Alligators exposed to PFAS show autoimmune effects

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A recent study of alligators in the Cape Fear River found the animals had elevated levels of 14 different per- and polyfluoroalkyl (PFAS) chemicals in their blood serum, as well as clinical and genetic indicators of immune system effects. The work adds to the body of evidence connecting PFAS exposure with adverse immune system effects.

The research team, led by Scott Belcher, associate professor of biology at North Carolina State University, took blood samples and did health evaluations on 49 alligators living along the Cape Fear River between 2018 and 2019. They compared these results to a reference population of 26 alligators from Lake Waccamaw, located in the adjoining Lumber River basin.

“We looked at 23 different PFAS and saw clear differences between both types and levels of PFAS in the two populations,” Belcher says. “We detected an average of 10 different PFAS in the Cape Fear River samples, compared to an average of five different PFAS in the Lake Waccamaw population.

“Additionally, blood concentrations of fluoroethers such as Nafion byproduct 2 were present at higher concentrations in alligators from the Cape Fear River basin, whereas these levels were much lower—or not detected—in alligators from Lake Waccamaw. Our data showed that as we moved downstream from Wilmington to Bald Head Island, overall PFAS concentrations decreased.”

But the most unusual observation the team made was that alligators in the Cape Fear River had a number of unhealed or infected lesions.

“Alligators rarely suffer from infections,” Belcher says. “They do get wounds, but they normally heal quickly. Seeing infected lesions that weren’t healing properly was concerning and led us to look more closely at the connections between PFAS exposure and changes in the immune systems of the alligators.”

A qRT-PCR genetic analysis revealed significantly elevated levels of interferon-alpha (INF-α) responsive genes in the Cape Fear River alligators: their levels were 400 times higher than those of the Lake Waccamaw alligators, which had much lower PFAS blood concentrations.

“INF-α is a secreted immune protein involved in stimulating ,” Belcher says. “The set of INF-α responsive genes we analyzed are normally involved with viral infections. In humans, chronic (or long-term) high expression of this set of genes is an important indicator of autoimmune diseases, especially lupus. Additionally, some PFAS exposures in humans are linked with chronic autoimmune disorders like and thyroid disease.

“When we see elevated expression of INF-α in these alligators, then, it tells us that something in these alligators’ immune responses is being disrupted.”

With five years’ worth of sampling data, much of it taken from the same alligators on an annual basis, the researchers are in a good position to continue following PFAS exposure and health changes in both individuals and the larger populations within both habitats.

“Alligators are a sentinel species—harbingers of dangers to human health,” Belcher says. “Seeing these associations between PFAS exposure and disrupted immune function in the Cape Fear River alligators supports connections between adverse human and animal health effects and PFAS exposure.”

The work appears in Frontiers in Toxicology and was supported by the National Institute of Environmental Health Sciences (award numbers P42ES031009, P30 ES025128 and T32ES007046), North Carolina Sea Grant, and the North Carolina Policy Collaboratory. Belcher is corresponding author of the work, which is part of a collaboration with the PFAS testing network and Cape Fear River Watch.



More information:
Blood Concentrations of Per- and Polyfluoroalkyl Substances are Associated with Autoimmune-like Effects in American Alligators from Wilmington, North Carolina, Frontiers in Toxicology (2022). DOI: 10.3389/ftox.2022.1010185

Citation:
Alligators exposed to PFA

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Hexbyte Glen Cove Disclosures on auditor firings are useless in forecasting restatement trouble, study shows

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Mandatory Securities and Exchange Commission disclosures about the reasons behind auditor firings are useless for assessing whether restatement trouble lies ahead for the company, according to new research from the University of Notre Dame.

Firing an auditor creates ambiguity. Is the company trying to find a better auditor, or is it trying to avoid a restatement (revision of previous financial statements to correct an error) for problems that the auditor is unearthing? And, while many restatements are the result of innocent mistakes and basic misinterpretation, some can raise red flags pointing to potential fraud or incompetence.

While most seasoned investors realize that companies tend to be cagey about their reasons for firing auditors, the research finds the disclosures are useless to an extreme. “Opaque Auditor Dismissal Disclosures: What Does Timing Reveal that Disclosures Do Not?” is forthcoming in the Journal of Accounting and Public Policy from Jeffrey Burks, the Thomas and Therese Grojean Family Associate Professor of Accountancy in Notre Dame’s Mendoza College of Business, and Jennifer Sustersic Stevens of Ohio University.

In a sample of some 1,400 auditor firings, company revelations of disagreements with the auditor or other auditor concerns exhibit no systematic ability to forecast whether the company will restate its financial statements.

“The lack of predictive ability suggests that companies’ decisions to disclose such auditor concerns are so inconsistent and uncommon—even though the regulation requires their disclosure—that no predictive power results,” said Burks, who researches financial accounting and misstatements.

Instead of looking at what companies say in the disclosure, the researchers recommend investors pay attention to when the disclosure comes out.

“Any firing that happens after the second fiscal quarter signals an above-average chance of a future restatement,” Burks said. “Firings that occur in the third or fourth fiscal quarters or during the period of audit fieldwork after year-end increase the chances of future restatement by roughly 40 percent.”

The researchers reason that firings after the first half of the year are suspicious because companies almost always sign up auditors early in the fiscal year. Thus, most any firing that occurs after the early-year sign-up period means the company changed its mind about the auditor within the span of months.

“What would prompt such a quick change of mind?” Burks asked. “A prime possibility would be brewing disputes with the auditor about potential misstatements.”

Despite this intuitive connection between late firings and disputes, the researchers find that companies are no more likely to disclose disputes for late firings than they are for early firings, again suggesting that companies tend not to be forthcoming about the underlying reasons for the firing.

The SEC has changed the disclosure regulation related to Section 4.01 8-K forms multiple times over the decades to try to force more transparent disclosure about firings, but the study shows such efforts have been ineffective. As an alternative to more rule changes, the researchers suggest the Public Company Accounting Oversight Board and the SEC begin to regularly ask about the circumstances of auditor firings in their examinations.

“The SEC may want to investigate the possibility of including questions about auditor firings in its comment letter reviews of individual companies,” Burks suggested. “Such letters and the company responses to them already become public as a matter of course. The letters normally just stick to questions about the , but on at least one occasion the SEC asked about the reasons for an auditor firing, and received much more explanation than is normally included in the standard auditor firing .”

For example, prompted by the SEC’s question in a 2010 comment letter about why it fired its auditor, Blue Wave Group Inc. responded that the auditor misled the company about the expertise and documentation it possessed, did not have “the work ethic that the company felt was needed” and assigned a primary contact person who “was an associate still in school, not a seasoned professional.”

The company also provided specific examples when the partner was “very difficult to work with” and “vague and unhelpful,” and the stated that it stuck with the auditor longer than it wished because “it felt trapped that it had a 10-K due and it did not want to file late.”



More information:
Jeffrey J. Burks et al, Opaque auditor dismissal disclosures: What does timing reveal that disclosures do not?, Journal of Accounting and Public Policy (2021). DOI: 10.1016/j.jaccpubpol.2021.106905

Citation:

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Hexbyte Glen Cove 'Designer' pore shows selective traffic to and from the cell nucleus thumbnail

Hexbyte Glen Cove ‘Designer’ pore shows selective traffic to and from the cell nucleus

Hexbyte Glen Cove

The team reduced the complexity of nuclear pores down to a single, artificial Nucleoporin that they call ‘NupX’. This protein is based on the average properties of a class of Nucleoporins rich in the amino acid motif Glycine-Leucine-Phenylalanine-Glycine. In these simulation snapshots, each particle represents a whole amino acid. Credit: University of Groningen

The nucleus is the headquarters of a cell and molecules constantly move across the nuclear membrane through pores. The transport of these molecules is both selective and fast; some 1,000 molecules per second can move in or out. Scientists from the University of Groningen and Delft University of Technology, both in the Netherlands, and a colleague from the Swedish Chalmers University of Technology, have developed an artificial model of these pores using simple design rules, which enabled them to study how this feat is accomplished. Their results were published on 31 March in Nature Communications.

Nuclear pores are extremely complicated structures. The pore itself is a big protein complex and the opening of the pore is filled with a dense network of disordered proteins called nucleoporins. These proteins regulate selective transport, but exactly how they do this is still unclear. “The nuclear pore complex is one of the biggest structures in the cell,” explains Patrick Onck, professor of Micromechanics at the University of Groningen. “We previously studied the pores in all their complexity, but for this study, we created a drastically simplified ‘designer’ pore to investigate the essential physical mechanisms of transport.”

Nanopore

First, the team analyzed the composition of the nucleoporins to design a simplified, ‘average’ version, which they termed nucleoporin X, or NupX for short. These proteins are made up of domains comprising phenylalanine (F) and glycine (G) amino acids in tandem, and these play an essential role in transport. These FG repeats are separated by ‘spacers’ of other amino acids. In addition to the FG repeats, some nucleoporins also contain domains of glycine, leucine, phenylalanine and glycine, or GLFG repeats. The team designed proteins that contain both domains, separated by spacers of ten amino acids.

NupX was tested in two different systems: it was studied experimentally, attached to a surface and added to artificial nanopores that were ‘drilled’ in a ‘membrane’ of silicon nitride, and through . The experiments were performed at Delft University of Technology, while the simulations were prepared and executed in Groningen, mostly by Henry de Vries, a Ph.D. student in Onck’s laboratory.

Snapshot of the computer simulations, showing that nanopores filled with NupX-proteins allow specific transport proteins (chaperones) to pass. At the same time, the pores efficiently block any non-specific molecules. Credit: University of Groningen

Transport ticket

The nucleoporins were tested for interactions with non-specific proteins and with chaperones, which are proteins that act as transport tickets through the pore. In the cell, large molecules that must be transported into or out of the nucleus can only do so when they are attached to such a chaperone. The artificial nucleoporins selectively interacted with the chaperones but not with the non-specific proteins. This demonstrated that the NupX pores are fully functional: they are able to facilitate selective transport. De Vries: “However, the experiments showed that transport through the artificial pores occurs but not what happens inside the pore. With our simulations, we showed what exactly happens inside the pore as the chaperones translocate, while the non-specific proteins do not interact with the pore at all.”

The simulations also revealed how the FG and the GLFG nucleoporins were distributed inside the pore. “Recent studies suggested that they would be in different places in and that this might help to create selectivity,” says De Vries. “However, we found that they were homogenously distributed and yet we still saw selectivity.” Another suggestion was that the amino acids that make up the spacers are important for the selectivity. “Our results showed that the specific sequence of amino acids in the spacer doesn’t matter since we used random sequences. The only important part is the ratio of charged amino acids to hydrophobic within the spacers, which determines the stickiness of the proteins.”

Redundancy

The final conclusion of the study is that a very simple system in nucleoporins that has limited variation still produces a selective pore. “What is needed is a certain density of these FG nucleoporins,” says Onck. “These form a barrier, which can only be breached by the chaperones.” This begs the question of why the pores contain a very large number of different nucleoporins in nature. Onck: “We know that nature doesn’t always come up with optimized solutions. However, their redundancy could very well have a function in natural pores.”

The fact that the very simple artificial system already reproduces selective transport mechanisms means that the scientists now have an excellent tool to study the physical principles that regulate nuclear function. Onck: “This could lead to new fundamental insights but also to new applications, for example in creating filtration systems, or in the design of artificial cells.”



More information:
Alessio Fragasso et al, A designer FG-Nup that reconstitutes the selective transport barrier of the nuclear pore complex, Nature Communications (2021). DOI: 10.1038/s41467-021-22293-y

Citation:
‘Designer’ pore shows selective traffic to and from the cell nucleus (2021, March 31)
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