-anti-p53-TAT conjugates were retained longer in cells overexpressing p53-specific than non–p53-specific ¹¹¹In-mIgG (mouse IgG from murine plasma)-TAT controls, but not in null p53 cells. Results: In vivo SPECT imaging showed enhanced uptake of ¹¹¹In-anti-p53-TAT, versus ¹¹¹In-mIgG-TAT, in high-expression p53^R175H and medium-expression wild-type p53 but not in null p53 tumor xenografts. The results were confirmed in mice bearing genetically engineered KPC mouse–derived pancreatic ductal adenocarcinoma tumors. Imaging with ¹¹¹In-anti-p53-TAT was possible in KPC mice bearing spontaneous p53^R172H pancreatic ductal adenocarcinoma tumors. Conclusion: We demonstrate the feasibility of noninvasive in vivo molecular imaging of p53 in tumor tissue using a radiolabeled TAT-modified monoclonal antibody.

Understanding which patients with human epidermal growth factor receptor 2 (HER2)–negative or –low metastatic breast cancer (MBC) benefit from HER2-targeted strategies is urgently needed. We assessed the whole-body heterogeneity of HER2 expression on ⁸⁹Zr-trastuzumab PET (HER2 PET) and the diagnostic performance of HER2 PET in a large series of patients, including HER2-negative and -low MBC. Methods: In the IMPACT-MBC study, patients with newly diagnosed and nonrapidly progressive MBC of all subtypes were included. Metastasis HER2 status was determined by immunohistochemistry and in situ hybridization.⁸⁹Zr-trastuzumab uptake was quantified as SUV_max and SUV_mean. HER2 immunohistochemistry was related to the quantitative ⁸⁹Zr-trastuzumab uptake of all metastases and corresponding biopsied metastasis, uptake heterogeneity, and qualitative scan evaluation. A prediction algorithm for HER2 immunohistochemistry positivity based on uptake was developed. Results: In 200 patients, ⁸⁹Zr-trastuzumab uptake was quantified in 5,163 metastases, including 186 biopsied metastases. With increasing HER2 immunohistochemistry status, uptake was higher (geometric mean SUV_max of 7.0, 7.6, 7.3, and 17.4 for a HER2 immunohistochemistry score of 0, 1, 2, or 3+, respectively; P < 0.001). High uptake exceeding 14.6 (90th percentile) was observed in one third of patients with a HER2-negative or -low metastasis biopsy. The algorithm performed best when lesion site and size were incorporated (area under the curve, 0.86; 95% CI, 0.79–0.93). Conclusion: HER2 PET had good diagnostic performance in MBC, showing considerable whole-body HER2 heterogeneity and uptake above background in HER2-negative and -low MBC. This provides novel insights into HER2-negative and -low MBC compared with standard HER2 immunohistochemistry on a single biopsy.

The Winnipeg Jets will be without defenceman Logan Stanley for the short-term future.

The Governing Body took a number of decisions that require action by Contracting Parties. This communication draws the attention of Contracting Parties to those decisions that are addressed to [...]

The answer depends on how you feel about cluster headaches

Many cultures have found ways to preserve the human body after death, but how? In this one-minute video, our Ask Smithsonian Host, Eric Schulze, wraps up the answer.

Obviously it's a bad idea to go out into space without a trusty spacesuit, but what exactly happens?

Think you know everything about your own body? Test your smarts against this one-minute video, where Ask Smithsonian host Eric Schulze uncovers the facts behind five popular myths about the human body.

A scientist used at-home experiments to test whether cats hesitated when moving through increasingly shorter or narrower openings

On this day in 1912, a team found the remains of Robert Falcon Scott and the crew of the "Terra Nova" expedition. A would-be rescuer said he was forever haunted by the "horrible nightmare"

RCMP are investigating after officers discovered human remains in an abandoned, burned vehicle in Greenhill, N.S.

Quebec provincial police have confirmed that the body found in a Montreal nature park on Oct. 30 was that of kidnapping victim and cryptocurrency influencer Kevin Mirshahi.

The Drosophila embryonic central nervous system has been used for decades as a model for understanding the genetic regulation of axon guidance and other aspects of neural development. Foundational studies using antibody staining to examine the embryonic ventral nerve cord in wild-type and mutant animals led to the discovery of evolutionarily conserved genes that regulate fundamental aspects of axon guidance, including midline crossing of axons. The development of the regular, segmentally repeating structure of axon pathways in the ventral nerve cord can illustrate basic principles of axon guidance to beginning students and can also be used by expert researchers to characterize new mutants, detect genetic interactions between known genes, and precisely quantify variations in gene function in engineered mutant lines. Here, we describe a protocol for collecting and fixing Drosophila embryos and visualizing axon pathways in the embryonic ventral nerve cord using immunofluorescence or immunohistochemical staining methods. As embryogenesis in Drosophila takes ~24 h to complete, a 1-d collection yields embryos representing all stages of development from newly fertilized through ready-to-hatch larvae, allowing investigation of multiple developmental events within a single batch of collected embryos. The methods described in this protocol should be accessible to introductory laboratory courses as well as seasoned investigators in established research laboratories.

North American market leader speeds innovation and customization

During his time in OM’s International Intensive School of Missions in Panama, Colombian Juank Giovannetti discovers his calling.

Participants from around the world learnt to speak the language of love and laughter during an outreach to the indigenous tribes in Panama.

Her YouTube video explains exactly what happens to the human body after death, to try and demystify the experience.

OnePlus seems to be preparing to launch the OnePlus Ace 5 and Ace 5 Pro in China. The Chinese tech brand is yet to make an official announcement, but rumours about the duo continue to surface on the Web. As per a new leak, the OnePlus Ace 5 will run on the Snapdragon 8 Gen 3 chipset. The upcoming Ace 5 smartphones are also said to feature a metal middle frame.

Spotting ultra-processed foods in your pantry and understanding their impact can be a game-changer for your health and well-being.

The body of the MBBS student Srishti Sharma, a resident of Maihar in Madhya Pradesh, who died in a road accident in Russia, has been brought to New Delhi, Chief Minister Mohan Yadav said on Saturday.

It is most significant to note that while leading from the front, the Allahabad High Court in a most learned, laudable, landmark, logical and latest judgment titled Hazi Tahseen Khan vs Gandhi Mohan Saxena And Another in S.C.C. Revision No.: - 105 of 2024 that was pronounced as recently as on 07.11.

House Bill 195 requires law enforcement to wear and use body cameras NEWARK, Del. –  Alongside members of law enforcement, advocates and members of the General Assembly on Wednesday, Governor John Carney signed legislation requiring police officers and certain employees of the Department of Correction and the Department of Services for Children, Youth, and Their Families to […]

Noted Kannada actor and director Guruprasad was found dead in his Bengaluru apartment today, the police said.

A man has been arrested here in connection with the murder of a 50-year-old beautician in Rajasthan's Jodhpur whose body was chopped and buried in a pit by the accused, an official has said.

A body of a man has been found in a plastic bag in seven pieces on Mumbai's Gorai beach, the police said today.

[GroundUp] Former Lavender Hill gangster died on 29 October

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

The latest research on caffeine reveals why coffee and decaf can be so good for your health, but energy drinks can be lethal

After over a year of record-high global sea temperatures, the equatorial Atlantic is cooling off more quickly than ever recorded, which could impact weather around the world

A massive undertaking to map cancer tumours is providing new insights into how the disease forms, evolves and develops resistance to treatments

Title: Antibiotic Overuse May Be Bad for Body's Good Bacteria
Category: Health News
Created: 8/25/2011 11:01:00 AM
Last Editorial Review: 8/25/2011 12:00:00 AM

Title: Later Breakfast, Earlier Dinner Might Help You Shed Body Fat
Category: Health News
Created: 8/30/2018 12:00:00 AM
Last Editorial Review: 8/31/2018 12:00:00 AM

Title: Flu Shots for Kids Protect Everybody, Study Shows
Category: Health News
Created: 8/21/2020 12:00:00 AM
Last Editorial Review: 8/24/2020 12:00:00 AM

Title: Want That Pill to Work Fast? Your Body Position Matters
Category: Health News
Created: 8/17/2022 12:00:00 AM
Last Editorial Review: 8/17/2022 12:00:00 AM