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Mycobacterium xenopi, a nontuberculous mycobacterium (NTM), presents a significant diagnostic challenge in clinical practice, particularly in immunocompromised individuals. We report a case of M. xenopi infection in a liver transplant recipient on immunosuppressive medication. A 67-year-old male presented with chronic cough, anemia, and significant weight loss. Imaging studies revealed extensive pulmonary involvement with cavitations. More definitively, an acid-fast bacilli (AFB) bronchoalveolar lavage culture as well as an acid-fast bacilli (AFB) sputum culture confirmed M. xenopi infection. Treatment initiation with multiple antimicrobial agents was guided by susceptibility testing and published recommendations by the Infectious Disease Society of America and the American Thoracic Society guidelines from 2020 (Kurz, et al., 2020). This case emphasizes the importance of considering non-tubercular bacterial infections, particularly M. xenopi, in the differential diagnosis of respiratory symptoms in immunocompromised hosts. In addition to the case report, this paper provides a comprehensive review of the epidemiology, risk factors, clinical manifestations, diagnostic challenges, and treatment strategies for M. xenopi infections.

Abstract The aim of this study is to characterize cell type-specific transcriptional signatures in non-alcoholic steatohepatitis (NASH) to improve our understanding of the disease. We performed single-cell RNA sequencing on liver biopsies from 10 patients with NASH. We applied weighted gene co-expression network analysis and validated our findings using a publicly available RNA sequencing data set derived from 160 patients with non-alcoholic fatty liver disease (NAFLD) and 24 controls with normal liver histology. Our study provides a comprehensive single-cell analysis of NASH pathology in humans, describing 19,627 single-cell transcriptomes from biopsy-proven NASH patients. Our data suggest that the previous notion of ”NASH-associated macrophages” can be explained by an up-regulation of normally existing subpopulations of liver macrophages. Similarly, we describe two distinct populations of activated hepatic stellate cells, associated with the level of fibrosis. Finally, we find that the expression of several circulating markers of NAFLD are co-regulated in hepatocytes together with predicted effector genes from NAFLD genome-wide association studies (GWAS), coupled to abnormalities in the complement system. In sum, our single-cell transcriptomic data set provides insights into novel cell type-specific and general biological processes associated with inflammation and fibrosis, emphasizing the importance of studying cell type-specific biological processes in human NASH.

Stellate cells are principal neurons in the entorhinal cortex that contribute to spatial processing. They also play a role in the context of Alzheimer’s disease as they accumulate Amyloid beta early in the disease. Producing human stellate cells from pluripotent stem cells would allow researchers to study early mechanisms of Alzheimer’s disease, however, no protocols currently exist for producing such cells. In order to develop novel stem cell protocols, we characterize at high resolution the development of the porcine medial entorhinal cortex by tracing neuronal and glial subtypes from mid-gestation to the adult brain to identify the transcriptomic profile of progenitor and adult stellate cells. Importantly, we could confirm the robustness of our data by extracting developmental factors from the identified intermediate stellate cell cluster and implemented these factors to generate putative intermediate stellate cells from human induced pluripotent stem cells. Six transcription factors identified from the stellate cell cluster including RUNX1T1, SOX5, FOXP1, MEF2C, TCF4, EYA2 were overexpressed using a forward programming approach to produce neurons expressing a unique combination of RELN, SATB2, LEF1 and BCL11B observed in stellate cells. Further analyses of the individual transcription factors led to the discovery that FOXP1 is critical in the reprogramming process and omission of RUNX1T1 and EYA2 enhances neuron conversion. Our findings contribute not only to the profiling of cell types within the developing and adult brain’s medial entorhinal cortex but also provides proof-of-concept for using scRNAseq data to produce entorhinal intermediate stellate cells from human pluripotent stem cells in-vitro.

Little is known on how mitonuclear interactions influence genomic divergence among hybrid and parental lineages. A study of hybridizing wood warbler species complex finds a nuclear gene block with mitochondrial functions coevolves with mitochondrial genome, driven by climate-associated divergent selection underlying hybrid-parental population divergence.

Abstract Biodiversity monitoring projects using environmental DNA techniques are becoming increasingly widespread. However, these techniques depend heavily on the quality and richness of the available DNA reference database against which the DNA sequences are queried. To create a comprehensive DNA sequence database for future DNA‐based biodiversity assessments in Denmark, a national DNA reference database, DNAmark, was established, which contains organellar and/or nuclear reference data from vouchered museum species of plants, animals, and fungi from Denmark. Here, we present full or partial mitochondrial genomes of 182 Danish vertebrate species representing ca. 22% of vertebrate species observed in Denmark. Further, we demonstrate that storage conditions of the specimens accounted for ca. 50% of the total variation in mitochondrial DNA (mtDNA) preservation while the age of museum specimens had little effect: ca. 4%. In addition, we roughly estimate the cost of sequencing to be 25 EUR per specimen for obtaining sufficient amounts of DNA reads (ca. 200‐fold coverage) for reliable mitogenome assemblies while also obtaining low coverage genomic data. The large number of mitogenomes of Danish vertebrate species represents the initial groundwork for DNA‐based biodiversity assessments of vertebrates in Denmark and paves the way for practitioners to freely choose mitochondrial DNA markers.

The coronavirus disease 2019 (COVID-19) has forced clinicians globally to promptly establish the effective response plans in a very short timeframe. This article seeks to provide a comprehensive and universally applicable “Departmental Readiness Checklist,” readily available for anesthesiologists worldwide in response to any global crisis. We have made considerable efforts to ensure the information provided is supported by current knowledge and recommendations. Preparedness for pandemic readiness requires a concerted multidisciplinary effort and clear leadership to identify the potential issues to allow for appropriate planning and to promote education, teamwork, and clear communication at all phases of the pandemic. Departmental implementation requires both clinical and organizational expertise of the respective specialist groups, and there is a paucity of information for pandemic preparedness on a departmental level at this moment. The information provided are exclusively for staff anesthesiologists, directors of anesthesia departments, and hospital managers to guide and help in decision-making processes in the face of a pandemic and can be applied to mass casualty or natural disaster events.

Background: Endotracheal tube (ETT) intracuff pressure (PINTRACUFF) monitoring is not a mandatory part of daily anesthetic practice in many countries. Correct PINTRACUFF is required to ensure adequate ventilation, to prevent aspiration, and to avoid complications. The aim of this study was to objectively measure the PINTRACUFF in ETTs among patients from an Australian tertiary hospital to define the range of PINTRACUFF values seen in a setting without the use of routine objective monitoring. Patients and Methods: A prospective single-center audit of PINTRACUFF of 268 elective and emergency surgical patients undergoing general anesthesia with an ETT was performed. PINTRACUFF values were measured with a calibrated cuff manometer following the induction of anesthesia. Patient characteristics were compared between three patient groups of measured PINTRACUFF values: 20 cmH2O, 20–30 cmH2O, and >30 cmH2O. Results: To estimate the PINTRACUFF, only the auditory method was used among 66.0% of the patients, the tactile method was used in 18.3%, and the remainder used both or other methods. Following induction of anesthesia, the mean PINTRACUFF was 31.0 cmH2O (±standard deviation 16.4). The PINTRACUFF was 30 cmH2O had a marginally higher body mass index (BMI) compared to patients with a PINTRACUFF

Abstract To date, the development of disease-modifying therapies for Alzheimer’s disease (AD) has largely focused on the removal of amyloid beta Aβ fragments from the CNS. Proteomic profiling of patient fluids may help identify novel therapeutic targets and biomarkers associated with AD pathology. Here, we applied the Olink™ ProSeek immunoassay to measure 270 CSF and plasma proteins across 415 Aβ- negative cognitively normal individuals (Aβ- CN), 142 Aβ-positive CN (Aβ+ CN), 50 Aβ- mild cognitive impairment (MCI) patients, 75 Aβ+ MCI patients, and 161 Aβ+ AD patients from the Swedish BioFINDER study. A validation cohort included 59 Aβ- CN, 23 Aβ- + CN, 44 Aβ- MCI and 53 Aβ+ MCI. To compare protein concentrations in patients versus controls, we applied multiple linear regressions adjusting for age, gender, medications, smoking and mean subject-level protein concentration, and corrected findings for false discovery rate (FDR, q

BackgroundBroad community acceptance of a COVID-19 vaccination will be critical for effectively halting the spread of the virus. In this study, we focus on factors that differentiate those who are undecided from those who are either willing or unwilling to accept a prospective COVID-19 vaccine.MethodsAn online survey in May 2020 assessed Australian adults' willingness to receive a COVID-19 vaccine (yes, maybe, no). A multinomial logistical regression of responses (N = 1,313) was used to identify correlates of vaccine willingness between the three groups.Results65% were willing to vaccinate, with 27% being in the 'maybe' category. Respondents were more likely to be in the 'maybe' than the 'yes' group when they perceived COVID-19 to be less severe, had less trust in science, were less willing to vaccinate for influenza, and were female. They were more likely to be in the 'maybe' than 'no' group when they perceived COVID-19 as severe, and less likely to be a hoax, had more trust in science, and greater willingness to vaccinate for influenza. A repeat of the survey in November 2020 with a subset of participants found fewer of them saying yes to the vaccine (56%) and more saying maybe (31%).ConclusionsThe effectiveness of any COVID-19 vaccine rollout will be reliant on maximizing uptake. The significant number of people who remain undecided about whether or not to get a COVID-19 vaccine, despite the ongoing devastating consequences of the virus for individuals, communities, and economies, is concerning. Our findings aid current research seeking to inform policy regarding how to convince the undecided to vaccinate.

Introduction: The continuing opioid crisis poses unique challenges to remote and often under-resourced rural communities. Emergency medical service (EMS) providers serve a critical role in responding to opioid overdose for individuals living in rural or remote areas who experience opioid overdoses. They are often first at the scene of an overdose and are sometimes the only health care provider in contact with an overdose patient who either did not survive or refused additional care. As such, EMS providers have valuable perspectives to share on the causes and consequences of the opioid crisis in rural communities. Methods: EMS providers attending a statewide EMS conference serving those from greater Minnesota and surrounding states were invited to take a 2-question survey asking them to reflect upon what they believed to be the causes of the opioid crisis and what they saw as the solutions to the opioid crisis. Results were coded and categorized using a Consensual Qualitative Research approach. Results: EMS providers’ perceptions on causes of the opioid crisis were categorized into 5 main domains: overprescribing, ease of access, socioeconomic vulnerability, mental health concerns, and lack of resources and education. Responses focused on solutions to address the opioid crisis were categorized into 5 main domains: need for increased education, enhanced opioid oversight, increased access to treatment programs, alternative therapies for pain management, and addressing socioeconomic vulnerabilities. Conclusion: Along with the recognition that the opioid crisis was at least partially caused by overprescribing, rural EMS providers who participated in this study recognized the critical role of social determinants of health in perpetuating opioid-related harm. Participants in this study reported that education and increased access to treatment facilities and appropriate pain management, along with recognition of the role of social determinants of health in opioid dependency, were necessary steps to address the opioid crisis.

Introduction Ventilator-associated pneumonia (VAP) is a common healthcare-associated infection in the intensive care unit (ICU). Probiotics are defined as live microorganisms that may confer health benefits when ingested. Prior randomised trials suggest that probiotics may prevent infections such as VAP and Clostridioides difficile–associated diarrhoea (CDAD). PROSPECT (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial) is a multicentre, double-blinded, randomised controlled trial comparing the efficacy of the probiotic Lactobacillus rhamnosus GG with usual care versus usual care without probiotics in preventing VAP and other clinically important outcomes in critically ill patients admitted to the ICU.Methods and analysis The objective of E-PROSPECT is to determine the incremental cost-effectiveness of L. rhamnosus GG plus usual care versus usual care without probiotics in critically ill patients. E-PROSPECT will be performed from the public healthcare payer’s perspective over a time horizon from ICU admission to hospital discharge.We will determine probabilities of in-ICU and in-hospital events from all patients alongside PROSPECT. We will retrieve unit costs for each resource use item using jurisdiction-specific public databases, supplemented by individual site unit costs if such databases are unavailable. Direct costs will include medications, personnel costs, radiology/laboratory testing, operative/non-operative procedures and per-day hospital ‘hoteling’ costs not otherwise encompassed. The primary outcome is the incremental cost per VAP prevented between the two treatment groups. Other clinical events such as CDAD, antibiotic-associated diarrhoea and in-hospital mortality will be included as secondary outcomes. We will perform pre-specified subgroup analyses (medical/surgical/trauma; age; frailty status; antibiotic use; prevalent vs no prevalent pneumonia) and probabilistic sensitivity analyses for VAP, then generate confidence intervals using the non-parametric bootstrapping approach.Ethics and dissemination Study approval for E-PROSPECT was granted by the Hamilton Integrated Research Ethics Board of McMaster University on 29 July 2019. Informed consent was obtained from the patient or substitute decision-maker in PROSPECT. The findings of this study will be published in peer-reviewed journals.Trial registration number NCT01782755; Pre-results.

Abstract Background As the burden from the opioid epidemic continues to increase in the state of Minnesota and across the nation, the University of Minnesota College of Pharmacy seeks to design an innovative, comprehensive harm reduction curriculum in order to better train student pharmacists to serve the varied needs of the greater community. This study examines incoming individuals’ baseline knowledge of and attitudes toward harm reduction in order to better inform curriculum planning and to ultimately produce pharmacists capable of impacting the devastating effects of the opioid crisis. Methods Incoming first-year pharmacy students took a survey focused on their knowledge of opioid overdose and the drug naloxone and also provided written reflections on their perceptions of harm reduction. Data was coded using consensual qualitative research (CQR) into appropriate domains. Results Pharmacy students beginning their professional education revealed a lack of knowledge of proper response to an overdose situation, with 18.56% unfamiliar with the opioid antagonist drug naloxone. Close to 10% (9.58%) of students expressed unwillingness to do anything other than call an ambulance during an overdose event, while 8.98% were either unsure or felt that they would not feel compelled to do something to help. Qualitative coding revealed many barriers to students’ becoming capable harm reductionists, including lack of knowledge of substance use, addiction, and harm reduction, in addition to the presence of bias and stigma. Conclusion In order to interrupt the cycle of misinformation and stigma within the larger community and the subgroup of medical providers, gaps in student knowledge must be addressed in meaningful, specific ways over the course of their pharmacy education. Evaluating baseline knowledge and beliefs informs the design of a flexible, action-oriented curriculum to produce well-trained pharmacists ready to engage in finding solutions to the opioid crisis.

Abstract Background Hyperphosphorylation of microtubule-associated protein tau is a distinct feature of neurofibrillary tangles (NFTs) that are the hallmark of neurodegenerative tauopathies. O-GlcNAcylation is a lesser known post-translational modification of tau that involves the addition of N-acetylglucosamine onto serine and threonine residues. Inhibition of O-GlcNAcase (OGA), the enzyme responsible for the removal of O-GlcNAc modification, has been shown to reduce tau pathology in several transgenic models. Clarifying the underlying mechanism by which OGA inhibition leads to the reduction of pathological tau and identifying translatable measures to guide human dosing and efficacy determination would significantly facilitate the clinical development of OGA inhibitors for the treatment of tauopathies. Methods Genetic and pharmacological approaches are used to evaluate the pharmacodynamic response of OGA inhibition. A panel of quantitative biochemical assays is established to assess the effect of OGA inhibition on pathological tau reduction. A “click” chemistry labeling method is developed for the detection of O-GlcNAcylated tau. Results Substantial (>80%) OGA inhibition is required to observe a measurable increase in O-GlcNAcylated proteins in the brain. Sustained and substantial OGA inhibition via chronic treatment with Thiamet G leads to a significant reduction of aggregated tau and several phosphorylated tau species in the insoluble fraction of rTg4510 mouse brain and total tau in cerebrospinal fluid (CSF). O-GlcNAcylated tau is elevated by Thiamet G treatment and is found primarily in the soluble 55 kD tau species, but not in the insoluble 64 kD tau species thought as the pathological entity. Conclusion The present study demonstrates that chronic inhibition of OGA reduces pathological tau in the brain and total tau in the CSF of rTg4510 mice, most likely by directly increasing O-GlcNAcylation of tau and thereby maintaining tau in the soluble, non-toxic form by reducing tau aggregation and the accompanying panoply of deleterious post-translational modifications. These results clarify some conflicting observations regarding the effects and mechanism of OGA inhibition on tau pathology, provide pharmacodynamic tools to guide human dosing and identify CSF total tau as a potential translational biomarker. Therefore, this study provides additional support to develop OGA inhibitors as a treatment for Alzheimer’s disease and other neurodegenerative tauopathies.

Dopamine replacement therapy (DRT) alleviates motor symptoms in Parkinson’s disease but induces neuropsychiatric side-effects. This review evaluates recent research into the decision-making deficits caused by DRT arising because dopamine ‘overdoses’ a relatively-intact ventral striatum while replenishing the dorsal striatum. Consequently, patients on medication are worse at learning from losses but better at learning from wins than healthy controls. Additionally, due to greater disruption of medication on limbic than cognitive neural circuits, patients are poorer at decision-making under risk than decision-making under ambiguity. Particularly, task components related to ventral fronto-striatal and orbitofrontal regions are affected more than those related to dorsal and prefrontal regions. Selective deficits in feedback processing and outcome evaluation due to limbic overdose likely drive this effect.

The pursuit of Smart Living Technology is a recent trend in which technology is applied to daily life to increase efficiency, affordability and sustainability. The principle behind Smart Living Technology is that technology should be used to advance the needs of human beings and to increase the quality of life by the power of human creativity while at the same time sustaining the environment for future generations. As such, intelligent networks should be adopted to provide humans with full information to control an individual’s personal environment. Wireless technology can play a key role in enabling smart energy monitoring by allowing consumers to make more informed choices and to connect products and devices to a coordinated management system. The development of Smart Living Technology is based on the concept of user driven innovations. Various Living Labs have been established around the world as development centers for extension of this Smart Living Technology. In this paper, the background and current developments of Smart Living Technology are reviewed, followed by real examples taking place in Taiwan. Finally, the focus and future plan for Taiwan are discussed including a strategy for further development of Smart Living Technology in Taiwan.

Respiratory viral infections are strongly associated with asthma exacerbations. Rhinovirus is most frequently-detected pathogen; followed by respiratory syncytial virus; metapneumovirus; parainfluenza virus; enterovirus and coronavirus. In addition; viral infection; in combination with genetics; allergen exposure; microbiome and other pathogens; may play a role in asthma development. In particular; asthma development has been linked to wheezing-associated respiratory viral infections in early life. To understand underlying mechanisms of viral-induced airways disease; investigators have studied respiratory viral infections in small animals. This report reviews animal models of human respiratory viral infection employing mice; rats; guinea pigs; hamsters and ferrets. Investigators have modeled asthma exacerbations by infecting mice with allergic airways disease. Asthma development has been modeled by administration of virus to immature animals. Small animal models of respiratory viral infection will identify cell and molecular targets for the treatment of asthma.

Animals use an array of visual cues to gauge distance, and their underlying neural mechanisms remain largely unknown. Zebrafish larvae execute different hunting behaviors depending on distance to the prey, providing a simple model system in which to study this process. To identify distance cues, we presented equivalent prey stimuli at increasing distance and recorded hunting behaviors. We found that the initial convergence angle was lower for more distant prey, suggesting that they are able to gauge distance to the prey via monocular cues. We investigated blur as a possible monocular cue, and found that by artificially blurring the stimulus, we were able to reduce initial convergence and strike probability. This implicates blur as a distance cue in zebrafish prey capture, adds to our knowledge of how larvae are able to visually target and accurately capture prey. [ABSTRACT FROM AUTHOR]

The evolutionarily conserved MAP65 family proteins bundle anti-parallel microtubules (MTs). In Arabidopsis thaliana, mutations in the MAP65-3 gene lead to serious defects in MT organization in the phragmoplast and cause failures in cytokinesis. However, the functions of other ArabidopsisMAP65 isoforms are largely unknown. MAP65 functions were analyzed based on genetic interactions among different map65 mutations. Live-cell imaging and immunolocalization experiments revealed dynamic activities of two closely related MAP65 proteins in dividing cells. The map65-4 mutation caused synthetic lethality with map65-3 although map65-4 alone did not cause a noticeable phenotype. Furthermore, the introduction of an extra copy of the MAP65-4 gene significantly suppressed defects in cytokinesis and seedling growth caused by map65-3 because of restoring MT engagement in the spindle midzone. During mitosis, MAP65-4 first appeared at the preprophase band and persisted at the cortical division site afterwards. It was also concentrated on MTs in the spindle midzone and the phragmoplast. In the absence of MAP65-3, MAP65-4 exhibited greatly enhanced localization in the midzone of developing phragmoplast. Therefore, we have uncovered redundant but differential contributions of MAP65-3 and MAP65-4 to engaging and bundling anti-parallel MTs in the phragmoplast and disclosed a novel action of MAP65-4 at the cortical cell division site.

In plants, anisotropic cell expansion depends on cortical microtubules that serve as tracks along which macromolecules and vesicles are transported by the motor kinesins of unknown identities. We used cotton (Gossypium hirsutum) fibers that underwent robust elongation to discover kinesins that are involved in cell elongation and found Gh KINESIN-4A expressed abundantly. The motor was detected by immunofluorescence on vesicle-like structures that were associated with cortical microtubules. In Arabidopsis thaliana, the orthologous motor At KINESIN-4A/FRA1, previously implicated in cellulose deposition during secondary growth in fiber cells, was examined by live-cell imaging in cells expressing the fluorescently tagged functional protein. The motor decorated vesicle-like particles that exhibit a linear movement along cortical microtubules with an average velocity of 0.89 μm/min, which was significantly different from those linked to cellulose biosynthesis. We also discovered that At KINESIN-4A/FRA1 and the related At KINESIN-4C play redundant roles in cell wall mechanics, cell elongation, and the axial growth of various vegetative and reproductive organs, as the loss of At KINESIN-4C greatly enhanced the defects caused by a null mutation at the KINESIN-4A/FRA1 locus. The double mutant displayed a lack of cell wall softening at normal stages of rapid cell elongation. Furthermore, enhanced deposition of arabinose-containing carbohydrate was detected in the kinesin-4 mutants. Our findings established a connection between the Kinesin-4-based transport of cargoes containing non-cellulosic components along cortical microtubules and cell wall mechanics and cell elongation in flowering plants.

The spindle assembly checkpoint (SAC) ensures faithful chromosome segregation during cell division by monitoring kinetochore-microtubule attachment. Plants produce both sequence-conserved and diverged SAC components, and it has been largely unknown how SAC activation leads to the assembly of these proteins at unattached kinetochores to prevent cells from entering anaphase. In Arabidopsis thaliana, the noncanonical BUB3.3 protein was detected at kinetochores throughout mitosis, unlike MAD1 and the plant-specific BUB1/MAD3 family protein BMF3 that associated with unattached chromosomes only. When BUB3.3 was lost by a genetic mutation, mitotic cells often entered anaphase with misaligned chromosomes and presented lagging chromosomes after they were challenged by low doses of the microtubule depolymerizing agent oryzalin, resulting in the formation of micronuclei. Surprisingly, BUB3.3 was not required for the kinetochore localization of other SAC proteins or vice versa. Instead, BUB3.3 specifically bound to BMF3 through two internal repeat motifs that were not required for BMF3 kinetochore localization. This interaction enabled BMF3 to recruit CDC20, a downstream SAC target, to unattached kinetochores. Taken together, our findings demonstrate that plant SAC utilizes unconventional protein interactions for arresting mitosis, with BUB3.3 directing BMF3's role in CDC20 recruitment, rather than the recruitment of BUB1/MAD3 proteins observed in fungi and animals. This distinct mechanism highlights how plants adapted divergent versions of conserved cell cycle machinery to achieve specialized SAC control. [ABSTRACT FROM AUTHOR]

The kinetochore scaffold 1 (KNL1) protein recruits spindle assembly checkpoint (SAC) proteins to ensure accurate chromosome segregation during mitosis. Despite such a conserved function among eukaryotic organisms, its molecular architectures have rapidly evolved so that the functional mode of plant KNL1 is largely unknown. To understand how SAC signaling is regulated at kinetochores, we characterized the function of the KNL1 gene in Arabidopsis thaliana. The KNL1 protein was detected at kinetochores throughout the mitotic cell cycle, and null knl1 mutants were viable and fertile but exhibited severe vegetative and reproductive defects. The mutant cells showed serious impairments of chromosome congression and segregation, that resulted in the formation of micronuclei. In the absence of KNL1, core SAC proteins were no longer detected at the kinetochores, and the SAC was not activated by unattached or misaligned chromosomes. Arabidopsis KNL1 interacted with SAC essential proteins BUB3.3 and BMF3 through specific regions that were not found in known KNL1 proteins of other species, and recruited them independently to kinetochores. Furthermore, we demonstrated that upon ectopic expression, the KNL1 homolog from the dicot tomato was able to functionally substitute KNL1 in A. thaliana, while others from the monocot rice or moss associated with kinetochores but were not functional, as reflected by sequence variations of the kinetochore proteins in different plant lineages. Our results brought insights into understanding the rapid evolution and lineage-specific connection between KNL1 and the SAC signaling molecules. [ABSTRACT FROM AUTHOR]