South Africans must insist on innovative solutions and new policies to ensure that when the country emerges from this governance and economic crisis, it does so not only aware of the country’s weaknesses but also primed to effect the necessary changes, writes Pieter du Toit.

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.

Wera, a four-year-old terrier cross, has found her way home to a Calgary-care organization after fraudsters tricked the dog's foster family.

Surrey director of cricket Alec Stewart has reluctantly accepted there could yet be a long-term good for the county game if it is wiped out in 2020.

The Stormers look set to receive a boost with centre Rikus Pretorius signing a contract extension.

After six weeks of negotiating, the UN Security Council was close to agreeing on a resolution for a global ceasefire during the Covid-19 pandemic. Seems fair, right? Let's agree to stop killing each other for a while, so we can focus on the virus that's killing us instead?

China proposed that the text explicitly mention a commitment by member nations to support the efforts of the World Health Organization — who Donald Trump has blamed (without evidence) for withholding information on the coronavirus outbreak.

So the US looked at the resolution and said "LOL no," despite last minute efforts to reach a compromise. As The Guardian reports:

On Thursday night, French diplomats thought they had engineered a compromise in which the resolution would mention UN “specialized health agencies” (an indirect, if clear, reference to the WHO).

The Russian mission signaled that it wanted a clause calling for the lifting of sanctions that affected the delivery of medical supplies, a reference to US punitive measures imposed on Iran and Venezuela. However, most security council diplomats believed Moscow would withdraw the objection or abstain in a vote rather than risk isolation as the sole veto on the ceasefire resolution.

While everyone else seemed game to go along with these compromises, the US insisted it was one big Chinese trick. As one diplomat told CNN:  "This discussion has been taken hostage by issues that do not have to do with the real issues at stake. Instead it has been transformed into a fight between the US and China. Read the rest

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The post REPORT: Actor says ‘rule of law is dead’ until Barr is ‘impeached’ appeared first on Dennis Michael Lynch.

John Hillman - the 101-year-old Second World War veteran who has been walking laps around the courtyard of his Oak Bay retirement home in hopes of raising $101,000 for charity - has surpassed his goal.

8 November 2013

18 June 2014

Research Event

Event participants

Jeremy Gordon, Director, China Business Services
Chair: Roderic Wye, Associate Fellow, Asia Programme, Chatham House

Members Event

Event participants

Professor Joseph S Nye, University Distinguished Service Professor, Harvard Kennedy School of Government
Chair: Gideon Rachman, Chief Foreign Affairs Commentator, Financial Times

30 September 2015

Members Event

Event participants

Dr Mukulika Banerjee, Director, South Asia Centre, London School of Economics
Nandan Nilekani, Co-founder and Chairman, EkStep; Chairman, Unique Identification Authority of India (UIAI) (2009-14)
Dr Gareth Price, Senior Research Fellow, Asia Programme, Chatham House
Mihir Swarup Sharma, India Columnist, Bloomberg View; Senior Fellow, Observer Research Foundation, New Delhi
Chair: James Crabtree, Contributing Editor, Financial Times; Senior Visiting Fellow, Lee Kuan Yew School of Public Policy

6 January 2017 , Volume 93, Number 1

Reiterlied posted a photo:

A tribute to Pirates I made last year when winter was coming to an end.

(You can find the blog post I wrote last year at Stuck in Plastic: www.stuckinplastic.com/2019/04/week-17-ching-shih/)

The investigation into the fatal shooting in Brunswick, Georgia, will also look at a neighbor of suspects Gregory and Travis McMichael who recorded video of the incident, authorities said.

Ousted vaccine expert Rick Bright said he is "frustrated at our inability to be heard as scientists."

The government said it's distributing the promising coronavirus drug, remdesivir, to some hard-hit states. Eventually, all 50 states should get it.

Travel blogger and photographer Andy Luten drove 4,200 miles across six states to see the grounded jets, detailing the shocking state of aviation.

Attorney General Bill Barr explained that the FBI did not conduct “a bonafide counterintelligence investigation” in the case that led former Trump national security adviser Michael Flynn to plead guilty to federal investigators in 2017.Barr, speaking in an exclusive interview with CBS News after the Justice Department dropped its case against Flynn on Thursday, said that his review of the case found Bureau investigators laid “a perjury trap” for Flynn in a January 2017 White House interview.“They didn’t warn him, the way that would usually be required by the Department, they bypassed the Justice Department, they bypassed the protocols at the White House, and so forth,” Barr stated. “These were things that persuaded me that there was not a legitimate counterintelligence investigation.”Former FBI director James Comey admitted in a December 2018 interview that he “sent” the agents to interview Flynn, adding that it was “something I probably wouldn’t have done or maybe gotten away with in a more organized administration.”In its Thursday court filing, the Justice Department explained that it was “not persuaded” that Flynn’s interview, which led to his guilty plea for lying to FBI agents Peter Strzok and Joe Pientka, had proper predication and was materially relevant.Comey tweeted his disappointment, following the decision, saying "the DOJ has lost its way."> The DOJ has lost its way. But, career people: please stay because America needs you. The country is hungry for honest, competent leadership.> > -- James Comey (@Comey) May 7, 2020Barr pointed to recently-released information that showed the FBI moved to close its surveillance of Flynn after finding “no derogatory information” about the retired general’s contacts with Russians, only for Strzok to keep the case open, leading to the eventual interview.“They were closing the investigation, in December [2016], they started that process and on January 4, they were closing it. When they heard about the phone call, which the FBI had the transcripts to — there was no question as to what was discussed, the FBI knew exactly what was discussed — and General Flynn, being the former director of the DIA, said to them, ‘you listen to everything, you know what was said,’” Barr explained.“So there’s no mystery about the call, but they initially tried some theories of how could open another investigation, which didn’t fly, and then they found out that they had not technically closed the earlier investigation, and they kept it open for the expressed purpose of trying to catch — lay a perjury trap — for General Flynn,” he added. A different filing released last week showed handwritten notes from an FBI official that questioned if the goal of Flynn’s White House interview was “to get him to lie, so we can prosecute him or get him fired.”Barr also did not comment on whether those that sought to entrap Flynn would face criminal charges, pointing to U.S. Attorney John Durham’s probe into the origins of the Trump-Russia investigation and saying his team was “in the middle” of “looking at the whole pattern of conduct.”“I’m going to wait until all the evidence is [in], and I get their recommendations as to what they found and how serious it is. But, if we were to find wrongdoing, in the sense of any criminal act, obviously we would follow through on that,” Barr said. “But again, just because something may even stink to high heaven, and appear to everyone to be bad, we still have to apply the right standard and be convinced that there is a violation of a criminal statute and that we can prove it beyond a reasonable doubt. The same standard applies to everybody.”

Bacterial products such as lipopolysaccharides (or endotoxin) cause systemic inflammation, resulting in a substantial global health burden. The onset, progression, and resolution of the inflammatory response to endotoxin are usually tightly controlled to avoid chronic inflammation. Members of the NF-κB family of transcription factors are key drivers of inflammation that activate sets of genes in response to inflammatory signals. Such responses are typically short-lived and can be suppressed by proteins that act post-translationally, such as the SOCS (suppressor of cytokine signaling) family. Less is known about direct transcriptional regulation of these responses, however. Here, using a combination of in vitro approaches and in vivo animal models, we show that endotoxin treatment induced expression of the well-characterized transcriptional repressor Krüppel-like factor 3 (KLF3), which, in turn, directly repressed the expression of the NF-κB family member RELA/p65. We also observed that KLF3-deficient mice were hypersensitive to endotoxin and exhibited elevated levels of circulating Ly6C+ monocytes and macrophage-derived inflammatory cytokines. These findings reveal that KLF3 is a fundamental suppressor that operates as a feedback inhibitor of RELA/p65 and may be important in facilitating the resolution of inflammation.

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.

Protease-activated receptor 2 (PAR-2) is activated by secreted proteases from immune cells or fungi. PAR-2 is normally expressed basolaterally in differentiated nasal ciliated cells. We hypothesized that epithelial remodeling during diseases characterized by cilial loss and squamous metaplasia may alter PAR-2 polarization. Here, using a fluorescent arrestin assay, we confirmed that the common fungal airway pathogen Aspergillus fumigatus activates heterologously-expressed PAR-2. Endogenous PAR-2 activation in submerged airway RPMI 2650 or NCI–H520 squamous cells increased intracellular calcium levels and granulocyte macrophage–colony-stimulating factor, tumor necrosis factor α, and interleukin (IL)-6 secretion. RPMI 2650 cells cultured at an air–liquid interface (ALI) responded to apically or basolaterally applied PAR-2 agonists. However, well-differentiated primary nasal epithelial ALIs responded only to basolateral PAR-2 stimulation, indicated by calcium elevation, increased cilia beat frequency, and increased fluid and cytokine secretion. We exposed primary cells to disease-related modifiers that alter epithelial morphology, including IL-13, cigarette smoke condensate, and retinoic acid deficiency, at concentrations and times that altered epithelial morphology without causing breakdown of the epithelial barrier to model early disease states. These altered primary cultures responded to both apical and basolateral PAR-2 stimulation. Imaging nasal polyps and control middle turbinate explants, we found that nasal polyps, but not turbinates, exhibit apical calcium responses to PAR-2 stimulation. However, isolated ciliated cells from both polyps and turbinates maintained basolateral PAR-2 polarization, suggesting that the calcium responses originated from nonciliated cells. Altered PAR-2 polarization in disease-remodeled epithelia may enhance apical responses and increase sensitivity to inhaled proteases.

Prevention of aberrant cutaneous wound repair and appropriate regeneration of an intact and functional integument require the coordinated timing of fibroblast and keratinocyte migration. Here, we identified a mechanism whereby opposing cell-specific motogenic functions of a multifunctional intracellular and extracellular protein, the receptor for hyaluronan-mediated motility (RHAMM), coordinates fibroblast and keratinocyte migration speed and ensures appropriate timing of excisional wound closure. We found that, unlike in WT mice, in Rhamm-null mice, keratinocyte migration initiates prematurely in the excisional wounds, resulting in wounds that have re-surfaced before the formation of normal granulation tissue, leading to a defective epidermal architecture. We also noted aberrant keratinocyte and fibroblast migration in the Rhamm-null mice, indicating that RHAMM suppresses keratinocyte motility but increases fibroblast motility. This cell context–dependent effect resulted from cell-specific regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) activation and expression of a RHAMM target gene encoding matrix metalloprotease 9 (MMP-9). In fibroblasts, RHAMM promoted ERK1/2 activation and MMP-9 expression, whereas in keratinocytes, RHAMM suppressed these activities. In keratinocytes, loss of RHAMM function or expression promoted epidermal growth factor receptor–regulated MMP-9 expression via ERK1/2, which resulted in cleavage of the ectodomain of the RHAMM partner protein CD44 and thereby increased keratinocyte motility. These results identify RHAMM as a key factor that integrates the timing of wound repair by controlling cell migration.

β-1,3-d-Glucan is a ubiquitous glucose polymer produced by plants, bacteria, and most fungi. It has been used as a diagnostic tool in patients with invasive mycoses via a highly-sensitive reagent consisting of the blood coagulation system of horseshoe crab. However, no method is currently available for measuring β-1,6-glucan, another primary β-glucan structure of fungal polysaccharides. Herein, we describe the development of an economical and highly-sensitive and specific assay for β-1,6-glucan using a modified recombinant endo-β-1,6-glucanase having diminished glucan hydrolase activity. The purified β-1,6-glucanase derivative bound to the β-1,6-glucan pustulan with a KD of 16.4 nm. We validated the specificity of this β-1,6-glucan probe by demonstrating its ability to detect cell wall β-1,6-glucan from both yeast and hyphal forms of the opportunistic fungal pathogen Candida albicans, without any detectable binding to glucan lacking the long β-1,6-glucan branch. We developed a sandwich ELISA-like assay with a low limit of quantification for pustulan (1.5 pg/ml), and we successfully employed this assay in the quantification of extracellular β-1,6-glucan released by >250 patient-derived strains of different Candida species (including Candida auris) in culture supernatant in vitro. We also used this assay to measure β-1,6-glucan in vivo in the serum and in several organs in a mouse model of systemic candidiasis. Our work describes a reliable method for β-1,6-glucan detection, which may prove useful for the diagnosis of invasive fungal infections.

Inter-α-inhibitor is a proteoglycan essential for mammalian reproduction and also plays a less well-characterized role in inflammation. It comprises two homologous “heavy chains” (HC1 and HC2) covalently attached to chondroitin sulfate on the bikunin core protein. Before ovulation, HCs are transferred onto the polysaccharide hyaluronan (HA) to form covalent HC·HA complexes, thereby stabilizing an extracellular matrix around the oocyte required for fertilization. Additionally, such complexes form during inflammatory processes and mediate leukocyte adhesion in the synovial fluids of arthritis patients and protect against sepsis. Here using X-ray crystallography, we show that human HC1 has a structure similar to integrin β-chains, with a von Willebrand factor A domain containing a functional metal ion-dependent adhesion site (MIDAS) and an associated hybrid domain. A comparison of the WT protein and a variant with an impaired MIDAS (but otherwise structurally identical) by small-angle X-ray scattering and analytical ultracentrifugation revealed that HC1 self-associates in a cation-dependent manner, providing a mechanism for HC·HA cross-linking and matrix stabilization. Surprisingly, unlike integrins, HC1 interacted with RGD-containing ligands, such as fibronectin, vitronectin, and the latency-associated peptides of transforming growth factor β, in a MIDAS/cation-independent manner. However, HC1 utilizes its MIDAS motif to bind to and inhibit the cleavage of complement C3, and small-angle X-ray scattering–based modeling indicates that this occurs through the inhibition of the alternative pathway C3 convertase. These findings provide detailed structural and functional insights into HC1 as a regulator of innate immunity and further elucidate the role of HC·HA complexes in inflammation and ovulation.

Bacterial biofilms are cellular communities that produce an adherent matrix. Exopolysaccharides are key structural components of this matrix and are required for the assembly and architecture of biofilms produced by a wide variety of microorganisms. The human bacterial pathogens Escherichia coli and Salmonella enterica produce a biofilm matrix composed primarily of the exopolysaccharide phosphoethanolamine (pEtN) cellulose. Once thought to be composed of only underivatized cellulose, the pEtN modification present in these matrices has been implicated in the overall architecture and integrity of the biofilm. However, an understanding of the mechanism underlying pEtN derivatization of the cellulose exopolysaccharide remains elusive. The bacterial cellulose synthase subunit G (BcsG) is a predicted inner membrane–localized metalloenzyme that has been proposed to catalyze the transfer of the pEtN group from membrane phospholipids to cellulose. Here we present evidence that the C-terminal domain of BcsG from E. coli (EcBcsGΔN) functions as a phosphoethanolamine transferase in vitro with substrate preference for cellulosic materials. Structural characterization of EcBcsGΔN revealed that it belongs to the alkaline phosphatase superfamily, contains a Zn2+ ion at its active center, and is structurally similar to characterized enzymes that confer colistin resistance in Gram-negative bacteria. Informed by our structural studies, we present a functional complementation experiment in E. coli AR3110, indicating that the activity of the BcsG C-terminal domain is essential for integrity of the pellicular biofilm. Furthermore, our results established a similar but distinct active-site architecture and catalytic mechanism shared between BcsG and the colistin resistance enzymes.

Immigration is a prominent part of the United States’ DNA, despite concerns about immigrants’ ability to integrate. An examination of recent immigrant inflows shows newcomers to the United States are integrating well, based on language proficiency, socioeconomic attainment, political participation, residential locale, and social interaction indicators.

Illegal immigration is possible in large part because of illegal employment. This report shows the underlying drivers of illegal hiring vary based on the type of employer, the nature of the industry, state of the economy, and a country’s labor market institutions, employment legislation, immigration systems, and even culture.

The report examines U.S. immigration and international development policies, which have unique objectives and respond to distinct political and administrative constraints, and points out that international development has never been a U.S. immigration policy objective; nonetheless, it is an unintended consequence.

While aspects of the U.S. immigration system facilitate newcomers’ contributions to economic growth and competitiveness, others undermine them. Reforms are needed to enhance the job-creating power of U.S. employers and strengthen the system’s ability to select effectively from the large pool of foreign workers.

This report explores the migration patterns and demographics of Black African immigrants in the United States, examining their admission channels, human-capital characteristics, and labor market performance. The authors also provide an analysis of these immigrants' integration prospects.

The EU-U.S. relationship is one of the most significant partnerships among wealthy nations. Interconnections between the two on migration issues make dialogue necessary and inevitable, as each relies on each other to attain a number of policy objectives, most clearly in the case of travel and border security.

Civil society provides a crucial link between governments and the communities they represent—infusing policy processes with grassroots knowledge to which governments may not otherwise have access. Looking at the European Union’s efforts to engage with civil society in its “neighborhood,” this report examines the benefits, challenges, and mechanisms to building dialogue and cooperation on migration and development.

Since 1970, the immigrant populations from Mexico and Central America living in the United States have increased significantly: rising by a factor of 20 even as the total U.S. immigrant population increased four-fold over the period. This demographic report examines the age, educational, and workforce characteristics of these immigrants.

Showcasing joint research by MPI and the European University Institute and funded by the European Commission, this event featured discussion on some of the most promising reform proposals on both sides of the Atlantic. Speakers discuss the project’s comparative research, which draws on MPI’s longstanding experience advising European and North American governments on immigration.

European dominance in U.S. immigration flows has decreased significantly since World War II, a result of economic, demographic, and policy trends on both sides of the Atlantic. Today, migration from European Union Member States to the United States, while small, is characterized by a substantial numbers of European scientists, professionals, and businesspeople.

The United States has historically offered unparalleled economic opportunity to successive generations of immigrants and their children, poised to play an increasing role in the U.S. economy. But the lasting impact of job loss and slower growth over the next decade will translate into fewer opportunities for workers—and immigrants may prove the most vulnerable.

This final report summarizes and reflects upon the key findings of the Improving EU and U.S. Immigration Systems: Learning from Experience comparative research project undertaken by MPI and the European University Institute through a grant from the European Commission.

Written from, different angles and spaces, the poems below testify to the great force of motherhood, which nurtures, strengthens, and manifests love. Happy Mother’s Day – Ann-Margaret Lim Words My mother loved words. Not necessarily in...