#Mitochondrial fragmentation

[blueoaknx]

Mitochondrial Dysfunction in Spinal Muscular Atrophy (SMA)

Introduction

Spinal Muscular Atrophy (SMA) is a severe neurodegenerative disorder that predominantly affects motor neurons, resulting in progressive muscle weakness and atrophy. The condition is caused by mutations in the survival motor neuron 1 (SMN1) gene, which leads to the loss of SMN protein, a critical factor for motor neuron survival. Although the primary defect lies in the motor neurons, increasing evidence suggests that mitochondrial dysfunction plays a pivotal role in the pathophysiology of SMA. Mitochondria, the powerhouse of the cell, are crucial for cellular energy production and regulation of various metabolic pathways. In the context of SMA, mitochondrial dysfunction has been linked to impaired cellular energy metabolism, oxidative stress, and neuronal death.

This article reviews the emerging role of mitochondrial dysfunction in SMA, examining its impact on motor neurons, the cellular processes involved, and the potential for mitochondrial-targeted therapies.

Mitochondrial Dysfunction in SMA: A Pathophysiological Overview

Mitochondria are essential organelles responsible for generating ATP through oxidative phosphorylation, controlling cellular metabolism, and mediating cell death mechanisms. In SMA, deficits in SMN protein affect multiple cellular pathways, including mitochondrial function. SMN is known to be involved in the biogenesis and maintenance of mitochondria. When its expression is reduced, mitochondrial dysfunction occurs in several ways, contributing to the progressive nature of SMA.

Impaired Mitochondrial Biogenesis

Mitochondrial biogenesis refers to the process by which new mitochondria are formed within cells. This process is tightly regulated by nuclear and mitochondrial signals, with the peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) being a key regulator of mitochondrial biogenesis. Studies in SMA models have shown that a reduction in SMN protein leads to downregulation of PGC-1α, resulting in decreased mitochondrial biogenesis. This reduced mitochondrial mass is particularly detrimental to motor neurons, which have high energy demands due to their long axonal projections and rapid neurotransmitter signaling.

Mitochondrial Dysfunction and ATP Production

Mitochondrial dysfunction in SMA results in decreased ATP production. ATP is required for essential cellular functions such as protein synthesis, ion transport, and maintaining membrane potential. In motor neurons, impaired ATP generation leads to cellular energy deficits that exacerbate neurodegeneration. Mitochondrial dysfunction also disrupts calcium homeostasis, as mitochondria play a central role in buffering intracellular calcium levels. Elevated intracellular calcium levels can activate enzymes that degrade cellular components, further contributing to cell death in motor neurons.

Oxidative Stress

One of the most significant consequences of mitochondrial dysfunction is the increased production of reactive oxygen species (ROS). Mitochondria are the main source of ROS in cells, and under normal conditions, the antioxidant defense systems neutralize these reactive molecules. However, in SMA, defective mitochondrial function leads to excessive ROS production, which overwhelms the cell’s ability to detoxify them. ROS are highly reactive and can damage cellular structures such as proteins, lipids, and DNA, ultimately contributing to oxidative stress and neuronal injury.

Mitochondrial Dynamics and Morphology

Mitochondrial morphology is highly dynamic, with the organelles undergoing fusion and fission events in response to cellular needs. In SMA, the balance between these processes is disrupted. Studies have shown that reduced SMN levels lead to an increase in mitochondrial fragmentation, a characteristic of mitochondrial dysfunction. Fragmented mitochondria are less efficient in energy production and more prone to damage. Additionally, the fragmented mitochondria in SMA models exhibit impaired mitochondrial transport along axons, further hindering motor neuron function.

Mitochondrial Quality Control

Mitochondrial quality control mechanisms, such as mitophagy, are critical for maintaining mitochondrial health. Mitophagy is the process by which damaged mitochondria are selectively degraded by autophagosomes. In SMA, defects in SMN protein affect the cellular machinery responsible for mitophagy, leading to the accumulation of dysfunctional mitochondria. This impairment in mitochondrial turnover accelerates neurodegeneration by allowing damaged mitochondria to persist, increasing oxidative stress, and triggering cellular apoptosis.

Mitochondrial Dysfunction in Different Types of SMA

SMA is classified into several types based on age of onset and severity, including Type I (Werdnig-Hoffmann disease), Type II, Type III, and Type IV. Mitochondrial dysfunction is observed in all types, but its extent varies depending on the severity of the disease.

SMA Type I

This is the most severe form of SMA, typically presenting in infants before six months of age. These children experience profound muscle weakness and may not survive beyond the first two years of life without intervention. In Type I, mitochondrial dysfunction is particularly pronounced, with severe mitochondrial fragmentation, impaired ATP production, and significant oxidative damage observed in motor neurons. The severity of mitochondrial dysfunction correlates with the extent of neurodegeneration in the spinal cord.

SMA Type II

Type II SMA presents later in infancy or early childhood, with affected individuals showing progressive muscle weakness but with a longer life expectancy compared to Type I. Mitochondrial dysfunction in Type II is still significant but less severe than in Type I. There is evidence of mitochondrial fragmentation and altered mitochondrial dynamics, but motor neurons in Type II patients may still retain some capacity for mitochondrial biogenesis and ATP production, contributing to the slower progression of the disease.

SMA Type III and IV

SMA Type III and IV are milder forms of the disease, with onset typically in childhood or adulthood. While mitochondrial dysfunction is present, it is less pronounced than in Type I and II. In these types, mitochondrial dynamics, ATP production, and oxidative stress are affected, but the clinical presentation is less severe, and individuals often experience a normal or near-normal life expectancy.

Conclusion

Mitochondrial dysfunction is a central feature of the pathophysiology of Spinal Muscular Atrophy (SMA). Reduced SMN protein leads to impaired mitochondrial biogenesis, altered mitochondrial dynamics, increased oxidative stress, and mitochondrial dysfunction. These defects contribute to the progressive degeneration of motor neurons and muscle weakness seen in SMA. Understanding the complex interplay between SMN deficiency and mitochondrial dysfunction provides valuable insights into the disease mechanisms and offers new avenues for therapeutic intervention. Mitochondrial-targeted approaches, including enhancing mitochondrial biogenesis, antioxidant therapy, and modulation of mitochondrial dynamics, hold promise for improving the quality of life and outcomes for SMA patients.

Ongoing research into mitochondrial dysfunction in SMA is crucial for identifying novel treatment strategies that can complement existing therapies and slow disease progression. As therapeutic options evolve, mitochondrial health will likely become an important consideration in the management of SMA, offering hope for more effective treatments in the future.

[coochiequeens]

Womens history just got richer.

When the deeply patriarchal Romans first encountered Celtic tribes living in modern-day France and Great Britain in the first century B.C.E., their reaction to the roles of the sexes was one of surprise and dismay. The tasks of men and women “have been exchanged, in a manner opposite to what obtains among us,” wrote one Roman historian.

New evidence from Celtic graves now confirms that at least one part of Britain was a woman’s world long before the Romans arrived—and for centuries afterward. One ancient British tribe known as the Durotriges based its family structure—and perhaps property inheritance—on kinship between mothers and daughters. Men, meanwhile, left home to live with their wives’ families, a practice known as matrilocality that has never been seen before in European prehistory.

The work, published today in Nature, helps explain why women in Iron Age Britain are often buried with high-status grave goods such as mirrors and even chariots, says Ludwig Maximilian University of Munich archaeologist Carola Metzner-Nebelsick, who was not involved with the research. “It’s a fantastic result,” she says. “It really helps explain the archaeological record.”

Ancient histories—not least Julius Caesar’s 50 B.C.E. account of invading Gaul—hinted at female empowerment among the Celts. “They wrote about it because they found it so weird,” says Trinity College Dublin geneticist Lara Cassidy.

Many modern historians assumed the accounts were exaggerated; they dismissed rich female graves from the time as outliers. But over the past few decades, archaeologists comparing burial practices at hundreds of Iron Age sites from Britain to Germany began to think there was a kernel of truth to the Roman reports.

The Durotriges cemeteries, located in the far south of England near the city of Bournemouth, offered a way for Cassidy and her team to investigate. Burials there began around 100 B.C.E., roughly 150 years before Roman forces invaded the island. Unusually for Iron Age Britain, the tribe didn’t cremate their dead. Instead they buried them close to home, in the hills surrounding their farmsteads.

Whereas men were laid to rest with a joint of meat and perhaps a pot containing a beverage to sustain them on their journey into the afterlife, Durotriges women are often found with elaborate offerings including mirrors, combs, jewelry, and even swords. “If you judge social status by burial goods, then female burials have vastly more than male,” says Bournemouth University archaeologist Miles Russell, a co-author of the new paper.

Over the past 4 years, researchers sequenced DNA from dozens of Durotriges skeletons in a set of cemeteries in Dorset, England. By matching identical fragments of genetic material from different individuals, they reconstructed a family tree that spanned six generations—many of whom were female descendants of a single female founder. Two-thirds of the people in the kin group buried in the cemetery shared a rare type of mitochondrial gene, a form of DNA inherited only from the mother, including some of the men who shared the same female ancestor.

Other genetic evidence from the Durotriges cemeteries pointed to matrilocality, showing that men joined the clan from other families. “Women are staying close to family and are embedded in the support network they’ve known since childhood,” Cassidy notes. “It’s the husband who’s coming in as a stranger and is dependent on the wife’s family.” Women were evidently a force to be reckoned with in this part of Iron Age Britain.

Archaeologists have found that members of Great Britain’s Durotriges tribe often buried women with more grave goods than men.Miles Russell/Bournemouth University

Such patterns could help explain finds elsewhere in the Celtic world, where women were sometimes buried with rich grave goods or even chariots. “We’re thinking this could have been quite widespread,” Cassidy says.

To gather further evidence, she and her colleagues re-examined previously published genomes from more than 150 sites in Britain and Europe stretching back to the Stone Age. Starting around 500 B.C.E., the diversity in people’s mitochondrial DNA declined, the team found, suggesting more of them shared the same female ancestors. There was no matching decline in the diversity of Y chromosomes, which are passed from fathers to sons.

That suggests communities across Britain were anchored by specific female lines, with men marrying in from outside. “The signal they see in [the Durotriges] case study can be reproduced in other British sites,” says Max Planck Institute for Evolutionary Anthropology archaeogeneticist Joscha Gretzinger, who was not involved with the work. “That’s quite a smoking gun.”

The study is part of a growing use of DNA to reconstruct genetic kinship in the deep past—and use it to shed light on the structure of past societies. University of Liverpool archaeologist Rachel Pope says the research is starting to highlight the wide variety of social organization people practiced in the past, something archaeology has hinted at over the past 2 decades.

Some of the earliest kinship studies using ancient DNA, for example, showed that Stone Age farmers in Britain and France living in the fifth millennium B.C.E. were organized patrilocally, with women leaving their homes to marry while men stayed put. The new data from Durotriges suggest that by the Iron Age, 4000 years later, something had shifted. “This is quite exciting,” Pope says. “There are moments in time in which societies seem to have a lot of high female status.”

[herpsandbirds]

Convergent evolution of Amphidromus-like colourful arboreal snails and phylogenetic relationship of East Asian camaenids, with description of a new Aegistohadra species

Parin Jirapatrasilp, Chih-Wei Huang, Chung-Chi Hwang, Chirasak Sutcharit and Chi-Tse Lee

ABSTRACT

East Asian terrestrial snails of the family Camaenidae are diverse in terms of genus and species numbers, shell morphology and mode of living. This family also includes colourful conical arboreal snails that traditionally have been assigned to the genus Amphidromus. Yet, the present study shows that, despite their deceiving conchological similarity, some of these East Asian arboreal snails do not belong to the genus Amphidromus or the subfamily Camaeninae. The presence of a dart complex comprising a mucous gland, a dart sac, an accessory sac and a proximal accessory sac, along with a pronounced penial caecum and molecular phylogenetic analyses revealed that former ‘Amphidromus’ dautzenbergi, ‘A.’ roemeri and ‘Camaena’ mirifica, and one additional new species belong to Aegistohadra (subfamily Bradybaeninae).  Aegistohadra dautzenbergi, comb. nov. and Aegistohadra roemeri, comb. nov. are conical with colourful spiral bands, whereas Aegistohadra mirifica, comb. nov. and Aegistohadra zhangdanae, sp. nov. are heliciform to conical with colourful, variegated spiral and transverse banding patterns. DNA sequence analyses also revealed that each variety of Aegistohadra dautzenbergi could not be differentiated by mitochondrial (cytochrome c oxidase subunit I and 16S rRNA) gene fragments. The phylogenetic position of Aegistohadra within the East Asian camaenids revealed that the similar appearance in shell morphology, microhabitat use and diet to arboreal snails in the genus Amphidromus is homoplastic. Moreover, the presence or absence of a dart complex is also homoplastic and is unsuitable for suprageneric classification. By contrast, the presence of a flagellum and a penial caecum is useful for the suprageneric classification.

Read the paper here:

CSIRO PUBLISHING | Invertebrate Systematics

[darkmaga-returns]

Story at-a-glance

The term Electromagnetic Radiation (EMR) Syndrome is gaining recognition to better describe the symptoms — like headaches, dizziness, and fatigue — linked to electromagnetic fields (EMFs), which millions of people experience today

This growing recognition of EMR Syndrome is shifting the focus from blaming affected individuals to addressing the health risks of wireless radiation. Advocates push for safer technology and policy changes

Individuals affected by EMR Syndrome suffer from severe symptoms like cognitive issues, sleep disturbances, and heart problems, often leading to isolation and lifestyle adjustments to reduce exposure

Researchers link EMFs to mitochondrial damage, DNA fragmentation, and neurological issues. Studies suggest prolonged exposure contributes to chronic diseases, reproductive health problems, and even cancer

Using wired internet connections, avoiding smart appliances, disabling Wi-Fi at night, and minimizing cellphone use are strategies that help protect against EMF-related health effects

[typhlonectes]

A remarkable new deep-sea nereidid (Annelida: Nereididae) with gills

Tulio F. Villalobos-Guerrero,Sonja Huč,Ekin Tilic,Avery S. Hiley,Greg W. Rouse

Abstract

Nereidid polychaetes are well known from shallow marine habitats, but their diversity in the deep sea is poorly known. Here we describe an unusual new nereidid species found at methane seeps off the Pacific coast of Costa Rica. Specimens of Pectinereis strickrotti gen. nov., sp. nov. had been observed dating back to 2009 swimming just above the seafloor at ~1,000 m depth but were not successfully captured until 2018. Male epitokes were collected as well as a fragment of an infaunal female found in a pushcore sample. The specimens were all confirmed as the same species based on mitochondrial COI. Phylogenetic analyses, including one based on available whole mitochondrial genomes for nereidids, revealed no close relative, allowing for the placement of the new species in its own genus within the subfamily Nereidinae. This was supported by the unusual non-reproductive and epitokous morphology, including parapodial cirrostyles as pectinate gills, hooked aciculae, elfin-shoe-shaped ventral cirrophores, and elongate, fusiform dorsal ligules emerging sub-medially to enlarged cirrophores. Additionally, the gill-bearing subfamily Dendronereidinae, generally regarded as a junior synonym of Gymnonereidinae, is reviewed and it is here reinstated and as a monogeneric taxon.

Read the paper here:

A remarkable new deep-sea nereidid (Annelida: Nereididae) with gills | PLOS ONE

[girldickman]

This is probably the biggest news in paleontology to come out in a while.

Previously, the only remains we had of this group of humans were some teeth, a partial jawbone, and a fragment of a finger bone. But through examining its mitochondrial DNA, we were able to identify them as a group of humans distinct from Homo Sapiens and Homo Neanderthalensis. Unfortunately, the remains we had were not enough to give it a formal taxonomy.

Cut to 2018, and a worker in China hands in a fossil skull to some scientists, claiming that his grandfather had found it in the 1930's and didn't tell anyone until his death. In 2021, it was identified as a distinct human species and named Homo Longi, or Dragon Man.

This year, another study was done on the Homo Longi skull, looking for DNA. The study was able to find some mitochondrial DNA, revealing that the Homo Longi skull was actually that of a Denisovan.

Now that we have a more complete specimen, I think it will be easier for us to identify remains in the future. I'm also expecting a small debate over whether the species should remain Homo Longi or be called something else, but I think it will end up remaining Homo Longi.

See below for an article on this

[dertaglichedan]

Blood test could detect Parkinson’s disease before symptoms emerge

Researchers have developed a simple and “cost-effective” blood test capable of detecting Parkinson’s disease long before symptoms emerge, according to a study.

About 153,000 people live with Parkinson’s in the UK, and scientists who undertook the research said the test could “revolutionise” an early diagnosis of Parkinson’s disease, “paving the way for timely interventions and improved patient outcomes”.

Parkinson’s is a progressive neurological condition in which nerve cells in the brain are lost over time. This leads to a reduction of the chemical dopamine which plays an important part in controlling movement.

This new test, which the Times reports costs £80, analyses small pieces of genetic material known as transfer RNA fragments (tRFs) in the blood, focusing on a repetitive RNA sequence that accumulates in Parkinson’s patients.

It also looks at a parallel decline in mitochondrial RNA, which deteriorates as the disease progresses. Mitochondria exist inside cells and generate energy.

By measuring the ratio between these biomarkers, researchers said the test “offers a highly accurate, non-invasive, rapid and affordable diagnostic tool, providing hope for early interventions and treatments that could change the course of the disease”.

On a scale where a score of 1 indicates a perfect test while 0.5 shows the test is no better than flipping a coin, the test scored 0.86, the Times reported.

The best clinical tests presently used on patients showing early signs of the disease scored 0.73, according to the study published in the journal Nature Aging.

The test uses the same PCR technology used during the pandemic to confirm Covid cases. It works by amplifying the genetic material being targeted, which allows it to be detected.

“This discovery represents a major advancement in our understanding of Parkinson’s disease and offers a simple, minimally invasive blood test as a tool for early diagnosis,” said Prof Hermona Soreq of the Hebrew University of Jerusalem, who supervised the study. “By focusing on tRFs, we’ve opened a new window into the molecular changes that occur in the earliest stages of the disease.”

Prof David Dexter, director of research at Parkinson’s UK, said: “This research represents a new angle to explore in the search for a biological marker for Parkinson’s. In this case the marker can be identified and measured in the blood which makes it attractive for a future patient-friendly diagnostic test for Parkinson’s.

“More work is needed to continue to test and validate this possible test, especially understanding how it can distinguish between other conditions that have similar early signs to Parkinson’s.”

[geneticteacher123]

DNA fingerprinting techniques: (RFLP markers use to analyze variation and location of restriction sites) + ( AFLP markers use to analyze specific fragments of genomic DNA) + (STR markers use to analyze short repeat sequence 4 to 6 base pairs) + (VNTR markers use to analyze longer repeat sequence 10 to 100 base pairs) + (SNP markers use to examine single nucleotide variation at specific positions in genome in form of allele specific oligonucleotides) + (Mitochondrial DNA use to track maternal lineages) + (Y-chromosome use to track paternal lineages) + (Whole Genome Sequencing use to generate highly comprehensive informative genetic profile) (Watch Related Video in #geneticteacher) #geneticteacher

[blueoaknx]

Mitochondrial Dysfunction in Cardiovascular Disease

 Introduction

Mitochondria are essential organelles responsible for the production of cellular energy in the form of adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). The heart, due to its continuous contractile activity, has a high energy demand and is critically dependent on mitochondrial function for normal physiological and pathological processes. Mitochondrial dysfunction has emerged as a central mechanism in the pathogenesis of cardiovascular diseases (CVDs), including ischemic heart disease, heart failure, hypertension, and arrhythmias. This technical overview discusses the molecular mechanisms of mitochondrial dysfunction in cardiovascular disease, its impact on cellular and organ function, and the potential therapeutic strategies to mitigate mitochondrial-related pathophysiology in CVDs.

Mitochondrial Function in Cardiovascular Cells

Mitochondria are highly dynamic organelles that perform several key functions crucial for the health of cardiovascular cells. They are involved in:

ATP Production via Oxidative Phosphorylation: In the mitochondria, energy production is driven by the electron transport chain (ETC), which is composed of complex I-IV embedded in the inner mitochondrial membrane. Electrons derived from NADH and FADH2 produced during the citric acid cycle are transferred through these complexes to ultimately reduce oxygen to water at complex IV. This electron transfer drives proton pumps that create an electrochemical gradient (proton motive force) across the inner mitochondrial membrane, which is utilized by ATP synthase (complex V) to produce ATP.

Calcium Homeostasis: Mitochondria play a crucial role in buffering intracellular calcium concentrations. They take up calcium from the cytoplasm in response to cellular signaling and help maintain cellular homeostasis by storing calcium in the matrix and releasing it when required for cellular signaling. Dysregulation of mitochondrial calcium handling can lead to pathophysiological conditions such as mitochondrial permeability transition (MPT) and cell death.

Reactive Oxygen Species (ROS) Production: Mitochondria are the primary source of ROS due to the incomplete reduction of oxygen molecules during electron transport in the ETC. Under normal conditions, low levels of ROS act as signaling molecules. However, excessive ROS generation due to mitochondrial dysfunction can cause oxidative stress, which damages cellular components such as lipids, proteins, and mitochondrial DNA (mtDNA), contributing to the pathogenesis of cardiovascular diseases.

Apoptosis and Cell Death: Mitochondria are central regulators of apoptosis. The release of pro-apoptotic factors such as cytochrome c from the mitochondrial intermembrane space into the cytoplasm triggers caspase activation, leading to programmed cell death. Mitochondrial dysfunction in cardiovascular tissues can lead to inappropriate cell death, contributing to the progression of CVDs.

Molecular Mechanisms of Mitochondrial Dysfunction in Cardiovascular Disease

Mitochondrial dysfunction in cardiovascular disease can result from several factors, including oxidative damage, altered mitochondrial dynamics, mutations in mitochondrial DNA, and defects in mitochondrial signaling. Below are the primary molecular mechanisms contributing to mitochondrial dysfunction in cardiovascular pathologies:

1. Oxidative Stress and ROS Accumulation

Excessive ROS generation is a hallmark of mitochondrial dysfunction and a major contributor to cardiovascular disease progression. Under normal conditions, the ETC produces ROS as a byproduct of electron transfer; however, under pathological conditions such as ischemia, hypoxia, or heart failure, there is an increase in mitochondrial ROS production. This increase is due to the altered electron flow through the ETC, particularly at complex I and III, which results in the incomplete reduction of oxygen.

The accumulation of ROS causes oxidative damage to mitochondrial lipids, proteins, and mtDNA. For instance, lipid peroxidation of mitochondrial membranes leads to membrane destabilization and disruption of mitochondrial function. ROS also modify proteins involved in mitochondrial dynamics and bioenergetics, impairing the capacity of mitochondria to generate ATP. Furthermore, oxidative damage to mtDNA leads to mutations that compromise the mitochondrial respiratory chain complexes, creating a vicious cycle of mitochondrial dysfunction.

2. Mitochondrial Permeability Transition (MPT) and Calcium Overload

Mitochondrial permeability transition is a critical event in mitochondrial dysfunction. The opening of the mitochondrial permeability transition pore (mPTP) occurs when the inner mitochondrial membrane becomes permeable to ions and small molecules, disrupting the electrochemical gradient required for ATP production. Under pathological conditions such as ischemia-reperfusion injury, excessive ROS and calcium overload activate the mPTP, leading to mitochondrial swelling, loss of membrane potential, and the release of pro-apoptotic factors (e.g., cytochrome c), triggering cell death.

Calcium overload plays a significant role in mitochondrial dysfunction. During stress conditions like ischemia, excessive intracellular calcium is taken up by mitochondria, causing mitochondrial matrix expansion and rupture of the mitochondrial membrane. This exacerbates cellular injury and promotes cell death pathways in the myocardium, contributing to myocardial infarction and heart failure.

3. Mitochondrial Dynamics Dysregulation

Mitochondrial dynamics refer to the continuous processes of mitochondrial fusion and fission that maintain mitochondrial quality and function. In response to cellular stress, mitochondria can undergo fission to segregate damaged components or fusion to promote functional compensation. Mitochondrial fission is regulated by dynamin-related protein 1 (DRP1), while fusion is mediated by mitofusins (MFN1 and MFN2) and optic atrophy 1 (OPA1). In cardiovascular diseases, this dynamic balance is often disrupted, leading to mitochondrial fragmentation, reduced mitochondrial function, and increased susceptibility to apoptosis.

In heart failure, for example, the upregulation of DRP1 and downregulation of fusion proteins contribute to mitochondrial fragmentation, reduced ATP production, and elevated ROS levels. This dysfunction is exacerbated by altered signaling pathways, including those associated with autophagy (mitophagy), which is responsible for removing damaged mitochondria. Dysfunctional mitophagy further impairs mitochondrial quality control, worsening cardiac injury.

4. Mitochondrial DNA Mutations

Mitochondrial DNA is more prone to mutations than nuclear DNA due to its proximity to the ETC and lack of protective histones. In cardiovascular diseases, mutations in mtDNA contribute to defective mitochondrial function. For example, mutations in genes encoding subunits of the OXPHOS complexes (such as ATP6, ND1, or CYTB) lead to impaired ATP synthesis and defective mitochondrial bioenergetics, contributing to myocardial ischemia and heart failure.

Mitochondrial mutations may also affect the regulation of ROS production and the activation of apoptotic pathways, accelerating tissue damage and organ dysfunction.

Therapeutic Approaches Targeting Mitochondrial Dysfunction in Cardiovascular Disease

Given the critical role of mitochondria in cardiovascular disease, several therapeutic strategies have been developed to target mitochondrial dysfunction and restore normal mitochondrial function. These include:

1. Mitochondrial Antioxidants

Mitochondrial-targeted antioxidants, such as MitoQ, MitoTEMPO, and SkQ1, have been developed to specifically target ROS within mitochondria. These compounds aim to reduce oxidative stress, limit mitochondrial damage, and improve mitochondrial function. Clinical studies are ongoing to assess the efficacy of these antioxidants in reducing myocardial injury and improving outcomes in heart failure and ischemic heart disease.

2. Mitochondrial Biogenesis Activation

Stimulating mitochondrial biogenesis to increase the number of functional mitochondria is another potential therapeutic strategy. Activators of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a key regulator of mitochondrial biogenesis, are being investigated as potential treatments for heart failure. Exercise training is a natural way to activate PGC-1α and increase mitochondrial function, which has been shown to improve cardiac outcomes in patients with heart failure.

3. MPTP Inhibition

Inhibitors of the mPTP, such as cyclosporine A, have been studied for their potential to prevent ischemia-reperfusion injury by inhibiting pore opening. By preserving mitochondrial integrity, these inhibitors may help reduce myocardial damage and improve survival after myocardial infarction.

4. Gene Therapy and Mitochondrial Transplantation

Gene therapy approaches, including the use of CRISPR/Cas9 to correct mitochondrial DNA mutations, hold promise in treating mitochondrial diseases. Additionally, mitochondrial transplantation, where healthy mitochondria are delivered to damaged cardiac cells, is an emerging area of research, with the potential to restore mitochondrial function and improve heart function in patients with severe myocardial injury.

Conclusion

Mitochondrial dysfunction plays a central role in the pathogenesis of cardiovascular diseases, contributing to impaired ATP production, increased ROS production, and cell death. Understanding the molecular mechanisms underlying mitochondrial dysfunction provides critical insights into the development of novel therapeutic strategies. Approaches targeting mitochondrial biogenesis, oxidative stress, mitochondrial dynamics, and mPTP inhibition offer promising avenues for the treatment of cardiovascular diseases and could lead to more effective management of conditions such as heart failure, ischemic heart disease, and hypertension. However, further research and clinical trials are needed to fully elucidate the potential of these therapeutic strategies in improving cardiovascular health.

[evoldir]

Fwd: Graduate position: ArkansasStateU.EvolutionaryGenomics

Begin forwarded message: > From: evoldir@evol.biology.mcmaster.ca > Subject: Graduate position: ArkansasStateU.EvolutionaryGenomics > Date: 30 October 2024 at 04:11:16 GMT > To: rdmpage@gmail.com > > > The Sweet Lab at Arkansas State University is recruiting a PhD > student to work on an NSF-funded project that seeks to understand the > evolution of fragmented mitochondrial genomes in parasitic lice. The > student will use molecular and bioinformatic approaches to address > hypotheses related to genomic evolution, mito-nuclear coevolution, and > phylogenetics. The student will also be part of a collaborative team that > includes researchers from Arkansas State, the University of Illinois, > and Purdue University. Funding is available in the form of a Research > Assistantship for at least two years and Teaching Assistantships for > the remaining time in the program. > > Arkansas State offers a Ph.D. program in Molecular Biosciences > (https://ift.tt/c9ay7In). > Applicants who are citizens or permanent residents of the U.S. are > also eligible to apply to be funded as a trainee in the UandI-DEECoDE > program, which provides access to funds for travel and a one-year > stipend. UandI-DEECoDE (pronounced “You and I decode”), which > stands for Understanding Invasion and Disease Ecology and Evolution > through Computational Data Education, is a research traineeship that > aims to address the absence of interdisciplinarity across invasion > biology, disease ecology, and data science by effectively bridging these > disciplines and improving the pace and magnitude of scientific discovery > across these fields (https://ift.tt/N1lsLc9). > > Qualifications: Applicants should have a B.S. degree in biology, > bioinformatics, evolutionary biology, or a related field. Competitive > applicants will also have experience with a programming language (Python, > Perl, R, etc.), bioinformatics (phylogenetics, molecular evolution, etc.), > and/or basic molecular lab skills (DNA extractions, PCR, etc.). An M.S. in > evolutionary biology, bioinformatics, or a related field is preferred > but not required. GRE scores are preferred, but not absolutely required > for admission into the graduate program. > > Application: To apply, please send the following materials to Dr. Drew > Sweet (asweet@astate.edu) with the subject line “PhD application”: > 1) a one-page cover letter detailing your interest in the position, 2) > CV, 3) unofficial transcripts, 4) a writing sample (if possible), and 5) > contact information for three professional references. > > Deadline: January 1, 2025 > > Please send any questions about the position to asweet@astate.edu. > > > > Andrew D. Sweet, Ph.D. > Assistant Professor of Evolutionary Biology > Department of Biological Sciences > Arkansas State University > Jonesboro, AR USA > Website: https://ift.tt/RBgGM5k > > > > asweet@astate.edu > > (to subscribe/unsubscribe the EvolDir send mail to > golding@mcmaster.ca

[willyskristina]

Apoptosis Assays Market

Apoptosis Assays Market Size, Share, Trends: Thermo Fisher Scientific Inc. Leads

Shift Towards Multiplexed and High-Throughput Apoptosis Assays for Comprehensive Cell Death Analysis

Market Overview:

The global apoptosis assays market is expected to develop at a CAGR of 8.2% between 2024 and 2031. North America now dominates the market, accounting for over 35% of total worldwide share. Key metrics include the expanding prevalence of chronic diseases, increased R&D investments in drug discovery, and the growing use of high-throughput screening techniques.

The Apoptosis Assays Market is expanding rapidly, owing to a growing emphasis on personalised treatment and increased need for targeted cancer medicines. The market is seeing an increase in technological improvements, particularly in flow cytometry and high-content screening technologies, which improve the accuracy and efficiency of apoptosis detection. Furthermore, the rising uses of apoptosis tests in stem cell research and regenerative medicine are creating new opportunities for market growth.

DOWNLOAD FREE SAMPLE

Market Trends:

The Apoptosis Assays Market is seeing a substantial shift towards multiplexed and high-throughput assays, driven by the need for more thorough and efficient cell death studies. This shift allows researchers to assess several apoptotic characteristics, such as caspase activation, mitochondrial membrane potential, and DNA fragmentation, in a single experiment. The use of sophisticated assays is especially prevalent in drug discovery and development processes, where rapid and reliable screening of vast chemical libraries is essential.

For example, a recent study in the Journal of Biomolecular Screening found that using multiplexed apoptosis assays in high-throughput screening campaigns resulted in a 40% reduction in false positives when compared to standard single-parameter assays. This increase in accuracy and efficiency is fuelling demand for multiplexed apoptosis assay kits and reagents. Furthermore, the use of artificial intelligence and machine learning algorithms in data analysis improves the interpretation of complicated apoptotic information, allowing researchers to detect subtle trends and prospective treatment candidates more efficiently.

The move towards multiplexed and high-throughput apoptosis testing is encouraging collaborations between academic institutions and pharmaceutical businesses. These collaborations aim to create new test formats and broaden the usage of apoptosis assays in fields like immunology and neurodegenerative disease research. As a result, the market is seeing a boom in product innovation, with several major manufacturers releasing next-generation apoptosis detection platforms with higher sensitivity, repeatability, and throughput.

Market Segmentation:

Caspase assays dominate the Apoptosis Assays Market, accounting for approximately 40% of the market share in 2023. Caspase assays have emerged as the leading sector in the Apoptosis Assays Market, owing to their high specificity and sensitivity in detecting important hallmarks of programmed cell death. These assays are essential for a variety of applications, including drug development, toxicity assessment, and fundamental cell biology research. Caspase assays dominate because of their versatility in detecting both early and late phases of apoptosis, as well as their compatibility with a variety of detection platforms.

Recent advances in caspase assay technologies have strengthened their commercial position. For example, the advent of real-time caspase assays has allowed researchers to track apoptosis dynamics in live cells, providing important insights into the temporal features of cell death. A study published in Nature Methods found that real-time caspase tests might identify apoptosis initiation up to 4 hours sooner than standard end-point assays, considerably increasing the sensitivity of drug screening programs.

The pharmaceutical sector has been a major driver of the caspase assays segment, with a growing number of drug discovery programs including these assays into their screening processes. Over 60% of oncology drug discovery projects currently use caspase-based assays in their early-stage chemical screening processes, according to Biotechnology Innovation Organisation (BIO) research. The importance of apoptosis in cancer progression, as well as the possibility of caspase-targeted medicines in cancer treatment, are driving this widespread acceptance. Furthermore, the combination of caspase assays and high-content imaging systems has created new opportunities for multiplexed investigation of apoptotic processes. Leading life science businesses reported a 30% year-over-year increase in multiplexed caspase assay kit sales, indicating a growing demand for complete apoptosis profiling in university and industrial research contexts. This tendency is projected to continue driving the caspase assays segment further in the coming years.

Market Key Players:

Thermo Fisher Scientific Inc.

Merck KGaA

Bio-Rad Laboratories, Inc.

Becton, Dickinson and Company

Abcam plc

Promega Corporation

Contact Us:

Name: Hari Krishna

Email us: hari.krishna@aurorawaveintellects.com

Website: https://aurorawaveintellects.com/

[anumberofhobbies]

Introduction Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystem disease that is often characterized by postexertional malaise (PEM);1,2 even minor activity can cause the patient to experience a 'crash' in physical and/or mental energy. However, symptoms experienced by these patients fall along a broad spectrum ranging from mild to severe (e.g., bedridden). Therefore, to properly diagnose the patient as having ME/CFS, a clinician refers to a checklist of conditions specific to the disease such as those outlined in the Canadian Consensus Criteria (CCC).3 For example, the CCC considers a patient to have ME/CFS if they present with symptoms of reduced energy levels, PEM, interrupted sleep patterns, muscle pain and weakness, as well as two or more autonomic, neuroendocrine, and immune manifestations.

Since the 1980s, there has been considerable research comparing healthy controls and patients with ME/CFS where several abnormalities of the autonomic and central nervous system (CNS) have been correlated with positron emission tomography studies, revealing vast neuroinflammation.4 Oxidative stress has also been linked to ME/CFS,5 which may negatively impact the metabolic and immune systems, as well as contribute to increased blood–brain barrier (BBB) permeability6 allowing the passage of larger blood components including antibodies (Abs) and other immune cells into the CNS.7

Autoimmunity, which has been reported in people with ME/CFS,8 results from diminished self-tolerance where more self-antigens are seen as foreign substrates. For example, fatigue, which is correlated with PEM in ME/CFS, occurs as a major symptom in other autoimmune, mitochondrial, and infectious diseases;9,10 therefore, PEM in ME/CFS may be the result of poor self-tolerance combined with microbial exposure involving molecular mimicry.11−13

Symptoms of ME/CFS also overlap with those of other autoimmune diseases, in particular, multiple sclerosis (MS).14 MS is an inflammatory disease of the CNS primarily characterized by demyelination, which is the breakdown of the myelin sheath, leading to impaired signal transmission along the axon.15 Here, myelin basic protein (MBP), which maintains the integrity of the myelin sheath in the healthy CNS, dissociates from the membrane during citrullination.16 As a consequence, MBP and its fragments are then free to enter the cytoplasm, general blood supply,17 and cerebral spinal fluid where they can trigger an autoimmune response.

Demyelination may also be a common denominator with ME/CFS where some patients experience symptoms of muscle pain and weakness as a results of diminished nerve function.18 To strengthen this idea, there are several reports of abnormal brain magnetic resonance imagining (MRI) studies in patients with ME/CFS.19−25 Based on images with white/gray matter hyperintensities and cerebral atrophy, Cook et al. found that ME/CFS patients had a higher level of physical impairment (motor and cognitive functions) compared to patients with normal MRI scans.26,27 Furthermore, there is a growing body of literature on COVID-related research postpandemic (e.g., Long-COVID) that makes a strong connection to ME/CFS;28 this suggests that COVID-19 infection may act as a precursor/trigger for ME/CFS. Demyelination in particular, which has been reported numerous times in cases of COVID-19,29−32 may play a larger role in neurological-related symptoms in patients recently diagnosed with ME/CFS.

[dickgreyson]

hey since you're in med school do you want to help me learn about obligate intercellular pathogens /j (don't take this seriously I'm just suffering)

Suffering w u babe im one nighting my review paper abt mitochondrial dysfunction causing dna fragmentation in geriatric oocytes leading to chromosomal nondisjunction

[thisisnotwhathappens]

Okay so this whole thread is a goldmine. But I've got to insert my favorite bit of hominin knowledge.

Have y'all heard of Denny? Denny, or Denisova 11, is a 90,000 year old 13 year old girl found in Denisova Cave in the Altai Mountains of Russia! What makes her so fascinating is that we were able to extract mtDNA from her (mitochondrial DNA is the DNA transmitted from your matriline, and it preserves better than nuclear DNA). Her mother was a Neanderthal, and her father was a Denisovan, a really mysterious group of hominins that we only really have tooth fragments of! Her dad also had a bit of neanderthal ancestry of his own, charting back something like 300-600 generations back. One of the people who helped discover this was Svante Pääbo, a bisexual man, who won the 2022 Nobel Prize in physiology or medicine for his contributions to understanding extinct hominin genomes and human evolution! The other scientist was Vivianne Slon! I'd have to re-read the papers to go into a further analysis about how this links, but it's such a cool bit of human evolution that I had to chime in!

Do we have data on whether the earliest modern human x neanderthal crosses were more commonly produced by a neanderthal man and sapiens sapiens woman, or vice versa?

Do we have some neanderthal woman to blame for the species' apparent instinct to see a weirdly long lanky skinny frail man and instantly get the urge to mount him?

[geneticteacher123]

DNA fingerprinting or DNA Typing or DNA Profiling or DNA Testing Determine variation among individuals at DNA level on principle of polymorphism of DNA sequences to compare samples (Match or mismatch) such as paternity test and criminal scene, Steps of DNA fingerprinting initiate by collect samples for DNA extraction to proceed polymerase chain reaction and gel electrophoresis for bands visualization to compare matching bands, DNA fingerprinting techniques: (RFLP markers use to analyze variation and location of restriction sites) + ( AFLP markers use to analyze specific fragments of genomic DNA) + (STR markers use to analyze short repeat sequence 4 to 6 base pairs) + (VNTR markers use to analyze longer repeat sequence 10 to 100 base pairs) + (SNP markers use to examine single nucleotide variation at specific positions in genome in form of allele specific oligonucleotides) + (Mitochondrial DNA use to track maternal lineages) + (Y-chromosome use to track paternal lineages) + (Whole Genome Sequencing use to generate highly comprehensive informative genetic profile), In example of paternity test child band match father band and mismatch mother band, Child inheritance from father and mother: If father heterozygous at locus A and homozygous and locus B and mother heterozygous at each locus A and B hence child combine one allele from each parent, Example of criminal scene: if DNA profile of crime scene match suspect strong evidence that suspect was present at crime scene while if DNA profile of crime scene doesn't match suspect may be eliminate from enquiry, DNA fingerprinting use in paternity test and criminal investigations and disease identification and anthropology studies and agriculture and livestock breeding and quality control in biotechnology (Watch Related Video in #geneticteacher) #geneticteacher

[bromatologist]

Father’s Pre-Conception Diet Influences Offspring’s Health

Research led by German Research Center for Environmental Health (GmbH) in Neuherberg, Germany found that a father's diet before conception can affect their children's health. Using data from over 3,000 families and experiments with mice, they discovered that sperm exposed to a high-fat diet influenced offspring's susceptibility to metabolic diseases. The study highlights the role of paternal health in child development and suggests the need for preventive health care for men before conception.