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For those who seek the thrill of adventure and the rush of adrenaline, the Smoky Mountains present a vast playground of untamed wilderness and exhilarating activities. This majestic region is not just for the serene soul seeking peace in nature but also for the adventure lovers who crave excitement and challenge. From the rugged trails to the rapid waters, the Smokies offer a diverse array of experiences that cater to every kind of thrill-seeker. Let’s delve into ten thrilling activities that promise to ignite your adventurous spirit in the heart of the Smokies. 1. Hiking to Alum Cave Bluffs The journey to Alum Cave Bluffs is one of the most rewarding adventures the Smokies have to offer. This 4.6-mile hike is not just a physical challenge; it’s a passage through the varying moods of the mountains. As you ascend through the dense forest, you’ll encounter unique geological features, like Arch Rock, and the sweeping views from Inspiration Point. The trail culminates at Alum Cave Bluff, offering spectacular vistas. It’s an immersive experience that combines physical exertion with the tranquil beauty of the natural surroundings. 2. Jeep Ride Adventures For those who prefer their adventures on wheels, a Jeep ride through the Smoky Mountains provides an exhilarating way to explore the rugged landscapes. The winding mountain roads and off-road trails offer a thrilling ride with panoramic views that are simply unmatched. For Jeep owners, the experience can be further enhanced by customizing their vehicles with accessories from local outfitters like Smoky Mountain Off-Road Outfitters. Adding specialized Jeep badges not only personalizes your ride but also commemorates your adventure in the Smokies, making each journey as unique as the trails you choose to explore. 3. Whitewater Rafting on the Pigeon River Whitewater rafting on the Pigeon River is an adrenaline-packed activity that draws adventure-seekers from all over. The river features sections suitable for all levels, from the gentle flows ideal for beginners to the challenging Class III and IV rapids that test even the most experienced rafters. This exhilarating experience not only offers a thrilling ride through the rapids but also provides a unique perspective of the Smokies’ natural beauty, all from the heart of the river. 4. Ziplining Through the Canopy Ziplining offers a bird’s-eye view of the Smokies’ breathtaking landscapes, making it a must-try for anyone seeking adventure. Gliding through the canopy, adventurers can experience the forest in a way that’s impossible to do so from the ground. The sensation of flying above the trees, with the wind in your face and the valley below, is both exhilarating and serene. Zipline tours in the Smokies cater to a range of ages and thrill levels, ensuring that everyone can enjoy the rush of soaring through the air. 5. Mountain Biking on the Trails Mountain biking in the Smokies offers an off-road adventure that combines physical challenge with the natural beauty of the mountains. The region boasts a variety of trails, from gentle forest paths to rugged mountain tracks that require skill and endurance. Biking through these landscapes offers a unique way to explore the wilderness, with the added thrill of navigating the terrain at speed. It’s an activity that appeals to both seasoned bikers and those looking to try something new and exciting. 6. Rock Climbing and Bouldering The rugged terrain of the Smoky Mountains offers prime spots for rock climbing and bouldering, providing both beginners and seasoned climbers with the perfect setting to test their skills. The region’s natural rock formations offer a variety of climbs, from short, challenging boulders to towering cliff faces that demand endurance and technique. Climbing in the Smokies is not just about getting an adrenaline rush; it’s an opportunity to connect with the raw beauty of the mountains, offering a sense of achievement and exhilaration that is unmatched. 7. Horseback Riding Through the Forest Horseback riding through the Smoky Mountains offers a unique blend of adventure and tranquility. It’s an opportunity to explore the dense forests and rolling hills at a leisurely pace, allowing for a deeper connection with the natural surroundings. Riding trails meander through the heart of the Smokies, offering riders stunning views and the chance to encounter wildlife in their natural habitat. Whether you’re an experienced rider or trying it for the first time, horseback riding is a wonderful way to experience the Smokies’ serene beauty. 8. Fishing in Mountain Streams Fishing in the pristine mountain streams of the Smokies is an adventure that combines the thrill of the catch with the peace of being surrounded by nature. The clear, cool waters are home to a variety of fish, including trout, providing both challenge and reward for anglers. Fishing in the Smokies is not just about the sport; it’s an immersive experience that allows you to slow down and appreciate the subtle beauty of the mountain landscapes. Whether you’re fly fishing or using traditional methods, the streams of the Smokies offer a serene yet adventurous escape. 9. Exploring Caves and Caverns Delving into the caves and caverns of the Smoky Mountains is an adventure that takes you beneath the surface of the earth into a world of ancient rock formations, hidden chambers, and underground streams. Cave exploration in the Smokies allows adventurers to experience the thrill of discovery and the awe of natural wonders that have formed over millions of years. The cool, dark environments of these caves provide a stark contrast to the lush, vibrant landscapes above, offering a unique and thrilling exploration experience. 10. Camping Under the Stars Camping in the Smoky Mountains is the ultimate adventure for those who wish to immerse themselves fully in the natural beauty of the region. Whether you’re setting up camp in a designated campground or venturing into the backcountry, camping allows you to connect with the wilderness in a profound way. Sleeping under the stars, waking up to the sounds of nature, and living off the land are experiences that not only challenge but also rejuvenate the spirit. Camping here offers a blend of adventure, tranquility, and a deep connection with the natural world. Conclusion: More Than A Rush! The Smoky Mountains are a treasure trove of adventures, offering a plethora of activities for those who seek the thrill of the outdoors. The best part is that these adventures not only provide an adrenaline rush but also allow you to connect with nature in an intimate and memorable way. Whether you’re a seasoned adventurer or looking to step out of your comfort zone, the Smokies invite you to explore, challenge yourself, and create unforgettable memories amidst their majestic landscapes.

The post An Adventure Lover’s Guide For a Trip to The Smokies appeared first on Geeky Traveller.

Cate Blanchett intepreta Catherine Ravenscroft, uma famosa jornalista investigativa que recebe anonimamente um romance no qual ela é, indiscutivelmente, a personagem central

"Researchers at the University of Texas have unveiled a new thermal interface material that could revolutionize cooling, outperforming top liquid metal solutions by up to 72% in heat dissipation," writes Slashdot reader jjslash. "This breakthrough not only improves energy efficiency but also enables higher-density data center setups, cutting cooling costs and energy usage significantly." TechSpot reports: Thanks to a mechanochemically engineered combination of the liquid metal alloy Galinstan and ceramic aluminum nitride, this thermal interface material, or TIM, outperformed the best commercial liquid metal cooling products by a staggering 56-72% in lab tests. It allowed dissipation of up to 2,760 watts of heat from just a 16 square centimeter area. The material pulls this off by bridging the gap between the theoretical heat transfer limits of these materials and what's achieved in real products. Through mechanochemistry, the liquid metal and ceramic ingredients are mixed in an extremely controlled way, creating gradient interfaces that heat can flow across much more easily. Beyond just being better at cooling, the researchers claim that the higher performance reduces the energy needed to run cooling pumps and fans by up to 65%. It also unlocks the ability to cram more heat-generating processors into the same space without overheating issues. [...] As for how you can get your hands on the material: it's yet to make it out of the labs. The UT team has so far only tested it successfully at small scales but is now working on producing larger batches to put through real-world trials with data center partners. The material has been detailed in a paper published in the journal Nature Nanotechnology.

Read more of this story at Slashdot.

Analyst Alex de Waal looks at how the US president-elect could deal with conflicts on the continent.

The journey of this year's tree from the West Midlands to the West End ahead of tonight's switch on.

Apple has released macOS Sonoma 14.7.1 and MacOS Ventura 13.7.1 for Mac users who have not yet updated to MacOS Sequoia, of which MacOS Sequoia 15.1 with Apple Intelligence was just released. macOS Sonoma 14.7.1 and macOS Ventura 13.7.1 both contain many security fixes, making them important updates to install for Mac user who are ... Read More

With school on break, along with all the homework, tests and early start times that come with it, parents often assume that young people’s stress and anxiety will take a pause as well. However, that’s not always the case, especially as the novelty of summer dwindles. Without the daily structure of school and extracurricular activities, kids may struggle with boredom or restlessness. Maintaining a routine during the summer can be a powerful tool for supporting children’s mental health, and parents can play a crucial role in establishing and reinforcing this structure.

We want readers to make connections between books and their own lives and the world around them. Connecting real experiences for kids with literary ones is something that I’ve found also helps readers value books and knowledge. And it is so much fun to extend the pages of a story into a real-world activity!

Over the past decade, parent advocacy groups led a grassroots movement resulting in most states adopting dyslexia-specific legislation, with many states mandating the use of the Orton-Gillingham (OG) approach to reading instruction. Orton-Gillingham is a direct, explicit, multisensory, structured, sequential, diagnostic, and prescriptive approach to reading for students with or at risk for word-level reading disabilities (WLRD). Evidence from a prior synthesis and What Works Clearinghouse reports yielded findings lacking support for the effectiveness of OG interventions.

Steve Vonder Haar recently released an outstanding research report about the online webcasting event services business.

He states that consumers of webcasting services have been motivated by two priorities: 1) the desire to keep costs low; and 2) the desire to keep involvement of their own IT departments to a minimum. For this reason, major webcasting event service providers, like ON24, have enjoyed their greatest success at the ends of the market spectrum: low cost self-provisioning services and high touch premium webcasting services.

The premium end of the market has been bolstered by the complexity of the client's needs, which has kept fees high and competition at bay. The low end of the market had become increasingly commoditized.

He concludes that service providers are going to have to push more to the middle of that spectrum and identify more companies that require well-produced webcasts for the market to continue growing.

He also mentions that the complexity of webcast events that has traditionally protected the major service providers is no longer a significant barrier to entry. Sophisticated webcasting software offered on a Software as a Service (SaaS) basis allows any number of production companies, agencies, and event companies to compete on an equal footing with the ON24s and the OnStreams.

According to Hoovers, the US marketing and services industry includes about 35,000 companies with combined annual revenue of about $80 billion. The industry is fragmented because the top 50 companies generate less than 40 percent of that revenue. In other words, there are a large number of potential buyers of enterprise webcasting software that want to compete for online event services business at a time when traditional advertising revenues are falling and internet advertising revenues are growing. Internet communications are definitely going to become a greater point of emphasis for these companies.

I am unable to attached the report, but you can request a copy at the Interactive Media Strategies website.

There appeared to be a definite frost between first lady Jill Biden and Vice President Kamala Harris during a Veterans Day event at Arlington National Cemetery on Monday. A close-up […]

The post Footage of Jill Biden and Kamala Harris Sitting Side-by-Side at Veterans Day Event Goes Viral appeared first on The Western Journal.

Sir Kenny Dalglish hailed nine-time Major champion Gary Player and expressed his delight at Liverpool's position at the top of the Premier League during his visit to South Africa this weekend.

Sanctions must not prevent humanitarian work in Ukraine Expert comment NCapeling 30 May 2022

Restrictions on supply of certain items and financial sanctions can impede vital relief unless adequate safeguards are put in place such as exceptions or general licences.

Sanctions play a major role in the response to Russia’s invasion of Ukraine. The United Nations (UN) has not imposed sanctions, but an important number of states have done so. They have imposed a wide array of restrictions and the number of targeted – or ‘designated’ – persons is unprecedented.

The public has been captivated by the freezing of oligarchs’ assets. There is ongoing discussion about seizing them to provide compensation for war damage. Debate continues about how far to ban oil and gas imports.

One aspect of the sanctions has received far less attention, even though it can exacerbate the effect of the conflict on civilians. Some of the trade restrictions and financial sanctions pose immediate and concrete challenges to the capacity of humanitarian organizations to work in Ukraine and in neighbouring states.

Trade sanctions imposed by the European Union (EU) and UK prohibit the export or supply of certain goods and technology in the transport, telecommunications, energy, and oil or mineral exploration sectors to non-government-controlled areas of the Donetsk or Luhansk oblasts, or for use there.

Restricted items include technical equipment which is necessary for humanitarian operations, such as water pumps and refrigerating equipment, but also far more mundane items such as vehicles for transport of persons and goods, and office equipment that are necessary for humanitarian organizations trying to work in the region.

Designations can reduce options for support

Financial sanctions also raise problems. Some are immediately apparent. Significantly for humanitarian operations, the two de facto republics of Donetsk and Luhansk are designated by the EU, the UK, and the US. Consequently, it is prohibited to make funds or assets available to them directly or indirectly.

This prohibition covers the payment of any taxes, licences, and other fees to these authorities, as well as the provision of assets to ministries under their control in the course of humanitarian operations, such as ministries of health and education.

Designations of other entities may also be relevant, such as Russian ‘state enterprises’ which operate in these areas and are the sole providers of commodities necessary for humanitarian response, such as heating fuel.

These are the designations which most obviously impact humanitarian response. However, more than 1,000 persons and entities have been designated and humanitarian organizations must avoid purchasing goods and services from them.

Risk-averse commercial partners

Commercial actors – such as banks, insurers, freight companies and commodity providers – whose services are required by humanitarian organizations must also comply with the sanctions. Experience shows that the due diligence measures adopted by humanitarian organizations do not always allay concerns of risk-averse sectors such as banks.

Fears of violating the sanctions, coupled with the fact humanitarian organizations are rarely profitable clients, have led them to severely restrict the services they provide.

This is not the first occasion the problem has arisen. What is different in relation to Ukraine is the number of designated persons and the ‘sanctions packages’ adopted in quick succession. As compliance officers struggle to keep abreast, their institutions become even more risk-averse.

For UK banks, the situation is exacerbated by the adoption of the Economic Crime (Transparency and Enforcement) Act 2022. This amends existing rules by removing the requirement for the UK Treasury to prove knowledge or reasonable cause to suspect that a transaction violated sanctions, imposing strict liability for sanctions violations.

Time for the UK to follow others

The EU, the US, Switzerland, and other states which have imposed sanctions have sought to mitigate their adverse effects by including safeguards for humanitarian action. Although the UK has largely replicated the measures adopted by the EU in terms of restrictions and designations, it lags behind in including such safeguards.

The UK trade restrictions and financial sanctions do not include exceptions for humanitarian action. While several general licences have been issued, none relate to humanitarian operations.

Instead, the UK measures foresee only the possibility of applying for specific licences – from the Treasury in the case of financial sanctions and the Department of International Trade for trade restrictions. But obtaining specific licences is a time-consuming process which is simply not appropriate for emergency response.

If the UK is to show it is serious about responding to the immense needs caused by the invasion it must introduce appropriate safeguards in its sanctions – either in the form of exceptions or general licences.

What matters is they cover all key humanitarian organizations responding to the Ukraine crisis that are subject to UK sanctions – either because they are UK persons or because their funding agreements with the UK government require them to comply with UK measures.

These include UN agencies, funds and programmes, components of the International Red Cross and Red Crescent Movement, and non-governmental organizations (NGOs) responding to the crisis in Ukraine and neighbouring states. The provision must also clearly extend to commercial entities which provide necessary services for humanitarian operations.

Given the UK recently adopted an exception along similar lines in relation to the Afghanistan sanctions, there is a valuable precedent for Ukraine.

Members of the B-cell lymphoma (BCL-2) protein family regulate mitochondrial outer membrane permeabilization (MOMP), a phenomenon in which mitochondria become porous and release death-propagating complexes during the early stages of apoptosis. Pro-apoptotic BCL-2 proteins oligomerize at the mitochondrial outer membrane during MOMP, inducing pore formation. Of current interest are endogenous factors that can inhibit pro-apoptotic BCL-2 mitochondrial outer membrane translocation and oligomerization. A mitochondrial-derived peptide, Humanin (HN), was reported being expressed from an alternate ORF in the mitochondrial genome and inhibiting apoptosis through interactions with the pro-apoptotic BCL-2 proteins. Specifically, it is known to complex with BAX and BID. We recently reported the fibrillation of HN and BAX into β-sheets. Here, we detail the fibrillation between HN and BID. These fibers were characterized using several spectroscopic techniques, protease fragmentation with mass analysis, and EM. Enhanced fibrillation rates were detected with rising temperatures or pH values and the presence of a detergent. BID fibers are similar to those produced using BAX; however, the structures differ in final conformations of the BCL-2 proteins. BID fibers display both types of secondary structure in the fiber, whereas BAX was converted entirely to β-sheets. The data show that two distinct segments of BID are incorporated into the fiber structure, whereas other portions of BID remain solvent-exposed and retain helical structure. Similar analyses show that anti-apoptotic BCL-xL does not form fibers with humanin. These results support a general mechanism of sequestration of pro-apoptotic BCL-2 proteins into fibers by HN to inhibit MOMP.

20 August 2020

The divalent anion sodium symporter (DASS) family (SLC13) plays critical roles in metabolic homeostasis, influencing many processes, including fatty acid synthesis, insulin resistance, and adiposity. DASS transporters catalyze the Na+-driven concentrative uptake of Krebs cycle intermediates and sulfate into cells; disrupting their function can protect against age-related metabolic diseases and can extend lifespan. An inward-facing crystal structure and an outward-facing model of a bacterial DASS family member, VcINDY from Vibrio cholerae, predict an elevator-like transport mechanism involving a large rigid body movement of the substrate-binding site. How substrate binding influences the conformational state of VcINDY is currently unknown. Here, we probe the interaction between substrate binding and protein conformation by monitoring substrate-induced solvent accessibility changes of broadly distributed positions in VcINDY using a site-specific alkylation strategy. Our findings reveal that accessibility to all positions tested is modulated by the presence of substrates, with the majority becoming less accessible in the presence of saturating concentrations of both Na+ and succinate. We also observe separable effects of Na+ and succinate binding at several positions suggesting distinct effects of the two substrates. Furthermore, accessibility changes to a solely succinate-sensitive position suggests that substrate binding is a low-affinity, ordered process. Mapping these accessibility changes onto the structures of VcINDY suggests that Na+ binding drives the transporter into an as-yet-unidentified conformational state, involving rearrangement of the substrate-binding site–associated re-entrant hairpin loops. These findings provide insight into the mechanism of VcINDY, which is currently the only structurally characterized representative of the entire DASS family.

Ventilator-associated pneumonia (VAP) is a common hospital-acquired infection, leading to high morbidity and mortality. Currently, bronchoalveolar lavage (BAL) is used in hospitals for VAP diagnosis and guiding treatment options. Although BAL collection procedures are invasive, alternatives such as endotracheal aspirates (ETA) may be of diagnostic value, however, their use has not been thoroughly explored. Longitudinal ETA and BAL were collected from 16 intubated patients up to 15 days, of which 11 developed VAP. We conducted a comprehensive LC–MS/MS based proteome and metabolome characterization of longitudinal ETA and BAL to detect host and pathogen responses to VAP infection. We discovered a diverse ETA proteome of the upper airways reflective of a rich and dynamic host-microbe interface. Prior to VAP diagnosis by microbial cultures from BAL, patient ETA presented characteristic signatures of reactive oxygen species and neutrophil degranulation, indicative of neutrophil mediated pathogen processing as a key host response to the VAP infection. Along with an increase in amino acids, this is suggestive of extracellular membrane degradation resulting from proteolytic activity of neutrophil proteases. The metaproteome approach successfully allowed simultaneous detection of pathogen peptides in patients' ETA, which may have potential use in diagnosis. Our findings suggest that ETA may facilitate early mechanistic insights into host-pathogen interactions associated with VAP infection and therefore provide its diagnosis and treatment.

Le ventre est l’une des parties du corps où il est plus difficile de perdre de la graisse. Souvent, la meilleure solution pour arriver à perdre de la graisse à cet endroit précis du corps consiste à manger sainement et équilibré. Cependant, quels sont les aliments qui brûlent les graisses du ventre sans danger pour la […]

L’article Quels sont les aliments qui brûlent rapidement les graisses du ventre ? est apparu en premier sur Ortho Doc France.

The increasing consumption of high-fat foods combined with a lack of exercise is a major contributor to the burden of obesity in humans. Aerobic exercise such as running is known to provide metabolic benefits, but how the over-consumption of a high fat diet (HFD) and exercise interact is not well characterized at the molecular level. Here, we examined the plasma proteome in mice for the effects of aerobic exercise as both a treatment and as a preventative regime for animals on either HFD or a healthy control diet. This analysis detected large changes in the plasma proteome induced by the HFD, such as increased abundance of SERPINA7, ALDOB, and down-regulation of SERPINA1E, CFD (adipsin). Some of these changes were significantly reverted using exercise as a preventative measure, but not as a treatment regime. To determine if either the intensity, or duration, of exercise influenced the outcome, we compared high-intensity interval training (HIIT) and endurance running. Endurance running slightly out-performed HIIT exercise, but overall, both provided similar reversion in abundance of plasma proteins modulated by the high-fat diet including SERPINA7, APOE, SERPINA1E, and CFD. Finally, we compared the changes induced by over-consumption of HFD to previous data from mice fed an isocaloric high saturated fat (SFA) or polyunsaturated fat (PUFA) diet. This identified several common changes including increased APOC2 and APOE, but also highlighted changes specific for either over-consumption of HFD (ALDOB, SERPINA7, CFD), SFA-based diets (SERPINA1E), or PUFA-based diets (Haptoglobin - Hp). Together, these data highlight the importance of early intervention with exercise to revert HFD-induced phenotypes and suggest some of the molecular mechanisms leading to the changes in the plasma proteome generated by high fat diet consumption. Web-based interactive visualizations are provided for this dataset (larancelab.com/hfd-exercise), which give insight into diet and exercise phenotypic interactions on the plasma proteome.

Innovative Financing for Humanitarian Energy Interventions Research paper sysadmin 28 February 2019

This paper explores the increase in resources and funding needed to improve the access of displaced people to modern and sustainable energy services.

Summary

• In settings that host displaced and refugee communities, energy can act as an enabler for improved healthcare, education and access to clean water. More efficient sources of energy can also save money that can be reinvested in life-saving interventions. A range of challenges exist that inhibit the uptake and effective management of cleaner energy solutions in displacement settings. These are magnified by a lack of available and appropriate funding.
• The current funding gap is significant. In many cases, involving the private sector (both enterprises and investors) is viewed as a way to accelerate delivery of sustainable energy solutions, leverage additional capital, efficiency and expertise, and adopt more sustainable and market-based approaches.
• Displacement settings are an extreme example of complex and unpredictable operating environments. Traditional approaches to the financing of energy access will not be supported by the risk/return characteristics of this market opportunity, so alternative structures are needed.
• Such structures can include mechanisms such as grants, guarantees, ‘results-based financing’ and ‘impact bonds’. These blended financial instruments should aim to leverage first losses – whereby, in the case of default, the first loss is taken by the ‘impact-first’ investors, or guarantors, thereby fully or partially protecting ‘finance-first’ investors.
• Given the specific constraints of displacement settings, any financing mechanisms at present are likely to fall between the categories of providing ‘more efficient aid’ and ‘more efficient aid through markets’. They are likely to constitute a transitional step from grant-making towards the use of commercial investment vehicles.
• While a number of financial mechanisms could be applied to attract private-sector engagement, most remain theoretical, with few being implemented extensively or at scale. Where such financial mechanisms have already been used, access to relevant data is poor, especially in circumstances where the desired outcomes were not achieved.
• The Moving Energy Initiative (MEI) completed feasibility work into the concept of an energy humanitarian fund and found that, while a need for this type of facility has emerged, it sits in a difficult position between energy access, climate and humanitarian funding sources. Key donors are needed to drive forward innovative financing vehicles and further testing of these mechanisms, in order to generate market data and evidence for further iterations and additional investments.

VOLUME 289 (2014) PAGES 6604–6618In Fig. 4G, in the foxi1 panel, the images in Fig. 4G, i and l, corresponding to “smad1 MO” and “smad5 MO + samd1/9 mRNA” samples, respectively, were inadvertently reused during figure preparation. This error has now been corrected using images pertaining to each treatment and sample. This correction does not affect the results or conclusions of the work.jbc;295/52/18650/F4F1F4Figure 4G.

Members event 1 February 2023 — 7:00PM TO 7:30PM Anonymous (not verified) 1 February 2023 Chatham House

Members event (open ticket) 1 February 2023 — 9:00PM TO 10:00PM Anonymous (not verified) 1 February 2023 Chatham House and Online

The move to assume broad powers over the Providence school system illustrates both the attraction and challenges of high-profile approaches to troubled or low-performing schools and districts.

Spending millions to guard against COVID-19 spread, district leaders also must convince parents school buildings are safe.

Palmyra-Eagle, a mostly rural school district in Southeast Wisconsin, lost more than half its students to surrounding districts and then taxpayers voted to dissolve the district.

EAU CLAIRE— This weekend saw the first basketball games for Blugold men’s and women’s basketball during the Market & Johnson Blugold Tip-Off Tournament. The games were the first to be played at the Sonnentag Event Center, a part of the new $122 million multi-purpose facility which opened earlier this year. The event center has a capacity of 3,500 people for sporting events as compared to the ...

Wen Grace Chen
Nov 9, 2022; 42:8498-8507
Symposium and Mini-Symposium

Umut Güçlü
Jul 8, 2015; 35:10005-10014
BehavioralSystemsCognitive

Alzheimer's disease (AD) and Alzheimer's disease-related dementias (ADRDs) are broad-impact multifactorial neurodegenerative diseases. Their complexity presents unique challenges for developing effective therapies. This review highlights research presented at the 2024 Society for Neuroscience meeting which emphasized the gut microbiome's role in AD pathogenesis by influencing brain function and neurodegeneration through the microbiota–gut–brain axis. This emerging evidence underscores the potential for targeting the gut microbiota to treat AD/ADRD.

Cochlear hair cells (HCs) sense sound waves and allow us to hear. Loss of HCs will cause irreversible sensorineural hearing loss. It is well known that DNA damage repair plays a critical role in protecting cells in many organs. However, how HCs respond to DNA damage and how defective DNA damage repair contributes to hearing loss remain elusive. In this study, we showed that cisplatin induced DNA damage in outer hair cells (OHCs) and promoted OHC loss, leading to hearing loss in mice of either sex. Cisplatin induced the expression of Brca1, a DNA damage repair factor, in OHCs. Deficiency of Brca1 induced OHC and hearing loss, and further promoted cisplatin-induced DNA damage in OHCs, accelerating OHC loss. This study provides the first in vivo evidence demonstrating that cisplatin mainly induces DNA damage in OHCs and that BRCA1 promotes repair of DNA damage in OHCs and prevents hearing loss. Our findings not only demonstrate that DNA damage–inducing agent generates DNA damage in postmitotic HCs but also suggest that DNA repair factors, like BRCA1, protect postmitotic HCs from DNA damage–induced cell death and hearing loss.

Thalamocortical pathways from the rodent ventral posterior (VP) thalamic complex to the somatosensory cerebral cortex areas are a key model in modern neuroscience. However, beyond the intensively studied projection from medial VP (VPM) to the primary somatosensory area (S1), the wiring of these pathways remains poorly characterized. We combined micropopulation tract-tracing and single-cell transfection experiments to map the pathways arising from different portions of the VP complex in male mice. We found that pathways originating from different VP regions show differences in area/lamina arborization pattern and axonal varicosity size. Neurons from the rostral VPM subnucleus innervate trigeminal S1 in point-to-point fashion. In contrast, a caudal VPM subnucleus innervates heavily and topographically second somatosensory area (S2), but not S1. Neurons in a third, intermediate VPM subnucleus innervate through branched axons both S1 and S2, with markedly different laminar patterns in each area. A small anterodorsal subnucleus selectively innervates dysgranular S1. The parvicellular VPM subnucleus selectively targets the insular cortex and adjacent portions of S1 and S2. Neurons in the rostral part of the lateral VP nucleus (VPL) innervate spinal S1, while caudal VPL neurons simultaneously target S1 and S2. Rostral and caudal VP nuclei show complementary patterns of calcium-binding protein expression. In addition to the cortex, neurons in caudal VP subnuclei target the sensorimotor striatum. Our finding of a massive projection from VP to S2 separate from the VP projections to S1 adds critical anatomical evidence to the notion that different somatosensory submodalities are processed in parallel in S1 and S2.

The early polygraph machine was considered the most scientific way to detect deception—but that was a myth

The Governing Body took a number of decisions that require action by Contracting Parties. This communication draws the attention of Contracting Parties to those decisions that are addressed to [...]

On Friday, 7 December during the 160th session of the Council, a side event on the Africa Solidarity Trust [...]

On 5 November 2020, from 12.30 to 14.30hrs, FAO Director-General, Dr QU Dongyu, will host a virtual High-Level event launching the Food Coalition. This dialogue will call for international cooperation [...]