It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Tuesday, April 09, 2024
Haiti's Gangs Try Their Hand at Piracy, Hijacking a Ship Full of Food
Haiti's gang warlords have turned the country into a disaster zone, abusing the citizenry and shutting down commercial transport in and out of the country. As if their violent behavior ashore were not enough, two gangs recently decided to turn to piracy, hijacking a cargo ship full of food at one of the nation's largest terminals.
Last Thursday, members of the 5 Seconds and Taliban gangs (no relation to the Afghan Taliban) captured the freighter Magalie at Port-Au-Prince's Varreux terminal district, according to local media. They made off with one-sixth of the cargo of rice, Haiti's primary staple food, and they took all of the crewmembers hostage, police said. Kidnapping is rampant in Haiti, and has long been a favored form of piracy worldwide.
On Saturday, Haiti's National Police stormed the ship in a gunfight that lasted for five hours, the agency said. Two officers were injured in the altercation and an unspecified number of gangmembers were killed, and the vessel was safely recovered. Haiti's National Port Authority assisted with transport for the boarding teams.
The fate of the crew is not known, according to Haiti Libre. A video provided by police showed the Magalie making way astern off the coast, apparently being towed on the hip by a large tug.
Port-au-Prince's waterfront operations have come under attack by gangs multiple times, disrupting the flow of aid and supplies. Vandals damaged the Varreux Power Plant last month, and briefly occupied and looted the nation's largest container terminal, CPS. The terminal's waterside operations were closed for weeks (and may still be shut, according to the UN's Famine Early Warning System Network).
NTU Singapore scientists grow ‘mini kidneys,’ revealing new insights into metabolic defects and potential therapy for polycystic kidney disease
NANYANG TECHNOLOGICAL UNIVERSITY
Scientists at Nanyang Technological University, Singapore (NTU Singapore) have successfully grown ‘mini kidneys’ in the lab and grafted them into live mice, revealing new insights into the metabolic defects and a potential therapy for polycystic kidney disease.
‘Mini kidneys,’ or kidney organoids, are kidney-like structures grown in the lab using stem cells. In the study led by NTU’s Lee Kong Chian School of Medicine (LKCMedicine), researchers grew the organoids using skin cells derived from patients with polycystic kidney disease (PKD), a prevalent form of genetic condition that affects 1 in 1000 individuals across all ethnicities. [1]
People with PKD often progress to end-stage kidney disease between their 50s and 60s, with the standard treatment options available being dialysis or a kidney transplant. However, dialysis significantly compromises a patient’s quality of life, while a transplanted kidney can be challenging to acquire. One other option is the Food and Drug Administration (FDA) approved drug Tolvaptan, which is very costly and has severe side effects on the liver.
To address the need for more effective treatment for PKD patients, the NTU research team sought to better understand the disease by engrafting their newly developed mini kidneys into mice.
Previous studies were conducted on mini kidneys grown in a dish, which could only partly mimic the kidney structure and function. The NTU scientists engrafted the mini kidneys into live mice to comprehensively replicate the pathological features of kidney disease, including blood flow, fluid movement (tubular fluid) and cellular communication with other organs.
Lead investigator Assistant Professor Xia Yun at LKCMedicine said, “Engrafting the kidney organoid in mice provided us with a physiologically sophisticated approach to studying polycystic kidney disease as we were able to successfully emulate critical disease characteristics similar to those observed in human kidney patients.”
Critical disease characteristics included abnormalities like the spontaneous formation of cysts in the kidneys and the subsequent damage to its tiny tubes.
In their study, reported in the scientific journal Cell Stem Cell, the NTU research team said that they believed their engrafted mini kidneys were high quality because cysts sustained without extra stress stimulation or chemicals, even after they were removed from the live mice for further investigations in a dish. In contrast, previous kidney organoids grown in a dish cannot form cysts without stress stimulation.
Co-investigator Assistant Professor Foo Jia Nee at LKCMedicine said, “The similarity between the disease manifestation observed in our engrafted mini kidney model and the real-life experiences of polycystic kidney disease patients suggest that growing kidney organoids and engrafting them into live mice could be beneficial in studying the disease and a useful tool to test new treatments.”
Metabolic defects in polycystic kidney disease
Scientists have long known that abnormalities in a structure on kidney cells, or the primary cilium, cause cysts to form in kidneys. However, tests to understand the regulatory mechanism and relationship between the primary cilium and cell metabolism (autophagy) in live mice with PKD, have not been possible until now.
By studying the development of PKD in live mice and testing cellular pathways, researchers found evidence that boosting autophagy could reduce the severity of cysts in the mini kidney.
After establishing that boosting autophagy could reduce cysts, the NTU scientists shortlisted 22 drugs known for their effects on cell metabolism and tested them in the lab. Results showed that minoxidil, a clinical drug widely used to cure hypertension and hair loss, effectively reduced cyst formation in the novel mouse model.
Asst Prof Xia Yun said, “Our study has demonstrated how cysts in polycystic diseased kidneys can be reduced by boosting autophagy, suggesting that this could be a promising treatment for PKD. Moreover, the proven clinical safety of minoxidil may allow it to be quickly re-purposed to treat PKD patients in clinic. However, more research will be needed to establish this potential.”
Commenting as an independent expert, Associate Professor Ng Kar Hui, Senior Consultant, Division of Paediatric Nephrology, Dialysis and Renal Transplantation, Department of Paediatrics, Khoo Teck Puat – National University Children's Medical Institute, National University Hospital, said, “Polycystic kidney disease is one of the biggest causes of chronic kidney diseases among adults. An effective treatment may potentially ameliorate the rising numbers of people with kidney failure in Singapore. The establishment of such models in live organisms brings us one step closer to finding more treatment options.
In future studies, the NTU team will test the efficacy of minoxidil and adapt the mini kidney models to investigate other burgeoning kidney diseases without a strong genetic underpinning, such as diabetic kidney disease.
***END***
Image of microscopic cystic kidney organoids derived from patient induced pluripotent stem cells.
Immunofluorescence image of a polycystic kidney disease organoid.
Kidney organoid models reveal cilium-autophagy metabolic axis as a therapeutic target for PKD both in vitro and in vivo
Researchers identify an economic solution to Canada's opioid crisis
Waterloo student uses mathematical modelling to bring awareness to opioid-related death reduction method
UNIVERSITY OF WATERLOO
Nasal-administered naloxone is more cost-effective and could help reduce the number of opioid-related fatalities compared to the current publicly funded intermuscular version, a new study has found.
Since 2016, Canada's opioid crisis has worsened, with over 40,000 opioid-related deaths, or about 22 deaths per day. Most of these accidental deaths (88 per cent) occur in British Columbia, Alberta and Ontario.
An effective way to help prevent opioid-related deaths is through community pharmacy-based naloxone programs. Currently, intramuscular naloxone is publicly funded across Canada, but it can be stress-inducing and difficult for bystanders to administer naloxone through a syringe. Intranasal naloxone, used as a simple nasal spray, is only publicly funded in Ontario, Quebec and the Northwest Territories.
The study by University of Waterloo researchers found a research gap in identifying the cost-effectiveness of implementing intranasal naloxone distribution across Canada through public funding. Mathematical modelling conducted by Waterloo researchers confirmed that intranasal naloxone is cost-effective when distributed to all Canadians and could help save additional lives. Based on the model, 151 deaths will be prevented per 10,000 people.
"Think of an EpiPen," said Ashley Cid, a PhD candidate in Waterloo's School of Pharmacy, which offers North America's most innovative pharmacy curriculum by integrating biomedical and pharmacy science with clinical, behavioural and social sciences that emphasizes patient-focused care.
"Similarly, naloxone is effective, safe, easy to use and is a medication meant to save someone's life regardless of whether you take opioid medication for a prescription or not. Providing publicly funded intranasal naloxone kits can effectively manage and reduce opioid-related fatalities due to increased distribution."
Cid adds that naloxone is a harm-reduction measure and does not increase the risk of opioid use. She believes policymakers should consider publicly funding intranasal naloxone across Canada and increasing distribution as it would help to mitigate the immediate public health opioid crisis and save more lives, especially in provinces like Alberta and British Columbia, where high rates of deaths are occurring.
"Providing intranasal naloxone through community pharmacies would have an immediate impact and be a great solution to increase access to publicly funded naloxone kits," Cid said. "I hope someday naloxone will be kept in first aid kits in your car, purse or home for emergencies."
Ontario’s proposed plan to broaden alcohol sales will harm people
CANADIAN MEDICAL ASSOCIATION JOURNAL
The Ontario government’s plans to broaden alcohol sales to privately operated stores in the province could lead to higher consumption rates and related harms, write commentary authors in CMAJ (Canadian Medical Association Journal) https://www.cmaj.ca/lookup/doi/10.1503/cmaj.240069.
“These changes will result in a 289% increase in the number of alcohol stores in Ontario (n = 2935 in March 2023, per the Liquor Control Board of Ontario), will likely reduce the price of alcohol, and will represent the biggest shift in decades with respect to how alcohol is sold in Canada,” write Drs. Norman Giesbrecht, Centre for Addiction and Mental Health and University of Toronto, and Daniel Myran, Bruyère Research Institute and The Ottawa Hospital, Ottawa, Ontario.
Extensive evidence indicates that these changes will increase alcohol use and associated harms, such as deaths, hospital visits and admissions, violence, and chronic disease. For example, an analysis of the first 2 years of alcohol sales in Ontario grocery stores found alcohol-related emergency department visits increased by more than 6% in areas with alcohol in grocery stores compared to those without.
The authors call for additional polices to help reduce the risk of negative effects of this policy change.
“We propose instituting policies at the provincial and federal level — including strengthening minimum pricing on alcohol, mandating warning labels on all alcoholic beverages, and increasing access to screening and treatment for alcohol use disorders — to partially mitigate potential harms and costs from these changes.”
Although it is difficult to quantify the harms that may occur, the “public health imperative” posed by these changes warrants action and perhaps a rethink by the Ontario government.
Harms and costs of proposed changes in how alcohol is sold in Ontario
Understanding the link between family physician characteristics and COVID-19 vaccination gaps
CANADIAN MEDICAL ASSOCIATION JOURNAL
New research examining the characteristics of physicians with the largest share of patients unvaccinated against SARS-CoV-2 may help increase vaccination rates going forward. The study, published in CMAJ (Canadian Medical Association Journal) https://www.cmaj.ca/lookup/doi/10.1503/cmaj.230816, found that family physicians in Ontario with the largest percentage of unvaccinated patients generally served patients living in marginalized neighbourhoods and had less support in their practices.
Researchers analyzed linked data on 9060 family physicians with more than 10 million enrolled patients and calculated the percentage of patients unvaccinated against SARS-CoV-2 per physician. They compared family physicians (n = 906) caring for the largest proportion of unvaccinated patients (top 10%) with the rest of the comprehensive-care family physicians in Ontario. They found the group with the largest proportion of unvaccinated patients were more likely to be male, to have trained outside Canada, to be older (mean age of 56 v. 49 years), and to work in a fee-for-service model than the remaining 90% of physicians.
“The family physicians with the most unvaccinated patients were also more likely to be solo practitioners and less likely to practise in team-based models, meaning they may have fewer support staff in their clinics,” says Dr. Jennifer Shuldiner, lead author and scientist, Women’s College Hospital, Toronto, Ontario. “This illustrates the ongoing inverse relationship between the need for care, and its accessibility and utilization. In other words, the practices with the highest need receive the fewest resources.”
As many of the physicians with the largest percentage of unvaccinated patients served people living in marginalized neighbourhoods, awareness of cultural differences in perspectives on vaccination should be considered.
“Many marginalized communities have a history of neglect from government (municipal, provincial, federal) and health care, and this may lead to mistrust in public health initiatives,” the study authors write. “Interventions to support these communities should include meaningful community engagement and consideration for age-, language-, and culturally appropriate communication tools to assist primary care in boosting vaccine uptake.”
Although the majority of SARS-CoV-2 vaccines were not administered by family physicians, clinicians have an important role to play in educating patients about the benefits of vaccination.
“We know that relationships with trusted family physicians can positively influence patients’ decisions,” explains Dr. Noah Ivers, senior author and clinician scientist, Women’s College Hospital. “Our study highlights the need to create equitable systems and processes that create opportunities for primary care teams to play a crucial role in influencing both general and SARS-CoV-2-specific vaccine-related decision-making.”
Expanding primary care teams in marginalized neighbourhoods and using hotspot strategies to focus public health resources in under-vaccinated communities could help support public health initiatives like vaccination.
Characteristics of primary care practices by proportion of patients unvaccinated against SARS-CoV-2: a cross-sectional cohort study
Bringing multidrug-resistant pathogens to their knees
Fluorous lipopetides act as highly effective antibiotics
WILEY
Multidrug-resistant bacterial infections that cannot be treated by any known antibiotics pose a serious global threat. In the journal Angewandte Chemie, a Chinese research team has now introduced a method for the development of novel antibiotics to fight resistant pathogens. The drugs are based on protein building blocks with fluorous lipid chains.
Antibiotics are often prescribed far too readily. In many countries they are distributed without prescriptions and administered in factory farming: prophylactically to prevent infections and enhance performance. As a result, resistance is on the rise—increasingly against reserve antibiotics as well. The development of innovative alternatives is essential.
It is possible to learn some lessons from the microbes themselves. Lipoproteins, small protein molecules with fatty acid chains, are widely used by bacteria in their battles against microbial competitors. A number of lipoproteins have already been approved for use as drugs. The common factors among the active lipoproteins include a positive charge and an amphiphilic structure, meaning they have segments that repel fat and others that repel water. This allows them to bind to bacterial membranes and pierce through them to the interior.
A team led by Yiyun Cheng at East China Normal University in Shanghai aims to amplify this effect by replacing hydrogen atoms in the lipid chain with fluorine atoms. These make the lipid chain simultaneously water-repellant (hydrophobic) and fat-repellant (lipophobic). Their particularly low surface energy strengthens their binding to cell membranes while their lipophobicity disrupts the cohesion of the membrane.
The team synthesized a spectrum (substance library) of fluorous lipopeptides from fluorinated hydrocarbons and peptide chains. To link the two pieces, they used the amino acid cysteine, which binds them together via a disulfide bridge. The researchers screened the molecules by testing their activity against methicillin-resistant Staphylococcus aureus (MRSA), a widespread, highly dangerous strain of bacteria that is resistant to nearly all antibiotics. The most effective compound they found was “R6F”, a fluorous lipopeptide made of six arginine units and a lipid chain made of eight carbon and thirteen fluorine atoms. To increase biocompatibility, the R6F was enclosed within phospholipid nanoparticles.
In mouse models, R6F nanoparticles were shown to be very effective against sepsis and chronic wound infections by MRSA. No toxic side effects were observed. The nanoparticles seem to attack the bacteria in several ways: they inhibit the synthesis of important cell-wall components, promoting collapse of the walls; they also pierce the cell membrane and destabilize it; disrupt the respiratory chain and metabolism; and increase oxidative stress while simultaneously disrupting the antioxidant defense system of the bacteria. In combination, these effects kill the bacteria—other bacteria as well as MRSA. No resistance appears to develop.
These insights provide starting points for the development of highly efficient fluorous peptide drugs to treat multi-drug resistant bacteria.
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About the Author
Dr. Yiyun Cheng is Professor of Materials Chemistry and Biotechnology at the School of Life Sciences, East China Normal University. His research interests focus on the rational design of biomaterials for cytosolic delivery of biomacromolecules such as DNA, RNA, protein and peptide.
A Fluorous Peptide Amphiphile with Potent Antimicrobial Activity for the Treatment of MRSA-induced Sepsis and Chronic Wound Infection
Coral researchers awarded EXIST start-up funding
Start-up aims to make sustainable coral farming commercially viable and boost the protection of wild corals
UNIVERSITY OF OLDENBURG
Coral farming based on sexual propagation, leading to a more sustainable coral trade and helping to protect coral reefs – this is the goal of SciReef, a new start-up which is emerging from a research transfer project. SciReef is based on the research conducted by Dr Samuel Nietzer and Dr Mareen Möller in the Environmental Biochemistry research group at the Wilhelmshaven site of the University of Oldenburg’s (Germany) Institute for Chemistry and Biology of the Marine Environment (ICBM). The Federal Ministry for Economic Affairs and Climate Action (BMWK) and the European Social Fund Plus (ESF Plus) support the innovative start-up with around 920,000 euros in EXIST Transfer of Research funding over the next two years. Peter Schupp, Professor of Environmental Biochemistry at the ICBM, will be the start-up’s scientific mentor. The project will receive additional support from the university's Founding and Innovation Center (GIZ). The researchers are also collaborating with Tropic Marin AG, a seawater aquarium supplies company based in Hünenberg (Switzerland).
SciReef wants to propagate stony corals via natural reproduction
“We are delighted about the funding and hope to be able to build a sustainable company that will contribute to the protection of wild corals,” said Nietzer, the future managing director of SciReef. In addition to covering the personnel costs for three scientific and one administrative member of staff, the funding includes around 250,000 euros to cover material costs such as chemicals, equipment and consumables. With its EXIST programme, the BMWK supports innovative, sustainable spin-offs that involve high-risk resource development at universities and other research institutions.
SciReef’s goal is to propagate stony corals via their natural sexual reproduction process and then grow out the young corals in aquaria. Commercial production of corals using sexual propagation methods has not been possible to date, meaning that the trade in corals currently relies on the asexual fragmentation technique and wild harvesting, which can pose a problem for reefs at the local level. If the project succeeds, it could lead to the global coral trade becoming considerably more environmentally sustainable and less reliant on wild harvesting. To protect their reefs, many countries have imposed export restrictions which, together with the rising logistics costs, are making the coral trade increasingly expensive. An additional advantage of the sexual reproduction technique is that it allows the breeding of corals with specific characteristics, for example new colour variants that don’t occur in nature. Compared to fragmentation, the most commonly used method to produce corals, in which a large coral is split into a number of smaller ones, sexual reproduction leads to a much higher genetic diversity. Fragmented corals, on the other hand, are clones and thus identical to the original colony.
Oldenburg scientists were first in Germany to successfully breed stony corals via sexual reproduction
The researchers will build on the basic techniques developed in the course of their earlier research. A few years ago, they became the first team of scientists in Germany to successfully breed stony corals in the lab through sexual reproduction. The young corals thus produced are much better adapted to aquarium conditions than those imported from tropical oceans.
One critical aspect of the new production method envisaged by SciReef will be to improve the “settlement” process in which the free-swimming coral larvae attach to a solid substrate. The experts plan to use chemical compounds that prompt the larvae to settle on specially designed artificial substrates. Over the last 15 years the Environmental Biochemistry research group has been able to isolate and identify one such compound.
Another equally decisive factor will be finding ways to improve the conditions for the young corals’ development once they have settled, since they are particularly fragile at this early stage. To this end, SciReef plans to optimise key factors such as nutrition, lighting and the chemical composition of the water in the aquariums and inoculate the young corals with special microalgae in order to improve survival rates.
A female stony coral releases eggs into the water. Together with the sperm that the male coral also releases into the water, this process is the basis for the sexual reproduction of corals.
CREDIT
University of Oldenburg / Samuel Nietzer
A spawning stony coral Acropora. Thousands of small eggs float above the coral in the water.
CREDIT
University of Oldenburg / Mareen Möller
METHOD OF RESEARCH
Experimental study
SUBJECT OF RESEARCH
Animals
Unlocking the genetic secrets of Pterocarya hupehensis: a phylogeographic study on the impact of environmental changes and geographical barriers
MAXIMUM ACADEMIC PRESS
Environmental factors and geographical barriers have historically shaped species' genetic structures, with the Sino-Japanese Floristic Region and Sichuan Basin being key study areas. Research has highlighted the role of the Qinghai-Tibet Plateau uplift and East Asian monsoon on biodiversity, yet the dynamics of species around the Sichuan Basin during the Miocene climate change, and how species characteristics and geographic barriers affected their genetic patterns remains underexplored. Most phylogeographic studies focus on chloroplast DNA, overlooking pollen-mediated gene flow in wind-pollinated species like the conservation-concerned Pterocarya hupehensis. This gap underscores the need for studies incorporating species-specific traits and gene flow mechanisms to enhance our understanding of phylogeographic patterns.
To investigate the phylogeographic history of Pterocarya hupehensis, researchers employed cpDNA sequence variation analysis, RAD-seq reads for nuclear DNA analysis, and ecological niche modeling. The cpDNA analysis revealed 91 polymorphisms and 24 haplotypes across 17 populations. The phylogenetic network resolved two main haplotype lineages (western and eastern lineages) and a divergence dating back to the middle Miocene (16.7 Mya). RAD-seq analysis of 122 samples identified 2,889 SNPs. Admixture analysis revealed that the genetic structure of P. hupehensis consisted of two lineages and detected genetic introgression in five populations. The researchers further analyzed the population demographic histories by ML tree, and found two strong signals with a high migration weight, indicating unidirectional gene flow in populations. Ecological niche modeling suggested that P. hupehensis population expansion occurred during the last interglacial period and suitable area for P. hupehensis in the western and southern Sichuan Basin were predicted to shrink under global warming. In addition, the cpDNA data revealed further divergence of the eastern lineage compared to nuclear DNA, suggesting that pollen flow is more influential than seed flow in shaping genetic structure.
In summary, this study underscores the importance of considering both seed and pollen-mediated gene flows in understanding the phylogeographic patterns of wind-pollinated relict species, highlighting the role of historical climate changes and geographical barriers in shaping current genetic distributions. The findings emphasize the need for conservation efforts focused on both exsitu and in situ strategies to protect this vulnerable species amidst environmental changes and human activities.
1.Eastern China Conservation Centre for Wild Endangered Plant Resources, Shanghai Chenshan Botanical Garden, Shanghai 201602, China
2.College of Life Sciences, Shanghai Normal University, Shanghai 200234, China
3.Plant Phylogenetics and Conservation Group, Center for Integrative Conservation, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Kunming 650223, China
4.Southeast Asia Biodiversity Research Institute, Chinese Academy of Sciences, Naypyidaw 05282, Myanmar
5.College of Forestry and Biotechnology, Zhejiang A&F University, Hangzhou 311300, China
6.Department of Biology and Botanic Garden, University of Fribourg, Fribourg 1700, Switzerland
7.Natural History Museum Fribourg, Fribourg 1700, Switzerland
About Yi-Gang Song
Yi-Gang Song finished his PhD at the University of Fribourg (Department of Biology) and is now developing his research group at the Chenshan Plant Science Research Center of the Chinese Academy of Sciences in Shanghai, China. His main research interests are phylogeny, phylogeography and conservation biogeography of the genus Quercus (Fagaceae) and the genus Pterocarya (Juglandaceae). In the framework of the project Zelkova he is a tree expert and coordinator of the field work in China.