Loss of Smell Therapies Informed by Olfactory Receptor Spatial Mapping

A new study published in Cell titled, “A spatial code governs olfactory receptor choice and aligns sensory maps in the nose and brain,” led by researchers from Harvard Medical School (HMS) has created the first detailed map of the spatial distribution of over 1,000 olfactory receptors in the epithelium. The study informs the development of therapies for loss of smell, where treatment options are limited.

The researchers examined approximately 5.5 million neurons in more than 300 individual mice using single-cell sequencing and spatial transcriptomics. Results showed that neurons are organized into tight, overlapping, horizontal stripes from the top to the bottom of the nose based on the type of smell receptor expressed. This highly organized receptor map was consistent across mouse models and mirrored the organization of smell maps in the brain. Similar maps have been observed in vision, hearing, and touch.

Notably, the olfactory map was informed by a gradient of retinoic acid in the nose, which allowed each neuron to express the correct type of smell receptor based on its spatial location.  

“Our results bring order to a system that was previously thought to lack order, which changes conceptually how we think this works,” said Sandeep (Robert) Datta, PhD, professor of neurobiology at HMS and senior author and corresponding author of the study. “We show that development can achieve this feat of organizing a thousand different smell receptors into an incredibly precise map that’s consistent across animals.” 

The authors also found that the receptor map in the nose matches up with smell maps in the olfactory bulb of the brain, shedding insight into how information moves from the nose to the brain. 

While sensory maps that describe how receptors in the eye, ear, and skin are organized to capture and interpret auditory, visual, and touch information, mapping olfactory receptors has been a longstanding challenge due to high receptor diversity. As an example, mice have approximately 20 million olfactory neurons that express more than a thousand types of smell receptors, compared with only three main types of visual receptors for color vision. Each type of smell receptor detects a unique subset of odor molecules. 

The team is also studying smell receptors in human tissue to understand to what degree the smell map is consistent across species to inform treatments, such as stem cell therapies and loss of smell and its consequences, such as an increased risk of depression. 

“Smell has a really profound and pervasive effect on human health, so restoring it is not just for pleasure and safety but also for psychological well-being,” Datta said. “Without understanding this map, we’re doomed to fail in developing new treatments.” 

The post Loss of Smell Therapies Informed by Olfactory Receptor Spatial Mapping appeared first on GEN – Genetic Engineering and Biotechnology News.

<![CDATA[New US patent backs Denovo’s ANK3 biomarker guiding DB104 for treatment‑resistant depression, highlighting promising efficacy in selected patients.]]>
<![CDATA[Lifestyle medicine pillars help reshape depression and anxiety treatment in psychiatry.]]>

Acupoint temperature as a biomarker: infrared thermography in the diagnosis of adolescents with major depressive disorder

BackgroundThe prevalence of adolescent major depressive disorder (MDD) is rising; however, diagnosis relies on subjective measures due to a lack of objective biomarkers. This study explored infrared thermography (IRT) as a non-invasive tool to quantify thermal radiation characteristics of acupoints in adolescents with MDD. The objective was to establish diagnostic models based on acupoint temperature-derived biomarkers.MethodsA prospective, multi-center observational study enrolled 108 participants (65 adolescents with MDD and 43 healthy controls [HCs]). We first examined correlations between acupoint temperatures and depression severity using Pearson analysis. Multiple linear and binary logistic regression models were developed to diagnose MDD and assess severity. The diagnostic model for MDD was visualized as a nomogram and validated using Receiver Operating Characteristic (ROC) curves, Hosmer-Lemeshow tests, calibration plots, and decision curve analysis (DCA). Internal validation was performed using the bootstrap method.ResultsAmong 27 acupoints analyzed, adolescents with MDD exhibited altered acupoint temperatures at Taiyang (EX-HN5), Quchi (LI11), Yanggu (SI5), and Waiqiu (GB36). Subsequent Pearson correlation analysis revealed negative correlations between the infrared relative temperatures of Taiyang (EX-HN5), Quchi (LI11), and Waiqiu (GB36) and depression severity (P = 0.001, r = -0.319; P = 0.022, r = -0.229; P = 0.001, r = -0.325) and a weak positive correlation between the infrared relative temperature of Yanggu (SI5) and depression severity (P = 0.043, r = 0.202). Building on these findings, two diagnostic models were developed: a linear regression model for depression severity of adolescents (Y = 52.25-9.52*TEX-HN5-13.07*TGB36) and a logistic regression model for adolescents with MDD diagnosis (P = ex/(1+ex), x = 0.22-1.14*TEX-HN5+0.45*TSI5-2.19*TGB36). The nomogram-based model demonstrated good calibration (Hosmer-Lemeshow P = 0.855), discrimination (AUC = 0.785, 95%CI: 0.693 – 0.876), and clinical utility. Internal validation using the bootstrap method produced a C-index of 0.752 (95% CI: 0.617 – 0.877), further confirming the model’s robustness.ConclusionsIn conclusion, acupoint temperature-based models show promising efficacy for the objective and non-invasive diagnosis and severity quantification of adolescents with MDD, offering valuable tools for early clinical intervention. Future studies should validate these findings across diverse populations and integrate multi-modal biomarkers to enhance diagnostic precision.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT06750640.

Effects of bifrontal-transcranial direct current stimulation combined with music listening on sleep quality, cortical activation and functional connectivity in patients with insomnia: a randomised controlled trial by fNIRS

BackgroundAlthough music listening and transcranial direct current stimulation (tDCS) alone have certain effects in the treatment of insomnia, the sleep regulatory effects and neural mechanisms of the combined treatment in patients with insomnia disorder (ID) are unclear. This study aimed to investigate the efficacy of combined bifrontal-tDCS (F3: anode, F4: cathode) with music listening in patients with ID using functional near-infrared spectroscopy (fNIRS).Methods76 ID patients were randomly divided into an intervention group (n=38) and a control group (n=38), and received 4 weeks of a total of 20 sessions of music + tDCS therapy and music + sham tDCS therapy (30-second stimulation with fade-in/fade-out to mimic somatic sensations), respectively. The Pittsburgh Sleep Quality Index Scale (PSQI), Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), and Perceived Stress Scale (PSS-14) were compared between the two groups before and after treatment. Oxy-haemoglobin (HbO2) concentration and functional connectivity (FC) were assessed during the verbal fluency task using fNIRS.ResultsCompared with the control group, the PSQI total score (mean difference: -2.57 points, 95% CI: -4.43 to -0.71, p = 0.001), PSQI sub-scores except “sleep disturbance and daytime dysfunction”, SDS and SAS scores of the intervention group improved significantly after treatment. It was observed by fNIRS that the HbO2 concentration in the medial prefrontal cortex (mPFC), left dorsolateral prefrontal cortex (DLPFC), right ventrolateral prefrontal cortex, and right superior frontal cortex (SFC) increased significantly after treatment in the intervention group but was not superior to the control group. In addition, the FC enhancement of left SFC-left DLPFC and left SFC-mPFC after treatment was significantly better in the intervention group than in the control group, and the PSQI improvement was positively correlated with the FC enhancement of channel-averaged and left SFC-right DLPFC.ConclusionsCombining bifrontal-tDCS with music listening is more helpful in improving sleep quality and prefrontal functional connectivity in ID patients compared with music listening alone. For ID patients, music electrical stimulation headphones may be a safe, effective, and convenient new treatment strategy.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2400086233.

Prevalence of Cognitive Distortion Markers in a Suicide Prevention Chat Service: Mixed Methods Study

Background: Suicide helplines increasingly employ chat services to aid those in urgent need, but the wording and structure of text-driven exchanges may affect their effectiveness. Objective: Given the association of cognitive distortions with depression and anxiety, this study investigated their prevalence in the language of individuals seeking help from the Dutch 113 suicide helpline. Methods: We observed the prevalence of cognitive distortions for both help seekers and counselors in a large volume of chat sessions (N=71,148) of the Dutch 113 suicide chat helpline using natural language processing. The results were compared to 2 large collections of online text data from Dutch social media and web content. Results: We found that nearly all types of cognitive distortions are more prevalent in the language of help seekers compared to the control group of helpline counselors. Distortions of the personalizing, emotional reasoning, and mental filtering types were, respectively, 20.22, 7.87, and 4.53 times more prevalent among help seekers, revealing a distinct pattern of thought and language among individuals affected by suicidality. Conclusions: Our results raise the prospect of improving the effectiveness of online therapeutic interventions that target cognitive distortions through lexical analysis that detects the cognitive and lexical markers of suicidality.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/00f57a522b7e20d230db8854f4090023" />

The Download: Musk and Altman’s legal showdown, and AI’s profit problem

This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology.

Elon Musk and Sam Altman are going to court over OpenAI’s future

Elon Musk and OpenAI CEO Sam Altman head to trial this week in a case with sweeping consequences. Ahead of OpenAI’s IPO, the court could rule on whether the company can exist as a for-profit enterprise. It could even oust its leadership.

Musk, an OpenAI co-founder, claims he was deceived into bankrolling the firm under false pretenses. He’s seeking $134 billion in damages, the removal of Altman and president Greg Brockman, and the company’s restoration to a non-profit.

Find out how the trial could upend the global AI race.

—Michelle Kim

The missing step between hype and profit

In a celebrated South Park episode, a community of gnomes sneak out at night to steal underpants. Why? The gnomes present their pitch deck. “Phase 1: Collect underpants. Phase 2: ? Phase 3: Profit.” It’s a business plan that captures the current state of AI. 

Companies have built the tech (Step 1) and promised transformation (Step 3). But how they get there is still a big question mark. Read about the potential paths forward.


—Will Douglas Heaven

This story originally appeared in The Algorithm, our weekly newsletter giving you the inside track on all things AI. Sign up to receive it in your inbox every Monday.

Welcome to the era of weaponized deepfakes

For years, experts have warned that deepfakes could be deployed in malicious ways. These dangers are now here.

Cheap, accessible models now produce weaponized deepfakes—from sexually explicit images to political propaganda—that look startlingly real. They’re already inciting violence, changing minds, and sowing mistrust, with women and marginalized groups disproportionately affected.

Experts fear that they’re cratering trust and critical thinking. Here’s why they’re alarmed.

—Eileen Guo

Weaponized deepfakes are on our list of the 10 Things That Matter in AI Right Now, MIT Technology Review’s guide to what’s really worth your attention in the busy, buzzy world of AI. 

The must-reads

I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.

1 OpenAI has ended its exclusive partnership with Microsoft
The new deal allows OpenAI to court rivals such as Amazon. (Reuters $)
+ Microsoft will still license OpenAI’s tech, but no longer exclusively. (NYT $)
+ OpenAI is missing key growth targets ahead of its IPO. (WSJ $)

2 Google has signed a classified AI deal with the Pentagon
It permits AI use for “any lawful government purpose.” (The Information $)
+ Over 600 Google workers had called for a block on the deal. (QZ)
+ AI firms are set to train military versions of their models on classified data. (MIT Technology Review)

3 The EU has told Google to open Android to AI rivals
It wants to end Gemini’s built-in advantage. (Ars Technica)
+ Google calls the move an “unwarranted intervention.” (WSJ $)
+ A final decision is expected by the end of July. (Reuters $)

4 OpenAI is reportedly developing an AI-first smartphone
It would replace apps with agents. (TechCrunch)
+ Qualcomm and MediaTek may be developing its processors. (Gizmodo)

5 A brain implant for depression is moving into human testing
The FDA has approved a human study of the device. (Wired $)
+ BCIs have thus far struggled to reach the market. (MIT Technology Review)

6 A populist backlash against AI is gaining momentum in rural America
From Indiana to Idaho, voters are pushing back against the technology. (NYT $)
+ Anti-AI protests are expanding worldwide. (MIT Technology Review)

7 DeepSeek has priced its new model 97% below OpenAI’s GPT-5.5
It aims to attract more enterprises, developers, and agent-based users. (SCMP)
+ Here are three reasons why DeepSeek V4 matters. (MIT Technology Review)

8 AI now generates a third of new websites
A study found it’s making the web more cheery and less verbose. (404 Media)

9 Top talent is leaving Big Tech to launch their own AI startups
Meta, Google, and OpenAI are facing a brain drain. (CNBC)

10 Taylor Swift is trademarking her voice and image
The Grammy winner has been the target of numerous deepfakes. (NBC News)
+ A growing number of celebrities are fighting AI with trademarks. (BBC)

Quote of the day

“The reality is people don’t like him.”

—Judge Yvonne Gonzalez Rogers reacts to prospective jurors confessing their negative views of Elon Musk ahead of his legal battle with Sam Altman, The Verge reports.

One More Thing


How covid conspiracy theories led to an alarming resurgence in AIDS denialism

When Joe Rogan falsely declared that “party drugs” were an “important factor in AIDS,” several million people were listening. He also asserted that AZT, the earliest drug used to treat AIDS, killed people “quicker” than the disease itself—another claim that has been disproven.

Such comments illustrate an unmistakable resurgence in AIDS denialism: a false collection of theories arguing either that HIV does not cause AIDS or that there is no such thing as HIV at all. By the dawn of the millennium, these claims had largely fallen out of favour. That changed when the coronavirus arrived.

Follow the digital path from Covid skepticism to the return of a deadly conspiracy theory.


—Anna Merlan

We can still have nice things

A place for comfort, fun and distraction to brighten up your day. (Got any ideas? Drop me a line.)

+ Explore the planets from your laptop with this live sky map.
+ This marathon DJ set from Daphni is an incredible journey through electronic music.
+ NASA’s stunning Artemis II wallpapers bring a high-res piece of deep space to your phone.
+ This fascinating GPS explainer breaks down how your phone figures out exactly where you are.