Search

Extensive research on marine algae, especially on their health-promoting properties, has been conducted. Various ingredients with potential biomedical applications have been discovered and extracted from marine algae. Alginate oligosaccharides are low molecular weight alginate polysaccharides present in cell walls of brown algae. They exhibit various health benefits such as anti-inflammatory, anti-microbial, anti-oxidant, anti-tumor and immunomodulation. Their low-toxicity, non-immunogenicity, and biodegradability make them an excellent material in biomedicine. Alginate oligosaccharides can be chemically or biochemically modified to enhance their biological activity and potential in pharmaceutical applications. This paper provides a brief overview on alginate oligosaccharides characteristics, modification patterns and highlights their vital health promoting properties. • Alginate oligosaccharide has good biosafety, biocompatibility and bioavailability. • Composition and structure of oligosaccharide affects its final biological activity. • Alginate oligosaccharides are potential biomedicines with promising prospects. [ABSTRACT FROM AUTHOR]

Many electroactive microorganisms (EAMs) are known as dissimilatory iron-reducing bacteria (DIRB) which can access iron as an electron acceptor to transfer electrons during the process of respiration. Previous research has shown that magnetic susceptibility (χlf) could be used as an indicator of DIRB activities. However, the relationship between χlf and electroactivity of EAMs is still unclear. Here, we report that after sediments of the Sha River enriched with amorphous iron, the χlf of enrichment cultures increased dramatically. The reactor inoculated with higher χlf enrichment cultures started earlier and had a higher peak voltage (0.228 V), higher power density (310.14 mW m −2 ) and higher coulombic efficiency (10.16%) than lower χlf cultures. Sequencing of bacterial 16S rRNA gene amplicons and χlf measurement revealed that relative abundance of dominant phyla Proteobacteria increased with χlf values in sediments. Further analysis of cyclic voltammetry curves and bacterial terminal-restriction fragment length polymorphism (T-RFLP) of bacterial rRNA genes indicated that the improved performance of the MFCs might be due to a highly electroactive microbial community that the 162 bp terminal restriction fragments (TRFs) originated from. Our results suggested a potential correlation between χlf and presence of EAM indicating a promising route for fast screening in complex environments. [ABSTRACT FROM AUTHOR]

The yeast Saccharomyces cerevisiae is capable of responding to various environmental stresses, such as salt stress. Such responses require a complex network and adjustment of the gene expression network. The goal of this study is to further understand the molecular mechanism of salt stress response in yeast, especially the molecular mechanism related to genes BDF1 and HAL2. The Bromodomain Factor 1 (Bdf1p) is a transcriptional regulator, which is part of the basal transcription factor TFIID. Cells lacking Bdf1p are salt sensitive with an abnormal mitochondrial function. We previously reported that the overexpression of HAL2 or deletion of HDA1 lowers the salt sensitivity of bdf1Δ. To better understand the mechanism behind the HAL2-related response to salt stress, we compared three global transcriptional profiles ( bdf1Δ vs WT, bdf1Δ + HAL2 vs bdf1Δ, and bdf1Δhda1Δ vs bdf1Δ) in response to salt stress using DNA microarrays. Our results reveal that genes for iron acquisition and cellular and mitochondrial remodeling are induced by HAL2. Overexpression of HAL2 decreases the concentration of nitric oxide. Mitochondrial iron-sulfur cluster (ISC) assembly also decreases in bdf1Δ + HAL2. These changes are similar to the changes of transcriptional profiles induced by iron starvation. Taken together, our data suggest that mitochondrial functions and iron homeostasis play an important role in bdf1Δ-induced salt sensitivity and salt stress response in yeast. [ABSTRACT FROM AUTHOR]

Mislocalization of TAR DNA binding protein 43 kDa (TARDBP, or TDP-43) is a principal pathological hallmark identified in cases of neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). As an RNA binding protein, TDP-43 serves in the nuclear compartment to repress non-conserved cryptic exons to ensure the normal transcriptome. Multiple lines of evidence from animal models and human studies support the view that loss of TDP-43 leads to neuron loss, independent of its cytosolic aggregation. However, the underlying pathogenic pathways driven by the loss-of-function mechanism are still poorly defined. We employed a genetic approach to determine the impact of TDP-43 loss in pyramidal neurons of the prefrontal cortex (PFC). Using a custom-built miniscope imaging system, we performed repetitive in vivo calcium imaging from freely behaving mice for up to 7 months. By comparing calcium activity in PFC pyramidal neurons between TDP-43 depleted and TDP-43 intact mice, we demonstrated remarkably increased numbers of pyramidal neurons exhibiting hyperactive calcium activity after short-term TDP-43 depletion, followed by rapid activity declines prior to neuron loss. Our results suggest aberrant neural activity driven by loss of TDP-43 as the pathogenic pathway at early stage in ALS and FTD. • Loss of TDP-43 in PFC pyramidal neurons elicits aberrant calcium activity. • Short-term loss of TDP-43 triggers hyperactivity in pyramidal neurons of the PFC. • Rapid activity declines following the initial hyperactivity in pyramidal neurons lacking TDP-43 before neuron loss. [ABSTRACT FROM AUTHOR]

Bromodomain-containing transcription factor, a kind of important regulating protein, can recognize and bind to acetylated histone. The homologous genes, BDF1 and BDF2, in Saccharomyces cerevisiae, respectively, encode a bromodomain-containing transcription factor. Previously study has demonstrated that both BDF1 and BDF2 participate in yeast salt stress response. Bdf1p deletion cells are sensitive to salt stress and this phenotype is suppressed by its homologue BDF2 in a dosage-dependent manner. In this study, we show that the histone deacetylase SIR2 over-expression enhanced dosage-dependent compensation of BDF2. SIR2 over-expression induced a global transcription change, and 1959 gene was down-regulated. We deleted some of the most significant down-regulated genes and did the spot assay. The results revealed that LSP1, an upstream component of endocytosis pathway, and CIN5, a transcription factor that mediates cellular resistance to stresses, can enhance salt resistance of bdf1∆. Further analysis demonstrated that under salt stress the endocytosis is over-activated in bdf1∆ but was recovered in bdf1∆ lsp1∆. To our best knowledge, this is the first report that the transcription factor Bdf1p regulates endocytosis under salt stress via LSP1, a major component of eisosomes that regulate the sites of endocytosis. [ABSTRACT FROM AUTHOR]

The Saccharomyces cerevisiae Bdf1p associates with the basal transcription complexes TFIID and acts as a transcriptional regulator. Lack of Bdf1p is salt sensitive and displays abnormal mitochondrial function. The nucleotidase Hal2p detoxifies the toxic compound 3′ -phosphoadenosine-5′-phosphate (pAp), which blocks the biosynthesis of methionine. Hal2p is also a target of high concentration of Na+. Here, we reported that HAL2 overexpression recovered the salt stress sensitivity of bdf1Δ. Further evidence demonstrated that HAL2 expression was regulated indirectly by Bdf1p. The salt stress response mechanisms mediated by Bdf1p and Hal2p were different. Unlike hal2Δ, high Na+ or Li+ stress did not cause pAp accumulation in bdf1Δ and methionine supplementation did not recover its salt sensitivity. HAL2 overexpression in bdf1Δ reduced ROS level and improved mitochondrial function, but not respiration. Further analyses suggested that autophagy was apparently defective in bdf1Δ, and autophagy stimulated by Hal2p may play an important role in recovering mitochondrial functions and Na+ sensitivity of bdf1Δ. Our findings shed new light towards our understanding about the molecular mechanism of Bdf1p-involved salt stress response in budding yeast. [ABSTRACT FROM AUTHOR]

[Display omitted] • SMF enhanced metabolic pathways related to H 2 production of C. pasteurianum. • Maximum H 2 production and production rate were achieved with 3.2 mT SMF application. • Carbon conversion efficiency was significant increased with 3.2 mT SMF application. Microbial fermentation plays important roles in hydrogen production. Various methods to promote hydrogen production are being developed. Here, different magnetic field intensities (2.7 mT, 3.2 mT and 9.1 mT) were applied to the glucose fermentation system of Clostridium pasteurianum to evaluate the feasibility and effect of statistic magnetic field on hydrogen production. The results showed that the magnetic field intensity of 3.2 mT effectively enhanced the hydrogen production. The total glucose consumption reached 0.64 ± 0.010 mmol, the maximum hydrogen yield reached 2.34 ± 0.020 mol H 2 /mol glucose, and the maximum hydrogen production rate reached 0.065 ± 0.002 mmol/h. Compared with the control, the maximum biomass, carbon conversion efficiency and energy conversion efficiency were elevated by 366%, 114%, and 26.8%, respectively. Our results provide a new way for promotion of hydrogen production, better understanding of the interaction mechanism between magnetic field and microorganisms and for optimizing the hydrogen production. [ABSTRACT FROM AUTHOR]

Background: Anhydrobiotes, such as the yeast Saccharomyces cerevisiae, are capable of surviving almost total loss of water. Desiccation tolerance requires an interplay of multiple events, including preserving the protein function and membrane integrity, preventing and mitigating oxidative stress, maintaining certain level of energy required for cellular activities in the desiccated state. Many of these crucial processes can be controlled and modulated at the level of organelle morphology and dynamics. However, little is understood about what organelle perturbations manifest in desiccation-sensitive cells as a consequence of drying or how this differs from organelle biology in desiccation-tolerant organisms undergoing anhydrobiosis. Results: In this study, electron and optical microscopy was used to examine the dynamic changes of yeast cells during the desiccation process. Dramatic structural changes were observed during the desiccation process, including the diminishing of vacuoles, decrease of lipid droplets, decrease in mitochondrial cristae and increase of ER membrane, which is likely caused by ER stress and unfolded protein response. The survival rate was significantly decreased in mutants that are defective in lipid droplet biosynthesis, or cells treated with cerulenin, an inhibitor of fatty acid synthesis. Conclusion: Our study suggests that the metabolism of lipid droplets and membrane may play an important role in yeast desiccation tolerance by providing cells with energy and possibly metabolic water. Additionally, the decrease in mitochondrial cristae coupled with a decrease in lipid droplets is indicative of a cellular response to reduce the production of reactive oxygen species. [ABSTRACT FROM AUTHOR]

Water is essential to all life on earth. It is a major component that makes up living organisms and plays a vital role in multiple biological processes. It provides a medium for chemical and enzymatic reactions in the cell and is a major player in osmoregulation and the maintenance of cell turgidity. Despite this, many organisms, called anhydrobiotes, are capable of surviving under extremely dehydrated conditions. Less is known about how anhydrobiotes adapt and survive under desiccation stress. Studies have shown that morphological and physiological changes occur in anhydrobiotes in response to desiccation stress. Certain disaccharides and proteins, including heat shock proteins, intrinsically disordered proteins, and hydrophilins, play important roles in the desiccation tolerance of anhydrobiotes. In this review, we summarize the recent findings of desiccation tolerance in the budding yeast Saccharomyces cerevisiae . We also propose that the yeast under desiccation could be used as a model to study neurodegenerative disorders.

Objective: Muscle dysfunction caused by repetitive work or strain in the neck region can interfere muscle responses. Muscle dysfunction can be an important factor in causing cervical spondylosis. However, there has been no research on how the biomechanical properties of the upper cervical spine change when the suboccipital muscle group experiences dysfunction. The objective of this study was to investigate the biomechanical evidence for cervical spondylosis by utilizing the finite element (FE) approach, thus and to provide guidance for clinicians performing acupoint therapy., Methods: By varying the elastic modulus of the suboccipital muscle, the four FE models of C0-C3 motion segments were reconstructed under the conditions of normal muscle function and muscle dysfunction. For the two normal condition FE models, the elastic modulus for suboccipital muscles on both sides of the C0-C3 motion segments was equal and within the normal range In one muscle dysfunction FE model, the elastic modulus on both sides was equal and greater than 37 kPa, which represented muscle hypertonia; in the other, the elastic modulus of the left and right suboccipital muscles was different, indicating muscle imbalance. The biomechanical behavior of the lateral atlantoaxial joint (LAAJ), atlanto-odontoid joint (ADJ), and intervertebral disc (IVD) was analyzed by simulations, which were carried out under the six loadings of flexion, extension, left and right lateral bending, left and right axial rotation., Results: Under flexion, the maximum stress in LAAJ with muscle imbalance was higher than that with normal muscle and hypertonia, while the maximum stress in IVD in the hypertonic model was higher than that in the normal and imbalance models. The maximum stress in ADJ was the largest under extension among all loadings for all models. Muscle imbalance and hypertonia did not cause overstress and stress distribution abnormalities in ADJ., Conclusion: Muscle dysfunction increases the stress in LAAJ and in IVD, but it does not affect ADJ., (© 2024. The Author(s).)

Background: Although internet gaming disorder (IGD) has been included in the DSM-5 for approximately 10 years, debate remains regarding its existence and classification., Methods: The current research incorporated three approaches. First, implicit association tests were used to examine for potential dissociation between wanting and liking in IGD. Second, brain features in wanting and liking circuits were tested and compared with tobacco use disorder (TUD) when performing a cue-craving task to explore the neural features of wanting and liking. Third, dopaminergic systems were investigated in IGD and TUD using neuromelanin-sensitive MRI., Results: The implicit association test results supported a wanting-liking dissociation in IGD participants. Functional MRI data suggested neural correlates underlying wanting-liking dissociation in IGD and TUD participants, with positive correlations suggesting greater dissociation with increasing addiction severity. Neuromelanin results suggest dopaminergic differences in IGD and TUD relative to healthy control participants., Conclusions: A wanting-liking dissociation in IGD participants suggests gaming motivations in IGD relating to incentive sensitization rather than hedonic responses. The neuromelanin-sensitive MRI results suggest dopaminergic involvement in IGD and TUD. The findings suggest similar brain-behaviour mechanisms for IGD and TUD based on an incentive-sensitization model for addiction, having implications for potential therapeutic strategies and policy-based interventions.

Objective: To evaluate the effects of our self-developed endotracheal tube fixation device in mechanically ventilated patients., Methods: In a dual-centre randomised controlled trial, patients who were expected to require mechanical ventilation for over 48 h were assigned to the observation group (using self-developed device) or the control group (using the traditional device). The primary endpoint was the incidence of endotracheal intubation-related pressure injury (EIRPI)., Results: Fifty-one patients in the observation group and 54 patients in the control group were analysed. The incidence of EIRPI was 7.8% in the observation group and 33.3% in the control group (p = 0.001). Lip pressure injury (PI) occurred in 0 versus 14 (25.9%) patients in the observation versus control groups (p < 0.001). Both oral-mucosal and facial PIs were similar between the two groups., Conclusions: The use of the novel device reduced the incidence of EIRPI, especially lip PI. Trial registration Chinese Clinical Trial Registry ChiCTR2300078132. Registered on 29 November 2023., (© 2024. The Author(s).)

Background/aims: The reciprocal promotion of cancer and stroke occurs due to changes in shared risk factors, such as metabolic pathways and molecular targets, creating a "vicious cycle." Cancer plays a direct or indirect role in the pathogenesis of ischemic stroke (IS), along with the reactive medical approach used in the treatment and clinical management of IS patients, resulting in clinical challenges associated with occult cancer in these patients. The lack of reliable and simple tools hinders the effectiveness of the predictive, preventive, and personalized medicine (PPPM/3PM) approach. Therefore, we conducted a multicenter study that focused on multiparametric analysis to facilitate early diagnosis of occult cancer and personalized treatment for stroke associated with cancer., Methods: Admission routine clinical examination indicators of IS patients were retrospectively collated from the electronic medical records. The training dataset comprised 136 IS patients with concurrent cancer, matched at a 1:1 ratio with a control group. The risk of occult cancer in IS patients was assessed through logistic regression and five alternative machine-learning models. Subsequently, select the model with the highest predictive efficacy to create a nomogram, which is a quantitative tool for predicting diagnosis in clinical practice. Internal validation employed a ten-fold cross-validation, while external validation involved 239 IS patients from six centers. Validation encompassed receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and comparison with models from prior research., Results: The ultimate prediction model was based on logistic regression and incorporated the following variables: regions of ischemic lesions, multiple vascular territories, hypertension, D-dimer, fibrinogen (FIB), and hemoglobin (Hb). The area under the ROC curve (AUC) for the nomogram was 0.871 in the training dataset and 0.834 in the external test dataset. Both calibration curves and DCA underscored the nomogram's strong performance., Conclusions: The nomogram enables early occult cancer diagnosis in hospitalized IS patients and helps to accurately identify the cause of IS, while the promotion of IS stratification makes personalized treatment feasible. The online nomogram based on routine clinical examination indicators of IS patients offered a cost-effective platform for secondary care in the framework of PPPM., Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00354-8., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s), under exclusive licence to European Association for Predictive, Preventive and Personalised Medicine (EPMA) 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Due to sensitive scaling of the wavelength and the visible-light absorption properties with the device dimension, traditional passive silicon photonic devices with asymmetric waveguide structures cannot achieve polarization control at the visible wavelengths. In this work, a simple and small polarization beam splitter (PBS) for a broad visible-light band, using a tailored silicon nitride (Si 3 N 4 ) ridge waveguide, is presented, which is based on the distinct optical distribution of two fundamental orthogonal polarized modes in the ridge waveguide. The bending loss for different bending radii and the optical coupling properties of the fundamental modes for different Si 3 N 4 ridge waveguide configurations are analyzed. A PBS composed of a bending ridge waveguide structure and a triple-waveguide directional coupler was fabricated on the Si 3 N 4 thin film. The TM excitation of the device based on a bending ridge waveguide structure shows a polarization extinction ratio (PER) of ≥ 20 dB with 33 nm bandwidth (624-657 nm) and insertion loss (IL) ≤ 1 dB at the through port. The TE excitation of the device, based on a triple-waveguide directional coupler with coupling efficiency distinction between the TE 0 and TM 0 modes, shows a PER of ≥ 18 dB with 50 nm bandwidth (580-630 nm) and insertion loss (IL) ≤ 1 dB at the cross port. The on-chip Si 3 N 4 PBS device is found to possess the highest known PER at a visible broadband range and small (43 µm) footprint. It should be useful for novel photonic circuit designs and further exploration of Si 3 N 4 PBSs.

Background: Impaired decision-making was observed in internet gaming disorder (IGD), however, these studies did not differentiate 'hard' to 'easy' decisions, and only the 'hard' decision-making could reveal the mechanism underlying this issue., Methods: We recruited forty-eight individuals with IGD and forty-six recreational internet game users (RGUs) as a control group in this study. fMRI data were collected when they were finishing a value-matching delayed discount task (DDT), which included easy and hard decisions judging based on the indifference points of every participant. The correlations between brain responses during DDT and IGD severity and the effective connectivity between brain regions were calculated., Results: Compared to RGUs, IGD subjects showed enhanced activation in the orbitofrontal cortex (OFC) when facing hard choices, and this feature was associated with IGD severity. In addition, individuals with IGD showed increased effective connectivity from the OFC to the dorsolateral prefrontal cortex and the OFC to the occipital lobe and decreased effective connectivity from the occipital lobe to the OFC., Conclusion: The current study showed that the abnormal activation in the OFC was associated with IGD severity and higher OFC-DLPFC/OFC-occipital lobe effective connectivity and lower occipital lobe-OFC effective connectivity when individuals with IGD faced different choices in the DDT. These findings suggest the neural mechanisms of impulsive decision-making in individuals with IGD due to dysfunction with subjective evaluation and dysfunction of the connection with the executive control system., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Nearly 30% of patients with relapsed breast cancer present activating mutations in estrogen receptor alpha (ERα) that confer partial resistance to existing endocrine-based therapies. We previously reported the development of H3B-5942, a covalent ERα antagonist that engages cysteine-530 (C530) to achieve potency against both wild-type (ERαWT) and mutant ERα (ERαMUT). Anticipating that the emergence of C530 mutations could promote resistance to H3B-5942, we applied structure-based drug design to improve the potency of the core scaffold to further enhance the antagonistic activity in addition to covalent engagement. This effort led to the development of the clinical candidate H3B-6545, a covalent antagonist that is potent against both  ERαWT/MUT, and maintains potency even in the context of ERα C530 mutations. H3B-6545 demonstrates significant activity and superiority over standard-of-care fulvestrant across a panel of ERαWT and ERαMUT palbociclib sensitive and resistant models. In summary, the compelling preclinical activity of H3B-6545 supports its further development for the potential treatment of endocrine therapy-resistant ERα+ breast cancer harboring wild-type or mutant ESR1, as demonstrated by the ongoing clinical trials (NCT03250676, NCT04568902, NCT04288089)., Summary: H3B-6545 is an ERα covalent antagonist that exhibits encouraging preclinical activity against CDK4/6i naïve and resistant ERαWT and ERαMUT tumors., (©2022 The Authors; Published by the American Association for Cancer Research.)

The budding yeast Saccharomyces cerevisiae is capable of surviving extreme water loss for a long time. However, less is known about the mechanism of its desiccation tolerance. In this study, we revealed that in an exponential culture, all desiccation tolerant yeast cells were in G1 phase and had condensed chromosomes. These cells share certain features of stationary G0 cells, such as low metabolic level. They were also replicatively young, compared to the desiccation sensitive G1 cells. A similar percentage of chromosome-condensed cells were observed in stationary phase but the condensation level was much higher than that of the log-phase cells. These chromosome-condensed stationary cells were also tolerant to desiccation. However, the majority of the desiccation tolerant cells in stationary phase do not have condensed chromosomes. We speculate that the log-phase cells with condensed chromosome might be a unique feature developed through evolution to survive unpredicted sudden changes of the environment., Competing Interests: Conflict of Interest: The authors declare no conflict of interests., (Copyright: © 2021 Zhang and Zhang.)

Background: Low-cost raw materials such as lignocellulosic materials have been utilized in second-generation ethanol production process. However, the sequential and slow conversion of xylose into target products remains one of the main challenges for realizing efficient industrial lignocellulosic biorefinery., Results: By applying different constant potentials to different microbial electrolysis cells with xylose as the sole carbon source, we analyzed the output of metabolites, microbial community structures, electron flow, and carbon flow in the process of xylose electro-fermentation by domesticated activated sludge. The bioreactors produced currents when applying positive potentials. The peak currents of the + 0.242 V, + 0.542 V and + 0.842 V reactors were 0.96 × 10 -6 A, 3.36 × 10 -6 A and 6.43 × 10 -6 A, respectively. The application of potentials promoted the xylose consumption, and the maximum consumption rate in the + 0.542 V reactor was 95.5%, which was 34.8 times that of the reactor without applied potential. The potential application also promoted the production of ethanol and acetate. The maximum ethanol yield (0.652 mol mol -1 xylose) was obtained in the + 0.842 V reactor. The maximum acetate concentration (1,874 µmol L -1 ) was observed in the + 0.842 V reactor. The optimal potential for ethanol production was + 0.842 V with the maximum ethanol yield and energy saving. The application of positive potential caused the microorganisms to carry out ethanol fermentation, and the application of negative potential forced the microorganisms to carry out acetic fermentation. The potential application changed the diversity and community structure of microorganisms in the reactors, and the two most significantly changed families were Paenibacillaceae and Bacillaceae., Conclusion: The constructed microbial electrolysis cells with different potentials obtained better production yield and selectivity compared with the reactor without applied potential. Our work provides strategies for the subsequent fermentation processes with different needs., (© 2021. The Author(s).)

Background: Internet gaming disorder (IGD) is a type of behavioral addiction characterized by poorly controlled and interfering patterns of game playing. Studies have suggested that the IGD is usually accompanied by increased desire or craving for gaming, suggesting that secondary rewards related to gaming may become more salient than those for primary rewards like food. However, this hypothesis has not been formally tested and potential neural mechanisms remain unclear., Methods: This is a functional magnetic resonance imaging (fMRI) study. Twenty-one IGD subjects and 23 matched individuals with recreational game use (RGU) were scanned when exposed to gaming (secondary rewards), food (primary rewards) and neutral cues. Group-by-cue-type interaction analyses and subsequent within-group analyses for fMRI data were performed and seed-based functional connectivity (FC) analyses explored further potential neural features., Results: IGD subjects' subjective craving responses to gaming cues were higher than to food cues, while the opposite was observed in RGU subjects. Group-by-cue interaction effects implicated the precuneus and precuneus-caudate FC. Simple effect analysis showed that for IGD subjects, gaming-related cues elicited higher FC in precuneus-caudate relationships than did food-related cues. In the RGU subjects, the opposite was observed. Significant correlations were found between brain features and craving scores., Conclusions: These results support the hypothesis regarding imbalances in sensitivities to different types of reward in IGD, and suggest neural mechanisms by which craving for gaming may make secondary rewards more salient than primary ones, thus promoting participation in addictive patterns of gaming.

To evaluate the potential of an integrated clinical test to detect diverse classes of somatic and germline mutations relevant to pediatric oncology, we performed three-platform whole-genome (WGS), whole exome (WES) and transcriptome (RNA-Seq) sequencing of tumors and normal tissue from 78 pediatric cancer patients in a CLIA-certified, CAP-accredited laboratory. Our analysis pipeline achieves high accuracy by cross-validating variants between sequencing types, thereby removing the need for confirmatory testing, and facilitates comprehensive reporting in a clinically-relevant timeframe. Three-platform sequencing has a positive predictive value of 97-99, 99, and 91% for somatic SNVs, indels and structural variations, respectively, based on independent experimental verification of 15,225 variants. We report 240 pathogenic variants across all cases, including 84 of 86 known from previous diagnostic testing (98% sensitivity). Combined WES and RNA-Seq, the current standard for precision oncology, achieved only 78% sensitivity. These results emphasize the critical need for incorporating WGS in pediatric oncology testing.

Alginate lyase is a biocatalyst that degrades alginate to produce oligosaccharides, which have many bioactive functions and could be used as renewable biofuels. Here we report a simple and sensitive plate assay for screening alginate lyase-excreting microorganisms from brown algae. Brown algae Laminaria japonica, Sargassum horneri and Sargassum siliquatrum were cultured in sterile water. Bacteria growing on the surface of seaweeds were identified and their capacity of excreting alginate lyase was analyzed. A total of 196 strains were recovered from the three different algae samples and 12 different bacterial strains were identified capable of excreting alginate lyases. Sequence analysis of the 16S rRNA gene revealed that these alginate lyase-excreting strains belong to eight genera: Paenibacillus (4/12), Bacillus (2/12), Leclercia (1/12), Isoptericola (1/12), Planomicrobium (1/12), Pseudomonas (1/12), Lysinibacillus (1/12) and Sphingomonas (1/12). Further analysis showed that the LJ-3 strain (Bacillus halosaccharovorans) had the highest enzyme activity. To our best knowledge, this is the first report regarding alginate lyase-excreting strains in Paenibacillus, Planomicrobium and Leclercia. We believe that our method used in this study is relatively easy and reliable for large-scale screening of alginate lyase-excreting microorganisms.

Altered nuclear size is associated with many cancers, and determining whether cancer-associated changes in nuclear size contribute to carcinogenesis necessitates an understanding of mechanisms of nuclear size regulation. Although nuclear import rates generally positively correlate with nuclear size, NTF2 levels negatively affect nuclear size, despite the role of NTF2 (also known as NUTF2) in nuclear recycling of the import factor Ran. We show that binding of Ran to NTF2 is required for NTF2 to inhibit nuclear expansion and import of large cargo molecules in Xenopus laevis egg and embryo extracts, consistent with our observation that NTF2 reduces the diameter of the nuclear pore complex (NPC) in a Ran-binding-dependent manner. Furthermore, we demonstrate that ectopic NTF2 expression in Xenopus embryos and mammalian tissue culture cells alters nuclear size. Finally, we show that increases in nuclear size during melanoma progression correlate with reduced NTF2 expression, and increasing NTF2 levels in melanoma cells is sufficient to reduce nuclear size. These results show a conserved capacity for NTF2 to impact on nuclear size, and we propose that NTF2 might be a new cancer biomarker., (© 2016. Published by The Company of Biologists Ltd.)

Background: Aldosterone has been implicated in a variety of organ fibroses, but its role and mechanism in liver fibrosis remain unclear., Methods: Rat primary hepatic stellate cells (HSCs) were isolated, cultured, and characterized. HSCs were incubated with aldosterone (10(-6) M) for 4 h, 8 h, 12 h, 24 h, and 48 h, after which TGF-β1 (transforming growth factor beta 1) expression was measured by real-time PCR. Rat HSCs were treated with different concentrations of aldosterone (10(-6) M, 10(-7) M, 10(-8) M, and 10(-9) M), and the expressions of PAI-1 (plasminogen activator inhibitor-1) and TGF-β1 were determined by measuring mRNA and protein. HSCs were incubated in groups containing aldosterone (10(-6) M), spironolactone (10(-5) M), both aldosterone and spironolactone, or neither aldosterone nor spironolactone (control), after which mRNA and protein expression of PAI-1 and TGF-β1 were measured. Collagen I expression was detected by immunohistochemical analysis of supernatants of the aldosterone (10(-6) M), TGF-β1, and aldosterone plus TGF-β1 groups. SMAD expression was detected in rat HSC control, HSC plus aldosterone (10(-6) M), HSC plus TGF-β1, and HSC plus aldosterone plus TGF-β1 groups., Results: HSCs were incubated with aldosterone for 4 h, 8 h, 12 h, 24 h, and 48 h after which TGF-β1 expression was measured. We found that TGF-β1 expression increased in a time dependent manner and reached a peak at 24 h. The expression of TGF-β1 in groups treated with aldosterone for 4 h, 8 h, 12 h, and 24 h was significantly different from the control group (P < 0.01). No significant difference was seen in TGF-β1 expression between the groups treated with aldosterone for 24 h and 48 h (P > 0.05). Compared with the control group, TGF-β1 expression was significantly increased after incubation with different concentrations of aldosterone (10(-6) M, 10(-7) M, 10(-8) M, and 10(-9) M) (P < 0.01). There were significant differences in the expression of TGF-β1 between 10(-6) M and 10(-7) M aldosterone treatment groups (P < 0.01). Compared with the control group, the expression of PAI-1 was significantly increased after incubation with different concentrations of aldosterone (10(-6) M, 10(-7) M, 10(-8) M, and 10(-9) M) (P < 0.01). PAI-1 expression was increased in the aldosterone, spironolactone, and aldosterone plus spironolactone groups. The expression of PAI-1 was significantly enhanced in the aldosterone and aldosterone plus spironolactone groups compared with the control group (P < 0.01). There was a marked enhancement of collagen I expression in the aldosterone, TGF-β1, and aldosterone plus TGF-β1 groups (P < 0.05). Collagen I expressions in the aldosterone and TGF-β1 groups were significantly different from the aldosterone plus TGF-β1 group (P < 0.01). Compared with the control group, SMAD expression was markedly elevated in the aldosterone, TGF-β1, and aldosterone plus TGF-β1 groups (P < 0.05). The expression of SMAD was significantly increased in the aldosterone plus TGF-β1 group compared with the aldosterone group (P < 0.01)., Conclusion: This study demonstrated that aldosterone promoted HSC activation and the expression of TGF-β1, PAI-1, and collagen in hepatic fibrosis progression and that spironolactone administration partially reversed the effects. The aldosterone promotional effect on hepatic fibrosis was partially mediated by TGF-β1.

The molecular mechanism of acetic acid tolerance in yeast remains unclear despite of its importance for efficient cellulosic ethanol production. In this study, we examined the effects of histone H3/H4 point mutations on yeast acetic acid tolerance by comprehensively screening a histone H3/H4 mutant library. A total of 24 histone H3/H4 mutants (six acetic acid resistant and 18 sensitive) were identified. Compared to the wild-type strain, the histone acetic acid-resistant mutants exhibited improved ethanol fermentation performance under acetic acid stress. Genome-wide transcriptome analysis revealed that changes in the gene expression in the acetic acid-resistant mutants H3 K37A and H4 K16Q were mainly related to energy production, antioxidative stress. Our results provide novel insights into yeast acetic acid tolerance on the basis of histone, and suggest a novel approach to improve ethanol production by altering the histone H3/H4 sequences., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Phosphatidylserine decarboxylase, which is embedded in the inner mitochondrial membrane, synthesizes phosphatidylethanolamine (PE) and, in some cells, synthesizes the majority of this important phospholipid. Normal levels of PE can decline with age in the brain. Here we used yeast and worms to test the hypothesis that low levels of PE alter the homeostasis of the Parkinson disease-associated protein α-synuclein (α-syn). In yeast, low levels of PE in the phosphatidylserine decarboxylase deletion mutant (psd1Δ) cause decreased respiration, endoplasmic reticulum (ER) stress, a defect in the trafficking of the uracil permease, α-syn accumulation and foci, and a slow growth phenotype. Supplemental ethanolamine (ETA), which can be converted to PE via the Kennedy pathway enzymes in the ER, had no effect on respiration, whereas, in contrast, this metabolite partially eliminated ER stress, decreased α-syn foci formation, and restored growth close to that of wild-type cells. In Caenorhabditis elegans, RNAi depletion of phosphatidylserine decarboxylase in dopaminergic neurons expressing α-syn accelerates neurodegeneration, which supplemental ETA rescues. ETA fails to rescue this degeneration in worms that undergo double RNAi depletion of phosphatidylserine decarboxylase (psd-1) and choline/ETA phosphotransferase (cept-1), which encodes the last enzyme in the CDP-ETA Kennedy pathway. This finding suggests that ETA exerts its protective effect by boosting PE through the Kennedy pathway. Overall, a low level of PE causes ER stress, disrupts vesicle trafficking, and causes α-syn to accumulate; such cells likely die from a combination of ER stress and excessive accumulation of α-syn.

The yeast cell wall plays an important role in maintaining cell morphology, cell integrity and response to environmental stresses. Here, we report that salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA (ρ 0 ). Upon salt treatment, the cell wall is thickened, broken and becomes more sensitive to the cell wall-perturbing agent sodium dodecyl sulfate (SDS). Also, SCW11 mRNA levels are elevated in ρ 0 cells. Deletion of SCW11 significantly decreases the sensitivity of ρ 0 cells to SDS after salt treatment, while overexpression of SCW11 results in higher sensitivity. In addition, salt stress in ρ 0 cells induces high levels of reactive oxygen species (ROS), which further damages the cell wall, causing cells to become more sensitive towards the cell wall-perturbing agent., Competing Interests: Conflict of interest: The authors declare no conflict of interest.

Objective: Hepatopulmonary syndrome (HPS) is considered as a triad of chronic liver disease, pulmonary vascular ectasia and severe hypoxemia. The study aims to investigate the pathological mechanism of intra-abdominal pressure (IAP) in HPS and establish a novel mouse model., Methods: Fifty male ICR mice were randomly divided into experimental and control group, receiving subcutaneous injection of carbon tetrachloride and water, respectively. Mice in experimental group were then divided into 4 sub-groups with the intraperitoneal injection of different volume of albumin to form different IAP (0, 5, 10 and 20 cmH2O). All the mice were then sacrificed 24 hours later and blood gas analysis was conducted. In addition, liver and lung histopathology was also examined., Results: Blood gas analysis in different IAP suggested the respiratory alkalosis. Arterial partial pressure of oxygen significantly decreased in the IAP=10 cmH2O (68.13 ± 3.56, P<0.01) and 20 cmH2O (66.00 ± 3.78, P<0.01). Alveolar-arterial oxygen pressure difference increased markedly in the IAP=10 cmH2O (54.60 ± 6.80, P<0.001) and 20 cmH2O (57.04 ± 5.60, P<0.001). According to lung histopathology, macrophages were found to accumulate in the alveolar spaces and the widened alveolar walls were detected. In addition, there was visible blood stasis in the alveolar walls and numerous red blood cells extravasated into air space in the IAP=10 and 20 cmH2O., Conclusions: Our study suggested that intra-abdominal hypertension was a significant pathological mechanism of HPS. Meanwhile, we have established a novel mouse model that will now be optimized with further investigation of the mechanism and therapeutic targets of HPS.

Objective: Hepatorenal syndrome is one of the serious complications of cirrhosis and closely associated with the increasing intra-abdominal pressure (IAP). The study aims to explore the potential mechanism of intra-abdominal hypertension in the development of hepatorenal syndrome in mouse models., Methods: Eighty male mice were randomly divided into model group (subcutaneous injection of carbon tetrachloride) and control group (subcutaneous injection of olive oil). After 12 weeks, parts of the mice were sacrificed and liver histopathology was detected. Then, albumin (30 g/L) and normal saline were separately injected into the peritoneal cavity of mice to induce the different IAP levels (0, 5, 10 and 20cmH2O). Blood urea nitrogen, serum creatinine and renal histopathology were examined 24 hours later., Results: Blood urea nitrogen and serum creatinine levels were statistically significant high in the group of IAP= 10 and 20cmH2O as compared with the IAP= 0cmH2O. From results of renal histopathology, the constrictive renal tubular lumen and inflammatory infiltration in the interstitial were observed in groups of IAP= 5 and 10cmH2O. Besides, the formed casts and hyperemia in the renal interstitial could be detected in group of IAP= 20cmH2O. The cellular swelling and edema of renal tubular epithelial cells were found in model group simultaneously., Conclusions: Our study suggested that intra-abdominal hypertension was a significant pathological mechanism and a potential independent risk factor of hepatorenal syndrome.

Parkinson disease (PD) results from the slow, progressive loss of dopaminergic neurons in the substantia nigra. Alterations in α-synuclein (aSyn), such as mutations or multiplications of the gene, are thought to trigger this degeneration. Here, we show that aSyn disrupts mitogen-activated protein kinase (MAPK)-controlled stress signaling in yeast and human cells, which results in inefficient cell protective responses and cell death. aSyn is a substrate of the yeast (and human) polo-like kinase Cdc5 (Plk2), and elevated levels of aSyn prevent Cdc5 from maintaining a normal level of GTP-bound Rho1, which is an essential GTPase that regulates stress signaling. The nine N-terminal amino acids of aSyn are essential for the interaction with polo-like kinases. The results support a unique mechanism of PD pathology.

The neurokinin 3 receptor (NK3R) is a G protein-coupled receptor that is expressed in brain and is highly expressed by magnocellular vasopressinergic neurons in both the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus. Hyperosmolarity causes a ligand-mediated internalization of NK3Rs to the cytoplasm and to the nuclei of vasopressinergic PVN neurons. This receptor activation-dependent pathway is presumed to be a means to directly transmit synaptic signals from the cell membrane to the nucleus. The present study evaluated in vivo the subnuclear domains that associate with NK3R. Rats were administered 2 M NaCl (intragastric) or no intragastric load, and 40 min later, the PVN was dissected and nuclei were isolated. Using double-immuno-transmission electron microscopy (TEM), we show that, compared with controls, hyperosmolarity causes a significant increase in NK3R Immunogold beads in the nucleus of PVN neurons. Furthermore, NK3R spatially colocalized with histone H4 and with highly acetylated H4 in nuclei isolated from the PVN of rats administered 2 M NaCl, but not in nuclei from control rats. Next, coimmunoprecipitation experiments showed that acetylated H4, as well as acetylated H3, were pulled down with NK3R in the PVN nuclear enriched fraction from rats treated with 2 M NaCl, but not from control rats. In response to hyperosmolarity, NK3R is transported to the nucleus of PVN neurons and associates with transcriptionally active chromatin, where it may influence the transcription of genes.