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- ArticleFan J, He N, He Q, Liu Y, Ma Y, Fu X, Liu Y, Huang P, Chen X.Nanoscale. 2015 Dec 21;7(47):20055-62.A novel sandwich nanomedicine (GO-BNN6) for near-infrared (NIR) light responsive release of nitric oxide (NO) has been constructed by self-assembly of graphene oxide (GO) nanosheets and a NO donor BNN6 through the π-π stacking interaction. The GO-BNN6 nanomedicine has an extraordinarily high drug loading capacity (1.2 mg BNN6 per mg GO), good thermal stability, and high NIR responsiveness. The NO release from GO-BNN6 can be easily triggered and effectively controlled by adjusting the switching, irradiation time and power density of NIR laser. The intracellular NIR-responsive release of NO from the GO-BNN6 nanomedicine causes a remarkable anti-cancer effect.
- ArticleH Almotairi K.Heliyon. 2023 Sep;9(9):e20055.This study considers the case of unreliable equipment subjected to random failures that induce high maintenance and environmental costs. We consider situations where the equipment is located in remote areas, which are difficult to access, and situations where there could be confinement linked to a pandemic, making it impossible to perform the replacement of the failed equipment. In such situations, the objective is to explore the possibility of providing a system with self-maintenance capabilities to a certain extent by adding redundant (stand-by) identical modules. Both the designs (with and without passive redundancy) are considered. A mathematical cost model is developed for each alternative to help decide whether to adopt redundancy and determine the optimal number of redundant modules, which minimises the total expected cost. The latter includes the costs related to the acquisition, maintenance, and recycling of failed modules. A numerical example is presented, and a sensitivity study is performed to investigate the effect of variations in relevant input parameters on the optimal design.
- ArticleWang Y, Lin S, Li C, Shi Y, Guan W.Medicine (Baltimore). 2020 May;99(19):e20055.INTRODUCTION: Sleep apnea-hypopnea syndrome (SAHS) is a multifactorial disease characterized by recurrent hypopnea or respiratory interruption during sleep, which causes intermittent hypoxemia, hypercapnia, and sleep structure disturbances. An association between ankylosing spondylitis (AS) and the type of SAHS has rarely been reported in the literature. Here, we present a case of SAHS in a patient with AS and discuss the possible mechanism underlying the type of SAHS.
PATIENT CONCERNS: A 46-year-old man presented with a 15-year history of AS. He had been receiving sulfasalazine for symptomatic relief and had never been on immunosuppressive therapy.
DIAGNOSIS: The patient was diagnosed with SAHS in addition to AS.
INTERVENTIONS: We instituted treatment with methylprednisolone (5 mg, oral, daily), leflumomide (20 mg, oral, daily), bicyclol tablets (25 mg, oral, 3 times a day), and ursodeoxycholic acid tablets (10 mg/kg, oral, daily). The patient received etanercept (50 mg, sc, once a week) as his condition deteriorated. In addition, for management of SAHS symptoms, the patient received nasal continuous positive airway pressure (CPAP) during sleep.
OUTCOMES: Six months after commencement of the treatment, the clinical manifestations of SAHS and AS had significantly improved.
CONCLUSIONS: We hypothesize that patients with AS are prone to sleep apnea due to airway compression, central depression of respiration, abnormal inflammatory responses. Hence, careful assessment toward potential SAHS symptoms should be considered especially in patients with AS. - ArticleShaikh AS, Pavurala R, Gou E.Cureus. 2021 Nov;13(11):e20055.Approximately 20% of patients with newly diagnosed colorectal cancer present with distant metastatic disease. Brain metastasis from colorectal cancer is uncommon and usually associated with metachronous metastases in other organs. We describe a rare case of a 49-year-old patient presenting with headaches and left-sided weakness found to have a solitary brain metastasis from primary rectal cancer. Primary rectal cancer, young age, lung and liver metastases, and KRAS mutation are risk factors associated with brain metastases in patients with colorectal cancer. Intracranial imaging should be considered as part of the workup in the staging of colorectal cancer in patients who are at high risk of brain metastasis.
- ArticleSirocko F, Albert J, Britzius S, Dreher F, Martínez-García A, Dosseto A, Burger J, Terberger T, Haug G.Sci Rep. 2022 11 21;12(1):20055.Lake sediment records from Holzmaar and the infilled maar of Auel (Eifel, Germany) are used to reconstruct landscape changes and megafauna abundances. Our data document a forested landscape from 60,000 to 48,000 yr b2k and a stepwise vegetation change towards a glacial desert after 26,000 yr b2k. The Eifel landscape was continuously inhabited from 48,000 to 9000 yr b2k by large mammals, documented by the presence of spores of coprophilous fungi from Sordaria and Sporormiella fungi that grow on fecal remains of the megafauna. Megafauna reached higher numbers during cold stadial climates but was present also during the warmer interstadials. Highest abundance was at 56,500/48,500/38,500/33,000/27,000/21,000/16,200/14,000 yr b2k, i.e. under different climate regimes. Some of these dates were associated with clear human presence, which indicates that megafauna was not overkilled by humans. In contrast, human presence could quite likely have been stimulated by the abundant food supply. Megafauna presence decreased significantly when tree abundance increased during interstadials. The Megafauna disappeared finally at 11,400 yr b2k with the development of the early Holocene forest cover, which appears to be the most important threshold for megafauna presence.
- ArticleChu X, Chen X, Wan Q, Zheng Z, Du Q.J Biol Chem. 2016 09 16;291(38):20055-67.The large nuclear mitotic apparatus (NuMA) protein is an essential player in mitotic spindle assembly and maintenance. We report here the identification of Astrin, a spindle- and kinetochore-associated protein, as a novel interactor of NuMA. We show that the C-terminal tail of NuMA can directly bind to the C terminus of Astrin and that this interaction helps to recruit Astrin to microtubules. Knockdown of NuMA by RNA interference dramatically impaired Astrin recruitment to the mitotic spindle. Overexpression of the N terminus of mammalian homologue of Drosophila Pins (LGN), which blocks the microtubule binding of NuMA and competes with Astrin for NuMA binding, also led to similar results. Furthermore, we found that cytoplasmic dynein is required for the spindle pole accumulation of Astrin, and dynein-mediated transport is important for balanced distribution of Astrin between spindle poles and kinetochores. On the other hand, if Astrin levels are reduced, then NuMA could not efficiently concentrate at the spindle poles. Our findings reveal a direct physical link between two important regulators of mitotic progression and demonstrate the critical role of the NuMA-Astrin interaction for accurate cell division.
- ArticleKanbayashi Y, Sakaguchi K, Ishikawa T, Takayama K, Taguchi T.Sci Rep. 2021 10 08;11(1):20055.This retrospective study aimed to identify predictors for the development of palbociclib-induced neutropenia. This study retrospectively analysed 78 breast cancer patients who had received palbociclib at our hospital between January 2018 and May 2020. For the regression analysis of factors associated with palbociclib-induced neutropenia, variables were extracted manually from medical charts. The level of palbociclib-induced neutropenia was evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events (version 5). Multivariate ordered logistic regression analysis was performed to identify predictors for the development of neutropenia. Optimal cut-off thresholds were determined using receiver operating characteristic (ROC) analysis. Values of P < 0.05 (2-tailed) were considered significant. Significant factors identified included concomitant use of statin (odds ratio [OR] = 0.104, 95% confidence interval [CI] = 0.018-0.598; P = 0.011) and body mass index (BMI) (OR = 1.118, 95% CI = 1.007-1.241; P = 0.037). ROC analysis revealed that neutropenia (grade 4) was more likely to occur with a BMI ≥ 22.3 kg/m2. In conclusion, no concomitant use of statins and high BMI were identified as significant predictors for the development of palbociclib-induced neutropenia.
- ArticleGirma G, Nida H, Tirfessa A, Lule D, Bejiga T, Seyoum A, Mekonen M, Nega A, Dessalegn K, Birhanu C, Bekele A, Gebreyohannes A, Ayana G, Tesso T, Ejeta G, Mengiste T.Plant Genome. 2020 11;13(3):e20055.Understanding population genetic structure and diversity of a crop is essential in designing selection strategies in plant breeding. About 2010 Ethiopian sorghum accessions were phenotyped for different traits at multiple locations. A subset of the collection, 1628 accessions, predominantly landraces, some improved varieties, and inbred lines were genotyped by sequencing. Phenotypic data revealed association of important traits with different sorghum growing agro-climatic regions, high genetic diversity and the presence of rare natural variation in the Ethiopian sorghum germplasm. Subsequent genotypic analysis determined optimum number of sub-populations, distinct cluster groups and ancestries of each sorghum accessions. To improve utilization of germplasm, a core subset of 387 lines were selected following posteriori grouping of genotypes based on cluster groups obtained through GBS analysis followed by stratified random sampling using quantitative traits. In order to evaluate how well this new sorghum and millet innovation lab (SMIL) collection from Ethiopia is represented within the largest world sorghum collection at United States Department of Agriculture - National Plant Germplasm System (USDA-NPGS) and the sorghum association panel (SAP), comparisons were conducted based on SNP data. The SMIL collection displayed high genetic diversity with some redundancy with the USDA-NPGS germplasm but SAP showed clear distinction. Furthermore, genome-environment association analysis identified candidate genes associated with adaptation to abiotic factors, that will be important for exploitation of adaptive potential to different environments. In summary, our results described the diversity and relationship of sorghum collections, representativeness of developed core and provide novel insights into candidate genes associated to abiotic stress tolerance.
- ArticleShi M, Yang L, Chen Z, Kan A, Chen S, He T, Zhang J.Sci Rep. 2023 Nov 16;13(1):20055.Vacuum Insulation Panels (VIPs) are highly efficient thermal insulation materials with extremely low thermal conductivity based on the vacuum principle. With the sealing properties of the gas barrier envelopes, a long service life of the VIP is obtained. The mechanism and influence factors of gas and water vapor permeability were mathematically analyzed to explore the influence of gas barrier envelopes on the thermal performance of VIPs. Three typical gas barriers were studied, and the selection of the gas barrier and other aspects of optimization were involved. The relationships among temperature, humidity, solubility coefficient, diffusion coefficient, and permeability were concluded, which shows that temperature has a much greater effect on the permeability of the gas barrier relative to humidity. The numerical analysis and influencing factors of VIPs' service life were also exemplified with three different types of gas barrier envelopes. The experimental results show that depending on the environment, the temperature has a major impact on the effective thermal conductivity and service life of VIP. The research was significant in the selection of gas barriers, the optimization of the performance, and the development of vacuum insulation material.
- ArticleZhou C, Liu Y, Chen K, Dai Z, Ma T, Wang Y, Ren S, Deng J, Zhang R, Tian F, Zhang Y, Zeng H, Yang S.Sci Rep. 2020 Nov 18;10(1):20055.Galfenol (Iron-gallium) alloys have attracted significant attention as the promising magnetostrictive materials. However, the as-cast Galfenols exhibit the magnetostriction within the range of 20-60 ppm, far below the requirements of high-resolution functional devices. Here, based on the geometric crystallographic relationship, we propose to utilize the 90°-domain switching to improve the magnetostriction of Galfenols by tuning the crystal growth direction (CGD) along the easy magnetization axis (EMA). Our first-principles calculations demonstrate that Pt doping can tune the CGD of Galfenol from [110] to [100], conforming to the EMA. Then, it is experimentally verified in the (Fe0.83Ga0.17)100-xPtx (x = 0, 0.2, 0.4, 0.6, 0.8 and 1.0) alloys and the magnetostriction is greatly improved from 39 ppm (x = 0, as-cast) to 103 ppm (x = 0.8, as-cast) and 188 ppm (x = 0.8, directionally solidified), accompanying with the increasing CGD alignment along [100]. The present study provides a novel approach to design and develop high-performance magnetostrictive materials.
- ArticleCai P, Hong Y, Ci S, Wen Z.Nanoscale. 2016 Dec 08;8(48):20048-20055.Electrochemical catalysis of O2-incorporated reactions is a promising strategy for metal-air batteries. The performance of metal-air batteries is determined by the catalytic activities of the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). Therefore, developing efficient catalysts with superior activities for the ORR and OER is of great significance to expand the application range of metal-air batteries. Herein, CoFe alloy nanoparticles adhered to the inside wall of nitrogen doped carbon nanotubes (CoFe@NCNTs) are synthesized and can function as a Janus particle to efficiently catalyze the ORR and OER with desirable activities in 0.1 M KOH solution. Specifically, the CoFe@NCNTs present an onset potential of 0.95 V and a half-wave potential of 0.84 V as an ORR catalyst. When used as an air-cathode catalyst for a Zn-air battery, the CoFe@NCNTs cathode performs better than a Pt/C cathode, showing a high open-circuit potential of 1.45 V, a maximum power density of 150 mW cm-2 and an average specific capacity of 808 mA h gzn-1 at current densities from 2 mA cm-2 to 10 mA cm-2.
- ArticleMicha DN, Silvares Junior RT.Sci Rep. 2019 Dec 27;9(1):20055.In this work, we revisit the theoretical study on the conversion efficiency of series-connected multijunction solar cells. The theoretical method, based on the detailed balance model, is then applied to devices with 2 to 6 junctions under different illumination conditions. As results, (i) we show that the peaks in the efficiency distribution occur for recurrent values of bottom junction bandgap energy corresponding to atmospheric absorption in the solar spectrum, and (ii) we demonstrate that variations in the number of junctions, in the incident solar spectrum, and in the concentration factor lead to changes in the optimum bandgap energy set but that the bottom junction bandgap energy only changes among the recurrent values presented before. Additionally, we highlight that high conversion efficiencies take place for a broad distribution of bandgap energy combination, which make the choice of materials for the device more flexible. Therefore, based on the overall results, we propose more than a hundred III-V, II-VI and IV semiconductor material candidates to compose the bottom junction of highly efficient devices.
- ArticleWu H, Jiang K, Yin N, Ma X, Zhao G, Qiu C, Deng G.Oncotarget. 2017 Mar 21;8(12):20042-20055.The purpose of this study was to investigate the effects of thymol on lipopolysaccharide (LPS)-induced inflammatory responses and to clarify the potential mechanism of these effects. LPS-induced mouse endometritis was used to confirm the anti-inflammatory action of thymol in vivo. RAW264.7 cells were used to examine the molecular mechanism and targets of thymol in vitro. In vivo, thymol markedly alleviated LPS-induced pathological injury, myeloperoxidase (MPO) activity, and the production of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in mice. Further studies were performed to examine the expression of the Toll-like receptor 4 (TLR4) -mediated nuclear factor-κB (NF-κB) pathway. These results showed that the expression of the TLR4-mediated NF-κB pathway was inhibited by thymol treatment. In vitro, we observed that thymol dose-dependently inhibited the expression of TNF-α, IL-1β, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW264.7 cells. Moreover, the results obtained from immunofluorescence assays also indicated that thymol dose-dependently suppressed LPS-induced reactive oxygen species (ROS) production. Silencing of TLR4 inhibited NF-κB pathway activation. Furthermore, H2O2 treatment increased the phosphorylation of p65 and IκBα, which were decreased when treated with N-acetyl cysteine or thymol. In conclusion, the anti-inflammatory effects of thymol are associated with activation of the TLR4 or ROS signaling pathways, contributing to NF-κB activation, thereby alleviating LPS-induced oxidative and inflammatory responses.
- ArticleZhang Y, Zhang J, Tse K, Wong L, Chan C, Deng B, Zhu J.Sci Rep. 2016 Feb 01;6:20055.Determining accurate absolute surface energies for polar surfaces of semiconductors has been a great challenge in decades. Here, we propose pseudo-hydrogen passivation to calculate them, using density functional theory approaches. By calculating the energy contribution from pseudo-hydrogen using either a pseudo molecule method or a tetrahedral cluster method, we obtained (111)/(111) surfaces energies of Si, GaP, GaAs, and ZnS with high self-consistency. This method quantitatively confirms that surface energy is determined by the number and the energy of dangling bonds of surface atoms. Our findings may greatly enhance the basic understandings of different surfaces and lead to novel strategies in the crystal growth.
- ArticleGuo J, Dai J, Peng X, Wang Q, Wang S, Lou X, Xia F, Zhao Z, Tang BZ.ACS Nano. 2021 12 28;15(12):20042-20055.Synergistic phototherapy provides a promising strategy to conquer the hypoxia and heterogeneity of tumors and realize a better therapeutic effect than monomodal photodynamic therapy (PDT) or photothermal therapy (PTT). The development of efficient multifunctional organic phototheranostic systems still remains a challenging task. Herein, 9,10-phenanthrenequinone (PQ) with strong electron-withdrawing ability is conjugated with the rotor-type electron-donating triphenylamine derivatives to create a series of tailor-made photosensitizers. The highly efficient Type I reactive oxygen species generation and outstanding photothermal conversion capacity are tactfully integrated into these PQ-cored photosensitizers. The underlying photophysical and photochemical mechanisms of the combined photothermal and Type I photodynamic effects are deciphered by experimental and theoretical methods and are closely associated with the active intramolecular bond stretching vibration, facilitated intersystem crossing, and specific redox cycling activity of the PQ core. Both in vitro and in vivo evaluations demonstrate that the nanoagents fabricated by these PQ-based photosensitizers are excellent candidates for Type I photodynamic and photothermal combined antitumor therapy. This study thus broadens the horizon for the development of high-performance PTT/Type I PDT nanoagents for synergistic phototheranostic treatments.
- ArticleCvetanovic M, Mitchell JE, Patel V, Avner BS, Su Y, van der Saag PT, Witte PL, Fiore S, Levine JS, Ucker DS.J Biol Chem. 2006 Jul 21;281(29):20055-67.The purpose of physiological cell death is the noninflammatory clearance of cells that have become inappropriate or nonfunctional. Consistent with this function, the recognition of apoptotic cells by professional phagocytes, including macrophages and dendritic cells, triggers a set of potent anti-inflammatory responses manifest on multiple levels. The immediate-early inhibition of proinflammatory cytokine gene transcription in the phagocyte is a proximate consequence of recognition of the apoptotic corpse, independent of subsequent engulfment and soluble factor involvement. Here, we show that recognition is linked to a characteristic signature of responses, including MAPK signaling events and the ablation of proinflammatory transcription and cytokine secretion. Specific recognition and response occurs without regard to the origin (species, tissue type, or suicidal stimulus) of the apoptotic cell and does not involve Toll-like receptor signaling. These features mark this as an innate immunity fundamentally distinct from the discrimination of "self" versus "other" considered to be the hallmark of conventional immunity. This profound unconventional innate immune discrimination of effete from live cells is as ubiquitous as apoptotic cell death itself, manifest by professional and nonprofessional phagocytes and nonphagocytic cell types alike. Innate apoptotic immunity provides an intrinsic anti-inflammatory circuit that attenuates proinflammatory responses dynamically and may act systemically as a powerful physiological regulator of immunity.
- ArticleLiaqat F, Vosqa UT, Khan F, Haleem A, Shaik MR, Siddiqui MRH, Khan M.ACS Omega. 2023 Jun 06;8(22):20042-20055.This work reports an environmentally friendly and economically feasible green synthesis of monometallic oxides (SnO2 and WO3) and their corresponding mixed metal oxide (SnO2/WO3-x) nanostructures from the aqueous Psidium guajava leaf extract for light-driven catalytic degradation of a major industrial contaminant, methylene blue (MB). P. guajava is a rich source of polyphenols that acts as a bio-reductant as well as a capping agent in the synthesis of nanostructures. The chemical composition and redox behavior of the green extract were investigated by liquid chromatography-mass spectrometry and cyclic voltammetry, respectively. Results acquired by X-ray diffraction and Fourier transform infrared spectroscopy confirm the successful formation of crystalline monometallic oxides (SnO2 and WO3) and bimetallic SnO2/WO3-x hetero-nanostructures capped with polyphenols. The structural and morphological aspects of the synthesized nanostructures were analyzed by transmission electron microscopy and scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy. Photocatalytic activity of the synthesized monometallic and hetero-nanostructures was investigated for the degradation of MB dye under UV light irradiation. Results indicate a higher photocatalytic degradation efficiency for mixed metal oxide nanostructures (93.5%) as compared to pristine monometallic oxides SnO2 (35.7%) and WO3 (74.5%). The hetero-metal oxide nanostructures prove to be better photocatalysts with reusability up to 3 cycles without any loss in degradation efficiency or stability. The enhanced photocatalytic efficiency is attributed to a synergistic effect in the hetero-nanostructures, efficient charge transportation, extended light absorption, and increased adsorption of dye due to the enlarged specific surface area.
- ArticleYin M, Liao Z, Huang YJ, Liu Z, Yuan X, Gomez D, Wang LE, Wei Q.PLoS One. 2011;6(5):e20055.The repair of DNA double-strand breaks (DSBs) is the major mechanism to maintain genomic stability in response to irradiation. We hypothesized that genetic polymorphisms in DSB repair genes may affect clinical outcomes among non-small cell lung cancer (NSCLC) patients treated with definitive radio(chemo)therapy. We genotyped six potentially functional single nucleotide polymorphisms (SNPs) (i.e., RAD51 -135G>C/rs1801320 and -172G>T/rs1801321, XRCC2 4234G>C/rs3218384 and R188H/rs3218536 G>A, XRCC3 T241M/rs861539 and NBN E185Q/rs1805794) and estimated their associations with overall survival (OS) and radiation pneumonitis (RP) in 228 NSCLC patients. We found a predictive role of RAD51 -135G>C SNP in RP development (adjusted hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.31-0.86, P = 0.010 for CG/CC vs. GG). We also found that RAD51 -135G>C and XRCC2 R188H SNPs were independent prognostic factors for overall survival (adjusted HR = 1.70, 95% CI, 1.14-2.62, P = 0.009 for CG/CC vs. GG; and adjusted HR = 1.70; 95% CI, 1.02-2.85, P = 0.043 for AG vs. GG, respectively) and that the SNP-survival association was most pronounced in the presence of RP. Our study suggests that HR genetic polymorphisms, particularly RAD51 -135G>C, may influence overall survival and radiation pneumonitis in NSCLC patients treated with definitive radio(chemo)therapy. Large studies are needed to confirm our findings.
- ArticleKo H, Choi BS, Choe JS, Kim KJ, Kim JH, Youn CJ.Opt Express. 2017 Aug 21;25(17):20045-20055.Most polarization-based BB84 quantum key distribution (QKD) systems utilize multiple lasers to generate one of four polarization quantum states randomly. However, random bit generation with multiple lasers can potentially open critical side channels that significantly endangers the security of QKD systems. In this paper, we show unnoticed side channels of temporal disparity and intensity fluctuation, which possibly exist in the operation of multiple semiconductor laser diodes. Experimental results show that the side channels can enormously degrade security performance of QKD systems. An important system issue for the improvement of quantum bit error rate (QBER) related with laser driving condition is further addressed with experimental results.
- ArticleTan JE, Wong SC, Gan SK, Xu S, Lam KP.J Biol Chem. 2001 Jun 08;276(23):20055-63.B lymphocytes lacking the adaptor protein B cell linker (BLNK) do not proliferate in response to B cell antigen receptor (BCR) engagement. We demonstrate here that BCR-activated BLNK(-)/- B cells fail to enter the cell cycle, and this is due to their inability to induce the expression of the cell cycle regulatory proteins such as cyclin D2 and cyclin-dependent kinase 4. BCR-stimulated BLNK(-)/- B cells also do not up-regulate the cell survival protein Bcl-x(L), which may be necessary for the cells to complete the cell cycle. In addition, BLNK(-)/- B cells exhibit a high rate of spontaneous apoptosis in culture. Examination of the various BCR-activated signaling pathways in mouse BLNK(-)/- B cells reveals the intact activation of Akt and mitogen-activated protein kinases but the impaired activation of nuclear factor (NF)-kappaB that is known to regulate genes involved in cell proliferation and survival. The inability to activate NF-kappaB in BCR-stimulated BLNK(-)/- B cells is due to a failure to induce the degradation of the inhibitory kappaB protein. In all these aspects, BLNK(-)/- B cells resemble xid B cells that have a mutation in Bruton's tyrosine kinase (Btk). Recently, phospholipase C (PLC)-gamma2 has also been demonstrated to be essential for NF-kappaB activation. Since BLNK has been shown separately to interact with both Btk and PLC-gamma2, our finding of normal Btk but impaired PLC-gamma2 activation in BCR-stimulated BLNK(-)/- B cells strongly suggests that BLNK orchestrates the formation of a Btk-PLC-gamma2 signaling axis that regulates NF-kappaB activation. Taken together, the NF-kappaB activation defect may be sufficient to explain the similar defects in BCR-induced B cell proliferation and T cell-independent immune responses in BLNK(-)/-, Btk(-)/-, and PLC-gamma2(-)/- mice.