Genetically-encoded targeted protein degradation technology to remove endogenous condensation-prone proteins and improve crop performance.

Effective modulation of gene expression in plants is achievable through tools like CRISPR and RNA interference, yet methods for directly modifying endogenous proteins remain lacking. Here, we identify the E3 ubiquitin ligase E3TCD1 and develope a Targeted Condensation-prone-protein Degradation (TCD) strategy. The X-E3TCD1 fusion protein acts as a genetically engineered degrader, selectively targeting endogenous proteins prone to condensation.

In situ osteogenic activation of mesenchymal stem cells by the blood clot biomimetic mechanical microenvironment.

Blood clots (BCs) play a crucial biomechanical role in promoting osteogenesis and regulating mesenchymal stem cell (MSC) function and fate. This study shows that BC formation enhances MSC osteogenesis by activating Itgb1/Fak-mediated focal adhesion and subsequent Runx2-mediated bone regeneration. Notably, BC viscoelasticity regulates this effect by modulating Runx2 nuclear translocation.

Categorization of 34 computational methods to detect spatially variable genes from spatially resolved transcriptomics data.

In the analysis of spatially resolved transcriptomics data, detecting spatially variable genes (SVGs) is crucial. Numerous computational methods exist, but varying SVG definitions and methodologies lead to incomparable results. We review 34 state-of-the-art methods, classifying SVGs into three categories: overall, cell-type-specific, and spatial-domain-marker SVGs.

Chromosome-level genome assembly of the sweet potato rot nematode Ditylenchus destructor.

Ditylenchus destructor, commonly known as the potato rot nematode, is a significant plant-parasitic pathogen affecting over 120 plant species globally. Effective control measures for D. destructor are limited, underscoring the need a high-quality reference genome to understand its pathogenic mechanisms.

Thyroid cancer.

In recent decades, the diagnosis of thyroid cancer, especially the papillary type, has increased significantly due to the use of imaging techniques such as ultrasound. For this reason, it is essential to rationalize diagnosis and treatment, since the behavior of thyroid cancer varies from slow-progressing tumors to highly aggressive ones. The application of risk assessment systems for ultrasound images and the optimization of cytology incorporating molecular studies allows cases to be stratified in order to select therapy on an individual basis.

Cancer evolution: from Darwin to the Extended Evolutionary Synthesis.

The fundamental evolutionary nature of cancer has been recognized for decades. Increasingly powerful genetic and single cell sequencing technologies, as well as preclinical models, continue to unravel the evolution of premalignant cells, and progression to metastatic stages and to drug-resistant end-stage disease. Here, we summarize recent advances and distil evolutionary principles and their relevance for the clinic.

Myosin Heavy Chain Myopathy and Immune-Mediated Muscular Disorders.

Several inflammatory myopathies have an infectious or immune-mediated basis in the horse. Myosin heavy chain myopathy is caused by a codominant missense variant in MYH1 and has 3 clinical presentations: immune-mediated myositis, calciphylaxis, and nonexertional rhabdomyolysis in Quarter Horse-related breeds. An infarctive form of purpura hemorrhagica affects numerous breeds, presenting with focal firm, painful muscle swelling, and subsequent infarction of multiple tissues.

Advances in systematic conservation planning to meet global biodiversity goals.

Systematic conservation planning (SCP) involves the cost-effective placement and application of management actions to achieve biodiversity conservation objectives. Given the political momentum for greater global nature protection, restoration, and improved management of natural resources articulated in the targets of the Global Biodiversity Framework, assessing the state-of-the-art of SCP is timely. Recent advances in SCP include faster and more exact algorithms and software, inclusion of ecosystem services and multiple facets of biodiversity (e.

Identification of the molecular characterization and tumor microenvironment of thoracic inflammatory myofibroblastic tumors.

Background: Inflammatory myofibroblastic tumors (IMTs), rare soft tissue neoplasms, are characterized by a blend of myofibroblastic proliferation and inflammatory features. While generally characterized by slow growth, IMTs can exhibit locally aggressive behavior, and in rare instances, metastasize to distant sites. This study elucidated the clinical characteristics, molecular profile, and tumor microenvironment of thoracic IMTs.

Time persistence of the fMRI resting-state functional brain networks.

Time persistence is a fundamental property of many complex physical and biological systems; thus understanding the phenomenon in the brain is of high importance. Time persistence has been explored at the level of stand-alone neural time-series, but since the brain functions as an interconnected network, it is essential to examine time persistence at the network level. Changes in resting-state networks have been previously investigated using both dynamic (i.

The Rbfox1/LASR complex controls alternative pre-mRNA splicing by recognition of multipart RNA regulatory modules.

The Rbfox proteins regulate alternative pre-mRNA splicing by binding to the RNA element GCAUG. In the nucleus, most of Rbfox is bound to the large assembly of splicing regulators (LASR), a complex of RNA-binding proteins that recognize additional RNA motifs. However, it remains unclear how the different subunits of the Rbfox/LASR complex act together to bind RNA and regulate splicing.

Functional impairment in COPD can be predicted using genomic-derived data.

Objective: Reduced functional capacity and muscle weakness are two major contributors to functional impairment in chronic obstructive pulmonary disease (COPD). The underlying causes of functional impairment are poorly understood and, therefore, we sought to investigate the contribution of genetic factors.

Methods: We conducted a cross-sectional analysis of sociodemographic, clinical and genetic information of people with COPD.

Low-coverage whole genome sequencing of low-grade dysplasia strongly predicts advanced neoplasia risk in ulcerative colitis.

Background: The risk of developing advanced neoplasia (AN; colorectal cancer and/or high-grade dysplasia) in ulcerative colitis (UC) patients with a low-grade dysplasia (LGD) lesion is variable and difficult to predict. This is a major challenge for effective clinical management.

Objective: We aimed to provide accurate AN risk stratification in UC patients with LGD.

Tracking transmission through transposable elements in uropathogenic and commensal .

Aim: To investigate the nucleotide sequences associated with transposable elements carrying bla allelic variants as potential markers for the transmission of antimicrobial resistance genes between domestic animals, humans and the environment.

Materials & Methods: We conducted whole-genome sequencing and analyzed the nucleotide sequences of most abundant bla allelic variants (bla, bla, and bla) in commensal Escherichia coli ( = 20) from household members in Quito and uropathogenic E. coli (UPEC) ( = 149) isolated from nine clinics in Quito, Ecuador.

Analytical and Clinical Validation of the Plasma-Based Guardant360 CDx Test for Assessing HER2 (ERBB2) Mutation Status in Patients with Non-Small-Cell Lung Cancer for Treatment with Trastuzumab Deruxtecan in DESTINY-Lung01/02.

This study demonstrates the analytical and clinical validity of the approved (United States and Japan) plasma-based Guardant360 companion diagnostic (CDx) test for selecting patients with human epidermal growth factor receptor 2 (HER2 [ERBB2])-mutated (HER2m) non-small-cell lung cancer (NSCLC) for trastuzumab deruxtecan (T-DXd) treatment. Concordance between the Guardant360 CDx test and the plasma-based AVENIO ctDNA Expanded Kit Assay (AVENIO), as well as the tissue-based clinical trial assays (CTAs) was investigated. Clinical utility was assessed by comparing T-DXd clinical efficacy results of patients in DESTINY-Lung01/02 who tested positive for HER2 mutations using the Guardant360 CDx test to benchmark efficacy results from DESTINY-Lung01/02.

Risk stratification and exercise recommendations in cardiomyopathies and channelopathies: a practical guide for the multidisciplinary team.

Exercise offers a plethora of health benefits. However, certain genetic and acquired diseases such as cardiomyopathies and channelopathies are associated with sudden cardiac death during exercise. Several factors complicate exercise prescription in individuals living with these conditions.

Frozen versus fresh embryo transfer in women with low prognosis for in vitro fertilisation treatment: pragmatic, multicentre, randomised controlled trial.

Objective: To test the hypothesis that a freeze-all strategy would increase the chance of live birth compared with fresh embryo transfer in women with low prognosis for in vitro fertilisation (IVF) treatment.

Design: Pragmatic, multicentre, randomised controlled trial.

Setting: Nine academic fertility centres in China.

Genomes reveal pervasive distant hybridization in nature among cyprinid fishes.

Background: Genomic data have unveiled a fascinating aspect of the evolutionary past, showing that the mingling of different species through hybridization has left its mark on the histories of numerous life forms. However, the relationship between hybridization events and the origins of cyprinid fishes remains unclear.

Results: In this study, we generated de novo assembled genomes of 8 cyprinid fishes and conducted phylogenetic analyses on 24 species.

SSL-VQ: Vector-quantized variational autoencoders for semi-supervised prediction of therapeutic targets across diverse diseases.

Motivation: Identifying effective therapeutic targets poses a challenge in drug discovery, especially for uncharacterized diseases without known therapeutic targets (e.g. rare diseases, intractable diseases).

The developmental and genetic basis of male genitalia evolution in Drosophilids.

Reproductive organs are among the most variable and rapidly evolving structures in the animal kingdom, probably due to sexual selection. In insects, the diverse morphology of male genitalia is often one of the few visible characteristics that can reliably distinguish closely related species, making it crucial for taxonomic classification. Consistent with this, males of the model organism Drosophila melanogaster and its closely related species display remarkable variations in genital morphology.

SCoT and ISSR based conservation genetics of Calligonum polygonoides Linn.: An endangered species of Thar desert.

Calligonum polygonoides, an endangered species of desert due to poor regeneration and overexploitation, which requires immediate conservation attention. Genetic diversity analysis is crucial for effective conservation and management initiatives, for elite genotypes. Therefore, in the present study, SCoT (start codon target) and ISSR (inter simple sequence repeat) markers were used to investigate the genetic variability in 120 individuals of Calligonum polygonoides.

Optimising medium chain carboxylate production in xylan mixed-culture monofermentation.

This work investigates the optimization of medium-chain carboxylate (MCC) production through xylan mixed-culture monofermentation. The pH screening in batch assays showed that the hydrolysis stage and selectivity towards MCC precursors were optimised at pH 6. Subsequently, a continuous stirred tank reactor (CSTR) and a Sequential Batch Reactor (SBR) were operated at different Hydraulic Retention Times (HRT), revealing that the SBR at HRT 2 days yielded the highest caproic acid since lactic acid availability and chain elongation process were balanced.

Clinical perspective on pluripotent stem cells derived cell therapies for the treatment of neurodegenerative diseases.

Self-renewal capacity and potential to differentiate into almost any cell type of the human body makes pluripotent stem cells a valuable starting material for manufacturing of clinical grade cell therapies. Neurodegenerative diseases are characterized by gradual loss of structure or function of neurons, often leading to neuronal death. This results in gradual decline of cognitive, motor, and physiological functions due to the degeneration of the central nervous systems.

Mitral Valve Prolapse Caused by TLL1 Gain-of-Function Mutation.

Background: Mitral valve prolapse (MVP) is a common cardiac valvular anomaly that can be caused by mutations in genes of various biological pathways. Individuals of three generations of a kindred presented with apparently dominant heredity of isolated MVP.

Methods: Clinical evaluation and echocardiography for all complying family members (n=13).

A novel amino-pyrimidine inhibitor suppresses tumor growth via microtubule destabilization and Bmi-1 down-regulation.

Colorectal cancer (CRC), one of the diseases posing a threat to global health, according to the latest data, is the third most common cancer globally and the second leading cause of cancer-related deaths. The development and refinement of novel structures of small molecular compounds play a crucial role in tumor treatment and overcoming drug resistance. In this study, our objective was to screen and characterize novel compounds for overcoming drug resistance via the B Lymphoma Mo-MLV insertion region 1 (Bmi-1) reporter screen assay.