L-Fucose-Rich Sulfated Glycans from Edible Brown Seaweed: A Promising Functional Food for Obesity and Energy Expenditure Improvement.

The global obesity epidemic, exacerbated by the sedentary lifestyle fostered by the COVID-19 pandemic, presents a growing socioeconomic burden due to decreased physical activity and increased morbidity. Current obesity treatments show promise, but they often come with expensive medications, frequent injections, and potential side effects, with limited success in improving obesity through increased energy expenditure. This study explores the potential of a refined sulfated polysaccharide (SPSL), derived from the brown seaweed Scytosiphon lomentaria (SL), as a safe and effective anti-obesity treatment by promoting energy expenditure. Chemical characterization revealed that SPSL, rich in sulfate and L-fucose content, comprises nine distinct sulfated glycan structures. In vitro analysis demonstrated potent anti-lipogenic properties in adipocytes, mediated by the downregulation of key adipogenic modulators, including 5' adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor γ (PPARγ) pathways. Inhibiting AMPK attenuated the anti-adipogenic effects of SPSL, confirming its involvement in the mechanism of action. Furthermore, in vivo studies using zebrafish models showed that SPSL increased energy expenditure and reduced lipid accumulation. These findings collectively highlight the therapeutic potential of SPSL as a functional food ingredient for mitigating obesity-related metabolic dysregulation by promoting energy expenditure. Further mechanistic and preclinical investigations are warranted to fully elucidate its mode of action and evaluate its efficacy in obesity management, potentially offering a novel, natural therapeutic avenue for this global health concern.

Effects of myofibril-palatinose conjugate as a phosphate substitute on meat emulsion quality.

The objective of this study was to investigate a replacement for phosphate in meat products. Protein structural modification was employed in this study, and grafted myofibrillar protein (MP) with palatinose was added to meat emulsion without phosphate. Here, 0.15% of sodium polyphosphate (SPP) was replaced by the same (0.15%) concentration and double (0.3%) the concentration of grafted MP. Although the thermal stability was decreased, the addition of transglutaminase could increase stability. The rheological properties and pH also increased with the addition of grafted MP and transglutaminase. The addition of grafted protein could be perceived by the naked eye by observing a color difference before cooking, but it was not easy to detect after cooking. The cooking loss, emulsion stability, water holding capacity, lipid oxidation, and textural properties improved with the addition of grafted MP. However, the excessive addition of grafted MP and transglutaminase was not recommended to produce a high quality of phosphate replaced meat emulsion, and 0.15% was identified as a suitable addition ratio of grafted MP.

Effect of Crude Polysaccharides from Ecklonia cava Hydrolysate on Cell Proliferation and Differentiation of Hanwoo Muscle Stem Cells for Cultured Meat Production.

Ecklonia cava, a brown seaweed native to the East Asian coast, is known for its unique composition, including polysaccharides, polyphenols, and phlorotannins. Fucoidan is a sulfated polysaccharide widely used as a functional ingredient in foods. This study obtained crude polysaccharides (ECC_CPS) from E. cava celluclast enzymatic hydrolysate using ethanol precipitation. ECC_CPS increased cell viability during the proliferation of Hanwoo muscle satellite cells (HMSCs). The effect of ECC_CPS on the expression of proliferation-related markers was confirmed as MYF5 and MYOD expression significantly increased, whereas PAX7 expression was maintained. The evaluation of cell migration activity has a major impact on cell proliferation and differentiation, and the cell migration index significantly increased with ECC_CPS treatment (p < 0.01). This was related to the HGF/MET pathway and FAK pathway. Treatment with ECC_CPS promoted differentiation at the cell differentiation stage, thereby increasing the expression of differentiation markers, such as MYH2, MYH7, and MYOG (p < 0.001 or p < 0.01). Therefore, our findings imply that crude polysaccharide obtained from E. cava can be an additive ingredient that enhances the proliferation and differentiation of muscle satellite cells used in the manufacture of cultured meat products.

Andrographolide suppresses aerobic glycolysis and induces apoptotic cell death by inhibiting pyruvate dehydrogenase kinase 1 expression.

Metabolic disorder is a major characteristic of cancer cells, and controlling genes involved in metabolic shifts can be an effective strategy for cancer treatment. Andrographolide (AG), a diterpenoid lactone, is widely recognized as a natural anticancer drug due to its ability to inhibit cancer growth. The present study aimed to investigate the mechanism underlying the mitochondrial­mediated anticancer effect of AG by inhibiting pyruvate dehydrogenase kinase 1 (PDK1) expression in lung cancer cells. Cells were treated with AG and PDK1 mRNA and protein expression was determined using reverse transcription­quantitative PCR and western blotting, respectively. As a result, AG significantly inhibited the viability of human lung cancer cells and suppressed aerobic glycolysis by decreasing lactate generation. AG further decreased the PDK1 protein and mRNA levels in a dose­dependent manner. AG­induced cell death was assessed by flow cytometry and fluorescence microscopy. AG induced apoptotic cell death that was associated with the cleavage of poly (ADP ribose) polymerase, activation of caspase­3, and mitochondrial damage, which was associated with an increase in reactive oxygen species and loss of mitochondrial membrane potential. AG­induced cell death was partially suppressed via PDK1 overexpression in lung cancer cells. Therefore, the anticancer effects of AG on human lung cancer cells may negatively regulate the expression of PDK1.

Peptides inhibiting angiotensin-I-converting enzyme: Isolation from flavourzyme hydrolysate of Protaetia brevitarsis larva protein and identification.

Many angiotensin-I-converting enzyme (ACE) inhibitory peptides are used to prevent and manage hypertension. In this study, ACE inhibitory peptides were isolated from an insect protein that is attracting attention for it potential antihypertensive activity. Protaetia brevitarsis larva protein was enzymatically hydrolyzed by Flavourzyme®, and the hydrolysate was shown to inhibit ACE. Subsequent fractionation, using ultrafiltration and gel permeation chromatography followed by liquid chromatography-tandem mass spectrometry analysis, identified four previously unknown peptides with significant ACE inhibition characteristics (Ser-Tyr, Pro-Phe, Tyr-Pro-Tyr, and Trp-Ile). The highest inhibition activity observed for Trp-Ile. These peptides stimulated production of NO in human umbilical vein endothelial cells and, based on molecular docking analysis, exerted their inhibitory effects via hydrogen bonding with the ACE receptor active site. Thus, the identified peptides can be considered as promising candidates for ACE inhibition and have potential to be used as functional food ingredients.

TNF-α promotes α-synuclein propagation through stimulation of senescence-associated lysosomal exocytosis.

Cell-to-cell propagation of α-synuclein is thought to be the underlying mechanism of Parkinson's disease progression. Recent evidence suggests that inflammation plays an important role in the propagation of protein aggregates. However, the mechanism by which inflammation regulates the propagation of aggregates remains unknown. Here, using in vitro cultures, we found that soluble factors secreted from activated microglia promote cell-to-cell propagation of α-synuclein and further showed that among these soluble factors, TNF-α had the most robust stimulatory activity. Treatment of neurons with TNF-α triggered cellular senescence, as shown by transcriptomic analyses demonstrating induction of senescence-associated genes and immunoanalysis of senescence phenotype marker proteins. Interestingly, secretion of α-synuclein was increased in senescent neurons, reflecting acquisition of a senescence-associated secretory phenotype (SASP). Using vacuolin-1, an inhibitor of lysosomal exocytosis, and RNAi against rab27a, we demonstrated that the SASP was mediated by lysosomal exocytosis. Correlative light and electron microscopy and immunoelectron microscopy confirmed that propagating α-synuclein aggregates were present in electron-dense lysosome-like compartments. TNF-α promoted the SASP through stimulation of lysosomal exocytosis, thereby increasing the secretion of α-synuclein. Collectively, these results suggest that TNF-α is the major inflammatory factor that drives cell-to-cell propagation of α-synuclein by promoting the SASP and subsequent secretion of α-synuclein.

Recent Progress on the Localization of PLK1 to the Kinetochore and Its Role in Mitosis.

The accurate distribution of the replicated genome during cell division is essential for cell survival and healthy organismal development. Errors in this process have catastrophic consequences, such as birth defects and aneuploidy, a hallmark of cancer cells. PLK1 is one of the master kinases in mitosis and has multiple functions, including mitotic entry, chromosome segregation, spindle assembly checkpoint, and cytokinesis. To dissect the role of PLK1 in mitosis, it is important to understand how PLK1 localizes in the specific region in cells. PLK1 localizes at the kinetochore and is essential in spindle assembly checkpoint and chromosome segregation. However, how PLK1 localizes at the kinetochore remains elusive. Here, we review the recent literature on the kinetochore recruitment mechanisms of PLK1 and its roles in spindle assembly checkpoint and attachment between kinetochores and spindle microtubules. Together, this review provides an overview of how the local distribution of PLK1 could regulate major pathways in mitosis.

Senescence and impaired DNA damage responses in alpha-synucleinopathy models.

α-Synuclein is a crucial element in the pathogenesis of Parkinson's disease (PD) and related neurological diseases. Although numerous studies have presented potential mechanisms underlying its pathogenesis, the understanding of α-synuclein-mediated neurodegeneration remains far from complete. Here, we show that overexpression of α-synuclein leads to impaired DNA repair and cellular senescence. Transcriptome analysis showed that α-synuclein overexpression led to cellular senescence with activation of the p53 pathway and DNA damage responses (DDRs). Chromatin immunoprecipitation analyses using p53 and γH2AX, chromosomal markers of DNA damage, revealed that these proteins bind to promoters and regulate the expression of DDR and cellular senescence genes. Cellular marker analyses confirmed cellular senescence and the accumulation of DNA double-strand breaks. The non-homologous end joining (NHEJ) DNA repair pathway was activated in α-synuclein-overexpressing cells. However, the expression of MRE11, a key component of the DSB repair system, was reduced, suggesting that the repair pathway induction was incomplete. Neuropathological examination of α-synuclein transgenic mice showed increased levels of phospho-α-synuclein and DNA double-strand breaks, as well as markers of cellular senescence, at an early, presymptomatic stage. These results suggest that the accumulation of DNA double-strand breaks (DSBs) and cellular senescence are intermediaries of α-synuclein-induced pathogenesis in PD.

Epigenetic control of centromere: what can we learn from neocentromere?

BACKGROUND: The centromere is the special region on a chromosome, which serves as the site for assembly of kinetochore complex and is essential for maintaining genomic integrity. Neocentromeres are new centromeres that form on the non-centromeric regions of the chromosome when the natural centromere is disrupted or inactivated. Although neocentromeres lack the typical features found in centromeres, cells with neocentromeres divide normally during mitosis and meiosis. Neocentromeres not only arise naturally but their formation can also be induced experimentally. Therefore, neocentromeres are a great tool for studying functions and formation of centromeres. OBJECTIVE: To study neocentromeres and use that knowledge to gain insights into the epigenetic regulation of canonical centromeres. DISCUSSION: Here, we review the characteristics of naturally occurring centromeres and neocentromeres and those of experimentally induced neocentromeres. We also discuss the mechanism of centromere formation and epigenetic regulation of centromere function, which we learned from studying the neocentromeres. Although neocentromeres lack main features of centromeres, such as presence of repetitive ⍺-satellite DNA and pericentric heterochromatin, they behave quite similar to the canonical centromere, indicating the epigenetic nature of the centromere. Still, further investigation will help to understand the formation and maintenance of the centromere, and the correlation to human diseases. CONCLUSION: Neocentromeres helped us to understand the formation of canonical centromeres. Also, since neocentromeres are associated with certain cancer types, knowledge about them could be helpful to treat cancer.

Natural Extracts as Inhibitors of Microorganisms and Lipid Oxidation in Emulsion Sausage during Storage.

Food additives are required to maintain the freshness and quality of foods, particularly meats. However, chemical additives may not be preferred by consumers, and natural materials with antimicrobial and antioxidant effects may be used as replacements for common chemical additives. Accordingly, in this study, we compared the antimicrobial and antioxidant activities of natural compounds extracted with ethanol and hot water, and emulsion sausage prepared with natural ethanol extracts was analyzed for pH, color, thiobarbituric acid reactive substances (TBARS), and Clostridium perfringens growth during storage. The antimicrobial activities of 49 natural extract candidates against Listeria monocytogenes, C. perfringens, Salmonella spp., and Escherichia coli were analyzed, and six natural materials with excellent antibacterial activities, i.e., Elaeagnus umbellata Thunb. f. nakaiana (Araki) H. Ohba, Punica granatum L., Ecklonia cava, Nelumbo nucifera Gaertner, and Schisandra chinensis (Turcz.) Baill., and Rubus coreanus Miq. were evaluated to determine their total polyphenol contents and DPPH radical scavenging activities. The total polyphenol contents of ethanol extracts were higher than those of hot water extracts, whereas DPPH radical scavenging activity was found to be higher in hot water extracts. The TBARS values of emulsion sausages were significantly increased as storage time increased, and the TBARS values of emulsion sausages prepared with natural extracts were lower than those of control sausages. Natural extract-treated emulsion sausages showed a 99% reduction in bacterial contents compared with untreated sausages on day 2, with greater than 99.9% reduction after day 3. Thus, these results demonstrated that natural extracts could have applications as natural preservatives in meat products.

Identification and Functional Characterization of Two Noncoding RNAs Transcribed from Putative Active Enhancers in Hepatocellular Carcinoma.

Enhancers have been conventionally perceived as cis-acting elements that provide binding sites for trans-acting factors. However, recent studies have shown that enhancers are transcribed and that these transcripts, called enhancer RNAs (eRNAs), have a regulatory function. Here, we identified putative eRNAs by profiling and determining the overlap between noncoding RNA expression loci and eRNA-associated histone marks such as H3K27ac and H3K4me1 in hepatocellular carcinoma (HCC) cell lines. Of the 132 HCC-derived noncoding RNAs, 74 overlapped with the eRNA loci defined by the FANTOM consortium, and 65 were located in the proximal regions of genes differentially expressed between normal and tumor tissues in TCGA dataset. Interestingly, knockdown of two selected putative eRNAs, THUMPD3-AS1 and LINC01572, led to downregulation of their target mRNAs and to a reduction in the proliferation and migration of HCC cells. Additionally, the expression of these two noncoding RNAs and target mRNAs was elevated in tumor samples in the TCGA dataset, and high expression was associated with poor survival of patients. Collectively, our study suggests that noncoding RNAs such as THUMPD3-AS1 and LINC01572 (i.e., putative eRNAs) can promote the transcription of genes involved in cell proliferation and differentiation and that the dysregulation of these noncoding RNAs can cause cancers such as HCC.

NPAS4 regulates the transcriptional response of the suprachiasmatic nucleus to light and circadian behavior.

The suprachiasmatic nucleus (SCN) is the master circadian pacemaker in mammals and is entrained by environmental light. However, the molecular basis of the response of the SCN to light is not fully understood. We used RNA/chromatin immunoprecipitation/single-nucleus sequencing with circadian behavioral assays to identify mouse SCN cell types and explore their responses to light. We identified three peptidergic cell types that responded to light in the SCN: arginine vasopressin (AVP), vasoactive intestinal peptide (VIP), and cholecystokinin (CCK). In each cell type, light-responsive subgroups were enriched for expression of neuronal Per-Arnt-Sim (PAS) domain protein 4 (NPAS4) target genes. Further, mice lacking Npas4 had a longer circadian period under constant conditions, a damped phase response curve to light, and reduced light-induced gene expression in the SCN. Our data indicate that NPAS4 is necessary for normal transcriptional responses to light in the SCN and critical for photic phase-shifting of circadian behavior.

Methyltransferase-like protein 7A (METTL7A) promotes cell survival and osteogenic differentiation under metabolic stress.

While bone has an inherent capacity to heal itself, it is very difficult to reconstitute large bone defects. Regenerative medicine, including stem cell implantation, has been studied as a novel solution to treat these conditions. However, when the local vascularity is impaired, even the transplanted cells undergo rapid necrosis before differentiating into osteoblasts and regenerating bone. Thus, to increase the effectiveness of stem cell transplantation, it is quintessential to improve the viability of the implanted stem cells. In this study, given that the regulation of glucose may hold the key to stem cell survival and osteogenic differentiation, we investigated the molecules that can replace the effect of glucose under ischemic microenvironment of stem cell transplantation in large bone defects. By analyzing differentially expressed genes under glucose-supplemented and glucose-free conditions, we explored markers such as methyltransferase-like protein 7A (METTL7A) that are potentially related to cell survival and osteogenic differentiation. Overexpression of METTL7A gene enhanced the osteogenic differentiation and viability of human bone marrow stem cells (hBMSCs) in glucose-free conditions. When the in vivo effectiveness of METTL7A-transfected cells in bone regeneration was explored in a rat model of critical-size segmental long-bone defect, METTL7A-transfected hBMSCs showed significantly better regenerative potential than the control vector-transfected hBMSCs. DNA methylation profiles showed a large difference in methylation status of genes related to osteogenesis and cell survival between hBMSCs cultured in glucose-supplemented condition and those cultured in glucose-free condition. Interestingly, METTL7A overexpression altered the methylation status of related genes to favor osteogenic differentiation and cell survival. In conclusion, it is suggested that a novel factor METTL7A enhances osteogenic differentiation and viability of hBMSCs by regulating the methylation status of genes related to osteogenesis or survival.

Physicochemical properties and oxidative stability of duck fat-added margarine for reducing the use of fully hydrogenated soybean oil.

Soybean oil (SBO) and fully hydrogenated soybean oil (FHSBO) have been used for margarine production. However, SBO-based margarine requires a considerable amount of trans fatty acid-containing FHSBO due to its low melting point. We aimed to reduce the FHSBO content in margarine by employing duck fat, which has a higher melting point than SBO. Margarines were prepared using different ratios of duck fat and reduced levels of SBO and FHSBO. Physicochemical, sensory, and oxidative properties of the margarines were evaluated. The quality characteristics of margarine improved when duck fat replaced SBO and FHSBO. Furthermore, the lipid oxidation parameters were lower in duck fat-added margarines than the control during storage at 60 °C for 28 days. The margarine containing 80% duck fat showed the best sensory properties. Collectively, duck fat can replace SBO in margarine while reducing the use of FHSBO and maintaining desirable physicochemical properties, oxidative stability, and sensory properties.

Clean Label Meat Technology: Pre-Converted Nitrite as a Natural Curing.

Clean labeling is emerging as an important issue in the food industry, particularly for meat products that contain many food additives. Among synthetic additives, nitrite is the most important additive in the meat processing industry and is related to the development of cured color and flavor, inhibition of oxidation, and control of microbial growth in processed meat products. As an alternative to synthetic nitrite, pre-converted nitrite from natural microorganisms has been investigated, and the applications of pre-converted nitrite have been reported. Natural nitrate sources mainly include fruits and vegetables with high nitrate content. Celery juice or powder form have been used widely in various studies. Many types of commercial starter cultures have been developed. S. carnosus is used as a critical nitrate reducing microorganism and lactic acid bacteria or other Staphylococcus species also were used. Pre-converted nitrite has also been compared with synthetic nitrite and studies have been aimed at improving utilization by exploiting the strengths (positive consumer attitude and decreased residual nitrite content) and limiting the weaknesses (remained carcinogenic risk) of pre-converted nitrite. Moreover, as concerns regarding the use of synthetic nitrites increased, research was conducted to meet consumer demands for the use of natural nitrite from raw materials. In this report, we review and discuss various studies in which synthetic nitrite was replaced with natural materials and evaluate pre-converted nitrite technology as a natural curing approach from a clean label perspective in the manufacturing of processed meat products.

Bub1 kinase in the regulation of mitosis.

Accurate chromosome segregation is required for cell survival and organismal development. During mitosis, the spindle assembly checkpoint acts as a safeguard to maintain the high fidelity of mitotic chromosome segregation by monitoring the attachment of kinetochores to the mitotic spindle. Bub1 is a conserved kinase critical for the spindle assembly checkpoint. Bub1 also facilitates chromosome alignment and contributes to the regulation of mitotic duration. Here, focusing on the spindle assembly checkpoint and on chromosome alignment, we summarize the primary literature on Bub1, discussing its structure and functional domains, as well its regulation and roles in mitosis. In addition, we discuss recent evidence for roles of Bub1 beyond mitosis regulation in TGFß signaling and telomere replication. Finally, we discuss the involvement of Bub1 in human diseases, especially in cancer, and the potential of using Bub1 as a drug target for therapeutic applications.

Infection-related hospitalization following ureteroscopic stone treatment: results from a surgical collaborative.

BACKGROUND: Unplanned hospitalization following ureteroscopy (URS) for urinary stone disease is associated with patient morbidity and increased healthcare costs. To this effect, AUA guidelines recommend at least a urinalysis in patients prior to URS. We examined risk factors for infection-related hospitalization following URS for urinary stones in a surgical collaborative. METHODS: Reducing Operative Complications from Kidney Stones (ROCKS) is a quality improvement (QI) initiative from the Michigan Urological Surgery Improvement Collaborative (MUSIC) consisting of academic and community practices in the State of Michigan. Trained abstractors prospectively record standardized data elements from the health record in a web-based registry including patient characteristics, surgical details and complications. Using the ROCKS registry, we identified all patients undergoing primary URS for urinary stones between June 2016 and October 2017, and determined the proportion hospitalized within 30 days with an infection-related complication. These patients underwent chart review to obtain clinical data related to the hospitalization. Multivariable logistic regression analysis was performed to determine risk factors for hospitalization. RESULTS: 1817 URS procedures from 11 practices were analyzed. 43 (2.4%) patients were hospitalized with an infection-related complication, and the mortality rate was 0.2%. Median time to admission and length of stay was 4 and 3 days, respectively. Nine (20.9%) patients did not have a pre-procedure urinalysis or urine culture, which was not different in the non-hospitalized cohort (20.5%). In hospitalized patients, pathogens included gram-negative (61.5%), gram-positive (19.2%), yeast (15.4%), and mixed (3.8%) organisms. Significant factors associated with infection-related hospitalization included higher Charlson comorbidity index, history of recurrent UTI, stone size, intra-operative complication, and procedures where fragments were left in-situ. CONCLUSIONS: One in 40 patients are hospitalized with an infection-related complication following URS. Awareness of risk factors may allow for individualized counselling and management to reduce these events. Approximately 20% of patients did not have a pre-operative urine analysis or culture, and these findings demonstrate the need for further study to improve urine testing and compliance.

Effects of replacing pork fat with grape seed oil and gelatine/alginate for meat emulsions.

The effects of using grape seed oil in combination with gelatine and alginate on the physicochemical characteristics of meat emulsions were examined. Four different meat emulsions were manufactured and half the conventional fat was substituted with pre-emulsified grape seed oil with gelatine and/or alginate: T1, only grape seed oil; T2, grape seed oil and gelatine; T3, grape seed oil and alginate, T4, grape seed oil, gelatine, and alginate. Meat emulsion containing only pork back fat was compared as control. Results revealed that T4 was moister, lighter, more viscous, and stable in emulsion than control and value of ash contents of T4 was higher than those of control. Moreover, the value of fat content, pH, firmness, chewiness, toughness, and lipid oxidation of the T4 meat emulsion were lower than those of control. The meat emulsions with emulsified grape seed oil were more principally elastic than viscous and appearent viscosity was the highest in T4. In conclusion, instead of using each ingredient alone, pre-emulsified grape seed oil, gelatine, and alginate can replace partial pork fat with in meat emulsion formulations results in optimized meat processing properties.

PASNet: pathway-associated sparse deep neural network for prognosis prediction from high-throughput data.

BACKGROUND: Predicting prognosis in patients from large-scale genomic data is a fundamentally challenging problem in genomic medicine. However, the prognosis still remains poor in many diseases. The poor prognosis may be caused by high complexity of biological systems, where multiple biological components and their hierarchical relationships are involved. Moreover, it is challenging to develop robust computational solutions with high-dimension, low-sample size data. RESULTS: In this study, we propose a Pathway-Associated Sparse Deep Neural Network (PASNet) that not only predicts patients' prognoses but also describes complex biological processes regarding biological pathways for prognosis. PASNet models a multilayered, hierarchical biological system of genes and pathways to predict clinical outcomes by leveraging deep learning. The sparse solution of PASNet provides the capability of model interpretability that most conventional fully-connected neural networks lack. We applied PASNet for long-term survival prediction in Glioblastoma multiforme (GBM), which is a primary brain cancer that shows poor prognostic performance. The predictive performance of PASNet was evaluated with multiple cross-validation experiments. PASNet showed a higher Area Under the Curve (AUC) and F1-score than previous long-term survival prediction classifiers, and the significance of PASNet's performance was assessed by Wilcoxon signed-rank test. Furthermore, the biological pathways, found in PASNet, were referred to as significant pathways in GBM in previous biology and medicine research. CONCLUSIONS: PASNet can describe the different biological systems of clinical outcomes for prognostic prediction as well as predicting prognosis more accurately than the current state-of-the-art methods. PASNet is the first pathway-based deep neural network that represents hierarchical representations of genes and pathways and their nonlinear effects, to the best of our knowledge. Additionally, PASNet would be promising due to its flexible model representation and interpretability, embodying the strengths of deep learning. The open-source code of PASNet is available at https://github.com/DataX-JieHao/PASNet .

TPXL-1 activates Aurora A to clear contractile ring components from the polar cortex during cytokinesis.

During cytokinesis, a signal from the central spindle that forms between the separating anaphase chromosomes promotes the accumulation of contractile ring components at the cell equator, while a signal from the centrosomal microtubule asters inhibits accumulation of contractile ring components at the cell poles. However, the molecular identity of the inhibitory signal has remained unknown. To identify molecular components of the aster-based inhibitory signal, we developed a means to monitor the removal of contractile ring proteins from the polar cortex after anaphase onset. Using this assay, we show that polar clearing is an active process that requires activation of Aurora A kinase by TPXL-1. TPXL-1 concentrates on astral microtubules coincident with polar clearing in anaphase, and its ability to recruit Aurora A and activate its kinase activity are essential for clearing. In summary, our data identify Aurora A kinase as an aster-based inhibitory signal that restricts contractile ring components to the cell equator during cytokinesis.