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The cortico-basal ganglia-thalamo-cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behaviour, and the natural history of many neurological and neuropsychiatric disorders. Classically, this network is conceptualized to contain three information channels: motor, limbic and associative1-4. Yet this three-channel view cannot explain the myriad functions of the basal ganglia. We previously subdivided the dorsal striatum into 29 functional domains on the basis of the topography of inputs from the entire cortex5. Here we map the multi-synaptic output pathways of these striatal domains through the globus pallidus external part (GPe), substantia nigra reticular part (SNr), thalamic nuclei and cortex. Accordingly, we identify 14 SNr and 36 GPe domains and a direct cortico-SNr projection. The striatonigral direct pathway displays a greater convergence of striatal inputs than the more parallel striatopallidal indirect pathway, although direct and indirect pathways originating from the same striatal domain ultimately converge onto the same postsynaptic SNr neurons. Following the SNr outputs, we delineate six domains in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify six parallel cortico-basal ganglia-thalamic subnetworks that sequentially transduce specific subsets of cortical information through every elemental node of the cortico-basal ganglia-thalamic loop. Thalamic domains relay this output back to the originating corticostriatal neurons of each subnetwork in a bona fide closed loop.
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Ganglios Basales/citología , Corteza Cerebral/citología , Vías Nerviosas , Neuronas/citología , Tálamo/citología , Animales , Ganglios Basales/anatomía & histología , Corteza Cerebral/anatomía & histología , Masculino , Ratones , Ratones Endogámicos C57BL , Tálamo/anatomía & histologíaRESUMEN
Although epigenetic mechanisms of gene expression regulation have recently been implicated in memory consolidation and persistence, the role of nucleosome-remodeling is largely unexplored. Recent studies show that the functional loss of BAF53b, a postmitotic neuron-specific subunit of the BAF nucleosome-remodeling complex, results in the deficit of consolidation of hippocampus-dependent memory and cocaine-associated memory in the rodent brain. However, it is unclear whether BAF53b expression is regulated during memory formation and how BAF53b regulates fear memory in the amygdala, a key brain site for fear memory encoding and storage. To address these questions, we used viral vector approaches to either decrease or increase BAF53b function specifically in the lateral amygdala of adult mice in auditory fear conditioning paradigm. Knockdown of Baf53b before training disrupted long-term memory formation with no effect on short-term memory, basal synaptic transmission, and spine structures. We observed in our qPCR analysis that BAF53b was induced in the lateral amygdala neurons at the late consolidation phase after fear conditioning. Moreover, transient BAF53b overexpression led to persistently enhanced memory formation, which was accompanied by increase in thin-type spine density. Together, our results provide the evidence that BAF53b is induced after learning, and show that such increase of BAF53b level facilitates memory consolidation likely by regulating learning-related spine structural plasticity.SIGNIFICANCE STATEMENT Recent works in the rodent brain begin to link nucleosome remodeling-dependent epigenetic mechanism to memory consolidation. Here we show that BAF53b, an epigenetic factor involved in nucleosome remodeling, is induced in the lateral amygdala neurons at the late phase of consolidation after fear conditioning. Using specific gene knockdown or overexpression approaches, we identify the critical role of BAF53b in the lateral amygdala neurons for memory consolidation during long-term memory formation. Our results thus provide an idea about how nucleosome remodeling can be regulated during long-term memory formation and contributes to the permanent storage of associative fear memory in the lateral amygdala, which is relevant to fear and anxiety-related mental disorders.
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Actinas/metabolismo , Amígdala del Cerebelo/fisiología , Proteínas Cromosómicas no Histona/metabolismo , Proteínas de Unión al ADN/metabolismo , Miedo/fisiología , Consolidación de la Memoria/fisiología , Neuronas/metabolismo , Nucleosomas/metabolismo , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Plasticidad Neuronal/fisiologíaRESUMEN
UNLABELLED: MicroRNAs (miRNAs) are small, noncoding RNAs that posttranscriptionally regulate gene expression in many tissues. Although a number of brain-enriched miRNAs have been identified, only a few specific miRNAs have been revealed as critical regulators of synaptic plasticity, learning, and memory. miR-9-5p/3p are brain-enriched miRNAs known to regulate development and their changes have been implicated in several neurological disorders, yet their role in mature neurons in mice is largely unknown. Here, we report that inhibition of miR-9-3p, but not miR-9-5p, impaired hippocampal long-term potentiation (LTP) without affecting basal synaptic transmission. Moreover, inhibition of miR-9-3p in the hippocampus resulted in learning and memory deficits. Furthermore, miR-9-3p inhibition increased the expression of the LTP-related genes Dmd and SAP97, the expression levels of which are negatively correlated with LTP. These results suggest that miR-9-3p-mediated gene regulation plays important roles in synaptic plasticity and hippocampus-dependent memory. SIGNIFICANCE STATEMENT: Despite the abundant expression of the brain-specific microRNA miR-9-5p/3p in both proliferating and postmitotic neurons, most functional studies have focused on their role in neuronal development. Here, we examined the role of miR-9-5p/3p in adult brain and found that miR-9-3p, but not miR-9-5p, has a critical role in hippocampal synaptic plasticity and memory. Moreover, we identified in vivo binding targets of miR-9-3p that are involved in the regulation of long-term potentiation. Our study provides the very first evidence for the critical role of miR-9-3p in synaptic plasticity and memory in the adult mouse.
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Hipocampo/metabolismo , MicroARNs/metabolismo , Plasticidad Neuronal/fisiología , Reconocimiento en Psicología/fisiología , Animales , Condicionamiento Psicológico/fisiología , Homólogo 1 de la Proteína Discs Large , Distrofina/metabolismo , Conducta Exploratoria/fisiología , Miedo/fisiología , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Guanilato-Quinasas/metabolismo , Células HEK293 , Hipocampo/citología , Humanos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , MicroARNs/genética , Plasticidad Neuronal/efectos de los fármacos , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Reconocimiento en Psicología/efectos de los fármacos , Sinapsinas/genética , Sinapsinas/metabolismo , Transducción GenéticaRESUMEN
A comprehensive understanding of neuronal diversity and connectivity is essential for understanding the anatomical and cellular mechanisms that underlie functional contributions. With the advent of single-cell analysis, growing information regarding molecular profiles leads to the identification of more heterogeneous cell types. Therefore, the need for additional orthogonal recombinase systems is increasingly apparent, as heterogeneous tissues can be further partitioned into increasing numbers of specific cell types defined by multiple features. Critically, new recombinase systems should work together with pre-existing systems without cross-reactivity in vivo. Here, we introduce novel site-specific recombinase systems based on ΦC31 bacteriophage recombinase for labeling multiple cell types simultaneously and a novel viral strategy for versatile and robust intersectional expression of any transgene. Together, our system will help researchers specifically target different cell types with multiple features in the same animal.
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Integrasas , Recombinasas , Animales , Recombinasas/genética , Integrasas/genética , Vectores Genéticos , Neuronas/metabolismo , TransgenesRESUMEN
The meta-reinforcement learning (meta-RL) framework, which involves RL over multiple timescales, has been successful in training deep RL models that generalize to new environments. It has been hypothesized that the prefrontal cortex may mediate meta-RL in the brain, but the evidence is scarce. Here we show that the orbitofrontal cortex (OFC) mediates meta-RL. We trained mice and deep RL models on a probabilistic reversal learning task across sessions during which they improved their trial-by-trial RL policy through meta-learning. Ca2+/calmodulin-dependent protein kinase II-dependent synaptic plasticity in OFC was necessary for this meta-learning but not for the within-session trial-by-trial RL in experts. After meta-learning, OFC activity robustly encoded value signals, and OFC inactivation impaired the RL behaviors. Longitudinal tracking of OFC activity revealed that meta-learning gradually shapes population value coding to guide the ongoing behavioral policy. Our results indicate that two distinct RL algorithms with distinct neural mechanisms and timescales coexist in OFC to support adaptive decision-making.
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Refuerzo en Psicología , Recompensa , Ratones , Animales , Corteza Prefrontal/fisiología , Aprendizaje Inverso/fisiologíaRESUMEN
OBJECTIVES: Healthcare workers in hospitals (HHCWs), a notably increasing workforce, face various occupational hazards. A high incidence of cancer among HHCWs has been observed; however, the cancer incidence status among HHCWs in South Korea is yet to be studied. This study aimed to assess cancer incidence among HHCWs in South Korea. METHODS: We constructed a retrospective cohort of HHCWs using National Health Insurance claims data, including cancer incidence status and vital status, from 2007 to 2015. Those who had worked in hospitals for at least three years were defined as HHCWs. Standardized incidence ratios (SIRs) for all cancer types and standardized mortality ratios were calculated. RESULTS: A total of 107,646 HHCWs were followed up, and the total follow-up duration was 905,503 person-years. Compared to the total workers, female HHCWs showed significantly higher SIR for all cancers (observed cases = 1480; SIR = 1.25; 95% confidence interval [CI] = 1.06-1.47). The incidence of breast cancer among female HHCWs was significantly higher compared to that among total workers (observed cases = 376; SIR = 1.21; 95% CI = 1.09-1.36). CONCLUSIONS: Our findings indicate that female HHCWs have an elevated probability of developing cancer, which suggests that occupational risk factors such as night-shift work, anti-neoplastic medications, stressful jobs, and ionizing radiation should be assessed. Further investigation and occupational environment improvement activities are required.
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This study investigates the operating characteristics of AlGaN/GaN high-electron-mobility transistors (HEMTs) by applying HfO2 as the passivation layer. Before analyzing HEMTs with various passivation structures, modeling parameters were derived from the measured data of fabricated HEMT with Si3N4 passivation to ensure the reliability of the simulation. Subsequently, we proposed new structures by dividing the single Si3N4 passivation into a bilayer (first and second) and applying HfO2 to the bilayer and first passivation layer only. Ultimately, we analyzed and compared the operational characteristics of the HEMTs considering the basic Si3N4, only HfO2, and HfO2/Si3N4 (hybrid) as passivation layers. The breakdown voltage of the AlGaN/GaN HEMT having only HfO2 passivation was improved by up to 19%, compared to the basic Si3N4 passivation structure, but the frequency characteristics deteriorated. In order to compensate for the degraded RF characteristics, we modified the second Si3N4 passivation thickness of the hybrid passivation structure from 150 nm to 450 nm. We confirmed that the hybrid passivation structure with 350-nm-thick second Si3N4 passivation not only improves the breakdown voltage by 15% but also secures RF performance. Consequently, Johnson's figure-of-merit, which is commonly used to judge RF performance, was improved by up to 5% compared to the basic Si3N4 passivation structure.
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Green algae have been receiving widespread attention for their use as biofertilizers for agricultural production, but more studies are required to increase the efficiency of their use. This study aimed to investigate the effects of different levels of Chlorella fusca CHK0059 application on strawberry plant growth and fruit quality. A total of 800 strawberry seedlings were planted in a greenhouse and were grown for seven months under different Chlorella application rates: 0 (control), 0.1, 0.2, and 0.4% of the optimal cell density (OCD; 1.0 × 107 cells mL-1). The Chlorella application was conducted weekly via an irrigation system, and the characteristics of fruit samples were monitored monthly over a period of five months. The growth (e.g., phenotype, dry weight, and nutrition) and physiological (e.g., Fv/Fm and chlorophylls) parameters of strawberry plants appeared to be enhanced by Chlorella application over time, an enhancement which became greater as the application rate increased. Likewise, the hardness and P content of strawberry fruits had a similar trend. Meanwhile, 0.2% OCD treatment induced the highest values of soluble solid content (9.3-12 °Brix) and sucrose content (2.06-2.97 g 100 g-1) in the fruits as well as fruit flavor quality indices (e.g., sugars:acids ratio and sweetness index) during the monitoring, whilst control treatment represented the lowest values. In addition, the highest anthocyanin content in fruits was observed in 0.4% OCD treatment, which induced the lowest incidence of grey mold disease (Botrytis cinerea) on postharvest fruits for 45 days. Moreover, a high correlation between plants' nutrients and photosynthetic variables and fruits' sucrose and anthocyanin contents was identified through the results of principal component analysis. Overall, C. fusca CHK0059 application was found to promote the overall growth and performance of strawberry plants, contributing to the improvement of strawberry quality and yield, especially in 0.2% OCD treatment.
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In this study, we propose an optimized AlGaN/GaN high-electron-mobility transistor (HEMT) with a considerably improved breakdown voltage. First, we matched the simulated data obtained from a basic T-gate HEMT with the measured data obtained from the fabricated device to ensure the reliability of the simulation. Thereafter, to improve the breakdown voltage, we suggested applying a gate-head extended structure. The gate-head-top and gate-head-bottom lengths of the basic T-gate HEMT were symmetrically extended by 0.2 µm steps up to 1.0 µm. The breakdown voltage of the 1.0 µm extended structure was 52% higher than that of the basic T-gate HEMT. However, the cutoff frequency (fT) and maximum frequency (fmax) degraded. To minimize the degradation of fT and fmax, we additionally introduced a gate-recessed structure to the 1.0 µm gate-head extended HEMT. The thickness of the 25 nm AlGaN barrier layer was thinned down to 13 nm in 3 nm steps, and the highest fT and fmax were obtained at a 6 nm recessed structure. The fT and fmax of the gate-recessed structure improved by 9% and 28%, respectively, with respect to those of the non-gate-recessed structure, and further improvement of the breakdown voltage by 35% was observed. Consequently, considering the trade-off relationship between the DC and RF characteristics, the 1.0 µm gate-head extended HEMT with the 6 nm gate-recessed structure was found to be the optimized AlGaN/GaN HEMT for high-power operations.
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Recently, there has been a growing interest in the controlled alignment and robust bonding process of nanowires (NWs) on nanoelectronic devices. In this paper, we developed an innovative process for the fabrication of NW-based devices by room-temperature and low-pressure compressive transfer printing of NWs, in which NWs could be simultaneously aligned and bonded onto the metal electrodes. In this process, chemically synthesized NWs were first transferred and aligned on an intermediate substrate by contact printing and then finally printed onto a target substrate with mechanically soft Au electrodes, which enables the embedding of aligned NWs under low-pressure (5 bar) and room-temperature condition. The resulting contact between NW and Au electrodes exhibits Schottky behavior and high mechanical bonding strength (>567 MPa). The electrical characteristics could be converted from Schottky to Ohmic contact through thermal annealing treatment at 250 °C for 5 min due to Cr diffusion and direct Cr-ZnO contact formation. The applications of the fabricated devices as ultraviolet (UV) and gas sensors were successfully demonstrated. Furthermore, NW-based electronic devices were fabricated on a flexible substrate by using this process and showed mechanical and electrical robustness under mechanical bending conditions.
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The ubiquitin-proteasome system (UPS) is a ubiquitous, major pathway of protein degradation that is involved in most cellular processes by regulating the abundance of certain proteins. Accumulating evidence indicates a role for the UPS in specific functions of neurons. In this chapter, we first introduce the role of the UPS in neuronal function and the mechanism of UPS regulation following synaptic activity. Then, we focus on the recently revealed, distinct role of the UPS in the destabilization of a reactivated memory. Finally, we discuss the physiological role of this destabilization process. The reactivated memory may undergo modification from the initial memory depending on the context in which the memory is reactivated, which we will term memory reorganization. We will introduce the role of the protein degradation-dependent destabilization process for memory reorganization and suggest a hypothetical model combining the recent findings.
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Memoria a Largo Plazo/fisiología , Proteínas del Tejido Nervioso/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Sinapsis/metabolismo , Transmisión Sináptica/fisiología , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Humanos , Modelos Neurológicos , Plasticidad Neuronal/fisiología , Neuronas/metabolismo , Complejo de la Endopetidasa Proteasomal/genética , Proteolisis , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
COVID-19 has caused tremendous damage to global economies, and similar health crises are expected to happen again. This study tests whether slack resources would enable companies to prepare for such uncertainties. Specifically, we explored the influence of the COVID-19 patient occurrence on corporate financial performance and the buffering effect of financial slacks using Chinese listed companies' data during 2021. We also examined whether this effect differs across firms' financial health and industry. Test results are as follows. First, consistent with the recent studies on pandemics, the degree of COVID-19 prevalence had a negative impact on the Chinese company's financial performance, and slack resources offset this adverse effect. Second, slack's buffering effects appeared mostly in financially constrained companies. Third, such effects mostly appeared in industries vulnerable to the COVID-19 shock. In the business environment of 2021, adapted to COVID-19, our main test result seems to mainly come from companies with a greater need for slack. Our tests imply that, despite differences in the degree of accessibility to resources, excess resources help companies overcome the COVID-19 crisis, which means that firms can more efficiently respond to economic shocks such as COVID-19 if they reserve past profits as free resources. This study contributes to the literature in that there is limited research on the slack resources' buffering effect on the COVID-19 shock and that this study works as a robustness test as it uses data from one of the East Asian regions at a time when the control of COVID-19 was relatively consistent and successful, which can limit the effect of COVID-19 and slacks.
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COVID-19 , Humanos , COVID-19/epidemiología , Pandemias , Organizaciones , Industrias , China/epidemiologíaRESUMEN
Experimental and numerical analysis of the drop-on-demand inkjet was conducted to determine the jetting characteristics and meniscus motion under the control of the ink supply pressure. A single transparent nozzle inkjet head driven by a piezoelectric actuator was used to eject droplets. To control ink supply pressure, the pressure of the air in the reservoir was regulated by a dual valve pressure controller. The inkjet performance and the motion of the meniscus were evaluated by visualization and numerical simulation. A two-dimensional axisymmetric numerical simulation with the dynamic mesh method was performed to simulate the inkjet dynamics, including the actual deformation of the piezoelectric actuator. Numerical simulation showed good agreement with the experimental results of droplet velocity and volume with an accuracy of 87.1%. Both the experimental and simulation results showed that the drop volume and velocity were linearly proportional to the voltage change. For the specific voltages, an analysis of the effect of the ink supply pressure control was conducted. At the maximum negative pressure, -3 kPa, the average velocity reductions were 0.558 and 0.392 m/s in the experiment and simulation, respectively, which were 18.7 and 11.6% less than those of the uncontrolled case of 0 kPa. Therefore, the simulation environment capable of simulating the entire inkjet dynamics, including meniscus movement regarded to be successfully established. The average volume reductions were 18.7 and 6.97 pL for the experiment and simulation, respectively, which were 21.7 and 9.17% less than those of the uncontrolled case. In the results of the meniscus motion simulation, the damping of the residual vibration agreed well with the experimental results according to the ink supply pressure change. Reducing the ink supply pressure reduced the speed and volume, improved the damping of residual vibrations, and suppressed satellite drops. Decreasing ink supply pressure can be expected to improve the stability and productivity of inkjet printing.
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To compare the risk of developing gastrointestinal (GI) cancer according to industrial groups, we performed a retrospective cohort study using the database of the Korea National Health Insurance Service (NHIS). We calculated the age-standardized incidence ratios (SIRs) and 95% confidence intervals (95% CIs) for the types of GI cancers according to the Korean Standard Industrial Classification (KSIC) compared with the whole employee population. The highest SIR for all GI cancer was found in the "Mining and quarrying" section (SIR, 1.30; 95% CI, 1.14-1.47), followed by the "Transportation and storage" section (SIR, 1.27; 95% CI, 1.24-1.30). Miners and quarriers had the highest risk of developing gastric cancer (SIR, 1.29; 95% CI, 1.06-1.55) and cancer of the liver and intrahepatic bile ducts (SIR, 1.48; 95% CI, 1.17-1.86). Transportation workers had the highest SIR of cancer of the lip, oral cavity, and pharynx (SIR, 1.27; 95% CI, 1.13-1.43) and cancers of the rectum, anus, and anal canal (SIR, 1.27; 95% CI, 1.19-1.35). There were distinct GI cancers with an elevated risk in each industry group. Our findings imply that distinct cancer prevention programs should be developed for each industrial sector.
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This study investigates the operational characteristics of AlGaN/GaN high-electron-mobility transistors (HEMTs) by applying a slant-gate structure and drain-side extended field-plate (FP) for improved breakdown voltage. Prior to the analysis of slant-gate-based HEMT, simulation parameters were extracted from the measured data of fabricated basic T-gate HEMTs to secure the reliability of the results. We suggest three different types of slant-gate structures that connect the basic T-gate electrode boundary to the 1st and 2nd SiN passivation layers obliquely. To consider both the breakdown voltage and frequency characteristics, the DC and RF characteristics of various slant-gate structures including the self-heating effect were analyzed by TCAD simulation. We then applied a drain-side extended FP to further increase the breakdown voltage. The maximum breakdown voltage was achieved at the FP length of 0.4 µm. Finally, we conclude that the slant-gate structures can improve breakdown voltage by up to 66% without compromising the frequency characteristics of the HEMT. When the drain-side FP is applied to a slant-gate structure, the breakdown voltage is further improved by up to 108%, but the frequency characteristics deteriorate. Therefore, AlGaN/GaN HEMTs with an optimized slant-gate-based structure can ultimately be a promising candidate for high-power and high-frequency applications.
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Green and renewable energy is the key to overcoming energy-related challenges such as fossil-fuel depletion and the worsening of environmental habituation. Among the different clean energy sources, hydrogen is considered the most impactful energy carrier and is touted as an alternate fuel for clean energy needs. Even though noble metal catalysts such as Pt, Pd, and Au exhibit excellent hydrogen evolution reaction (HER) activity in acid media, their earth abundance and capital costs are highly debatable. Hence, developing cost-effective, earth-abundant, and conductive electrocatalysts is crucial. In particular, various two-dimensional (2D) transition metal carbides and their compounds are gradually emerging as potential alternatives to noble metal-based catalysts. Owing to their improved hydrophilicity, good conductivity, and large surface areas, these 2D materials show superior stability and excellent catalytic performances during the HER process. This review article is a compilation of the different synthetic protocols, their impact, effects of doping on molybdenum and tungsten carbides and their derivatives, and their application in the HER process. The paper is more focused on the detailed strategies for improving the HER activity, highlights the limits of molybdenum and tungsten carbide-based electrocatalysts in electro-catalytic process, and elaborates on the future advancements expected in this field.
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The number of cases and incidence rates of laryngeal and lung cancers have been increasing globally. Therefore, identifying the occupational causes of such cancers is an important concern for policymakers to prevent cancers and deaths. We used national health insurance service claims data in Korea. We included 10,786,000 workers aged between 25 and 64 years. In total, 74,366,928 total person-years of follow-up were included in this study with a mean follow-up of 6.89 years for each person. The standardized incidence ratio (SIR) and 95% confidence intervals (CIs) referenced with the total workers were estimated. For laryngeal cancer, increased SIRs were observed in the land transportation industry among male workers (SIR [95% CI]: 1.65 [1.02-2.53]). For lung cancer, elevated SIRs were observed in the industries including animal production (1.72 [1.03-2.68]), fishing (1.70 [1.05-2.60]), mining (1.69 [1.22-2.27]), travel (1.41 [1.00-1.93]), and transportation (1.22 [1.15-1.30]) among male workers. For female works, healthcare (2.08 [1.04-3.72]) and wholesale (1.88 [1.18-2.85]) industries were associated with a high risk of lung cancer. As an increased risk of respiratory tract cancers has been identified in employees associated with certain industries, appropriate policy intervention is needed to prevent occupational cancers.
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A single protein can be multifaceted depending on the cellular contexts and interacting molecules. LIN28A is an RNA-binding protein that governs developmental timing, cellular proliferation, differentiation, stem cell pluripotency, and metabolism. In addition to its best-known roles in microRNA biogenesis, diverse molecular roles have been recognized. In the nervous system, LIN28A is known to play critical roles in proliferation and differentiation of neural progenitor cells (NPCs). We profiled the endogenous LIN28A-interacting proteins in NPCs differentiated from human induced pluripotent stem (iPS) cells using immunoprecipitation and liquid chromatography-tandem mass spectrometry. We identified over 500 LIN28A-interacting proteins, including 156 RNA-independent interactors. Functions of these proteins span a wide range of gene regulatory processes. Prompted by the interactome data, we revealed that LIN28A may impact the subcellular distribution of its interactors and stress granule formation upon oxidative stress. Overall, our analysis opens multiple avenues for elaborating molecular roles and characteristics of LIN28A.
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The basal ganglia regulate a wide range of behaviors, including motor control and cognitive functions, and are profoundly affected in Parkinson's disease (PD). However, the functional organization of different basal ganglia nuclei has not been fully elucidated at the circuit level. In this study, we investigated the functional roles of distinct parvalbumin-expressing neuronal populations in the external globus pallidus (GPe-PV) and their contributions to different PD-related behaviors. We demonstrate that substantia nigra pars reticulata (SNr)-projecting GPe-PV neurons and parafascicular thalamus (PF)-projecting GPe-PV neurons are associated with locomotion and reversal learning, respectively. In a mouse model of PD, we found that selective manipulation of the SNr-projecting GPe-PV neurons alleviated locomotor deficit, whereas manipulation of the PF-projecting GPe-PV neurons rescued the impaired reversal learning. Our findings establish the behavioral importance of two distinct GPe-PV neuronal populations and, thereby, provide a new framework for understanding the circuit basis of different behavioral deficits in the Parkinsonian state.