Comprehensive maps of neuronal connectivity provide a foundation for understanding the structure of neural circuits. In a circuit, neurons are diverse in morphology, electrophysiology, gene expression, activity, and other neuronal properties. Thus, constructing a comprehensive connectivity map requires associating various properties of neurons, including their connectivity, at cellular resolution. A commonly used approach is to use the gene expression profiles as an anchor to which all other neuronal properties are associated. Recent advances in genomics and anatomical techniques dramatically improved the ability to determine and associate the long-range projections of neurons with their gene expression profiles. These studies revealed unprecedented details of the gene–projection relationship, but also highlighted conceptual challenges in understanding this relationship. In this article, I delve into the findings and the challenges revealed by recent studies using state-of-the-art neuroanatomical and transcriptomic techniques. Building upon these insights, I propose an approach that focuses on understanding the gene–projection relationship through basic features in gene expression profiles and projections, respectively, that associate with underlying cellular processes. I then discuss how the developmental trajectories of projections and gene expression profiles create additional challenges and necessitate interrogating the gene–projection relationship across time. Finally, I explore complementary strategies that, together, can provide a comprehensive view of the gene–projection relationship.

Mammalian astrocytes have regional roles within the brain parenchyma. Indeed, the notion that astrocytes are molecularly heterogeneous could help explain how the central nervous system (CNS) retains embryonic positional information through development into specialized regions into adulthood. A growing body of evidence supports the concept of morphological and molecular differences between astrocytes in different brain regions, which might relate to their derivation from regionally patterned radial glia and/or local neuron inductive cues. Here, we review evidence for regionally encoded functions of astrocytes to provide an integrated concept on lineage origins and heterogeneity to understand regional brain organization, as well as emerging technologies to identify and further investigate novel roles for astrocytes.

Over the past decades the zebrafish has emerged as an excellent model organism with which to study the biology of all glial cell types in nervous system development, plasticity, and regeneration. In this review, which builds on the earlier work by Lyons and Talbot in 2015, we will summarize how the relative ease to manipulate the zebrafish genome and its suitability for intravital imaging have helped understand principles of glial cell biology with a focus on oligodendrocytes, microglia, and astrocytes. We will highlight recent findings on the diverse properties and functions of these glial cell types in the central nervous system and discuss open questions and future directions of the field.

Most childhood cancers possess distinct clinicopathological profiles from those seen in adulthood, reflecting their divergent mechanisms of carcinogenesis. Rather than depending on the decades-long, stepwise accumulation of changes within a mature cell that defines adult carcinomas, many pediatric malignancies emerge rapidly as the consequence of random errors during development. These errors—whether they be genetic, epigenetic, or microenvironmental—characteristically block maturation, resulting in phenotypically primitive neoplasms. Only an event that falls within a narrow set of spatiotemporal parameters will forge a malignant clone; if it occurs too soon then the event might be lethal, or negatively selected against, while if it is too late or in an incorrectly primed precursor cell then the necessary intracellular conditions for transformation will not be met. The precise characterization of these changes, through the study of normal tissues and tumors from patients and model systems, will be essential if we are to develop new strategies to diagnose, treat, and perhaps even prevent childhood cancer.

Redox reactions control fundamental biochemical processes, including energy production, metabolism, respiration, detoxification, and signal transduction. Cancer cells, due to their generally active metabolism for sustained proliferation, produce high levels of reactive oxygen species (ROS) compared to normal cells and are equipped with antioxidant defense systems to counteract the detrimental effects of ROS to maintain redox homeostasis. The KEAP1-NRF2 system plays a major role in sensing and regulating endogenous antioxidant defenses in both normal and cancer cells, creating a bivalent contribution of NRF2 to cancer prevention and therapy. Cancer cells hijack the NRF2-dependent antioxidant program and exploit a very unique metabolism as a trade-off for enhanced antioxidant capacity. This work provides an overview of redox metabolism in cancer cells, highlighting the role of the KEAP1-NRF2 system, selenoproteins, sulfur metabolism, heme/iron metabolism, and antioxidants. Finally, we describe therapeutic approaches that can be leveraged to target redox metabolism in cancer.

The broad application of noninvasive imaging has transformed preclinical cancer research, providing a powerful means to measure dynamic processes in living animals. While imaging technologies are routinely used to monitor tumor growth in model systems, their greatest potential lies in their ability to answer fundamental biological questions. Here we present the broad range of potential imaging applications according to the needs of a cancer biologist with a focus on some of the common biological processes that can be used to visualize and measure. Topics include imaging metastasis; biophysical properties such as perfusion, diffusion, oxygenation, and stiffness; imaging the immune system and tumor microenvironment; and imaging tumor metabolism. We also discuss the general ability of each approach and the level of training needed to both acquire and analyze images. The overall goal is to provide a practical guide for cancer biologists interested in answering biological questions with preclinical imaging technologies.

The Respiratory Intensive Care Assembly of the European Respiratory Society gathered in Berlin to organise the third Respiratory Failure and Mechanical Ventilation Conference in February 2024. The conference covered key points of acute and chronic respiratory failure in adults. During the 3-day conference ventilatory strategies, patient selection, diagnostic approaches, treatment and health-related quality of life topics were addressed by a panel of international experts. In this article, lectures delivered during the event have been summarised by early career members of the Assembly and take-home messages highlighted.

Missing or inaccessible lung function measurements, gathered over time, have the potential to stagnate or impair clinical care decisions being made. This jeopardises patient safety and often contributes to excessive resource utilisation. Data integration is fundamental to clinical decision-making and entails amalgamating lung function data from multiple sources in a user-friendly format. Despite this, current systems for recording lung function data are suboptimal, with copious gaps in the clinical picture arising from missing or inaccessible lung function measurements. This article discusses the importance of data integration for lung function, with a call to action for key stakeholders involved in the performance, management and interpretation of such tests.

Advancements in immunotherapy in the perioperative setting have revolutionised the treatment of resectable nonsmall cell lung cancer (NSCLC). Here we present the methodology and results of the clinical trial CheckMate 816 demonstrating the benefit of neoadjuvant therapy with nivolumab plus chemotherapy compared with chemotherapy alone. Furthermore, this article discusses the implications for future practice in resectable NSCLC and the need for future research.

Lung cancer is one of the leading causes of death worldwide. It can broadly be divided into small cell lung cancer (SCLC) and nonsmall cell lung cancer. There have been many advances over the recent years in both fields. The purpose of this review is to provide a concise summary of SCLC for the general respiratory readership.

Palliative care pertains to the holistic multidimensional concept of "patient-centred" care. It is an interprofessional specialty, primarily aiming to improve quality of care for cancer patients and their families, from the time of diagnosis of malignant disease, over the continuum of cancer care, and extending after the patient's death to the period of bereavement to support the patient's family. There are various complex and frequently unmet needs of lung cancer patients and their families/caregivers, not only physical but also psychological, social, spiritual and cultural. Systematic monitoring of patients’ symptoms using validated questionnaires and patient-reported outcomes (PROs), on a regular basis, is highly encouraged and recommended in recent guidelines on the role of PRO measures in the continuum of cancer clinical care. It improves patient–physician communication, physician awareness of symptoms, symptom control, patient satisfaction, health-related quality of life and cost-effectiveness. This implies that all treating physicians should improve their skills in communication with lung cancer patients/relatives and become more familiar with this multidimensional assessment, repeatedly screening patients for palliative care needs. Therefore, they should receive education and training to develop palliative care knowledge, skills and attitudes. This review is dedicated to lung cancer palliative care essentials that should be within the competences of treating physicians, i.e. pneumologists/thoracic oncologists.

Season six's latest episode introduced Laszlo's father—and chaos inevitably followed.

Tim Miller hopes Amazon's anthology series will help viewers appreciate the "blood, sweat, and tears" Firewalk Studios put into the scrapped game.

The leak caught national intelligence officials by surprise and led to an embarrassing Air Force Inspector General investigation.

A new report by the global union Education International shows that AI can degrade the quality of education, worsen working conditions for teachers and provide inferior schooling for students.

The post Artificial Intelligence can cause fake education appeared first on rabble.ca.

Video game workers face challenges from employers in their efforts to unionize in Canada.

The post Dual boss battle: video game workers face-off multiple employers at once appeared first on rabble.ca.

The City of Vancouver council has reneged on a previous commitment to a living wage for its employees.

The post City of Vancouver to lowest paid workers: Let them eat cuts! appeared first on rabble.ca.

Deepfakes can be close to indistinguishable from authentic video, and are now being used to perpetrate gender based abuse.

The post Deepfakes and gender based violence appeared first on rabble.ca.

Danielle Smith says she is “100 per cent committed” to a leaked plan to replace Alberta Health Services with new health boards, agencies, bureaucracy, all directed out of her office.

The post UCP set to announce plan to bust up AHS appeared first on rabble.ca.

That anyone could witness or directly experience the increasingly frequent and intense heat domes, droughts, floods and record high temperatures and claim we don’t have a problem is insanity!

The post Don’t buy-in to climate science denialism appeared first on rabble.ca.

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HARI SREENIVASAN: The desire of the Kurds along Iraq’s northern border to govern themselves is receiving more resistance from Iraq’s central government. Iraqi army forces are demanding Kurdish troops withdraw from oil fields and military bases around Kirkuk, a city in the Kurdistan region that voted for independence last month. Kirkuk also has 10% of Iraq’s known oil reserves. Washington Post’s Loveday Morris is in Baghdad covering this standoff joins me now via Skype. First of all the significance of this. Why is it so important?

LOVEDAY MORRIS: There’s been a longtime conflict between Baghdad and Kurdistan over these disputed territories. Most significant of which is Kirkuk because of the oil reserves. But the referendum last month has really sharpened these disputes because you have Baghdad opposing independence and so it feels like they have to restate its territorial claims these areas. So that’s why we’re seeing a lot of tension right now.

HARI SREENIVASAN: And just to give people a little bit of a brief timeline – Iraqi forces control this area for a while and then in June ISIS took over the area and now it’s kind of back in Kurdish hands?

LOVEDAY MORRIS: Right. So in June 2014 Iraq lost control of a lot of the areas and we have this huge collapse in the face of an ISIS offensive. Over 100,000 soldiers fled and Kurdish forces moved in some of these areas – some of them maybe took from ISIS and others just moved into into the vacuum. And so Iraqi forces have been in these areas since June 2014. And that’s their main demand that they return to the areas.

HARI SREENIVASAN: What’s the likelihood that this standoff right now turns violent? Into some sort of a civil war?

LOVEDAY MORRIS:: I think at this point both sides don’t want violence. Al-Abadi, the prime minister, is really trying to defuse the situation by saying there’s going to be no military attack. But at the same time there is this buildup of forces so that I think they are trying to, in a way, intimidate the Kurds to withdraw from some areas but they don’t want to see a fight per say. But in this really tense situation there can be a small spark and things can turn violent quite easily.

HARI SREENIVASAN: Thank you.

The post Iraqi, Kurdish forces in standoff, weeks after Kurdish vote for independence appeared first on PBS NewsHour.

Watch President Donald Trump and the Greek prime minister’s joint news conference in the player above.

WASHINGTON — President Donald Trump says the U.S. stands with Greece as they recover from their economic crisis. He is speaking with Prime Minister Alexis Tsipras at the White House in a joint news conference.

The U.S. president says the two leaders have discussed defense, energy, commerce and trade.

Trump is praising Greece for its defense spending under NATO and is noting a potential sale to Greece to upgrade its F-16 aircraft, which he says would be worth up to $2.4 billion and generate thousands of U.S. jobs.

Tsipras says his country has made economic strides and is “leaving behind the economic model that led to the crisis.” He says Greece’s relationship with the U.S. is “more important than ever.”

The post WATCH: Trump and Greek prime minister hold joint news conference appeared first on PBS NewsHour.

HUNDREDS of travellers’ holiday plans are in disarray after all Tigerair flights in and out of Bali were cancelled again today and early tomorrow.

ROLLING UPDATES:Malcolm Turnbull heads into tomorrow’s Liberal Party campaign launch with the economy and stability firmly front and centre.

Ministers must follow the UK Government and extend rates relief for businesses in Scotland, Anas Sarwar has said.

As parts of Spain are on alert for new flood warnings, Dominic Hinde meets the volunteers still involved in the aftermath and recovery following the initial disaster

The accountancy firm has opened a new office in the Scottish town

The plane is hailed as 'one of the most advanced aircraft available on the market'

A rural housing project branded as ‘truly transformative’ has been completed

Emergency services were called to the Glebe Place area of the town

The SNP's Westminster leader has announced he is to contest a seat at Holyrood – and will ‘double-job’ as an MP and MSP if he wins.

Motorists have been urged to plan ahead with a major bridge due to close for work is carried out.  

The technology will deliver enhanced day-to-day and major incident response capability

A Scottish distillery has hailed the opening of a new 'dining destination' amid an expansion push.

Sir Andy Murray will swap Centre Court for the stage next summer as he embarks on a tour discussing his illustrious tennis career.

A baroque fiddle believed to have been played by Robert Burns will be performed live on stage in the United States for the first time.

A new digital-first Gaelic language production will be launched in Scotland after a joint agreement between BBC Alba and BBC Scotland.

The best way to predict the review score of a game is to play a demo of it. So never trouble another for what you can do yourself. For every minute you are playing you lose sixty seconds of ignorance. And without Pokémon tooth brushing games, life would be a mistake.

The post RPG Cast – Episode 547: “Cancer Inducing External Hardrive” appeared first on RPGamer.

It’s an extra large podcast this week. Alex, Kelley, Nathan, Chris, and Anna Marie break down all they’ve been playing. A huge news week is covered with colourful commentary. And we go off on more than one tangent. Help us, we’re incorrigible.

The post RPG Cast – Episode 556: “Chris Is Right for Once!” appeared first on RPGamer.

This week we finally figure out if Dark Souls ripped off Breath of the Wild. We also get really worked up over Bethesda. When is Game Pass coming to PS5, again?

The post RPG Cast – Episode 557: “PS5 Crunchwrap Supreme!” appeared first on RPGamer.

Josh is having an Ys-y time. Anna Marie ranks all the slime families. Robert gets notified every time google kills a product. And Chris tells everyone to blink on cue.

The post RPG Cast – Episode 572: “Partly Cloudy Souls With a Chance of Roguelike” appeared first on RPGamer.

Chris snuggles his Teddy body pillow. Kelley signs up for rare Pokémon. Josh sacrifices children (what?!). Meanwhile Anna Marie is off celebrating her birthday by spreading the hork.

The post RPG Cast – Episode 593: “Banished to the Prince Dimension” appeared first on RPGamer.

Chris gets caught up on Columbo while queueing for FFXIV. Eclipse steals the show from Kelley by opening the Chrome dev tools. And Josh sells all his Spoony Bard NFTs.

The post RPG Cast – Episode 613: “Nancy New Year” appeared first on RPGamer.

Kelley graduates from Canada. Josh discovers Tactics Advance is an isekai. Meanwhile Chris calculates the skill check for suplexing a train.

The post RPG Cast – Episode 619: “That One Time I Got Reincarnated as a Canadian Yankee in King Arthur’s Court” appeared first on RPGamer.

Kelley goes down the Sega Strategy Game Rabbit Hole. Chris becomes a doily shill. And Josh wants Sega to release Valkyria Chronicles as many times as it takes until people like it!

The post RPG Cast – Episode 629: “Legally Distinct Ghost Rider” appeared first on RPGamer.

Chris wonders if Pokémon is the future where the vegans win? Kelley just notices Josh's discord avatar is Joshua. Josh asks, "What is a mana game, but a miserable pile of menus?"

The post RPG Cast – Episode 650: “The Yodagrinch” appeared first on RPGamer.

Chris learns that Star Wars has all the nudie mods and bans it from his mod manager. Kelley is an apologist for Big the Cat. Jason draws stick sticks with his feet.

The post RPG Cast – Episode 678: “Dagon Qest Incasition” appeared first on RPGamer.