Aspirin prevents colorectal cancer by regulating the abundance of Enterococcus cecorum and TIGIT+Treg cells.

Although aspirin can reduce the incidence of colorectal cancer (CRC), there is still uncertainty about its significance as a treatment for CRC, and the mechanism of aspirin in CRC is not well understood. In this study, we used aspirin to prevent AOM/DSS-induced CRC in mice, and the anti-CRC efficacy of aspirin was assessed using haematoxylin and eosin (H&E) staining and by determining the mouse survival rate and tumour size. 16S rDNA sequencing, flow cytometry (FCM), and Western blotting were also conducted to investigate the changes in the gut microbiota, tumour immune microenvironment, and apoptotic proteins, respectively. The results demonstrated that aspirin significantly exerted anti-CRC effects in mice. According to 16S rDNA sequencing, aspirin regulated the composition of the gut microbiota and dramatically reduced the abundance of Enterococcus cecorum. FCM demonstrated that there were more CD155 tumour cells and CD4 + CD25 + Treg cells showed increased TIGIT levels. Moreover, increased TIGIT expression on Treg cells is associated with reduced Treg cell functionality. Importantly, the inhibition of Treg cells is accompanied by the promotion of CD19 + GL-7 + B cells, CD8 + T cells, CD4 + CCR4 + Th2 cells, and CD4 + CCR6 + Th17 cells. Overall, aspirin prevents colorectal cancer by regulating the abundance of Enterococcus cecorum and TIGIT + Treg cells.

Probiotic powder ameliorates colorectal cancer by regulating Bifidobacterium animalis, Clostridium cocleatum, and immune cell composition.

Based on the relationship between the gut microbiota and colorectal cancer, we developed a new probiotic powder for treatment of colorectal cancer. Initially, we evaluated the effect of the probiotic powder on CRC using hematoxylin and eosin staining, and evaluated mouse survival rate and tumor size. We then investigated the effects of the probiotic powder on the gut microbiota, immune cells, and apoptotic proteins using 16S rDNA sequencing, flow cytometry, and western blot, respectively. The results showed that the probiotic powder improved the intestinal barrier integrity, survival rate, and reduced tumor size in CRC mice. This effect was associated with changes in the gut microbiota. Specifically, the probiotic powder increased the abundance of Bifidobacterium animalis and reduced the abundance of Clostridium cocleatum. In addition, the probiotic powder resulted in decreased numbers of CD4+ Foxp3+ Treg cells, increased numbers of IFN-γ+ CD8+ T cells and CD4+ IL-4+ Th2 cells, decreased expression of the TIGIT in CD4+ IL-4+ Th2 cells, and increased numbers of CD19+ GL-7+ B cells. Furthermore, the expression of the pro-apoptotic protein BAX was significantly increased in tumor tissues in response to the probiotic powder. In summary, the probiotic powder ameliorated CRC by regulating the gut microbiota, reducing Treg cell abundance, promoting the number of IFN-γ+ CD8+ T cells, increasing Th2 cell abundance, inhibiting the expression of TIGIT in Th2 cells, and increasing B cell abundance in the immune microenvironment of CRC, thereby increasing the expression of BAX in CRC.

microRNA-140-5p from human umbilical cord mesenchymal stem cells-released exosomes suppresses preeclampsia development.

This work unraveled the action of human umbilical cord mesenchymal stem cells-released exosomes (huc-MSCs-EXO) transfer of miR-140-5p in preeclampsia (PE). miR-140-5p and follistatin-like 3 (FSTL3) expression in placental tissues of PE patients was tested. EXO were isolated from huc-MSCs. Hypoxic trophoblast cells were co-cultured with huc-MSCs-EXO. Cell biological functions, angiogenesis, and inflammation were evaluated. Suppressed miR-140-5p and induced FSTL3 levels were measured in PE. Huc-MSCs-EXO drove biological functions and angiogenesis while hindering inflammation in hypoxic trophoblast cells. Increasing miR-140-5p further improved the positive role of huc-MSCs-EXO for hypoxic trophoblast cells, but the miR-140-5p-mediated effect in hypoxic trophoblast cells was abrogated by overexpressing FSTL3. miR-140-5p from huc-MSCs-EXO suppresses PE through repressing FSTL3.

Multidimensional Face Representation in a Deep Convolutional Neural Network Reveals the Mechanism Underlying AI Racism.

The increasingly popular application of AI runs the risk of amplifying social bias, such as classifying non-white faces as animals. Recent research has largely attributed this bias to the training data implemented. However, the underlying mechanism is poorly understood; therefore, strategies to rectify the bias are unresolved. Here, we examined a typical deep convolutional neural network (DCNN), VGG-Face, which was trained with a face dataset consisting of more white faces than black and Asian faces. The transfer learning result showed significantly better performance in identifying white faces, similar to the well-known social bias in humans, the other-race effect (ORE). To test whether the effect resulted from the imbalance of face images, we retrained the VGG-Face with a dataset containing more Asian faces, and found a reverse ORE that the newly-trained VGG-Face preferred Asian faces over white faces in identification accuracy. Additionally, when the number of Asian faces and white faces were matched in the dataset, the DCNN did not show any bias. To further examine how imbalanced image input led to the ORE, we performed a representational similarity analysis on VGG-Face's activation. We found that when the dataset contained more white faces, the representation of white faces was more distinct, indexed by smaller in-group similarity and larger representational Euclidean distance. That is, white faces were scattered more sparsely in the representational face space of the VGG-Face than the other faces. Importantly, the distinctiveness of faces was positively correlated with identification accuracy, which explained the ORE observed in the VGG-Face. In summary, our study revealed the mechanism underlying the ORE in DCNNs, which provides a novel approach to studying AI ethics. In addition, the face multidimensional representation theory discovered in humans was also applicable to DCNNs, advocating for future studies to apply more cognitive theories to understand DCNNs' behavior.

Clinical Characteristics of Pregnant Women With Coronavirus Disease 2019 in Wuhan, China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a pandemic. Despite the growing number of patients with COVID-19 infection, data on the clinical characteristics of pregnant patients are still limited. METHODS: We retrospectively included childbearing-age female patients with laboratory-confirmed COVID-19 at Renmin Hospital of Wuhan University from January 15 to February 23, 2020. Demographic, clinical, radiological, laboratory, and treatment data were reviewed. Clinical characteristics of pregnant and nonpregnant patients were compared. RESULTS: One hundred eleven childbearing-age women with COVID-19 were included, including 16 patients (14.4%) with severe or critical disease. Compared with nonpregnant patients (n = 80), pregnant patients (n = 31) were less likely to have dyspnea (16.1% vs 37.5%), asthenia (3.2% vs 33.8%), and ≥3 symptoms (22.6% vs 45.0%); had a significantly higher neutrophil count (5.2 vs 2.5 ×109/L) and a higher percentage of CD3+ cells (76.7% vs 73.7%) and CD8+ cells (32.3% vs 28.4%); and had a dramatically lower percentage of lymphocytes (18.2% vs 31.8%), a lower CD4+/CD8+ ratio (1.2 vs 1.4), and a lower level of IgG (9.8 vs 11.9 g/L). Of note, pregnant patients had a significantly lower percentage of severe disease (3.2% vs 18.8%) and a substantially higher level of inflammation markers including neutrophil-to-lymphocyte ratio (4.4 vs 1.9) and systematic inflammatory index (812.8 vs 354.7) than nonpregnant patients. Seventeen live births were recorded, and all of these showed negative results of postnatal COVID-19 detection together with a normal Apgar score. CONCLUSIONS: Pregnant patients with COVID-19 had a lower level of severity and an enhanced inflammatory response and cell immunity when compared with nonpregnant patients.

Transcranial direct current stimulation over the right DLPFC selectively modulates subprocesses in working memory.

BACKGROUND: Working memory, as a complex system, consists of two independent components: manipulation and maintenance process, which are defined as executive control and storage process. Previous studies mainly focused on the overall effect of transcranial direct current stimulation (tDCS) on working memory. However, little has been known about the segregative effects of tDCS on the sub-processes within working memory. METHOD: Transcranial direct current stimulation, as one of the non-invasive brain stimulation techniques, is being widely used to modulate the cortical activation of local brain areas. This study modified a spatial n-back experiment with anodal and cathodal tDCS exertion on the right dorsolateral prefrontal cortex (DLPFC), aiming to investigate the effects of tDCS on the two sub-processes of working memory: manipulation (updating) and maintenance. Meanwhile, considering the separability of tDCS effects, we further reconfirmed the causal relationship between the right DLPFC and the sub-processes of working memory with different tDCS conditions. RESULTS: The present study showed that cathodal tDCS on the right DLPFC selectively improved the performance of the modified 2-back task in the difficult condition, whereas anodal tDCS significantly reduced the performance of subjects and showed an speeding-up tendency of response time. More precisely, the results of discriminability index and criterion showed that only cathodal tDCS enhanced the performance of maintenance in the difficult condition. Neither of the two tDCS conditions affected the performance of manipulation (updating). CONCLUSION: These findings provide evidence that cathodal tDCS of the right DLPFC selectively affects maintenance capacity. Besides, cathodal tDCS also serves as an interference suppressor to reduce the irrelevant interference, thereby indirectly improving the working memory capacity. Moreover, the right DLPFC is not the unique brain regions for working memory manipulation (updating).

The influence of spatial frequency content on facial expression processing: An ERP study using rapid serial visual presentation.

Spatial frequency (SF) contents have been shown to play an important role in emotion perception. This study employed event-related potentials (ERPs) to explore the time course of neural dynamics involved in the processing of facial expression conveying specific SF information. Participants completed a dual-target rapid serial visual presentation (RSVP) task, in which SF-filtered happy, fearful, and neutral faces were presented. The face-sensitive N170 component distinguished emotional (happy and fearful) faces from neutral faces in a low spatial frequency (LSF) condition, while only happy faces were distinguished from neutral faces in a high spatial frequency (HSF) condition. The later P3 component differentiated between the three types of emotional faces in both LSF and HSF conditions. Furthermore, LSF information elicited larger P1 amplitudes than did HSF information, while HSF information elicited larger N170 and P3 amplitudes than did LSF information. Taken together, these results suggest that emotion perception is selectively tuned to distinctive SF contents at different temporal processing stages.

MnCo2 O4 /MoO2 Nanosheets Grown on Ni foam as Carbon- and Binder-Free Cathode for Lithium-Oxygen Batteries.

Carbon is usually used as cathode material for Li-O2 batteries. However, the discharge product, such as Li2 O2 and LiO2 , could react with carbon to form an insulating lithium carbonate layer, resulting in cathode passivation and capacity fading. To solve this problem, the development of non-carbon cathodes is highly desirable. Herein, we successfully synthesized MnCo2 O4 (MCO) nanoparticles anchored on porous MoO2 nanosheets that are grown on Ni foam (current collector) (MCO/MoO2 @Ni), acting as a carbon- and binder-free cathode for Li-O2 batteries, in an attempt to improve the electrical conductivity, electrocatalytic activity, and durability. This MCO/MoO2 @Ni electrode delivers excellent cyclability (more than 400 cycles) and rate performance (voltage gap of 0.75 V at 5000 mA g-1 ). Notably, the battery with this electrode exhibits a high energy efficiency (higher than 85 %). The advanced electrochemical performance of MCO/MoO2 @Ni can be attributed to its high electrical conductivity, excellent stability, and outstanding electrocatalytic activity. This work offers a new strategy to fabricate high-performance Li-O2 batteries with non-carbon cathode materials.

Molecular analysis of non-specific protection against murine malaria induced by BCG vaccination.

Although the effectiveness of BCG vaccination in preventing adult pulmonary tuberculosis (TB) has been highly variable, epidemiologic studies have suggested that BCG provides other general health benefits to vaccinees including reducing the impact of asthma, leprosy, and possibly malaria. To further evaluate whether BCG immunization protects against malarial parasitemia and to define molecular correlates of this non-specific immunity, mice were vaccinated with BCG and then challenged 2 months later with asexual blood stage Plasmodium yoelii 17XNL (PyNL) parasites. Following challenge with PyNL, significant decreases in parasitemia were observed in BCG vaccinated mice relative to naïve controls. To identify immune molecules that may be associated with the BCG-induced protection, gene expression was evaluated by RT-PCR in i) naïve controls, ii) BCG-vaccinated mice, iii) PyNL infected mice and iv) BCG vaccinated/PyNL infected mice at 0, 1, 5, and 9 days after the P. yoelii infection. The expression results showed that i) BCG immunization induces the expression of at least 18 genes including the anti-microbial molecules lactoferrin, eosinophil peroxidase, eosinophil major basic protein and the cathelicidin-related antimicrobial peptide (CRAMP); ii) an active PyNL infection suppresses the expression of important immune response molecules; and iii) the extent of PyNL-induced suppression of specific genes is reduced in BCG-vaccinated/PyNL infected mice. To validate the gene expression data, we demonstrated that pre-treatment of malaria parasites with lactoferrin or the cathelicidin LL-37 peptide decreases the level of PyNL parasitemias in mice. Overall, our study suggests that BCG vaccination induces the expression of non-specific immune molecules including antimicrobial peptides which may provide an overall benefit to vaccinees by limiting infections of unrelated pathogens such as Plasmodium parasites.

Malaria infections do not compromise vaccine-induced immunity against tuberculosis in mice.

BACKGROUND: Given the considerable geographic overlap in the endemic regions for malaria and tuberculosis, it is probable that co-infections with Mycobacterium tuberculosis and Plasmodium species are prevalent. Thus, it is quite likely that both malaria and TB vaccines may be used in the same populations in endemic areas. While novel vaccines are currently being developed and tested individually against each of these pathogens, the efficacy of these vaccines has not been evaluated in co-infection models. To further assess the effectiveness of these new immunization strategies, we investigated whether co-infection with malaria would impact the anti-tuberculosis protection induced by four different types of TB vaccines in a mouse model of pulmonary tuberculosis. PRINCIPAL FINDINGS: Here we show that the anti-tuberculosis protective immunity induced by four different tuberculosis vaccines was not impacted by a concurrent infection with Plasmodium yoelii NL, a nonlethal form of murine malaria. After an aerogenic challenge with virulent M. tuberculosis, the lung bacterial burdens of vaccinated animals were not statistically different in malaria infected and malaria naïve mice. Multi-parameter flow cytometric analysis showed that the frequency and the median fluorescence intensities (MFI) for specific multifunctional T (MFT) cells expressing IFN-γ, TNF-α, and/or IL-2 were suppressed by the presence of malaria parasites at 2 weeks following the malaria infection but was not affected after parasite clearance at 7 and 10 weeks post-challenge with P. yoelii NL. CONCLUSIONS: Our data indicate that the effectiveness of novel TB vaccines in protecting against tuberculosis was unaffected by a primary malaria co-infection in a mouse model of pulmonary tuberculosis. While the activities of specific MFT cell subsets were reduced at elevated levels of malaria parasitemia, the T cell suppression was short-lived. Our findings have important relevance in developing strategies for the deployment of new TB vaccines in malaria endemic areas.

Snapin-regulated late endosomal transport is critical for efficient autophagy-lysosomal function in neurons.

Neuron maintenance and survival require late endocytic transport from distal processes to the soma where lysosomes are predominantly localized. Here, we report a role for Snapin in attaching dynein to late endosomes through its intermediate chain (DIC). snapin(-/-) neurons exhibit aberrant accumulation of immature lysosomes, clustering and impaired retrograde transport of late endosomes along processes, reduced lysosomal proteolysis due to impaired delivery of internalized proteins and hydrolase precursors from late endosomes to lysosomes, and impaired clearance of autolysosomes, combined with reduced neuron viability and neurodegeneration. The phenotypes are rescued by expressing the snapin transgene, but not the DIC-binding-defective Snapin-L99K mutant. Snapin overexpression in wild-type neurons enhances late endocytic transport and lysosomal function, whereas expressing the mutant defective in Snapin-DIC coupling shows a dominant-negative effect. Altogether, our study highlights new mechanistic insights into how Snapin-DIC coordinates retrograde transport and late endosomal-lysosomal trafficking critical for autophagy-lysosomal function, and thus neuronal homeostasis.

Snapin associates with late endocytic compartments and interacts with late endosomal SNAREs.

Late endocytic membrane trafficking delivers target materials and newly synthesized hydrolases into lysosomes and is critical for maintaining an efficient degradation process and cellular homoeostasis. Although some features of late endosome-lysosome trafficking have been described, the mechanisms underlying regulation of this event remain to be elucidated. Our previous studies showed that Snapin, as a SNAP25 (25 kDa synaptosome-associated protein)-binding protein, plays a critical role in priming synaptic vesicles for synchronized fusion in neurons. In the present study, we report that Snapin also associates with late endocytic membranous organelles and interacts with the late endosome-targeted SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) complex. Using a genetic mouse model, we further discovered that Snapin is required to maintain a proper balance of the late endocytic protein LAMP-1 (lysosome-associated membrane protein-1) and late endosomal SNARE proteins syntaxin 8 and Vti1b (vesicle transport through interaction with target SNAREs homologue 1b). Deleting the snapin gene in mice selectively led to the accumulation of these proteins in late endocytic organelles. Thus our present study suggests that Snapin serves as an important regulator of the late endocytic fusion machinery, in addition to its established role in regulating synaptic vesicle fusion.

Snapin facilitates the synchronization of synaptic vesicle fusion.

Synaptic vesicle (SV) fusion is a fine-tuned process requiring a concert of fusion machineries. Using cortical neurons from snapin-deficient mice, we reveal a role for Snapin in facilitating synchronous release. In addition to reduced frequency of miniature excitatory postsynaptic currents (mini-EPSCs) and smaller release-ready vesicle pool (RRP) size, snapin deficiency results in EPSCs with multiple peaks and increased rise and decay times, reflecting "desynchronized" SV fusion. These defects impair both synaptic precision and efficacy during sustained neurotransmission. Transient expression of Snapin not only rescues the slowed kinetics of EPSCs, but also further accelerates the rate found in wild-type neurons. Furthermore, expression of Snapin-C66A, a dimerization-defective mutant with impaired interactions with SNAP-25 and Synaptotagmin, reduces the RRP size but exhibits less effect on synchronized fusion. Our studies provide mechanistic insights into a dual role of Snapin in enhancing the efficacy of SV priming and in fine-tuning synchronous SV fusion.

[Sensory gating P50 in schizophrenic patients with and without homicide].

OBJECTIVE: To investigate the change of sensory gating P50 in schizophrenic patients with and without homicide. METHODS: The auditory evoked potentials P50 were recorded from 26 schizophrenic patients with homicide (Sch group), 27 schizophrenic patients without homicide (non-Sch group) and 32 normal controls (NC) using conditioning/testing paradigm presented with auditory double click stimuli by EGI 256 dense array. And the same time, their clinical symptoms were evaluated by positive and negative symptom scale (PANSS). RESULTS: (1) Compared with NC, two Sch groups showed no significant difference in amplitude and latency of S1-P50 [amplitude: NC, Sch group, non-Sch group at Fz: (2.4 + or - 1.6) microV, (2.5 + or - 1.5) microV, (3.4 + or - 2.7) microV; latency: NC, Sch group, non-Sch group at Fz: (68 + or - 19) ms, (67 + or - 20) ms, (61 + or - 19) ms; respectively], but a higher amplitude and delayed latency of S2-P50 [amplitude: NC, Sch group, non-Sch group at Fz: (0.8 + or - 0.7) microV, (2.5 + or - 1.6) microV, (3.3 + or - 2.2) microV; latency: NC, Sch group, non-Sch group at Fz: (50 + or - 26) ms, (75 + or - 19) ms and (70 + or - 24) ms respectively] (P < 0.01), and no significant difference in amplitude and latency of S2-P50 between two Sch groups. (2) Compared with NC, two Sch groups showed a higher S2/S1 ratio [NC, Sch group, non-Sch group at Fz: 35 + or - 26, 153 + or - 137, 125 + or - 85, respectively], lower S2-S1 [NC, Sch group, non Sch group at Fz: 1.69 + or - 1.55, 0.08 + or - 2.41 and 0.17 + or - 2.30, respectively] and 100 (1-S2/S1) [NC, Sch group, non-Sch group at Fz: 65 + or - 26, -53 + or - 137 and -25 + or - 85 respectively] (P < 0.01). And there was no significant difference in S2/S1 ratio, S2-S1 and 100 (1-S2/S1) between two Sch groups. (3) Two Sch groups showed no significant difference in PANSS total, P scale, N scale, and G scale [Sch group: (110 + or - 27), (26 + or - 10), (29 + or - 7), (55 + or - 12); non Sch group: (105 + or - 27), (24 + or - 8), (28 + or - 10) and (53 + or - 12) respectively] (P > 0.05), and no significant correlation with S2/S1 ratio, S2-S1 and 100(1-S2/S1) (P > 0.05). CONCLUSION: Sensory gating deficit exists in schizophrenic patients with and without homicide. And it can be quantified by measuring auditory evoked potential P50, but sensory gating P50 has no difference between schizophrenic patients with and without homicide.

Docking of axonal mitochondria by syntaphilin controls their mobility and affects short-term facilitation.

Proper distribution of mitochondria within axons and at synapses is critical for neuronal function. While one-third of axonal mitochondria are mobile, a large proportion remains in a stationary phase. However, the mechanisms controlling mitochondrial docking within axons remain elusive. Here, we report a role for axon-targeted syntaphilin (SNPH) in mitochondrial docking through its interaction with microtubules. Axonal mitochondria that contain exogenously or endogenously expressed SNPH lose mobility. Deletion of the mouse snph gene results in a substantially higher proportion of axonal mitochondria in the mobile state and reduces the density of mitochondria in axons. The snph mutant neurons exhibit enhanced short-term facilitation during prolonged stimulation, probably by affecting calcium signaling at presynaptic boutons. This phenotype is fully rescued by reintroducing the snph gene into the mutant neurons. These findings demonstrate a molecular mechanism for controlling mitochondrial docking in axons that has a physiological impact on synaptic function.

The role of Snapin in neurosecretion: snapin knock-out mice exhibit impaired calcium-dependent exocytosis of large dense-core vesicles in chromaffin cells.

Identification of the molecules that regulate the priming of synaptic vesicles for fusion and the structural coupling of the calcium sensor with the soluble N-ethyl maleimide sensitive factor adaptor protein receptor (SNARE)-based fusion machinery is critical for understanding the mechanisms underlying calcium-dependent neurosecretion. Snapin binds to synaptosomal-associated protein 25 kDa (SNAP-25) and enhances the association of the SNARE complex with synaptotagmin. In the present study, we abolished snapin expression in mice and functionally evaluated the role of Snapin in neuroexocytosis. We found that the association of synaptotagmin-1 with SNAP-25 in brain homogenates of snapin mutant mice is impaired. Consequently, the absence of Snapin in embryonic chromaffin cells leads to a significant reduction of calcium-dependent exocytosis resulting from a decreased number of vesicles in releasable pools. Overexpression of Snapin fully rescued this inhibitory effect in the mutant cells. Furthermore, Snapin is relatively enriched in the purified large dense-core vesicles of chromaffin cells and associated with synaptotagmin-1. Thus, our biochemical and electrophysiological studies using snapin knock-out mice demonstrate that Snapin plays a critical role in modulating neurosecretion by stabilizing the release-ready vesicles.

Safety assessment for genetically modified sweet pepper and tomato.

The coat protein (CP) gene of cucumber mosaic virus (CMV) was cloned from a Chinese CMV isolate, the CaMV promoter and NOS terminator added and the gene construct was transformed into both sweet pepper and tomato plants to confer resistance to CMV. Safety assessments of these genetically modified (GM) plants were conducted. It was found that these two GM products showed no genotoxicity either in vitro or in vivo by the micronucleus test, sperm aberration test and Ames test. Animal feeding studies showed no significant differences in growth, body weight gain, food consumption, hematology, blood biochemical indices, organ weights and histopathology between rats or mice of either sex fed with either GM sweet pepper or tomato diets compared with those with non-GM diets. These results demonstrate that the CMV-resistant sweet pepper and tomato are comparable to the non-GM counterparts in terms of food safety.

Ca2+-dependent phosphorylation of syntaxin-1A by the death-associated protein (DAP) kinase regulates its interaction with Munc18.

Syntaxin-1 is a key component of the synaptic vesicle docking/fusion machinery that binds with VAMP/synaptobrevin and SNAP-25 to form the SNARE complex. Modulation of syntaxin binding properties by protein kinases could be critical to control of neurotransmitter release. Using yeast two-hybrid selection with syntaxin-1A as bait, we have isolated a cDNA encoding the C-terminal domain of death-associated protein (DAP) kinase, a calcium/calmodulin-dependent serine/threonine protein kinase. Expression of DAP kinase in adult rat brain is restricted to particular neuronal subpopulations, including the hippocampus and cerebral cortex. Biochemical studies demonstrate that DAP kinase binds to and phosphorylates syntaxin-1 at serine 188. This phosphorylation event occurs both in vitro and in vivo in a Ca2+-dependent manner. Syntaxin-1A phosphorylation by DAP kinase or its S188D mutant, which mimics a state of complete phosphorylation, significantly decreases syntaxin binding to Munc18-1, a syntaxin-binding protein that regulates SNARE complex formation and is required for synaptic vesicle docking. Our results suggest that syntaxin is a DAP kinase substrate and provide a novel signal transduction pathway by which syntaxin function could be regulated in response to intracellular [Ca2+] and synaptic activity.