Research Highlights

Nanoparticle therapy continues to be an attractive avenue of targeted and personalised therapies. A molecular nano-conjugate developed by Zeng et al. effectively targets cancer cells and aids in their diagnosis, therapy, and also optimises innate immune responses.

Despite ample investigation on cis-regulatory alterations in evolution, the contribution of these effects to environmental adaptation is poorly understood. Ballinger and colleagues dissected the cis- and trans-regulatory impact on gene expression associated with the adaptation of house mice to temperate and tropical climates, highlighting potential mechanisms acting at a short evolutionary timescale.

The physical properties of the cells and proteins surrounding a tumor play a crucial role in determining the spread of the cancer. How they change cancer cells to suppress the immune response against them is an interesting question addressed in a recent study from Liu et al., which describes how increased stiffness of the tissue around the tumor decreases the amount of a protein—cyclic GMP-AMP synthase—in cancer cells, ultimately blocking the immune response to cancer.

As a monogamous species, the prairie vole is a common model for social neuroscience. Gustison and colleagues mapped a whole-brain histological atlas of the prairie vole and used this atlas to identify a neural network of pair-bonding behaviour. The study reveals coordinated neural networks in mated pairs and highlights the influence of social bonding on neural processing in the adult prairie vole brain.

Nanopores have the potential to revolutionize the field of protein sequencing, but due to the biochemical complexity of polypeptide sequences, they have remained mostly theoretical. In recent work, Sauciuc et al. engineer the protein nanopore CytK to produce an electroosmotic force capable of translocating unfolded polypeptides regardless of their charge distributions, an important step toward single-file protein nanopore sequencing.

Plant organs shift their directional growth in response to environmental stimuli through tropisms. Arabidopsis roots exhibit positive hydrotropism (towards water) and negative phototropism (away from light). In a recent study, Pang and colleagues demonstrated that root phototropism is regulated by the activity of two proteins in the elongation zone that also play essential roles in hydrotropism.

The cerebellum is more than just motor control: over the past 30 years, the notion that the “little brain” participates in cognitive functions and emotional response has grown to encompass social-related behaviors. Chao et al. bring to light the role of the cerebellar vermis in orchestrating a specific component of social memory in mice.

Retinal degenerative diseases are often multifaceted and difficult to treat, instead requiring more targeted or personalized therapeutic solutions. Recent work by Liu et al. reveals one such pipeline to engineer extracellular vesicles that can selectively reduce the spread of retinal inflammation and prevent the progression of vision loss in rodent models of retinal degeneration. This approach is representative of a new wave of precision medicines with the potential to treat these otherwise incurable diseases.

Although liquid-liquid phase separation (LLPS) has been extensively studied in various cellular and organismal contexts, the link between functional influence of a genetic mutation and LLPS with respect to human diseases is poorly understood. A recent article by Mensah et al. looks at a rare genetic disease to identify a frameshift mutation, which triggered aberrant phase separation and nucleolar dysregulation, linking genetic variants to a dysregulation of biomolecular condensates.

Behavioral results suggest that learning by trial-and-error (i.e., reinforcement learning) relies on a teaching signal, the prediction error, which quantifies the difference between the obtained and the expected reward. Evidence suggests that distinct cortico-striatal circuits are recruited to encode better-than-expected (positive prediction error) and worst-than-expected (negative prediction error) outcomes. A recent study by Villano et al.¹ provides evidence for differential networks that underlie learning from positive and negative prediction errors in humans using real-life behavioral data. More specifically, they found that university students are more likely to update beliefs concerning grade expectations following positive rather than negative prediction errors.

Cilia assembly and function require intraflagellar transport (IFT), a mechanism that uses “trains” to transport cargoes into and out of cilia. While much has been learned about IFT in the past decades, IFT train assembly, loading of cargo and transport regulation have remained poorly understood. In a recent study, Hesketh, Mukhopadhyay and colleagues obtained the complete structure of the IFT-A complex, a key element of IFT trains. By modelling IFT-A into anterograde trains and performing structure-guided mutagenesis, the authors uncover how the IFT-A complex polymerizes and forms carriages to accomplish its distinctive functions.

The BIL1/BZR1 transcription factor is known to regulate transcriptional responses to the brassinosteroid class of phytohormones by directly recognizing short cis regulatory elements in promoters. A new study by Shohei Nosaki, Nobutaka Mitsuda, and colleagues published in Nature Plants indicates that binding of this transcription factor is additionally affected by nucleobases that influence DNA shape but are not directly contacted by BIL1/BZR1.

Anti-retroviral therapy with drugs like dolutegravir is a powerful tool in both the treatment and prevention of HIV, but is limited by strict adherence to a daily therapeutic regimen. In a recent study, Deodhar, Sillman, and colleagues developed a dolutegravir prodrug that offers long-lasting protection against HIV infection, with the potential to dramatically improve anti-retroviral therapy efficacy.

While recent advances in plant single-cell RNA sequencing (scRNA-seq) have made numerous strides in identifying novel regulatory events, transcriptional profiling of certain cell types, such as phloem poles, has not yet been thoroughly investigated. A recent article by Otero et al. utilized cell-type specific marker lines and a second-generation single-cell approach to uncover transcriptomic landscapes specifying protophloem-adjacent cells, as well as identify a set of important transcription factors (TFs) signifying early phloem development.

The viruses infecting bacteria, known as phages, carry a wondrous diversity of enzymes known as endolysins, which are responsible for opening cellular doors, like the membrane or wall, so that newly minted phages are set free. In a recent study, Oechslin and colleagues explored the evolutionary mystery of lactococcal endolysin biodiversity, suggesting that these endolysins are flexible and can be used as kinds of skeleton keys to open a broad range of cellular doors.

Oligodendrocytes are derived from a subtype of glia called oligodendrocyte precursor cells (OPCs). The potential functions of OPCs beyond oligodendrogenesis however, have remained elusive. In their latest study, Auguste et al. demonstrate that OPCs could play a regulatory role in synaptic connectivity in the developing and adult mouse visual cortex - a function that is independent of oligodendrogenesis.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, with less than 10% of patients surviving more than five years. A major challenge of PDAC is understanding the complexity of the tumor architecture and identifying targetable cellular phenotypes that can inform clinical decision-making. Hwang et al. recently harnessed spatially-resolved transcriptomics to characterize gene expression profiles across PDAC tumor slices and identified recurrent expression patterns in malignant and fibroblast cellular neighborhoods that correlated with treatment outcomes.

Soil microbiota, including arbuscular mycorrhizal fungi (AMF), are critical for plant nutrition in non-agricultural ecosystems. A new study by Edlinger et al. shows that agricultural soils are negatively impacted by fungicide use and generally have lower AMF diversity and abundance.

More than twenty years have passed since the first complex genetic circuits were implemented in the model bacteria, Escherichia coli. Yet, translating these circuits to other clinically-relevant bacteria remains a challenge. In a recent study, Huang and colleagues applied engineered transcription factors to control the growth of a microbial community of Bacteroides species.

Many genetic disorders are a result of single or multiple genome abnormalities. A possible approach to circumvent genetic disorders is to use gene editing agents to correct these mistakes, but a major challenge remains in the mode of delivery of gene editing agents to different regions of the body. Banskota et al. present the use of engineered DNA-free virus-like particles (eVLPs) to deliver base editors to different organs in a mice model for improved outcomes, highlighting the potential of eVLPS to deliver base editors and as an efficient delivery mechanism, leveraging the advantages of viral and nonviral delivery methods.