This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"In Wolfram syndrome (WFS), intracellular endoplasmic reticulum stress and reduced levels of the protein wolframin lead to diabetes and neurodegeneration. In addition, deficiency of the wolframin-encoding gene, WFS1, is known to disrupt calcium balance and change mitochondrial dynamics. Unfortunately, there is no effective treatment for WFS, but better characterization of its mechanisms might aid in therapy development. To further investigate WFS, a recent study analyzed the mRNA transcript and protein profiles in a human cell WFS model. The levels of proteins in various signaling pathways differed between the WFS cells and normal control cells. For example, proteins involved in oxidative phosphorylation, the major energy-producing pathway in mitochondria, were downregulated in the WFS cells. while proteins in other energy generation pathways were upregulated..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"New research published in the journal Anesthesiology provides fresh insights into how volatile anesthetics affect the central nervous system. Although anesthesia has been practiced for nearly 75 years, the precise cellular mechanisms driving anesthetic responses have remained ambiguous. Recent reports suggest mitochondria have a key role in the process, but prior research has only studied this connection in neurons. Now, researchers argue that astrocytes are also important, particularly when it comes to emergence from anesthesia. To reach this conclusion, the team produced a novel knockout mouse lacking the mitochondrial complex I gene known as Ndufs4. In the model, gene knockout is induced only in astrocytes of adult animals – the other cell types comprising the central nervous system retain functional copes of the gene. The result is astrocyte-specific mitochondrial dysfunction..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Synovitis is one of the most common and serious musculoskeletal diseases in horses, causing osteoarthritis and lameness. While available pharmaceutical treatments can reduce joint pain and inflammation, they are expensive and unable to prevent disease progression. Recently, researchers have started looking toward fibroblast-like synoviocytes (FLS) for the development of new treatment options. FLS are cells that produce lubricating proteins to protect cartilage from injury, But they lose their protective features and begin to produce inflammatory chemicals in horses with synovitis and ultimately cause the failure of the FLS mitochondrial machinery, cell death, and joint degeneration. A team of researchers thus transferred healthy mitochondria from immune cells into FLS to determine whether doing so could restore FLS function. They found decreases in cell proliferation and death after mitochondrial transfer as well as a reduction in the production of inflammatory proteins..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Stroke is the leading cause of death worldwide. Scientists are finding that mitochondrial abnormalities play a central role in stroke. A recent study suggests that deactivating the protein SIAH2 could help mitochondria and the brain cells they power survive stroke in mice. Oxygen deprivation, which makes stroke fatal, activates SIAH2. Once activated, SIAH2 signals the breakdown of mitochondrial and cellular proteins key to survival. Aiming to curb this damage, researchers switched off the gene controlling SIAH2 formation in mouse neurons. and observed what happened after artificially inducing stroke. They found that without SIAH2, neurons suffered low damage during stroke. preserving the machinery that keeps mitochondria alive and well. Understanding how this switch operates in humans is crucial. as it could lead to drugs that target SIAH2 and help reduce the mortality of stroke..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Notch signaling is the key to many binary decisions metazoan cells make during development. Downstream signals from Notch trigger transcriptional remodeling that resolves dichotomies like differentiation between developmental cell fates. In the "Notch on" state, the Notch intracellular domain (NICD) relocates to the nucleus and binds to the protein RBPJ. While Notch activation is well studied, the transition to the "Notch off" state, where NICD and RBPJ dissociate, is not well understood. Recent research using phylogenetic analysis, computational biochemistry, and in vitro experiments suggests that heat flux is an important regulator of Notch signaling. The researchers determined that NICD senses temperature changes through its ankyrin domain. The ankyrin domain is highly conserved across species and contains β-hairpins enriched for charged amino acids. These charged amino acids amplify destabilizing electrostatic interactions, making the domain vulnerable to heat destruction..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

In this project, you will explore a real-world problem, and then work through a series of steps to analyze that problem, research ways the problem could be solved, then propose a possible solution to that problem. Often, there are no specific right or wrong solutions, but sometimes one particular solution may be better than others. The key is making sure you fully understand the problem, have researched some possible solutions, and have proposed the solution that you can support with information / evidence.Begin by reading the problem statement in Step 1. Take the time to review all the information provided in the statement, including exploring the websites, videos and / or articles that are linked. Then work on steps 2 through 8 to complete this problem-based learning experience.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Metabolic syndrome is becoming increasingly common among humans and domestic animals and is thought to be linked to dysfunction in adipose tissue components, including adipose progenitor stem cells (ASCs). The proteins PTP1B and LMPTP have been implicated in the development of metabolic disorders, but their roles in adipogenic differentiation of ASCs and modulation of mitochondrial dynamics in these cells remain unclear. To clarify this issue, a recent study treated ASCs from metabolically impaired horses with PTP1B and LMPTP inhibitors in vitro. Both selective inhibitors enhanced the differentiation of ASCs into adipose cells and increased the expression of PPARγ, a master adipogenesis regulator, while the LMPTP inhibitor increased the expression of adiponectin, which helps protect against metabolic disorders. The compounds also improved antioxidant defense and altered mitochondrial bioenergetics..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"The human protein Tid-1 sits at the nexus of many key cellular processes and signaling pathways. These processes include cellular proliferation, growth, survival, aging, apoptosis, and even movement. Tid-1 is a member of the heat shock protein 40 family and helps other proteins fold correctly after translation or refold after a damaging stress event. Dysregulated Tid-1 behavior is involved in numerous human diseases including cancers, cardiomyopathies, and neurodegenerative disorders. Given its wide influence within the cell, Tid-1 could be a key biomarker or even therapeutic target for these diseases, but to leverage Tid-1 effectively, researchers need to understand its functionality in detail. To this end, a team of scientists consolidated the current research on human Tid-1. They found that Tid-1’s protein-protein interactions corresponded to its roles in various diseases and provide insight into how Tid-1 affects pathogenic developments..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Mitochondrial stress is a key trigger of innate immune responses. Sources of stress include environmental changes, genetic mutations, and pathogenic infection. Mitochondria respond by releasing mitochondrial DAMPs and cytochrome c into the cytosol that induce inflammation and apoptosis through activating inflammasomes, cGAS and apoptotic caspases. One way cells manage mitochondrial stress is by eliminating dysfunctional mitochondria, a process known as “mitophagy.” Mitophagy regulatory pathways are classified as ubiquitin (Ub)-dependent or Ub-independent (receptor-dependent). Growing evidence shows that mitophagy can be induced by certain bacteria and viruses. Co-opting the mitophagy process enables these pathogens to evade hosts’ immune defense. Much remains to be learned about the mechanisms that pathogens employ to hijack host mitophagy. Understanding these mechanisms could point to new therapeutic strategies for fighting infection and related diseases..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Calcineurin is a serine/threonine phosphatase that serves as a critical bridge between calcium signaling and the phosphorylation states of numerous important substrates. But despite being studied for approximately 40 years, exactly how calcineurin is activated in humans and other organisms is not yet fully understood. Structurally, calcineurin is a heterodimer expressed as three different isoforms: α, β, and γ each featuring a catalytic domain, a B chain binding helix, the regulatory domain, an autoinhibitory domain, and an unstructured C-terminal domain of unknown function. Disorder is a key hallmark of calcineurin’s structure. The intrinsically disordered regulatory domain could facilitate the rapid activation of calcineurin during calcium signaling. Increasing evidence suggests that calcineurin is a vital component of various signaling pathways. But even more work is needed to understand calcineurin’s versatility including how certain substrates bind to calcineurin..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Cancers are complex diseases largely characterized by rapid cellular proliferation. This can be slowed by regulated cell death mechanisms like ferroptosis. Ferroptosis is triggered by extensive peroxidation of cell membrane phospholipids by reactive oxygen species (ROS), but ferroptosis can be inhibited by enzymes that undo peroxidation like GPX4. Another enzyme, DHODH, supports GPX4 and is vital to the production of pyrimidine nucleotides, critical building blocks for rapidly proliferating cells. In theory, this would make inhibiting DHODH a valuable therapeutic target for cancer by freeing up ferroptosis and hampering proliferation. However, this is complicated by the “Warburg effect,” which is common in some cancer cells. The Warburg effect is a shift away from using mitochondria for energy to other metabolic processes, which has knock-on effects..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"People with chronic alcoholism exhibit signs of neurodegeneration, but the reasons for this have been unclear. Ethanol-induced calcium overload is known to cause an imbalance in mitochondrial dynamics, and results in the formation of a protein complex called the NLRP3 inflammasome, which initiates an inflammatory form of cell death. Researchers have now determined calcium’s role in the degeneration of neuronal cells exposed to ethanol. They found that ethanol exposure increases NMDA receptor (NMDAR) expression in neuronal cells, which causes calcium to rush into the cells, resulting in calcium overload and CaMKII activation. Activated CaMKII then phosphorylates dynamin-related protein 1 (Drp1) and JNK1 and phosphorylated Drp1 is relocated to the mitochondria, which undergo dysfunction. The phosphorylation of JNK1 activates the NLRP3 inflammasome and exacerbates ROS accumulation, ultimately leading cells to their death..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Atherosclerosis is a chronic inflammatory process where lipids accumulate along the arterial wall. One key protein in atherosclerosis development is AIBP (Apolipoprotein A-I binding protein). AIBP exists both inside and outside cells, but only secreted AIBP is well characterized in atherosclerosis. A recent study found that AIBP is highly expressed in human and mouse atherosclerotic lesions and that the AIBP was concentrated within the inner membrane of macrophage mitochondria. Macrophages are immune cells that can have pro- or anti-inflammatory phenotypes. The interplay between these phenotypes plays a pathogenic role in atherosclerosis. In this study, blocking the production of AIBP in bone marrow aggravated atherosclerosis and increased macrophage infiltration in a mouse model. This bone-marrow-specific AIBP deficiency increased the cleavage of the protein PINK1 (PTEN-induced putative kinase 1)..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.