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Visualizing the inside of cells at previously impossible resolutions provides vivid insights into how they work
Many microscopy techniques have won Nobel Prizes over the years. Advancements like cryo-ET that allow scientists to see the individual atoms of cells can…
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All life is made up of cells several magnitudes smaller than a grain of salt. Their seemingly simple-looking structures mask the intricate and complex molecular activity that enables them to carry out the functions that sustain life. Researchers are beginning to be able to visualize this activity to a level of detail they haven’t been able to before.
Biological structures can be visualized by either starting at the level of the whole organism and working down, or starting at the level of single atoms and working up. However, there has been a resolution gap between a cell’s smallest structures, such as the cytoskeleton that supports the cell’s shape, and its largest structures, such as the ribosomes that make proteins in cells.
By analogy of Google Maps, while scientists have been able to see entire cities and individual houses, they did not have the tools to see how the houses came together to make up neighborhoods. Seeing these neighborhood-level details is essential to being able to understand how individual components work together in the environment of a cell.
New tools are steadily bridging this gap. And ongoing development of one particular technique, cryo-electron tomography, or cryo-ET, has the potential to deepen how researchers study and understand how cells function in health and disease.
As the former editor-in-chief of Science magazine and as a researcher who has studied hard-to-visualize large protein structures for decades, I have witnessed astounding progress in the development of tools that can determine biological structures in detail. Just as it becomes easier to understand how complicated systems work when you know what they look like, understanding how biological structures fit together in a cell is key to understanding how organisms function.
A brief history of microscopy
In the 17th century, light microscopy first revealed the existence of cells. In the 20th century, electron microscopy offered even greater detail, revealing the elaborate structures within cells, including organelles like the endoplasmic reticulum, a complex network of membranes that play key roles in protein synthesis and transport.
From the 1940s to 1960s, biochemists worked to separate cells into their molecular components and learn how to determine the 3D structures of proteins and other macromolecules at or near atomic resolution. This was first done using X-ray crystallography to visualize the structure of myoglobin, a protein that supplies oxygen to muscles.
Over the past decade, techniques based on nuclear magnetic resonance, which produces images based on how atoms interact in a magnetic field, and cryo-electron microscopy have rapidly increased the number and complexity of the structures scientists can visualize.
What is cryo-EM and cryo-ET?
Cryo-electron microscopy, or cryo-EM, uses a camera to detect how a beam of electrons is deflected as the electrons pass through a sample to visualize structures at the molecular level. Samples are rapidly frozen to protect them from radiation damage. Detailed models of the structure of interest are made by taking multiple images of individual molecules and averaging them into a 3D structure.
Cryo-ET shares similar components with cryo-EM but uses different methods. Because most cells are too thick to be imaged clearly, a region of interest in a cell is first thinned by using an ion beam. The sample is then tilted to take multiple pictures of it at different angles, analogous to a CT scan of a body part – although in this case the imaging system itself is tilted, rather than the patient. These images are then combined by a computer to produce a 3D image of a portion of the cell.
The resolution of this image is high enough that researchers – or computer programs – can identify the individual components of different structures in a cell. Researchers have used this approach, for example, to show how proteins move and are degraded inside an algal cell.
Many of the steps researchers once had to do manually to determine the structures of cells are becoming automated, allowing scientists to identify new structures at vastly higher speeds. For example, combining cryo-EM with artificial intelligence programs like AlphaFold can facilitate image interpretation by predicting protein structures that have not yet been characterized.
Understanding cell structure and function
As imaging methods and workflows improve, researchers will be able to tackle some key questions in cell biology with different strategies.
The first step is to decide what cells and which regions within those cells to study. Another visualization technique called correlated light and electron microscopy, or CLEM, uses fluorescent tags to help locate regions where interesting processes are taking place in living cells.
Comparing the genetic difference between cells can provide additional insight. Scientists can look at cells that are unable to carry out particular functions and see how this is reflected in their structure. This approach can also help researchers study how cells interact with each other.
Cryo-ET is likely to remain a specialized tool for some time. But further technological developments and increasing accessibility will allow the scientific community to examine the link between cellular structure and function at previously inaccessible levels of detail. I anticipate seeing new theories on how we understand cells, moving from disorganized bags of molecules to intricately organized and dynamic systems.
Jeremy Berg does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.
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One city held a mass passport-getting event
A New Orleans congressman organized a way for people to apply for their passports en masse.
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While the number of Americans who do not have a passport has dropped steadily from more than 80% in 1990 to just over 50% now, a lack of knowledge around passport requirements still keeps a significant portion of the population away from international travel.
Over the four years that passed since the start of covid-19, passport offices have also been dealing with significant backlog due to the high numbers of people who were looking to get a passport post-pandemic.
Related: Here is why it is (still) taking forever to get a passport
To deal with these concurrent issues, the U.S. State Department recently held a mass passport-getting event in the city of New Orleans. Called the "Passport Acceptance Event," the gathering was held at a local auditorium and invited residents of Louisiana’s 2nd Congressional District to complete a passport application on-site with the help of staff and government workers.
'Come apply for your passport, no appointment is required'
"Hey #LA02," Rep. Troy A. Carter Sr. (D-LA), whose office co-hosted the event alongside the city of New Orleans, wrote to his followers on Instagram (META) . "My office is providing passport services at our #PassportAcceptance event. Come apply for your passport, no appointment is required."
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The event was held on March 14 from 10 a.m. to 1 p.m. While it was designed for those who are already eligible for U.S. citizenship rather than as a way to help non-citizens with immigration questions, it helped those completing the application for the first time fill out forms and make sure they have the photographs and identity documents they need. The passport offices in New Orleans where one would normally have to bring already-completed forms have also been dealing with lines and would require one to book spots weeks in advance.
These are the countries with the highest-ranking passports in 2024
According to Carter Sr.'s communications team, those who submitted their passport application at the event also received expedited processing of two to three weeks (according to the State Department's website, times for regular processing are currently six to eight weeks).
While Carter Sr.'s office has not released the numbers of people who applied for a passport on March 14, photos from the event show that many took advantage of the opportunity to apply for a passport in a group setting and get expedited processing.
Every couple of months, a new ranking agency puts together a list of the most and least powerful passports in the world based on factors such as visa-free travel and opportunities for cross-border business.
In January, global citizenship and financial advisory firm Arton Capital identified United Arab Emirates as having the most powerful passport in 2024. While the United States topped the list of one such ranking in 2014, worsening relations with a number of countries as well as stricter immigration rules even as other countries have taken strides to create opportunities for investors and digital nomads caused the American passport to slip in recent years.
A UAE passport grants holders visa-free or visa-on-arrival access to 180 of the world’s 198 countries (this calculation includes disputed territories such as Kosovo and Western Sahara) while Americans currently have the same access to 151 countries.
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Fast-food chain closes restaurants after Chapter 11 bankruptcy
Several major fast-food chains recently have struggled to keep restaurants open.
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Competition in the fast-food space has been brutal as operators deal with inflation, consumers who are worried about the economy and their jobs and, in recent months, the falling cost of eating at home.
Add in that many fast-food chains took on more debt during the covid pandemic and that labor costs are rising, and you have a perfect storm of problems.
It's a situation where Restaurant Brands International (QSR) has suffered as much as any company.
Related: Wendy's menu drops a fan favorite item, adds something new
Three major Burger King franchise operators filed for bankruptcy in 2023, and the chain saw hundreds of stores close. It also saw multiple Popeyes franchisees move into bankruptcy, with dozens of locations closing.
RBI also stepped in and purchased one of its key franchisees.
"Carrols is the largest Burger King franchisee in the United States today, operating 1,022 Burger King restaurants in 23 states that generated approximately $1.8 billion of system sales during the 12 months ended Sept. 30, 2023," RBI said in a news release. Carrols also owns and operates 60 Popeyes restaurants in six states."
The multichain company made the move after two of its large franchisees, Premier Kings and Meridian, saw multiple locations not purchased when they reached auction after Chapter 11 bankruptcy filings. In that case, RBI bought select locations but allowed others to close.
Image source: Chen Jianli/Xinhua via Getty
Another fast-food chain faces bankruptcy problems
Bojangles may not be as big a name as Burger King or Popeye's, but it's a popular chain with more than 800 restaurants in eight states.
"Bojangles is a Carolina-born restaurant chain specializing in craveable Southern chicken, biscuits and tea made fresh daily from real recipes, and with a friendly smile," the chain says on its website. "Founded in 1977 as a single location in Charlotte, our beloved brand continues to grow nationwide."
Like RBI, Bojangles uses a franchise model, which makes it dependent on the financial health of its operators. The company ultimately saw all its Maryland locations close due to the financial situation of one of its franchisees.
Unlike. RBI, Bojangles is not public — it was taken private by Durational Capital Management LP and Jordan Co. in 2018 — which means the company does not disclose its financial information to the public.
That makes it hard to know whether overall softness for the brand contributed to the chain seeing its five Maryland locations after a Chapter 11 bankruptcy filing.
Bojangles has a messy bankruptcy situation
Even though the locations still appear on the Bojangles website, they have been shuttered since late 2023. The locations were operated by Salim Kakakhail and Yavir Akbar Durranni. The partners operated under a variety of LLCs, including ABS Network, according to local news channel WUSA9.
The station reported that the owners face a state investigation over complaints of wage theft and fraudulent W2s. In November Durranni and ABS Network filed for bankruptcy in New Jersey, WUSA9 reported.
"Not only do former employees say these men owe them money, WUSA9 learned the former owners owe the state, too, and have over $69,000 in back property taxes."
Former employees also say that the restaurant would regularly purchase fried chicken from Popeyes and Safeway when it ran out in their stores, the station reported.
Bojangles sent the station a comment on the situation.
"The franchisee is no longer in the Bojangles system," the company said. "However, it is important to note in your coverage that franchisees are independent business owners who are licensed to operate a brand but have autonomy over many aspects of their business, including hiring employees and payroll responsibilities."
Kakakhail and Durranni did not respond to multiple requests for comment from WUSA9.
bankruptcy pandemicUncategorized
Industrial Production Increased 0.1% in February
From the Fed: Industrial Production and Capacity Utilization
Industrial production edged up 0.1 percent in February after declining 0.5 percent in January. In February, the output of manufacturing rose 0.8 percent and the index for mining climbed 2.2 p…
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Industrial production edged up 0.1 percent in February after declining 0.5 percent in January. In February, the output of manufacturing rose 0.8 percent and the index for mining climbed 2.2 percent. Both gains partly reflected recoveries from weather-related declines in January. The index for utilities fell 7.5 percent in February because of warmer-than-typical temperatures. At 102.3 percent of its 2017 average, total industrial production in February was 0.2 percent below its year-earlier level. Capacity utilization for the industrial sector remained at 78.3 percent in February, a rate that is 1.3 percentage points below its long-run (1972–2023) average.Click on graph for larger image.
emphasis added
This graph shows Capacity Utilization. This series is up from the record low set in April 2020, and above the level in February 2020 (pre-pandemic).
Capacity utilization at 78.3% is 1.3% below the average from 1972 to 2022. This was below consensus expectations.
Note: y-axis doesn't start at zero to better show the change.
The second graph shows industrial production since 1967.Industrial production increased to 102.3. This is above the pre-pandemic level.
Industrial production was above consensus expectations.
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