How to resolve AdBlock issue? 
News
Parkinson’s disease is a neurodegenerative movement disorder that progresses relentlessly. It gradually impairs a person’s ability to function until they ultimately become immobile and often develop dementia. In the U.S. alone, over a million people are afflicted with Parkinson’s, and new cases and overall numbers are steadily increasing.
There is currently no treatment to slow or halt Parkinson’s disease. Available drugs don’t slow disease progression and can treat only certain symptoms. Medications that work early in the disease, however, such as Levodopa, generally become ineffective over the years, necessitating increased doses that can lead to disabling side effects. Without understanding the fundamental molecular cause of Parkinson’s, it’s improbable that researchers will be able to develop a medication to stop the disease from steadily worsening in patients.
Many factors may contribute to the development of Parkinson’s, both environmental and genetic. Until recently, underlying genetic causes of the disease were unknown. Most cases of Parkinson’s aren’t inherited but sporadic, and early studies suggested a genetic basis was improbable.
Nevertheless, everything in biology has a genetic foundation. As a geneticist and molecular neuroscientist, I have devoted my career to predicting and preventing Parkinson’s disease. In our newly published research, my team and I discovered a new genetic variant linked to Parkinson’s that sheds light on the evolutionary origin of multiple forms of familial parkinsonism, opening doors to better understand and treat the disease.
Genetic linkages and associations
In the mid-1990s, researchers started looking into whether genetic differences between people with or without Parkinson’s might identify specific genes or genetic variants that cause the disease. In general, I and other geneticists use two approaches to map the genetic blueprint of Parkinson’s: linkage analysis and association studies.
Linkage analysis focuses on rare families where parkinsonism, or neurological conditions with similar symptoms to Parkinson’s, is passed down. This technique looks for cases where a disease-causing version of the gene and Parkinson’s appear to be passed down in the same person. It requires information on your family tree, clinical data and DNA samples. Relatively few families, such as those with more than two living, affected relatives willing to participate, are needed to expedite new genetic discoveries.
“Linkage” between a pathogenic genetic variant and disease development is so significant that it can inform a diagnosis. It has also become the basis of many lab models used to study the consequences of gene dysfunction and how to fix it. Linkage studies, like the one my team and I published, have identified pathogenic mutations in over 20 genes. Notably, many patients in families with parkinsonism have symptoms that are indistinguishable from typical, late-onset Parkinson’s. Nevertheless, what causes inherited parkinsonism, which typically affects people with earlier-onset disease, may not be the cause of Parkinson’s in the general population.
Conversely, genome-wide association studies, or GWAS, compare genetic data from patients with Parkinson’s with unrelated people of the same age, gender and ethnicity who don’t have the disease. Typically, this involves assessing how frequently in both groups over 2 million common gene variants appear. Because these studies require analyzing so many gene variants, researchers need to gather clinical data and DNA samples from over 100,000 people.
Although costly and time-consuming, the findings of genome-wide association studies are widely applicable. Combining the data of these studies has identified many locations in the genome that contribute to the risk of developing Parkinson’s. Currently, there are over 92 locations in the genome that contain about 350 genes potentially involved in the disease. However, GWAS locations can be considered only in aggregate; individual results are not helpful in diagnosis nor in disease modeling, as the contribution of these individual genes to disease risk is so minimal.
Together, “linked” and “associated” discoveries imply a number of molecular pathways are involved in Parkinson’s. Each identified gene and the proteins they encode typically can have more than one effect. The functions of each gene and protein may also vary by cell type. The question is which gene variants, functions and pathways are most relevant to Parkinson’s? How do researchers meaningfully connect this data?
Parkinson’s disease genes
Using linkage analysis, my team and I identified a new genetic mutation for Parkinson’s disease called RAB32 Ser71Arg. This mutation was linked to parkinsonism in three families and found in 13 other people in several countries, including Canada, France, Germany, Italy, Poland, Turkey, Tunisia, the U.S. and the U.K.
Although the affected individuals and families originate from many parts of the world, they share an identical fragment of chromosome 6 that contains RAB32 Ser71Arg. This suggests these patients are all related to the same person; ancestrally, they are distant cousins. It also suggests there are many more cousins to identify.
With further analysis, we found RAB32 Ser71Arg interacts with several proteins previously linked to early- and late-onset parkinsonism as well as nonfamilial Parkinson’s disease. The RAB32 Ser71Arg variant also causes similar dysfunction within cells.
Together, the proteins encoded by these linked genes optimize levels of the neurotransmitter dopamine. Dopamine is lost in Parkinson’s as the cells that produce it progressively die. Together, these linked genes and the proteins they encode regulate specialized autophagy processes. In addition, these encoded proteins enable immunity within cells.
Such linked genes support the idea that these causes of inherited parkinsonism evolved to improve survival in early life because they enhance immune response to pathogens. RAB32 Ser71Arg suggest how and why many mutations have originated, despite creating a susceptible genetic background for Parkinson’s in later life.
RAB32 Ser71Arg is the first linked gene researchers have identified that directly connects the dots between prior linked discoveries. The proteins encoded bring together three important functions of the cell: autophagy, immunity and mitochondrial function. While autophagy releases energy stored in the cell’s trash, this needs to be coordinated with another specialized component within the cell, mitochondria, that are the major supplier of energy. Mitochondria also help to control cell immunity because they evolved from bacteria the cell’s immune system recognizes as “self” rather than as an invading pathogen to destroy.
Identifying subtle genetic differences
Finding the molecular blueprint for familial Parkinson’s is the first step to fixing the faulty mechanisms behind the disease. Like the owner’s manual to your car’s engine, it provides a practical guide of what to check when the motor fails.
Just as each make of motor is subtly different, what makes each person genetically susceptible to nonfamilial Parkinson’s disease is also subtly different. However, analyzing genetic data can now test for types of dysfunction in the cell that are hallmarks of Parkinson’s disease. This will help researchers identify environmental factors that influence the risk of developing Parkinson’s, as well as medications that may help protect against the disease.
More patients and families participating in genetic research are needed to find additional components of the engine behind Parkinson’s. Each person’s genome has about 27 million variants of the 6 billion building blocks that make up their genes. There are many more genetic components for Parkinson’s that have yet to be found.
As our discovery illustrates, each new gene that researchers identify can profoundly improve our ability to predict and prevent Parkinson’s.
Matthew Farrer, Professor of Neurology, University of Florida
This article is republished from The Conversation under a Creative Commons license. Read the original article.
This will be the fourth meeting for the Federal Advisory Committee to provide the Forest Service with recommended updates for the Northwest Forest Plan Amendment.
The meeting will take place at the Redding Rancheria Trinity Health Center, 81 Arbuckle Court, Weaverville.
The secretary of agriculture established this committee to support ongoing efforts to amend the Northwest Forest Plan.
The Federal Advisory Committee brings together representatives with diverse perspectives, experiences and expertise — including community, tribal, government and other interest groups from across the Northwest Forest Plan landscape to inform the plan amendment.
This group is helping the agency identify ways to effectively conserve key resources while considering social, ecological, and economic conditions and needs.
FAC meetings are open to the public with an opportunity to submit comments. Details on meetings, including how the public can provide information to the committee is posted on the regional website.
The Federal Advisory Committee does not replace the public involvement process or the public’s opportunity to engage directly with the Forest Service regarding Northwest Forest Plan amendment efforts during the planning process.
The Northwest Forest Plan covers 24.5 million acres of federally managed lands in northwestern California, western Oregon, and Washington. It was established in 1994 to address threats to threatened and endangered species while also contributing to social and economic sustainability in the region.
After nearly 30 years, the Northwest Forest Plan needs to be updated to accommodate changed ecological and social conditions.
Of note, forests in California included in the NWFP FACA planning are:
1. Klamath National Forest and Butte Valley National Grassland;
2. Lassen National Forest;
3. Mendocino National Forest;
4. Modoc National Forest;
5. Six Rivers National Forest;
6. Shasta-Trinity National Forest.
Additional information about the Northwest Forest Plan is available here.
For more about USDA Forest Service, visit www.fs.usda.gov/r6.
At the April 4 meeting, City Manager Alan Flora led a discussion with the council on the county’s Southeast Regional Wastewater System and issues that have arisen with regard to a new housing development.
“This hasn’t been a very good year for the sewer system in Clearlake,” which is what initiated the discussion, Flora said.
Flora said Special Districts Administrator Scott Harter was invited but had another meeting.
One of the chief issues related to Konocti Gardens, a new 102-unit low-income apartment project built on 11 acres at 3930 Old Highway 53, developed by CSI Construction Co.
Flora said that although Konocti Gardens is ready to come online and be occupied in June, the county won’t allow the project to connect to the wastewater system until upgrades are made to the system.
That means the apartment complex won’t be online until October or November, “causing some pretty significant financial impacts to the project,” Flora said.
Flora said that the decision not to let the complex connect to the system was based on a capacity analysis required by Special Districts for projects over 20 units. He said he wasn’t sure why, but the city didn’t receive the draft report until early February.
That report indicated there is 2,200 feet of pipe in the collection system that would be over capacity as a result of this project, Flora said.
Flora noted later in the discussion that the city had been told by the county that the capacity plan was a formality and that everything would be fine, “but it wasn’t.”
He said the county did an updated sewer model in 2022. “This is a section of the collection system that is a problem with or without development.”
It was the city’s understanding, Flora said, that there aren’t areas of significant concern in the city for collection other than Highlands Harbor, which has spills every time there is a significant rain event.
However, based on this most recent capacity analysis, Special Districts won’t allow Konocti Gardens to connect to the sewer system, Flora said.
As a result, the county — including Supervisor Bruno Sabatier — along with the city and the developer have been having almost weekly meetings. “There’s some promising progress” in the developer being able to get occupancy, Flora said.
Flora said Special Districts is open to doing things to speed up design and construction of the needed upgrades.
If construction can’t be completed, there will be a design for a bypass from that project around the impacted area and added back into the system in another area with capacity to handle it, Flora said.
Flora said Lacosan’s system had a large wastewater spill last winter, and six to seven spills this winter totaling close to one million gallons that have hit water bodies, including Clear Lake, within the Southeast system.
He said Konocti Gardens really illustrates the fact that Lacosan has millions of dollars in reserves that have been accumulated and no apparent upgrade plan for the system. Meantime, Highlands Harbor has been a decades-long problem.
All these things lead to, “what can the city do to get some more answers here and maybe be a little bit more involved,” Flora said.
He added, “It is a little bit unusual that most of the infrastructure was developed before the city was incorporated.”
When the incorporation happened — which occurred in 1980 — it was required that the sanitation district’s board of directors provide at least one seat to the city. Flora said city staff found a 1983 resolution in which the city delegated that seat back to the Board of Supervisors.
Flora said he met the week before with County Administrative Officer Susan Parker, Board Chair Bruno Sabatier and Vice Chair EJ Crandell to share the city’s research and what they believe to be the county’s obligation, which is to give the city a seat on the sanitation district board.
There may be another arrangement with the county. “Ultimately, the city just wants this to work,” Flora said.
He said his discussions led him to conclude the county is interested in meeting and talking more about the situation, and figuring out a way for the city’s concerns to be addressed.
The council ended up unanimously adopting a resolution requesting a role in the direct governance of Lacosan’s operations of the Southeast Regional Collection System.
In other business, the council held the second reading of Ordinance No. 269-2024 updating Clearlake Municipal Code Section 3-5 relating to fire mitigation fees.
The change in the ordinance did not include changing the fire mitigation fees. Flora said they decided to hold off on adopting any changes by resolution until there is interest to have a countywide discussion on fire mitigation fees and construction.
When asked by council members about when the matter could be wrapped up, Flora said it could be done by the end of the fiscal year in the summer.
Also on Thursday, the council presents a proclamation declaring April 2024 as Sexual Assault Awareness Month and a proclamation declaring April 14 to 20 as Public Safety
Telecommunicators Week, offered certificates of appreciation for the Bunny Brunch and received the Recreation and Events Department’s quarterly report.
Email Elizabeth Larson at
MATH will meet at 6 p.m. Thursday, April 11, in the Middletown Community Meeting Room/Library at 21256 Washington St., Middletown. The meeting is open to the public.
To join the meeting via Zoom click on this link; the meeting ID is 869-1824-5695, pass code is 808449. Call in at 669-900-6833.
MATH is meeting earlier than usual in order to hold a community workshop on the area plan.
The meeting will get started with an update on the Middletown Art Center’s Water Basket Project.
The town hall’s members also will discuss and consider approving MATH’s proposed response to the Lake County Community Development Department’s request for a review of the updated Guenoc Valley Project. The deadline to respond is April 12.
At 6:10 p.m., MATH will host the Lake County 2050-Middletown Area Plan Update community workshop.
Community Development Department Director Mireya Turner and her staff, along with planning consultant PlaceWorks, will provide an overview presentation of the process for the Middletown Area Plan Update.
The two-hour workshop will include breakout sessions and time for public input, questions and answers.
MATH’s next meeting will take place on May 9.
MATH — established by resolution of the Lake County Board of Supervisors on Dec. 12, 2006 — is a municipal advisory council serving the residents of Anderson Springs, Cobb, Coyote Valley (including Hidden Valley Lake), Long Valley and Middletown.
For more information email
Email Elizabeth Larson at
The Department of Alcoholic Beverage Control, or ABC, recognizes the importance of Alcohol Awareness Month every April due to the high number of alcohol-related deaths each year in the U.S.
According to the Centers for Disease Control, about 178,000 people die each year from excessive alcohol use. In 2021, 13,384 people died in alcohol-related car crashes, according to the National Highway Traffic Safety Administration, or NHTSA.
"This month serves as an important reminder to engage in conversations about the risks associated with excessive alcohol consumption and to encourage safe and responsible behavior.” said ABC Director Joseph McCullough.
ABC regulates the sale, manufacture, and distribution of alcohol in California.
The department recognizes the serious health and public safety concerns surrounding alcohol, especially when it is misused.
Licensees and bystanders are also encouraged to do their part by reporting any signs of excessive or underage drinking to local authorities.
The effects of alcohol misuse are both deadly and expensive. Alcohol is the fourth-leading cause of preventable death in the United States, according to the National Institute on Alcohol Abuse and Alcoholism, and has a role in at least 7.1% of all emergency room visits.
The financial burden of alcohol misuse cost the U.S. an estimated $249 billion per year. NHTSA estimates that drunk driving crashes cost the U.S. $68.9 billion annually.
Assemblymember James C. Ramos (D-San Bernardino) authored the 2022 legislation that took effect a year ago.
“The Feather Alert is a tool to enlist the public’s assistance when a Native American might be at peril,” Ramos said. “Earlier this year, the Assembly reviewed the effectiveness of this important tool one year after it began, and listened to tribal members and law enforcement. We are committed to ensuring that this lifesaving notification system works effectively and easily for families worried about missing loved ones.”
Since the Feather Alert’s implementation, tribal communities made five requests, but the California Highway Patrol, in consultation with local law enforcement, granted activation in two instances. Of the two approved alerts, only one missing individual was found.
AB 1863 would streamline the process for activating the Feather Alert and make it more easily accessible.
The proposed changes would also expand definitions of endangered and missing for purposes of the alert notification and would require the CHP to issue a reason for denying activation within 48 hours.
“We carry the strength of our ancestors to ensure our tribal citizens are safe and protected,” said Bear River of the Rohnerville Rancheria Chairwoman Josefina Frank. “The work that has been done on AB 1863 has provided tribal nations their voices back to ensure we end MMIP.”
Chairwoman Frank continued, “We are the voice and movement for those we have lost, those who are hurting and the generations to come.”
“We are grateful to Assemblymember Ramos for introducing the Feather Alert and putting forth AB 1863 this session to directly address concerns from those at the forefront of this crisis,” Pechanga Band of Indians Councilwoman Catalina Chacon said. “Allowing our tribal governments to communicate directly with the State affirms our sovereignty, saves critical time, and will further help bring our missing people home safely.”
“I thank Assemblymember Ramos for creating this mechanism to quickly get the word out when Indigenous people go missing or are at risk,” said Yurok Tribal Chairman Joe James.
In citing his support for AB 1863 James stated, “We supported previous legislation that created this alert because it will help reduce the disproportionate rate of Missing and Murdered Indigenous People cases in California. The next generation of Indigenous California should not have to live in a world where they have to worry about family members going missing or worse. With the updates in this legislation, we will take action to address the remaining root causes of this complex crisis.”
AB 1863 is sponsored by the Bear River of the Rohnerville Rancheria, the Pechanga Band of Mission Indians and the Yurok Tribe.