Alternative splicing of its 5'-UTR limits CD20 mRNA translation and enables resistance to CD20-directed immunotherapies.

Aberrant skipping of coding exons in CD19 and CD22 compromises the response to immunotherapy in B-cell malignancies. Here, we showed that the MS4A1 gene encoding human CD20 also produces several messenger RNA (mRNA) isoforms with distinct 5' untranslated regions. Four variants (V1-4) were detected using RNA sequencing (RNA-seq) at distinct stages of normal B-cell differentiation and B-lymphoid malignancies, with V1 and V3 being the most abundant. During B-cell activation and Epstein-Barr virus infection, redirection of splicing from V1 to V3 coincided with increased CD20 positivity. Similarly, in diffuse large B-cell lymphoma, only V3, but not V1, correlated with CD20 protein levels, suggesting that V1 might be translation-deficient. Indeed, the longer V1 isoform contained upstream open reading frames and a stem-loop structure, which cooperatively inhibited polysome recruitment. By modulating CD20 isoforms with splice-switching morpholino oligomers, we enhanced CD20 expression and anti-CD20 antibody rituximab-mediated cytotoxicity in a panel of B-cell lines. Furthermore, reconstitution of CD20-knockout cells with V3 mRNA led to the recovery of CD20 positivity, whereas V1-reconstituted cells had undetectable levels of CD20 protein. Surprisingly, in vitro CD20-directed chimeric antigen receptor T cells were able to kill both V3- and V1-expressing cells, but the bispecific T-cell engager mosunetuzumab was only effective against V3-expressing cells. To determine whether CD20 splicing is involved in immunotherapy resistance, we performed RNA-seq on 4 postmosunetuzumab follicular lymphoma relapses and discovered that in 2 of them, the downregulation of CD20 was accompanied by a V3-to-V1 shift. Thus, splicing-mediated mechanisms of epitope loss extend to CD20-directed immunotherapies.

Tag-free fluorometric aptasensor for detection of chromium(VI) in foods via SYBR Green I signal amplification and aptamer structure transition.

BACKGROUND: In response to growing concerns regarding heavy metal contamination in food, particularly chromium (Cr)(VI) contamination, this study presented a simple, sensitive and practical method for Cr(VI) detection. RESULTS: A magnetic separation-based capture-exponential enrichment ligand system evolution (SELEX) method was used to identify and characterize DNA aptamers with a high affinity for Cr(VI). An aptamer, Cr-15, with a dissociation constant (Kd) of 4.42 ± 0.44 µmol L-1 was obtained after only eight rounds of selection. Further innovative methods combining molecular docking, dynamic simulation and thermodynamic analysis revealed that CrO4 2- could bind to the 19th and 20th guanine bases of Cr-15 via hydrogen bonds. Crucially, a label-free fluorometric aptasensor based on SYBR Green I was successfully constructed to detect CrO4 2-, achieving a linear detection range of 60-300 nmol L-1 with a lower limit of detection of 44.31 nmol L-1. Additionally, this aptasensor was able to quantitatively detect CrO4 2- in grapes and broccoli within 40 min, with spike recovery rates ranging from 89.22% to 108.05%. The designed fluorometric aptasensor exhibited high selectivity and could detect CrO4 2- in real samples without sample processing or target pre-enrichment. CONCLUSION: The aptasensor demonstrated its potential as a reliable tool for monitoring Cr(VI) contamination in fruit and vegetable products. © 2024 Society of Chemical Industry.

The Treatment of Depersonalization-Derealization Disorder: A Systematic Review.

Depersonalization-derealization disorder (DPD) is characterized by persistent or recurrent experiences of detachment from oneself and surroundings, as well as a sense of unreality. Considering the inadequacy of current research on treatment, we performed a systematic review of the available pharmacotherapies, neuromodulations, and psychotherapies for DPD. The systematic review protocol was based on PRISMA 2020 guidelines and pre-registered. The PubMed, Web of Science, PsycINFO, Embase, the Cochrane Library, Scopus, and ScienceDirect databases were searched from inception to June 2021. All treatments for DPD and all study types, including controlled and observational studies as well as case reports, were assessed. Of the identified 17,540 studies, 41 studies (four randomized controlled trials, one non-randomized controlled trial, 10 case series, and 26 case reports) involving 300 participants met the eligibility criteria. We identified 30 methods that have been applied independently or in combination to treat DPD since 1955. The quality of these studies was considered. The relationship between individual differences, such as symptoms, comorbidities, history, and duration since onset, and treatment effects was explored. The results suggest that a series of treatments, such as pharmacotherapies, neuromodulation, and psychotherapies, could be considered in combination. However, the quality and quantity of studies were generally low considering the high prevalence of DPD. The review concludes with suggestions for future research and an urgent call for more high-quality research.

Protectin Conjugates in Tissue Regeneration 1 Inhibits Macrophage Pyroptosis by Restricting NLRP3 Inflammasome Assembly to Mitigate Sepsis via the cAMP-PKA Pathway.

Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel anti-inflammatory and proresolving lipid mediator biosynthesized from docosahexaenoic acid. Excessive activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome and consequent pyroptosis are involved in diverse inflammatory diseases. However, how PCTR1 affects NLRP3 inflammasome activation and pyroptosis are still unclear. Here, we demonstrated that PCTR1 inhibited NLRP3 inflammasome activation and pyroptosis. These results show that PCTR1 dose-dependently inhibited gasdermin D cleavage in lipopolysaccharide (LPS)-primed murine primary macrophages upon nigericin stimulation. Additionally, PCTR1 treatment after LPS priming inhibited caspase-1 activation and subsequent mature interleukin-1ß release independent of the nuclear factor-kappa B pathway. PCTR1 exerted its inhibitory effects by blocking NLRP3-apoptosis-associated speck-like protein containing a CARD (ASC) interaction and ASC oligomerization, thereby restricting NLRP3 inflammasome assembly. However, the inhibitory effect of PCTR1 could be reversed by KH7 and H89, which are the inhibitors of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway. Moreover, PCTR1 treatment alleviated lung tissue damage and improved mouse survival in LPS-induced sepsis. Our study unveils the molecular mechanism of negative regulation of NLRP3 inflammasome activation and pyroptosis by a novel lipid mediator and suggests that PCTR1 may serve as a potential treatment option for NLRP3-inflammasome driven diseases.

Adaptive divergence and genetic vulnerability of relict species under climate change: a case study of Pterocarya macroptera.

BACKGROUND AND AIMS: Understanding adaptive genetic variation and whether it can keep pace with predicted future climate change is critical in assessing the genetic vulnerability of species and developing conservation management strategies. The lack of information on adaptive genetic variation in relict species carrying abundant genetic resources hinders the assessment of genetic vulnerability. Using a landscape genomics approach, this study aimed to determine how adaptive genetic variation shapes population divergence and to predict the adaptive potential of Pterocarya macroptera (a vulnerable relict species in China) under future climate scenarios. METHODS: We applied restriction site-associated DNA sequencing (RAD-seq) to obtain 8244 single-nucleotide polymorphisms (SNPs) from 160 individuals across 28 populations. We examined the pattern of genetic diversity and divergence, and then identified outliers by genetic differentiation (FST) and genotype-environment association (GEA) methods. We further dissected the effect of geographical/environmental gradients on genetic variation. Finally, we predicted genetic vulnerability and adaptive risk under future climate scenarios. KEY RESULTS: We identified three genetic lineages within P. macroptera: the Qinling-Daba-Tianmu Mountains (QDT), Western Sichuan (WS) and Northwest Yunnan (NWY) lineages, which showed significant signals of isolation by distance (IBD) and isolation by environment (IBE). IBD and IBE explained 3.7-5.7 and 8.6-12.8 % of the genetic structure, respectively. The identified GEA SNP-related genes were involved in chemical defence and gene regulation and may exhibit higher genetic variation to adapt to the environment. Gradient forest analysis revealed that the genetic variation was mainly shaped by temperature-related variables, indicating its adaptation to local thermal environments. A limited adaptive potential was suggested by the high levels of genetic vulnerability in marginal populations. CONCLUSIONS: Environmental gradient mainly shaped the population differentiation of P. macroptera. Marginal populations may be at high risk of extinction, and thus proactive management measures, such as assisted gene flow, are required to ensure the survival of these populations.

Cyclothymic Temperament, Physical Neglect, and Earlier Age of Onset Predict Poor Medication Adherence in Patients With Bipolar Disorder.

ABSTRACT: Individual-level risk factors may predict poor medication adherence (PMA) in bipolar disorder (BD). This study aimed to evaluate the association between affective temperament, childhood trauma, age of first onset, and PMA in patients with BD in China. A total of 168 patients completed the eight-item Morisky Medication Adherence Scale; the Short Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire; and the Childhood Trauma Questionnaire-Short Form. Scores were then compared between PMA and non-PMA groups. Binary logistic regression showed that age of first onset was negatively correlated with PMA ( ß = -0.106, p = 0.002), whereas physical neglect and cyclothymic temperament were positively correlated with PMA ( ß = 0.143, p = 0.029; ß = 0.19, p = 0.001, respectively). These findings indicate that cyclothymic temperament, physical neglect, and earlier onset are predictors of PMA in patients with BD and that such patients may require further attention to improve medical compliance.

[Voluntary wheel running exercise regulates microglia polarization in hippocampus through STAT3 signal pathway to inhibit depression-like behavior induced by chronic stress in rats].

This paper was aimed to investigate the effect of voluntary wheel running exercise on depression-like behavior induced by chronic water immersion restraint stress (CWIRS) and the underlying mechanism. Sprague-Dawley (SD) rats received CWIRS to induce depression-like behavior and 4-week voluntary wheel running exercise. Meanwhile, the rats were treated with lipopolysaccharide (LPS) or STAT3 over-expression vector (pcDNA-STAT3) by intracerebroventricular injection. Behavioral tests were used to detect depression-like behavior. ELISA assay was used to detect levels of various inflammatory factors in the rat hippocampus. Western blot was used to detect protein expression levels of ionized calcium binding adaptor molecule 1 (Iba1), inducible nitric oxide synthase (iNOS), arginase 1 (Arg1), phosphorylated STAT3 (p-STAT3) and total STAT3 (t-STAT3). The results showed that, compared with stress group, stress + exercise group exhibited improved depression-like behavior, decreased interleukin-1ß (IL-1ß) and IL-6 levels, increased IL-4 and IL-10 levels, down-regulated Iba-1 and iNOS protein expression levels, up-regulated Arg1 protein expression level, and decreased p-STAT3/t-STAT3 ratio in hippocampal tissue. LPS reversed the improving effect of voluntary wheel running exercise on depression-like behavior in rats, and the over-expression of STAT3 reversed the promoting effects of voluntary wheel running on M2 polarization of microglial cells in rat hippocampus and depression-like behavior. These results suggest that voluntary wheel running ameliorates the depression-like behavior induced by CWIRS in rats, and the mechanism may be related to regulating hippocampal microglia polarization via STAT3 signaling pathway.

Posttreatment of Maresin1 Inhibits NLRP3 inflammasome activation via promotion of NLRP3 ubiquitination.

Maresin1 is a potent lipid mediator exhibiting potential anti-inflammatory activity in a variety of inflammatory diseases, however, the underlying mechanisms remain poorly understood. Excessive activation of NLRP3 inflammasome has been established in multiple inflammatory diseases. Here, we show that Maresin1 dose-dependently inhibited the NLRP3 inflammasome activation and subsequent caspase-1 activation and IL-1ß secretion. This inhibitory effect could be reversed by KH7 and H89, the inhibitors of the cAMP-PKA signaling pathway. Activation of PKA kinase induced by Maresin1 led to the K63-linked ubiquitination of NLRP3 in macrophages. Maresin1 attenuated serum IL-1ß secretion through inhibition of NLRP3 inflammasome in vivo using Nlrp3-deficient mouse models of lipopolysaccharide (LPS)-induced sepsis. Maresin1 also repressed MSU-induced peritonitis. This study suggests that Maresin1 is an inhibitor of NLRP3 inflammasome activation and can be used clinically in the treatment of NLRP3 inflammasome-driven inflammatory diseases.

Identification of molecular determinants that govern distinct STIM2 activation dynamics.

The endoplasmic reticulum (ER) Ca2+ sensors stromal interaction molecule 1 (STIM1) and STIM2, which connect ER Ca2+ depletion with extracellular Ca2+ influx, are crucial for the maintenance of Ca2+ homeostasis in mammalian cells. Despite the recent progress in unraveling the role of STIM2 in Ca2+ signaling, the mechanistic underpinnings of its activation remain underexplored. We use an engineering approach to direct ER-resident STIMs to the plasma membrane (PM) while maintaining their correct membrane topology, as well as Förster resonance energy transfer (FRET) sensors that enabled in cellulo real-time monitoring of STIM activities. This allowed us to determine the calcium affinities of STIM1 and STIM2 both in cellulo and in situ, explaining the current discrepancies in the literature. We also identified the key structural determinants, especially the corresponding G residue in STIM1, which define the distinct activation dynamics of STIM2. The chimeric E470G mutation could switch STIM2 from a slow and weak Orai channel activator into a fast and potent one like STIM1 and vice versa. The systemic dissection of STIM2 activation by protein engineering sets the stage for the elucidation of the regulation and function of STIM2-mediated signaling in mammals.

Isolation of Thalassobius mangrovi sp. nov., a novel bacterium in the family Rhodobacteraceae, from marine mangrove sediment.

A Gram-stain-negative, strictly aerobic and oval-shaped bacterial strain with a flagellum, designated GS-10T, was isolated from mangrove wetland sediment. GS-10T grew at 20-40 °C (optimum, 37 °C), in the pH range of 5.0-11.0 (optimum, 6.0-8.0) and under various NaCl concentrations from 1 to 11 % (w/v) (optimum, 5-6 %). The respiratory quinone was ubiquinone-10, and the predominant polar lipids were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The major fatty acids (>10 % of the total fatty acids) were summed feature 4 (C17 : 1iso I/anteiso B) and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The G+C content of the genomic DNA was 63.71 %. On the basis of the results from comparative analysis of the 16S rRNA gene sequence, GS-10T represents a member of the family Rhodobacteraceae and had the highest sequence similarity to Thalassobius gelatinovorus CECT 4357T (97.47 %), followed by Lutimaribacter pacificus W11-2BT (97.03 %), Marivita cryptomonadis CL-SK44T (96.83 %), Thalassobius autumnalis CECT 5118T (96.75 %) and Thalassobius mediterraneus CECT 5383T (96.68 %). Phylogenetic trees based on 16S rRNA gene sequences, multilocus sequence analysis (MLSA) and whole genome sequences revealed that GS-10T clustered with species within the genus Thalassobius. The average nucleotide identity (ANI) and the average amino acid identity (AAI) values were calculated from complete genome sequences and indicated that GS-10T represented a novel species of the genus Thalassobius, and the name Thalassobius mangrovi sp. nov. is proposed for this species. The type strain of Thalassobius mangrovi is GS-10T (=MCCC 1K03624T=KCTC 82131T).

Optical Control of CRAC Channels Using Photoswitchable Azopyrazoles.

The Ca2+ release-activated Ca2+ (CRAC) channels control many Ca2+-modulated physiological processes in mammals. Hyperactivating CRAC channels are known to cause several human diseases, including Stormorken syndrome. Here, we show the design of azopyrazole-derived photoswitchable CRAC channel inhibitors (designated piCRACs), which enable optical inhibition of store-operated Ca2+ influx and downstream signaling. Moreover, piCRAC-1 has been applied in vivo to alleviate thrombocytopenia and hemorrhage in a zebrafish model of Stormorken syndrome in a light-dependent manner.

Seed germination schedule and environmental context shaped the population genetic structure of subtropical evergreen oaks on the Yun-Gui Plateau, Southwest China.

The evergreen broadleaved forests (EBLFs) of Southwest China have a long-term stable environment and support a diverse flora, thus forming a global biodiversity hotspot. However, the key drivers that have shaped the genetic diversity patterns of species in these EBLFs are not well understood. Quercus delavayi, Q. schottkyana, and Q. kerrii are sympatric oak species with different seed biological traits that are typical for these EBLFs. This study combined multilocus phylogeography and ecological niche modeling to screen 33 Q. delavayi populations. Their population genetic structure was inferred in comparison with previous studies on Q. schottkyana and Q. kerrii. The seed germination traits of all three species were also investigated. cpDNAs showed a significant phylogeographic structure in Q. delavayi, which was not detected in Q. schottkyana or Q. kerrii. Quercus delavayi, Q. kerrii, and Q. schottkyana exhibited different pollen-to-seed migration ratios (r = 219, 117, and 22, respectively), which are linked to the germination schedules of acorns. The distributions of Q. delavayi and Q. schottkyana remained long-term stable since the last glacial maximum (LGM) with a similar nSSR genetic gradient change along latitude. Instead, Q. kerrii experienced a prominent range expansion since the LGM with genetic diversification between the East and the West of the Tanaka line due to environmental heterogeneity. These results identify seed traits and environmental heterogeneity as two key drivers that shape the population genetic structure of EBLF trees in Southwest China. These should be considered in regional forestry conservation and management.

Marisediminitalea mangrovi gen. nov., sp. nov., isolated from marine mangrove sediment, and reclassification of Aestuariibacter aggregatus as Marisediminitalea aggregata comb. nov.

Strain GS-14T was isolated from a mangrove sediment sample collected at Beilun Estuary National Nature Reserve, Guangxi Province, PR China. Cells were Gram-stain-negative, strictly aerobic and rod-shaped with a polar flagellum. Optimal growth occurred in the presence of 3-6 % (w/v) NaCl, at pH 6-8 and at a temperature of 37 °C. The predominant polar lipids were phosphatidylglycerol and phosphatidylethanolamine. Ubiquinone 8 (Q-8) was the sole respiratory quinone. The major fatty acids (>10 % of the total fatty acids) were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0. The DNA G+C content was 47.6 mol%. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain GS-14T had the highest sequence similarity to Aestuariibacter aggregatus WH169T (96.63 %), Aliiglaciecola coringensis AK49T (96.56 %) and Alteromonas lipolytica JW12T (96.22 %). In addition, the OrthoANIu value and dDDH values calculated from the genomes of strain GS-14T and A. aggregatus WH169T were 79.5 and 21.9 %, respectively. Based on the polyphasic taxonomic results, strain GS-14T is considered to represent a novel species in a new genus, for which the name Marisediminitalea mangrovi gen. nov., sp. nov. is proposed. The type strain of Marisediminitalea mangrovi is GS-14T (=KCTC 72401T=MCCC 1K03622T). Because Aestuariibacter aggregatus WH169T clustered with strain GS-14T in the phylogenetic trees and was clearly separated from the two species within the genus Aestuariibacter, it is reclassified as a member of the genus Marisediminitalea as Marisediminitalea aggregata comb. nov. (type strain WH169T=CGMCC 1.8995T=LMG 25283T). The type species of the genus Marisediminitalea is Marisediminitalea aggregata gen. nov., comb. nov.

Functional characterization of CEP250 variant identified in nonsyndromic retinitis pigmentosa.

Retinitis pigmentosa (RP) is the most common manifestation of inherited retinal diseases with high degree of genetic, allelic, and phenotypic heterogeneity. CEP250 encodes the C-Nap1 protein and has been associated with various retinal phenotypes. Here, we report the identification of a mutation (c.562C>T, p.R188*) in the CEP250 in a consanguineous family with nonsyndromic RP. To gain insights into the molecular pathomechanism underlying CEP250 defects and the functional relevance of CEP250 variants in humans, we conducted a functional characterization of CEP250 variant using a novel Cep250 knockin mouse line. Remarkably, the disruption of Cep250 resulted in severe impairment of retinal function and significant retinal morphological alterations. The homozygous knockin mice showed significantly reduced retinal thickness and ERG responses. This study not only broadens the spectrum of phenotypes associated with CEP250 mutations, but also, for the first time, elucidates the function of CEP250 in photoreceptors using a newly established animal model.

Thalassotalea mangrovi sp. nov., a bacterium isolated from marine mangrove sediment.

A novel Gram-stain-negative, strictly aerobic bacterium that has a rod-like shape with a single polar flagellum in the exponential phase of growth and a spherical or ovoid shape without a flagellum in the stationary phase was isolated from a mangrove wetland sediment sample collected at Beilun Estuary National Nature Reserve, Guangxi Province, PR China and designated strain ZS-4T. This strain grew optimally at pH 6.0-8.0, at a temperature of 37 °C and in the presence of 3-4 % (w/v) NaCl. Its polar lipid profile included phosphatidylethanolamine, phosphatidylglycerol, one unidentified aminophospholipid and two uncharacterized lipids. Ubiquinone 8 (Q-8) was the sole respiratory quinone and the cellular fatty acids were dominated by C17 : 1ω8c and C16 : 0. A phylogenetic analysis based on the 16S rRNA gene sequence showed that strain ZS-4T exhibited its highest similarities to the type strains Thalassotalea litorea HMF4135T (97.8 %) and Thalassotalea ponticola GJSW-36T (95.9 %). A whole genome-level comparison of strain ZS-4T with T. litorea MCCC 1K03283T revealed an average nucleotide identity value of 75.6 % and a calculated DNA-DNA hybridization value of 19.6 %. In addition, the genomic DNA G+C content of strain ZS-4T was 45.9 mol%. Thus, based on analyses of its morphology, physiology, fatty acid composition and 16S rRNA gene sequence, strain ZS-4T should be considered a novel species of the genus Thalassotalea, with the proposed name Thalassotaleamangrovi sp. nov. The type strain is ZS-4T (=KCTC 72399T=MCCC 1K03630T).

Resolvin D1 Improves the Resolution of Inflammation via Activating NF-κB p50/p50-Mediated Cyclooxygenase-2 Expression in Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is a severe illness characterized by uncontrolled inflammation. The resolution of inflammation is a tightly regulated event controlled by endogenous mediators, such as resolvin D1 (RvD1). Cyclooxygenase-2 (COX-2) has been reported to promote inflammation, along with PGE2, in the initiation of inflammation, as well as in prompting resolution, with PGD2 acting in the later phase of inflammation. Our previous work demonstrated that RvD1 enhanced COX-2 and PGD2 expression to resolve inflammation. In this study, we investigated mechanisms underlying the effect of RvD1 in modulating proresolving COX-2 expression. In a self-limited ARDS model, an LPS challenge induced the biphasic activation of COX-2, and RvD1 promoted COX-2 expression during the resolution phase. However, it was significantly blocked by treatment of a NF-κB inhibitor. In pulmonary fibroblasts, NF-κB p50/p50 was shown to be responsible for the proresolving activity of COX-2. Additionally, RvD1 potently promoted p50 homodimer nuclear translocation and robustly triggered DNA-binding activity, upregulating COX-2 expression via lipoxin A4 receptor/formyl peptide receptor 2. Finally, the absence of p50 in knockout mice prevented RvD1 from promoting COX-2 and PGD2 expression and resulted in excessive pulmonary inflammation. In conclusion, RvD1 expedites the resolution of inflammation through activation of lipoxin A4 receptor/formyl peptide receptor 2 receptor and NF-κB p50/p50-COX-2 signaling pathways, indicating that RvD1 might have therapeutic potential in the management of ARDS.

Calcium store refilling and STIM activation in STIM- and Orai-deficient cell lines.

Mediated through the combined action of STIM proteins and Orai channels, store-operated Ca2+ entry (SOCE) functions ubiquitously among different cell types. The existence of multiple STIM and Orai genes has made it difficult to assign specific roles of each STIM and Orai homolog in mediating Ca2+ signals. Using CRISPR/Cas9 gene editing tools, we generated cells with both STIM or all three Orai homologs deleted and directly monitored store Ca2+ and Ca2+ signals. We found that unstimulated, SOCE null KO cells still retain 50~70% of ER Ca2+ stores of wildtype (wt) cells. After brief exposure to store-emptying conditions, acute refilling of ER Ca2+ stores was totally blocked in KO cells. However, after 24 h in culture, stores were eventually refilled. Thus, SOCE is critical for immediate refilling of ER Ca2+ but is dispensable for the maintenance of long-term ER Ca2+ homeostasis. Using the Orai null background triple Orai-KO cells, we examined the plasma membrane translocation properties of a series of truncated STIM1 variants. FRET analysis reveals that, even though PM tethering of STIM1 expedites the activation of STIM1 by facilitating its oligomerization, migration, and accumulation in ER-PM junctions, it is not required for the conformational switch, oligomerization, and clustering of STIM1. Even without overt puncta formation at ER-PM junctions, STIM11-491 and STIM11-666 could still rescue SOCE when expressed in STIM KO cells. Thus, ER-PM trapping and clustering of STIM molecules only facilitates the process of SOCE activation, but is not essential for the activation of Orai channels.

Geographical isolation and environmental heterogeneity contribute to the spatial genetic patterns of Quercus kerrii (Fagaceae).

Southwest China is one of the major global biodiversity hotspots. The Tanaka line, extending within southwestern China from its northwest to its southeast, is an important biogeographical boundary between the Sino-Japanese and Sino-Himalayan floristic regions. Understanding the evolutionary history of the regional keystone species would assist with both reconstructing historical vegetation dynamics and ongoing biodiversity management. In this research, we combined phylogeographic methodologies and species distribution models (SDMs) to investigate the spatial genetic patterns and distribution dynamics of Quercus kerrii, a dominant evergreen oak inhabiting southwest China lowland evergreen-broadleaved forests (EBLFs). A total of 403 individuals were sampled from 44 populations throughout southwest China. SDMs and mismatch distribution analysis indicated that Q. kerrii has undergone northward expansion since the Last Glacial Maximum (LGM). Quantitative analysis revealed that the range expansion of Q. kerrii since the LGM exceeded that of the sympatric mid-elevation species Quercus schottkyana, likely owing to their contrasting distribution elevations and habitat availabilities. The historical climate change since the LGM and the latitude gradient of the region played an important role in shaping the genetic diversity of Q. kerrii. The genetic differentiation index and genetic distance surface of Q. kerrii populations east of the Tanaka line exceeded those to its west. The long-term geographic isolation and environmental heterogeneity between the two sides of the Tanaka line might increase species divergence patterns and local adaptation. This study provides new insights into the historical dynamics of subtropical EBLFs and the changing biota of southwest China.

Integrated pipeline for inferring the evolutionary history of a gene family embedded in the species tree: a case study on the STIMATE gene family.

BACKGROUND: Because phylogenetic inference is an important basis for answering many evolutionary problems, a large number of algorithms have been developed. Some of these algorithms have been improved by integrating gene evolution models with the expectation of accommodating the hierarchy of evolutionary processes. To the best of our knowledge, however, there still is no single unifying model or algorithm that can take all evolutionary processes into account through a stepwise or simultaneous method. RESULTS: On the basis of three existing phylogenetic inference algorithms, we built an integrated pipeline for inferring the evolutionary history of a given gene family; this pipeline can model gene sequence evolution, gene duplication-loss, gene transfer and multispecies coalescent processes. As a case study, we applied this pipeline to the STIMATE (TMEM110) gene family, which has recently been reported to play an important role in store-operated Ca2+ entry (SOCE) mediated by ORAI and STIM proteins. We inferred their phylogenetic trees in 69 sequenced chordate genomes. CONCLUSIONS: By integrating three tree reconstruction algorithms with diverse evolutionary models, a pipeline for inferring the evolutionary history of a gene family was developed, and its application was demonstrated.

Distinctive gut microbial community structure in both the wild and farmed Swan goose (Anser cygnoides).

Swan goose (Anser cygnoides) is currently one of the most popular economic wildfowl for rare birds breeding industries in several provinces of China. However, the farmed Swan geese, reared in artificial environment and fed on both natural and artificial diets, display a reduced reproductive rate compared to wild species. Little is known about the gut microbiota of this species, which could play a role in nutrient and energy metabolism, immune homeostasis and reproduction. The present comparative study was designed to provide a first characterization of gut microbial communities related to both wild and farmed Swan geese by 16 S rRNA sequences using the Illumina HiSeq platform. The results showed that dominant microbial components in both groups consisted of Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria. The abundances of these four phyla were not statistically different between the groups. At the genus level, significantly decreased abundance of Clostridium and increased abundance of SMB53, Enterococcus and Paenibacillus were observed in farmed group compared to wild group. The marked differences of genus level group-specific microbes create a baseline for future Swan goose microbiology research and make a valuable contribution to forming relationships between gut microbiota and domestic bird reproduction.