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"Tang, Shuang"
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Inferring the energy sensitivity and band gap of electronic transport in a network of carbon nanotubes
Since the industrialization of single-phase nanomaterial-based devices is still challenging, intensive research focus has been given to complex materials consisting of multiple nanoscale entities, including networks and matrices of nanowires, nanotubes, nanoribbons, or other large molecules; among these complex materials, networks of carbon nanotubes are a typical example. Detailed knowledge of the energy sensitivity and band gap of electronic transport in such a material system is difficult to detect, despite its importance in electronic, energetic and sensing applications. Here, we propose a new methodology to obtain these quantities using the measured Seebeck coefficient at a certain temperature but different Fermi levels. We discover that the network consisting of semiconducting
(11,10)
-carbon nanotubes actually exhibits metallic transport at room temperature. It is also interesting to verify that intrananotube ballistic transport is dominant over diffusive scattering by long-range disorder, as well as the quantum hopping resistance at the contact points. The transport asymmetry ratio between the holes and electrons (1.75) is similar to the value observed in pristine graphene samples (1.50).
Journal Article
Developing a highly efficient hydroxytyrosol whole-cell catalyst by de-bottlenecking rate-limiting steps
Hydroxytyrosol is an antioxidant free radical scavenger that is biosynthesized from tyrosine. In metabolic engineering efforts, the use of the mouse tyrosine hydroxylase limits its production. Here, we design an efficient whole-cell catalyst of hydroxytyrosol in
Escherichia coli
by de-bottlenecking two rate-limiting enzymatic steps. First, we replace the mouse tyrosine hydroxylase by an engineered two-component flavin-dependent monooxygenase HpaBC of
E. coli
through structure-guided modeling and directed evolution. Next, we elucidate the structure of the
Corynebacterium glutamicum
VanR regulatory protein complexed with its inducer vanillic acid. By switching its induction specificity from vanillic acid to hydroxytyrosol, VanR is engineered into a hydroxytyrosol biosensor. Then, with this biosensor, we use in vivo-directed evolution to optimize the activity of tyramine oxidase (TYO), the second rate-limiting enzyme in hydroxytyrosol biosynthesis. The final strain reaches a 95% conversion rate of tyrosine. This study demonstrates the effectiveness of sequentially de-bottlenecking rate-limiting steps for whole-cell catalyst development.
Whole-cell catalyst-based hydroxytyrosol production is low. Here, the authors increase the efficiency of its production in
E. coli
by de-bottlenecking two enzymatic steps catalyzed by monooxygenase and tyramine oxidase using structure-based enzyme redesign or in vivo-directed evolution with the aid of a newly developed biosensor.
Journal Article
Promiscuous enzymatic activity-aided multiple-pathway network design for metabolic flux rearrangement in hydroxytyrosol biosynthesis
Genetic diversity is a result of evolution, enabling multiple ways for one particular physiological activity. Here, we introduce this strategy into bioengineering. We design two hydroxytyrosol biosynthetic pathways using tyrosine as substrate. We show that the synthetic capacity is significantly improved when two pathways work simultaneously comparing to each individual pathway. Next, we engineer flavin-dependent monooxygenase HpaBC for tyrosol hydroxylase, tyramine hydroxylase, and promiscuous hydroxylase active on both tyrosol and tyramine using directed divergent evolution strategy. Then, the mutant HpaBCs are employed to catalyze two missing steps in the hydroxytyrosol biosynthetic pathways designed above. Our results demonstrate that the promiscuous tyrosol/tyramine hydroxylase can minimize the cell metabolic burden induced by protein overexpression and allow the biosynthetic carbon flow to be divided between two pathways. Thus, the efficiency of the hydroxytyrosol biosynthesis is significantly improved by rearranging the metabolic flux among multiple pathways.
Metabolic engineering usually focuses on manipulating enzyme(s) within a single pathway. Here, the authors show that a promiscuous enzymatic activity-based multiple-pathway design can minimize cell metabolic burden and allow carbon flow rearrangement, leading to efficient hydroxytyrosol biosynthesis.
Journal Article
An Operational Multi-Radar Multi-Sensor QPE System in Taiwan
Over the last two decades, the Central Weather Bureau of Taiwan and the U.S. National Severe Storms Laboratory have been involved in a research and development collaboration to improve the monitoring and prediction of river flooding, flash floods, debris flows, and severe storms for Taiwan. The collaboration resulted in the Quantitative Precipitation Estimation and Segregation Using Multiple Sensors (QPESUMS) system. The QPESUMS system integrates observations from multiple mixed-band weather radars, rain gauges, and numerical weather prediction model fields to produce high-resolution (1 km) and rapid-update (10 min) rainfall and severe storm monitoring and prediction products. The rainfall products are widely used by government agencies and emergency managers in Taiwan for flood and mudslide warnings as well as for water resource management. The 3D reflectivity mosaic and QPE products are also used in high-resolution radar data assimilation and for the verification of numerical weather prediction model forecasts. The system facilitated collaborations with academic communities for research and development of radar applications, including quantitative precipitation estimation and nowcasting. This paper provides an overview of the operational QPE capabilities in the Taiwan QPESUMS system.
Journal Article
Neural correlates of novelty and appropriateness processing in externally induced constraint relaxation
Novelty and appropriateness are considered the two fundamental features of creative thinking, including insight problem solving, which can be performed through chunk decomposition and constraint relaxation. Based on a previous study that separated the neural bases of novelty and appropriateness in chunk decomposition, in this study, we used event-related functional magnetic resonance imaging (fMRI) to further dissociate these mechanisms in constraint relaxation. Participants were guided to mentally represent the method of problem solving according to the externally provided solutions that were elaborately prepared in advance and systematically varied in their novelty and appropriateness for the given problem situation. The results showed that novelty processing was completed by the temporoparietal junction (TPJ) and regions in the executive system (dorsolateral prefrontal cortex [DLPFC]), whereas appropriateness processing was completed by the TPJ and regions in the episodic memory (hippocampus), emotion (amygdala), and reward systems (orbitofrontal cortex [OFC]). These results likely indicate that appropriateness processing can result in a more memorable and richer experience than novelty processing in constraint relaxation. The shared and distinct neural mechanisms of the features of novelty and appropriateness in constraint relaxation are discussed, enriching the representation of the change theory of insight.
•Dissociated neural basis of novelty and appropriateness in constraint relaxation.•Both novelty and appropriateness processing were mediated by the TPJ.•The executive system (DLPFC) involved in novelty processing.•Episodic memory system (hippocampus) involved in appropriateness processing.•Emotion (amygdala) and reward (OFC) systems involved in appropriateness.
Journal Article
TREM2 activation alleviates neural damage via Akt/CREB/BDNF signalling after traumatic brain injury in mice
Background
Neuroinflammation is one of the most important processes in secondary injury after traumatic brain injury (TBI). Triggering receptor expressed on myeloid cells 2 (TREM2) has been proven to exert neuroprotective effects in neurodegenerative diseases and stroke by modulating neuroinflammation, and promoting phagocytosis and cell survival. However, the role of TREM2 in TBI has not yet been elucidated. In this study, we are the first to use COG1410, an agonist of TREM2, to assess the effects of TREM2 activation in a murine TBI model.
Methods
Adult male wild-type (WT) C57BL/6 mice and adult male TREM2 KO mice were subjected to different treatments. TBI was established by the controlled cortical impact (CCI) method. COG1410 was delivered 1 h after CCI via tail vein injection. Western blot analysis, immunofluorescence, laser speckle contrast imaging (LSCI), neurological behaviour tests, brain electrophysiological monitoring, Evans blue assays, magnetic resonance imaging (MRI), and brain water content measurement were performed in this study.
Results
The expression of endogenous TREM2 peaked at 3 d after CCI, and it was mainly expressed on microglia and neurons. We found that COG1410 improved neurological functions within 3 d, as well as neurological functions and brain electrophysiological activity at 2 weeks after CCI. COG1410 exerted neuroprotective effects by inhibiting neutrophil infiltration and microglial activation, and suppressing neuroinflammation after CCI. In addition, COG1410 treatment alleviated blood brain barrier (BBB) disruption and brain oedema; furthermore, COG1410 promoted cerebral blood flow (CBF) recovery at traumatic injury sites after CCI. In addition, COG1410 suppressed neural apoptosis at 3 d after CCI. TREM2 activation upregulated p-Akt, p-CREB, BDNF, and Bcl-2 and suppressed TNF-α, IL-1β, Bax, and cleaved caspase-3 at 3 d after CCI. Moreover, TREM2 knockout abolished the effects of COG1410 on vascular phenotypes and microglial states. Finally, the neuroprotective effects of COG1410 were suppressed by TREM2 depletion.
Conclusions
Altogether, we are the first to demonstrate that TREM2 activation by COG1410 alleviated neural damage through activation of Akt/CREB/BDNF signalling axis in microglia after CCI. Finally, COG1410 treatment improved neurological behaviour and brain electrophysiological activity after CCI.
Graphical Abstract
Journal Article
Herpes simplex virus ICP27 regulates alternative pre-mRNA polyadenylation and splicing in a sequence-dependent manner
The herpes simplex virus (HSV) infected cell culture polypeptide 27 (ICP27) protein is essential for virus infection of cells. Recent studies suggested that ICP27 inhibits splicing in a gene-specific manner via an unknown mechanism. Here, RNA-sequencing revealed that ICP27 not only inhibits splicing of certain introns in <1% of cellular genes, but also can promote use of alternative 5′ splice sites. In addition, ICP27 induced expression of pre-mRNAs prematurely cleaved and polyadenylated from cryptic polyadenylation signals (PAS) located in intron 1 or 2 of ∼1% of cellular genes. These previously undescribed prematurely cleaved and polyadenylated pre-mRNAs, some of which contain novel ORFs, were typically intronless, <2 Kb in length, expressed early during viral infection, and efficiently exported to cytoplasm. Sequence analysis revealed that ICP27-targeted genes are GC-rich (as are HSV genes), contain cytosine-rich sequences near the 5′ splice site, and have suboptimal splice sites in the impacted intron, suggesting that a common mechanism is shared between ICP27-mediated alternative polyadenylation and splicing. Optimization of splice site sequences or mutation of nearby cytosines eliminated ICP27-mediated splicing inhibition, and introduction of C-rich sequences to an ICP27-insensitive splicing reporter conferred this phenotype, supporting the inference that specific gene sequences confer susceptibility to ICP27. Although HSV is the first virus and ICP27 is the first viral protein shown to activate cryptic PASs in introns, we suspect that other viruses and cellular genes also encode this function.
Journal Article
Engineering and application of LacI mutants with stringent expressions
Optimal transcriptional regulatory circuits are expected to exhibit stringent control, maintaining silence in the absence of inducers while exhibiting a broad induction dynamic range upon the addition of effectors. In the Plac/LacI pair, the promoter of the lac operon in Escherichia coli is characterized by its leakiness, attributed to the moderate affinity of LacI for its operator target. In response to this limitation, the LacI regulatory protein underwent engineering to enhance its regulatory properties. The M7 mutant, carrying I79T and N246S mutations, resulted in the lac promoter displaying approximately 95% less leaky expression and a broader induction dynamic range compared to the wild‐type LacI. An in‐depth analysis of each mutation revealed distinct regulatory profiles. In contrast to the wild‐type LacI, the M7 mutant exhibited a tighter binding to the operator sequence, as evidenced by surface plasmon resonance studies. Leveraging the capabilities of the M7 mutant, a high‐value sugar biosensor was constructed. This biosensor facilitated the selection of mutant galactosidases with approximately a seven‐fold improvement in specific activity for transgalactosylation. Consequently, this advancement enabled enhanced biosynthesis of galacto‐oligosaccharides (GOS). Evolved mutant LacI displayed less leaky expression. Leveraging the mutant into a biosensor for high‐throughput screening of enzymes for biosynthesis of galacto‐oligosaccharides.
Journal Article
Potential distribution of the extremely endangered species Ostrya rehderiana (Betulaceae) in China under future climate change
Global climate change is a major threat to biodiversity, which may increase the extinction risk of rare species, particularly those like
Ostrya rehderiana
Chun (Betulaceae) with very few remaining extant wild individuals. We aimed to estimate the potential distribution of
O. rehderiana
under climate change and to analyze possible relevant climatic factors. Maximum entropy (Maxent) was employed to model the potential distribution of
O. rehderiana
under present and future climate scenarios. Suitable habitat areas in different periods and the main contributing climate factors were identified using species distribution models. The minimum temperature in winter and precipitation seasonality were the principal climatic factors influencing the establishment of
O. rehderiana
. The proportion of high potential distribution area in China was 3.91% and would further shrink significantly under changing climate, especially reduce by 97% under high radiative forcing. The extinction risk of
O. rehderiana
would still be extraordinarily high under future climate scenarios. The Tianmu and Luoxiao Mountains would be the only potential refugia for
O. rehderiana
in the future. Special conservation efforts are urgently required to rescue extremely endangered species as
O. rehderiana
. We propose priorities for the conservation region and suggestions for conservation management strategies.
Journal Article