Saturday, January 06, 2024

 

Unlocking the secrets of disease-causing fungus Aspergillus fumigatus


Ground-breaking research published in Nature Communications offers insights into deadly fungal disease, writes Dr Özgür Bayram of Maynooth University's Biology Department


Peer-Reviewed Publication

MAYNOOTH UNIVERSITY




An international team of researchers, led by Professor Gustavo Goldman of the University of São Paulo and Maynooth University’s Dr Özgür Bayram, has unveiled ground-breaking findings on Aspergillus fumigatus, which can cause deadly disease in humans.
 
The saprophytic fungus is notorious for causing a spectrum of human diseases, known collectively as aspergillosis, in individuals undergoing cancer treatments and organ transplants as well as those with cystic fibrosis and chronic obstructive pulmonary disease.
 
The human pathogen is at the forefront of the World Health Organization's priority list, ranking as the most significant among health-threatening fungal pathogens.
 
The study, published in the latest issue of the prestigious journal Nature Communications, sheds light on the intricate mechanisms underlying the virulence of Aspergillus fumigatus, specifically focusing on the crucial role of mycotoxin gliotoxin production. Gliotoxin helps this fungus to kill human immune cells including macrophages and neutrophiles.
 
Aspergillus fumigatus relies on a delicate balance in regulating gliotoxin production to prevent excess and mitigate toxicity to the fungus itself. The research team, led by Prof Goldman and Dr Bayram, identified the pivotal roles played by GliT oxidoreductase and GtmA methyltransferase in the self-protection mechanism of gliotoxin. Both enzymes were observed to be localised in the cytoplasm and vacuoles during gliotoxin production.
 
In a ground-breaking revelation, the study demonstrates the pivotal role of the Mitogen-Activated Protein kinase MpkA in both gliotoxin production and self-protection. MpkA was found to physically interact with GliT and GtmA, influencing their regulation and subsequent presence in vacuoles — an association not previously made or demonstrated in relation to gliotoxin production.
 
The researchers emphasise the significance of compartmentalisation of cellular events and the orchestrated interplay of these key enzymes for the effective production of gliotoxin and the self-defence mechanism of the fungus.
 
“We have been collaborating with international research teams using our expertise on identification of protein complexes. Our collaboration with Professor Goldman has led to high impact research on revealing the pathogenic traits of human pathogen Aspergillus fumigatus,” Dr Bayram said.
 
"Our work not only unravels the complex interplay of molecular actors within Aspergillus fumigatus but also underscores the importance of understanding these mechanisms for potential therapeutic interventions against aspergillosis.”

The findings contribute significantly to the understanding of fungal pathogenesis and open avenues for targeted approaches in combating diseases caused by Aspergillus fumigatus.
 
“The implications extend beyond mere discovery; there's potential for developing therapeutic approaches,” Dr Bayram said. “For instance, the newfound knowledge might lay the foundation for a treatment targeting aspergillus infections in patients. Such a breakthrough could have profound implications for individuals undergoing cancer treatments, organ transplants, those with cystic fibrosis, and those managing chronic obstructive pulmonary disease (COPD).”
 
The study was funded by São Paolo Research Foundation and Science Foundation Ireland. The research paper is titled: Aspergillus fumigatus mitogen-activated protein kinase MpkA is involved in gliotoxin production and self-protection.
 
The project involved a major collaborative effort between Maynooth University fungal biologists, Dr Özgür Bayram (Fungal Genetics and Secondary Metabolism), Dr Özlem Sarikaya Bayram (Agricultural Epigenetics) and molecular biotechnology researcher, Aimee Traynor.

 

Brazilian researchers discover two novel peptides with biotechnological potential in snake venom


Fragments of hemorrhagic toxins that may help treat high blood pressure were found in the venom of the pit viper Cotiara, which inhabits the South of Brazil, and that of the South American bushmaster, a denizen of tropical rainforests


Peer-Reviewed Publication

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO

Brazilian researchers discover two novel peptides with biotechnological potential in snake venom 

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THE VENOM OF THE SOUTH AMERICAN BUSHMASTER (LACHESIS MUTA) IS NOT ESPECIALLY POWERFUL, BUT THE SNAKE IS DANGEROUS BECAUSE OF THE LARGE AMOUNT OF VENOM IT INJECTS INTO ITS VICTIMS 

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CREDIT: SÁVIO STEFANINI SANT’ ANNA/INSTITUTO BUTANTAN




Brazilian snake and spider venoms continue to be a source of new discoveries with biotechnological potential. Two studies supported by FAPESP and recently published show how this is possible even in relatively well-studied species such as the lancehead pit viper Cotiara (Bothrops cotiara) and the South American bushmaster (Lachesis muta).

“Venoms never cease to surprise us. Even with so much accumulated knowledge, fresh discoveries are possible, such as unpredictable fragments that are parts of known proteins. Despite all the available technology, a great deal remains to be studied in these toxins,” said Alexandre Tashima, principal investigator for both studies. Tashima is a professor at the Federal University of São Paulo’s Medical School (EPM-UNIFESP) and is supported by FAPESP.

He was referring to a novel peptide (protein fragment) identified in B. cotiara’s venom and named Bc-7a. Although it is part of a protein that causes bleeding in the snake’s prey, in functional terms it is closer to peptides such as those at the origin of captopril, a drug that lowers blood pressure by inhibiting the activity of angiotensin-converting enzyme (ACE).

The latest study is reported in an article published in the journal Biochimie.

Many ACE-inhibiting molecules already exist, but the search continues because of adverse side effects such as a dry cough, dizziness, and high blood potassium levels. 

The peptide is one of 197 revealed by the study, 189 of them reported for the first time. In 2012, the group found 73 peptides in the same snake’s venom. According to the authors, the difference is due to the use in the more recent study of faster and more sensitive equipment than was available a decade ago, and to the larger number of peptide sequences to be gleaned from databases now.

In previous studies, Tashima and his group had found molecules with biotechnological potential in the venom of another snake, as well as two tarantula spiders (read more at: agencia.fapesp.br/35106 and agencia.fapesp.br/40490).

Bushmaster

A study involving bushmaster venom from L. muta, reported in an article published in Biochemical and Biophysical Research Communications, identified 151 peptides, of which 126 were previously unknown.

The researchers were particularly interested in a novel metalloproteinase-derived peptide called Lm-10a, a fragment of a hemorrhagic toxin that inhibits ACE and could potentially be used in a drug to treat blood pressure. Their analysis suggested that both Lm-10a from L. muta and Bc-7a from B. cotiara resulted from fragmentation processes during venom maturation in the snake’s venom gland and that many more novel peptides could be obtained from the toxins.

“In this kind of analysis, the protein sequence obtained is just a snapshot. Cleavage, enzymatic degradation and other processes generating novel peptides that aren’t necessarily detected occur all the time,” Tashima explained.

More research is needed to verify the real potential of the peptides they discovered. Moreover, the dynamic nature of toxin maturation points to the use by venomous snakes of various biological mechanisms to refine venom during their evolution.

“Despite advances in sequencing technology and the production of large amounts of data in recent years, much remains to be discovered about the vast universe of peptides and their biological roles. We must take advantage of our good fortune in being able to study these species, many of which will be extinct before they’ve even been discovered,” Tashima said.

About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.

 

Harnessing sensors, smart devices, and AI could transform agriculture


To meet the need for safe, sustainably-produced food for a growing global population, biosensing expert Azahar Ali points to smart, connective technologies yet to be fully explored.


Peer-Reviewed Publication

VIRGINIA TECH

Sustainable ag 

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TO ASSISTANT PROFESSOR AZAHAR ALI, THREE TECHNOLOGIES STAND OUT FOR THEIR POTENTIAL TO ADVANCE CLIMATE-SMART, PRECISION AGRICULTURE: WEARABLE AGRICULTURE SENSORS, SMART DEVICES, AND ARTIFICIAL INTELLIGENCE.

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CREDIT: PHOTO BY SAM DEAN FOR VIRGINIA TECH.




Biosensing engineer Azahar Ali, assistant professor of animal sciences and biological systems engineering at Virginia Tech, is bracing for the arrival of a fourth agricultural revolution.

It’s an era predicted to tap into the transformative potential of the connective technologies that have arisen in the Fourth Industrial Revolution. To Ali, three technologies stand out for their potential to advance climate-smart, precision agriculture: wearable agriculture sensors, Internet of Things-enabled — or “smart” — devices, and artificial intelligence (AI).

In a review article published by Advanced Intelligent Systems, Ali and colleagues Matin Ataei Kachouei of the School of Animal Sciences and Ajeet Kaushik of Florida Polytechnic University wrote that merging these cutting-edge technologies could create a paradigm shift in how the agricultural sector monitors food safety and quality and plant health and productivity worldwide.

For Ali, prioritizing rapid, accurate, early monitoring will be critical to sustainably and safely feeding the fast-growing global population, which is expected to be nearly 10 billion by 2050 and will require 50 percent more food to maintain the world’s food supply chain, according to the article.

According to the 2023 Global Agricultural Productivity, or GAP, Report, released through the College of Agriculture and Life Sciences, the growth of global agricultural productivity has significantly contracted and current efforts to sustainably expand production are inadequate.

Ali said researchers will need to collaborate to tap into the full potential of new technologies that could help producers keep up with future demand. Agronomists need to work with experts in engineering, human and veterinary medicine, and materials science.

“There’s a huge gap in this kind of collaboration,” Ali said. “I develop sensors, but I need to collaborate with experts in machine learning. We need to engage in more collaboration to solve the food crisis.”

In their article, Ali, Kachouei, and Kaushik laid out the recent progress researchers have made in applying sensors, smart devices, and AI in monitoring food and plants. They also describe the potential and challenges of combining the technologies.

Food sensor technology has seen remarkable development, they wrote, with a focus on measuring toxins, humidity, pH, freshness, temperature, contaminants, and pathogens. Keeping tabs on these factors is key to food safety, food quality, and high packaging standards.

The researchers described how these sensing capabilities could be enhanced when paired with other technologies: With the pairing of sensors and smart devices, food, livestock, and plant sensing systems could precisely collect data in real time, on site, and at a large scale. Next-generation networks could then quickly transmit the high-volume data generated by those systems.

AI could streamline data analysis through automatic data processing, the researchers wrote. AI could take on the volumes of data generated by smart sensors, Ali said. Combined, smart devices and AI also offer the potential for predictive analysis, enabling producers to proactively anticipate challenges such as disease outbreaks and weather patterns.

Throughout the article, Ali and his colleagues highlighted examples of how researchers are currently exploring integration of multiple technologies, including the development of electrochemical sensors used to detect disease biomarkers in cow milk, orange juice, and apple juice, and the use of microneedle-based integrated plant sensors alongside smartphone-based 3D-printed devices to detect viruses in tomatoes.

Ali and his colleagues see promise in these solutions, but they also noted existing challenges for tapping into the technologies of the fourth agricultural revolution: There are security concerns in data collection using smart sensors; the costs of sensors, network infrastructure, and data management could be prohibitive; and there could be internet connectivity issues when using smart devices in the rural or remote areas where many farms are located.

To address those challenges, Ali pointed back to collaboration, not only among scientists, but with policymakers and farmers. “To solve our common problems, we need to work together,” he said.

 

Revisiting Israel's freshwater fish species list through cutting-edge DNA barcoding technology


Peer-Reviewed Publication

THE HEBREW UNIVERSITY OF JERUSALEM

Sampling Near the Sea of Galilee 

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RONI TADMOR ON THE LEFT, ALONGSIDE THE LATE TOMER BOROVSKY ON THE RIGHT, CONDUCTING SAMPLING NEAR THE SEA OF GALILEE FOR THE COFFEE CHAIN.

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CREDIT: JAMES SHAPIRA FROM THE FISHERIES DIVISION OF THE MINISTRY OF AGRICULTURE, ISRAEL




Hebrew University of Jerusalem, Israel – A new study led by Dr. Roni Tadmor-Levi in the group of Prof. Lior David and a team of researchers from the Hebrew University of Jerusalem and Tel Aviv University, has shed new light on Israel's freshwater fish biodiversity. The study, initiated by the Israel Nature and Parks Authority, focused on DNA barcoding, has unveiled intriguing insights into the unique populations and species composition in the region, their genetic distinctiveness, with implications for conservation efforts.

Israel's geographical positioning as a continental bridge has endowed its freshwater fish fauna with a tapestry of species, originating from Africa, Asia, and Europe. Often, these species are endemic or represented by unique populations adapted to live at the peripheries of their distribution ranges. However, freshwater habitats, especially in arid regions, including parts of Israel, have been facing substantial pressures and disturbances, threatening biodiversity.

To address these challenges, a reliable inventory of species and populations can direct what and how to protect Israel’s biodiversity. The research team employed DNA barcoding, a cutting-edge technique that complements traditional species identification methods, to create a comprehensive database for Israel's freshwater fish. Over 200 specimens from the scientific collections stored at the Steinhardt Museum of Natural History representing more than 28 species underwent DNA barcoding analysis, yielding 71 distinct barcodes, with an astonishing 37% identified as new. This discovery underscores the unparalleled uniqueness of fish populations in Israel.

While most species showed alignment between morphological and molecular identifications, the study identified discrepancies in five genera, and lead to significant reconsiderations for 12 different species. Notably, the research suggests the consolidation of species and proposes taxonomic revisions. Among these proposals, Acanthobrama telavivensis (Lavnun ha’yarkon) is suggested as a junior synonym for Acanthobrama lissneri (Lavnun lisnner), and the potential splitting of Garra nana (Yableset)  into two distinct species, alongside establishing the presence of Garra jordanica and not Garra rufa (Red garra) in Israel and the near region.

Moreover, the study challenges previously reported classifications of certain species, such as Pseudophoxinus kervillei (Lavnunit ha’galil), suggesting discrepancies from neighboring regions. Similarly, in the case of Oxynoemacheilus (loach) species, combining DNA barcoding with morphology revisited how many and which species are in Israel.

Of significant importance is the revelation regarding Aphanius mento (Pearl-spotted killifish), indicating the likelihood of it being a species complex due to genetic and geographic disparities.

This comprehensive barcoding database not only prompts significant reconsiderations of species within the region but also identifies biodiversity 'hotspots,' notably the Sea of Galilee and the Beit She'an valley streams.

The implications of this study extend beyond taxonomy, advocating for a deeper understanding of fish species and their ecological dynamics. This research is poised to fuel further investigations into the region's fish species and their habitats, strengthening efforts towards monitoring and conserving Israel and the region's freshwater fish biodiversity.

According to Dr. Noam Leader  (Director of the Ecology Department) and Dr. Dana Milstein (Aquatic Ecologist) of the Science Division of the Israel Nature and Parks Authority, the Parks Authority works to preserve the diversity of fish fauna which are characteristic and unique to Israel, including 13 species that are protected species by law. The current study clarifies which species exist in Israel and makes it possible to better assess their distribution, and more importantly to identify those that are at risk. This information has great concervation value since it enables the Parks Authority to promote actions to protect endangered species (for example, the establishment of captive breeding centers), to adjust the  management of the aquatic habitats within the boundaries of nature reserves, as well as to emphasise the river rehabilitation activities that the Parks Authority is carrying out. The combination of knowledge and actions is what will ensure better protection of Israel's unique fish comminuty.

 

Resurrection consent: New study on attitudes to digital cloning of the dead


Peer-Reviewed Publication

DE GRUYTER





In a 2014 episode of sci-fi series Black Mirror, a grieving young widow reconnects with her dead husband using an app that trawls his social media history to mimic his online language, humor and personality. It works. She finds solace in the early interactions – but soon wants more.   

Such a scenario is no longer fiction. In 2017, the company Eternime aimed to create an avatar of a dead person using their digital footprint, but this “Skype for the dead” didn’t catch on. The machine-learning and AI algorithms just weren’t ready for it. Neither were we.

Now, in 2024, amid exploding use of Chat GPT-like programs, similar efforts are on the way. But should digital resurrection be allowed at all? And are we prepared for the legal battles over what constitutes consent?

In a study published in the Asian Journal of Law and Economics, Dr Masaki Iwasaki of Harvard Law School and currently an assistant professor at Seoul National University, explores how the deceased’s consent (or otherwise) affects attitudes to digital resurrection.

US adults were presented with scenarios where a woman in her 20s dies in a car accident. A company offers to bring a digital version of her back, but her consent is, at first, ambiguous. What should her friends decide?

Two options – one where the deceased has consented to digital resurrection and another where she hasn’t – were read by participants at random. They then answered questions about the social acceptability of bringing her back on a five-point rating scale, considering other factors such as ethics and privacy concerns.

Results showed that expressed consent shifted acceptability two points higher compared to dissent. “Although I expected societal acceptability for digital resurrection to be higher when consent was expressed, the stark difference in acceptance rates – 58% for consent versus 3% for dissent – was surprising,” says Iwasaki. "This highlights the crucial role of the deceased's wishes in shaping public opinion on digital resurrection."

In fact, 59% of respondents disagreed with their own digital resurrection, and around 40% of respondents did not find any kind of digital resurrection socially acceptable, even with expressed consent. “While the will of the deceased is important in determining the societal acceptability of digital resurrection, other factors such as ethical concerns about life and death, along with general apprehension towards new technology are also significant,” says Iwasaki.  

The results reflect a discrepancy between existing law and public sentiment. People’s general feelings – that the dead’s wishes should be respected – are actually not protected in most countries. The digitally recreated John Lennon in the film Forrest Gump, or animated hologram of Amy Winehouse reveal the ‘rights’ of the dead are easily overridden by those in the land of the living.

So, is your digital destiny something to consider when writing your will? It probably should be but in the current absence of clear legal regulations on the subject, the effectiveness of documenting your wishes in such a way is uncertain. For a start, how such directives are respected varies by legal jurisdiction. “But for those with strong preferences documenting their wishes could be meaningful,” says Iwasaki. “At a minimum, it serves as a clear communication of one’s will to family and associates, and may be considered when legal foundations are better established in the future.”

It’s certainly a conversation worth having now. Many generative AI chatbot services, such as like Replika (“The AI companion who cares”) and Project December (“Simulate the dead”) already enable conversations with chatbots replicating real people’s personalities. The service ‘You, Only Virtual’ (YOV) allows users to upload someone's text messages, emails and voice conversations to create a ‘versona’ chatbot. And, in 2020, Microsoft obtained a patent to create chatbots from text, voice and image data for living people as well as for historical figures and fictional characters, with the option of rendering in 2D or 3D.

Iwasaki says he’ll investigate this and the digital resurrection of celebrities in future research. “It’s necessary first to discuss what rights should be protected, to what extent, then create rules accordingly,” he explains. “My research, building upon prior discussions in the field, argues that the opt-in rule requiring the deceased's consent for digital resurrection might be one way to protect their rights.”

 

Why are bees making less honey? Study reveals clues in five decades of data


Peer-Reviewed Publication

PENN STATE




UNIVERSITY PARK, Pa. — Honey yields in the U.S. have been declining since the 1990s, with honey producers and scientists unsure why, but a new study by Penn State researchers has uncovered clues in the mystery of the missing honey.

Using five decades of data from across the U.S., the researchers analyzed the potential factors and mechanisms that might be affecting the number of flowers growing in different regions — and, by extension, the amount of honey produced by honey bees.

The study, recently published in the journal Environmental Research, found that changes in honey yields over time were connected to herbicide application and land use, such as fewer land conservation programs that support pollinators. Annual weather anomalies also contributed to changes in yields.

The data, pulled from several open-source databases including those operated by the United States Department of Agriculture (USDA) National Agricultural Statistics Service and USDA Farm Service Agency, included such information as average honey yield per honey bee colony, land use, herbicide use, climate, weather anomalies and soil productivity in the continental United States.

Overall, researchers found that climate conditions and soil productivity — the ability of soil to support crops based on its physical, chemical and biological properties — were some of the most important factors in estimating honey yields. States in both warm and cool regions produced higher honey yields when they had productive soils.

The eco-regional soil and climate conditions set the baseline levels of honey production, while changes in land use, herbicide use and weather influenced how much is produced in a given year, the researchers summarized.

Gabriela Quinlan, the lead author on the study and a National Science Foundation (NSF) postdoctoral research fellow in Penn State’s Department of Entomology and Center for Pollinator Research, said she was inspired to conduct the study after attending beekeeper meetings and conferences and repeatedly hearing the same comment: You just can’t make honey like you used to.

According to Quinlan, climate became increasingly tied to honey yields in the data after 1992.

“It’s unclear how climate change will continue to affect honey production, but our findings may help to predict these changes,” Quinlan said. “For example, pollinator resources may decline in the Great Plains as the climate warms and becomes more moderate, while resources may increase in the mid-Atlantic as conditions become hotter.”

Co-author on the paper Christina Grozinger, Publius Vergilius Maro Professor of Entomology and director of the Center for Pollinator Research, said that while scientists previously knew that many factors influence flowering plant abundance and flower production, prior studies were conducted in only one region of the U.S.

“What’s really unique about this study is that we were able to take advantage of 50 years of data from across the continental U.S.,” she said. “This allowed us to really investigate the role of soil, eco-regional climate conditions, annual weather variation, land use and land management practices on the availability of nectar for honey bees and other pollinators.”

One of the biggest stressors to pollinators is a lack of flowers to provide enough pollen and nectar for food, according to the researchers. Because different regions can support different flowering plants depending on climate and soil characteristics, they said there is growing interest in identifying regions and landscapes with enough flowers to make them bee friendly.

“A lot of factors affect honey production, but a main one is the availability of flowers,” she said. “Honey bees are really good foragers, collecting nectar from a variety of flowering plants and turning that nectar into honey. I was curious that if beekeepers are seeing less honey, does that mean there are fewer floral resources available to pollinators overall? And if so, what environmental factors were causing this change?”

For Quinlan, one of the most exciting findings was the importance of soil productivity, which she said is an under-explored factor in analyzing how suitable different landscapes are for pollinators. While many studies have examined the importance of nutrients in the soil, less work has been done on how soil characteristics like temperature, texture, structure — properties that help determine productivity — affect pollinator resources.

The researchers also found that decreases in soybean land and increases in Conservation Reserve Program land, a national conservation program that has been shown to support pollinators, both resulted in positive effects on honey yields.

Herbicide application rates were also important in predicting honey yields, potentially because removing flowering weeds can reduce nutritional sources available to bees.

“Our findings provide valuable insights that can be applied to improve models and design experiments to enable beekeepers to predict honey yields, growers to understand pollination services, and land managers to support plant–pollinator communities and ecosystem services,” Quinlan said.

To learn more about the land use, floral resources and weather in specific areas, visit the Beescape tool on the Center for Pollinator Research website.

David A.W. Miller, associate professor of wildlife population ecology, was also a co-author on the study.

The NSF Postdoctoral Research Fellowship in Biology Program and the USDA National Institute Food and Agriculture’s Pollinator Health Program and Data Science for Food and Agricultural Systems Programs helped support this research.