Photoelectrochemical properties of self-powered corundum-structured Ga2O3nanorod array/fluorine-doped SnO2photodetectors modulated by precursor concentrations.

Herein, corundum-structured Ga2O3(α-Ga2O3) nanorod array/fluorine-doped SnO2(FTO) structures have been fabricated by hydrothermal and thermal annealing processes with different precursor concentrations from 0.01 to 0.06 M. The diameter and length of the nanorod arrays are much larger with increasing precursor concentrations due to more nucleation sites and precursor ions participating in the reaction procedures. The optical bandgap decreases from 4.75 to 4.47 eV because of the tensile stress relieving with increasing the precursor concentrations. Based on self-powered photoelectrochemical (PEC) photodetectors, the peak responsivity is improved from ∼0.33 mA W-1for 0.06 M to ∼1.51 mA W-1for 0.02 M. Schottky junctions can be formed in PEC cells. More photogenerated carriers can be produced in wider depletion region. From Mott-Schottky plots, the depletion regions become much wider with decreasing the precursor concentrations. Therefore, the enhance responsivity is owing to the wider depletion regions. Due to the reduced possibility of photogenerated holes captured by traps ascribed from fewer green and yellow luminescence defects, smaller charge transfer resistance, and shorter transportation route, the decay time becomes much faster through decreasing the precursor concentrations. Compared with the other self-poweredα-Ga2O3-nanorod-array-based PEC photodetectors, it shows the fastest response time (decay time of 0.005 s/0.026 s) simply modulated by precursor concentrations for the first time without employing complex precursors, seed layers or special device designs. Compared with other high-responsivity monoclinic Ga2O3(ß-Ga2O3) self-powered photodetectors, our devices also show comparable response speed with simple control and design. This work provides the realization of fast-speed self-powered Ga2O3based solar-blind ultraviolet photodetectors by simple modulation processes and design, which is a significant guidance for their applications in warnings, imaging, computing, communication and logic circuit, in the future.

Inhibition of phosphoglycerate dehydrogenase induces ferroptosis and overcomes enzalutamide resistance in castration-resistant prostate cancer cells.

Phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in the first step of the serine synthesis pathway (SSP), is overexpressed in multiple types of cancers. The androgen receptor inhibitor enzalutamide (Enza) is the primary therapeutic drug for patients with castration-resistant prostate cancer (CRPC). However, most patients eventually develop resistance to Enza. The association of SSP with Enza resistance remains unclear. In this study, we found that high expression of PHGDH was associated with Enza resistance in CRPC cells. Moreover, increased expression of PHGDH led to ferroptosis resistance by maintaining redox homeostasis in Enza-resistant CRPC cells. Knockdown of PHGDH caused significant GSH reduction, induced lipid peroxides (LipROS) increase and significant cell death, resulting in inhibiting growth of Enza-resistant CRPC cells and sensitizing Enza-resistant CRPC cells to enzalutamide treatment both in vitro and in vivo. We also found that overexpression of PHGDH promoted cell growth and Enza resistance in CRPC cells. Furthermore, pharmacological inhibition of PHGDH by NCT-503 effectively inhibited cell growth, induced ferroptosis, and overcame enzalutamide resistance in Enza-resistant CRPC cells both in vitro and in vivo. Mechanically, NCT-503 triggered ferroptosis by decreasing GSH/GSSG levels and increasing LipROS production as well as suppressing SLC7A11 expression through activation of the p53 signaling pathway. Moreover, stimulating ferroptosis by ferroptosis inducers (FINs) or NCT-503 synergistically sensitized Enza-resistant CRPC cells to enzalutamide. The synergistic effects of NCT-503 and enzalutamide were verified in a xenograft nude mouse model. NCT-503 in combination with enzalutamide effectively restricted the growth of Enza-resistant CRPC xenografts in vivo. Overall, our study highlights the essential roles of increased PHGDH in mediating enzalutamide resistance in CRPC. Therefore, the combination of ferroptosis inducer and targeted inhibition of PHGDH could be a potential therapeutic strategy for overcoming enzalutamide resistance in CRPC.

Exploring a shared genetic signature and immune infiltration between spontaneous intracerebral hemorrhage and Helicobacter pylori infection.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is a devastating form of stroke with high morbidity, disability and mortality. Helicobacter pylori is a major pathogen responsible for chronic gastritis, leading to gastric ulcers and ultimately gastric cancer. Although it remains controversial whether H. pylori infection causes peptic ulcers under various traumatic stimuli, some related studies suggest that H. pylori infection may be an important factor in delaying peptic ulcer healing. However, the linking mechanism between ICH and H. pylori infection remain unclear. The purpose of this study was to examine the genetic features and pathways shared in ICH and H. pylori infection, and compare immune infiltration. METHODS: We used microarray data for ICH and H. pylori infection from the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was performed on both datasets using the R software and the limma package to find the common differentially expressed genes (DEGs). In addition, we performed functional enrichment analysis on DEGs, determined protein-protein interactions (PPIs), identified Hub genes using the STRING database and Cytoscape software, and constructed microRNA-messenger RNA (miRNA-mRNA) interaction networks. Additionally, immune infiltration analysis was performed with the R software and related R packages. RESULTS: A total of 72 DEGs were identified between ICH and H. pylori infection, including 68 upregulated genes and 4 downregulated genes. Functional enrichment analysis revealed that multiple signaling pathways are closely linked to both diseases. In addition, the cytoHubba plugin identified 15 important hub genes, namely PLEK, NCF2, CXCR4, CXCL1, FGR, CXCL12, CXCL2, CD69, NOD2, RGS1, SLA, LCP1, HMOX1, EDN1, and ITGB3.Also, the correlation analysis of immune cell fractions revealed a limited link between their immune-related common genes and immune cells. CONCLUSION: Through bioinformatics methods, this study revealed that there are common pathways and hub genes between ICH and H. pylori infection. Thus, H. pylori infection may have common pathogenic mechanisms with the development of peptic ulcer after ICH. This study provided new ideas for early diagnosis and prevention of ICH and H. pylori infection.

Immobilized lipase for sustainable hydrolysis of acidified oil to produce fatty acid.

Acidified oil is obtained from by-product of crops oil refining industry, which is considered as a low-cost material for fatty acid production. Hydrolysis of acidified oil by lipase catalysis for producing fatty acid is a sustainable and efficient bioprocess that is an alternative of continuous countercurrent hydrolysis. In this study, lipase from Candida rugosa (CRL) was immobilized on magnetic Fe3O4@SiO2 via covalent binding strategy for highly efficient hydrolysis of acidified soybean oil. FTIR, XRD, SEM and VSM were used to characterize the immobilized lipase (Fe3O4@SiO2-CRL). The enzyme properties of the Fe3O4@SiO2-CRL were determined. Fe3O4@SiO2-CRL was used to catalyze the hydrolysis of acidified soybean oil to produce fatty acids. Catalytic reaction conditions were studied, including amount of catalyst, reaction time, and water/oil ratio. The results of optimization indicated that the hydrolysis rate reached 98% under 10 wt.% (oil) of catalyst, 3:1 (v/v) of water/oil ratio, and 313 K after 12 h. After 5 cycles, the hydrolysis activity of Fe3O4@SiO2-CRL remained 55%. Preparation of fatty acids from high-acid-value by-products through biosystem shows great industrial potential.

[Research progress in signaling pathways related to treatment of functional dyspepsia with traditional Chinese medicine].

Functional dyspepsia(FD) is a prevalent functional gastrointestinal disease characterized by recurrent and long-lasting symptoms that significantly impact the quality of life of patients. Currently, western medicine treatment has not made breakthrough progress and mainly relies on symptomatic therapies such as gastrointestinal motility agents, acid suppressants, antidepressants/anxiolytics, and psychotherapy. However, these treatments have limitations in terms of insufficient effectiveness and safety. Traditional Chinese medicine(TCM) possesses unique advantages in the treatment of FD. Through literature search in China and abroad, it has been found that the mechanisms of TCM in treating FD is associated with various signaling pathways, and research on these signaling pathways and molecular mechanisms has gradually become a focus. The main signaling pathways include the SCF/c-Kit signaling pathway, 5-HT signaling pathway, CRF signaling pathway, AMPK signaling pathway, TRPV1 signaling pathway, NF-κB signaling pathway, and RhoA/ROCK2/MYPT1 signaling pathway. This series of signaling pathways can promote gastrointestinal motility, alleviate anxiety, accelerate gastric emptying, reduce visceral hypersensitivity, and improve duodenal micro-inflammation in the treatment of FD. This article reviewed the research on TCM's regulation of relevant signaling pathways in the treatment of FD, offering references and support for further targeted TCM research in the treatment of FD.

CAF-derived exosomes transmitted Gremlin-1 promotes cancer progression and decreases the sensitivity of hepatoma cells to sorafenib.

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide because of metastasis. An increasing number of studies have reported that cancer-associated fibroblasts (CAFs) have emerged as the largest component of the stroma and play a critical role in tumor-promoting processes. However, the effects of CAFs on cancer progression and the sensitivity of hepatoma cells to sorafenib are not well characterized. Here, we identified the proteome of CAF-derived exosomes, and unveiled that exosomal Gremlin-1 derived from CAFs contributes to epithelial-mesenchymal transition (EMT) of hepatoma cells and the decrease of the sorafenib sensitivity through regulating Wnt/ß-catenin and BMP signaling pathways. Compared to control subjects, the level of plasma exosomal Gremlin-1 was significantly increased in HCC patients. Further studies indicated that plasma exosomal Gremlin-1 may predict sorafenib response in HCC patients. Collectively, our findings uncover CAFs-derived Gremlin-1-rich exosomes promote EMT and decrease the sensitivity of hepatoma cells to sorafenib by Wnt/ß-catenin and BMP signaling.

KDM5A silencing transcriptionally suppresses the FXYD3-PI3K/AKT axis to inhibit angiogenesis in hepatocellular cancer via miR-433 up-regulation.

Hepatocellular cancer (HCC) has been reported to belong to one of the highly vascularized solid tumours accompanied with angiogenesis of human umbilical vein endothelial cells (HUVECs). KDM5A, an attractive drug target, plays a critical role in diverse physiological processes. Thus, this study aims to investigate its role in angiogenesis and underlying mechanisms in HCC. ChIP-qPCR was utilized to validate enrichment of H3K4me3 and KDM5A on the promotor region of miR-433, while dual luciferase assay was carried out to confirm the targeting relationship between miR-433 and FXYD3. Scratch assay, transwell assay, Edu assay, pseudo-tube formation assay and mice with xenografted tumours were conducted to investigate the physiological function of KDM5A-miR-433-FXYD3-PI3K-AKT axis in the progression of HCC after loss- and gain-function assays. KDM5A p-p85 and p-AKT were highly expressed but miR-433 was down-regulated in HCC tissues and cell lines. Depletion of KDM5A led to reduced migrative, invasive and proliferative capacities in HCC cells, including growth and a lowered HUVEC angiogenic capacity in vitro. Furthermore, KDM5A suppressed the expression of miR-433 by demethylating H3K4me3 on its promoterregion. miR-433 negatively targeted FXYD3. Depleting miR-433 or re-expressing FXYD3 restores the reduced migrative, invasive and proliferative capacities, and lowers the HUVEC angiogenic capacity caused by silencing KDM5A. Therefore, KDM5A silencing significantly suppresses HCC tumorigenesis in vivo, accompanied with down-regulated miR-433 and up-regulated FXYD3-PI3K-AKT axis in tumour tissues. Lastly, KDM5A activates the FXYD3-PI3K-AKT axis to enhance angiogenesis in HCC by suppressing miR-433.

miR-194 inhibits liver cancer stem cell expansion by regulating RAC1 pathway.

Liver cancer stem cells (CSCs) contribute to tumorigenesis, progression, drug resistance and recurrence of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver CSCs remains unclear. Herein, we observed low expression of miR-194 in chemoresistant HCC cells. A remarkable decrease of miR-194 was detected in EpCAM or CD133-positive liver CSCs and CSC-enriched hepatoma spheres. Interference miR-194 facilitated liver CSCs expansion by enhancing the self-renewal of liver CSCs. While up-regulating miR-194 inhibited liver CSCs expansion by suppressing the self-renewal of liver CSCs. Furthermore, hepatoma cells with miR-194 overexpression performed more sensitivity to sorafenib treatment. Mechanistically, functional studies found that Ras-related C3 botulinum toxin substrate 1 (RAC1) was a direct target of miR-194. Overexpression of miR-194 inhibited the expression of RAC1 in liver CSCs. Special RAC1 siRNA diminished the discrepancy in liver CSC proportion and the self-renewal capacity between miR-194 overexpression hepatoma cells and control cells, which further confirmed that RAC1 was required in miR-194-inhibited liver CSCs expansion. More importantly, downregulated expression of miR-194 was a predictor of poor prognosis of HCC patients.

Diamond based photodetectors for solar-blind communication.

High performance solar-blind photodetectors have been fabricated from diamond wafers. The peak responsivity is 13.0 A/W at 222 nm with a dark current of 0.93 nA under 60 V bias. The rise and decay times of the photodetector are about 1.3 µs and 203 µs, respectively. The responsivity and response time of the device are both among the best values ever reported for diamond-based photodetectors. A solar-blind optical communication system has been constructed by employing the diamond photodetector as a signal receiver for the first time. Benefiting from the high spectral selectivity of the diamond photodetector, the communication system has excellent anti-interference ability. The results reported in this paper may pave the way for the future application of diamond-based solar-blind photodetectors in confidential communications.

[Research progress in functional dyspepsia relevant to traditional Chinese medicine based on the theory of brain-gut axis].

The incidence of functional dyspepsia (FD) is closely related to the dysfunction of brain-gut axis (BGA). Brain gut peptide (BGP) is expressed in the brain and gastrointestinal tract, which is important factor involved in BGA. FD is in the category of "stomach cramps" and "small full" in traditional Chinese medicine (TCM). TCM believes that the brain and intestines are closely connected to each other and form a brain-gut interaction. Therefore, the intestinal function is regulated by the brain, which is consistent with the BGA theory of western medicine. Researchers for TCM verified that the clinical symptoms of FD could be alleviated by regulating BGP and/or BGA through experimental research, clinical prescription therapy, and clinical non-drug therapy. Although TCM has a unique therapeutic effect on the treatment of FD, it has not yet to verify that TCM exerts significant clinical efficacy on FD, which still requires high-quality evidence-based medical evidence verification.

RIM genes differentially contribute to organizing presynaptic release sites.

Tight coupling of Ca(2+) channels to the presynaptic active zone is critical for fast synchronous neurotransmitter release. RIMs are multidomain proteins that tether Ca(2+) channels to active zones, dock and prime synaptic vesicles for release, and mediate presynaptic plasticity. Here, we use conditional knockout mice targeting all RIM isoforms expressed by the Rims1 and Rims2 genes to examine the contributions and mechanism of action of different RIMs in neurotransmitter release. We show that acute single deletions of each Rims gene decreased release and impaired vesicle priming but did not alter the extracellular Ca(2+)-responsiveness of release (which for Rims gene mutants is a measure of presynaptic Ca(2+) influx). Moreover, single deletions did not affect the synchronization of release (which depends on the close proximity of Ca(2+) channels to release sites). In contrast, deletion of both Rims genes severely impaired the Ca(2+) responsiveness and synchronization of release. RIM proteins may act on Ca(2+) channels in two modes: They tether Ca(2+) channels to active zones, and they directly modulate Ca(2+)-channel inactivation. The first mechanism is essential for localizing presynaptic Ca(2+) influx to nerve terminals, but the role of the second mechanism remains unknown. Strikingly, we find that although the RIM2 C(2)B domain by itself significantly decreased Ca(2+)-channel inactivation in transfected HEK293 cells, it did not rescue any aspect of the RIM knockout phenotype in cultured neurons. Thus, RIMs primarily act in release as physical Ca(2+)-channel tethers and not as Ca(2+)-channel modulators. Different RIM proteins compensate for each other in recruiting Ca(2+) channels to active zones, but contribute independently and incrementally to vesicle priming.

Impacts of nomad sedentarization on social and ecological systems at multiple scales in Xinjiang Uyghur autonomous region, China.

China's government is now promoting the Nomad Sedentarization Project (NSP) in large areas of grassland as a solution for ecological restoration and poverty alleviation. To examine the effects of this policy, we conducted in-depth interviews at two of the project's sites and examined the social and ecological systems at village, county, and catchment scales in Jinghe County of Xinjiang. We found that (1) the NSP in one village greatly improved the household standard of living and changed their resource utilization modes; (2) the success in this village can be attributed to resources imported from the social and ecological systems at larger scales, and could not be repeated in a second nearby village with different constraints; and (3) the NSP is poorly adapted to local ecosystem characteristics, and may therefore have negative impacts at larger scales. To avoid these problems, holistic assessments are necessary to judge the NSP's impacts on social and ecological systems at multiple scales, and the program must be implemented cautiously to account for the potential risks in ecologically vulnerable areas.

VisTellAR: Embedding Data Visualization to Short-form Videos Using Mobile Augmented Reality.

With the rise of short-form video platforms and the increasing availability of data, we see the potential for people to share short-form videos embedded with data in situ (e.g., daily steps when running) to increase the credibility and expressiveness of their stories. However, creating and sharing such videos in situ is challenging since it involves multiple steps and skills (e.g., data visualization creation and video editing), especially for amateurs. By conducting a formative study (N=10) using three design probes, we collected the motivations and design requirements. We then built VisTellAR, a mobile AR authoring tool, to help amateur video creators embed data visualizations in short-form videos in situ. A two-day user study shows that participants (N=12) successfully created various videos with data visualizations in situ and they confirmed the ease of use and learning. AR pre-stage authoring was useful to assist people in setting up data visualizations in reality with more designs in camera movements and interaction with gestures and physical objects to storytelling.

Endocytosis at the maternal-fetal interface: balancing nutrient transport and pathogen defense.

Endocytosis represents a category of regulated active transport mechanisms. These encompass clathrin-dependent and -independent mechanisms, as well as fluid phase micropinocytosis and macropinocytosis, each demonstrating varying degrees of specificity and capacity. Collectively, these mechanisms facilitate the internalization of cargo into cellular vesicles. Pregnancy is one such physiological state during which endocytosis may play critical roles. A successful pregnancy necessitates ongoing communication between maternal and fetal cells at the maternal-fetal interface to ensure immunologic tolerance for the semi-allogenic fetus whilst providing adequate protection against infection from pathogens, such as viruses and bacteria. It also requires transport of nutrients across the maternal-fetal interface, but restriction of potentially harmful chemicals and drugs to allow fetal development. In this context, trogocytosis, a specific form of endocytosis, plays a crucial role in immunological tolerance and infection prevention. Endocytosis is also thought to play a significant role in nutrient and toxin handling at the maternal-fetal interface, though its mechanisms remain less understood. A comprehensive understanding of endocytosis and its mechanisms not only enhances our knowledge of maternal-fetal interactions but is also essential for identifying the pathogenesis of pregnancy pathologies and providing new avenues for therapeutic intervention.

Heparin is an effective treatment for preventing liver failure after hepatectomy.

BACKGROUND: Posthepatectomy liver failure (PHLF) is one of the most important causes of death following liver resection. Heparin, an established anticoagulant, can protect liver function through a number of mechanisms, and thus, prevent liver failure. AIM: To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy. METHODS: The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) v1. 4 pinpointed patients who had undergone hepatectomy for liver cancer, subdividing them into two cohorts: Those who were injected with heparin and those who were not. The statistical evaluations used were unpaired t-tests, Mann-Whitney U tests, chi-square tests, and Fisher's exact tests to assess the effect of heparin administration on PHLF, duration of intensive care unit (ICU) stay, need for mechanical ventilation, use of continuous renal replacement therapy (CRRT), incidence of hypoxemia, development of acute kidney injury, and ICU mortality. Logistic regression was utilized to analyze the factors related to PHLF, with propensity score matching (PSM) aiming to balance the preoperative disparities between the two groups. RESULTS: In this study, 1388 patients who underwent liver cancer hepatectomy were analyzed. PSM yielded 213 matched pairs from the heparin-treated and control groups. Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples. Further analysis in the matched cohorts confirmed a significant association, with heparin reducing the risk of PHLF (odds ratio: 0.518; 95% confidence interval: 0.295-0.910; P = 0.022). Additionally, heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations, diminished requirements for respiratory support and CRRT, and lower incidences of hypoxemia and ICU mortality. CONCLUSION: Liver failure is an important hazard following hepatic surgery. During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure. This indicates that heparin may provide a hopeful option for controlling PHLF.

Management and outcome of adult generalized tetanus in a Chinese tertiary hospital.

Background: Tetanus is a rare surgical infectious disease with a high reported relevant mortality. It still remains a serious problem in public health, particularly in low-income and middle-income countries. The purpose of this study was to investigate the management and prognosis of adult generalized tetanus in our hospital. Methods: A total of 20 adult generalized tetanus patients were recruited in this retrospective observational study. Patients were retrieved from the hospital data base via discharge diagnosis. Patients were divided into two groups (Severe or Non-severe tetanus group) based on the severity of tetanus by using the Ablett classification. The differences between the two groups were compared. Results: The study included 11 males (55%) and 9 females (45%). All tetanus patients recovered. The median age was 53.5 years [IQR: 19-78]. There were 1 mild (Grade 1) case (5%),5 moderate (Grade 2) cases (25%), 2 severe (Grade 3) cases (10%), and 12 very severe (Grade 4) cases (60%). Nineteen patients (95%) did not have tetanus immunization before. The majority of patients were farmers (60%), and came from rural areas (60%). Thirteen (65%) patients had a history of puncture injury. The rate of wound debridement after admission was 60% overall. Thirteen (65%) patients required mechanical ventilation for a median of 21 [IQR:12-41] days. Autonomic instability occurred in 13 (65%) patients. Pulmonary infections occurred in 12 (60%) patients. Median duration of hospital stay was 29.5 [IQR:12-68] days. More patients in the Severe group needed ICU admission, wound debridement, mechanical ventilation and heavy sedation combined with muscle relaxants (p < 0.05). The hospital stay was significantly longer in patients in the Severe group (p < 0.05). Conclusion: After effective treatment, all adult patients with generalized tetanus in this study were cured and discharged. Severe tetanus requires early ICU treatment, wound debridement and effective treatment of autonomic instability.

Molecular determinants of Gem protein inhibition of P/Q-type Ca2+ channels.

The RGK family of monomeric GTP-binding proteins potently inhibits high voltage-activated Ca(2+) channels. The molecular mechanisms of this inhibition are largely unclear. In Xenopus oocytes, Gem suppresses the activity of P/Q-type Ca(2+) channels on the plasma membrane. This is presumed to occur through direct interactions of one or more Gem inhibitory sites and the pore-forming Ca(v)2.1 subunit in a manner dependent on the Ca(2+) channel subunit ß (Ca(v)ß). In this study we investigated the molecular determinants in Gem that are critical for this inhibition. Like other RGK proteins, Gem contains a conserved Ras-like core and extended N and C termini. A 12-amino acid fragment in the C terminus was found to be crucial for and sufficient to produce Ca(v)ß-dependent inhibition, suggesting that this region forms an inhibitory site. A three-amino acid motif in the core was also found to be critical, possibly forming another inhibitory site. Mutating either site individually did not hamper Gem inhibition, but mutating both sites together completely abolished Gem inhibition without affecting Gem protein expression level or disrupting Gem interaction with Ca(v)2.1 or Ca(v)ß. Mutating Gem residues that are crucial for interactions with previously demonstrated RGK modulators such as calmodulin, 14-3-3, and phosphatidylinositol lipids did not significantly affect Gem inhibition. These results suggest that Gem contains two candidate inhibitory sites, each capable of producing full inhibition of P/Q-type Ca(2+) channels.

Direct inhibition of P/Q-type voltage-gated Ca2+ channels by Gem does not require a direct Gem/Cavbeta interaction.

The Rem, Rem2, Rad, and Gem/Kir (RGK) family of small GTP-binding proteins potently inhibits high voltage-activated (HVA) Ca(2+) channels, providing a powerful means of modulating neural, endocrine, and muscle functions. The molecular mechanisms of this inhibition are controversial and remain largely unclear. RGK proteins associate directly with Ca(2+) channel beta subunits (Ca(v)beta), and this interaction is widely thought to be essential for their inhibitory action. In this study, we investigate the molecular underpinnings of Gem inhibition of P/Q-type Ca(2+) channels. We find that a purified Gem protein markedly and acutely suppresses P/Q channel activity in inside-out membrane patches, that this action requires Ca(v)beta but not the Gem/Ca(v)beta interaction, and that Gem coimmunoprecipitates with the P/Q channel alpha(1) subunit (Ca(v)alpha(1)) in a Ca(v)beta-independent manner. By constructing chimeras between P/Q channels and Gem-insensitive low voltage-activated T-type channels, we identify a region encompassing transmembrane segments S1, S2, and S3 in the second homologous repeat of Ca(v)alpha(1) critical for Gem inhibition. Exchanging this region between P/Q and T channel Ca(v)alpha(1) abolishes Gem inhibition of P/Q channels and confers Ca(v)beta-dependent Gem inhibition to a chimeric T channel that also carries the P/Q I-II loop (a cytoplasmic region of Ca(v)alpha(1) that binds Ca(v)beta). Our results challenge the prevailing view regarding the role of Ca(v)beta in RGK inhibition of high voltage-activated Ca(2+) channels and prompt a paradigm in which Gem directly binds and inhibits Ca(v)beta-primed Ca(v)alpha(1) on the plasma membrane.

Adaptation of herders to droughts and privatization of rangeland-use rights in the arid Alxa Left Banner of Inner Mongolia.

Residents of arid areas have developed their own adaptive strategies and adaptive capability to cope with an unstable environment that experiences frequent droughts. These strategies and this capability are based on traditional practices that developed from a profound understanding of their environment, but both the strategies and the capability have been affected by institutional change. Specifically, rangeland-use rights in the Alxa Left Banner were privatized in 1996, and the implementation of this policy decreased the ability of local herders to use traditional solutions. In this paper, we describe the change in their adaptive capability after implementation of this policy. Traditionally, local knowledge of the heterogeneity of resources and of key resources based on a deep understanding of the local environment, combined with tight social relationships, let herders use three traditional grazing strategies (seasonal migration, long-distance migration, and raising a diversity of livestock species) to mitigate the impacts of drought. But privatization has nearly eliminated their ability to rely on these traditional strategies and has weakened the forms of social and other capital that supported these strategies and provided a high adaptive capability. We argue that this institutional change has adversely affected traditional practices and undermined the adaptive capability of herders. Consequently, managers of the Alxa Left Banner must find ways to restore the various forms of capital to restore the herders' adaptive capability, particularly given the growing need to account for future climate change.