ACS Infectious Diseases最新文献

Participation in research is supposed to be voluntary and informed. Yet it is difficult to ensure people are adequately informed about the potential uses of their biological materials when they donate samples for future research. We propose a novel consent framework which we call "demonstrated consent" that leverages blockchain technology and generative AI to address this problem. In a demonstrated consent model, each donated sample is associated with a unique non-fungible token (NFT) on a blockchain, which records in its metadata information about the planned and past uses of the sample in research, and is updated with each use of the sample. This information is accessible to a large language model (LLM) customized to present this information in an understandable and interactive manner. Thus, our model uses blockchain and generative AI technologies to track, make available, and explain information regarding planned and past uses of donated samples.

Hormone perception and signaling pathways play a fundamental regulatory function in the physiological processes of plants. Cytokinins, plant hormones, regulate cell division and meristem maintenance. The cytokinin signaling pathway is well-established in model plant Arabidopsis. Several negative feedback mechanisms, tightly controlling the cytokinin signaling output, were described previously. Here, we identified a new feedback mechanism executed through an alternative splicing of the cytokinin receptor AHK4/CRE1. A novel splicing variant named CRE1^int7 results from seventh intron retention, introducing a premature termination codon in the transcript. We show that CRE1^int7 is translated in planta into a truncated receptor lacking the C-terminal receiver domain essential for signal transduction. The CRE1^int7 can bind the cytokinin but cannot activate the downstream cascade. We present a novel negative feedback mechanism of the cytokinin signaling pathway facilitated by a decoy receptor, which can inactivate canonical cytokinin receptors via dimerization and compete with them for ligand binding. While a similar molecular mechanism is well-known in mammals, decoy receptors are rare in plants. Ensuring proper plant growth and development requires precise control of the cytokinin signaling pathway at several levels. The CRE1^int7 represents a yet unknown mechanism for fine-tuning the cytokinin signaling pathway in Arabidopsis.

Periodontal diseases, a group of complex conditions marked by an excessive immune response and periodontal tissue destruction, are a global health concern. Since 1990, the incidence of these diseases has doubled, with Western sub-Saharan Africa experiencing the highest burden. Accurate diagnosis and case identification are crucial for understanding the etiology, features of disease, research, treatment and prevention. Modern perspectives on periodontal disease classification are based on commonality among those affected. However, current literature is often plagued by methodological inconsistencies and focused on disease mechanisms in European populations. Health inequalities in low- and middle-income countries (LMICs) are exacerbated by these challenges, with sub-Saharan Africa, and Nigeria specifically, facing unique difficulties such as clinical personnel shortages and limited research infrastructure. This review explored disparities in periodontal disease research, care and outcomes in African populations. We highlighted these disparities and identified the factors contributing to inequities in periodontal health outcomes. We further demonstrated the critical need for inclusive and equitable healthcare and research practices tailored to the unique challenges faced by diverse populations and regions with limited resources. Addressing these disparities is essential for ensuring that advancements in healthcare are accessible to all, thereby improving global oral health and general health.

For decades, periodontitis has been considered to be a local inflammatory disease of the periodontal tissues in the oral cavity. Initially, associations of periodontitis with a multitude of noncommunicable diseases were each studied separately, and relationships were shown. The associations of periodontitis with morbidities, such as cardiovascular diseases, rheumatoid arthritis, diabetes mellitus, respiratory diseases, have been demonstrated. As most such studies were cross-sectional in nature, questions about causality cannot be univocally answered. And periodontitis as an independent risk factor for one systemic disease, becomes even more difficult to assess since recently periodontitis has also been associated with multimorbidity. Periodontitis and many systemic diseases share environmental, lifestyle and genetic risk factors, and share immunopathology. Moreover, suffering from one common noncommunicable disease may increase the susceptibility for another such chronic disease; the systemic effects of one condition may be one of various risk factors for another such disease. The overarching effect of any systemic disease is it causing a pro-inflammatory state in the individual; this has also been shown for periodontitis. Moreover, in periodontitis a prothrombotic state and elevated immunological activity have been shown. As such, when we consider periodontal disease as another systemic disease, it can affect the susceptibility and progression of other systemic diseases, and importantly, vice versa. And with this, it is not surprising that periodontitis is associated with a variety of other noncommunicable diseases. The medical definition of a systemic disease includes diseases that affect different organs and systems. Thus, the aim of this opinion paper is to propose that periodontitis should be considered a systemic disease in its own right and that it affects the individual's systemic condition and wellbeing. The dental and medical profession and researchers alike, should adapt this paradigm shift, advancing periodontal disease out of its isolated anatomical location into the total of chronic noncommunicable diseases, being for some conditions a comorbid disease and, vice versa, comorbidities can affect initiation and progression of periodontal disease.

Thousands of nuclear-encoded proteins are transported into chloroplasts through the TOC-TIC translocon that spans the chloroplast envelope membranes. A motor complex pulls the translocated proteins out of the TOC-TIC complex into the chloroplast stroma by hydrolyzing ATP. The Orf2971-FtsHi complex has been suggested to serve as the ATP-hydrolyzing motor in Chlamydomonas reinhardtii, but little is known about its architecture and assembly. Here, we report the 3.2-Å resolution structure of the Chlamydomonas Orf2971-FtsHi complex. The 20-subunit complex spans the chloroplast inner envelope, with two bulky modules protruding into the intermembrane space and stromal matrix. Six subunits form a hetero-hexamer that potentially provides the pulling force through ATP hydrolysis. The remaining subunits, including potential enzymes/chaperones, likely facilitate the complex assembly and regulate its proper function. Taken together, our results provide the structural foundation for a mechanistic understanding of chloroplast protein translocation.

Most coexisting insect species exhibit stunted growth compared to individual species on plants. This phenomenon reflects an interspecific antagonism drawing extensive attention, while the underlying mechanisms remain largely uncharacterized. Mirids (Apolygus lucorum) and cotton bollworms (Helicoverpa armigera) are two common cotton pests. We identified a secretory protein, ASP1, from the oral secretion of mirids, found in the nucleus of mirid-infested cotton leaves. ASP1 specifically targets the transcriptional co-repressor TOPLESS (TPL) and inhibits NINJA-mediated recruitment of TPL, promoting plant defense response and gossypol accumulation in cotton glands. ASP1-enhanced defense inhibits the growth of cotton bollworms on cotton plants, while having limited impact on mirids. The mesophyll-feeding characteristic allows mirids to avoid most cotton glands, invalidating cotton defense. Our investigation reveals the molecular mechanism by which mirids employ cotton defense to selectively inhibit the feeding of cotton bollworms.

Obligate biotrophs depend on living hosts for nutrient acquisition to complete their life cycle, yet the mechanisms by which hosts restrict nutrient availability to pathogens remain largely unknown. The fungal pathogen Sporisorium reilianum infects maize seedlings and causes head smut disease in inflorescences at maturity, while a cell wall-associated kinase, ZmWAK, provides quantitative resistance against it. In this study, we demonstrate that S. reilianum can rapidly activate ZmWAK kinase activity, which is sustained by the 407th threonine residue in the juxtamembrane domain, enabling it to interact with and phosphorylate ZmSnRK1α2, a conserved sucrose non-fermenting-related kinase α subunit. The activated ZmSnRK1α2 translocates from the cytoplasm to the nucleus, where it phosphorylates and destabilizes the transcription factor ZmWRKY53. The reduced ZmWRKY53 abundance leads to the downregulation of genes involved in transmembrane transport and carbohydrate metabolism, resulting in nutrient starvation for S. reilianum in the apoplast. Collectively, our study uncovers a WAK-SnRK1α2-WRKY53 signaling module in maize that conveys phosphorylation cascades from the plasma membrane to the nucleus to confer plant resistance against head smut in maize, offering new insights and potential targets for crop disease management.