Plasmodium vivax is a major cause of malaria, which poses an increased health burden on approximately one third of the world's population due to climate change. Primaquine, the preferred treatment for P. vivax malaria, is contraindicated in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, a common genetic cause of hemolytic anemia, that affects ∼2.5% of the world's population and ∼8% of the population in areas of the world where P. vivax malaria is endemic. The Seattle Structural Genomics Center for Infectious Disease (SSGCID) conducted a structure–function analysis of P. vivax N-myristoyltransferase (PvNMT) as part of efforts to develop alternative malaria drugs. PvNMT catalyzes the attachment of myristate to the N-terminal glycine of many proteins, and this critical post-translational modification is required for the survival of P. vivax. The first step is the formation of a PvNMT–myristoyl–CoA binary complex that can bind to peptides. Understanding how inhibitors prevent protein binding will facilitate the development of PvNMT as a viable drug target. NMTs are secreted in all life stages of malarial parasites, making them attractive targets, unlike current antimalarials that are only effective during the plasmodial erythrocytic stages. The 2.3 Å resolution crystal structure of the ternary complex of PvNMT with myristoyl-CoA and a novel inhibitor is reported. One asymmetric unit contains two monomers. The structure reveals notable differences between the PvNMT and human enzymes and similarities to other plasmodial NMTs that can be exploited to develop new antimalarials.

In this photo taken on February 10, 2020 a 'love kit' is seen on the bed in a room at the Dragonfly hotel in Mumbai.; Credit: PUNIT PARANJPE/AFP via Getty Images

A new survey shows that in the era of widespread vaccine availability, American couples are more satisfied in their relationships -- and some are even getting more experimental than they have been.

Led by Indiana University Kinsey Institute researcher Justin Lehmiller in collaboration with the website Lovehoney, which describes itself as “global sexual happiness experts,” the report looked at responses from 2,000 U.S. adults age 18-45, including an oversample of 200 who identified as LGBTQ, and among the major findings of the survey were that more than half (51 percent) of respondents said their sexual interests had changed during the pandemic, and many of those said they’d started trying things they hadn’t before. It also found that 44 percent of people surveyed said they were communicating better with their partner, and among singles surveyed 52 percent say they’re less interested in casual sex and more than a third of them said they weren’t interested in having sex on the first date.

Today on AirTalk, we’ll talk with Professor Lehmiller about the survey, its findings and how the pandemic impacted Americans’ views on relationships and sex.

Guest: 

Justin Lehmiller, social psychologist and research fellow at Indiana University’s Kinsey Institute who conducted the “Summer of Love” survey; author of “Tell Me What You Want: The Science of Sexual Desire and How It Can Help You Improve Your Sex Life” (Hachette Go, July 2020); host of the “Sex and Psychology” podcast; he tweets @JustinLehmiller

This content is from Southern California Public Radio. View the original story at SCPR.org.

The 'On the Floor' hitmaker introduces her mother to fans as she invites the matriarch to join her on stage and perform a duet at the Global Citizen concert in Los Angeles.

As Israel continues to block lifesaving humanitarian aid from entering northern Gaza, humanitarian organizations are describing its siege as “apocalyptic” and warning of mass Palestinian starvation and death. “The situation is absolutely desperate,” says Rachael Cummings of the aid group Save the Children International. Cummings joins us from Deir al-Balah in central Gaza, where aid organizations have been halted from entering the north. She responds to news of Israel’s bombing of a polio vaccination center in an area that had been marked for an official humanitarian pause, and the Knesset’s vote to ban the U.N. relief agency UNRWA.

Crucell Announces New Award of (Dollor) 110 Million for Paediatric Vaccine Quinvaxem(R) by UNICEF to Support Vaccination Program

Advaxis has announced that the U.S. Food and Drug Administration (FDA) has lifted the clinical hold on IND applications of its three drugs. Advaxis is

Vaccine also offers 65% protection against Delta variant, according to firm

The WHO has recognised TTS as a rare but serious adverse event linked to specific Covid-19 vaccines.

Tune into our new show Fox League Live on Channel 502 Monday to Friday at 6.30pm and on Saturday at 3pm and Sunday at 5pm.

Gold Coast skipper David Swallow has added his voice to football’s flu shot debate, saying players should not be forced to be immunised before the AFL season starts.

Tune into our new show Fox League Live on Channel 502 Monday to Friday at 6.30pm and on Saturday at 3pm and Sunday at 5pm.

Tune into our new show Fox League Live on Channel 502 Monday to Friday at 6.30pm and on Saturday at 3pm and Sunday at 5pm.

Tune into our new show Fox League Live on Channel 502 Monday to Friday at 6.30pm and on Saturday at 3pm and Sunday at 5pm.

Tune into our new show Fox League Live on Channel 502 Monday to Friday at 6.30pm and on Saturday at 3pm and Sunday at 5pm.

Tune into our new show Fox League Live on Channel 502 Monday to Friday at 6.30pm and on Saturday at 3pm and Sunday at 5pm.

Tune into our new show Fox League Live on Channel 502 Monday to Friday at 6.30pm and on Saturday at 3pm and Sunday at 5pm.

Tune into our new show Fox League Live on Channel 502 Monday to Friday at 6.30pm and on Saturday at 3pm and Sunday at 5pm.

Shanelle Cartwright, the wife of Gold Coast Titans forward Bryce Cartwright, posted the image of the teenage Holocaust victim to her Instagram story on Friday.

Crowds broke social distancing laws to protest on the steps of Parliament House in Melbourne on Sunday in an effort to lift 'absurd' COVID-19 lockdowns and reopen the nation.

Malaria is a devastating disease caused by a protozoan parasite. It affects over 300 million individuals and results in over 400 000 deaths annually, most of whom are young children under the age of five. Hexokinase, the first enzyme in glucose metabolism, plays an important role in the infection process and represents a promising target for therapeutic intervention. Here, cryo-EM structures of two conformational states of Plasmodium vivax hexokinase (PvHK) are reported at resolutions of ∼3 Å. It is shown that unlike other known hexokinase structures, PvHK displays a unique tetrameric organization (∼220 kDa) that can exist in either open or closed quaternary conformational states. Despite the resemblance of the active site of PvHK to its mammalian counterparts, this tetrameric organization is distinct from that of human hexokinases, providing a foundation for the structure-guided design of parasite-selective antimalarial drugs.

Bernice Hausman is chair of the Department of Humanities in the Penn State College of Medicine. She’s recognized for her research on vaccines and breastfeeding, including why both can be controversial in the United States. She has written several books, most recently "Anti/Vax: Reframing the Vaccination Controversy," which was published last year. WPSU's Anne Danahy spoke with Hausman about what we can learn from past vaccine controversies about the COVID-19 epidemic.

Anti-vax WAG Taylor Winterstein has said that there is a “strong core of families” in the NRL who are also anti-vaxxers that Australians would be “seriously surprised” about.

1. Dodging the flu shot doesn't make you an anti-vaxxer, says union  The Age
2. Shop owners in virus-free towns plead to reopen  The Age
3. UFC 249 preview - Ferguson v Gaethje, Cejudo v Cruz and…  BT Sport
4. Why the best team won't win in a year that will be mental as anything  Sydney Morning Herald
5. Wellbeing hit: modelling reveals huge cost of school closures  Sydney Morning Herald
6. View Full coverage on Google News

With coronavirus on the rampage, perhaps the people who don't believe in vaccinations will rethink their irresponsible position.

Tattoo artist Kat Von D also clears the air about parting ways with her beauty brand, her new vegan shoe line and her upcoming music career.

If the messages from anti-lockdown protests sound familiar, that's because the same people who protested a law to tighten vaccine laws in California are organizing the marches on Sacramento.

CYP450 enzymes are involved in biotransformation of chloroquine (CQ), but the role of the different metabolism profiles of this drug has not been properly investigated in relation to P. vivax recurrences. To investigate the influence of CYPs genotypes associated with CQ-metabolism on early recurrence rates of P. vivax, a case-control study was carried out. Cases included patients presenting an early recurrence (CQ-recurrent), defined as recurrence during the first 28 days after initial infection, plasma concentrations of CQ plus desethylchloroquine (DCQ, the major CQ metabolite) higher than 100 ng/mL. A control (CQ-responsive) with no parasite recurrence over the follow-up was also included. CQ and DCQ plasma levels were measured on Day 28. CQ CYPs (CYP2C8, CYP3A4 and CYP3A5) genotypes were determined by real-time PCR. An ex vivo study was conducted to verify CQ and DCQ efficacy in P. vivax isolates. The frequency of alleles associated with normal and slow metabolism was similar between the cases and controls for CYP2C8 (OR=1.45, 95% CI=0.51-4.14, p=0.570), CYP3A4 (OR=2.38, 95% CI=0.92-6.19, p=0.105) and CYP3A5 (OR=4.17, 95% CI=0.79-22.04, p=1.038) genes. DCQ levels were higher than CQ, regardless of the genotype. Regarding the DCQ/CQ rate, there was no difference between groups or between those patients who had a normal or mutant genotype. DCQ and CQ showed similar efficacy ex vivo. CYPs genotypes had no influence on early recurrence rates. Similar efficacy of CQ and DCQ ex vivo could explain the absence of therapeutic failure, despite presence of alleles associated with slow metabolism.

NetBSD uses the ptrace(2) system call to trace and debug other processes. The debugging process can also modify the internal registers, including the status (PSL) register, for the process being debugged. Besides the normal user-accessible flags, the VAX hardware also stores information about privilege levels and used stacks in the PSL. Those flags are only altered via the instruction REI (return from interrupt) or LDPCTX (load process context) and cannot be modified while running in "user" mode. NetBSD security page here.

How to hack VAX's.

A VAX decoy script to grab some accunts.

Pretty complete file on hacking VAX/VMS machines

Endothelial activation and microvascular dysfunction are key pathogenic processes in severe malaria. We evaluated the early role of these processes in experimentally induced Plasmodium falciparum and P. vivax infection. Participants were enrolled in induced blood-stage malaria clinical trials. Plasma osteoprotegerin, angiopoietin-2, and von Willebrand Factor (vWF) levels were measured as biomarkers of endothelial activation. Microvascular function was assessed using peripheral arterial tonometry and near-infrared spectroscopy, and the endothelial glycocalyx was assessed by sublingual videomicroscopy and measurement of biomarkers of degradation. Forty-five healthy, malaria-naive participants were recruited from 5 studies. Osteoprotegerin and vWF levels increased in participants following inoculation with P. vivax (n = 16) or P. falciparum (n = 15), with the angiopoietin-2 level also increasing in participants following inoculation with P. falciparum. For both species, the most pronounced increase was seen in osteoprotegerin. This was particularly marked in participants inoculated with P. vivax, where the osteoprotegerin level correlated with the levels of parasitemia and the malaria clinical score. There were no changes in measures of endothelial glycocalyx or microvascular function. Plasma biomarkers of endothelial activation increased in early P. falciparum and P. vivax infection and preceded changes in the endothelial glycocalyx or microvascular function. The more pronounced increase in osteoprotegerin suggests that this biomarker may play a role in disease pathogenesis.

Mycoplasma gallisepticum is the primary etiological agent of chronic respiratory disease in chickens. Live attenuated vaccines are most commonly used in the field to control the disease, but current vaccines have some limitations. Vaxsafe MG (strain ts-304) is a new vaccine candidate that is efficacious at a lower dose than the current commercial vaccine strain ts-11, from which it is derived. In this study, the transcriptional profiles of the trachea of unvaccinated chickens and chickens vaccinated with strain ts-304 were compared 2 weeks after challenge with M. gallisepticum strain Ap3AS during the chronic stage of infection. After challenge, genes, gene ontologies, pathways, and protein classes involved in inflammation, cytokine production and signaling, and cell proliferation were upregulated, while those involved in formation and motor movement of cilia, formation of intercellular junctional complexes, and formation of the cytoskeleton were downregulated in the unvaccinated birds compared to the vaccinated birds, reflecting immune dysregulation and the pathological changes induced in the trachea by infection with M. gallisepticum. Vaccination appears to protect the structural and functional integrity of the tracheal mucosa 2 weeks after infection with M. gallisepticum.

RiVax is a promising recombinant ricin toxin A subunit (RTA) vaccine antigen that has been shown to be safe and immunogenic in humans and effective at protecting rhesus macaques against lethal-dose aerosolized toxin exposure. We previously used a panel of RTA-specific monoclonal antibodies (MAbs) to demonstrate, by competition enzyme-linked immunosorbent assay (ELISA), that RiVax elicits similar serum antibody profiles in humans and macaques. However, the MAb binding sites on RiVax have yet to be defined. In this study, we employed hydrogen exchange-mass spectrometry (HX-MS) to localize the epitopes on RiVax recognized by nine toxin-neutralizing MAbs and one nonneutralizing MAb. Based on strong protection from hydrogen exchange, the nine MAbs grouped into four spatially distinct epitope clusters (namely, clusters I to IV). Cluster I MAbs protected RiVax's α-helix B (residues 94 to 107), a protruding immunodominant secondary structure element known to be a target of potent toxin-neutralizing antibodies. Cluster II consisted of two subclusters located on the "back side" (relative to the active site pocket) of RiVax. One subcluster involved α-helix A (residues 14 to 24) and α-helices F-G (residues 184 to 207); the other encompassed β-strand d (residues 62 to 69) and parts of α-helices D-E (154 to 164) and the intervening loop. Cluster III involved α-helices C and G on the front side of RiVax, while cluster IV formed a sash from the front to back of RiVax, spanning strands b, c, and d (residues 35 to 59). Having a high-resolution B cell epitope map of RiVax will enable the development and optimization of competitive serum profiling assays to examine vaccine-induced antibody responses across species.

The identification of biomarkers for patient stratification is fundamental to precision medicine efforts in oncology. Here, we identified two baseline, circulating immune cell subsets associated with overall survival in patients with metastatic pancreatic cancer who were enrolled in two phase II randomized studies of GVAX pancreas and CRS-207 immunotherapy. Single-cell mass cytometry was used to simultaneously measure 38 cell surface or intracellular markers in peripheral blood mononuclear cells obtained from a phase IIa patient subcohort (N = 38). CITRUS, an algorithm for identification of stratifying subpopulations in multidimensional cytometry datasets, was used to identify single-cell signatures associated with clinical outcome. Patients with a higher abundance of CD8⁺CD45RO^–CCR7^–CD57⁺ cells and a lower abundance of CD14⁺CD33⁺CD85j⁺ cells had improved overall survival [median overall survival, range (days) 271, 43–1,247] compared with patients with a lower abundance of CD8⁺CD45RO^–CCR7^–CD57⁺ cells and higher abundance of CD14⁺CD33⁺CD85j⁺ cells (77, 24–1,247 days; P = 0.0442). The results from this prospective–retrospective biomarker analysis were validated by flow cytometry in 200 patients with pancreatic cancer enrolled in a phase IIb study (P = 0.0047). The identified immune correlates provide potential prognostic or predictive signatures that could be employed for patient stratification.

Plasmodium vivax relapse is one of the major causes of sustained global malaria transmission. Primaquine (PQ) is the only commercial drug available to prevent relapses, and its efficacy is dependent on metabolic activation by cytochrome P450 2D6 (CYP2D6). Impaired CYP2D6 function, caused by allelic polymorphisms, leads to the therapeutic failure of PQ as a radical cure for P. vivax malaria. Here, we hypothesized that the host immune response to malaria parasites modulates susceptibility to P. vivax recurrences in association with CYP2D6 activity. We performed a 10-year retrospective study by genotyping CYP2D6 polymorphisms in 261 malaria-exposed individuals from the Brazilian Amazon. The immune responses against a panel of P. vivax blood-stage antigens were evaluated by serological assays. We confirmed our previous findings, which indicated an association between impaired CYP2D6 activity and a higher risk of multiple episodes of P. vivax recurrence (risk ratio, 1.75; 95% confidence interval [CI], 1.2 to 2.6; P = 0.0035). An important finding was a reduction of 3% in the risk of recurrence (risk ratio, 0.97; 95% CI, 0.96 to 0.98; P < 0.0001) per year of malaria exposure, which was observed for individuals with both reduced and normal CYP2D6 activity. Accordingly, subjects with long-term malaria exposure and persistent antibody responses to various antigens showed fewer episodes of malaria recurrence. Our findings have direct implications for malaria control, since it was shown that nonimmune individuals who do not respond adequately to treatment due to reduced CYP2D6 activity may present a significant challenge for sustainable progress toward P. vivax malaria elimination.

YouTube, Facebook crack down on two viral videos for spreading medical misinformation.

Covid-19 could be 'antidote to complacency' among those on the fence about vaccines, scientists say

Pinpointing the sources of myths that threaten the health of children could help get the truth out to where it is needed

A survey of five European countries revealed that parents in Spain have the most positive feelings towards vaccination, while their French counterparts have the least.

The protesters will demand the government lifts 'absurd' lockdown rules and reopen the nation immediately.

Cronulla captain Wade Graham has called out anti-vaxxers who refuse to get a flu shot, saying they should put their teammates above their own personal...

Gold Coast Titans star Bryce Cartwright has been one of the NRL's most prominent critics of vaccines, with his wife revealing last year the couple would not be vaccinating their children.

he Gold Coast Titans star back-rower indicated to team officials that he will refuse to get the jab when training resumed training on Monday as his anti-vaxxer wife stood by his decision.

None of her claims are scientifically proven, but NRL WAG Taylor Winterstein insists she has 'collected the crucial information needed to help break the coronavirus SCAMdemic.'

NRL WAGs Taylor Winterstein and Jade Grant came out in support of Bryce Cartwright, who told Gold Coast Titans doctors he would refuse the flu shot mandated by the league.

The Gold Coast Titans backrower is waiting to hear whether he can play when the season restarts on May 28 after telling team officials he will refuse the compulsory influenza injection.