"National Institute of Virology, Pune, has successfully developed the 1st indigenous anti-SARS-CoV-2 human IgG ELISA test kit for antibody detection of COVID-19," the minister said in one of a series of tweets. "This robust test will play a critical role in surveillance of proportion of population exposed to SARSCoV2 infection," he said.

A bodyguard of Eastern Cape Social Development MEC Siphokazi Mani-Lusithi has been arrested with four others by the Green Scorpions for illegal hunting on a private farm outside East London, as well as for breaking Covid-19 lockdown regulations.

Antibodies are widely used as cancer therapeutics, but their current use is limited by the low number of antigens restricted to cancer cells. A receptor tyrosine kinase, receptor tyrosine kinase-like orphan receptor 2 (ROR2), is normally expressed only during embryogenesis and is tightly down-regulated in postnatal healthy tissues. However, it is up-regulated in a diverse set of hematologic and solid malignancies, thus ROR2 represents a candidate antigen for antibody-based cancer therapy. Here we describe the affinity maturation and humanization of a rabbit mAb that binds human and mouse ROR2 but not human ROR1 or other human cell-surface antigens. Co-crystallization of the parental rabbit mAb in complex with the human ROR2 kringle domain (hROR2-Kr) guided affinity maturation by heavy-chain complementarity-determining region 3 (HCDR3)-focused mutagenesis and selection. The affinity-matured rabbit mAb was then humanized by complementarity-determining region (CDR) grafting and framework fine tuning and again co-crystallized with hROR2-Kr. We show that the affinity-matured and humanized mAb retains strong affinity and specificity to ROR2 and, following conversion to a T cell–engaging bispecific antibody, has potent cytotoxicity toward ROR2-expressing cells. We anticipate that this humanized affinity-matured mAb will find application for antibody-based cancer therapy of ROR2-expressing neoplasms.

....GOING TO DO WHEN THEY BELIEVE THEY APPLY TO THEM BUT THEY HAVEN'T BEEN HOLY SPIRIT BAPTIZED? TODAY'S CHRISTIANS HAVEN'T BEEN "QUICKENED BACK TO LIFE" (EPHESIANS 2:1)  BY HIS "POWER THAT CAME UPON THEM" (ACTS 1:8) WITH HOLY SPIRIT BAPTISM (ACTS 1:5) AS THEY WERE "BORN AGAIN OF THE SPIRIT" (JOHN 3:5-7) FROM THEIR "DEAD SPIRITS" (ROMANS 5:12-14) AND WERE "RESURRECTED" (I COR 15) FROM THEIR GRAVES" (EZEKIEL 37:12-14). WHAT ARE THESE "DEAD SPIRITS" GOING TO DO? 

1. India's research body partners with vaccine manufacturing company to develop indigenous vaccine for COVID-19  China.org.cn
2. India to develop ‘fully indigenous’ Covid vaccine as ICMR partners with Bharat Biotech  ThePrint
3. ICMR teams up with Bharat Biotech to develop Covid-19 vaccine  Times of India
4. ICMR partners with Bharat Biotech to develop an indigenous coronavirus vaccine  Times Now
5. ICMR joins with Hyderabad firm to develop COVID-19 vaccine  Northeast Now
6. View Full coverage on Google News

An OM Russia worker helps a young mother and her children living in a desperate situation.

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AIMO has requested the government to look at protecting the elders and senior citizens of the country and allow the working class to return to their livelihoods, by introducing a citizen risk assessment module.

The virtual cash can be used within six months from the purchase date, with limitless purchases and no minimum expenditure amount, blackout dates or redemption conditions.

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It is viewed as a rival body to the Kenya Football Coaches Association (Kefoca).

Company owners and executives top donors to Republican billionaire

ISLAMABAD: Senior vice president of the main opposition Pakistan Muslim League-Nawaz (PML-N) Shahid Khaqan Abbasi has urged the commission of inquiry on the sugar scam to include Prime Minister Imran Khan and the then finance minister Asad Umar in the investigation to find out the truth.

Talking to reporters after appearing before the commission with another senior party leader and former minister Khurram Dastagir Khan here on Saturday, Mr Abbasi said he had told the commission there would be no worth of its report if it did not summon the prime minister and Mr Umar, the then chairman of the Economic Coordination Committee (ECC) that had allowed export of sugar despite knowing it was not available in stock.

“We do not talk politics. We have presented facts before the commission. If the prime minister and the [former] ECC chairman are not called [for interrogation] there will be no worth of the commission’s report,” said Mr Abbasi, who had served as prime minister after disqualification of Nawaz Sharif in July 2017 as a result of the Supreme Court’s verdict in Al-Azizia corruption case.

Mr Abbasi had himself written a letter to the commission and offered his services to it by sharing his experiences in probing the sugar scam. He had stated that he would inform the commission how sugar scandals developed in the light of his experience as a former chief executive of the country.

Mr Abbasi held the prime minister directly responsible for over Rs100 billion sugar scam, saying the inquiry commission should ask him the reason for allowing sugar export despite the fact that the commodity was not available in surplus in the country and for not taking any step to prevent increase in its price. He said the export continued for 16 months with 45 per cent increase in the sugar price in the country, but the government took no notice of it.

The former prime minister alleged that the sugar mill owners earned Rs30 per kilogram extra due to this decision of the government. He said the increase in sugar price proved the decisions of the cabinet and the ECC to export sugar were wrong.

“There can be three factors behind this wrong decision. Either the prime minister is incompetent or corrupt or he is both. The facts prove he is incompetent as well as corrupt and the people of Pakistan are paying the price for it,” he said.

Mr Abbasi said he had told the inquiry commission it would not be able to understand the issue until it would not summon the members of the cabinet and the ECC.

“Is it not a matter of conflict of interests?” he asked, alleging those who made billions through the sugar scam were part of the federal cabinet.

Mr Abbasi said it was a clear, open and shut case as facts showed sugar was exported against the advice of the relevant authorities and continued to be exported for 16 months while prices rose. He said not only that, the government also imposed a special tax on sugar import to ensure the rise in price and exploitation of the people.

Replying to a question, the former prime minister said when the PML-N had left the government in 2018, the sugar price was Rs54 per kg. He said the PML-N had also given huge subsidy of over Rs20bn and even allowed the export, but at the same time it kept check on its price and brought the price down.

Responding to another query, he said they had not given anything in writing or any document, but they were ready to do so, if asked. However, he said, the minutes of the meetings of the cabinet and the ECC would be sufficient as evidence.

The federal cabinet in its meeting on April 28 had allowed three more weeks to the Sugar Forensic Commission (SFC) to compile its report on last year’s food crisis after the expiry of the April 25 deadline given for the task.

The commission headed by Federal Investigation Agency (FIA) Director General Wajid Zia had reportedly made a formal request to the federal government to grant it more time citing multiple reasons, including the situation created by coronavirus.

The commission had been constituted by the government in the first week of April following the release of two separate inquiry reports of the FIA on the issue of artificial shortage of sugar and wheat in the country and sudden increase in their prices last year.

The inquiry report on sugar had revealed names of many bigwigs, including Jahangir Tareen, former secretary general of the ruling Pakistan Tehreek-i-Insaf and a close confidant of Prime Minister Imran Khan, who had allegedly obtained benefit during the crisis.

The report had showed in the past few years sugar production was historically more than the local requirement and said therefore it was imperative to include this aspect related to export of sugar, including any subsidy given, its impact on local sugar prices and eventually major beneficiaries of such export subsidies, if any. The inquiry committee had found the sugar export was not justified as sugarcane production was expected to be low in harvesting season 2018-19 and with the export of sugar in Jan 2019, the prices of sugar sharply increased.

After the release of the report, the opposition had demanded that the PM take stern action against those who had been declared responsible for the crisis by the FIA committee.

PM Khan had vowed to take action, but said he would do so after receiving the forensic audit report from the commission he had constituted on the recommendation of the ‘initial’ reports. The commission comprises officials from a number of agencies and departments, including Intelligence Bureau and the Federal Board of Revenue.

Published in Dawn, May 10th, 2020

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As hundreds of test kits claim to offer accurate results on previous Covid-19 infection, scientists around the world are working hard to assess their accuracy

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At the Erasmus University Medical Centre in Rotterdam, Marion Koopmans and a team of scientists are going throught the laborious process of verifying antibody tests for Covid-19. Over the last two months, dozens of prospective tests have hit the market, and with many governments wanting to feed the results of large-scale testing into their decisions whether to end lockdowns, biological tests have rarely carried such weight.

Most of the tests are enthusiastically marketed, boasting of their ability to accurately detect whether someone has previously been infected with the Sars-CoV-2 virus. The painstaking job of proving whether the tests do what they say has fallen to a worldwide network of 12 independent centres, of which Koopmans’s team is one.

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Structures of the immunodominant protein P46 from M. hyopneumoniae has been determined by X-ray crystallography and it is shown that P46 can bind a diversity of oligosaccharides, particularly xylose, which exhibits a very high affinity for this protein. Structures of a monoclonal antibody, both alone and in complex with P46, that was raised against M. hyopnemoniae cells and specifically recognizes P46 are also reported.

Apoptosis is a crucial process by which multicellular organisms control tissue growth, removal and inflammation. Disruption of the normal apoptotic function is often observed in cancer, where cell death is avoided by the overexpression of anti-apoptotic proteins of the Bcl-2 (B-cell lymphoma 2) family, including Mcl-1 (myeloid cell leukaemia 1). This makes Mcl-1 a potential target for drug therapy, through which normal apoptosis may be restored by inhibiting the protective function of Mcl-1. Here, the discovery and biophysical properties of an anti-Mcl-1 antibody fragment are described and the utility of both the scFv and Fab are demonstrated in generating an Mcl-1 crystal system amenable to iterative structure-guided drug design.

New research on tiny spiders has revealed that their brains are so large that they fill their body cavities and overflow into their legs, say a team of scientists at the Smithsonian Tropical Research Institute in Panama.

The post Brains of tiny spiders fill their body cavities and legs, Smithsonian researchers discover appeared first on Smithsonian Insider.

Mycoplasma hyopneumoniae is a prokaryotic pathogen that colonizes the respiratory ciliated epithelial cells in swine. Infected animals suffer respiratory lesions, causing major economic losses in the porcine industry. Characterization of the immunodominant membrane-associated proteins from M. hyopneumoniae may be instrumental in the development of new therapeutic approaches. Here, the crystal structure of P46, one of the main surface-antigen proteins, from M. hyopneumoniae is presented and shows N- and C-terminal α/β domains connected by a hinge. The structures solved in this work include a ligand-free open form of P46 (3.1 Å resolution) and two ligand-bound structures of P46 with maltose (2.5 Å resolution) and xylose (3.5 Å resolution) in open and closed conformations, respectively. The ligand-binding site is buried in the cleft between the domains at the hinge region. The two domains of P46 can rotate with respect to each other, giving open or closed alternative conformations. In agreement with this structural information, sequence analyses show similarities to substrate-binding members of the ABC transporter superfamily, with P46 facing the extracellular side as a functional subunit. In the structure with xylose, P46 was also bound to a high-affinity (Kd = 29 nM) Fab fragment from a monoclonal antibody, allowing the characterization of a structural epitope in P46 that exclusively involves residues from the C-terminal domain. The Fab structure in the complex with P46 shows only small conformational rearrangements in the six complementarity-determining regions (CDRs) with respect to the unbound Fab (the structure of which is also determined in this work at 1.95 Å resolution). The structural information that is now available should contribute to a better understanding of sugar nutrient intake by M. hyopneumoniae. This information will also allow the design of protocols and strategies for the generation of new vaccines against this important swine pathogen.

Westley Heydeck, Brian A. Bayless, Alexander J. Stemm-Wolf, Eileen T. O'Toole, Amy S. Fabritius, Courtney Ozzello, Marina Nguyen, and Mark Winey

Basal bodies (BBs) are microtubule-based organelles that template and stabilize cilia at the cell surface. Centrins ubiquitously associate with BBs and function in BB assembly, maturation, and stability. Human POC5 (hPOC5) is a highly conserved centrin-binding protein that binds centrins through Sfi1p-like repeats and is required for building full-length, mature centrioles. Here, we use the BB-rich cytoskeleton of Tetrahymena thermophila to characterize Poc5 BB functions. Tetrahymena Poc5 (TtPoc5) uniquely incorporates into assembling BBs and is then removed from mature BBs prior to ciliogenesis. Complete genomic knockout of TtPOC5 leads to a significantly increased production of BBs yet a markedly reduced ciliary density, both of which are rescued by reintroduction of TtPoc5. A second Tetrahymena POC5-like gene, SFR1, is similarly implicated in modulating BB production. When TtPOC5 and SFR1 are co-deleted, cell viability is compromised, and levels of BB overproduction are exacerbated. Overproduced BBs display defective transition zone formation and a diminished capacity for ciliogenesis. This study uncovers a requirement for Poc5 in building mature BBs, providing a possible functional link between hPOC5 mutations and impaired cilia.

Source: Streetwise Reports   05/06/2020

Testing has been an Achilles heel of the coronavirus pandemic, but ProMIS Neurosciences Inc. (PMN:TSX; ARFXF:OTCQB) has partnered with Dr. Hans Frykman and the BC Neuroimmunology Lab to use its unique technology to create a more accurate antibody test for SARS-CoV-2, the virus that causes Covid-19.

Two main types of tests exist for Covid-19: one that detects the presence of the virus that causes Covid-19, which indicates a person has an active infection, and another that detects antibodies, showing that a person has been exposed to the virus.

The first test that was developed, a test for the presence of the virus, is used mainly to confirm diagnosis of Covid-19 in people who are showing symptoms such as a fever, a dry, persistent cough, difficulty breathing, a sense of restriction in the chest. "They are typical signs of Covid-19, but we would want to know if these are signs of the common flu or a bad cold or Covid-19. We know that Covid can progress really significantly very quickly, especially in individuals with underlying conditions," ProMIS CEO Dr. Elliot Goldstein told Streetwise Reports. "The number of tests is limited, but it's not actually the tests themselves but the reagents and systems you need to run the test that are in short supply."

"Anytime you conduct a test for the virus and get a negative response, the test indicates only that on that day at that time, the person does not have the virus. The person could have had Covid and recovered, or might have had an asymptomatic or very mild case. Or that person could get the virus tomorrow or in three days," Dr. Goldstein explained. "At any point in time the virus test helps indicate the prevalence of the virus—how many people are actually infected—if you test broadly, and at the time you do it, you can determine whether an individual is currently infected or not."

The second type of test, called serological tests or assays, is also known as an antibody test. "When a person is recovering from a viral infection, the immune system makes antibodies—also called immunoglobulins—that are specific to the virus. They neutralize the virus and help clear it out; that's part of the mechanism of why you get better," Dr. Goldstein explained.

One way to see if a person has had Covid is to test for antibodies. "A positive test means you've been exposed to the virus because, in the absence of a vaccine, that's the only way you would have the antibodies. While it's not 100% certain that antibodies neutralize the virus, based on experience with other coronaviruses, it is likely," Dr. Goldstein said. Having the virus neutralized should offer at least some protection against future re-infections.

People who have had positive virus tests know that they have Covid or had Covid and recovered, but many people are asymptomatic or may have had what felt like a light cold, and they want to know if they are at risk, or if they have some protection against the disease. "This is really important for frontline healthcare workers, people working 8-10 hours a day in intensive care or the emergency room with patients known to be very sick with Covid-19; even with protective equipment, they have significant exposure to the virus," Dr. Goldstein explained. "If someone has been through the disease and has natural antibodies, they can't infect someone else. What you want to know on an individual level is am I safe from infection and am I safe for other people."

Generally, antibody testing is a fairly common procedure, Dr. Goldstein explained. When you spin blood in a centrifuge, it separates into three parts: red blood cells, plasma and serum. Serum is where you find antibodies. "ELISA (enzyme-linked immunosorbent assay) is a standard test that looks for antibodies, but it is not specific enough for the Covid-19 virus."

The challenge is there are multiple coronaviruses. "Four different coronaviruses are responsible for the common cold, and then there are others like SARS and MERS. They all have the same sort of halo or corona of protein around the outside of it," Dr. Goldstein said. "They look like the old naval mines used in war. The whole family of coronaviruses look like that. The amino acid sequences of different coronaviruses are not identical but very similar; they share a lot of common structures. There are only really small differences and you can't really pick them up using the usual physical methods."

Studies have shown that up to 90% of individuals in Western countries have been exposed to one or more of the common cold coronaviruses and have antibodies against them. "They look very similar to the coronavirus causing Covid-19. So in Covid-19 antibody tests, the most important thing is it has to be highly specific for the Covid-19 antibodies and doesn't test positive when it identifies a common cold antibody. That is a false positive," said Dr. Goldstein. "It's actually much safer not to have a test that has a lot of false positives because you could base a behavioral decision on faulty information."

Dr. Goldstein cited an example. "If you are testing 1,000 people and there is a 90% prevalence for the cold virus, that means around 900 people have antibodies to the common cold. If the prevalence of the Covid-19 virus is 2%, roughly 20 of the 1,000 would have antibodies to the Covid-19 virus. Let's say the serology test has 95% specificity. That means five times out of 100, it will give a false positive, indicating the presence of Covid-19 antibodies when it is really picking up antibodies against the cold virus. What this means is 5% of 900, or 45 people, will test positive for Covid when they have not had it, and are making decisions based on incorrect information. The consequences of being wrong are dramatic and highlight the need for a very good, high-quality serological test."

How does this relate to Alzheimer's and other neurological diseases that are ProMIS' core competency? "In Alzheimer's, ALS, frontotemporal dementia, Parkinson's disease and other neurological disease, we've been able to use our proprietary, unique technology to identify sites on misfolded proteins that are driving these diseases. Our core technology is the capability to understand what's special about the bad proteins that are causing these diseases and then we can make antibodies highly selective against them. Our technology allows us to identify a region, an epitopes target, which is a series of four to six amino acids where the protein has misfolded. Not only do we know where this target site is located, importantly we also determine the shape (conformation) of this site. Proteins like amyloid and alpha synuclein and TDP 43 misfold and when these proteins misfold they become toxic, they kill neurons, resulting in disease," Dr. Goldstein explained.

ProMIS has transferred that thinking to the virus causing Covid-19. "The corona is composed of the spiky protein. Remember, we want to be able to distinguish between the coronavirus causing the common cold and the coronavirus causing Covid-19," Dr. Goldstein said. "If we can distinguish between the two, we can have an antibody test that's specific for Covid-19. We are looking at a region of the virus called the receptor binding domain, the RBD, that is part of the spike protein and how it attaches to cells. We have a core competency that allows us to identify sites, and not just the location of the sites, but the shape of the sites on complex protein molecules. That allows us then to use that knowledge to create either antibodies or to create serum tests, or even quite frankly, we can use those targets to create vaccines."

Using ProMIS' proprietary technology, the company has been able to "identify a site that we believe is only present on the Covid-19 virus and not on other coronaviruses. We are now initiating the synthesis of several different forms of that site; it's a small area," Dr. Goldstein stated. "That would then transfer to Dr. Hans Frykman's lab at University of British Columbia, a world-class serology lab. Then we will see if the targets we've identified are specific and selective antibodies against Covid-19."

When you test the serum of an individual, if they've been exposed to the virus and have the antibodies, "those antibodies should bind selectively and specifically to the target. So if the antibodies from the patient's serum are binding to the target site, we know it's a Covid-19 virus because that site is only visible in that shape on the Covid-19 virus and not the others. For the validation of our test, only in patients known to have had Covid-19 should we see binding of antibodies against Covid-19 to our target. The second validation is based on testing in serum from subjects known to have never been exposed to Covid-19 virus—such subjects have antibodies only from cold or other coronaviruses, and therefore the antibody test should be negative; there should be no binding. So we should only see binding in serum from a patient known to have recovered from COVID-19, and we should not see binding in serum from an individual known not to have been exposed to COVID-19," Dr. Goldstein explained.

"Our technology basically allows us to zero in with sniper-like precision on the structure of a protein and understand it, not only the structure overall but the shape of the regions on that protein and then that allows us to identify what is specific to that protein, in this case the spiky protein on the virus causing COVID-19," said Dr. Goldstein.

ProMIS expects to have initial results in June.

Disclosure:
1) Patrice Fusillo compiled this article for Streetwise Reports LLC and provides services to Streetwise Reports as an employee. She or members of her household own securities of the following companies mentioned in the article: None. She or members of her household are paid by the following companies mentioned in this article: None.
2) The following companies mentioned in this article are billboard sponsors of Streetwise Reports: ProMIS Neurosciences. Click here for important disclosures about sponsor fees.
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( Companies Mentioned: PMN:TSX; ARFXF:OTCQB, )

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