The master male sex determinant Gdf6Y of the turquoise killifish arose through allelic neofunctionalization.

Although sex determination is a fundamental process in vertebrate development, it is very plastic. Diverse genes became major sex determinants in teleost fishes. Deciphering how individual sex-determining genes orchestrate sex determination can reveal new actors in sexual development.

Strategies to enhance THz harmonic generation combining multilayered, gated, and metamaterial-based architectures.

Graphene has unique properties paving the way for groundbreaking future applications. Its large optical nonlinearity and ease of integration in devices notably makes it an ideal candidate to become a key component for all-optical switching and frequency conversion applications. In the terahertz (THz) region, various approaches have been independently demonstrated to optimize the nonlinear effects in graphene, addressing a critical limitation arising from the atomically thin interaction length.

Divergent roles of mA in orchestrating brown and white adipocyte transcriptomes and systemic metabolism.

N-methyladenosine (mA) is among the most abundant mRNA modifications, yet its cell-type-specific regulatory roles remain unclear. Here we show that mA methyltransferase-like 14 (METTL14) differentially regulates transcriptome in brown versus white adipose tissue (BAT and WAT), leading to divergent metabolic outcomes. In humans and mice with insulin resistance, METTL14 expression differs significantly from BAT and WAT in the context of its correlation with insulin sensitivity.

Coverage bias in small molecule machine learning.

Small molecule machine learning aims to predict chemical, biochemical, or biological properties from molecular structures, with applications such as toxicity prediction, ligand binding, and pharmacokinetics. A recent trend is developing end-to-end models that avoid explicit domain knowledge. These models assume no coverage bias in training and evaluation data, meaning the data are representative of the true distribution.

Comparing acute versus AIDS ART initiation on HIV-1 integration sites and clonal expansion.

Early antiretroviral therapy (ART) initiation is known to limit the establishment of the HIV reservoir, with studies suggesting benefits such as a reduced number of infected cells and a smaller latent reservoir. However, the long-term impact of early ART initiation on the dynamics of the infected cell pool remains unclear, and clinical evidence directly comparing proviral integration site counts between early and late ART initiation is limited. In this study, we used Linear Target Amplification-PCR (LTA-PCR) and Next Generation Sequencing to compare unique integration site (UIS) clonal counts between individuals who initiated ART during acute HIV infection stage (Acute-ART group) and those in the AIDS stage (AIDS-ART group).

Pseudomonas in the spotlight: emerging roles in the nodule microbiome.

While rhizobia have long been recognised as the primary colonisers of legume nodules, microbiome studies have revealed the presence of other bacteria in these organs. This opinion delves into the factors shaping the nodule microbiome and explores the potential roles of non-rhizobial endophytes, focusing particularly on Pseudomonas as prominent players. We explore the mechanisms by which Pseudomonas colonise nodules, their interactions with rhizobia, and their remarkable potential to promote plant growth and protect against pathogens.

Graft ischemia post cell transplantation to the brain: Glucose deprivation as the primary driver of rapid cell death.

Replacing cells lost during the progression of neurodegenerative disorders holds potential as a therapeutic strategy. Unfortunately, the majority of cells die post-transplantation, which creates logistical and biological challenges for cell therapy approaches. The cause of cell death is likely to be multifactorial in nature but has previously been correlated with hypoxia in the graft core.

A new hypothesis to explain disease dominance.

The onset and progression of dominant diseases are thought to result from haploinsufficiency or dominant negative effects. Here, we propose transcriptional adaptation (TA), a newly identified response to mRNA decay, as an additional cause of some dominant diseases. TA modulates the expression of so-called adapting genes, likely via mRNA decay products, resulting in genetic compensation or a worsening of the phenotype.

Deep learning model to identify and validate hypotension endotypes in surgical and critically ill patients.

Background: Hypotension is associated with organ injury and death in surgical and critically ill patients. In clinical practice, treating hypotension remains challenging because it can be caused by various underlying haemodynamic alterations. We aimed to identify and independently validate endotypes of hypotension in big datasets of surgical and critically ill patients using unsupervised deep learning.

Effect of applying a diabetes risk score on lifestyle counselling and shared decision-making in primary care: A pragmatic cluster randomised trial.

Aims: There is a lack of studies on the impact of diabetes risk scores on diabetes prevention. The aim of this study was to investigate the effect of applying a non-invasive diabetes risk score as component of routine health checks on counselling intensity and shared decision-making (SDM) in primary care.

Methods: Cluster randomised trial, in which primary care physicians (n = 30) enrolled participants (n = 315) with statutory health insurance without known diabetes, ≥ 35 years of age with a body mass index (BMI) ≥ 27.

Impact of anastomotic leak vs pneumonia on failure to rescue after transthoracic esophagectomy for cancer.

Background: Data about failure to rescue (FTR) after esophagectomy for cancer and its association with patient and procedure-related risk factors are limited. This study aimed to analyze such aspects, particularly focusing on the effect of pneumonia and anastomotic leak on FTR.

Methods: Patients who underwent an Ivor Lewis esophagectomy for cancer between 2008 and 2022 in 2 tertiary European centers were prospectively identified.

Sex hormone-dependent host-microbiome interactions and cardiovascular risk (XCVD): design of a longitudinal multi-omics cohort study.

Introduction: Cardiovascular diseases (CVDs) present differently in women and men, influenced by host-microbiome interactions. The roles of sex hormones in CVD outcomes and gut microbiome in modifying these effects are poorly understood. The XCVD study examines gut microbiome mediation of sex hormone effects on CVD risk markers by observing transgender participants undergoing gender-affirming hormone therapy (GAHT), with findings expected to extrapolate to cisgender populations.

Precuneus activity during retrieval is positively associated with amyloid burden in cognitively normal older carriers.

The precuneus is a site of early amyloid-beta (Aβ) accumulation. Previous cross-sectional studies reported increased precuneus fMRI activity in older adults with mild cognitive deficits or elevated Aβ. However, longitudinal studies in early Alzheimer's disease (AD) are lacking and the relationship to the Apolipoprotein-E () genotype is unclear.

Subthalamic nucleus deep brain stimulation in the beta frequency range boosts cortical beta oscillations and slows down movement.

Recordings from Parkinson's disease (PD) patients typically show strong beta-band oscillations (13-35Hz), which can be modulated by deep brain stimulation (DBS). While high-frequency DBS (>100Hz) ameliorates motor symptoms and reduces beta activity in basal ganglia and motor cortex, the effects of low-frequency DBS (<30Hz) are less clear. Clarifying these effects is relevant for the debate about the role of beta oscillations in motor slowing, which might be causal or epiphenomenal.

Deciphering compromised speech-in-noise intelligibility in older listeners: the role of cochlear synaptopathy.

Speech intelligibility declines with age and sensorineural hearing damage (SNHL). However, it remains unclear whether cochlear synaptopathy (CS), a recently discovered form of SNHL, significantly contributes to this issue. CS refers to damaged auditory-nerve synapses that innervate the inner hair cells and there is currently no go-to diagnostic test available.

Challenges in extracting and characterizing electrolytes from automotive lithium-ion cells.

Background: The demand for lithium-ion cells in the automotive industry is rapidly growing due to the increasing electrification of the transportation sector. The electrolyte composition plays a critical role in determining the lifetime and performance of these large-format cells. Additionally, advancements in this field are leading to frequent changes in both electrode materials and electrolyte formulations.

Single cell combined with laser ablation ICP-MS to study cisplatinum (IV) loaded nanoparticles penetration pathways in osteosarcoma spheroids.

Background: 3D cellular structures have been considered the following step in the evaluation of drugs penetration after 2D cultures since they are more physiologically representative in cancer cell biology. Here the penetration capabilities of Pt (IV)-loaded ultrasmall iron oxide nanoparticles in 143B osteosarcoma multicellular spheroids of different sizes is conducted by a multidimensional quantitative approach. Single cell (SC) and imaging techniques (laser ablation, LA) coupled to inductively coupled plasma-mass spectrometry (ICP-MS) are used to visualize their penetration pathways and distribution in comparison to those of cisplatin.