Important Hub Research Articles

The interplay between membrane viscosity and ligand-binding receptor kinetics in lipid bilayers

Plasma membranes appear as deformable systems wherein molecules are free to move and diffuse giving rise to condensed microdomains (composed of ordered lipids, transmembrane proteins and cholesterol) surrounded by disordered lipid molecules. Such denser and thicker regions, namely lipid rafts, are important communication hubs for cells. Indeed, recent experiments revealed how the most of active signaling proteins co-localize on such domains, thereby intensifying the biochemical trafficking of substances. From a material standpoint, it is reasonable to assume the bilayer as a visco-elastic body accounting for both in-plane fluidity and elasticity. Consequently, lipid rafts contribute to membrane heterogeneity by typically exhibiting higher stiffness and viscosity and by locally altering the bilayer dynamics and proteins activity. A chemo-mechanical model of lipid bilayer coupled with interspecific dynamics among the resident species (typically transmembrane receptors and trasporters) has been recently formulated to explain and predict how proteins regulate the dynamic heterogeneity of membrane. However, the explicit inclusion of the membrane viscosity in the model was not considered. To this aim, the present work enriches the constitutive description of the bilayer by modeling its visco-elastic behavior. This is done through a strain-level dependent viscosity able to theoretically trace back the alteration of membrane fluidity experimentally observed in lipid phase transitions. This provides new insights into how the quasi-solid and fluid components of lipid membrane response interact with the evolution of resident proteins by affecting the activity of raft domains, with effects on cell mechano-signaling.

Study on the Synergistic Development of "Smart + Green" Logistics Industry in Chongqing

Under the background of "digital economy" and "double carbon", logistics industry, as a typical industry with high input, high energy consumption and high emission, is imperative for its intelligent and green transformation. Chongqing, located in the southwest, is an important logistics hub, and the synergistic development of its logistics industry "smart + green" is of great significance to the economic growth and high-quality development of the industry. This paper constructs the index system for the synergistic development of smart logistics and green logistics, and analyzes the development level of smart logistics and green logistics as well as the level of coupling coordination in Chongqing from 2010 to 2022 by using entropy value method and coupling coordination degree model, with the aim of providing a reference for the government to improve the logistics policy as well as the active development of the logistics industry. The study shows that the overall development level of smart logistics and green logistics in Chongqing is on the rise, and the gap between the two is gradually narrowing, and the development level is gradually changing from green logistics development to synergistic development. The development trend of the coupling coordination degree of smart logistics and green logistics is good, and the coupling coordination degree gradually develops into high-quality coordination, and the trend of the coupling coordination degree is consistent with the trend of the development level of smart logistics, and smart logistics has a stronger role in promoting the synergistic development of the two. Among the subsystems, the scale of development, transportation capacity and digitization level in smart logistics and the level of resource utilization and energy use efficiency in green logistics are the short boards restricting the coordinated development of smart and green logistics, and the coordinating role between the subsystems needs to be strengthened.

ANTHROPOLOGICAL STUDY OF THE POPULATION OF SMOLENSK IN THE 16TH-17TH CENTURIES BASED ON THE MATERIALS FROM THE EXCAVATIONS AT PYATNITSKY DISTRICT

Introduction. The article analyzes materials dated to the 16th-17th centuries came from Smolensk. This period turned out to be one of the most complex and eventful in the history of the region, that's why every new detail is significant for the study. For a long time, Smolensk functioned as a boundary city and also as an important trade hub between the Muscovite Tsardom and the Polish-Lithuanian Commonwealth; so, the composition of its population may reflect the influence of the western neighbors. Materials and methods. There were examined the craniological materials discovered during the excavations at the Pyatnitsky district of the city in 2012. The necropolis dates back to the turn of the 16th-17th centuries, it is located on the high bank of the Dnieper near the fortress wall of the Smolensk Kremlin. The materials include 17 male and 19 female skulls. Classical and multidimensional biometric methods were used as statistical approaches. Results. The comparison beetween the studied sample and the other sample of the 12th century city population known from the literature has showed their high similarity, although the later sample tends to be slenderer. Statistically significant differences were recorded only for certain parameters of the skull. The comparison with the aggregated sample of the rural Smolensk region population dated to the 18th-19th centuries also revealed a significant difference for the cranial length and height and some parameters of the facial skeleton. Discriminant analysis showed a quite unique status of the studied sample, which differs from both synchronous urban groups and later samples of the rural population of the central region. There are also no processes of macrosomization observed for it. Conclusion. The absence of significant differences for most characteristics between the studied sample and the urban population of the 12th century can indicate the continuity of the morphological type of the Smolensk urban population. On the other hand, the intermediate position of the studied sample in relation to early and late comparative materials can indicate that the studied sample represents recent settlers from the rural area.

The emperor's new glass: The introduction of Carolingian wood ash glass in North Sea trade

AbstractMicro‐X‐ray fluorescence (XRF) screening of 244 glass sherds from Ribe, Denmark, identified 23 wood ash glasses. The closely dated finds pinpoint the arrival of the earliest wood ash glass produced in Western Europe in this important North Sea trading hub. This glass type was absent among glass from 700 to 790 CE but feature strongly from 790 to 810 CE. Electron microprobe analysis (EMPA) and laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) analysis of 24 glasses show the presence of four types. We show the strengths of classifying wood ash glass based on the glass‐producing sands and conclude that the earliest production took place on a considerable scale and had a major impact on glass circulation in Northern Europe in the ninth century.

Exploring older adults' motivation to use public libraries in South Korea using the attention, relevance, confidence, and satisfaction (ARCS) motivation model

Public libraries serve as important hubs for lifelong learning for older adults. Nevertheless, if library visits are perceived as discouraging and frustrating, they can be burdensome for this demographic. The perceptions of motivations influencing public library use among older adults was explored through 37 semi-structured interviews. Employing the ARCS (Attention, Relevance, Confidence, and Satisfaction) motivation model, a qualitative approach was adopted. The analysis aims to shed light on the motivations and perceptions of elderly library users. The significance lies in being the pioneer in applying the ARCS motivation model to library use among older adults within the framework of public libraries, highlighting profound implications for library services catering to this demographic. The findings will contribute to new methodologies in library user research, increase knowledge and interest in public library use among older adults, and provide concrete suggestions for library administrators and policymakers.

Evolution of New Energy Minerals Trade Pattern and Analysis of China’s Status Evolution

Copper, cobalt, nickel as the key raw materials for the new energy automobile industry, the supply and demand of resources and international trade are largely affected by the world economy and political pattern, and the risks and vulnerabilities of the resource industry chain are highlighted. Using the method of complex network to analyze the trade network of three kinds of mineral resources from the perspective of industrial chain, the following conclusions are drawn: (1) the global trade network of three kinds of new energy minerals in the whole industrial chain all presents the characteristics of complexity and connection enhancement, and has the characteristics of the network of the small world; (2) China has become an important hub in the global trade network of copper, cobalt, and nickel, and has a stronger ability to control the trade of other countries.

Passenger spatiotemporal distribution prediction in airport terminals based on physics-guided spatio-temporal graph convolutional network and its effect on indoor environment prediction

The airport as an important transportation hub plays a leading role in promoting sustainable cities and new-type urbanization. To boost safe, environmental-friendly and technologically advanced airports, the passenger travel behavior as a core that decides the resource allocation, system tuning and capacity dispatching, must be grasped. Previous research in passenger distribution prediction focused on physics-based methods or only mining temporal dynamics. In this work, a refined passenger distribution prediction was modeled based on a learning-based method embedding physical prior knowledge, and then its effects on indoor environment prediction were analyzed. Among them, based on insect intelligent building architecture, a virtual spatial graph was defined in Guangzhou Baiyun International Airport Terminal 2, then a Wi-Fi positioning system was constructed; Next, a physics-guided spatio-temporal graph convolutional network, considering both the spatial dependencies and the passenger arrival pattern extracted from cost-free flight schedules, was developed for domestic and international passenger distribution predictions with R2 over 0.87 and 0.76 respectively; Lastly, the contributions of predicted occupant densities to the indoor environment prediction were evaluated with results showing that the average R2 for indoor temperature, relative humidity and CO2 concentration prediction was enhanced by 0.4 %∼91.5 %, 0.2 %∼29.7 % and 0.4 %∼45.4 % respectively as the prediction horizon broadening.

Schlafen14 Impairs HIV-1 Expression in a Codon Usage-Dependent Manner.

Schlafen (SLFN) is a family of proteins upregulated by type I interferons with a regulatory role in translation. Intriguingly, SLFN14 associates with the ribosome and can degrade rRNA, tRNA, and mRNA in vitro, but a role in translation is still unknown. Ribosomes are important regulatory hubs during translation elongation of mRNAs rich in rare codons. Therefore, we evaluated the potential role of SLFN14 in the expression of mRNAs enriched in rare codons, using HIV-1 genes as a model. We found that, in a variety of cell types, including primary immune cells, SLFN14 regulates the expression of HIV-1 and non-viral genes based on their codon adaptation index, a measurement of the synonymous codon usage bias; consequently, SLFN14 inhibits the replication of HIV-1. The potent inhibitory effect of SLFN14 on the expression of the rare codon-rich transcript HIV-1 Gag was minimized by codon optimization. Mechanistically, we found that the endoribonuclease activity of SLFN14 is required, and that ribosomal RNA degradation is involved. Therefore, we propose that SLFN14 impairs the expression of HIV-1 transcripts rich in rare codons, in a catalytic-dependent manner.

Environmental Sanitation in Porto Alegre City, Brazil: A Basic Step towards Sustainable Development

Porto Alegre city, the capital of Rio Grande do Sul State, is an important medical, educational, and technological hub in Brazil. However, Porto Alegre faces critical challenges in achieving adequate environmental sanitation, hampering the development of the city, and negatively impacting the most socially vulnerable segments of the population. Although Porto Alegre’s sanitation plan aims at universal access to sewage collection and treatment services by 2035, some of the city’s sanitation indicators have deteriorated in recent years compared to other Brazilian cities. The inadequate or lack of proper sanitation (e.g., shortcomings in sewage collection and treatment, suboptimal management of solid waste, deficiencies in the distribution of treated water) contribute to the proliferation of disease vectors like mosquitoes and to the spread of infectious and parasitic diseases (e.g., toxoplasmosis, leishmaniasis, arboviral diseases). Recently, Porto Alegre’s population experienced a significant number of dengue infection cases. Climate change, social issues, and unplanned urbanization will further favor disease transmission in the region. In this Review, we provide an overview concerning the ecological, socio-economic, and public health aspects of Porto Alegre, drawing attention to the insufficient environmental sanitation in the city, a neglected problem by local authorities. We argue that this issue needs to be seriously addressed if Porto Alegre wants to realistically achieve sustainable development, protecting ecosystems and human health.

Abstract 6069: Discovery and preclinical development of orally bioavailable potent BTK degrader, and its early clinical development for the treatment of relapsed and refractory B-cell malignancies

Abstract Background : Bruton tyrosine kinase (BTK) is an important signaling hub that activates the B-cell receptor (BCR) signaling cascade, which is critical for growth and survival of B-cell lymphoma or leukemia. BTK inhibitors have shown anti-tumor activity in patients with B-NHL. However, nearly half of the patients on current BTK inhibitors discontinue the treatment due to adverse effects and/or mutation-induced drug resistance. A degrader is a heterobifunctional chemical compound aimed at eliminating disease-causing proteins, rather than simply inhibiting proteins’ enzymatic function, through the ubiquitin-proteasome system (UPS)-mediated protein degradation. This approach offers a unique solution for addressing relapse or refractory disease by removing overexpressed and mutated proteins, unlike traditional inhibitors. We thus designed UBX-382, a degrader targeting BTK. Results : UBX-382 showed superior degradation activity for both wild-type (WT) and mutant BTK proteins in a single-digit nanomolar range of half-maximal degradation concentration when compared to the competing degrader programs in diffuse large B-cell lymphoma cell line. UBX-382 effectively addressed 7 out of 8 previously reported resistant BTK mutants in in vitro experiments and outperformed ibrutinib, ARQ-531, and MT-802 in inhibiting tumor growth in murine xenograft models harboring WT or C481S mutant BTK-expressing TMD-8 cells. Remarkably, oral dosing of UBX-382 for <2 weeks led to complete tumor regression in 3 and 10 mg/kg groups in murine xenograft models. Following this, further optimization was carried out for potency and PK profile. We nominated the candidate for IND filing and are planning a phase 1 clinical trial. For the first-in-human, open-label, multicenter, phase 1 study, patients in part 1 (dose escalation with BOIN design) had R/R B-cell malignancies and had received at least 2 prior therapies. The candidate will be administered orally at 5 mg once daily followed by 2 days, for a 7-day schedule over 28-day cycles. Part 2 (dose expansion) consisted of disease-specific cohorts, including CLL/SLL, DLBCL, MCL, FL, MZL, and WM. The primary endpoints were safety and tolerability, along with the definition of the maximum tolerated dose. Secondary endpoints included pharmacokinetics/pharmacodynamics and preliminary efficacy. Conclusions : We have discovered potent BTK degrader exhibiting excellent anti-tumor activity in vitro and in vivo. In pre-clinical safety studies, the candidate of UBX demonstrated an acceptable safety profile. The candidate of UBX is currently preparing phase 1 clinical trials for hematological malignancies. Citation Format: Song Hee Lee, Sun-Mi Yoo, Ye Seul Lim, Han Wool Kim, Je Ho Ryu, Jong Hwan Lim. Discovery and preclinical development of orally bioavailable potent BTK degrader, and its early clinical development for the treatment of relapsed and refractory B-cell malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6069.

Research on the Evaluation of Comprehensive Logistics Capacity of Major Ports in Chengdu-Chongqing Economic Circle

Under the new development pattern with domestic circulation as the main body and domestic and international dual circulation promoting each other, it has become the general trend to promote the construction of the Chengdu-Chongqing Twin Cities Economic Circle and deeply integrate into the development of the Yangtze River Economic Belt. Located in the upper reaches of the Yangtze River, the Chengdu-Chongqing Economic Circle is an important hub connecting the east and west, and its port has become an important strategic resource for the economic development of the hinterland. Although the port has developed rapidly in recent years, there are still many shortcomings in the face of new situations and new requirements. By establishing an evaluation index system and using the entropy weight-TOPSIS method to evaluate the comprehensive logistics capacity of the main ports in the Chengdu-Chongqing Economic Circle, this paper finds that each port has problems such as unbalanced development and the level of collection and distribution to be improved, and gives corresponding countermeasures to provide reference for the future development and construction of inland ports.

International connection, local disconnection: The (heterogeneous) role of global cities in local and global innovation networks

Global cities function as important international innovation hubs and are key nodes in international business networks. Yet this focus on international knowledge networks may render it less likely that global cities establish and maintain intensive local innovation linkages with their surrounding areas. We argue that while the relationship between the global network orientation of global cities and their local linkages with their surrounding areas is negative, the strength of this relationship depends global city and surrounding regions' knowledge base and the ease of local linkage formation. Global linkages are expected to be more detrimental to the establishment of local linkages if the global city is a global technology leader, but less so if the surrounding region has a greater innovation strength and is more proximate to the global city. We find partial support for these hypotheses in an analysis of the collaborative innovation linkages of 21 U.S. global cities with 310 surrounding counties, 2001–2015.

Spatiotemporal Patterns and Risk Factors for Newcastle Disease Virus among Chickens in a Tanzania Live Bird Market

Village poultry plays a vital role in providing essential nutrition and income for rural communities in Africa. In this context, poultry are often traded through live bird markets (LBMs), which serve as central trading hubs where producers connect with traders and consumers, facilitating the flow of poultry products along the value chain. While they serve as important trading hubs, these markets create an environment where avian pathogens, like Newcastle disease virus (NDV) and avian influenza virus, can easily emerge and spread. Improving our understanding of the epidemiology of NDV in LBMs is important for assessing disease risks and identifying factors that contribute to its persistence. Local chickens at the Mawenzi LBM in Morogoro municipality were surveyed for NDV presence, its temporal and spatial distribution, and risk factors for NDV infection. Twenty-three percent of 659 local chickens sampled over a 1-year period were positive for NDV based on PCR. Increased odds of NDV infection were identified in chickens that had been in the market for 2 or more days prior to sampling and during the period extending from August through October. Four significant spatiotemporal clusters of NDV-positive chickens encompassing 13 villages were detected between August and October 2020, illustrating geographic hotspots of infection when NDV was most prevalent. Similar to the other LBMs, this market had enclosures with high densities of birds of mixed species, limited biosecurity, and the presence of birds with observable illness. Bird traders who source the chickens from the villages, described long transit times in mixed enclosures with limited sanitation practices and without consideration of sick birds or vaccination status prior to arriving at the LBM. This study highlights the need to invest in improvements to infrastructure and biosecurity for LBMs as well as training opportunities for increasing traders’ knowledge on hygiene and sanitation practices, animal welfare, and poultry biosecurity measures.

Conceptualizing Malaysian creative hubs: traversing normalcy to pandemicity and beyond

ABSTRACT Creative hubs have garnered considerable attention as a viable place for creatives to cluster, network and bounce ideas for new cultural, creative and technological innovations. Despite this overtly recognized functionality, creative hubs are granularly variegated. There is a call to investigate its covert interior and not just its overt exterior. This paper attempts to unravel and make discernible the types of creative hubs in Malaysia, where the concept is still nascent. Fathoming this concept amid the Covid-19 pandemic is timely given the way digitalization has radically realtered the form and functionalities of Malaysian creative hubs. Based on semi-structured interviews with 6 hub managers and 95 brief interviews with hub members, this paper highlights the way Malaysian creative hubs negotiate their shifting meanings during normalcy, and further morphs amid pandemicity and beyond. The findings highlight that physical hubs are still important and community-driven organic hubs are resilient towards sustainable urban development.

A Review of Power Transformer Vibration and Noise Caused by Silicon Steel Magnetostriction

As an important hub equipment in the power system, the power transformer has increasingly higher requirements for its reliability and safety with the rapid development of the power industry. However, the vibrations and noise generated during its operation not only cause a series of issues such as loose windings, core wear, and fatigue of fasteners, but also lead to anxiety and unease among nearby residents, severely affecting their physical and mental health. Therefore, the generation mechanism and control measures of vibration and noise in power transformers have attracted extensive attention from scholars. The magnetostrictive effect of silicon steel sheets is one of the important factors in the causes of transformer vibration and noise. This paper focuses on the magnetostrictive effect of silicon steel sheets. Firstly, the micro mechanism of magnetostriction is introduced. Secondly, based on current research status, the vibration and noise mechanism caused by magnetostriction are summarized, and the influencing factors, measurement, modeling, and noise reduction methods based on magnetostriction are summarized. Finally, based on the current research status and future development trends, prospects are proposed, aiming to provide references for subsequent research on transformer vibration and noise.

The Influence of Socio-Economic Facilities and Population Density on Landuse Changes in Gunungpati District, Semarang City

Land use still serves as a guide for urban development decisions, even though they are typically independent. Establishing important corporate hubs has made economic considerations a key driver in determining how the city’s land-use structure will be governed. The study investigates the influence of socio-economic facilities and population density on land use changes in Gunungpati district, Semarang City. The data processing technique used in this study was to make a map of the administrative area of Gunungpati District. The following data processing stage digitizes Gunungpati District images in 2011 and 2019 to determine land use. Then carry out the overlay process on the two land use maps of the Gunungpati District to find out changes in land use in 2011 and 2019. Qualitative data analysis was used in this study. The findings of land change map overlays between 2011 and 2019 were used for qualitative data map analysis. The findings demonstrate that settlements, which account for 2,255 hectares of land in Gunung Pati District, dominate land use, with Pakintelan Village having the highest residential land use. At the same time, the most minor land use is in the service sector, namely as much as 590 Ha. Land use in Gunungpati District in 2019 was dominated by residential land, namely 2,388 Ha, where the highest residential land use was in Sekaran Village, namely 250.76 Ha. The slightest use of land is on service land, which is 442.51 Ha, with the highest use of service land in Sekaran Village, which is 58.24 Ha. The dominant factors influencing changes in land use are the increase in social facilities and population density, which encourage land conversion and make it a more productive resource.

Integrated Bioinformatics Exploration and Preliminary Clinical Verification for the Identification of Crucial Biomarkers in Severe Cases of COVID-19.

Coronavirus disease 2019 (COVID-19) is a respiratory infectious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of this study is to identify reliable and accurate biomarkers for the early stratification of disease severity, a crucial aspect that is currently lacking for the impending phases of the next COVID-19 pandemic. In this study, we identified important module and hub genes related to clinical severe COVID-19 using differentially expressed genes (DEGs) screening combing weighted gene co-expression network analysis (WGCNA) in dataset GSE213313. We further screened and confirmed these hub genes in another two new independent datasets (GSE172114 and GSE157103). In order to evaluate these key genes' stability and robustness for diagnosing or predicting the progression of illness, we used RT-PCR validation of selected genes in blood samples obtained from hospitalized COVID-19 patients. A total of 968 and 52 DEGs were identified between COVID-19 patients and normal people, critical and non-critical patients, respectively. Then, using WGCNA, 10 modules were constructed. Among them, the blue module positively associated with clinic disease severity of COVID-19. From overlapped section between DEGs and blue module, 12 intersected common differential genes were obtained. Subsequently, these hub genes were validated in another two new independent datasets as well and 9 genes that overlapped showed a highly correlation with disease severity. Finally, the mRNA expression levels of these hub genes were tested in blood samples from COVID-19 patients. In severe cases, there was increased expression of MCEMP1, ANXA3, CD177, and SCN9A. In particular, MCEMP1 increased with disease severity, which suggested an unfavorable development and a frustrating prognosis. Using comprehensive bioinformatical analysis and the validation of clinical samples, we identified four major candidate genes, MCEMP1, ANXA3, CD177, and SCN9A, which are essential for diagnosis or development of COVID-19.

Evaluation of Low-Carbon Economic Efficiency under Industrial Clustering and Study of Regional Differences, Taking Xinjiang as an Example

As a major resource region, Xinjiang is both China’s energy security base and an important hub connecting Asia and Europe. Following the country’s call for carbon emission reduction, the Xinjiang government proposes to accelerate the construction of eight major industrial clusters in 2023. The concept of sustainable development is also reflected in the industrial clusters in areas such as new energy. In this study, we combined panel data from 14 regions and cities in Xinjiang from 2006 to 2020 and analyzed the synergy between the development of industrial clusters, carbon emissions, and economic growth using a coupling coordination degree model. Subsequently, we used the super-efficiency slack-based measure (SE-SBM) and Dagum’s Gini coefficient to analyze the spatial disequilibrium of efficiency measures and efficiency cases. The results show the following: (1) Overall, the industrial clusters, carbon emissions, and economic growth in the 14 regions and cities of Xinjiang are not well coordinated. The best reported level has been medium coordination, but there exists a certain degree of correlation among the three. (2) Low-carbon economic efficiency under the influence of industrial clusters in the 14 regions and cities shows significant regional differences. The regions and cities with low-carbon economic efficiency greater than 0.8, which is significantly better than the other regions in terms of efficiency, are all located in northern Xinjiang. (3) During the study period, the overall regional difference in low-carbon economic efficiency under industrial clusters in Xinjiang decreased from 0.183 to 0.17. However, the regional differences were still large. The conclusions indicate that policies for industrial clusters in Xinjiang can promote industrial development, and there may be a correlation between them and the low-carbon economy. This will effectively contribute to local sustainable development. However, overall regional differences are significant, and the degree of coordination is low. Therefore, we suggest that the government can share the advantages of development by constructing cross-regional cooperation platforms. At the same time, the Xinjiang government should make full use of the rich local wind and solar energy resources and explore a low-carbon path toward transforming the traditional energy industry. It can also be seen that industrial clusters in Xinjiang can effectively promote local sustainable development.

Conserved allosteric perturbation of the GTPase domains by region 1 of Ras hypervariable regions

Ras proteins are important intracellular signaling hubs that can interact with numerous downstream effectors and upstream regulators through their GTPase domains (G-domains) anchored to plasma membranes by the C-terminal hypervariable regions (HVRs). The biological functions of Ras were proposed to be regulated at multiple levels including the intramolecular G-domain-HVR interactions, of which the exact mechanism and specificity are still controversial. Here, we demonstrate that the HVRs, instead of having direct contacts, can weakly perturb the G-domains via an allosteric interaction that is restricted to a ∼20 Å range and highly conserved in the tested Ras isoforms (HRas and KRas4B) and nucleotide-bound states. The origin of this allosteric perturbation has been localized to a short segment (residues 167–171) coinciding with region 1 of HVRs, which exhibits moderate to weak α-helical propensities. A charge-reversal mutation (E168K) of KRas4B in region 1, previously described in the Catalog of Somatic Mutations in Cancer database, was found to induce similar chemical shift perturbations as truncation of the HVR does. Further membrane paramagnetic relaxation enhancement (mPRE) data show that this region 1 mutation alters the membrane orientations of KRas4B and moderately increases the relative population of the signaling-compatible state.

White matter network underlying semantic processing: evidence from stroke patients.

The hub-and-spoke theory of semantic representation fractionates the neural underpinning of semantic knowledge into two essential components: the sensorimotor modality-specific regions and a crucially important semantic hub region. Our previous study in patients with semantic dementia has found that the hub region is located in the left fusiform gyrus. However, because this region is located within the brain damage in patients with semantic dementia, it is not clear whether the semantic deficit is caused by structural damage to the hub region itself or by its disconnection from other brain regions. Stroke patients do not have any damage to the left fusiform gyrus, but exhibit amodal and modality-specific deficits in semantic processing. Therefore, in this study, we validated the semantic hub region from a brain network perspective in 79 stroke patients and explored the white matter connections associated with it. First, we collected data of diffusion-weighted imaging and behavioural performance on general semantic tasks and modality-specific semantic tasks (assessing object knowledge on form, colour, motion, sound, manipulation and function). We then used correlation and regression analyses to examine the association between the nodal degree values of brain regions in the whole-brain structural network and general semantic performance in the stroke patients. The results revealed that the connectivity of the left fusiform gyrus significantly predicted general semantic performance, indicating that this region is the semantic hub. To identify the semantic-relevant connections of the semantic hub, we then correlated the white matter integrity values of each tract connected to the left fusiform gyrus separately with performance on general and modality-specific semantic processing. We found that the hub region accomplished general semantic processing through white matter connections with the left superior temporal pole, middle temporal gyrus, inferior temporal gyrus and hippocampus. The connectivity between the hub region and the left hippocampus, superior temporal pole, middle temporal gyrus, inferior temporal gyrus and parahippocampal gyrus was differentially involved in object form, colour, motion, sound, manipulation and function processing. After statistically removing the effects of potential confounding variables (i.e. whole-brain lesion volume, lesion volume of regions of interest and performance on non-semantic control tasks), the observed effects remained significant. Together, our findings support the role of the left fusiform gyrus as a semantic hub region in stroke patients and reveal its crucial connectivity in the network. This study provides new insights and evidence for the neuroanatomical organization of semantic memory in the human brain.