Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N6-ethenoadenosine (1,N6-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2–mediated incision. Mass spectral analysis revealed that 1,N6-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N6-ϵrA. We also show that hpol η acts as a reverse transcriptase in the presence of damaged ribonucleotide 1,N6-ϵrA but has poor RNA primer extension activities. Steady-state kinetic analysis of reverse transcription and RNA primer extension showed that hpol η favors the addition of dATP and dGTP opposite 1,N6-ϵrA. We also found that RNase H2 recognizes 1,N6-ϵrA but has limited incision activity across from this lesion, which can lead to the persistence of this detrimental DNA adduct. We conclude that the damaged and unrepaired ribonucleotide 1,N6-ϵrA in DNA exhibits mutagenic potential and can also alter the reading frame in an mRNA transcript because 1,N6-ϵrA is incompletely incised by RNase H2.

Rationale: Despite its widespread use in oncology, the PET radiotracer ¹⁸F-FDG is ineffective for improving early detection of pancreatic ductal adenocarcinoma (PDAC). An alternative strategy for early detection of pancreatic cancer involves visualisation of high-grade pancreatic intraepithelial neoplasias (PanIN-3), generally regarded as the non-invasive precursors of PDAC. The DNA damage response is known to be hyper-activated in late-stage PanINs. Therefore, we investigated whether the SPECT imaging agent, ¹¹¹In-anti-H2AX-TAT, allows visualisation of the DNA damage repair marker H2AX in PanIN-3s in an engineered mouse model of PDAC, to facilitate early detection of PDAC. Methods: Genetically engineered KPC mice (KRasLSL.G12D/+; p53LSL.R172H/+; PdxCre) were imaged with ¹⁸F-FDG and ¹¹¹In-anti-H2AX-TAT. PanIN/PDAC presence visualised by histology was compared with autoradiography and immunofluorescence. Separately, the survival of KPC mice imaged with ¹¹¹In-anti-H2AX-TAT was evaluated. Results: In KPC mouse pancreata, H2AX expression was increased in high-grade PanINs, but not in PDAC, corroborating earlier results obtained from human pancreas sections. Uptake of ¹¹¹In-anti-H2AX-TAT, but not ¹¹¹In-IgG-TAT or ¹⁸F-FDG, within the pancreas was positively correlated with the age of KPC mice, which was correlated with the number of high-grade PanINs. ¹¹¹In-anti-H2AX-TAT localises preferentially in high-grade PanIN lesions, but not in established PDAC. Younger, non-tumour-bearing KPC mice that show uptake of ¹¹¹In-anti-H2AX-TAT in the pancreas survive significantly shorter than mice with physiological ¹¹¹In-anti-H2AX-TAT uptake. Conclusion: ¹¹¹In-anti-H2AX-TAT imaging allows non-invasive detection of DNA damage repair signalling upregulation in pre-invasive PanIN lesions and is a promising new tool to aid in the early detection and staging of pancreatic cancer.

It does not matter that he does not listen to you, That you’d rather he say your neck Is as graceful as an antelopes, Perhaps he’s not accustomed to lying. If he bought you an expensive phone you, Dropped in the bath the next day, would You, In yellow, Say he does not love you? […]

1 June 2012 , Volume 68, Number 4

Eyes in the skies keeping watch on a planet under stress. Click on the PDF link to view the graphic

In February World Health Organization (WHO) declared the microcephaly epidemic in South America an international public health emergency. Today, the US Centers for Disease Control and Prevention, the CDC, has confirmed that it’s is Zika virus which is causing that microcephaly.  The outbreak was originally spotted in Recife, in Brazil, and it’s...

Clinical studies have suggested that changes in peripheral nerve microcirculation may contribute to nerve damage in diabetic polyneuropathy (DN). High-sensitivity troponin T (hsTNT) assays have been recently shown to provide predictive values for both cardiac and peripheral microangiopathy in type 2 diabetes (T2D). This study investigated the association of sciatic nerve structural damage in 3 Tesla (3T) magnetic resonance neurography (MRN) with hsTNT and N-terminal pro-brain natriuretic peptide serum levels in patients with T2D. MRN at 3T was performed in 51 patients with T2D (23 without DN, 28 with DN) and 10 control subjects without diabetes. The sciatic nerve’s fractional anisotropy (FA), a marker of structural nerve integrity, was correlated with clinical, electrophysiological, and serological data. In patients with T2D, hsTNT showed a negative correlation with the sciatic nerve’s FA (r = –0.52, P < 0.001), with a closer correlation in DN patients (r = –0.66, P < 0.001). hsTNT further correlated positively with the neuropathy disability score (r = 0.39, P = 0.005). Negative correlations were found with sural nerve conduction velocities (NCVs) (r = –0.65, P < 0.001) and tibial NCVs (r = –0.44, P = 0.002) and amplitudes (r = –0.53, P < 0.001). This study is the first to show that hsTNT is a potential indicator for structural nerve damage in T2D. Our results indirectly support the hypothesis that microangiopathy contributes to structural nerve damage in T2D.

Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N6-ethenoadenosine (1,N6-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2–mediated incision. Mass spectral analysis revealed that 1,N6-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N6-ϵrA. We also show that hpol η acts as a reverse transcriptase in the presence of damaged ribonucleotide 1,N6-ϵrA but has poor RNA primer extension activities. Steady-state kinetic analysis of reverse transcription and RNA primer extension showed that hpol η favors the addition of dATP and dGTP opposite 1,N6-ϵrA. We also found that RNase H2 recognizes 1,N6-ϵrA but has limited incision activity across from this lesion, which can lead to the persistence of this detrimental DNA adduct. We conclude that the damaged and unrepaired ribonucleotide 1,N6-ϵrA in DNA exhibits mutagenic potential and can also alter the reading frame in an mRNA transcript because 1,N6-ϵrA is incompletely incised by RNase H2.

OBJECTIVE

Acrylamide exposure from daily-consumed food has raised global concern. We aimed to assess the exposure-response relationships of internal acrylamide exposure with oxidative DNA damage, lipid peroxidation, and fasting plasma glucose (FPG) alteration and investigate the mediating role of oxidative DNA damage and lipid peroxidation in the association of internal acrylamide exposure with FPG.

By Emily Reynolds. Participants whose self-esteem was based on financial success felt more lonely and disconnected from others.

The tremors, which arrived in the midst of the COVID-19 pandemic, was the worst the Croatian capital has seen in 140 years

The Museo de la Massacre de Ponce and Casa Paoli were among the buildings affected by Saturday's tremors

Using the lunar module as a lifeboat and employing techniques never before considered, the astronauts' ordeal ended triumphantly

A contemporary weapons expert is about to test a medieval war hammer on a steel breastplate from that era. The aim is to find out how much damage this fearsome instrument of death could deal.

An industrial building in Thunder Bay was slightly damaged in a fire late Thursday afternoon.

Residents are cleaning up damage to hundreds of homes and businesses caused by floods in the northern Alberta hamlet of Fort Vermilion.

Disaster relief funding for punishing spring floods is welcome news to civic leaders in northern Alberta.

Speech by Mr Fehmi Mehmeti, Governor of the Central Bank of the Republic of Kosovo, at the press conference where the details of the measures taken by the CBK for maintaining health in the economy were given, Pristina, 3 April 2020.

Source: Public News Service - Economists warn that the costs of climate change in the U.S. – including from the health impacts of air pollution and natural disasters such as hurricanes and wildfires – could top $350 billion annually in the next 10 years.

Smoking during pregnancy has been related to thicker carotid intima media thickness in young adults, and this was also shown in neonates.

This study is the first to show that the effect of smoking during pregnancy on the vasculature of children is (still) visible at the age of 5 years. Pregnancy appears to be the critical period for this damage to occur. (Read the full article)

Moisture damage and mold increase the risk of asthma and asthmatic symptoms. However, the location of the damage, or the specific group of children who are at greater risk of asthma, is rarely taken into account.

Inspector-observed moisture damage or mold in the child’s bedroom, living room, or kitchen increased the risk of asthma and persistent asthma during a 6-year follow-up. Atopic children may be more susceptible to the effects of moisture damage and mold. (Read the full article)

Recent studies highlight the abundance of commensal coagulase-negative staphylococci (CoNS) on healthy skin. Evidence suggests that CoNS actively shape the skin immunological and microbial milieu to resist colonization or infection by opportunistic pathogens, including methicillin resistant Staphylococcus aureus (MRSA), in a variety of mechanisms collectively termed colonization resistance. One potential colonization resistance mechanism is the application of quorum sensing, also called the Accessory Gene Regulator (agr) system, which is ubiquitous among staphylococci. Common and rare CoNS make autoinducing peptides (AIPs) that function as MRSA agr inhibitors, protecting the host from invasive infection. In a screen of CoNS spent media we found that Staphylococcus simulans, a rare human skin colonizer and frequent livestock colonizer, released potent inhibitors of all classes of MRSA agr signaling. We identified three S. simulans agr classes, and have shown intraspecies cross-talk between non-cognate S. simulans agr types for the first time. The S. simulans AIP-I structure was confirmed, and the novel AIP-II and AIP-III structures were solved via mass spectrometry. Synthetic S. simulans AIPs inhibited MRSA agr signaling with nanomolar potency. S. simulans in competition with MRSA reduced dermonecrotic and epicutaneous skin injury in murine models. Addition of synthetic AIP-I also effectively reduced MRSA dermonecrosis and epicutaneous skin injury in murine models. These results demonstrate potent anti-MRSA quorum sensing inhibition by a rare human skin commensal, and suggest that cross-talk between CoNS and MRSA may be important in maintaining healthy skin homeostasis and preventing MRSA skin damage during colonization or acute infection.

DOVER, Del. — Too much rain at the wrong time, like Delaware experienced in April and May, has destroyed several high dollar crops and threatens the yield of many others, leaving farmers to wonder what the future holds. In surveying the state and listening to farmers, Secretary of Agriculture Michael T. Scuse made a request […]

DOVER, Del. — A recent increase in severe deer damage to agricultural crops on two portions of Redden State Forest in Sussex County has created public deer harvest opportunities to assist local farmers. Through a partnership with DNREC’s Division of Fish & Wildlife, the Delaware Department of Agriculture’s Forest Service is opening specific portions of […]

The trail at the St. Jones Reserve (DNERR) near Dover is temporarily closed past the first marsh boardwalk as a result of damage caused by storms.

Humans are causing irreversible damage to the planet from burning fossil fuels, the biggest ever study of the available science concluded in a report designed to spur the fight against climate change.

Humans are causing irreversible damage to the planet from burning fossil fuels, the biggest ever study of the available science concluded in a report designed to spur the fight against climate change.

On 13 September 2017, EDF and ERDF lost their fight to declare null and void the contracts they entered into further to bids that were rigged by Nexans France (“Nexans”), Prysmian Energies Câbles et Systèmes (“Prysmian...

Bunge SA v Nidera BV [2015] UKSC 43 This case was first brought to the attention of the Commercial Court in June 2013, when an appeal on the ruling of the first arbitral panel was sought by the Claimant, Bunge SA (“Bunge”). The matter at...

Kim Sang-jo, Chairman of the Fair Trade Commission, said, "Our commission will soon announce plans to stop the practice of large companies using technology of small enterprises without proper compensation." He held a press conference on August 13 at the Sejong government complex in relation to his agency's bid to root out unfair practices in the retail industry and said, "The biggest obstacle for small- and medium-sized enterprises for their further development is the uneven relationship with...

Strongman Haftar denies Tripoli government claims shelling by his forces caused civilian casualties

[Dalsan Radio] The International Rescue Committee has warned that many cases are going untested and undetected. Somalia has faced decades of violence and cycles of drought and floods, leaving its health care system ill-equipped to respond to this outbreak. The International Rescue Committee (IRC) has been preparing for the spread of coronavirus by training health care staff to screen patients for symptoms and safely isolate potential cases.

With timely and well-targeted programs, policy makers can prevent the health crisis from deepening into a wider economic and financial crisis. This could sow the seeds of economic recovery.  

A Reuters examination has found that widespread crop damage covering millions of acres of Midwestern farmland has its roots in weak regulatory oversight and corporate secrecy.

Extreme storms Hurricane Florence and Typhoon Mangkhut have caused destruction and taken lives across the globe this week, forcing millions to evacuate their homes

Title: Tysabri May Treat Myelin Sheath Damage From MS
Category: Health News
Created: 4/29/2009 2:00:00 AM
Last Editorial Review: 4/29/2009 12:00:00 AM

Title: Chewing Khat Linked to Severe Liver Damage
Category: Health News
Created: 4/28/2010 6:10:00 PM
Last Editorial Review: 4/29/2010 12:00:00 AM

Title: Type 2 Diabetes May Damage Hearing, Study Finds
Category: Health News
Created: 4/27/2016 12:00:00 AM
Last Editorial Review: 4/28/2016 12:00:00 AM

Title: AHA News: Domestic Abuse May Do Long-Term Damage to Women's Health
Category: Health News
Created: 2/18/2020 12:00:00 AM
Last Editorial Review: 2/19/2020 12:00:00 AM

ABSTRACT

Bacillus anthracis is a spore-forming bacterium that causes devastating infections and has been used as a bioterror agent. This pathogen can survive hostile environments through the signaling activity of two-component systems, which couple environmental sensing with transcriptional activation to initiate a coordinated response to stress. In this work, we describe the identification of a two-component system, EdsRS, which mediates the B. anthracis response to the antimicrobial compound targocil. Targocil is a cell envelope-targeting compound that is toxic to B. anthracis at high concentrations. Exposure to targocil causes damage to the cellular barrier and activates EdsRS to induce expression of a previously uncharacterized cardiolipin synthase, which we have named ClsT. Both EdsRS and ClsT are required for protection against targocil-dependent damage. Induction of clsT by EdsRS during targocil treatment results in an increase in cardiolipin levels, which protects B. anthracis from envelope damage. Together, these results reveal that a two-component system signaling response to an envelope-targeting antimicrobial induces production of a phospholipid associated with stabilization of the membrane. Cardiolipin is then used to repair envelope damage and promote B. anthracis viability.

IMPORTANCE Compromising the integrity of the bacterial cell barrier is a common action of antimicrobials. Targocil is an antimicrobial that is active against the bacterial envelope. We hypothesized that Bacillus anthracis, a potential weapon of bioterror, senses and responds to targocil to alleviate targocil-dependent cell damage. Here, we show that targocil treatment increases the permeability of the cellular envelope and is particularly toxic to B. anthracis spores during outgrowth. In vegetative cells, two-component system signaling through EdsRS is activated by targocil. This results in an increase in the production of cardiolipin via a cardiolipin synthase, ClsT, which restores the loss of barrier function, thereby reducing the effectiveness of targocil. By elucidating the B. anthracis response to targocil, we have uncovered an intrinsic mechanism that this pathogen employs to resist toxicity and have revealed therapeutic targets that are important for bacterial defense against structural damage.

Mutations in X-linked methyl-CpG-binding protein 2 (MECP2) cause Rett syndrome (RTT). To identify functional pathways that could inform therapeutic entry points, we carried out a genetic screen for secondary mutations that improved phenotypes in Mecp2/Y mice after mutagenesis with N-ethyl-N-nitrosourea (ENU). Here, we report the isolation of 106 founder animals that show suppression of Mecp2-null traits from screening 3177 Mecp2/Y genomes. Whole-exome sequencing, genetic crosses, and association analysis identified 22 candidate genes. Additional lesions in these candidate genes or pathway components associate variant alleles with phenotypic improvement in 30 lines. A network analysis shows that 63% of the genes cluster into the functional categories of transcriptional repression, chromatin modification, or DNA repair, delineating a pathway relationship with MECP2. Many mutations lie in genes that modulate synaptic signaling or lipid homeostasis. Mutations in genes that function in the DNA damage response (DDR) also improve phenotypes in Mecp2/Y mice. Association analysis was successful in resolving combinatorial effects of multiple loci. One line, which carries a suppressor mutation in a gene required for cholesterol synthesis, Sqle, carries a second mutation in retinoblastoma binding protein 8, endonuclease (Rbbp8, also known as CtIP), which regulates a DDR choice in double-stranded break (DSB) repair. Cells from Mecp2/Y mice have increased DSBs, so this finding suggests that the balance between homology-directed repair and nonhomologous end joining is important for neuronal cells. In this and other lines, two suppressor mutations confer greater improvement than one alone, suggesting that combination therapies could be effective in RTT.

Annelies Wouters, Jan-Pieter Ploem, Sabine A. S. Langie, Tom Artois, Aziz Aboobaker, and Karen Smeets

Pluripotent stem cells hold great potential for regenerative medicine. Increased replication and division, such is the case during regeneration, concomitantly increases the risk of adverse outcomes through the acquisition of mutations. Seeking for driving mechanisms of such outcomes, we challenged a pluripotent stem cell system during the tightly controlled regeneration process in the planarian Schmidtea mediterranea. Exposure to the genotoxic compound methyl methanesulfonate (MMS) revealed that despite a similar DNA-damaging effect along the anteroposterior axis of intact animals, responses differed between anterior and posterior fragments after amputation. Stem cell proliferation and differentiation proceeded successfully in the amputated heads, leading to regeneration of missing tissues. Stem cells in the amputated tails showed decreased proliferation and differentiation capacity. As a result, tails could not regenerate. Interference with the body-axis-associated component β-catenin-1 increased regenerative success in tail fragments by stimulating proliferation at an early time point. Our results suggest that differences in the Wnt signalling gradient along the body axis modulate stem cell responses to MMS.

Molecular radiotherapy using ¹⁷⁷Lu-DOTATATE is a most effective treatment for somatostatin receptor–expressing neuroendocrine tumors. Despite its frequent and successful use in the clinic, little or no radiobiologic considerations are made at the time of treatment planning or delivery. On positive uptake on octreotide-based PET/SPECT imaging, treatment is usually administered as a standard dose and number of cycles without adjustment for peptide uptake, dosimetry, or radiobiologic and DNA damage effects in the tumor. Here, we visualized and quantified the extent of DNA damage response after ¹⁷⁷Lu-DOTATATE therapy using SPECT imaging with ¹¹¹In-anti-H2AX-TAT. This work was a proof-of-principle study of this in vivo noninvasive biodosimeter with β-emitting therapeutic radiopharmaceuticals. Methods: Six cell lines were exposed to external-beam radiotherapy (EBRT) or ¹⁷⁷Lu-DOTATATE, after which the number of H2AX foci and the clonogenic survival were measured. Mice bearing CA20948 somatostatin receptor–positive tumor xenografts were treated with ¹⁷⁷Lu-DOTATATE or sham-treated and coinjected with ¹¹¹In-anti-H2AX-TAT, ¹¹¹In-IgG-TAT control, or vehicle. Results: Clonogenic survival after external-beam radiotherapy was cell-line–specific, indicating varying levels of intrinsic radiosensitivity. Regarding in vitro cell lines treated with ¹⁷⁷Lu-DOTATATE, clonogenic survival decreased and H2AX foci increased for cells expressing high levels of somatostatin receptor subtype 2. Ex vivo measurements revealed a partial correlation between ¹⁷⁷Lu-DOTATATE uptake and H2AX focus induction between different regions of CA20948 xenograft tumors, suggesting that different parts of the tumor may react differentially to ¹⁷⁷Lu-DOTATATE irradiation. Conclusion: ¹¹¹In-anti-H2AX-TAT allows monitoring of DNA damage after ¹⁷⁷Lu-DOTATATE therapy and reveals heterogeneous damage responses.

Prostate-specific membrane antigen (PSMA)–targeting α-radiation therapy (TAT) is an emerging treatment modality for metastatic castration-resistant prostate cancer. There is a subgroup of patients with poor response despite sufficient expression of PSMA in their tumors. The aim of this work was to characterize PSMA-TAT–nonresponding lesions by targeted next-generation sequencing. Methods: Of 60 patients treated with ²²⁵Ac-PSMA-617, we identified 10 patients who presented with a poor response despite sufficient tumor uptake in PSMA PET/CT. We were able to perform CT-guided biopsies with histologic validation of the nonresponding lesions in 7 of these nonresponding patients. Specimens were analyzed by targeted next-generation sequencing interrogating 37 DNA damage-repair–associated genes. Results: In the 7 tumor samples analyzed, we found a total of 15 whole-gene deletions, deleterious or presumably deleterious mutations affecting TP53 (n = 3), CHEK2 (n = 2), ATM (n = 2), and BRCA1, BRCA2, PALB2, MSH2, MSH6, NBN, FANCB, and PMS1 (n = 1 each). The average number of deleterious or presumably deleterious mutations was 2.2 (range, 0–6) per patient. In addition, several variants of unknown significance in ATM, BRCA1, MSH2, SLX4, ERCC, and various FANC genes were detected. Conclusion: Patients with resistance to PSMA-TAT despite PSMA positivity frequently harbor mutations in DNA damage-repair and checkpoint genes. Although the causal role of these alterations in the patient outcome remains to be determined, our findings encourage future studies combining PSMA-TAT and DNA damage-repair–targeting agents such as poly(ADP-ribose)-polymerase inhibitors.

City of Windsor payouts on personal injury and property damage claims totaled $2.1 million in 2019, the lowest number in eight years. The total — for settlements as well as court decisions — was well below the $3 million budgeted for the hundreds of claims made each year against the city for everything from trip-and-falls, […]

THE CORONAVIRUS lockdown is now causing serious damage to the UK's economy, Tory MP Steve Baker has warned - stressing he was now "gravely concerned" at the situation

Like most of us, Adam Tooze is stuck at home. The British-born economic historian and Columbia University professor of history had been on leave this school year to write a book about climate change. But now he’s studying a different global problem. There are more than 700,000 cases of COVID-19 in the United States and over 2 million infections worldwide. It’s also caused an economic meltdown. More than 18 million Americans have filed for unemployment in recent weeks, and Goldman Sachs analysts predict that U.S. gross domestic product will decline at an annual rate of 34 percent in the second quarter.

Tooze is an expert on economic catastrophes. He wrote the book Crashed: How a Decade of Financial Crises Changed the World, about the 2008 economic crisis and its aftermath. But even he didn’t see this one coming. He hadn’t thought much about how pandemics could impact the economy—few economists had. Then he watched as China locked down the city of Wuhan, in a province known for auto manufacturing, on January 23; as northern Italy shut down on February 23; and as the U.S. stock market imploded on March 9. By then, he knew he had another financial crisis to think about. He’s been busy writing ever since. Tooze spoke with Nautilus from his home in New York City.

What do you make of the fact that, in three weeks, more than 16 million people in the U.S. have filed for unemployment?

The structural element here—and this is quite striking, when you compare Europe, for instance, to the U.S.—is that America has and normally celebrates the flexibility and dynamism of its labor market: The fact that people move between jobs. The fact that employers have the right to hire and fire if they need to. The downside is that in a shock like this, the appropriate response for an employer is simply to let people go. What America wasn’t able to do was to improvise the short-time working systems that the Europeans are trying to use to prevent the immediate loss of employment to so many people.

The disadvantage of the American system that reveals itself in a crisis like this is that hiring and firing is not easily reversible. People who lose jobs don’t necessarily easily get them back. There is a fantasy of a V-shaped recovery. We literally have never done this before, so we don’t know one way or another how this could happen. But it seems likely that many people who have lost employment will not immediately find reemployment over the summer or the fall when business activity resumes something like its previous state. In a situation with a lot of people with low qualifications in precarious jobs at low income, the damage from that kind of interruption of employment in sectors notably which are already teetering on the edge—the chain stores, which are quite likely closing anyway, and fragile malls, which were on the edge of dying—it’s quite likely that this shock will also induce disproportionately large amounts of scarring.

What role has wealth and income inequality played during this crisis?

The U.S. economic system is bad enough in a regular crisis. In one like this, where you shut the entire economy down in a matter of weeks, the damage is barely conceivable. There are huge disparities, all of which ultimately are rooted in social structures of race and class, and in the different types of jobs that people have. The profound inequality in American society has been brought home for us in everyone’s families, where there is a radical disparity between the ability of some households to sustain the education of their children and themselves living comfortably at home. Twenty-five percent of kids in the United States appear not to have a stable WiFi connection. They have smartphones. That seems practically universal. But you can’t teach school on a smartphone. At least, that technology is not there.

Presumably by next year something like normality returns. But forever after we’ll live under the shadow of this having happened.

President Trump wants the economy to reopen by May. Would that stop the economic crisis?

Certainly that is presumably what drives that haste to restart the economy and to lift intense social distancing provisions. There is a sense that we can’t stand this. And that has a lot to do with deep fragilities in the American social system. If all Americans live comfortably in their own homes, with the safety of a regular paycheck, with substantial savings, with health insurance that wasn’t conditional on precarious employment, and with unemployment benefits that were adequate and that were rolled out to most people in this society if they needed them, then there wouldn’t be such a rush. But that isn’t America as we know it. America is a society in which half of families have virtually no financial cushion; in which small businesses, which are so often hailed as the drivers of job creation, the vast majority of owners of them live hand-to-mouth; in which the unemployment insurance system really is a mockery; and with health insurance directly tied to employment for the vast majority of the people. A society like that really faces huge pressures if the economy is shut down.

How is the pandemic-induced economic collapse we’re facing now different from what we faced in 2008?

This is so much faster. Early this year, America had record-low unemployment numbers. And last week or so already we probably broke the record for unemployment in the United States in the period since World War II. This story is moving so fast that our statistical systems of registration can’t keep up. So we think probably de facto unemployment in the U.S. right now is 13, 14, 15 percent. That’s never happened before. 2007 to 2008 was a classic global crisis in the sense that it came out of one particular over-expanded sector, a sector which is very well known for its volatility, which is real estate and construction. It was driven by a credit boom.

What we’re seeing this time around is deliberately, government-ordered, cliff edge, sudden shutdown of the entire economy, hitting specifically the face-to-face human services—retail, entertainment, restaurants—sector, which are, generally speaking, lagging in cyclical terms and are not the kind of sectors that generate boom-bust cycles.

Are we better prepared this time than in 2008?

You’d find it very hard to point to anyone in the policymaking community at the beginning of 2020 who was thinking of pandemic risk. Some people were. Former Treasury Secretary and former Director of the National Economic Council Larry Summers, for example, wrote a paper about pandemic flu several years ago, because of MERS and SARS, previous respiratory illnesses caused by coronaviruses. But it wasn’t top of stack at the beginning of this year. So we weren’t prepared in that sense. But do we know what to do now if we see the convulsions in the credit markets that we saw at the beginning of March? Yes. Have the central banks done it? Yes. Did they use some of the techniques they employed in ’08? Yes. Did they know that you had to go in big and you had to go in heavy and hard and quickly? Yes. And they have done so on an even more gigantic scale than in ’08, which is a lesson learned in ’08, too: There’s no such a thing as too big. And furthermore, the banks, which were the fragile bit in ’08, have basically been sidelined.

You’ve written that the response to the 2008 crisis worked to “undermine democracy.” How so, and could we see that again with this crisis?

The urgency that any financial crisis produces forces governments’ hands—it strips the legislature, the ordinary processes of democratic deliberation. When you’re forced to make very dramatic, very rapid decisions—particularly in a country as chronically divided as the U.S. is on so many issues—the risk that you create opportunities for demagogues of various types to take advantage of is huge. We know what the response of the Tea Party was to the ’08, ’09 economic crisis. They created an extraordinarily distorted vision of what had happened and then rode that to see extraordinary influence over the Republican party in the years that followed. And there is every reason to think that we might be faced with similar stresses in the American political system in months to come.

The U.S. economic system is bad enough in a regular crisis. In one like this, where you shut the entire economy down in a matter of weeks, the damage is barely conceivable.

How should we be rethinking the economy to buffer against meltdowns like this in the future?

We clearly need to have a far more adequate and substantial medical capacity. There’s no alternative to a comprehensive publicly backstopped or funded health insurance system. Insofar as you haven’t got that, your capacity to guarantee the security in the most basic and elementary sense of your population is not there. When you have a system in which one of the immediate side effects, in a crisis like this, is that large parts of your hospital system go bankrupt—one of the threats to the American medical system right now—that points to something extraordinarily wrong, especially if you’re spending close to 18 percent of GDP on health, more than any other society on the planet.

What about the unemployment insurance system?

America needs to have a comprehensive unemployment insurance system. It can be graded by local wage rates and everything else. But the idea that you have the extraordinary disparities that we have between a Florida and a Georgia at one end, with recipiency rates in the 11, 12, 13, 14, 15 percent, and then states which actually operate an insurance system, which deserve the name—this shouldn’t be accepted in a country like the U.S. We would need to look at how short-time working models might be a far better way of dealing with shocks of this kind, essentially saying that there is a public interest in the continuity of employment relationships. The employer should be investing in their staff and should not be indifferent as to who shows up for work on any given day.

What does this pandemic teach us about living in a global economy?

There are a series of very hard lessons in the recent history of globalization into which the corona shock fits—about the peculiar inability of American society, American politics, and the American labor market to cushion shocks that come from the outside in a way which moderates the risk and the damage to the most vulnerable people. If you look at the impact of globalization on manufacturing, industry, inequality, the urban fabric in the U.S., it’s far more severe than in other societies, which have basically been subject to the same shock. That really needs to raise questions about how the American labor market and welfare system work, because they are failing tens of millions of people in this society.

You write in Crashed not just about the 2008 crisis, but also about the decade afterward. What is the next decade going to look like, given this meltdown?

I have never felt less certain in even thinking about that kind of question. At this point, can either you or I confidently predict what we’re going to be doing this summer or this autumn? I don’t know whether my university is resuming normal service in the fall. I don’t know whether my daughter goes back to school. I don’t know when my wife’s business in travel and tourism resumes. That is unprecedented. It’s very difficult against that backdrop to think out over a 10-year time horizon. Presumably by next year something like normality returns. But forever after we’ll live under the shadow of this having happened. Every year we’re going to be anxiously worrying about whether flu season is going to be flu season like normal or flu season like this. That is itself something to be reckoned with.

How will anxiety and uncertainty about a future pandemic-like crisis affect the economy?

When we do not know what the future holds to this extent, it makes it very difficult for people to make bold, long-term financial decisions. This previously wasn’t part of the repertoire of what the financial analysts call tail risk. Not seriously. My sister works in the U.K. government, and they compile a list every quarter of the top five things that could blow your departmental business up. Every year pandemics are in the top three. But no one ever acted on it. It’s not like terrorism. In Britain, you have a state apparatus which is geared to address the terrorism risk because it’s very real—it’s struck many times. Now all of a sudden we have to take the possibility of pandemics that seriously. And their consequences are far more drastic. How do we know what our incomes are going to be? A very large part of American society is not going to be able to answer that question for some time to come. And that will shake consumer confidence. It will likely increase the savings rate. It’s quite likely to reduce the desire to invest in a large part of the U.S. economy.

Max Kutner is a journalist in New York City. He has written for Newsweek, The Boston Globe, and Smithsonian. Follow him on Twitter @maxkutner.

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