The sensory cells of hearing, outer and inner hair cells, are located in the cochlea, where the arrival sound waves cause the ‘hairs’ of the inner hair cells to bend, sending a signal through the nerves to the brain, which interprets the sound we hear.
For the past century, scientific belief was that each sensory cell has its own ‘optimal frequency’, to which the hair cell responds most strongly. This idea means that a sensory cell with an optimal frequency of 1000Hz would be much less responsive to sounds of slightly lower or higher frequency. It has also been assumed that all parts of the cochlea work in the same way. Now, however, researchers have discovered that this is not so for sensory cells that process sound with frequencies under 1000Hz, considered to be low-frequency sound, where the vowel sounds in human speech lie.
“Our study shows that many cells in the inner ear react simultaneously to low-frequency sound. We believe that this makes it easier to experience low-frequency sounds than would otherwise be the case, since the brain receives information from many sensory cells at the same time,” said Professor Anders Fridberger at Linköping University, senior author of the study published in Science Advances.
The scientists believe that this construction of our hearing system makes it more robust. If some sensory cells are damaged, many others remain that can send nerve impulses to the brain.
As well as the vowel sounds of human speech, many of the sounds that go to make up music also lie in this low-frequency area. Middle C on a piano, for example, has a frequency of 262Hz.
These results may eventually be significant for people with severe hearing impairments. The most successful treatment currently available in such cases is a cochlear implant, in which electrodes are placed into the cochlea.
“The design of current cochlear implants is based on the assumption that each electrode should only give nerve stimulation at certain frequencies, in a way that tries to copy what was believed about the function of our hearing system. We suggest that changing the stimulation method at low frequencies will be more similar to the natural stimulation, and the hearing experience of the user should in this way be improved,” says Anders Fridberger.
The researchers now plan to examine how their new knowledge can be applied in practice. One of the projects they are investigating concerns new methods to stimulate the low-frequency parts of the cochlea.
These results come from experiments on the cochlea of guinea pigs, whose hearing in the low-frequency region is similar to that of humans.
Scanning electron micrograph of Lassa virus budding off a Vero cell. Image credit: National Institute of Allergy and Infectious Diseases, NIH
Scientists have found that viruses lurking inside cells may be on the ‘watch’ for information from their environment to choose when to multiply and burst out. The work, published in Frontiers in Microbiology, has implications for antiviral drug development.
A virus’s ability to sense its environment, including elements produced by its host, adds “another layer of complexity to the viral-host interaction,” said senior author Ivan Erill, professor of biological sciences. Currently, viruses use that ability to their benefit. But in the future, he says, “we could exploit it to their detriment.”
Not a coincidence
The new study focused on bacteriophages, viruses which infect bacteria – also known as ‘phages.’ The phages in the study can only infect their hosts when the bacterial cells have special appendages, called pili and flagella, that help the bacteria move and mate. The bacteria produce a protein called CtrA that controls when they generate these appendages. The new paper shows that many appendage-dependent phages have patterns in their DNA where the CtrA protein can attach, called binding sites. A phage having a binding site for a protein produced by its host is unusual, explained Prof Erill.
Even more surprising, Erill and the paper’s first author Elia Mascolo, a PhD student in Erill’s lab, found through detailed genomic analysis that these binding sites were not unique to a single phage, or even a single group of phages. Many different types of phages had CtrA binding sites – but they all needed their hosts to have pili and/or flagella to infect them. It couldn’t be a coincidence, they decided.
The ability to monitor CtrA levels “has been invented multiple times throughout evolution by different phages that infect different bacteria,” Prof Erill said. This convergent evolution indicates that the trait is useful.
Timing is everything
Another wrinkle in the story: The first phage in which the research team identified CtrA binding sites infects a particular group of bacteria called Caulobacterales. Caulobacterales are an especially well-studied group of bacteria, because they exist in two forms: a free-swimming ‘swarmer’ form which has pili/flagella, and a ‘stalked’ form that attaches to a surface and lacks those appendages. In these bacteria, CtrA also regulates the cell cycle, determining whether a cell will divide evenly into two more of the same cell type, or divide asymmetrically to produce one swarmer and one stalk cell.
Because the phages can only infect swarmer cells, it’s in their best interest only to burst out of their host when there are many swarmer cells available to infect. Generally, Caulobacterales live in nutrient-poor environments, and they are very spread out. “But when they find a good pocket of microhabitat, they become stalked cells and proliferate,” Prof Erill said, eventually producing large quantities of swarmer cells.
“We hypothesise the phages are monitoring CtrA levels, which go up and down during the life cycle of the cells, to figure out when the swarmer cell is becoming a stalk cell and becoming a factory of swarmers,” Prof Erill said, “and at that point, they burst the cell, because there are going to be many swarmers nearby to infect.”
Listening in
Unfortunately, the method to prove this hypothesis is labour-intensive and extremely difficult, so that wasn’t part of this latest paper — although Erill and colleagues hope to tackle that question in the future. However, the research team sees no other plausible explanation for the proliferation of CtrA binding sites on so many different phages, all of which require pili/flagella to infect their hosts. Even more interesting, they note, are the implications for viruses that infect humans.
“Everything that we know about phages, every single evolutionary strategy they have developed, has been shown to translate to viruses that infect plants and animals,” he said. “It’s almost a given. So if phages are listening in on their hosts, the viruses that affect humans are bound to be doing the same.”
There are a few other documented examples of phages monitoring their environment in interesting ways, but none include so many different phages employing the same strategy against so many bacterial hosts.
Prof Erill predicts that more examples of this will be found, and his lab is already discovering more.
New therapeutic avenues
The key takeaway from this research is that “the virus is using cellular intel to make decisions,” Erill says, “and if it’s happening in bacteria, it’s almost certainly happening in plants and animals, because if it’s an evolutionary strategy that makes sense, evolution will discover it and exploit it.”
For example, to optimize its strategy for survival and replication, an animal virus might want to know what kind of tissue it is in, or how robust the host’s immune response is to its infection. While it might be unsettling to think about all the information viruses could gather and possibly use to make us sicker, these discoveries also open up avenues for new therapies.
“If you are developing an antiviral drug, and you know the virus is listening in on a particular signal, then maybe you can fool the virus,” Erill said. “We are just starting to realise how actively viruses have eyes on us – how they are monitoring what’s going on around them and making decisions based on that. “It’s fascinating.”
For people with established cardiovascular disease (CVD), consuming more dairy products was linked to worse health outcomes, according to a study in the European Journal of Preventive Cardiology. However, the type of dairy product appeared to make a difference, with the outcomes for cheese remaining unclear.
In patients with stable angina, significant associations with stroke, cardiovascular mortality, and all-cause mortality were seen with increasing daily intakes of total dairy and milk over follow-up of 5 to 14 years.
While acute myocardial infarction (MI) had no clear linear relationship with total dairy intake or milk consumption, a risk increase was seen for butter consumption of more than 2g per 1000kcal of daily intake.
Data were also inconclusive when it came to cheese consumption and CVD risk, with no significant associations between greater cheese consumption with acute MI, stroke, CVD mortality, or all-cause mortality.
Thus, the study draws a more complicated picture of dairy’s risks that supports other observational data suggesting that different dairy products may have different effects. “We can speculate that at least part of the differential associations seen for milk, butter, and cheese may be because cheese contains intact MFGM [milk fat globule membrane], while milk and butter does [sic] not,” the researchers wrote.
Dairy is “probably harmful” overall, the verdict on cheese is unclear, and some of the fermented dairy products may be less dangerous if dairy is to be consumed at all, commented Andrew Freeman, MD, a cardiologist at National Jewish Health in Denver, who was not involved with the study.
Even without a randomised trial, Dr Freeman said in an interview, “there’s enough signal in the noise to draw the conclusion that higher-fat dairy products, the number one source of saturated fat in our diet, are probably not going to be helpful to human health, and heart health in particular.”
He nevertheless cautioned that there may be worldwide variation in the effects of dairy products, which may be different between countries that place more restrictions on raising cattle with chemicals such as growth hormones.
Nevertheless, the global PURE study of people around the world consistently found the best outcomes from eating a balanced diet including lots of fruits and vegetables and a modest amount of dairy, unprocessed red meat, and nuts and legumes. The PURE investigators had also reported that at least two servings of dairy per day was linked with less CVD and mortality, compared with no dairy.
“Dairy is a heterogenous food group with divergent health effects and dairy products should therefore be investigated individually,” the researchers maintained.
Their data was drawn from 1929 patients with stable angina (80% men, mean age 62 years) from the Western Norway B Vitamin Intervention Trial.
All had undergone coronary angiography due to suspected coronary artery disease or aortic stenosis in 1999–2004. Use of preventive medications was high and included aspirin (90%), statins (90%), and beta-blockers (77%).
Participants self-reported dietary habits on a food frequency questionnaire. Average dairy intake was 169g/1000 kcal; mostly milk (133g/1000 kcal).
Bias and confounding were possible due to the observational nature of the study: people who ate more dairy already tended to eat less meat, vegetables, fruit and berries, fish, and potatoes. These individuals also got more calories from protein and less from fats (except saturated fats).
Further limitations include the lack of additional dietary evaluations over years of follow-up and the potential for participants to mischaracterize their diets on a survey.
A 3D map of the islets in the human pancreas. Source: Wikimedia
The autoimmune destruction of the pancreatic beta-cells in type 1 diabetes (T1D) has been studied extensively, yet the mystery of what causes autoimmunity is unknown. In a new study, researchers present a testable hypothesis to explain the initiation of autoimmunity – which, if validated, this would allow early detection and possible prevention of T1D in susceptible individuals. This hypothesis is discussed in the journal Diabetes.
“Previous studies have focused on the triggers, genes and proteins that differentiate individuals with T1D from those without diabetes with a focus on the b-cell (b-cells create antibodies) as a target of immune destruction and blood glucose as the main abnormality. Our focus is on metabolic communication as an early instigator with the b-cell as an active participant together with the immune cells,” explained corresponding author Barbara Corkey, PhD, professor at Boston University School of Medicine.
Prof Corkey’s research led her to hypothesise that autoimmunity induction results from one or more major inflammatory events in individuals with susceptible human leukocyte antigens phenotypes plus elevated sensitivity to cytokines and free fatty acids (FFA).
“Illnesses or environmental agents that dramatically increase cytokine production and/or elevate FFA initiate autoimmune destruction in individuals with specific genetic features. Thus, early prevention should be aimed at decreasing elevated lipids and diminishing excessive simultaneous elevation of cytokines or cytokine- and lipid-induced immune cell proliferation,” she said.
Prof Corkey believes that the characteristics that make individuals susceptible to autoimmune destruction could also apply to other autoimmune diseases such as toxic shock syndrome and possibly long COVID.
A new guideline published in Clinical & Experimental Allergy will help non-allergist clinicians evaluate and test patients for potential penicillin allergies.
Penicillin allergy labels are carried by 5.6% of the general population, with a seemingly higher incidence in hospitalised patients. About 95% of penicillin allergy labels are incorrect when tested.
Over the past 10 years, the clinical ramifications of a label of ‘penicillin allergy’ have been clearly defined. A diagnosis of penicillin allergy increases the risk of MRSA, Clostriodes difficile or VRE infections and death; presumably through increased use of alternatives to beta-lactam antibiotics. It also increases the duration of hospital admissions and has significant implications for the cost of health care. Several studies have shown the healthcare costs of the label and the economic benefits of removing incorrect labels.
Despite widespread evidence of its harms, resources are not available in the NHS for penicillin allergy testing, prompting the development of this guideline.
The guideline was developed by the Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI) along with a committee of experts and key stakeholders.
The aim of this guideline is to provide a framework for the set-up and delivery of penicillin allergy de-labelling services by non-allergists by using drug provocation testing. The intended users are non-allergists with an interest in clarifying the penicillin allergy status of their patients. The target population is adult and children with an untested label of penicillin allergy.
There are separate recommendations for adults and children within the guideline.
“The intended users are non-allergists with an interest in clarifying the penicillin allergy status of their patients. The guideline details appropriate patient selection, risk stratification, minimum safety standards, conduct of a drug provocation test, and the degree of oversight required from allergy or immunology specialists,” the authors wrote. “The guideline will be reviewed 5 years from original publication date.”
